http://www.iaees.org/publications/journals/np/np.asp International Academy of Ecology and Environmental Sciences Network Pharmacology (ISSN 2415-1084); Publisher: International Academy of Ecology and Environmental Sciences; Address: Unit 3, 6/F., Kam Hon Industrial Building, 8 Wang Kwun Road, Kowloon Bay, Hong Kong; Tel: 00852-2138 6086; Fax: 00852-3069 195; E-mail: office@iaees.org RSS is a means of receiving content across the internet without having to visit websites directly. When you see the RSS tag on a web page, then you know that site offers an RSS feed. You may download a RSS reader (e.g., at http://www.iaees.org/tools/RSSOwl-java.zip). Install it on your computer and create a new folder, and then create a new feed with a RSS feed address, e.g., http://www.iaees.org/publications/journals/piaees/rss.xml, then set something. Any update of RSS feed site will automatically reach your RSS reader. If you have subscribed an online journal by RSS, journal contents or articles will reach you once the latest issue is available or the latest article is published. http://www.iaees.org/publications/journals/np/online-version.asp International Academy of Ecology and Environmental Sciences Network pharmacology is an interdisciplinary science based on pharmacology, network biology, systems biology, bioinformatics, computational science, and other related scientific disciplines. In particular, it is a network-based science, just like other new proposed sciences (Zhang, 2016c). The NETWORK PHARMACOLOGY (ISSN 2415-1084) is an open access (BOAI definition), peer/open reviewed online journal (users are free to read, download, copy, distribute, print, search, or link to the full texts of the articles) that considers scientific articles in all different areas of network pharmacology. It devotes to understand the network interactions between a living organism and drugs that affect normal or abnormal biochemical function. It tries to exploit the pharmacological mechanism of drug action in the biological network, and helps to find drug targets and enhance the drug's efficacy. The goal of this journal is to keep a record of the state-of-the-art research and promote the research work in these fast moving areas.The scope of Network Pharmacology covers but not limits to: (1) theories, algorithms and software of network pharmacology; (2) theory, methods and case studies on dynamics, optimization and control of pharmacological networks (here generally refer to disease network, disease - disease, disease - drug, drug - drug, drug - target network, network targets - disease, and drug targets - disease network, etc.); (3) network analysis of disease/drug related pharmacological networks; (4) various pharmacological networks and interactions; (5) factors that affect drug metabolism, etc. http://www.iaees.org/publications/journals/np/articles/2016-1(1)/network-pharmacology-a-further-description.pdf WenJun Zhang.Network Pharmacology,2016,1(1):1-14 Network pharmacology devotes to understand the pharmacological mechanism of drug action in the network perspective. Based on previous studies, in present article I further outlined and defined the aims, scope, theory and methodology of network pharmacology. http://www.iaees.org/publications/journals/np/articles/2016-1(1)/generate-networks-with-power-law-distributed-degrees.pdf WenJun Zhang, Xin Li.Network Pharmacology,2016,1(1):15-35 In present study I proposed a method for generating biological networks based on power-law (p(x)=x-lamda) and exponential-law (p(x)=e-lamda x) distribution functions. Given the parameter of power-law or exponential-law distribution function, lamda, the algorithm generates an expected frequency distribution according to the given parameter, thereafter creates an adjacency matrix in which (practical) frequency distribution of node degrees matches the expected frequency distribution. The results showed that power-law distribution function performs much better than exponential-law distribution function in generating networks. Using the revised algorithm, tumor related networks (pathways) are simulated and predicted. The results prove that the algorithm is overall effective in predicting network links (14.6-21.2 percent of correctly predicted links against 0.1-3.4 percent of that for random assignments). Matlab codes of the algorithms are given also. http://www.iaees.org/publications/journals/np/articles/2016-1(1)/Matlab-program-for-stepwise-regression.pdf Yanhong Qi, GuangHua Liu, WenJun Zhang.Network Pharmacology,2016,1(1):36-41 The stepwise linear regression is a multi-variable regression for identifying statistically significant variables in the linear regression equation. In present study, we presented the Matlab program of stepwise regression. http://www.iaees.org/publications/journals/np/articles/2016-1(1)/Matlab-program-for-finding-shortest-paths.pdf WenJun Zhang.Network Pharmacology,2016,1(1):42-53 The Floyd algorithm is used to find shortest paths in a graph or network. In present article I present full Matlab codes of the Floyd algorithm for using in the studies of network pharmacology. As an example, it is used to find shortest paths in a tumor pathway. http://www.iaees.org/publications/journals/np/articles/2016-1(2)/identifying-hierarchical-sub-networks-modules.pdf WenJun Zhang.Network Pharmacology,2016,1(2):54-65 Some networks, including biological networks, consist of hierarchical sub-networks / modules. Based on my previous study, in present study a method for both identifying hierarchical sub-networks / modules and weighting network links is proposed. It is based on the cluster analysis in which between-node similarity in sets of adjacency nodes is used. Two matrices, linkWeightMat and linkClusterIDs, are achieved by using the algorithm. Two links with both the same weight in linkWeightMat and the same cluster ID in linkClusterIDs belong to the same sub-network / module. Two links with the same weight in linkWeightMat but different cluster IDs in linkClusterIDs belong to two sub-networks / modules at the same hirarchical level. However, a link with an unique cluster ID in linkClusterIDs does not belong to any sub-networks / modules. A sub-network / module of the greater weight is the more connected sub-network / modules. Matlab codes of the algorithm are presented. http://www.iaees.org/publications/journals/np/articles/2016-1(2)/finding-trees-in-the-network.pdf WenJun Zhang.Network Pharmacology,2016,1(2):66-73 Both DFS and Minty algorithms are used to find trees in a network (graph). In present article I present full Matlab codes of the two algorithms for using in the studies of network pharmacology. Trees are found in tumor pathways. http://www.iaees.org/publications/journals/np/articles/2016-1(3)/methods-for-sensitivity-analysis-of-systems-and-networks.pdf WenJun Zhang.Network Pharmacology,2016,1(3):74-81 A network may considerably change with certain nodes, links, flows, or parameters. To find the most important nodes, links, or other parameters to determine network structure or performance is of significant. Sensitivity analysis is originated from systems science. It explores the relationship between parametric change and systematic output, and is used to find important parameters in the system model. In principle, the sensitivity analysis used in systems science can also be extended to network analysis in which the model output means network output, network stability, network flow, network structure, or other indices, and model input means network nodes, network links, network parameters, etc. In present article, some methods for sensitivity analysis of systems / networks are described in detail. http://www.iaees.org/publications/journals/np/articles/2016-1(3)/find-cut-nodes-and-bridges-in-the-network.pdf WenJun Zhang.Network Pharmacology,2016,1(3):82-85 A connected graph X is a block, if and only if for any three vertices u, v and w in X, there exists a path from u to w and the path does not contain v. In present article I present full Matlab codes of the algorithm for finding cut nodes and bridges in the network. http://www.iaees.org/publications/journals/np/articles/2016-1(4)/model-for-dynamics-of-occurrence-probability-of-missing-links.pdf WenJun Zhang.Network Pharmacology,2016,1(4):86-94 In most of the link prediction methods, all predicted missing links are ranked according to their scores. In the practical application of prediction results, starting from the first link that has the highest score in the ranking list, we verify each link one by one through experiments or other ways. Nevertheless, how to find an occurrence pattern of true missing links in the ranking list has seldomly reported. In present study, I proposed a mathematical model for relationship between cumulative number of predicted true missing links (y) and cumulative number of predicted missing links (x): y=K(1-e-rx/K), where K is the expected total number of true missing links, and r is the intrinsic (maximum) occurrence probability of true missing links. It can be used to predict the changes of occurrence probability of true missing links, assess the effectiveness of a prediction method, and help find the mechanism of link missing in the network. The model was validated by six prediction methods using the data of tumor pathways. http://www.iaees.org/publications/journals/np/articles/2016-1(4)/risk-administration-in-centralized-and-distributed-software-development.pdf Riaz Shah, F. Bahadur, Sheraz Ahmed, Faiza Kanwal.Network Pharmacology,2016,1(4):95-103 Risk administration is used to increase the possibility of success of any future project by exploring its reservations. It will meet all the remedies to make the software development project successful by keeping in view all the future problems that may occur during the project process. It includes the identification of risk and their assessment in the project course and tries to make improvement to make project constructive. Risk administration goals are to overcome project task risks those are identified before starting of the project and during the implementation. This paper describes the phases in the risk administration process and provided methods to analysis and safety of administration. The paper focuses on a study risk administration in centralized and distributed software development projects. This study recognizes valuable, constant and free communication as the basics for victorious risk administration. Therefore, it registers all incoming information memorize much in the same pattern as the "black box" device during an aircraft flight. The description and evaluation tools are also included, may be used during the risk administration study in the software development atmosphere. http://www.iaees.org/publications/journals/np/articles/2017-2(1)/metabolic-pathway-of-non-alcoholic-fatty-liver-disease.pdf WenJun Zhang, YuTing Feng.Network Pharmacology,2017,2(1):1-12 Nonalcoholic fatty liver disease (NAFLD) is a systematic and complex disease involving various cytokines/metabolites. In present article, we use methodology of network biology to analyze network properties of NAFLD metabolic pathway. It is found that the metabolic pathway of NAFLD is not a typical complex network with power-law degree distribution, p(x)=x^(-4.4275), x not less than 5. There is only one connected component in the metabolic pathway. The calculated cut cytokines/metabolites of the metabolic pathway are SREBP-1c, ChREBP, ObR, AMPK, IRE1alpha, ROS, PERK, elF2alpha, ATF4, CHOP, Bim, CASP8, Bid, CxII, Lipogenic enzymes, XBP1, and FFAs. The most important cytokine/metabolite for possible network robustness is FFAs, seconded by TNF-alpha. It is concluded that FFAs is the most important cytokine/metabolite in the metabolic pathway, seconded by ROS. FFAs, LEP, ACDC, CYP2E1, and Glucose are the only cytokines/metabolites that affect others without influences from other cytokines/metabolites. Finally, the IDs matrix for identifying possible sub-networks/modules is given. However, jointly combining the results of connectedness analysis and sub-networks/modules identification, we hold that there are not significant sub-networks/modules in the pathway. http://www.iaees.org/publications/journals/np/articles/2017-2(1)/finding-the-shortest-tree-in-the-network.pdf WenJun Zhang.Network Pharmacology,2017,2(1):13-16 In present article, I present full Matlab codes of Kruskal algorithm for calculating the shortest tree and use it in tumor pathway. http://www.iaees.org/publications/journals/np/articles/2017-2(2)/basic-statistics-of-medicinal-attributes-and-functions.pdf WenJun Zhang.Network Pharmacology,2017,2(2):17-37 Based on the Pharmacopoeia of the People's Republic of China, Chinese Materia Medica, and other resources, I collected a total of 1127 Chinese herbal medicines mainly with recorded chemical composition. Of which 210 families and approximately 2000 species of medicinal plants and fungi were involved. According to the comparison, in total of 69 medicinal attributes (Shu Xing) and 78 medicinal functions (Gon Xiao), including 22 medicinal organs or tissues, 7 taste attributes, 5 medicinal properties, 1 toxicity attribute, 22 chemical composition categories, 12 meridians and collaterals (Gui Jing), and 78 medicinal functions were determined. All of the Chinese herbal medicines were numerically coded according to drug name, species, family, 69 medicinal attributes and 78 medicinal functions. Finally, an interactive coding database, CHM-DATA, which contains 8 tables, was obtained. Statistics, e.g., totals, frequencies or probabilities, percentages, etc., were calculated on the basis of total population of medicines and families. http://www.iaees.org/publications/journals/np/articles/2017-2(2)/networks-and-mechanisms-of-medicinal-attributes-and-functions.pdf WenJun Zhang.Network Pharmacology,2017,2(2):38-66 In present study, the database, CHM-DATA, with 1127 Chinese herbal medicines mainly having recorded chemical composition, involving 7 taste attributes, 5 medicinal properties, 1 toxicity attribute, 22 chemical composition categories, 12 meridians and collaterals (Gui Jing), and 78 medicinal functions (Gong Xiao), was used to calculate point correlations between these 125 attributes. Totally four relational networks, i.e., the networks for medicinal attributes and functions, for chemical composition and meridians and collaterals, for meridians and collaterals and medicinal functions, and for meridians and collaterals were constructed based on the significant point correlations. Network analysis indicated that the former three ones are scale-free complex networks and the last one tends to be a random network. Node degrees of the four networks follow power-law distribution. Detailed between-attribute relationships and medicinal mechanisms were revealed. For example, concerning chemical composition categories, alkaloids and amines have positive correlation / correspondence. More alkaloids correspond to more amines. Alkaloids negatively correlate with volatile oils / ordinary oils, carbohydrates / starch, ketones / flavonoids, and olefins. Alkaloids mainly function in decrease internal heat, dry dampness, etc. Organic acids and alkaloids have negative correlation. More organic acids mean the less alkaloids. Organic acids mainly act on large intestine meridians and collaterals, and function in moisten dryness. As for meridians and collaterals, kidney meridians and collaterals negatively correlate with lung meridians and collaterals, stomach meridians and collaterals, and large intestine meridians and collaterals. Kidney meridians and collaterals positively function in consolidate or warm kidney, invigorate male impotence (Yang) or strengthen male essence, strengthen bones and muscles, stop diarrheal, regulate menstruation or promote blood flow, relieve rheumatism or lubricate the joints, and negatively function in clear away heat, and detoxification. http://www.iaees.org/publications/journals/np/articles/2017-2(3)/canonical-correlation-functions-between-attribute-classes.pdf WenJun Zhang.Network Pharmacology,2017,2(3):67-81 In present study I used the data from CHM-DATA, the interactive database of 1127 Chinese herbal medicines. Canonical correlation functions were determined for taste attribute class (7 taste attributes), medicinal property class (5 medicinal properties), chemical composition class (22 chemical composition categories), meridians and colleterals class (12 meridians and colleterals), and medicinal function class (77 medicinal functions). Linear eignmodels were also developed for Chinese herbal medicines. Theoretically the attribute values of any Chinese herbal medicines meet the corresponding linear eignmodel. Matlab codes for canonical correlation analysis and linear eignmodel were given. Finally, the canonical correlation network for attribute classes of Chinese herbal medicines was constructed. http://www.iaees.org/publications/journals/np/articles/2017-2(3)/classification-and-network-analysis-of-medicinal-functions.pdf WenJun Zhang.Network Pharmacology,2017,2(3):82-104 In present study I used the data from CHM-DATA, the interactive database of 1127 Chinese herbal medicines with 78 medicinal functions (attributes). The relational network for medicinal functions of Chinese herbal medicines was constructed using my earlier data and methods. Results of network analysis showed that the network is a scale-free complex network at the significance level of alpha=0.01. It was demonstrated that Clear away heat, Detoxification, Remove lung-heat or nourish lung, Promote secretion of saliva or body, Relieve pain, Regulate or enhance energy flow (Qi), Nourish or warm spleen / stomach / Qi, and Dispel endogenous wind, are the most influential medicinal functions. Seven main modules, corresponding links and module functions were identified and three of them were (Clear away heat, Detoxification, Relieve pain, Regulate or enhance energy flow (Qi)), (Loosen the bowels, Moisten dryness, Tonify blood, Nourish essential fluid (Yin), Inhibit or break energy flow (Qi)), and (Relieve external syndrome, Induce perspiration, Relieve muscular spasm, Expose exthanthema or promote eruption). PCA of 78 medicinal functions demonstrated that the medicinal functions 1-50 accounted for 79% of the total variance. There were not absolutely significant components and medicinal functions. The 78 components from PCA were substantially 78 independent and comprehensive medicinal functions. Major medicinal functions for every component can be simply determined by their importance and contribution coefficients in the component. New medicinal definition for some the most important principal components were given. Category characteristics of medicinal functions were described. At a certain level, for example, the medicinal functions -Consolidate or warm kidney, -Whet the appetite or reinforce stomach, Cool blood, -Regulate or enhance energy flow (Qi), -Nourish or warm spleen / stomach / Qi, Clear away heat, Detoxification, and Dispel endogenous cold, are the major attributes of the principal component F1. Of which the medicinal functions with the same sign (+ or -) have the same direction of medicinal action. Results of system cluster analysis demonstrated that (Consolidate or warm kidney, Invigorate male impotence (Yang) or strengthen male essence), (Relieve constipation, Loosen the bowels), and (Clear away heat, Detoxification) were classified into a class respectively at the earliest stage. They were the most similar medicinal functions from each other. Finally, some principles for incorporation and generation of medicinal functions were discussed and Matlab codes for PCA and system cluster analysis were given. http://www.iaees.org/publications/journals/np/articles/2017-2(4)/drug-induced-deaths-in-European-countries.pdf WenJun Zhang.Network Pharmacology,2017,2(4):114-120 In present study, data of drug-induced deaths in 29 European countries were used to analyze the profile and trend of drug-induced deaths recorded for total population, males and females in order to provide some basic information on adverse effects and misuse of drugs. The results showed that Germany (28501 deaths) and United Kindom (22537 deaths) have the greatest accumalted number (1995-2014) of drug-induced deaths, followed by Italy (14134 deaths) and Spain (11133 deaths). Germany (23%) and United Kingdom (18%) held the highest percentage of drug-induced deaths in Europe, followed by Italy (12%), Spain (9%), Sweden (4%), and Norway (4%), etc. For males, United Kindom (24%) and Germany (20%) held the highest percentage, followed by Poland (8%), Italy (6%), etc. Similarly, Germany (25%) and United Kingdom (18%) are the highest in death percentage of males, followed by Italy (13%), etc. Not less than 1 death/yr, the European countries with the highest linear growth of drug-induced deaths for total population (p less than 0.05) are Turkey (33.2 deaths/yr) and Sweden (21.6 deaths/yr), followed by Ireland (8.9 deaths/yr), Estonia (7.3 deaths/yr), Finland (6.5 deaths/yr), Lithuania (2.6 deaths/yr), and Romania (2.3 deaths/yr). Not less than 1 death/yr, the European countries with the highest linear decline of drug-induced deaths for total population (p less than 0.05) are Italy (-53.9 deaths/yr) and Germany (-42.1 deaths/yr), followed by Spain (-21.6 deaths/yr), Portugal (-9.8 deaths/yr), Czech Republic (-2.9 deaths/yr), and Hungry (-1.5 deaths/yr). In average, the number of drug-induced deaths for both total population and males in Europe declined at the annual rate of 2 deaths, and that for females grew at the annual rate of 0.1 death. Generally the continuous growth of drug-induced deaths was mostly attributed to the growth of drug uses, the deteriorated medical service, or the promotion of diagnostic levels, etc. However, the continuous decline of drug-induced deaths was mostly attributed to the enhancement of medical service and the improvement of drug uses. More attention may be focused on females for proper drug uses. Both proper drug uses and improved drug design in reducing adverse effects are needed in the future. http://www.iaees.org/publications/journals/np/articles/2018-3(1-2)/trend-of-cancer-induced-deaths-in-Europe.pdf WenJun Zhang.Network Pharmacology,2018,3(1-2):1-9 In present study, data of standardised death rates of malignant neoplasms per 100000 inhabitants in 31 European countries during 1994-2013 were used to analyze the profile and trend of cancer-induced deaths. The results showed that malignant neoplasm of trachea, bronchus and lung (about 25%) is the No. 1 cancer in 31 European countries, second by malignant neoplasm of prostate (men) (22%), third by malignant neoplasms of breast (women) (16%) and colon, rectosigmoid junction, rectum, anus and anal canal (16%). Finland, Bulgaria, Switherland, and Portugal, etc., are the countries with the least death rate of total cancers. Hungary has the highest death rate of total cancers in 31 European countries, followed by Croatia, etc. Portugal, Sweden and Finland, etc., have the least death rate, and Hungary, Denmark, Netherlands, and Poland have the highest in the death rate of malignant neoplasm of prostate (men). Romania, Malta, and Italy, etc., have the lowest rate, and Norway has one of the highest death rate in malignant neoplasm of prostate (men). Spain shows the lowest death rate, and Denmark and Malta have the highest death rate in malignant neoplasm of breast (women). Greece, Finland and Switzerland are the three countries with the least death rate and Hungary has the highest in death rate in malignant neoplasm of colon, rectosigmoid junction, rectum, anus and anal canal. In average, the standardized death rates of all types of cancers in recorded European countries declined significantly during the recorded period 1994-2013. Death rate of all childhood cancers in Bulgaria and Estonia declines mostly in 31 countries, followed by Romania and Czech. Czech, Poland, and Netherlands decline mostly in death rate of malignant neoplasm of trachea, bronchus and lung. Conversely, the death rate of Macedonia and Romania increases most significantly; Germany and Sweden increase in death rate also. Belgium declines mostly in death rate of malignant neoplasm of prostate (men), followed by France, Austria, etc. And Latvia and Estonia increase most quickly. Malta has the greatest decline in death rate of malignant neoplasm of breast (women), followed by Netherlands, Denmark, etc. The death rate in Croatia increases significantly. According to these statistics and knowledge, the major external factors, smoking / drinking, environmental pollution, late marriage / late childbearing, unhealthy sexual behavior, unhealthy dietary behavior, less physical excise, and workplace stress, etc., may have contributed to most cancer-induced deaths in Europe. http://www.iaees.org/publications/journals/np/articles/2018-3(3-4)/carcass-characteristics-and-intestinal-morphology-of-Japanese-quail.pdf Majid Mohammadi.Network Pharmacology,2018,3(3-4):10-17 This experiment was conducted to evaluate the effects of feeding Ephedra and protexin on performance and some carcass characteristics and intestinal morphology of Japanese quail. A total of 240 seven days old quail chicks were divided into 8 treatments with 3 replicates as factorial randomized design. The treatments were divided as basal diet with no protexin and Ephedra kept as control, and 0.02 % (E1), 0.04% (E2) and 0.06 % (E3) Ephedra with 0.01 % or without protexin as P0 and P1 were used respectively. The live body weight gains and feed consumption of birds were measured individually feed conversion efficiency were calculated. At the end of the trial for investigating the effect of using protexin and Ephedra supplementation on performance of quails, 2 birds form each replicates were slaughtered and some blood samples were taken for hematological parameters determination. Data showed that using of protexin and Ephedra increased feed intake (FI) in treatments compared to control. Also body weight (BW) (g/d) and Pre-slaughter weigh (g) were higher in protexin and Ephedra compared to the control. There were no significant differences (p less than 0.05) for feed conversation ratio (FCR) among treatments. Data showed that using of protexin and Ephedra could increase carcass yield (g), breast and drumstick meat percentage none significantly. Data showed that heart and intestine weight also increased by using protexin and Ephedra (p less than 0.05). Morphological investigations showed that using protexin and Ephedra could increase the length, width and height of intestinal villus. Data from this study showed that protexin and Ephedra may be used as ingredient in quails ration without harming effects on performance and carcass quality of birds. http://www.iaees.org/publications/journals/np/articles/2019-4(1-2)/naturalness-and-preference-for-species-selection-of-Chinese-medicinal-plants.pdf WenJun Zhang, GuangHua Liu.Network Pharmacology,2019,4(1-2):1-5 In present study, the electivity index was used to estimate the preference for species selection of Chinese medicinal seed plants based on the code database of Chinese herbal medicine, CHM-DATA Ver. 1.0 (Zhang, 2017a-d) and the world's seed plant data. The results showed that people consciously select Chinese medicinal seed plants from the families Polygonaceae and Ranunculaceae, followed by Liliaceae, Solanaceae, Umbelliferae, etc., and people avoid select medicinal seed plant species from Cyperaceae and Gramineae, followed by Euphorbiaceae, Leguminosae, Compositae, Cruciferae, Rubiaceae, Convolvulaceae, Orchidaceae, Polygonaceae, Scrophulariaceae, Dianthus, Malvaceae, and Rosaceae, etc. http://www.iaees.org/publications/journals/np/articles/2019-4(3-4)/antibiotics-in-hospital-effluents.pdf O.P. Bansal.Network Pharmacology,2019,4(3-4):6-30 Antibiotics since their inception are widely used for medical remedies for human and animals. Due to global economic prosperity, the consumption of antibiotics has increased during the last decade. The misuse, overuse, and application of antibiotics as manure has caused elevated development of multi-antibiotic-resistant bacteria posing environmental pollutant and causes serious risks to human and veterinary health. Antibiotics in the environment affect fundamental ecological processes, biogeochemical cycling and organic contaminant degradation via microbial communities. Antibiotics in the environment affect microbial community structure and function in two ways: direct (short-term) and indirect (long-term). The indirect effect causes the development of antibiotic-resistant bacteria and bacterial strains which can degrade them by metabolic or cometabolic processes. This review presents the global occurrence of antibiotics in drinking water, sewage water, hospital effluents, river water, sediments, and manures. The results denote the concentration of antibiotics in water samples and soils are in the high range causing chronic toxicity in aquatic systems. This review also provides an overview regarding the antibiotics resistant bacteria and genes developed and regarding their remediation. As the use of antibiotics is expected to increase in the next decade due to the aging population and standard of living, the antibiotics will pose an additional environmental risk. http://www.iaees.org/publications/journals/np/articles/2020-5(1-2)/Matlab-software-package-for-image-processing-and-analysis.pdf WenJun Zhang.Network Pharmacology,2020,5(1-2):1-32 In present study, I developed a powerful Matlab-based software package, imageProcAnal (Version 1.0), for image processing and analysis. Several modules were available for uses. Functions to resize, crop, rotate, dilate, pixelate and watermark images are included in Basic module. Adjustment of image edge, contrast and gamma factor is available in Adjustment module. In Denoising module, four elementary denoising methods and their joint uses are provided for image filtering and denoising. In Edge and Contour Detection module, five methods for detection of image edge and contour are provided. Also three methods for image sharpening are available in Sharpening module. Segmentation module includes three methods for image segmentation. Connected components recognition can be made in Object Recognition module. In Analysis module, Pearson correlation measure was provided to align images. Pearson correlations and p values among images can be obtained. Mutiple methods across different modules can be sequentially and jointly used to achieve ideal image. Finally, some examples for image processing can be found in Demo module. In addition to conventional methods, I proposed two new methods for image segmentation, i.e., TDOS (Two-Dimensional Ordered Segmentation) and MWAS (Moving Windows Averaging Segmentation). In TDOS, which is based on two-dimensional ordered cluster analysis, the pixels belonging to the same segment (class) are adjoint and are not separated by any of remaining segments. MWAS is based on moving windows averaging method for transect boundary detection. Algorithms of TDOS and MWAS were given, and full Matlab codes of MWAS were given. http://www.iaees.org/publications/journals/np/articles/2020-5(3-4)/a-generalized-model-for-overlap-infection-of-pathogens.pdf GuangHua Liu, YanHong Qi, WenJun Zhang.Network Pharmacology,2020,5(3-4):33-37 From the same source or multiple sources, the pathogen may trigger multiple infection processes, and each infection process will cause different theoretical incidence. However, some of the previously infected individuals may be re-infected in the ongoing infection process, that is, the previous and ongoing infections overlap. The higher the previous incidence, the greater the subsequent infections overlap. In the total incidence calculation, the overlap should be removed. In this study, an infection overlap model, based on the probability principles, was proposed as the following: A(ti)=B(t1), i=1; A(ti)=B(ti)(1-Sum(j=1, i-1)A(tj)), i=2,3,..., where A(ti) is the newly occurred infection incidence in i-th infection, ti is the time for occurrence of i-th infection, and B(ti) is the theoretical incidence calculated. The total incidence dynamics is thus: S(ti)=Sum(j=1, i)A(tj), i=1,2,3, ... The model can be used as a fundamental model frame for the epidemic with repeated re-infections by pathogens. http://www.iaees.org/publications/journals/np/articles/2021-6(1-2)/a-discretized-dynamic-model-for-development-of-insecticide-resistance.pdf WenJun Zhang, GuangHua Liu.Network Pharmacology,2021,6(1-2):1-8 In this article, a discretized dynamic model was proposed to describe the development of insecticide resistance. Variables as dosage, timing and frequency of insecticide applications, mutation rate, insecticide-resistant individual's fitness, etc., were included in the model. The model was validated using sensitivity analysis. The model was finally used to evaluate the effect of mixed use of bioinsecticide and chemical insecticide to reduce insecticide resistance. The model can be used to predict the dynamic development of insecticide resistance and to evaluate the effect of various factors on insecticide resistance. http://www.iaees.org/publications/journals/np/articles/2021-6(3-4)/beer-supply-chain-simulated-annealing.pdf Ajay Singh Yadav, Anupam Swami, Navin Ahlawat, Tarun Kumar Arora, Pavan Kumar Chaubey, Karan Pathak.Network Pharmacology,2021,6(3-4):9-23 The impact of the Covid-19 epidemic on inventory management in the supply of the brewing industry is an important part of inventory management in the region and has been a key factor in the overall profitability of the industrial situation. It consists of several steps through which the material goes through different stages to reach the end customer. The impact of the Covid-19 epidemic on the supply chain management of the three-tier brewery industry includes low-cost beer, beer warehouses, and retail locations. A coordinated approach between rates is needed to adjust the chain for lower stocks and lower costs, and thus higher profits. In this paper, we discuss the impact of the three-step coordination of the Covid-19 scourge on the supply chain management of the brewery and one brewery that provides one type of product to distribution centers for each brewery and then for individuals beer industry retailer. The mathematical model is based on the coordinated effects of the Covid-19 catastrophe on the management of the brewery's supply chain, which is solved by using a traveling salesman to improve the ant colony with better values for decision-making and targeting operations. A numerical model is provided and the results obtained here are compared with these methods. http://www.iaees.org/publications/journals/np/articles/2022-7(1-2)/imgResize-Matlab-software-for-resizing-images.pdf WenJun Zhang.Network Pharmacology,2022,7(1-2):1-4 In present study, I developed the Matlab based software for resizing images, imgResize (Version 1.0). Various images with formats as PNG, JPG, GIF, etc., can be resized with specified scales or pixels. Users can choose different methods for resizing images. The excutable software, full Matlab codes and user guide were given. http://www.iaees.org/publications/journals/np/articles/2022-7(3-4)/identifications-of-Aloe-vera-fractions.pdf Eman Tawfik, Mayar Medhat.Network Pharmacology,2022,7(3-4):5-12 Many of the health benefits associated with Aloe vera have been attributed to the polysaccharides contained in the gel of the leaves. These biological activities include promotion of wound healing, antifungal activity, hypoglycemic or antidiabetic effects anti-inflammatory, anticancer, immunomodulatory and gastroprotective properties. There are several mechanisms which contribute to the immunological protection enjoyed by normal persons. Among these mechanisms the ingestion of bacteria and other potentially harmful agents by certain white blood cells and the formation of antibodies. Aloe gel contains substances which are active both in stimulating phagocytosis as well as stimulating the formation of antibodies. These effects include the potential of whole leaf or inner fillet gel liquid preparations of A. vera to enhance the intestinal absorption and bioavailability of co-administered compounds as well as enhancement of skin permeation. In addition, important pharmaceutical applications such as the use of the dried A. vera gel powder as an excipient in sustained release pharmaceutical dosage forms were outlined. http://www.iaees.org/publications/journals/np/articles/2023-8(1-2)/topological-structure-of-tumor-signaling-pathways.pdf WenJun Zhang, XueBing Huang.Network Pharmacology,2023,8(1-2):1-26 Tumorigenesis is a multifactor and multistep process, of which the change of metabolic signaling pathways plays a key role. Most of the previous studies on tumor signaling pathways focused mainly on the metabolic process and chemical processes of some selected metabolites, the tumorigenesis induced by abnormal signaling from mutation of this metabolite or gene, and the chemical structure of ligands, receptors and signaling proteins. However their network biology is seldom studied. Based on the previous studies, the present study was conducted to further analyze the topological structure of tumor signaling pathways using Pajek and UCINET software. Some critical metabolites were found and sensitivity analyses for signaling pathways were conducted. Centrality and core skeleton analysis showed that the crucial metabolites of AKT signaling pathway are Akt-p and Akt; the crucial metabolites of JAK-STAT signaling pathway are JAKs and 23(STATs-P)2; the crucial metabolites of p53 signaling pathway are p53-P-P, Gene Expression, Ac-p53 and (Ac-p53-P)2; the crucial metabolites of Ras signaling pathway are Ras-GTP, Ras-GDP and MEKK1; the crucial metabolites of TNF signaling-pathway are MEKIKs-P-NIK-P and TRADD, and for VEGF signaling pathway, the crucial metabolites are PIP3 and ANGIOGENESIS. The performance of cascade model was poor in predicting topological properties of tumor signaling pathways. http://www.iaees.org/publications/journals/np/articles/2023-8(3-4)/information-system-Chinese-herbal-medicines.pdf WenJun Zhang, QingShun Wei.Network Pharmacology,2023,8(3-4):27-63 In present study, we developed the web database CHM-DATA Version 1.2 based on the previous database CHM-DATA Version 1.0 (Zhang, 2017a), a database of attributes and functions of Chinese herbal medicines. The information system of attributes and functions of Chinese herbal medicines (ISAFCHM) was developed based on CHM-DATA Version 1.2, which is used for online query of attributes and functions of Chinese herbal medicines. In this system, there are more than 1,000 kinds of Chinese herbal medicines (about 2,000 species of plants or fungi), about 200 families, about 80 kinds of attributes and typical chemical composition categories and, nearly 100 medicinal functions, etc. Users can choose to list the complete set of information on the attributes and functions of Chinese herbal medicines, or can choose to list the filtered information according to selected keywords (about 1,500 keywords in total) for medicine name, species, family, medicinal organs or tissues, taste attributes, medicinal properties, toxicity attribuite, chemical composition categories, meridians and collaterals, and medicinal functions,, etc. Each piece information of Chinese herbal medicines includes the following content: medicine name, pinyin name, Latin scientific name, international standard name, family name, medicinal organs or tissues, taste attributes, medicinal properties, toxicity attribuite, chemical composition categories, meridians and collaterals, and medicinal functions, etc. Different from the information system based on static web pages, the present system ISAFCHM is based on the web database, with only about five files, small storage space, easy to upgrade, maintain and update, low error rate, and conducive to information mining and analysis. More importantly, it is beneficial for users to find interesting information. At the bottom left of each page of ISAFCHM, there is Google Translate, which can translate the Chinese on the current page into any selected language, thus realizing the internationalization of ISAFCHM. http://www.iaees.org/publications/journals/np/articles/2024-9(1-2)/standalone-executable-software-for-network-visualization.pdf WenJun Zhang.Network Pharmacology,2024,9(1-2):1-10 A standalone executable software for network visualization, netVisual 2.0, was developed based on the previous studies. It can be used in Windows operating systems and is not dependent upon any runtime environment. Based on the data of network information, netVisual 2.0 will generate a HTML file from which a network can be visualized and user-interacted in the web browsers. Both netVisual 2.0 and demonstration data files were given. http://www.iaees.org/publications/journals/np/articles/2024-9(3-4)/a-projector-and-a-screen-saver.pdf WenJun Zhang.Network Pharmacology,2024,9(3-4):11-23 Computer software will help biological researchers view and handle bio-graphics and images. Two standalone executable image viewers, Projector 1.0.exe and scrSaver 1.0.scr, which can be used to play JPG, BMP or ICO image files automatically and continually in Windows operating systems, were developed in present study. Projector 1.0 is an image projector and scrSaver 1.0 is a screen saver. In the Projector 1.0, users can set the time duration for displaying every image, choose random or sequential displaying and choose to stretch images or remain their original sizes on screen. After downloading and decompressing the package, copy and put them in any local folder containing multiple images. Double-click to run them. For scrSaver 1.0, the screen will enter the screen saver pattern, and randomly play the images in the folder. For the two software, they will exit the playing when there is a mouse or keyboard action. Both software and demo image files were given in a free package. http://www.iaees.org/publications/journals/np/articles/2025-10(1-2)/head-tilt-exercise-significantly-lowers-blood-pressure.pdf WenJun Zhang, YanHong Qi.Network Pharmacology,2025,10(1-2):1-13 In present study, the effect of head tilt excise for lowering blood pressure is experimented. The results show that there is a significant difference between systolic blood pressures before and during one-time excise, between diatolic blood pressures before and during one-time excise, and between cardiac rates before and during one-time excise. Systolic blood pressure and diastolic blood pressure will decline 7 mmHg and 3 mmHg during one-time head tilt excise. Cardiac rate will decline 2 beats/min during one-time head tilt excise. Systolic blood pressure benefits mostly from one-time head tilt excise, seconded by diatolic blood pressure, and cardiac rate benefits least from one-time head tilt excise. The effect of one-time head tilt excise for lowering systolic blood pressure and cardiac rate significantly increases with systolic blood pressure and cardiac rate respectively. There is a significant difference between systolic blood pressures before and after 15-min head tilt excise, and between diatolic blood pressures before and after 15-min head tilt excise. Systolic blood pressure and diatolic blood pressure will decline 8 mmHg and 5 mmHg respectively after 15-min head tilt excise. There is not significant difference between cardiac rates before and after 15-min head tilt excise. Systolic blood pressure benefits mostly from 15-min head tilt excise, seconded by diatolic blood pressure, and cardiac rate may not benefit from 15-min head tilt excise. The effect of 15-min head tilt excise for lowering systolic blood pressure, diastolic blood pressure and cardiac rate significantly increases with systolic blood pressure, diastolic blood pressure and cardiac rate respectively. The effect of 15-min head tilt excise in lowering diatolic blood pressure significantly increases with time (days). In average, diastolic blood pressure declines 6 mmHg after one month. The effect in systolic blood pressure slightly increases with time. However for cardiac rate, the effect is not significant. On the mechanism of head tilt excise in lowering blood pressure, we hold that tilting head back interferes with the transmission of nerve signals from the brain to the organs, weakens sympathetic nerve activity, stimulates vagus nerve activity, decreases the secretion of angiotensin and some other blood pressure related substances to blood vessels, and reduces cardiac rate. While the long-term exercise can cause the sympathetic nerve activity related to blood pressure to become permanently blunted and thus lead to permenent declining of blood pressure. Finally, we conclude that head tilt excise can be used as an effective treatment measure for instantly or permanently lowering blood pressure. http://www.iaees.org/publications/journals/np/articles/2025-10(3-4)/web-based-data-generator-for-Mendelian-Randomization.pdf WenJun Zhang.Network Pharmacology,2025,10(3-4):14-111 In present study, a data generator for Mendelian Randomization (MR) was presented. It is a comprehensive web-based tool designed for Mendelian Randomization (MR) analysis. It provides an integrated workflow for processing genetic association data, automatic harmonization, correlation matrix generation, and MR input construction. The tool supports both univariate and multivariate MR analyses. http://www.iaees.org/publications/journals/np/articles/2026-11(1-2)/a-multi-source-GWAS-data-fetcher.pdf WenJun Zhang.Network Pharmacology,2026,11(1-2):1-61 In present study, a multi-source GWAS (Genome-Wide Association Study) data fetchor for Mendelian Randomization (MR) analysis was presented. The data fetcher is a web-based application designed to retrieve, harmonize, and export GWAS summary statistics from multiple legitimate public repositories for Mendelian Randomization (MR) analysis. The system implements a modular architecture that integrates with major GWAS data sources, standardizes heterogeneous data formats, harmonizes genetic variants across datasets, validates data quality through statistical filtering, and exports analysis-ready files in standard MR formats. The algorithm processes exposure and outcome traits through a multi-stage pipeline that ensures data integrity and compatibility with downstream MR analysis methods. The tool supports both univariate and multivariate MR analyses. http://www.iaees.org/publications/journals/np/articles/2027-12(1-2)/head-tilt-exercises-significantly-enhance-heart-rate-variability.pdf WenJun Zhang.Network Pharmacology,2027,12(1-2):1-8 Heart rate variability (HRV) is one of the most important indicators for heart and overall health. In present study, the effect of long-term head tilt excises on HRV is experimented. The results demonstrated that heart rate variability can be enhanced through long-term head tilt excises. In addition, HRV decreases as the increase of pulse wave velocity. Pulse pressure increases as the increase of pulse wave velocity. Diastolic pressure decreases as the increase of pulse wave velocity. The physiological mechanism by which long-term head tilt exercises enhance HRV is that the exercises reduce sympathetic nervous activity and increase parasympathetic nervous activity by squeezing the back of the neck. Long-term head tilt exercises can help maintain sympathetic activity at a lower level while keeping parasympathetic activity at a higher level, thereby enhancing HRV.