Loading [MathJax]/jax/output/SVG/jax.js
Review

Free-radicals and advanced chemistries involved in cell membrane organization influence oxygen diffusion and pathology treatment

  • Received: 08 December 2016 Accepted: 13 March 2017 Published: 06 April 2017
  • A breakthrough has been discovered in pathology chemistry related to increasing molecular structure that can interfere with oxygen diffusion through cell membranes. Free radicals can crosslink unsaturated low-viscosity fatty acid oils by chain-growth polymerization into more viscous liquids and even solids. Free radicals are released by mitochondria in response to intermittent hypoxia that can increase membrane molecular organization to reduce fluidity and oxygen diffusion in a possible continuing vicious cycle toward pathological disease. Alternate computational chemistry demonstrates molecular bond dynamics in free energy for cell membrane physiologic movements. Paired electrons in oxygen and nitrogen atoms require that oxygen bonds rotate and nitrogen bonds invert to seek polar nano-environments and hide from nonpolar nano-environments thus creating fluctuating instability at a nonpolar membrane and polar biologic fluid interface. Subsequent mechanomolecular movements provide free energy to increase diffusion by membrane transport of molecules and oxygen into the cell, cell-membrane signaling/recognition/defense in addition to protein movements for enzyme mixing. In other chemistry calcium bonds to membrane phosphates primarily on the outer plasma cell membrane surface to influence the membrane firing threshold for excitability and better seal out water permeation. Because calcium is an excellent metal conductor and membrane phosphate headgroups form a semiconductor at the biologic fluid interface, excess electrons released by mitochondria may have more broad dissipation potential by safe conduction through calcium atomic-sized circuits on the outer membrane surface. Regarding medical conditions, free radicals are known to produce pathology especially in age-related disease in addition to aging. Because cancer cell membranes develop extreme polymorphism that has been extensively followed in research, accentuated easily-visualized free-radical models are developed. In terms of treatment, use of vitamin nutrient supplements purported to be antioxidants that remove free radicals has not proved worthwhile in clinical trials presumably due to errors with early antioxidant measurements based on inaccurate colorimetry tests. However, newer covalent-bond shrinkage tests now provide accurate measurements for free-radical inhibitor hydroquinone and other molecules toward drug therapy.

    Citation: Richard C Petersen. Free-radicals and advanced chemistries involved in cell membrane organization influence oxygen diffusion and pathology treatment[J]. AIMS Biophysics, 2017, 4(2): 240-283. doi: 10.3934/biophy.2017.2.240

    Related Papers:

    [1] Alessia Marigo . Equilibria for data networks. Networks and Heterogeneous Media, 2007, 2(3): 497-528. doi: 10.3934/nhm.2007.2.497
    [2] Yuntian Zhang, Xiaoliang Chen, Zexia Huang, Xianyong Li, Yajun Du . Managing consensus based on community classification in opinion dynamics. Networks and Heterogeneous Media, 2023, 18(2): 813-841. doi: 10.3934/nhm.2023035
    [3] Alessandra Pluda . Evolution of spoon-shaped networks. Networks and Heterogeneous Media, 2016, 11(3): 509-526. doi: 10.3934/nhm.2016007
    [4] Mahendra Piraveenan, Mikhail Prokopenko, Albert Y. Zomaya . On congruity of nodes and assortative information content in complex networks. Networks and Heterogeneous Media, 2012, 7(3): 441-461. doi: 10.3934/nhm.2012.7.441
    [5] Henri Berestycki, Jean-Pierre Nadal, Nancy Rodíguez . A model of riots dynamics: Shocks, diffusion and thresholds. Networks and Heterogeneous Media, 2015, 10(3): 443-475. doi: 10.3934/nhm.2015.10.443
    [6] Shui-Nee Chow, Xiaojing Ye, Hongyuan Zha, Haomin Zhou . Influence prediction for continuous-time information propagation on networks. Networks and Heterogeneous Media, 2018, 13(4): 567-583. doi: 10.3934/nhm.2018026
    [7] Michael Baur, Marco Gaertler, Robert Görke, Marcus Krug, Dorothea Wagner . Augmenting k-core generation with preferential attachment. Networks and Heterogeneous Media, 2008, 3(2): 277-294. doi: 10.3934/nhm.2008.3.277
    [8] Alessia Marigo . Optimal traffic distribution and priority coefficients for telecommunication networks. Networks and Heterogeneous Media, 2006, 1(2): 315-336. doi: 10.3934/nhm.2006.1.315
    [9] Werner Creixell, Juan Carlos Losada, Tomás Arredondo, Patricio Olivares, Rosa María Benito . Serendipity in social networks. Networks and Heterogeneous Media, 2012, 7(3): 363-371. doi: 10.3934/nhm.2012.7.363
    [10] Giovanni Scardoni, Carlo Laudanna . Identifying critical traffic jam areas with node centralities interference and robustness. Networks and Heterogeneous Media, 2012, 7(3): 463-471. doi: 10.3934/nhm.2012.7.463
  • A breakthrough has been discovered in pathology chemistry related to increasing molecular structure that can interfere with oxygen diffusion through cell membranes. Free radicals can crosslink unsaturated low-viscosity fatty acid oils by chain-growth polymerization into more viscous liquids and even solids. Free radicals are released by mitochondria in response to intermittent hypoxia that can increase membrane molecular organization to reduce fluidity and oxygen diffusion in a possible continuing vicious cycle toward pathological disease. Alternate computational chemistry demonstrates molecular bond dynamics in free energy for cell membrane physiologic movements. Paired electrons in oxygen and nitrogen atoms require that oxygen bonds rotate and nitrogen bonds invert to seek polar nano-environments and hide from nonpolar nano-environments thus creating fluctuating instability at a nonpolar membrane and polar biologic fluid interface. Subsequent mechanomolecular movements provide free energy to increase diffusion by membrane transport of molecules and oxygen into the cell, cell-membrane signaling/recognition/defense in addition to protein movements for enzyme mixing. In other chemistry calcium bonds to membrane phosphates primarily on the outer plasma cell membrane surface to influence the membrane firing threshold for excitability and better seal out water permeation. Because calcium is an excellent metal conductor and membrane phosphate headgroups form a semiconductor at the biologic fluid interface, excess electrons released by mitochondria may have more broad dissipation potential by safe conduction through calcium atomic-sized circuits on the outer membrane surface. Regarding medical conditions, free radicals are known to produce pathology especially in age-related disease in addition to aging. Because cancer cell membranes develop extreme polymorphism that has been extensively followed in research, accentuated easily-visualized free-radical models are developed. In terms of treatment, use of vitamin nutrient supplements purported to be antioxidants that remove free radicals has not proved worthwhile in clinical trials presumably due to errors with early antioxidant measurements based on inaccurate colorimetry tests. However, newer covalent-bond shrinkage tests now provide accurate measurements for free-radical inhibitor hydroquinone and other molecules toward drug therapy.


    Social networking is currently sustaining the exchange of information among individuals, societies, and nations. An ever-increasing number of individuals tend to share their experiences and comments partially or entirely through online media platforms such as Weibo [1] and Facebook. The privacy features of social networks can remove communication barriers between individuals, allowing them to express themselves candidly and openly. Anyone can freely express and share their feelings [2], assess others' perspectives, and acknowledge supported opinions on social media platforms. Central to the entire communication discipline in social networks stems from viral marketing [3]. This strategic approach to information diffusion has been widely adopted in various domains, including product promotion [4], personalized recommendations [5], targeted advertising [6], the selection of influential users [7,8,9,10].

    Information diffusion phenomena in social networks has brought about both immense convenience and potential threats in the dissemination of groundbreaking ideas. The perceptions of individuals within a social network have the ability to influence the commenting behavior and awareness of their neighboring users, leading to intermittent changes in the network topology. These individual perceptions, known as user influence, are critical for understanding user behavior, uncovering network propagation dynamics, and examining topology evolutions. The influence maximization (IM) problem, which was formulated by Kempe et al. [11], is a challenging issue that has been proven to be NP-hard. Cecilia et al. [12] discovered that examining the citizenship competencies plays an important role in a complex system like a society, and it is crucial to study their effects given the significance of these competences in shaping social systems. Within the domain of social network analysis, IM emerges as a pivotal undertaking involving carefully selecting a seed group within a given social network to maximize its influence on a broad spectrum of individuals. This optimization problem holds profound significance for the process of refining information diffusion strategies to accomplish diverse objectives, which can range from viral marketing and opinion-shaping to social mobilization. When executed adeptly, IM engenders remarkable enhancements in the efficiency and effectiveness of such campaigns. Notably, within the context of viral marketing, IM facilitates the identification of potential customers, thereby curtailing marketing costs and bolstering profits. Furthermore, IM plays a pivotal role in molding public opinion across various domains such as politics, health, and the environment, while also galvanizing individuals for social causes encompassing protests, donations, and petitions. By harnessing IM effectively, substantial dividends can be reaped, efficiently leveraging the power of social networks to accomplish a multitude of objectives. By employing diffusion cascades, it becomes possible to optimize the reach of influence for the chosen seed set [13,14]. Identifying influential nodes within social networks offers invaluable insight into the underlying mechanisms that govern information diffusion phenomena, thereby informing effective strategies for message propagation. Moreover, the exploration of IM contributes to the development of novel algorithms and techniques that maximize the extent and impact of information dissemination in social networks.

    An independent cascade (a stochastic diffusion model) is generally employed in IM to simulate the dissemination of information by seed nodes. The spread of influence is commonly measured in terms of the number of activated users. However, the majority of research in IM has focused on stochastic diffusion patterns, and few studies have explored the global-scale role approximation of social network users. In reality, each user in a social network plays a specific role, whether as an opinion leader, a structural hole user, or an ordinary user. All of them contribute to the overall diffusion of information. This study takes into account the social reality that users with similar roles in a social network exhibit comparable behaviors and attributes. For instance, structural hole users can facilitate the exchange between two communities in a social network, while ordinary users typically receive information passively. By identifying user roles in a social network, researchers can better understand the mechanisms behind information diffusion phenomena and develop more accurate models for solving IM problems.

    In recent years, several user role identification studies have recommended the knowledge contribution approach proposed in [15]. This approach identifies three user roles, namely givers, takers, and matchers, based on their knowledge contribution to disseminated information. Research context in light electric vehicle applications promotes the differentiation of more roles such as the vigilant user, passive collaborator, active decision-maker, and ambassador [16]. This four-dimensional role classification, determined by participation degrees, is particularly important in the service promotion of electric vehicles. Some studies [17,18] have emphasized the importance of user role division in the information diffusion process. However, these studies have yet to consider the key factor of user roles in the existing IM research. Furthermore, network structure information has not been fully incorporated into studies on user role division.

    The study delves into a novel network embedding algorithm that integrates user role information, thereby adding a fresh and invaluable perspective to the realm of efficient IM solutions. In particular, the proposed approach utilizes network embedding's benefits to incorporate similarities between users' global roles, and is hence termed as role-based network embedding (RbNE). This methodology entails the mapping of social network nodes into a fixed-dimensional space, whereby they are represented as low-dimensional vectors that capture both the structural and user role information. After calculating the embedding vectors of nodes, a novel logical propagation network can be constructed based on their similarities. Finally, a greedy heuristic algorithm is introduced to select a seed set of k nodes.

    The main contributions of our work are enumerated as follows:

    1. To address the existing gap in the literature where network structure information is not fully incorporated into role division analyses, we propose a novel user role division algorithm that incorporates both coarse-grained user role division (CGURD) and fine-grained user role division (FGURD). CGURD aims to divide users into different groups based on their overall contribution to the network, while FGURD focuses on identifying more precise user roles based on their relationships with neighboring nodes. By combining these two approaches, we can achieve a more comprehensive understanding of user roles in social networks, which can provide new insights into the IM problem.

    2. Current research has not examined the effects of the user's global roles in efforts to solve the IM problem. A systematic understanding of how the global roles contribute to capturing the seed set with the most significant influence is still lacking. Therefore, this paper proposes a novel network embedding algorithm, entitled RbNE, to preserve the approximation between users' global roles. Subsequently, a greedy heuristic algorithm, named RbneIM, is developed to select the seed set S. This algorithm considers the users' global roles as an essential factor in selecting the seed set and enables the identification of users who can maximize the influence spread in a social network.

    3. Our study extensively evaluates the performance of RbneIM on four real-world datasets. The experimental results indicate that our approach significantly outperforms the state-of-the-art methods, thereby demonstrating its superior performance in terms of solving the IM problem.

    The task of IM was initially specified in social networks. Accordingly, this paper follows the same applied background. A social network can be represented by a two-tuple G=(V,E), where V={v1,v2,...,vn} and EV×V={eij} represent a set of n nodes and a set of edges between the nodes, respectively. An edge eij=(vi,vj) indicates a potential relationship between nodes vi and vj, which is also associated with a weight wij0 of their connection strength. Table 1 summarizes the notations employed in this paper.

    Table 1.  Notations used in this paper.
    Notation Description of notation
    V The set of nodes in a social network
    E The set of edges in a social network
    A User characteristic matrix A|V|×D
    S Selected set of seed nodes, SV
    Nei(u) Direct neighbors of node u
    Infuv Local influence of node u on node v
    B(u) Betweenness centrality of node u
    OLIu Opinion leader influence score of node u
    NC(u) Network constraint coefficient value of node u
    Sim(u,v) Relationship between node u and node v
    Pr(Vv) Probability of being activated by v's neighbors
    Pr(VS) Probability of being activated by seed nodes S

     | Show Table
    DownLoad: CSV

    In social networks, many spreading processes can be modeled as complex chain reactions. Kempe et al. [19] introduced two probability diffusion models, namely independent cascade (IC) and linear threshold (LT), to explain these processes. A framework based on submodular functions is proposed to analyze the performance guarantees of algorithms for influence problems. Kempe et al. show that a greedy strategy can be within 63% of optimal for several classes of models, and they present computational experiments that demonstrate the superiority of their approximation algorithms over other node-selection heuristics. Among them, LT models are commonly involved as an extremely representative framework for understanding these mechanisms. This study evaluates the effectiveness of the seed node selection using the LT model [20]. We assume that a node vV of a social network G is influenced by each incoming neighbor weight w[0,1], which contributes to the idea behind the LT. An inactive user becomes active once the number of its neighbors reaches a certain threshold θ of active states. Specifically, each node v in a social network G has a threshold θ in the interval [0,1], representing the conditional value of the node v being activated. The activation of node v can be formalized as follows:

    uNei(v)wuvθ (2.1)

    where Nei(v) refers to the direct neighbors of node u. Specifically, in the LT model, each node has two attributes: threshold and weight. A node's threshold is a value between 0 and 1, indicating how many active neighbors it needs to become activated. The weight of a neighbor is also a value between 0 and 1, representing the neighbor's influence on the node. If the threshold of a node i is t and the neighbor set is N, then the node i will be activated under the following condition:

    (jN,the total weight of j when activated)t (2.2)

    where the total weight of j when activated refers to the sum of all edge weights connecting to node j.

    In social network analysis, IM is a crucial concept that involves selecting a subset of nodes or edges in a given network to maximize the impact of a particular objective. Individual characteristics and the effects between individuals are expressed in the form of social network topology. Hence, influence has both global and local scopes. A node with stronger global influence in a network has the ability to control the spread of information and behavior in the network. Moreover, a small subset of highly influential nodes in a social network can control the propagation of most of the information. Thus, selecting the correct seed nodes is crucial to achieving maximum impact in the spread of information in a social network. IM technology is useful for identifying critical nodes to maximize the impact of information diffusion throughout the network. Compared to a random selection of nodes, IM technology can predict and quantify influence, leading to more effective resource allocation and planning strategies. A node's influence on another node is considered local influence, and the more a node influences another node, the more the latter will follow and imitate the former's behavior in the social network. The process of defining node influence through local influence and network structure can yield better results, taking into account the requirements of different applications. Studies of dynamic social network nodes' influence has mostly been on static network topologies, examining users' influence or users' influence variation on static topologies over time.

    The literature on IM problems can be traced back to a study by Domingos and Richardson [21]. Kempe et al. [19] then formulated the IM problem for the first time and presented two essential conclusions. First, IM issues can be modeled as a class of discrete optimization problems. Second, IM problems are NP-hard, which limits the development of existing IM approaches. Most of the current approaches rely on simple greedy calculations, traversing each node in the social network to calculate its marginal impact benefit. Nodes with larger marginal impact benefits are then included in the seed set S. The formation process can be expressed as follows.

    uargmaxu(VS)σ(Su)σ(S) (2.3)

    where the value of σ(S) represents the propagation range of a node set S, typically measured by the number of activated nodes. To construct the final seed set, greedy methods have been commonly employed to select the nodes with the highest influence benefit continuously. However, these methods have been criticized for their low efficiency and high time complexity, making them impractical for large-scale networks. As a result, recent research has focused on improving the extensibility and efficiency of the IM problem.

    Most research on IM is based on traditional propagation models such as IC and LT [20] and their variations. However, some studies have shown that the IC and LT models may not accurately approximate influence. To address this issue, Oriedi et al. [22] proposed a selective breadth-first traversal algorithm that efficiently generates an optimal seed set for IM. According to their argument, using models like the IC and LT models may result in an incorrect influence estimation. The authors have proposed an algorithm to create the best seed set for maximizing influence. They have tested their method using real data and proved that it is better than traditional IM algorithms. Oriedi et al. have effectively developed a more precise approach for modeling social network influence. Similarly, Sun et al. [23] introduced the self-Aactivation IC (SAIC) model that incorporates self-activation as an additional factor in influence propagation, where nodes can be self-activated and selected as seeds. They characterized two optimization problems arising from self-activation: preemptive IM (PIM) and boosted PIM (BPIM). Specifically, the PIM problem involves identifying nodes that can reach the most number of nodes before other self-activated nodes if self-activated. In contrast, the BPIM problem aims to select seeds that are guaranteed to reach the most number of nodes before other self-activated nodes. They proposed scalable algorithms for both PIM and BPIM to address these challenges and assessed their approximation guarantees. The results of their study indicate that the algorithms perform much better than baseline methods, particularly for the PIM problem and the BPIM problem when there are varying self-activation behaviors among nodes.

    Guo and Wu [24] investigated adaptive influence maximization with multiple activations problems, which take into account that not all users are willing to become influencers in the seed set. The researchers addressed a problem wherein each user is connected with a probability of activation as a seed, allowing for multiple triggers. To mathematically model this scenario, Guo and Wu have proposed a novel concept called adaptive-dr-submodularity, defined on the domain of an integer lattice, to maximize an adaptive monotone and dr-submodular functions while satisfying the expected knapsack constraint. This problem has not been previously investigated in existing studies, necessitating a comprehensive exploration of its approximability. They have developed a strategy that combines an adaptive greedy policy with sampling techniques to tackle the challenge of estimating expected influence spread while maintaining the approximation ratio and reducing time complexity. Other related work can be found in [25,26,27,28]. Luo et al. [25] have proposed the iterative competitive opinion maximization model, which aims to maximize the total opinions in competitive scenarios by combining user opinions and rival strategies. Unlike existing IM approaches, this model effectively suppresses the propagation of negative opinions and identifies optimal responses to opponents' seed node choices. The authors employ an iterative inference algorithm based on the greedy strategy to reduce computational complexity and achieve optimal outcomes. Zhang and Zhang [26] investigated the computational complexity of IM and analyzed the approximation guarantee of the greedy algorithm within the generalized model. Their research introduces a coordination game model that offers a game-theoretic perspective on IM. This model extends existing frameworks such as the majority vote model and the LT model. Furthermore, the incorporation of strategies to improve the algorithm's performance represents a significant contribution to the existing body of literature. However, as mentioned in the introduction section, every user in a social network plays a role in disseminating information. The previous IM studies mentioned above ignore the global-scale role approximation of users in the network. Liu et al. [27] introduced CONE, an active learning framework designed to address the estimation of user opinions in multi-round campaigns involving influence propagation. Their methodological approach to modeling user preference data is notable for their ability to handle scenarios in which prior knowledge of user opinions is unavailable. This approach holds practical implications, particularly in viral marketing, and including precision advertising and reputation management domains. Banerjee et al. [28] have presented a pioneering model, termed UIC, to overcome the existing constraints in the literature. The UIC model stands out by integrating users' economic factors into their product adoption and purchase decisions, aiming to maximize social welfare and foster customer loyalty within the network. Additionally, the authors shed light on the underexplored realm of complementary items, which has received limited scrutiny in previous studies on multiple items.

    Several recent studies on IM have effectively utilized deep learning techniques to identify and evaluate user influence in social networks [29,30,31,32,33,34,35,36]. These studies have shown promising results in the area of improving the performance of IM algorithms. Keikha et al. [29] have presented a novel methodology to tackle the challenge of IM on interconnected networks, employing deep learning techniques. Their proposed algorithm harnesses the power of deep learning for feature engineering, allowing for the preservation of both local and global structural information. By showcasing monotonicity and submodularity, the algorithm provides an assurance of an optimal solution. Notably, this study pioneers the utilization of network embedding to address the IM problem, marking a significant advancement in the field. Zhan et al. [30] proposed a general framework called NE-IM that leverages representation learning to address computational cost and improve stability. NE-IM contains two components: structure-based embedding and feature-based embedding. Their work incorporates heterogeneous information in IM models and applies representation learning to improve the efficiency and accuracy of IM models. Tian et al. [31] proposed two topic-aware social influence propagation models based on IC and LT models and developed a deep influence evaluation model to evaluate the user influence under different circumstances. They encoded the feature of each node by a vector, which enabled them to construct a solution efficiently without considering the complex graph structure. Their network learns a generalized heuristic framework to solve the NP-hard TIM problem using meta-learning, without requiring specialized knowledge and improving advertising injections. Li et al. [32] have presented a framework aimed at maximizing market influence in the USA domestic air passenger transportation market by adjusting flight frequencies. They used neural networks to predict market influence while considering several features such as air carrier performance features and transportation network features. They integrated neural networks to predict market influence and developed an adaptive gradient ascent method for solving the nonlinear optimization problem in flight frequency optimization. Zhang et al. [33] designed a network dynamic GCN to extract the in-depth structural information of social networks for IM. The proposed algorithm utilizes a leader fake labeling mechanism to generate node labels that are helpful for seed node selection during training. Finally, a heuristic method based on the Mahalanobis distance was developed to select influential seed nodes with learned node representations. Li et al. [34] suggested a Gaussian propagation model based on social networks and a multi-dimensional space modeling approach for propagation simulation. Their approach uses an improved CELF algorithm to accelerate the IM algorithm and evaluate the proposed technique based on theoretical proofs. Li et al. [35] then proposed a new approach to IM in social networks that takes into account multi-dimensional characteristics such as user emotions and group features. Specifically, Li et al. defined user emotion power and cluster credibility as measures of the interaction effects of individual emotions and proposed a potential influence user discovery algorithm based on an emotion aggregation mechanism to locate seed candidate sets. Li et al. [36] proposed a novel adaptive agent-based evolutionary approach to solve the IM problem in dynamic and large-scale social networks. A key component of the proposed approach is an adaptive solution optimizer that drives the evolutionary process and adapts candidate solutions dynamically. Motivated by the success of these works, our paper aims to take the next step and integrate the global role information of users in the final embedding vector using network embedding. By incorporating this additional information, our proposed method will further enhance the accuracy and effectiveness of IM in social networks.

    Network representation learning, also known as network embedding [], has garnered significant attention in recent years. This technology aims to transform a network's features into a low-dimensional continuous representation matrix while retaining the network structure and inherent properties. Recent advances in deep learning have enabled researchers to generate node embeddings through social network analysis techniques, such as DeepWalk [38], LINE [39], and node2vec [40]. These techniques utilize a prearranged random walk strategy to construct a corpus that displays the connections between the network components while preserving the characteristics of the network structure. The SkipGram model [41] is employed to acquire the node vector representation of a network. This model uses the context of words to identify the underlying relationships between nodes in the network. After an extensive process, the low-dimensional embedding representations of the nodes in the network are established, allowing a greater understanding of the network structure and the underlying relationships between nodes. Although these random walk methods have been proven to achieve better performance in network embedding, they ignore nodes' global structure and properties. Analyzing these global structures and node characteristics is essential to understanding the network accurately. Consequently, a few investigators have started to integrate network exploration techniques with other node properties. For example, Keikha et al. [42] devised a network embedding algorithm, community aware random walk for network embedding (CARE), that aims to conserve the local neighborhood and community information of a network while maintaining its global structure.

    Drawing on prior literature, we innovatively utilized random walks to extract the embedding matrix of the target network. Diverging from previous studies, our novel approach places emphasis on incorporating the user's global role information. This integration enables a comprehensive representation of roles and their local neighbors within the network. As a result, our methodology provides an enhanced perspective of the user's network position and their potential associations with other users.

    Information dissemination is a complex process due to the dynamic influence of one user on another [43]. The structural attributes of users in a social network reflect their roles in different communities. In this context, the primary challenge is to understand how the network structure affects the dissemination of information in a role-divided scenario. Most of the existing random walk methods based on the network structure only consider the influence of the direct domain nodes in a network, such as edge propagation probabilities between two nodes, while ignoring the roles of users in the network. Users with similar roles in the network tend to have similar structural attributes, and previous research methods have not accurately captured this feature.

    Figure 1 shows a classic social network scenario. Each node in the network represents a user, and the connection table between the nodes indicates the relationship between the users. In addition, the shared colors (yellow or red) in the figure imply that these nodes have similar global roles. Two communities, labeled as C1 and C2, are also depicted in the figure, each having its own opinion leaders (yellow nodes 1 and 4) that usually have similar attributes, such as higher node degrees. Red nodes 2 and 3 span multiple communities and typically play a critical role in the exchange of community information. Such red users are generally called structural hole nodes in a social network. This example highlights two essential aspects of following users on social networks:

    Figure 1.  Case network.

    1. Similar user roles usually have similar attributes;

    2. Different user roles have distinct functions in the exchange of information.

    The global role information of users in the network plays a vital role in information dissemination. In the traditional random walk sampling process, first-order or high-order neighbor nodes are considered, but the similarity of users with similar global roles is overlooked. In network representation learning, we hope that similar nodes in the network will eventually have similar vector representations. Therefore, users with comparable global roles should have corresponding vector representations. However, conventional or biased random walks cannot accurately approximate the user's global role. This paper addresses this limitation by incorporating the user's global role into the traditional random walk process. By sampling from the training corpus, we obtain the vector representation of each node. In the upcoming research, the aim is to investigate the role division of users in the network. The problem will be approached from two perspectives. First, the focus will be on CGURD. Second, the issue of user role division will be addressed in greater detail.

    In a given social network G(V,E), it is possible to represent its attributes or structural characteristics using a matrix A of dimensions |V|×D, where D represents the embedded dimension in A|V|×D. Users in the network with similar attributes or structural characteristics are expected to belong to the same role set. This study aims to map each user Vi to its corresponding role Rj in the set of user roles R=R1,R2,...,RK. It is assumed that user roles in the network can be classified into K categories where K is significantly smaller than |V|, i.e., k|V|. Our aim is to determine a mapping function ϕ:ViRk that can map each user to its role R based on its attributes or structural information.

    In network representation learning, the concepts of coarse-grained and fine-grained refer to two distinct levels of abstraction concerning the network graph. Coarse-grained clustering aims to consolidate nodes to maximize their similarity within groups while minimizing the similarity between groups. This method typically produces larger clusters consisting of nodes with similar properties or roles in the network. Conversely, fine-grained clustering aims to group nodes with highly specific features or roles, resulting in smaller clusters with nodes possessing more precise properties or roles within the network.

    Coarse-grained clustering typically yields smaller clusters comprising nodes with more specific properties or roles, facilitating the identification of larger-scale patterns and communities in the network. This approach is especially advantageous when computational efficiency is a priority. In contrast, fine-grained clustering focuses on identifying highly specific patterns or roles within the network. As a result, this approach may generate a larger number of clusters and require more computational resources. Nevertheless, the fine-grained approach offers valuable insights into the intricate structural properties and relationships present in the network.

    We can intuitively express the simple mapping of vector Ai by using either its cumulative sum or average value. Specifically, this can be expressed as follows:

    ϕ(x)=R(x1+x2+x3+...+xD)or=R((x1+x2+x3+...+xD)/D) (3.1)

    The vector x=[Ai1,Ai2,Ai3,...,AiD] is obtained from the matrix A, where R(x) represents the specific user role of x. This means that when a vector value x is input, its corresponding role category is output. It should be noted that if the matrix A represents the structural characteristics of users, such as the adjacency matrix of social network G, then the sum of features for each user represents the degree of its node. Intuitively, the mapping relationship described above is divided based on the node degree of users.

    Unfortunately, Eq (3.1) is not interpretable if the matrix A represents the attribute characteristics of the nodes. Therefore, we need an alternative approach to address this issue. In this paper, we introduce the Non-negative matrix factorization (NMF) algorithm to handle this problem. The process of obtaining user roles from the user characteristic matrix can be represented in Figure 2:

    Figure 2.  Diagram of NMF decomposition of user characteristic matrix A.

    Based on the concept of NMF matrix decomposition, the dimensionality of the user characteristic matrix A|V|×D can be reduced using the following iterative formula:

    A|V|×DR|V|×M×FM×D (3.2)

    In the NMF algorithm, we utilize the search matrix R|V|×M=[r1 r2 rM]R+|V|×M and the coefficient matrix FM×D=[f1 f2 fD]R+M×D to reduce the dimensionality of the user characteristic matrix A|V|×D. Among them, M is the number of basis vectors and is often much smaller than |V| or D, i.e., M|V|,MD. In this paper, the matrix R is regarded as a user role matrix, where each row represents the role feature vector to which the user belongs. On the other hand, the F matrix represents the probability of each role to which each user belongs. We aim to minimize the loss function:

    L(R,F)=argminR,F(12ARF2+R(R,F))s.t. R,F0 (3.3)

    The final user role matrix R is obtained after minimizing the loss function with a regularization penalty R(R,F). Afterward, the matrix RR|V|×M is partitioned into K disjoint sets of nodes V1,V2,...,VK by solving the k-means objective as follows:

    minVi,i[1,K]Kj=1riVjricj2,where cj=uiVjri|Vj| (3.4)

    In the process described above, the user role division algorithm can be described as Algorithm 1.

    Algorithm 1 CGURD(A, K, max_iter)
    Input:
            The matrix of user's characteristic AR|V|×D
            Number of user role types K
            The number of algorithm iterations iter
    Output:
            User role partition dictionary RoleDic
    1:  Initialize dictionary RoleDic to empty
    2:  Initialize the value of M to satisfy M|V|,MD
    3:  Perform SVD decomposition on initial matrix A
    4:  Randomly initialize RR|V|×M, FRM×D
    5:  For iter in range(1, max_iter + 1) do
    6:         If L(R,F)1e4 then
    7:                 Update matrix R by gradient descent
    8:                 Update matrix F by gradient descent
    9:          else
    10:                 break
    11:         end if
    12:   end for
    13:  Perform k-means clustering by applying Eq (3.4).
    14:  Get node label and map to RoleDic
    15:   return RoleDic

     | Show Table
    DownLoad: CSV

    To analyze the characteristics of user roles during information dissemination in online social networks, this study classifies all users into three categories: opinion leaders, spanner holes, and ordinary users. The definition and primary properties of a node are illustrated in Figure 1. using a simple example.

    Opinion leader: This refers to the minority of individuals at the core of the network who serve as a crucial source of information and influence within the community, capable of shaping the attitudes of the majority. As illustrated in the figure above, the yellow node is located at the center of the community to which it belongs, representing an opinion leader.

    Structural hole users: Structural hole users are in a key position in the network but differ from opinion leader nodes in terms of high influence. They significantly impact the depth and breadth of information dissemination by acting as bridges between different communities. As demonstrated in the above figure, the red nodes represent such users.

    Ordinary users: In the context of online social networks, ordinary users refer to those who do not possess the characteristics of structural holes or belong to a group of opinion leaders. Despite not having a central position in the network, ordinary users represent the majority of users and are considered edge users. They play a crucial role in information dissemination. In the presented figure, the white nodes depict ordinary users, emphasizing their significance as an integral part of the network. Although ordinary user nodes may not directly affect the global structure and evolution of the network like influential user nodes, they are also an indispensable part of the social network. Ordinary users nodes play the following roles in the benefits of social networks:

    ● Provide content: Ordinary users can provide rich and diverse content to social networks, attract more users to join the network and increase the value of the whole social network.

    ● Spreading information: Ordinary users can spread information and opinions by their own behavior, so they can help content and opinion diffusion by spreading and reposting even if they have no influence.

    ● Guide the diffusion of the network: Ordinary users establish their own social relationships, improve their exposure rate, and then attract more ordinary users like them to join the network, thus contributing to the prosperity and development of social networks.

    Online social network users exhibit several significant traits, prompting the search for a viable approach to differentiate user roles based on these attributes.

    (1) Opinion leader influence

    The present study focuses on identifying opinion leaders within the network by analyzing both the local and global characteristics of users and studying each node's influence. In the information dissemination process, the local influence that node u has on node v is determined by two main factors. First, the influence of node u itself is typically evaluated by its degree within the social network. Second, the number of mutual friends of node u that have an influence on node v which can be measured by the Jaccard coefficient.

    Infuv=α1D(u)+α2|Nei(u)Nei(v)||Nei(u)Nei(v)| (3.5)

    where, Infuv represents the local influence of node u on node v. D(u) is an expression related to 1-hop neighbors of user u, which is applied to measure the local influence of user u. Nei(u) is the set of direct neighbors of u. Jaccard's coefficient |Nei(u)Nei(v)||Nei(u)Nei(v)| is a widely-used measure to estimate the mutual friends of nodes u and v, and it is adopted to calculate the local influence of nodes u and v. The balance-parameters α1 and α2 satisfy α1+α2=1. The formula to calculate D(i) is as follows:

    D(i)=Nei(i)KGNei(k) (3.6)

    To calculate the influence value for node i on its neighbors, the influence-gathering equation is used. This equation takes into account the local influence of the node i on node v and the influence of each node by other nodes. After obtaining the local influence of a node, we can calculate the influence value for node i on its neighbors using Eq (3.7):

    Infi=1|N(i)|vN(i)Infvi (3.7)

    where N(i) is the neighbor set of node i. In terms of the global influence of nodes in social networks, this study focuses on the betweenness centrality of nodes.

    B(u)=v,k,uV,vkuPvukPvkˆB(u)=B(u)vuku,vPvukPvk (3.8)

    Equation (3.8) defines the betweenness centrality of a node, which is used to determine the global influence of nodes in social networks. Here, Pvk represents the number of shortest paths between two nodes v and k, while Pvuk represents the number of shortest paths between nodes v and k passing through node u. ˆB(u) stands for the normalized global influence. Finally, we can obtain the betweenness centrality of node u.

    This study combines local and global structural information to obtain the influence of node i in the entire network.

    OLIu=β1Infu+β2B(u) (3.9)

    where OLIu represents the opinion leader influence OLI score of node u.

    In order to achieve a balance between global and local influences in the calculation of OLIu, the balance parameters β1 and β2 are utilized. These parameters are designed to adjust the relative weight of each factor, and they are subject to the constraint that their sum must equal 1. By combining global and local structural information, the opinion leader index of each node can be determined. The process of identifying opinion leaders in social networks is described in Algorithm 2.

    Algorithm 2 OLI(G, α1, α2, β1, β2, k)
    Input:
            Network: G(V,E)
            Node local influence balance parameters: α1 and α2
            OLI balance parameters: β1 and β2
            Number of nodes selected: k
    Output:
            Top k opinion leader set: OLIsList
    1:  Initialize OLIsList to empty
    2:  Initialize the list OLIsVal to store the OLI value of each node
    3:  for u in V do
    4:         Get D(u) by using Eq (3.6)
    5:         Initialize temporary variable val to zero
    6:         Calculate the betweenness centrality of nodes in network by using Eq (3.8)
    7:         for v in Nei(u) do
    8:                 Get by equation |Nei(u)Nei(v)||Nei(u)Nei(v)| and store into temp
    9:                  val = val + temp
    10:          end for
    11:         Calculate Infu=1kGlen(Nei(k))val (reference Eq (3.7))
    12:         Get betweenness centrality of node u and store into B(u)
    13:         Get OLIu by using Eq (3.9)
    14:         Append OLIu to OLIsVal
    15:  end for
    16:  Sort the node by score
    17:  Get top k nodes
    18:   return OLIsList

     | Show Table
    DownLoad: CSV

    As presented in Table 2, we employed diverse methods to assess the influence of nodes in the case network, which is illustrated in Figure 1.

    Table 2.  A case study to compare the calculation results for OLI.
    Node DC BC CC EC OLI
    1 0.5000 0.6040 0.5380 0.5790 0.3830
    2 0.1430 0.3850 0.5190 0.2540 0.2120
    3 0.1430 0.0769 0.4000 0.1090 0.0585
    4 0.4290 0.5110 0.5000 0.2510 0.3250
    5 0.2140 0.0055 0.3780 0.3510 0.0577
    6 0.1430 0.0000 0.3680 0.2840 0.0388
    7 0.1430 0.1040 0.4120 0.2100 0.0722
    8 0.0714 0.0000 0.3410 0.0767 0.0100
    9 0.1430 0.0000 0.3500 0.1100 0.0438
    10 0.1430 0.0000 0.3680 0.2840 0.0388
    11 0.1430 0.0000 0.3680 0.2550 0.0429
    12 0.1430 0.0000 0.3680 0.2550 0.0429
    13 0.2140 0.0934 0.3890 0.1470 0.0892
    14 0.1430 0.0000 0.3680 0.1220 0.0396
    15 0.1430 0.0000 0.3500 0.1100 0.0438
    sum 2.8584 1.7798 6.0170 3.3977 1.4982

     | Show Table
    DownLoad: CSV

    To evaluate the effectiveness of our proposed approach, we compared it against several well-known centrality measures, including degree centrality (DC), betweenness centrality (BC), closeness centrality (CC), and eigenvector centrality (EC). The final row of Table 2 displays the sum of values for each method. It is worth noting that the sum of the respective columns for each method is different. In order to visualize the data more intuitively, we employed a stacked line chart to demonstrate the trends in the different node measurement methods within the case network, as illustrated in Figure 3.

    Figure 3.  Stacked line graph of the changing trend of various node measurement methods for the case network.

    The network structure depicted in Figure 1 reveals that node 1 and node 4 have higher centrality, which is consistent with the trends illustrated in Figure 3 for all methods. Figure 3 indicates that the proposed OLI method exhibits a similar trend as the other methods, but with a higher degree of discrimination. Therefore, compared to the other methods evaluated in Table 2, the method proposed in this paper performs better. For the case network structure of Figure 1, we set α1 and α2 to 0.8 and 0.2, respectively, and β1 and β2 to 0.5 each. Since the network structure is small, this study emphasizes the node's own influence when computing the local influence of the node. The local and global structural information of the nodes are integrated, and the same weight is assigned to the node's local influence and global influence to calculate the final OLI.

    (2) Structural hole score

    Burt's theory of structural holes [44] explains the competitive relationships in social networks. In the realm of social networks, it is a common occurrence for individuals with similar professional or personal interests to seek each other out and form tight-knit communities. The ties between these groups, however, tend to be comparatively sparse. In network parlance, nodes that serve as inter-group conduits, known as "structural holes", play a crucial role in facilitating the exchange of information across community boundaries. As shown in Figure 1, nodes 2 and 3 act as bridges for communication between two communities. The ability of a node to utilize structural holes is measured by the network constraint coefficient, as shown in Eq (3.10). A smaller network constraint coefficient indicates a greater possibility of structural holes, which can be beneficial for information dissemination.

    The network constraint coefficient value for node u is denoted by NC(u):

    NC(u)=vNei(u)(wuv+kNei(v)wvkwku)2,(k,u,vVand ku,v) (3.10)

    where, wuv represents the ratio of the energy invested by node u to maintain the relationship with node v to the total energy invested by node u, as shown in Eq (3.11).

    wuv=weightuvkNei(u)weightuk (3.11)

    Equation (3.10) is applied to calculate the network constraint coefficient value for all nodes in the network. In an unweighted graph, the edge weight weightuv is equal to 1 if there is a connecting edge between node u and node v, and it represents the weight value of the edge from node u to node v otherwise. After calculating the network constraint coefficient values for all nodes, we can identify the first k nodes with smaller values as the target structural hole nodes.

    (3) Ordinary nodes

    The selection thresholds for opinion leaders and structural hole users in the network are determined as γ1 and γ2, respectively, based on the findings of Wu et al. [45]. According to their study, only 1% of users in a network are considered as opinion leaders or structural hole users. However, they play a crucial role in creating or participating in 50% of the links in the network. To obtain the set of ordinary user nodes in the network, Equation 3.12 is utilized.

    Or=VOpSt,(|Op|=|V|γ1 , |St|=|V|γ2) (3.12)

    where Or represents a collection of ordinary nodes, Op represents a collection of opinion leader nodes, St represents a collection of structural hole nodes, and V represents all nodes in the network. Finally, the process of FGURD of nodes in the network can be described by Algorithm 3.

    Algorithm 3 FGURD(G, α1, α2, β1, β2, γ1, γ2)
    Input:
            Network: G(V,E)
            Node local influence balance-parameters: α1 and α2
            OLI balance-parameters: β1 and β2
            Threshold for the number of opinion leaders and structural hole users: γ1 and γ2
    Output:
            User role partition dictionary RoleDic
    1:  Initialize dictionary RoleDic to empty
    2:  OLNumber=|V|γ1
    3:   SHNumber=|V|γ2
    4:  Get OLNumber opinion leaders in the network via Algorithm 1.
    5:  Initialize the list SHsList to empty
    6:  for u in V do
    7:         Calculate network constraint coefficient value by Eq (3.10) and Eq (3.11).
    8:         Add node network constraint coefficient value to SHsList
    9:  end for
    10:  Sort SHsList in reverse order; select SHNumber nodes
    11:  Get ordinary nodes by Eq (3.12).
    12:  Map the node to the corresponding role and add them to RoleDic
    13:  return RoleDic

     | Show Table
    DownLoad: CSV

    In the previous section, the process of identifying user roles in social networks was discussed. To obtain network embedding representations of users that preserve the local structure and global role approximations, a random walk-based network embedding approach is adopted, as illustrated in Figure 4. First, the role of nodes in the network is calculated using either Algorithm 1 or Algorithm 3. Second, the first-order or second-order local approximation of the node is captured by the random walk of the topological structure, and the approximation of the global role of the node is preserved through the random walk of the node role. By combining all random walks into one corpus, node embeddings can be learned by training the SkipGram model with negative sampling [46]. The SkipGram model can predict the conditional probability of co-occurrence among words within a fixed window size, and maximizing this probability allows the model to obtain vector representations of words in the corpus. The objective of the SkipGram model is to maximize the average log probability of a sequence of training words w1, w2, w3, ..., wT, as shown in the equation above.

    max1TTt=1winjwin,j0logp(wt+jwt) (3.13)

    where the parameter win represents a predefined window size, with a larger value leading to more additional training examples and potentially higher accuracy. The softmax function is employed to estimate the probability distribution of p(wt+jwt), which is defined as follows:

    p(wOwI)=exp(vTwOvwI)Ww=1exp(vTwvwI) (3.14)

    where the word representations of "input" and "output" data are denoted as vw and vw, respectively. W is the total number of words in the vocabulary.

    Figure 4.  Addition of user role random walks to train the network embedding.

    In the context of network embedding, the random walk algorithm is commonly used to generate sequences of nodes. Starting from an initial node uG, the algorithm randomly selects a neighboring node and moves to it. This process is repeated for a predefined number of steps. A method for network embedding called Role-based Random Walk Network Embedding (RbNE) has been developed, and its pseudocode is presented in Algorithm 4. RbNE takes a social network as input and outputs low-dimensional representations for each node in the network, where nodes with similar roles will have similar representations. To obtain the node representations in RbNE, each node in the network is first divided into roles using either Algorithm 1 or Algorithm 3, which correspond to CGURD and FGURD, respectively. Then, the role of the node is used to perform random walk simulation, resulting in the node's representation. The random walk network embedding methods that are divided by user roles in Algorithm 1 and Algorithm 2 are named RbNE-CG and RbNE-FG, respectively. The parameter settings for the algorithms are detailed in the corresponding sections.

    Algorithm 4 RbNE(G, len, number, win, d)
    Input:
            Social network: G(V,E)
            Maximum length of random walk: len
            Number of random walks: number
            Window length: win
            Final representation size: d
    Output:
            Matrix of node representations: ΦR|V|×d
    1:  Initialize walks to empty
    2:  Divide user roles through Algorithm 1 or Algorithm 3, and store the results in RoleDic
    3:  for node u in V do
    4:         Get the list of roles Rolesu=RoleDic[u]
    5:         walk1 = TraditionalRandomWalk(G, u, len)
    6:          walk2 = RolebasedWalk(G, u, Rolesu, len)
    7:         Append walk1 to walks
    8:         Append walk2 to walks
    9:   end for
    10:  SkipGram(Φ, walks, win)
    11:   return Φ

     | Show Table
    DownLoad: CSV

    The traditional random walk method (line 5, Algorithm 4 captures the local approximation of nodes, similar to Deepwalk and node2vec. In contrast, the random walk method based on node role (line 6, Algorithm 4 captures the global node approximation. As a result, the final training corpus walks contains both the local neighbor approximation relationship and the global role approximation relationship of each node.

    Embedding techniques in network analysis entail the inclusion of neighboring nodes, degrees, labels, and other relevant attributes to impart specifications onto the individual nodes within the network. This approach unveils valuable associations and connections between nodes, ultimately amplifying the efficacy of both network analysis and machine learning methodologies.

    The representations of all nodes in the network G are now available and are denoted as ΦR|V|×d. To measure the relationship between any two nodes, the cosine similarity of their representation vectors can be calculated directly using the following equation:

    Sim(u,v)=ΦuΦvΦu×Φv (3.15)

    The relationship score between two nodes u and v is defined as Sim(u,v) in our approach. A higher score indicates a higher probability of node u influencing node v. Thus, a new logically structured network called a propagation probability network can be constructed, where the similarity between two nodes is determined by Eq (3.15). To simplify the network, a similarity threshold θ is introduced. Only when their similarity score is greater than θ is a logical connection edge added between two nodes u and v. Hence, the adjacency matrix representation of the connection strength between any two nodes in the network can be described as follows:

    pu,v={Sim(u,v),if Sim(u,v)θ0,otherwise (3.16)

    where θ represents the hyper parameter and θ belongs to the interval (0,1). By applying the weight calculation method, we can obtain the desired new logical structure network. In this structure, pu,v denotes the probability of information propagation from node u to node v. Assuming the independence of influence probabilities among users, the probability of node i being activated by its neighbor Nei(i) can be computed using the propagation probability of its friends:

    Pr(Vv)=1uNei(v)(1pu,v) (3.17)

    Similarly, the total influence spread of all non-seed nodes under the influence of the seed node set S can be quantified for each vertex uV:

    Pr(VS)=1|V|uV[1vS(1pu,v)]=11|V|uVvS(1pu,v) (3.18)

    The objective of the IM task is to increase the number of activated nodes influenced by the seed node set S, which is equivalent to maximizing the value of Pr(VS). Therefore, our optimization goal can be formulated as follows:

    argmaxS(Pr(VS))=argmaxS[11|V|uVvS(1pu,v)]=argminS[1|V|uVvS(1pu,v)] (3.19)

    As the direct optimization of the optimization goal is not feasible, a greedy heuristic algorithm is utilized in this study. Specifically, for undirected networks, a Connected components [19] type of heuristic is employed to compute the score for each node; and subsequently, the k nodes with the highest scores are chosen. Algorithm 5. presents the three-step procedure, which includes the following:

    1. Calculation of the similarity between each user utilizing the network embedding matrix Φ and construction of a new logical network structure matrix A (lines 2–3).

    2. Random deletion of edges according to their weights to acquire connected components in the network (lines 11–20).

    3. Assign each node a weight value based on the number of its neighbors and select the k nodes with the highest weight values as the seed node set (lines 21–28).

    By implementing this heuristic algorithm, the seed node set S can be effectively selected.

    The proposed RbneIM algorithm (Algorithm 5) has a time complexity of O(R|V|k), where R and k are both constants. The outer loop runs for a constant number of iterations R, while the inner loop traverses the network and the current cropped subgraph, which has a constant size k. In contrast, the RbNE algorithm (Algorithm 4) has greater time complexity determined by the most expensive of its three parts. First, Algorithm 3 is called to perform role division, which has a time complexity of O(|V|n), where n is the largest number of node neighbors in the network |Nei(i)|. Second, in the sampling process, the algorithm iterates according to the predefined sampling length len (constant) and randomly adds nodes to the sampling sequence according to predefined rules, which takes O(|V|len) time. Finally, the SkipGram algorithm has a time complexity of O(|V|). Therefore, the time complexity of the RbNE algorithm is O(|V|)(O(|V|n)+O(|V|len)+O(|V|)). Since n, k, and len are all constants, the final time complexity of the proposed RbneIM algorithm is O(|V|2). Several baseline methods utilize matrix operations, but this approach can lead to memory insufficiency when dealing with large-scale graphs. In contrast, the RbneIM method employs heuristic algorithms that significantly reduce the computational complexity, resulting in strong scalability.

    Algorithm 5 RbneIM(G, Φ, θ, P, R, k)
    Input:
            Social network: G(V,E)
            Embedding matrix of G: embeddingR|V|×d
            Hyper parameter of connecting edges: θ
            Propagation probability under Independent Cascade: P
            Number of iterations: R
            Number of seed nodes: k
    Output:
            Selected node seed list: Seeds
    1: Initialize Seeds to empty
    2: Calculate the cosine similarity matrix A of each node in the embedding matrix Φ via Eq (3.15)
    3: According to Eq (3.16), A[A<θ]=0 processing to get logical network structure L
    4: Initialize node's score dict score={0:0,1:0,2:0,...}
    5: for i=1...R, do
    6:        G=deepcopy(L)
    7:        Randomly select blocked edges by (1P)pij and remove them from G
    8:        Initialize connected components dict ccDict to empty
    9:        Initialize node's visited list vis=[false,...]
    10:        Initialize the count variable index=0
    11:        for nodeG do
    12:                if not vis[node] then
    13:                        vis[node]=true
    14:                        ccDict[index++]=[node]
    15:                        nodes=G.neighbors(node)
    16:                        for neinodes do
    17:                                if not vis[nei] then
    18:                                        vis[nei]=true
    19:                                        ccDict[index].append(nei)
    20:                                        nodes.append(G.neighbors(nei))
    21:                                end if
    22:                        end for
    23:                end if
    24:                Sort ccDict according to size
    25:                for componentccDict do
    26:                        nodes=ccDict.values()
    27:                        temp_score=1len(nodes)
    28:                        for nodenodes do
    29:                                score[node]+=temp_score
    30:                        end for
    31:                end for
    32:        end for
    33: end for
    34: Select k nodes with the smallest score from score
    35: return Seeds

     | Show Table
    DownLoad: CSV

    This section begins by presenting the social network dataset and parameter settings employed in this study. Subsequently, the baseline algorithm used is briefly introduced, followed by an analysis of the experimental findings.

    This study utilized six public real-world datasets to provide varying-sized networks. This aimed to assess the feasibility and effectiveness of the proposed IM method. Table 3 presents a comprehensive overview of the datasets. The datasets were carefully selected based on their diversity, which includes different types of social networks, ranging from online social networks to co-authorship networks. Moreover, the datasets contain a varying number of nodes and edges, ranging from small-scale networks to large-scale networks, thus providing a diverse range of networks for our analysis. By using such diverse datasets, we aim to evaluate the performance of our proposed method under different network settings, which can help to enhance the generalizability of our findings.

    Table 3.  Statistics for the datasets used in the experiments, including the number of nodes (#Node) and the number of edges (#Edge).
    Dataset #Node #Edge
    Dolphins 62 161
    Facebook_Caltech36 769 16662
    NetScience 1591 5880
    Cora 2710 5430
    Ca-GrQc 4158 26850
    Facebook-Government 7057 89428

     | Show Table
    DownLoad: CSV

    (i) Dolphins* [47]. The dataset used in this study is an undirected social network consisting of 62 dolphins living in a community off of Doubtful Sound, New Zealand. The dataset encompasses frequent associations between the dolphins in the form of links between them.

    *http://www-personal.umich.edu/mejn/netdata/

    (ii) Facebook_Caltech36 [48]. A social friendship network extracted from Facebook consisting of people as nodes, with edges representing friendship ties.

    https://networkrepository.com/socfb-Caltech36.php

    (iii) NetScience [49]. The NetScience dataset is a co-authorship network that involves scientists working on network theory and experiments. A visual representation of the largest component of this network can be accessed via the URL.

    http://www-personal.umich.edu/mejn/centrality/

    (iv) Cora§. The Cora dataset is a collection of machine learning papers, and it includes the citation relationships between them. These relationships are used to construct the network topology for this dataset.

    §https://linqs.soe.ucsc.edu/data

    (v) Ca-GrQc [50]. The Ca-GrQc dataset is a collaboration network of arXiv General Relativity and Quantum Cosmology. It is derived from the e-print arXiv and includes scientific collaborations between author papers submitted to the General Relativity and Quantum Cosmology categories. The dataset covers papers submitted between January 1993 and April 2003.

    http://snap.stanford.edu/data/ca-GrQc.html

    (vi) Facebook-Government|| [51].The data collection process involved gathering information on the Facebook pages of politicians in November 2017. The resulting network is represented as nodes, which correspond to the politician pages, and edges, which indicate mutual relationships between them.

    ||https://networkrepository.com/fb-pages-government.php

    We have plotted the frequency distribution of user node degrees to characterize the Cora and NetScience datasets.

    The user node degree distributions for the Cora and NetScience datasets are presented in Figure 5, indicating a power-law distribution. This suggests that certain users are more susceptible to influence from their social connections.

    Figure 5.  Node degree distribution of users on Cora and NetScience. The x axis represents the node degree of users, and the y axis represents the number of such users (valued as loglog).

    This paper introduces three typical initial ranking methods and a state-of-the-art IM method to evaluate the comparative performance of the proposed RbneIM method.

    (i) Random: Nodes are initially ranked randomly.

    (ii) Degree centrality [52]. Degree centrality measures the influence of a node based on the number of its neighbors, with nodes having higher degrees being considered as more influential.

    (iii) Betweenness centrality [53]. The betweenness centrality measures the extent to which a node acts as a bridge along the shortest paths between other nodes. A node with higher betweenness centrality has a greater number of shortest paths passing through it. The betweenness of node u is calculated by Eq (3.8).

    (iv) Pagerank centrality [54]. The PageRank centrality measures the importance of a node based on the structure of the network. It was originally created to evaluate the importance of web pages by using their link structures. Since then, it has been applied in various fields, such as social network analysis, link prediction and recommendation analysis.

    (v) DeepIM [29]. The DeepIM algorithm is the first to employ deep learning techniques to solve the IM problem. It uses the CARE algorithm [42] to learn node embeddings. Cosine similarity is employed to measure similarity between nodes, k similar nodes are recorded for each node, and a set of seed nodes is selected through statistical analysis.

    (vi) GCNIM [33].The research contributes to the field of social network analysis by proposing a new technique that overcomes the limitations of traditional algorithms and deep learning-based approaches while achieving high performance and efficiency in the area of seed set identification for IM tasks.

    (vii) ABEM [36]. The approach utilizes agent-based modeling and genetic algorithms to effectively address the complex task of selecting key influencers in a distributed environment. By leveraging these techniques, the approach identifies users' influence capability and optimizes the influencer set's selection. This innovative solution tackles the challenge of capturing real-time user and diffusion features, enabling the accurate and efficient identification of key influencers.

    It is noteworthy that this paper presents two algorithms, namely CGURD (Algorithm 1) and FGURD (Algorithm 3), for role division. The role division outcome will have an impact on the sampling outcome of the final random walk process, leading to a different embedding representation vector of the node under the two algorithms. Therefore, the use of these two node partitioning algorithms will ultimately influence the selection of seed nodes. In this paper, the RbneIM algorithm is executed using Algorithm 1. and Algorithm 3. for node division, resulting in RbneIM-CG and RbneIM-FG, respectively.

    (i) RbneIM-CG: This model utilizes the CGURD algorithm to determine the global role of users in the network. The RbNE algorithm is then employed to perform the sampling of the training corpus. The final selection of seed nodes is accomplished through RbneIM.

    (ii) RbneIM-FG: Compared with the RbneIM-CG model, only the user role division algorithm is different.

    This section presents an analysis of the key techniques proposed in this paper and compares them with existing approaches to demonstrate the feasibility of the proposed approach. IM is the foundation for introducing and understanding influence dissemination within social networks.

    (i) Our proposed methodology presents several advantages over existing deep learning IM methods. It leverages network embedding techniques to assign attribute values to user nodes, allowing for a more comprehensive analysis of user influence. Unlike other methods that primarily focus on a single global factor or the node's own attributes, our approach also takes into account the influence factor between users, providing a more nuanced understanding of influence dynamics in social networks. Additionally, our methodology considers attributes at multiple levels of granularity, enabling a more fine-grained analysis and capturing the diverse factors that contribute to user influence.

    (ii) Our study presents an innovative algorithm for user role division, integrating both CGURD and FGURD to offer a comprehensive and refined approach. The CGURD component of our algorithm focuses on classifying users into distinct groups based on their overall network contribution, allowing for a broader understanding of user roles. In contrast, the FGURD aspect concentrates on analyzing the relationships between users and their adjacent nodes to identify more specific and localized user roles. By combining CGURD and FGURD, our algorithm provides a robust and precise user role division strategy that captures the intricacies of user dynamics in the network. Furthermore, the methods evaluated in this paper employ various network embedding techniques, as outlined in Table 4.

    Table 4.  A detailed comparison of the model proposed in this paper and other studies.
    Methods Node attributes Nodes selected
    DeepIM DeepIM preserves both global and local macro properties of user nodes by utilizing network embedding techniques of deep learning methods. Random walk is used to assign values to nodes.
    ABEM Represents users as autonomous and proactive agents that possess the ability to communicate with their neighbors, extract information from the local environment, and estimate their influence capacity. ABEM utilizes agent-based modeling to identify potential influencers in changing real-world networks. The search scope of ABEM is continually updated through user agents, which is a task efficiently executed by the proposed algorithms.
    These algorithms maintain the existing potential influencers while concurrently modifying parts of the solutions.
    GCNIM A network dynamic GCN with adaptive layers according to different network scales was designed to obtain the information representation of node position influence. This method incorporates a leader fake labeling mechanism that automates the generation of node labels to facilitate the selection of seed nodes during model training.
    Ours The global location influence (Algorithm 1) attribute and the influence attribute between nodes (Algorithm 3) Our method encompasses both the local neighbor approximation relationship and the global role approximation relationship for every node (Algorithm 4).

     | Show Table
    DownLoad: CSV

    The experiments conducted in this study used default values for various parameters mentioned in the paper. Specifically, the node local influence balance parameters α1 and α2 in Eq (3.15) were set to 0.8 and 0.2, respectively. The OLI score balance parameters β1 and β2 in Eq (3.5) were set to 0.5 and 0.5, respectively. In Eq (3.12), the thresholds γ1 and γ2 for opinion leaders and structural hole nodes were set to 0.2 and 0.1, respectively. Other parameters used in the experiments were set as follows: random walk length len=80, random walk number number=10 and embedding matrix dimension d=256. The SkipGram training window size was set to win=5, and the negative sampling frequency and learning rate were both set to 0.025. The threshold θ=0.5 was used to establish a connection edge between any two nodes of the new logical network in Eq (3.16). In the RbneIM algorithm, the propagation probability of the IC model was set to 0.5, and the number of algorithm iterations R=20. The non-default value parameters for each dataset are shown in Table 5.

    Table 5.  Non-default values of parameters applied in experiments for six datasets.
    Dataset θ len γ1 γ2
    Dolphins 0.7 140 0.14 0.16
    Facebook_Caltech36 0.9 80 0.18 0.12
    NetScience 0.5 80 0.12 0.18
    Cora 0.5 20 0.18 0.12
    Ca-GrQc 0.1 40 0.12 0.18
    Facebook-Government 0.7 60 0.16 0.14

     | Show Table
    DownLoad: CSV

    All methods were implemented using Python 3, and the experiments were performed on a Windows OS with AMD Ryzen 5 3500U, 2.10 GHz CPU and 16 GB memory. Details of our software and hardware environments were as follows: Windows 11, Python ver. 3.6.6, NumPy ver. 1.19.2, NetworkX ver. 2.1, Gensim ver. 3.8.3, Pandas ver. 0.24.2, Matplotlib ver. 2.2.3.

    In Eq (3.16), a threshold parameter θ was defined to create a new logical network structure, which directly affects the performance of the RbneIM model. Therefore, the analysis of θ parameters is performed first. Seed node sizes were selected based on the dataset scale, ranging from 2 to 20 with a stride of 2 for the Dolphins dataset, and from 5 to 50 with a stride of 5 for the remaining datasets. Experimental results are displayed in Figure 6, where θ was chosen as a value between 0.1 to 0.9 with a step size of 0.2. The figure shows that different datasets have different optimal θ values. The influence spread was considered for various numbers of seed nodes, and a counting method was used to evaluate the pros and cons of each θ in the current dataset. The best performing θ was then selected for each dataset value. Finally, the chosen values for θ were 0.7, 0.9, 0.5, 0.5, 0.1 and 0.7 for the Dolphins, Facebook_Caltech36, Netscience, Cora, CA-GrQc and Facebook-Government datasets, respectively.

    Figure 6.  Effects of different values of θ (see Eq (3.16)) in the RbneIM algorithm on different datasets.

    We present a comprehensive comparison of the influence spread achieved by different algorithms, namely random, DC, BC, PageRank centrality, DeepIM and RbneIM, utilizing the LT model. The corresponding results are illustrated in Figure 7 for six distinct networks. Upon examining smaller datasets, as depicted in Figure 7a for Dolphins and Figure 7b for Facebook_Caltech36, we notice that the influence spread generated by various models exhibit similar outcomes. However, our proposed RbneIM method maintained its superior effectiveness. As the dataset size increased, both DeepIM and RbneIM consistently outperformed the other approaches by a substantial margin, with RbneIM exhibiting the highest level of performance. Experiments on multiple datasets demonstrated the superior performance of the proposed RbneIM method.

    Table 6.  The selection ratio experiment for opinion leaders and structural hole nodes, where the horizontal axis is γ1, and the vertical axis is six datasets respectively.
    Dataset 0.02 0.04 0.06 0.08 0.10 0.12 0.14 0.16 0.18 0.20
    Dolphins 51.4 51.7 51.8 51.1 51.1 50.5 51.92 51.2 46.2 50.3
    Facebook_Caltech36 567.3 568.4 570.6 558.1 554.4 576.5 578.9 580.9 585.4 574.2
    NetScience 303.6 305.2 305.9 310.3 312.5 317.2 312.8 310.3 303.6 310.4
    Cora 1343.0 1260.6 1297.7 1320.8 1322.0 1342.3 1342.9 1368.5 1381.7 1368.1
    Ca-GrQc 1009.2 1024.1 1069.3 1096.2 1107.3 1202.3 1188.1 1172.2 1158.8 1103.4
    Facebook-Government 3603.6 3374.1 3033.1 3112.9 3277.4 3312.3 3557.0 3642.8 3413.6 3376.1

     | Show Table
    DownLoad: CSV
    Figure 7.  Comparison of the simulation results for LT models with various baseline methods and different numbers of seed sets.

    Additionally, the size of the seed nodes selected for each dataset varied due to the differences in dataset size. For example, in the Dolphins network, the seed node size [2,4,6,...] was selected, with a maximum of 20 nodes selected for the seed node set. For Facebook_Caltech36, a maximum of 50 nodes were selected, and for the remaining datasets, up to 200 nodes were selected. The average results of LT simulations for each of the six networks, with varying numbers of seed nodes, are reported in Table 7.

    Table 7.  Average of experimental results of different seed node selection algorithms on six networks.
    Dataset Random Degree Betweenness Pagerank DeepIM RbneIM
    Dolphins 13.6 17.1 19.0 17.4 33.6 39.6
    Facebook_Caltech36 25.2 41.7 258.6 111.3 370.9 429.3
    NetScience 122.8 187.9 186.6 179.4 320.2 421.9
    Cora 118.5 185.1 237.1 185.8 634.2 930.2
    Ca-GrQc 86.7 178.5 263.4 182.4 614.9 664.8
    Facebook-Government 242.7 341.3 459.6 297.7 1795.3 2037.5

     | Show Table
    DownLoad: CSV

    The average influence diffusion of each algorithm on six datasets with different seed node numbers, taken from 20 experiments was calculated in Table 7. The results indicate that our proposed RbneIM algorithm outperforms the baseline algorithms, particularly Random and DC. Random selects the seed node randomly from any network node, while DC centrality uses the number of neighboring nodes in one hop. BC and PageRank centrality calculate the number of shortest paths through a node and the importance of its links, respectively. DeepIM takes into account the node community structure factor in the network embedding and calculates node similarity to select seed nodes. However, these baseline algorithms do not consider users' global role similarity, which reduces their efficiency in selecting seed nodes.

    As the proposed network embedding algorithm relies on a sequence of random walk sampling, an analysis was conducted to examine the impact of different random walk lengths on the RnbeIM model. To this end, the experiment involved selecting random walk lengths len ranging from 20 to 200 with a step size of 20; the analysis results are presented in Table 8. Seed node sets were determined based on the size of the datasets, with a size of 20 for the Dolphins dataset and 50 for the remaining datasets. Corresponding to the step size, the number of seed node sets was calculated, and 200 rounds of LT model propagation simulation were carried out. The final results represent the average value, with one decimal place reserved. The analysis in Table 8 highlights that different step lengths of various datasets have a notable impact on the experimental outcomes. The optimal result is identified in bold font in the table, and its corresponding random walk length was selected as the parameter value on this dataset. Table 5 presents the selected parameter values.

    Table 8.  Effect of different random walk lengths len on the experimental results.
    Dataset 20 40 60 80 100 120 140 160 180 200
    Dolphins 53.5 56.8 53.3 54.8 55.1 56.0 60.1 53.3 53.5 53.0
    Facebook_Caltech36 587.8 621.8 612.7 624.3 595.7 577.4 581.4 595.8 561.7 560.0
    NetScience 615.8 591.4 606.6 617.7 612.4 593.1 597.7 596.3 608.0 596.7
    Cora 1336.6 1317.0 1315.8 1329.1 1315.7 1310.5 1295.8 1311.6 1266.4 1254.9
    Ca-GrQc 1081.7 1200.4 1060.4 1114.4 1098.9 952.0 1081.2 1021.3 988.7 986.0
    Facebook-Government 1130.6 2671.5 3530.8 2836.7 2482.8 2280.4 2258.7 2252.8 1944.6 2100.3

     | Show Table
    DownLoad: CSV

    In addition, a comparison was made between the RbneIM-FG and RbneIM-CG models proposed in this paper on six datasets. It is noteworthy that in the previous experiments, the RbneIM model used the FGURD (Algorithm 3.) algorithm by default to divide user roles in the network, which is the RbneIM-FG model. The experimental results are presented in Figure 8, which shows that the RbneIM-FG model outperforms the RbneIM-CG model.

    Figure 8.  Comparative experiments of RbneIM-FG and RbneIM-CG on six datasets.

    The results clearly demonstrate that the use of a global influence algorithm alone to select the seed set yields extremely low propagation efficiency. However, by leveraging the proposed FGURD algorithm to identify different influence roles, the efficiency of influence propagation is significantly improved. The observed discrepancy in experimental outcomes underscores the inadequacy of relying solely on global influence. The proposed model combining global and local information for network embedding achieved the best results on the six datasets, serving as a confirmation of the method's effectiveness on IM issues.

    The paper sets the thresholds for opinion leaders and structural hole nodes as γ1 and γ2 (as described in Eq (3.12), respectively. The values of γ1 and γ2 are set to 0.2 and 0.1, respectively, in the parameter setting section. It should be noted that these values may vary depending on the network structure. Here, we assumed that 70% of the nodes in any social network are ordinary nodes. To explore the impact of varying these two parameters, this study included an experiment for which the result is presented in Table 6. The number of seed nodes was set to a fixed value for each dataset, with different divisions made based on the dataset size. For example, the Dolphins dataset was set to 20, while the Facebook_Caltech36 and Netscience datasets were set to 50. The remaining three datasets were set to 200. We varied the value of γ1 from 0.02 to 0.2 with a step size of 0.02, corresponding to γ2=0.3γ1. The optimal results are displayed in bold font in Table 6, and the corresponding x-axis value was selected as the value of γ1 for the dataset, with 0.3γ1 being the value of γ2. The selected parameter values are shown in Table 5.

    The present paper introduces a novel network embedding algorithm, named RbNE, for social networks; it incorporates users' global roles into the embedding process. The proposed RbNE approach merges the CGURD and FGURD methods, aiming at gathering both the overall contribution of the user to the network and the relationships between the user and its neighboring nodes. This results in a more comprehensive representation of the user's global role and approximate user information. Building on this embedding method, we propose a greedy heuristic algorithm, RbneIM, to solve the IM problem by fully integrating the global role information and filtering out the seed set.

    Previous studies have encountered challenges in effectively integrating both local and global information concerning users in social networks. A notable limitation has been the neglect of the IM problems' sensitivity to the global roles of users. Additionally, there is a lack of comprehensive understanding regarding the potential contribution of global roles in identifying seed sets that exhibit substantial influence. To address these gaps, this paper proposes the RbNEIM approach, which considers users' global role as a crucial criterion in selecting seed sets and identifying users with the potential to maximize their impact on social networks. We evaluated RbNEIM on six popular social network datasets and compared its performance with state-of-the-art methods and recent baselines. The results demonstrate that our proposed method outperforms existing techniques, highlighting its superior performance in terms of solving IM problems. In future work, we will explore the optimization potential of graph neural networks and attention mechanisms to further enhance the performance of RbNEIM.

    Experimental analysis reveals the following: (1) RbNEIM can combine global and local information for network embedding, and it can comprehensively maintain the approximation between the user's global roles; (2) By integrating heuristic calculation and role embedding methods, RbNEIM can significantly improve the performance of the IM problem by considering the user's global role as an essential factor in selecting the seed set and identifying users who can spread the maximum influence in the social network; (3) The proposed method is robust to hyperparameter tuning. The insights gained from this study have the potential to advance the development of future social networks and IM problems.

    The authors declare they have not used Artificial Intelligence (AI) tools in the creation of this article.

    This work is supported by the Science and Technology Program of Sichuan Province (Grant nos. 2023YFS0424, 2022YFG0378) and the National Natural Science Foundation (Grant nos. 61902324, 11426179, and 61872298).

    The authors declare that there is no conflict of interest.

    [1] Petersen R (2012) Reactive secondary sequence oxidative pathology polymer model and antioxidant tests, Int Res J Pure Appl Chem 2: 247–285.
    [2] Singer S, Nicolson G (1972) The fluid mosaic model of the structure of cell membranes. Science 175: 720–731. doi: 10.1126/science.175.4023.720
    [3] Nicolson G (2014) The fluid-mosaic model of membrane structure: still relevant to understanding the structure, function and dynamics of biological membranes after more than 40 years. Biochim Biophys Acta 1838: 1451–1466. doi: 10.1016/j.bbamem.2013.10.019
    [4] Michael J, Sircar S, (2011) The Cell Membrane, In: Fundamentals of Medical Physiology, New York: Thieme Medical Publishers, 9–16.
    [5] Jeong M, Kang J (2008) Acrolein, the toxic endogenous aldehyde, induces neurofilament-L aggregation. BMB Rep 41: 635–639. doi: 10.5483/BMBRep.2008.41.9.635
    [6] Torosantucci R, Mozziconacci O, Sharov V, et al. (2012) Chemical modifications in aggregates of recombinant human insulin induced by metal-catalyzed oxidation: covalent crosslinking via Michael addition to tyrosine oxidation products. Pharm Res 29: 2276–2293. doi: 10.1007/s11095-012-0755-z
    [7] Rubenstein M, Leibler L, Bastide J (1992) Giant fluctuations of crosslink positions in gels. Phys Rev Lett 68: 405–407. doi: 10.1103/PhysRevLett.68.405
    [8] Nossal R (1996) Mechanical properties of biological gels. Physica A 231: 265–276. doi: 10.1016/0378-4371(95)00455-6
    [9] Barsky S, Plischke M, Joos B, et al. (1996) Elastic properties of randomly cross-linked polymers Phys Rev E 54: 5370–5376.
    [10] Ulrich S, Zippelius A, Benetatos P (2010) Random networks of cross-linked directed polymers. Phys Rev E 81: 021802.
    [11] Rodriquez F, (1996) 11.3 Polymer degradation, In: Principles of Polymer Systems, 4 Eds., Washington D.C.: Taylor and Francis, 398–399.
    [12] Dröge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82: 47–95.
    [13] Valko M, Leibfritz D, Moncol J, et al. (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39: 44–84. doi: 10.1016/j.biocel.2006.07.001
    [14] Floyd R, Towner R, He T, et al. (2011) Translational research involving oxidative stress diseases of aging. Free Radic Biol Med 51: 931–941. doi: 10.1016/j.freeradbiomed.2011.04.014
    [15] Sena L, Chandel N ( 2012) Physiological roles of mitochondrial reactive oxygen species. Mol Cell 48: 158–167.
    [16] Labunskyy V, Gladyschev V (2013) Role of reactive oxygen species-mediated signaling in aging. Antioxid Redox Signal 19: 1362–1372. doi: 10.1089/ars.2012.4891
    [17] Hill S, Remmen H (2014) Mitochondrial stress signaling in longevity: a new role for mitochondrial function in aging. Redox Biol 2: 936–944. doi: 10.1016/j.redox.2014.07.005
    [18] Schieber M, Chandel N (2014) ROS function in redox signaling and oxidative stress. Curr Biol 24: R453–R462. doi: 10.1016/j.cub.2014.03.034
    [19] Girotti A (1998) Lipid hydroperoxide generation, turnover, and effector action in biological systems. J Lipid Res 39: 1529–1542.
    [20] Beckman K, Ames B (1998) The free radical theory of aging matures. Physiol Rev 78: 547–581.
    [21] Valko M, Rhodes C, Moncol, et al. (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interac 160: 1–40. doi: 10.1016/j.cbi.2005.12.009
    [22] Silva J, Coutinho O (2010) Free radicals in the regulation of damage and cell death-basic mechanisms and prevention. Drug Discov Ther 4: 144–167.
    [23] Jacob K, Hooten N, Trzeciak A, et al. (2013) Markers of oxidant stress that are clinically relevant in aging and age-related disease. Mech Ageing Dev 134: 139–157. doi: 10.1016/j.mad.2013.02.008
    [24] Phaniendra A, Jestadi D, Periyasamy L (2015) Free radicals: properties, sources, targets, and their implication in various diseases. Ind J Clin Biochem 30: 11–26.
    [25] Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol Soc 11: 298–300. doi: 10.1093/geronj/11.3.298
    [26] Shigenaga M, Hagen T, Ames B (1994) Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci USA 91: 10771–10778. doi: 10.1073/pnas.91.23.10771
    [27] Balaban R, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120: 483–495.
    [28] Harman D (2006) Free radical theory of aging: an update. Ann NY Acad Sci 1067: 10–21. doi: 10.1196/annals.1354.003
    [29] Colavitti R, Finkel T (2005) Reactive oxygen species as mediators of cellular senescence. IUBMB Life 57: 277–281. doi: 10.1080/15216540500091890
    [30] Ziegler D, Wiley C, Velarde M (2015) Mitochondrial effectors of cellular senescence: beyond the free radical theory of aging. Aging Cell 14: 1–7. doi: 10.1111/acel.12287
    [31] Eichenberger K, Böhni P, Wintehalter K, et al. (1982) Microsomal lipid peroxidation causes an increase in the order of the membrane lipid domain. FEBS Letters 142: 59–62. doi: 10.1016/0014-5793(82)80219-6
    [32] Kaplán P, Doval M, Majerová Z, et al. (2000) Iron-induced lipid peroxidation and protein modification in endoplasmic reticulum membranes. Protection by stobadine. Int J Biochem Cell Biol 32: 539–547. doi: 10.1016/S1357-2725(99)00147-8
    [33] Solans R, Motta C, Solá R, et al. (2000) Abnormalities of erythrocyte membrane fluidity, lipid composition, and lipid peroxidation in systemic sclerosis. Arthritis Rheum 43: 894–900. doi: 10.1002/1529-0131(200004)43:4<894::AID-ANR22>3.0.CO;2-4
    [34] Pretorius E, Plooy J, Soma P, et al. (2013) Smoking and fluidity of erythrocyte membranes: a high resolution scanning electron and atomic force microscopy investigation. Nitric Oxide 35: 42–46. doi: 10.1016/j.niox.2013.08.003
    [35] de la Haba C, Palacio J, Martínez P, et al. (2013) Effect of oxidative stress on plasma membrane fluidity of THP-1 induced macrophages. Biochim Biophys Acta 1828: 357–364. doi: 10.1016/j.bbamem.2012.08.013
    [36] Alberts B, Johnson A, Lewis J, et al. (2002) The Lipid Bilayer, In: Molecular Biology of the Cell, 4 Eds., New York: Garland Science.
    [37] Weijers R (2012) Lipid composition of cell membranes and its relevance in type 2 diabetes mellitus. Curr Diabetes Rev 8: 390–400. doi: 10.2174/157339912802083531
    [38] Benderitter M, Vincent-Genod L, Pouget J, et al. (2003) The cell membrane as a biosensor of oxidative stress induced by radiation exposure: a multiparameter investigation. Radiat Res 159: 471–483. doi: 10.1667/0033-7587(2003)159[0471:TCMAAB]2.0.CO;2
    [39] Zimniak P (2011) Relationship of electrophilic stress to aging. Free Radic Biol Med 51: 1087–1105. doi: 10.1016/j.freeradbiomed.2011.05.039
    [40] Wang S., Von Meerwall E, Wang SQ, et al. (2004). Diffusion and rheology of binary polymer mixtures. Macromolecules 37: 1641–1651. doi: 10.1021/ma034835g
    [41] Williams R (1989) NMR studies of mobility within protein structure. Euro J Biochem 183: 479–497.
    [42] Sapienza, P, Lee A (2010) Using NMR to study fast dynamics in proteins: methods and applications. Curr Opin Pharmacol 10: 723–730.
    [43] Petersen R (2014) Computational conformational antimicrobial analysis developing mechanomolecular theory for polymer biomaterials in materials science and engineering. Int J Comput Mater Sci Eng 3: 145003.
    [44] Goldstein D, (1990) Chapter 143 Serum Calcium, In: Walker H, Hall W, Hurst J, Editors, Clinical Methods: The History, Physical, and Laboratory Examinations, 3 Eds., Boston: Butterworths.
    [45] Tung IC (1991) Application of factorial design to SMC viscosity build-up. Polym Bull 25: 603–610.
    [46] Peters S, (1998) Particulate Fillers, In: Handbook of Composites, 2 Eds., New York: Chapman & Hall, 242–243.
    [47] Gaucheron F (2005) The minerals of milk. Reprod Nutr Dev 45: 473–483. doi: 10.1051/rnd:2005030
    [48] Komabayashi T, Zhu Q, Eberhart R, et al. (2016) Current status of direct pulp-capping materials for permanent teeth. Dent Mater J 35: 1–12.
    [49] Petersen R, Vaidya U, (2011) Chapter 16 Free Radical Reactive Secondary Sequence Lipid Chain-Lengthening Pathologies, In: Micromechanics/Electron Interactions for Advanced Biomedical Research, Saarbrücken: LAP LAMBERT Academic Publishing Gmbh & Co. KG., 233–287.
    [50] McMurry J, (2004) Organic Chemistry 6 Eds, Belmont, CA: Thompson Brooks/Cole., 136–138.
    [51] Esterbauer H, Schaur R, Zollner H (1991) Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 11: 81–128. doi: 10.1016/0891-5849(91)90192-6
    [52] Lovell M, Xie C, Markesbery W (2000) Acrolein, a product of lipid peroxidation, inhibits glucose and glutamate uptake in primary neuronal cultures. Free Radic Biol Med 29: 714–720. doi: 10.1016/S0891-5849(00)00346-4
    [53] Shi R, Rickett T, Sun W (2011) Acrolein-mediated injury in nervous system trauma and diseases. Mol Nutr Food Res 55: 1320–1331. doi: 10.1002/mnfr.201100217
    [54] Uchida K (1999) Current status of acrolein as a lipid peroxidation product. Trends Cardiovasc Med 9: 109–113. doi: 10.1016/S1050-1738(99)00016-X
    [55] Minko I, Kozekov I, Harris T, et al. (2009) Chemistry and biology of DNA containing 1,N2-deoxyguanosine adducts of the α,β-unsaturated aldehydes acrolein, crotonaldehyde, and 4-hydroxynonenal. Chem Res Toxicol 22: 759–778. doi: 10.1021/tx9000489
    [56] Singh M, Kapoor A, Bhatnagar A (2014) Oxidative and reductive metabolism of lipid-peroxidation derived carbonyls. Chem Biol Interact 234: 261–273.
    [57] Ishii T, Yamada T, Mori T, et al. (2007) Characterization of acrolein-induced protein cross-links. Free Radic Res 41: 1253–1260. doi: 10.1080/10715760701678652
    [58] Michael J, Sircar S, (2011) Electrophysiology of Ion Channels, In: Fundamentals of Medical Physiology, New York: Thieme Medical Publishers, 43–46.
    [59] Han P, Trinidad B, Shi J (2015) Hypocalcemia-induced seizure: demystifying the calcium paradox. ASN Neuro 7: 1–9.
    [60] Parekh A, Putney J (2005) Store-operated calcium channels. Physiol Rev 85: 757–810. doi: 10.1152/physrev.00057.2003
    [61] Sherwood L, (2004) Endocrine Control of Calcium Metabolism, In: Human Physiology, 5 Eds., Belmont, CA: Thomson-Brooks/Cole, 733–742.
    [62] Michael J, Sircar S, (2011) Mechanisms to Regulate Whole Body pH, In: Fundamentals of Medical Physiology, New York: Thieme Medical Publishers, 399–400.
    [63] Lide D, (1996) Electrical Resistivity of Pure Metals, In: Handbook of Chemistry and Physics, 77 Eds., New York: CRC Press, 12-40–12-41.
    [64] Jendrasiak G, Smith R (2004) The interaction of water with the phospholipid head group and its relationship to the lipid electrical conductivity. Chem Phys Lipids 131: 183–195. doi: 10.1016/j.chemphyslip.2004.05.003
    [65] Petersen R (2011) Bisphenyl-polymer/carbon-fiber-reinforced composite compared to titanium alloy bone implant. Int J Polym Sci 2011: 2341–2348.
    [66] Callister W, (1997) Room Temperature Electrical Resistivity Values for Various Engineering Materials Table C.9, In: Materials Science and Engineering, New York: John Wiley & Sons, 796–798.
    [67] Park B, Lakes R, (1992) Characterization of Materials II Table 4.1, In: Biomaterials, 2 Eds., New York: Plenum Press, 64.
    [68] Halliday D, Resnick R, Walker J, (1993) 46-2 Electrical Conductivity, In: Fundamentals of Physics, 4 Eds., New York: JohnWiley & Son, 1210.
    [69] Periodic Table of the Elements (2016) Sulfur-Electrical Properties accessed November 10, 2016. Available from: http://www.periodictable.com/Elements/016/data.html.
    [70] Clandinin M, Cheema S, Field C, et al. (1991) Dietary fat: exogenous determination of membrane structure and cell function. FASEB J 5: 2761–2769.
    [71] McMurry J, (2004) Biomolecules: Lipids, In: Organic Chemistry, 6 Eds., Belmont, CA: Thompson Brooks/Cole, 1027–1033.
    [72] Sherwood L, (2004) Lipids, In: Human Physiology, 5 Eds., Belmont, CA: Thomson-Brooks/Cole, A12–A13.
    [73] Villaláın J, Mateo C, Aranda F, et al. (2001) Membranotropic effects of the antibacterial agent triclosan. Arch Biochem Biophys 390: 128–136.
    [74] Guillén J, Bernabeu A, Shapiro S, et al. (2004) Location and orientation of Triclosan in phospholipid model membranes. Eur Biophys J 33: 448–453.
    [75] Alberts B, Johnson A, Lewis J, et al. (2002) Electron-Transport Chains and Their Proton Pumps, In: Molecular Biology of the Cell, 4 Eds., New York: Garland Science.
    [76] Sherwood L, (2004) Acid-Base Balance, In: Human Physiology, 5 Eds., Belmont, CA: Thomson-Brooks/Cole, 571–577.
    [77] Hüttemann M, Lee I, Grossman L, et al. (2012) Chapter X. phosphoylation of mammalian cytochrome c and cytochrome c oxidase in the regulation of cell destiny: respieration, apoptosis, and human disease. Adv Exp Med Biol 748: 237–264.
    [78] Srinivasan S, Avadhani N (2012) Cytochrome c oxidase dysfunction in oxidative stress. Free Radic Biol Med 53: 1252–1263. doi: 10.1016/j.freeradbiomed.2012.07.021
    [79] Finkel T, Holbrook N (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408: 239–247. doi: 10.1038/35041687
    [80] Brand M, Affourtit C, Esteves T, et al. (2004) Serial review: the powerhouse takes control of the cell: the role of mitochondria in signal transduction. Free Radic Biol Med 37: 755–767. doi: 10.1016/j.freeradbiomed.2004.05.034
    [81] Tosato M, Zamboni V, Ferrini A, et al (2007) The aging process and potential interventions to extend life expectancy. Clinical Interv Aging 2: 401–412.
    [82] Murphy M (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13. doi: 10.1042/BJ20081386
    [83] Kagan V, Wipf P, Stoyanovsky D, et al. (2009) Mitochondrial targeting of electron scavenging antioxidants: regulation of selective oxidation vs random chain reactions. Adv Drug Deliv Rev 61: 1375–1385. doi: 10.1016/j.addr.2009.06.008
    [84] Niizuma K, Yoshioka H, Chen H, et al. (2010) Mitochondrial and apoptotoc neuronal death signaling pathways in cerebral ischemia. Biochim Biophys Acta 1802: 92–99. doi: 10.1016/j.bbadis.2009.09.002
    [85] Michael J, Sircar S, (2011) Metabolic Pathways, In: Fundamentals of Medical Physiology, New York: Thieme Medical Publishers, 467–468.
    [86] Halliwell B (1987) Oxidants and human disease: some new concepts. FASEB J 1: 358–364.
    [87] Petersen R (2013) Free-radical polymer science structural cancer model: a review. Scientifica 2013: 143589.
    [88] Alberts B, Johnson A, Lewis J, et al. (2002) Proteins Function, In: Molecular Biology of the Cell, 4 Eds., New York: Garland Science.
    [89] Reineri S, Bertoni A, Sanna E, et al. (2007) Membrane lipid rafts coordinate estrogen-dependent signaling in human platelets. Biochim Biophys Acta 1773: 273–278. doi: 10.1016/j.bbamcr.2006.12.001
    [90] Pamplona R, Portero-Otin M, Requena J, et al. (1999) A low degree of fatty acid unsaturation leads to lower lipid peroxidation and lipoxidation-derived protein modification in heart mitochondria of the longevous pigeon than in the short-lived rat. Mech Ageing Dev 106: 283–286. doi: 10.1016/S0047-6374(98)00121-3
    [91] Wang Y, Cui P (2015) Reactive carbonyl species derived from omega-3 and omega-6 fatty acids. J Agric Food Chem 63: 6293–6296. doi: 10.1021/acs.jafc.5b02376
    [92] National Cancer Institute/National Institutes of Health/Department of Health and Human Services (2006) What You Need To Know About Cancer Bethesda, MD: NIH.
    [93] Weinhouse S, Warburg O, Burk D, et al. (1956) On respiratory impairment in cancer cells. Science 124: 269–270.
    [94] Gillies R, (2001) The Tumour Microenvironment: Causes and Consequences of Hypoxia and Acidity, Novartis Foundation Symposium 240, New York: JohnWiley & Sons.
    [95] Stavridis J, (2008) Oxidation: the Cornerstone of Carcinogenesis, New York: Springer.
    [96] Grek C, Tew K (2010) Redox metabolism and malignancy. Current Opin Pharmacol 10: 362–368. doi: 10.1016/j.coph.2010.05.003
    [97] Fogg V, Lanning N, MacKeigan J (2011) Mitochondria in cancer: at the crossroads of life and death. Chin J Cancer 30: 526–539. doi: 10.5732/cjc.011.10018
    [98] Hielscher A, Gerecht S (2015) Hypoxia and free radicals: role in tumor progression and the use of engineering-based platforms to address these relationships. Free Radic Biol Med 79: 281–291. doi: 10.1016/j.freeradbiomed.2014.09.015
    [99] Görlach A, Dimova E, Petry A, et al. (2015) Reactive oxygen species, nutrition, hypoxia and diseases: problems solved? Redox Biol 6: 372–385. doi: 10.1016/j.redox.2015.08.016
    [100] Tafani M, Sansone L, Limana F, et al. (2016) The interplay of reactive oxygen species, hypoxia, inflammation, and sirtuins in caner initiation and progression. Oxid Med Cell Longev 2016: 1–18.
    [101] Peacock J, Calhoun A, (2006) Polymer Chemistry Properties and Applications, Munich, Germany: Hanser.
    [102] Mironi-Harpaz I, Narkis M, Siegmann A (2007) Peroxide crosslinking of a styrene-free unsaturated polyester. J Appl Polym Sci 105: 885–892. doi: 10.1002/app.25385
    [103] Wang Y, Woodworth L, Han B (2011) Simultaneous measurement of effective chemical shrinkage and modulus evolutions during polymerization. Exp Mech 51: 1155–1169. doi: 10.1007/s11340-010-9410-y
    [104] Jansen K, Vreugd de J, Ernst L (2012) Analytical estimate for curing-induced stress and warpage in coating layers. J Appl Polym Sci 126: 1623–1630. doi: 10.1002/app.36776
    [105] Weinberg R, (2007) 14.3 The epithelial-mesenchymal transition and associated loss of E-cadherin expression enable carcinoma cells to become invasive, In: The Biology of Cancer, New York: Garland Science, 597–624.
    [106] Wenger J, Chun S, Dang D, et al. (2011) Combination therapy targeting cancer metabolism. Med Hypotheses 76: 169–172. doi: 10.1016/j.mehy.2010.09.008
    [107] Vinogradova T, Miller P, Kaverina I (2009) Microtubule network asymmetry in motile cells: role of Golgi-derived array. Cell Cycle 8: 2168–2174. doi: 10.4161/cc.8.14.9074
    [108] Lindberg U, Karlsson R, Lassing I, et al. (2008) The microfilament system and malignancy. Semin Cancer Biol 18: 2–11. doi: 10.1016/j.semcancer.2007.10.002
    [109] San Martín A, Griendling K (2010) Redox control of vascular smooth muscle migration. Antioxid Redox Signal 12: 625–640. doi: 10.1089/ars.2009.2852
    [110] Copstead LE, Banasik J, (2005) Pathophysiology, 6 Eds., St. Louis, MO: Elsevier Saunders, 221.
    [111] Li Z, Hannigan M, Mo Z, et al. (2003) Directional Sensing Requires Gβγ-Mediated PAK1 and PIXα-Dependent Activation of Cdc42. Cell 114: 215–227. doi: 10.1016/S0092-8674(03)00559-2
    [112] Hattori H, Subramanian K, Sakai J, et al. (2010) Small-molecule screen identifies reactive oxygen species as key regulators of neutrophile chemotaxis. PNAS 107: 3546–3551. doi: 10.1073/pnas.0914351107
    [113] Parisi F, Vidal M (2011) Epithelial delamination and migration: lessons from Drosophila. Cell Adh Migr 5: 366–372. doi: 10.4161/cam.5.4.17524
    [114] Barth A, Caro-Gonzalez H, et al. (2008) Role of adenomatous polyposis coli (APC) and microtubules in directional cell migration and neuronal polarization. Semin Cell Dev Biol 19: 245–251. doi: 10.1016/j.semcdb.2008.02.003
    [115] Dent E, Gupton S, et al. (2010) The growth cone cytoskeleton in axon outgrowth and guidance. Cold Spring Harb Perspect Biol 3: a001800.
    [116] Saraswathy S, Wu G, et al. (2006) Retinal microglial activation and chemotaxis by docosahexaenoic acid hydroperoxide. Invest Ophthalmol Vis Sci 47: 3656–3663. doi: 10.1167/iovs.06-0221
    [117] Dunlop R, Dean R, Rodgers K (2008) The impact of specific oxidized amino acids on protein turnover in J774 cells. Biochem J 410: 131–140. doi: 10.1042/BJ20070161
    [118] Darling E, Zauscher S, Block J (2007) A thin-layer model for viscoelastic, stress-relaxation testing of cells using atomic force microscopy: do cell properties reflect metastatic potential. Biophys J 92: 1784–1791. doi: 10.1529/biophysj.106.083097
    [119] Fleischer F, Ananthakrishnan R, (2007) Actin network architecture and elasticity in lamellipodia of melanoma cells. New J Phys 9: 420. doi: 10.1088/1367-2630/9/11/420
    [120] Pokorný J, Jandový A, Nedbalová (2012) Mitochondrial metabolism-neglected link of cancer transformation and treatment. Prague Med Rep 113: 81–94.
    [121] Qian Y, Luo J, Leonard S, et al. (2003) Hydrogen peroxide formation and actin filament reorganization by Cdc42 are essential for ethanol-induced in vitro angiogenesis. J Biol Chem 278: 16189–16197. doi: 10.1074/jbc.M207517200
    [122] Gawdzik B, Księzopolski J, Matynia T (2003) Synthesis of new free-radical initiators for polymerization. J Appl Polym Sci 87: 2238–2243. doi: 10.1002/app.11585
    [123] Miller Y, Worrall D, Funk C, et al. (2003) Actin polymerization in macrophages in response to oxidized LDL and apoptotic cells: role of 12/15-lipoxygenase and phosphoinositide 3-kinase. Mol Biol Cell 14: 4196–4206. doi: 10.1091/mbc.E03-02-0063
    [124] Ushio-Fukai M, Nakamura Y (2008) Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy. Cancer Lett 266: 37–52. doi: 10.1016/j.canlet.2008.02.044
    [125] Taparowsky E, Suard Y, Fasano O (1982) Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change. Nature 300: 762–765. doi: 10.1038/300762a0
    [126] Swaminathan V, Mythreye K, Tim O'Brien E, et al. (2011) Mechanical Stiffness grades metastatic potential in patient tumor cells and in cancer cell lines. Cancer Res 71: 5075–5080. doi: 10.1158/0008-5472.CAN-11-0247
    [127] Xu W, Mezencev R, Kim B, et al. (2012) Cell stiffness is a biomarker of the metastatic potential of ovarian cancer cells. PLoS ONE 7: e46609. doi: 10.1371/journal.pone.0046609
    [128] Hoyt K, Castaneda B, Zhang M, et al. (2008) Tissue elasticity properties as biomarkers for prostate cancer. Cancer Biomark 4: 213–225. doi: 10.3233/CBM-2008-44-505
    [129] Ghosh S, Kang T, Wang H, et al. (2011) Mechanical phenotype is important for stromal aromatase expression. Steroids 76: 797–801. doi: 10.1016/j.steroids.2011.02.039
    [130] Kraning-Rush C, Califano J, Reinhart-King C (2012) Cellular traction stresses increase with increasing metastatic potential. PLoS ONE 7: e32572. doi: 10.1371/journal.pone.0032572
    [131] Trichet L, Le Digabel J, Hawkins R, et al. Evidence of a large-scale mechanosensing mechanism for cellular adaptation to substrate stiffness. Proc Natl Acad Sci U.S.A. 109: 6933–6938.
    [132] Peto R, Doll R, Buckley J (1981) Can dietary beta-carotene materially reduce human cancer rates? Nature 290: 201–208. doi: 10.1038/290201a0
    [133] Shike M, Winawer S, Greenwald P, et al. (1990) Primary prevention of colorectal cancer. Bull World Health Organ 68: 337–385.
    [134] Dorgan J, Schatzkin A (1991) Antioxidant micronutrients in cancer prevention. Hematol Oncol Clin North Am 5: 43–68.
    [135] Chlebowski R, Grosvenor M (1994) The scope of nutrition intervention trials with cancer-related endpoints. Cancer 74: 2734–2738. doi: 10.1002/1097-0142(19941101)74:9+<2734::AID-CNCR2820741824>3.0.CO;2-U
    [136] Ziegler R, Mayne S, Swanson C (1996) Nutrition and lung cancer. Cancer Causes Control 7: 157–177. doi: 10.1007/BF00115646
    [137] Levander O (1997) Symposium: newly emerging viral diseases: what role for nutrition? J Nutr 127: 948S–950S.
    [138] Willett W (1999) Convergence of philosophy and science: the Third International Congress on Vegetarian Nutrition. Am J Clin Nutr 70(suppl): 434S–438S.
    [139] Meydani M (2000) Effect of functional food ingredients: vitamin E modulation of cardiovascular diseases and immune status in the elderly. Am J Clin Nutr 71(suppl): 1665S–1668S.
    [140] Simopoulos A (2001) The Mediterranean diets: what is so special about the diet of Greece? The scientific experience. J Nutr 131: 3065S–3073S.
    [141] Rock C, Demark-Wahnefried W (2002) Nutrition and survival after the diagnosis of breast cancer: a review of the evidence. J Clin Oncol 20: 3302–3316. doi: 10.1200/JCO.2002.03.008
    [142] Seifried H, McDonald S, Anderson D, et al. (2003) The antioxidant conundrum in cancer. Cancer Res 63: 4295–4298.
    [143] Männistö S, Smith-Warner S, Spiegelman D, et al. (2004) Dietary carotenoids and risk of lung cancer in a pooled analysis of seven cohort studies. Cancer Epidemiol Biomarkers Prev 13: 40–48. doi: 10.1158/1055-9965.EPI-038-3
    [144] Fraga C (2007) Plant polyphenols: how to translate their in vitro antioxidant actions to in vivo conditions. Life 59: 308–315.
    [145] Kushi L, Doyle C, McCullough M, et al. (2012) American cancer society guidelines on nutrition and physical activity for cancer prevention. CA Cancer J Clin 62: 30–67. doi: 10.3322/caac.20140
    [146] Heinonen O, Albanes D, Huttunen J, et al. (1994) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 330: 1029–1035. doi: 10.1056/NEJM199404143301501
    [147] Hennekens C, Buring J, Manson J, et al. (1996) Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 334: 1145–1149. doi: 10.1056/NEJM199605023341801
    [148] Omenn G, Goodman G, Thornquist M, et al. (1996) Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 334: 1150–1155. doi: 10.1056/NEJM199605023341802
    [149] Albanes D (1999) β-carotene and lung cancer: a case study. Am J Clin Nutr 69(suppl): 1345S–1350S.
    [150] Virtamo J, Albanes D, Huttunen J, et al. (2003) Incidence of cancer and mortality following α-tocopherol and β-carotene supplementation. JAMA 290: 476–485. doi: 10.1001/jama.290.4.476
    [151] Sommer A, Vyas K (2012) A global clilnical view on vitamin A and carotenoids. Am J Clin Nutr 96(suppl): 1204–1206.
    [152] Thompson I, Kristal A, Platz E (2014) Prevention of prostate cancer: outcomes of clinical trails and future opportunities. Am Soc Clin Oncol Educ Book 2014: e76–e80.
    [153] Virtamo J, Taylor P, Kontto J, et al (2014) Effects of α-tocopherol and β-carotene supplementation on cancer incidence and mortality: 18-year post-intervention follow-up of the alpha-tocopherol, beta-carotene cancer prevention (ATBC) study. Int J Cancer 135: 178–185. doi: 10.1002/ijc.28641
    [154] Yusuf S, Phil D, Dagenais G, et al. (2000) Vitamin E supplementation and cardiovascular events in high-risk patients. N Engl J Med 342: 154–160. doi: 10.1056/NEJM200001203420302
    [155] Devaraj S, Tang R, Adams-Huet B, et al. (2007) Effect of high-dose α-tocopherol supplementation on biomarkers of oxidative stress and inflammation and carotid atherosclerosis in patients with coronary artery disease. Am J Clin Nutr 86: 1392–1398.
    [156] Sesso H, Buring J, Christen W, et al (2008) Vitamins E and C in the prevention of cardiovascular disease in men. JAMA 300: 2123–2133.
    [157] Brigelius-Flohe R, Galli F (2010) Vitamin E: a vitamin still awaiting the detection of its biological function. Mol Nutr Food Res 54: 583–587. doi: 10.1002/mnfr.201000091
    [158] Schultz M, Leist M, Petrzika M, et al. (1995) Novel urinary metabolite of α-tocopherol, 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman, as an indicator of an adequate vitamin E supply. Am J Clin Nutr 62(suppl): 1527S–1534S.
    [159] Azzi A (2007) Molecular mechanism of α-tocopherol action. Free Radic Biol Med 43: 16–21. doi: 10.1016/j.freeradbiomed.2007.03.013
    [160] Boddupalli S, Mein J, Lakkanna S, et al. (2012) Induction of phase 2 antioxidant enzymes by broccoli sulforaphane: perspectives in maintaining the antioxidant activity of vitamins A, C, and E. Front Genet 3: 1–15.
    [161] Lü JM, Lin P, Yao Q, et al. (2010) Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems. J Cell Mol Med 14: 840–860. doi: 10.1111/j.1582-4934.2009.00897.x
    [162] Apak R, Güçlü K, Özyürek M, et al. (2008) Mechanism of antioxidant capacity assays and the CUPRAC (cupric ion reducing antioxidant capacity) assay. Microch Acta 160: 413–419.
    [163] Özyürek M, Bektaşoğlu B, Güçlü K, et al. (2008) Simultaneous total antioxidant capacity assay of lipohilic and hydrophilic antioxidants in the same acetone-water solution containing 2% methyl-β-cyclodextrin using the cupric reducing antioxidant capacity (CUPRAC) method. Anal Chim ACTA 630: 28–39. doi: 10.1016/j.aca.2008.09.057
    [164] McMurry J, (2004) Organic Chemistry, 6 Eds., Belmont, CA: Thompson Brooks/Cole, 403–405, 482–483, 486–487.
    [165] Dumas D, Muller S, Gouin F, et al. (1997) Membrane fluidity and oxygen diffusion in cholesterol enriched erythrocyte membrane. Arch Biochem Biophys 341: 34–39. doi: 10.1006/abbi.1997.9936
    [166] Cazzola R, Rondanelli M, Russo-Volpe S, et al. (2004) Decreased membrane fluidity and altered susceptibility to peroxidation and lipid composition in overweight and obese female erythrocytes. J Lipid Res 45: 1846–1851. doi: 10.1194/jlr.M300509-JLR200
    [167] Madmani M, Yusaf S, Tamr A, et al. (2014) Coenzyme Q10 for heart failure (Review). Cochrane Database Syst Rev 2014.
    [168] Watts G, Playford D, Croft K, et al. (2002). Coenzyme Q10 improves endothelial dysfunction of brachial artery in type II diabetes mellitus. Diabetologia 45:420–426.
    [169] DeCaprio A (1999) The toxicology of hydroquinone-relevance to occupational and environmental exposure. Crit Rev Toxicol 29: 283–330. doi: 10.1080/10408449991349221
    [170] McMurry J, (2004) 17.11 Reactions of Phenols, In: Organic Chemistry, 6 Eds., Belmont, CA: Thompson Brooks/Cole, 618–619.
    [171] Takata J, Matsunage K, Karube Y (2002) Delivery systems for antioxidant nutrients. Toxicology 180: 183–193. doi: 10.1016/S0300-483X(02)00390-6
    [172] Pifer, J, Hearne F, Friedlander B, et al. (1986) Mortality study of men employed at a large chemical plant, 1972 through 1982. J Occup Med 28: 438–444. doi: 10.1097/00043764-198606000-00011
    [173] Pifer J, Hearne F, Swanson F (1995) Mortality study of employees engaged in the manufacture and use of hydroquinone. Int Arch Occup Environ Health 67: 267–280. doi: 10.1007/BF00409409
    [174] Sterner J, Oglesby F, Anderson B (1947) Quinone vapors and their harmful effects. I Corneal and conjunctival injury. J Ind Hyg Toxicol 29: 60–73.
    [175] Carlson A, Brewer N (1953) Toxicity studies on hydroquinone. Proc Soc Exp Biol Med 84: 684–688. doi: 10.3181/00379727-84-20751
    [176] O'Donoghue J (2006) Hydroquinone and its analogues in dermatology-a risk-benefit viewpoint. J Cosmet Dermatol 5: 196–203. doi: 10.1111/j.1473-2165.2006.00253.x
    [177] Nordlund J, Grimes P, Ortonne J (2006) The safety of hydroquinone. JEADV 20: 781–787.
    [178] Arndt K, Fitzpatrick T (1965) Topical use of hydroquinone as a depigmenting agent. JAMA 194: 965–967. doi: 10.1001/jama.1965.03090220021006
    [179] Deisinger P, Hill T, English C (1996) Human exposure to naturally occurring hydroquinone. J Toxicol Env Health 47: 31–46.
    [180] Levitt J (2007) The safety of hydroquinone: a dermatologist's response to the 2006 Federal Register. J Am Acad Dermatol 57: 854–872. doi: 10.1016/j.jaad.2007.02.020
    [181] Marcus R, Sutin N (1985) Electron transfers in chemistry and biology. Biochim Biophys Acta 811: 265–322. doi: 10.1016/0304-4173(85)90014-X
    [182] Dumas D, Latger V, Viriot M-L, et al. (1999) Membrane fluidity and oxygen diffusion in cholesterol-enriched endothelial cells. Clin Hemorheol Microcirc 21: 255–261.
    [183] National Toxicology Program (1989) Toxicology and carcinogenesis studies of hydroquinone in F-344/N rats and B6C3F mice. NIH Publication : 90–2821.
    [184] Shibata MA, Hirose M, Tanaka H, et al. (1991) Induction of renal cell tumors in rats and mice, and enhancement of hepatocellular tumor development in mice after long-term hydroquinone treatment. Jap J Can Res 82: 1211–1219. doi: 10.1111/j.1349-7006.1991.tb01783.x
    [185] Poet T, Wu H, English J, et al (2004) Metabolic rate constants for hydroquinone in F344 rat and human liver isolated hepatocytes: application to a PBPK model. Toxicol Sci 82: 9–25. doi: 10.1093/toxsci/kfh229
    [186] MacDonald J (2004) Human carcinogenic risk evaluation, part IV: assessment of human risk of cancer from chemical exposure using a global weight-of-evidence approach. Toxicol Sci 82: 3–8. doi: 10.1093/toxsci/kfh189
    [187] Food and Drug Administration (2015) Hydroquinone studies under the national toxicology program (NTP). 11/27/2015. Accessed 11/2016, Available from: http://www.fda/gov/About FDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm203112.htm.
  • This article has been cited by:

    1. Xu Gu, Xiaoliang Chen, Min Yang, Yajun Du, Mingwei Tang, Bi-DNE: bilayer evolutionary pattern preserved embedding for dynamic networks, 2024, 10, 2199-4536, 3763, 10.1007/s40747-024-01352-z
    2. Wenzhan Zhang, Ziyao Liu, The influence maximization algorithm for integrating attribute graph clustering and heterogeneous graph transformer, 2024, 10, 24058440, e38916, 10.1016/j.heliyon.2024.e38916
    3. Minnu Elizabeth Ittan, Sudheep M. Elayidom, Midhun P. Mathew, 2024, chapter 3, 9798369392461, 65, 10.4018/979-8-3693-9246-1.ch003
  • Reader Comments
  • © 2017 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(9448) PDF downloads(1211) Cited by(30)

Other Articles By Authors

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog