{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T03:46:37Z","timestamp":1793677597501,"version":"4.5.1"},"reference-count":106,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T00:00:00Z","timestamp":1611619200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T00:00:00Z","timestamp":1611619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004846","name":"Beijing University of Chinese Medicine","doi-asserted-by":"publisher","award":["2019-JYB-TD010"],"award-info":[{"award-number":["2019-JYB-TD010"]}],"id":[{"id":"10.13039\/501100004846","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004846","name":"Beijing University of Chinese Medicine","doi-asserted-by":"publisher","award":["2018-zxfzjj-002"],"award-info":[{"award-number":["2018-zxfzjj-002"]}],"id":[{"id":"10.13039\/501100004846","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7202115"],"award-info":[{"award-number":["7202115"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Oligoasthenozoospermia (OA) is one of the most common types of male infertility affecting sperm count and sperm motility. Unfortunately, it is difficult for existing drugs to fundamentally improve the sperm quality of OA patients, because the pathological mechanism of OA has not been fully elucidated yet.<jats:italic>Morinda officinalis<\/jats:italic>\u2013<jats:italic>Lycium barbarum<\/jats:italic>coupled-herbs (MOLBCH), as traditional Chinese Medicines, has been widely used for treating OA over thousands of years, but its molecular mechanism is still unclear. For this purpose, we adopted a comprehensive approach integrated network pharmacology and molecular docking to reveal the bioactive components and potential targets of MOLBCH against OA. The results showed that MOLBCH alleviated apoptosis, promoted male reproductive function, and reduced oxidant stress in the treatment of OA. Ohioensin-A, quercetin, beta-sitosterol and sitosterol were the key bioactive components. Androgen receptor (AR), Estrogen receptor (ESR1), Mitogen-activated protein kinase 3 (MAPK3), RAC-alpha serine\/threonine-protein kinase (AKT1), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were the core potential targets. PI3K\/Akt signaling pathway, prostate cancer, AGE-RAGE signaling pathway in diabetic complications were the most representative pathways. Moreover, molecular docking was performed to validate the strong binding interactions between the obtained core components and targets. These observations provide deeper insight into the pathogenesis of OA and can be used to design new drugs and develop new therapeutic instructions to treat OA.<\/jats:p>","DOI":"10.1038\/s41598-020-80780-6","type":"journal-article","created":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T11:05:05Z","timestamp":1611659105000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Network pharmacology integrated molecular docking reveals the bioactive components and potential targets of Morinda officinalis\u2013Lycium barbarum coupled-herbs against oligoasthenozoospermia"],"prefix":"10.1038","volume":"11","author":[{"given":"Xue","family":"Bai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibo","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guimin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingru","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfei","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenquan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,26]]},"reference":[{"key":"80780_CR1","doi-asserted-by":"publisher","first-page":"2683","DOI":"10.1093\/humrep\/dep343","volume":"24","author":"F Zegers-Hochschild","year":"2009","unstructured":"Zegers-Hochschild, F. et al. The International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary on ART Terminology, 2009. Hum. Reprod. 24, 2683\u20132687 (2009).","journal-title":"Hum. Reprod."},{"key":"80780_CR2","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/j.eururo.2005.06.002","volume":"48","author":"GR Dohle","year":"2005","unstructured":"Dohle, G. R. et al. EAU guidelines on male infertility. Eur. Urol. 48, 703\u2013711 (2005).","journal-title":"Eur. Urol."},{"key":"80780_CR3","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1111\/andr.12420","volume":"5","author":"J Amory","year":"2017","unstructured":"Amory, J. et al. Isotretinoin administration improves sperm production in men with infertility from Oligoasthenozoospermia: a pilot study. Andrology 5, 1115\u20131123 (2017).","journal-title":"Andrology"},{"key":"80780_CR4","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1093\/humupd\/dmp048","volume":"16","author":"TG Cooper","year":"2010","unstructured":"Cooper, T. G. et al. World Health Organization reference values for human semen characteristics. Hum. Reprod. Update 16, 231\u2013245 (2010).","journal-title":"Hum. Reprod. Update"},{"key":"80780_CR5","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.fertnstert.2019.12.007","volume":"113","author":"B Singh","year":"2020","unstructured":"Singh, B., Reschke, L., Segars, J. & Baker, V. L. Frozen-thawed embryo transfer: the potential importance of the corpus luteum in preventing obstetrical complications. Fertil. Steril. 113, 252\u2013257 (2020).","journal-title":"Fertil. Steril."},{"key":"80780_CR6","doi-asserted-by":"publisher","first-page":"e13654","DOI":"10.1111\/and.13654","volume":"52","author":"E Illiano","year":"2020","unstructured":"Illiano, E., Trama, F. & Costantini, E. Could COVID-19 have an impact on male fertility?. Andrologia 52, e13654 (2020).","journal-title":"Andrologia"},{"key":"80780_CR7","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1038\/s41585-020-0319-7","volume":"17","author":"S Wang","year":"2020","unstructured":"Wang, S., Zhou, X., Zhang, T. & Wang, Z. The need for urogenital tract monitoring in COVID-19. Nat. Rev. Urol. 17, 314\u2013315 (2020).","journal-title":"Nat. Rev. Urol."},{"key":"80780_CR8","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1016\/j.fertnstert.2020.04.025","volume":"113","author":"J Segars","year":"2020","unstructured":"Segars, J. et al. Prior and novel coronaviruses, COVID-19, and human reproduction: what is known?. Fertil. Steril. 113, 1140\u20131149 (2020).","journal-title":"Fertil. Steril."},{"key":"80780_CR9","doi-asserted-by":"publisher","first-page":"7628125","DOI":"10.1155\/2019\/7628125","volume":"2019","author":"Z Yang","year":"2019","unstructured":"Yang, Z., Zhang, X., Chen, Z. & Hu, C. Effect of Wuzi Yanzong on reproductive hormones and TGF-beta1\/Smads signal pathway in rats with Oligoasthenozoospermia. Evid. Based Complement. Altern. Med. 2019, 7628125 (2019).","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"80780_CR10","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-3-030-32300-4_1","volume-title":"Male Infertility","author":"GL Machen","year":"2020","unstructured":"Machen, G. L. & Sandlow, J. I. Male Infertility 3\u201314 (Springer, Berlin, 2020)."},{"key":"80780_CR11","first-page":"508","volume":"58","author":"A Starc","year":"2019","unstructured":"Starc, A. et al. Infertility and sexual dysfunctions: a systematic literature review. Acta Clinica Croatica 58, 508\u2013515 (2019).","journal-title":"Acta Clinica Croatica"},{"key":"80780_CR12","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/S0015-0282(01)02966-1","volume":"77","author":"C Foresta","year":"2002","unstructured":"Foresta, C. et al. Use of recombinant human follicle-stimulating hormone in the treatment of male factor infertility. Fertil. Steril. 77, 238\u2013244 (2002).","journal-title":"Fertil. Steril."},{"key":"80780_CR13","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1007\/s00404-015-3707-0","volume":"292","author":"J Qin","year":"2015","unstructured":"Qin, J. et al. Assisted reproductive technology and risk of congenital malformations: a meta-analysis based on cohort studies. Arch. Gynecol. Obstet. 292, 777\u2013798 (2015).","journal-title":"Arch. Gynecol. Obstet."},{"key":"80780_CR14","first-page":"297","volume-title":"International Review of Neurobiology","author":"D Jiang","year":"2017","unstructured":"Jiang, D., Coscione, A., Li, L. & Zeng, B.-Y. International Review of Neurobiology Vol. 135, 297\u2013311 (Elsevier, New York, 2017)."},{"key":"80780_CR15","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1049\/iet-syb:20060032","volume":"1","author":"S Li","year":"2007","unstructured":"Li, S. et al. Understanding ZHENG in traditional Chinese medicine in the context of neuro-endocrine-immune network. IET Syst. Biol. 1, 51\u201360 (2007).","journal-title":"IET Syst. Biol."},{"key":"80780_CR16","first-page":"1","volume":"2014","author":"H Li","year":"2014","unstructured":"Li, H. et al. A network pharmacology approach to determine active compounds and action mechanisms of ge-gen-qin-lian decoction for treatment of type 2 diabetes. Evid. Based Complement. Altern. Med. 2014, 1\u201312 (2014).","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"80780_CR17","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1038\/nchembio.118","volume":"4","author":"AL Hopkins","year":"2008","unstructured":"Hopkins, A. L. Network pharmacology: the next paradigm in drug discovery. Nat. Chem. Biol. 4, 682\u2013690 (2008).","journal-title":"Nat. Chem. Biol."},{"key":"80780_CR18","first-page":"110","volume":"11","author":"L Shao","year":"2013","unstructured":"Shao, L. & Zhang, B. Traditional Chinese medicine network pharmacology: theory, methodology and application. Chin. J. Nat. Med. 11, 110\u2013120 (2013).","journal-title":"Chin. J. Nat. Med."},{"key":"80780_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-29764-1","volume":"8","author":"H Zuo","year":"2018","unstructured":"Zuo, H. et al. A network pharmacology-based approach to analyse potential targets of traditional herbal formulas: an example of Yu Ping Feng decoction. Sci. Rep. 8, 1\u201315 (2018).","journal-title":"Sci. Rep."},{"key":"80780_CR20","doi-asserted-by":"publisher","first-page":"5500","DOI":"10.1021\/ja00196a085","volume":"111","author":"GQ Zheng","year":"1989","unstructured":"Zheng, G. Q., Chang, C. J., Stout, T. J., Clardy, J. & Cassady, J. M. Ohioensin-A: a novel benzonaphthoxanthenone from Polytrichum ohioense. J. Am. Chem. Soc. 111, 5500\u20135501 (1989).","journal-title":"J. Am. Chem. Soc."},{"key":"80780_CR21","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1111\/j.1745-7262.2008.00306.x","volume":"10","author":"L Taepongsorat","year":"2008","unstructured":"Taepongsorat, L., Tangpraprutgul, P., Kitana, N. & Malaivijitnond, S. Stimulating effects of quercetin on sperm quality and reproductive organs in adult male rats. Asian J. Androl. 10, 249\u2013258 (2008).","journal-title":"Asian J. Androl."},{"key":"80780_CR22","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1002\/ptr.3100","volume":"24","author":"A Khaki","year":"2010","unstructured":"Khaki, A. et al. Beneficial effects of quercetin on sperm parameters in streptozotocin-induced diabetic male rats. Phytother. Res. 24, 1285\u20131291 (2010).","journal-title":"Phytother. Res."},{"key":"80780_CR23","doi-asserted-by":"publisher","first-page":"168","DOI":"10.2174\/2215083803666170615111759","volume":"3","author":"K Patel","year":"2017","unstructured":"Patel, K., Kumar, V., Verma, A., Rahman, M. & Patel, D. K. \u03b2-sitosterol: bioactive compounds in foods, their role in health promotion and disease prevention \u201ca concise report of its phytopharmaceutical importance\u201d. Curr. Tradit. Med. 3, 168\u2013177 (2017).","journal-title":"Curr. Tradit. Med."},{"key":"80780_CR24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-016-0001-8","volume":"6","author":"B Yang","year":"2016","unstructured":"Yang, B., Yang, Y.-S., Yang, N., Li, G. & Zhu, H.-L. Design, biological evaluation and 3D QSAR studies of novel dioxin-containing pyrazoline derivatives with thiourea skeleton as selective HER-2 inhibitors. Sci. Rep. 6, 1\u201312 (2016).","journal-title":"Sci. Rep."},{"key":"80780_CR25","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/S0015-0282(02)03105-9","volume":"77","author":"ID Sharlip","year":"2002","unstructured":"Sharlip, I. D. et al. Best practice policies for male infertility. Fertil. Steril. 77, 873\u2013882 (2002).","journal-title":"Fertil. Steril."},{"key":"80780_CR26","doi-asserted-by":"publisher","first-page":"364","DOI":"10.4103\/1008-682X.179249","volume":"18","author":"RP Smith","year":"2016","unstructured":"Smith, R. P., Lipshultz, L. I. & Kovac, J. R. Stem cells, gene therapy, and advanced medical management hold promise in the treatment of male infertility. Asian J. Androl. 18, 364 (2016).","journal-title":"Asian J. Androl."},{"key":"80780_CR27","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/978-1-4614-3335-4_20","volume-title":"Male Infertility","author":"A Rhoton-Vlasak","year":"2012","unstructured":"Rhoton-Vlasak, A. & Drury, K. C. Male Infertility 197\u2013206 (Springer, Berlin, 2012)."},{"key":"80780_CR28","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.lfs.2011.12.017","volume":"90","author":"H-E Byeon","year":"2012","unstructured":"Byeon, H.-E., Um, S. H., Yim, J. H., Lee, H. K. & Pyo, S. Ohioensin F suppresses TNF-\u03b1-induced adhesion molecule expression by inactivation of the MAPK, Akt and NF-\u03baB pathways in vascular smooth muscle cells. Life Sci. 90, 396\u2013406 (2012).","journal-title":"Life Sci."},{"key":"80780_CR29","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1016\/j.clnu.2013.08.011","volume":"33","author":"G Sharmila","year":"2014","unstructured":"Sharmila, G. et al. Chemopreventive effect of quercetin, a natural dietary flavonoid on prostate cancer in in vivo model. Clin. Nutr. 33, 718\u2013726 (2014).","journal-title":"Clin. Nutr."},{"key":"80780_CR30","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1002\/mnfr.200500036","volume":"49","author":"H van der Woude","year":"2005","unstructured":"van der Woude, H. et al. The stimulation of cell proliferation by quercetin is mediated by the estrogen receptor. Mol. Nutr. Food Res. 49, 763\u2013771 (2005).","journal-title":"Mol. Nutr. Food Res."},{"key":"80780_CR31","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1002\/jcp.22917","volume":"227","author":"P Bulzomi","year":"2012","unstructured":"Bulzomi, P. et al. The pro-apoptotic effect of quercetin in cancer cell lines requires ER\u03b2-dependent signals. J. Cell. Physiol. 227, 1891\u20131898 (2012).","journal-title":"J. Cell. Physiol."},{"key":"80780_CR32","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1002\/pros.23536","volume":"78","author":"LQ Meng","year":"2018","unstructured":"Meng, L. Q. et al. Quercetin protects against chronic prostatitis in rat model through NF-\u03baB and MAPK signaling pathways. Prostate 78, 790\u2013800 (2018).","journal-title":"Prostate"},{"key":"80780_CR33","doi-asserted-by":"publisher","first-page":"2583","DOI":"10.12659\/MSM.906172","volume":"24","author":"J Lu","year":"2018","unstructured":"Lu, J. et al. Quercetin inhibits the migration and invasion of HCCLM3 cells by suppressing the expression of p-Akt1, matrix metalloproteinase (MMP) MMP-2, and MMP-9. Med. Sci. Monit. 24, 2583 (2018).","journal-title":"Med. Sci. Monit."},{"key":"80780_CR34","unstructured":"Cabeza, M. et al. In Proceedings-Western Pharmacology Society 153\u2013155 (Western Pharmacology Society, 1998)."},{"key":"80780_CR35","doi-asserted-by":"publisher","first-page":"2538","DOI":"10.1016\/j.bbagen.2012.12.012","volume":"1830","author":"C Shi","year":"2013","unstructured":"Shi, C., Wu, F., Zhu, X. & Xu, J. Incorporation of \u03b2-sitosterol into the membrane increases resistance to oxidative stress and lipid peroxidation via estrogen receptor-mediated PI3K\/GSK3\u03b2 signaling. Biochim. Biophys. Acta BBA Gen. Subj. 1830, 2538\u20132544 (2013).","journal-title":"Biochim. Biophys. Acta BBA Gen. Subj."},{"key":"80780_CR36","doi-asserted-by":"publisher","first-page":"173004","DOI":"10.1016\/j.ejphar.2020.173004","volume":"873","author":"S Babu","year":"2020","unstructured":"Babu, S. et al. Beta-sitosterol attenuates insulin resistance in adipose tissue via IRS-1\/Akt mediated insulin signaling in high fat diet and sucrose induced type-2 diabetic rats. Eur. J. Pharmacol. 873, 173004 (2020).","journal-title":"Eur. J. Pharmacol."},{"key":"80780_CR37","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1111\/j.1365-2265.2006.02635.x","volume":"65","author":"A Ferlin","year":"2006","unstructured":"Ferlin, A. et al. Male infertility and androgen receptor gene mutations: clinical features and identification of seven novel mutations. Clin. Endocrinol. 65, 606\u2013610 (2006).","journal-title":"Clin. Endocrinol."},{"key":"80780_CR38","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1007\/s00345-003-0365-9","volume":"21","author":"G Dohle","year":"2003","unstructured":"Dohle, G., Smit, M. & Weber, R. Androgens and male fertility. World J. Urol. 21, 341\u2013345 (2003).","journal-title":"World J. Urol."},{"key":"80780_CR39","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.beem.2015.04.006","volume":"29","author":"L O'Hara","year":"2015","unstructured":"O\u2019Hara, L. & Smith, L. B. Androgen receptor roles in spermatogenesis and infertility. Best Pract. Res. Clin. Endocrinol. Metab. 29, 595\u2013605 (2015).","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"80780_CR40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/humupd\/dmg003","volume":"9","author":"E Yong","year":"2003","unstructured":"Yong, E., Loy, C. & Sim, K. Androgen receptor gene and male infertility. Hum. Reprod. Update 9, 1\u20137 (2003).","journal-title":"Hum. Reprod. Update"},{"key":"80780_CR41","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.mce.2016.03.024","volume":"428","author":"K Dumasia","year":"2016","unstructured":"Dumasia, K., Kumar, A., Deshpande, S., Sonawane, S. & Balasinor, N. Differential roles of estrogen receptors, ESR1 and ESR2, in adult rat spermatogenesis. Mol. Cell. Endocrinol. 428, 89\u2013100 (2016).","journal-title":"Mol. Cell. Endocrinol."},{"key":"80780_CR42","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1095\/biolreprod.109.079889","volume":"82","author":"A Joseph","year":"2010","unstructured":"Joseph, A. et al. Absence of estrogen receptor alpha leads to physiological alterations in the mouse epididymis and consequent defects in sperm function. Biol. Reprod. 82, 948\u2013957 (2010).","journal-title":"Biol. Reprod."},{"key":"80780_CR43","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1095\/biolreprod.109.080366","volume":"82","author":"A Joseph","year":"2010","unstructured":"Joseph, A., Shur, B. D., Ko, C., Chambon, P. & Hess, R. A. Epididymal hypo-osmolality induces abnormal sperm morphology and function in the estrogen receptor alpha knockout mouse. Biol. Reprod. 82, 958\u2013967 (2010).","journal-title":"Biol. Reprod."},{"key":"80780_CR44","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.mce.2011.12.018","volume":"351","author":"LJ Brokken","year":"2012","unstructured":"Brokken, L. J. et al. Association of polymorphisms in genes encoding hormone receptors ESR1, ESR2 and LHCGR with the risk and clinical features of testicular germ cell cancer. Mol. Cell. Endocrinol. 351, 279\u2013285 (2012).","journal-title":"Mol. Cell. Endocrinol."},{"key":"80780_CR45","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.molmed.2009.02.002","volume":"15","author":"MW Li","year":"2009","unstructured":"Li, M. W., Mruk, D. D. & Cheng, C. Y. Mitogen-activated protein kinases in male reproductive function. Trends Mol. Med. 15, 159\u2013168 (2009).","journal-title":"Trends Mol. Med."},{"key":"80780_CR46","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1016\/j.theriogenology.2010.11.031","volume":"75","author":"N Cocchia","year":"2011","unstructured":"Cocchia, N. et al. Effect of sod (superoxide dismutase) protein supplementation in semen extenders on motility, viability, acrosome status and ERK (extracellular signal-regulated kinase) protein phosphorylation of chilled stallion spermatozoa. Theriogenology 75, 1201\u20131210 (2011).","journal-title":"Theriogenology"},{"key":"80780_CR47","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1111\/j.1365-2605.2009.01000.x","volume":"33","author":"A Poplinski","year":"2010","unstructured":"Poplinski, A., T\u00fcttelmann, F., Kanber, D., Horsthemke, B. & Gromoll, J. Idiopathic male infertility is strongly associated with aberrant methylation of MEST and IGF2\/H19 ICR1. Int. J. Androl. 33, 642\u2013649 (2010).","journal-title":"Int. J. Androl."},{"key":"80780_CR48","doi-asserted-by":"publisher","first-page":"4213","DOI":"10.1210\/en.2006-0174","volume":"147","author":"T Rasoulpour","year":"2006","unstructured":"Rasoulpour, T., DiPalma, K., Kolvek, B. & Hixon, M. Akt1 suppresses radiation-induced germ cell apoptosis in vivo. Endocrinology 147, 4213\u20134221 (2006).","journal-title":"Endocrinology"},{"key":"80780_CR49","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.reprotox.2010.09.012","volume":"31","author":"J Santos-Ahmed","year":"2011","unstructured":"Santos-Ahmed, J. et al. Akt1 protects against germ cell apoptosis in the postnatal mouse testis following lactational exposure to 6-N-propylthiouracil. Reprod. Toxicol. 31, 17\u201325 (2011).","journal-title":"Reprod. Toxicol."},{"key":"80780_CR50","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.toxlet.2006.10.015","volume":"168","author":"D Gunnarsson","year":"2007","unstructured":"Gunnarsson, D., Nordberg, G. & Selstam, G. Differential effects of cadmium on the gene expression of seven-transmembrane-spanning receptors and GAPDH in the rat testis. Toxicol. Lett. 168, 51\u201357 (2007).","journal-title":"Toxicol. Lett."},{"key":"80780_CR51","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.ydbio.2009.08.002","volume":"334","author":"N Etkovitz","year":"2009","unstructured":"Etkovitz, N. et al. Bovine sperm acrosome reaction induced by G protein-coupled receptor agonists is mediated by epidermal growth factor receptor transactivation. Dev. Biol. 334, 447\u2013457 (2009).","journal-title":"Dev. Biol."},{"key":"80780_CR52","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/aja.2010.78","volume":"13","author":"H Breitbart","year":"2011","unstructured":"Breitbart, H. & Etkovitz, N. Role and regulation of EGFR in actin remodeling in sperm capacitation and the acrosome reaction. Asian J. Androl. 13, 106 (2011).","journal-title":"Asian J. Androl."},{"key":"80780_CR53","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1038\/318533a0","volume":"318","author":"J Adams","year":"1985","unstructured":"Adams, J. et al. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature 318, 533\u2013538 (1985).","journal-title":"Nature"},{"key":"80780_CR54","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/0092-8674(92)90123-T","volume":"69","author":"GI Evan","year":"1992","unstructured":"Evan, G. I. et al. Induction of apoptosis in fibroblasts by c-myc protein. Cell 69, 119\u2013128 (1992).","journal-title":"Cell"},{"key":"80780_CR55","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/1477-7827-7-65","volume":"7","author":"I Hammami","year":"2009","unstructured":"Hammami, I., Amara, S., Benahmed, M., May, M. V. E. & Mauduit, C. Chronic crude garlic-feeding modified adult male rat testicular markers: mechanisms of action. Reprod. Biol. Endocrinol. 7, 65 (2009).","journal-title":"Reprod. Biol. Endocrinol."},{"key":"80780_CR56","doi-asserted-by":"publisher","first-page":"364","DOI":"10.2527\/asasann.2017.751","volume":"95","author":"A Cupp","year":"2017","unstructured":"Cupp, A. et al. 751 Divergent vascular endothelial growth factor a (VEGFA) signaling determines spermatogonial stem cell fate. J. Anim. Sci. 95, 364\u2013364 (2017).","journal-title":"J. Anim. Sci."},{"key":"80780_CR57","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/j.cell.2014.02.055","volume":"157","author":"C Yee","year":"2014","unstructured":"Yee, C., Yang, W. & Hekimi, S. The intrinsic apoptosis pathway mediates the pro-longevity response to mitochondrial ROS in C elegans. Cell 157, 897\u2013909 (2014).","journal-title":"Cell"},{"key":"80780_CR58","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.toxlet.2015.06.015","volume":"237","author":"X-N Cao","year":"2015","unstructured":"Cao, X.-N. et al. Fine particulate matter leads to reproductive impairment in male rats by overexpressing phosphatidylinositol 3-kinase (PI3K)\/protein kinase B (Akt) signaling pathway. Toxicol. Lett. 237, 181\u2013190 (2015).","journal-title":"Toxicol. Lett."},{"key":"80780_CR59","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.1002\/ijc.22862","volume":"121","author":"S Shukla","year":"2007","unstructured":"Shukla, S. et al. Activation of PI3K-Akt signaling pathway promotes prostate cancer cell invasion. Int. J. Cancer 121, 1424\u20131432 (2007).","journal-title":"Int. J. Cancer"},{"key":"80780_CR60","doi-asserted-by":"publisher","first-page":"2441","DOI":"10.1039\/C4MB00287C","volume":"10","author":"J Du","year":"2014","unstructured":"Du, J. et al. KEGG-PATH: Kyoto encyclopedia of genes and genomes-based pathway analysis using a path analysis model. Mol. BioSyst. 10, 2441\u20132447 (2014).","journal-title":"Mol. BioSyst."},{"key":"80780_CR61","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1111\/j.1439-0272.2011.01178.x","volume":"44","author":"J Karimi","year":"2012","unstructured":"Karimi, J., Goodarzi, M., Tavilani, H., Khodadadi, I. & Amiri, I. Increased receptor for advanced glycation end products in spermatozoa of diabetic men and its association with sperm nuclear DNA fragmentation. Andrologia 44, 280\u2013286 (2012).","journal-title":"Andrologia"},{"key":"80780_CR62","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.phymed.2016.02.005","volume":"23","author":"YS Kim","year":"2016","unstructured":"Kim, Y. S., Jung, D. H., Lee, I.-S., Pyun, B.-J. & Kim, J. S. Osteomeles schwerinae extracts inhibits the binding to receptors of advanced glycation end products and TGF-\u03b21 expression in mesangial cells under diabetic conditions. Phytomedicine 23, 388\u2013397 (2016).","journal-title":"Phytomedicine"},{"key":"80780_CR63","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.diabres.2010.09.024","volume":"91","author":"J Karimi","year":"2011","unstructured":"Karimi, J., Goodarzi, M., Tavilani, H., Khodadadi, I. & Amiri, I. Relationship between advanced glycation end products and increased lipid peroxidation in semen of diabetic men. Diabetes Res. Clin. Pract. 91, 61\u201366 (2011).","journal-title":"Diabetes Res. Clin. Pract."},{"key":"80780_CR64","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.reprotox.2020.02.002","volume":"93","author":"TS Omolaoye","year":"2020","unstructured":"Omolaoye, T. S. & du Plessis, S. S. Male infertility: a proximate look at the advanced glycation end products. Reprod. Toxicol. 93, 169\u2013177 (2020).","journal-title":"Reprod. Toxicol."},{"key":"80780_CR65","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.mce.2007.11.011","volume":"282","author":"T Almog","year":"2008","unstructured":"Almog, T. & Naor, Z. Mitogen activated protein kinases (MAPKs) as regulators of spermatogenesis and spermatozoa functions. Mol. Cell. Endocrinol. 282, 39\u201344 (2008).","journal-title":"Mol. Cell. Endocrinol."},{"key":"80780_CR66","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ydbio.2005.08.001","volume":"286","author":"C-H Wong","year":"2005","unstructured":"Wong, C.-H. & Cheng, C. Y. Mitogen-activated protein kinases, adherens junction dynamics, and spermatogenesis: a review of recent data. Dev. Biol. 286, 1\u201315 (2005).","journal-title":"Dev. Biol."},{"key":"80780_CR67","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1002\/jemt.20704","volume":"72","author":"VA Guazzone","year":"2009","unstructured":"Guazzone, V. A., Jacobo, P., Theas, M. S. & Lustig, L. Cytokines and chemokines in testicular inflammation: a brief review. Microsc. Res. Tech. 72, 620\u2013628 (2009).","journal-title":"Microsc. Res. Tech."},{"key":"80780_CR68","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1097\/BOR.0b013e328304b6b5","volume":"20","author":"LA Garrett-Sinha","year":"2008","unstructured":"Garrett-Sinha, L. A., John, S. & Gaffen, S. L. IL-17 and the Th17 lineage in systemic lupus erythematosus. Curr. Opin. Rheumatol. 20, 519\u2013525 (2008).","journal-title":"Curr. Opin. Rheumatol."},{"key":"80780_CR69","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1530\/REP-10-0362","volume":"141","author":"P Jacobo","year":"2011","unstructured":"Jacobo, P., P\u00e9rez, C. V., Theas, M. S., Guazzone, V. A. & Lustig, L. CD4+ and CD8+ T cells producing Th1 and Th17 cytokines are involved in the pathogenesis of autoimmune orchitis. Reproduction 141, 249\u2013258 (2011).","journal-title":"Reproduction"},{"key":"80780_CR70","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/aja.2012.112","volume":"15","author":"O Celik","year":"2013","unstructured":"Celik, O., Kutlu, O., Tekcan, M., Celik-Ozenci, C. & Koksal, I. T. Role of TNF-related apoptosis-inducing ligand (TRAIL) in the pathogenesis of varicocele-induced testicular dysfunction. Asian J. Androl. 15, 269\u2013274 (2013).","journal-title":"Asian J. Androl."},{"key":"80780_CR71","doi-asserted-by":"publisher","first-page":"3403","DOI":"10.1002\/jcp.22703","volume":"226","author":"C Guido","year":"2011","unstructured":"Guido, C. et al. Human sperm physiology: estrogen receptor alpha (ER\u03b1) and estrogen receptor beta (ER\u03b2) influence sperm metabolism and may be involved in the pathophysiology of varicocele-associated male infertility. J. Cell. Physiol. 226, 3403\u20133412 (2011).","journal-title":"J. Cell. Physiol."},{"key":"80780_CR72","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1097\/01.LAB.0000079784.81186.B9","volume":"83","author":"CS Samuel","year":"2003","unstructured":"Samuel, C. S., Tian, H., Zhao, L. & Amento, E. P. Relaxin is a key mediator of prostate growth and male reproductive tract development. Lab. Investig. 83, 1055\u20131067 (2003).","journal-title":"Lab. Investig."},{"key":"80780_CR73","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/j.apsb.2015.07.001","volume":"5","author":"L Huang","year":"2015","unstructured":"Huang, L. & Fu, L. Mechanisms of resistance to EGFR tyrosine kinase inhibitors. Acta Pharmaceutica Sinica B 5, 390\u2013401 (2015).","journal-title":"Acta Pharmaceutica Sinica B"},{"key":"80780_CR74","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1055\/a-0859-1144","volume":"51","author":"S Raut","year":"2019","unstructured":"Raut, S., Deshpande, S. & Balasinor, N. H. Unveiling the role of prolactin and its receptor in male reproduction. Horm. Metab. Res. 51, 215\u2013219 (2019).","journal-title":"Horm. Metab. Res."},{"key":"80780_CR75","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1007\/s11255-013-0601-1","volume":"46","author":"LJ Velickovic","year":"2014","unstructured":"Velickovic, L. J. & Stefanovic, V. Hypoxia and spermatogenesis. Int. Urol. Nephrol. 46, 887\u2013894 (2014).","journal-title":"Int. Urol. Nephrol."},{"key":"80780_CR76","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1758-2946-6-13","volume":"6","author":"J Ru","year":"2014","unstructured":"Ru, J. et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J. Cheminform. 6, 13\u201319 (2014).","journal-title":"J. Cheminform."},{"key":"80780_CR77","doi-asserted-by":"publisher","first-page":"D1117","DOI":"10.1093\/nar\/gkx1028","volume":"46","author":"L Huang","year":"2018","unstructured":"Huang, L. et al. TCMID 20: a comprehensive resource for TCM. Nucleic Acids Res 46, D1117\u2013D1120 (2018).","journal-title":"Nucleic Acids Res"},{"key":"80780_CR78","doi-asserted-by":"publisher","first-page":"6964","DOI":"10.3390\/ijms13066964","volume":"13","author":"X Xu","year":"2012","unstructured":"Xu, X. et al. A novel chemometric method for the prediction of human oral bioavailability. Int. J. Mol. Sci. 13, 6964\u20136982 (2012).","journal-title":"Int. J. Mol. Sci."},{"key":"80780_CR79","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/S0169-409X(02)00003-0","volume":"54","author":"WP Walters","year":"2002","unstructured":"Walters, W. P. & Murcko, M. A. Prediction of \u201cdrug-likeness\u201d. Adv. Drug Deliv. Rev. 54, 255\u2013271 (2002).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"80780_CR80","doi-asserted-by":"publisher","first-page":"16160","DOI":"10.1038\/s41598-018-34509-1","volume":"8","author":"W Feng","year":"2018","unstructured":"Feng, W., Ao, H., Yue, S. & Peng, C. Systems pharmacology reveals the unique mechanism features of Shenzhu Capsule for treatment of ulcerative colitis in comparison with synthetic drugs. Sci. Rep. 8, 16160 (2018).","journal-title":"Sci. Rep."},{"key":"80780_CR81","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-019-56050-5","volume":"9","author":"F Li","year":"2019","unstructured":"Li, F. et al. A network pharmacology approach to reveal the protective mechanism of Salvia miltiorrhiza\u2013Dalbergia odorifera coupled-herbs on coronary heart disease. Sci. Rep. 9, 1\u201312 (2019).","journal-title":"Sci. Rep."},{"key":"80780_CR82","doi-asserted-by":"publisher","first-page":"D1102","DOI":"10.1093\/nar\/gky1033","volume":"47","author":"S Kim","year":"2019","unstructured":"Kim, S. et al. PubChem 2019 update: improved access to chemical data. Nucleic Acids Res. 47, D1102\u2013D1109 (2019).","journal-title":"Nucleic Acids Res."},{"key":"80780_CR83","doi-asserted-by":"publisher","first-page":"W32","DOI":"10.1093\/nar\/gku293","volume":"42","author":"D Gfeller","year":"2014","unstructured":"Gfeller, D. et al. SwissTargetPrediction: a web server for target prediction of bioactive small molecules. Nucleic Acids Res. 42, W32-38 (2014).","journal-title":"Nucleic Acids Res."},{"key":"80780_CR84","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/nbt1284","volume":"25","author":"MJ Keiser","year":"2007","unstructured":"Keiser, M. J. et al. Relating protein pharmacology by ligand chemistry. Nat. Biotechnol. 25, 197\u2013206 (2007).","journal-title":"Nat. Biotechnol."},{"key":"80780_CR85","doi-asserted-by":"publisher","first-page":"D204","DOI":"10.1093\/nar\/gku989","volume":"43","author":"C UniProt","year":"2015","unstructured":"UniProt, C. UniProt: a hub for protein information. Nucleic Acids Res. 43, D204-212 (2015).","journal-title":"Nucleic Acids Res."},{"key":"80780_CR86","doi-asserted-by":"publisher","first-page":"D833","DOI":"10.1093\/nar\/gkw943","volume":"45","author":"J Pinero","year":"2017","unstructured":"Pinero, J. et al. DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res. 45, D833\u2013D839 (2017).","journal-title":"Nucleic Acids Res."},{"key":"80780_CR87","doi-asserted-by":"publisher","first-page":"D948","DOI":"10.1093\/nar\/gky868","volume":"47","author":"AP Davis","year":"2019","unstructured":"Davis, A. P. et al. The comparative toxicogenomics database: update 2019. Nucleic Acids Res. 47, D948\u2013D954 (2019).","journal-title":"Nucleic Acids Res."},{"key":"80780_CR88","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/cpbi.27","volume":"58","author":"JS Amberger","year":"2017","unstructured":"Amberger, J. S. & Hamosh, A. Searching online mendelian inheritance in man (OMIM): a knowledgebase of human genes and genetic phenotypes. Curr. Protoc. Bioinform. 58, 1\u20132 (2017).","journal-title":"Curr. Protoc. Bioinform."},{"key":"80780_CR89","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/cpbi.5","volume":"54","author":"G Stelzer","year":"2016","unstructured":"Stelzer, G. et al. The GeneCards suite: from gene data mining to disease genome sequence analyses. Curr. Protoc. Bioinform. 54, 1\u201330 (2016).","journal-title":"Curr. Protoc. Bioinform."},{"key":"80780_CR90","doi-asserted-by":"publisher","first-page":"D36","DOI":"10.1093\/nar\/gku1055","volume":"43","author":"GR Brown","year":"2015","unstructured":"Brown, G. R. et al. Gene: a gene-centered information resource at NCBI. Nucleic Acids Res. 43, D36-42 (2015).","journal-title":"Nucleic Acids Res."},{"key":"80780_CR91","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498\u20132504 (2003).","journal-title":"Genome Res."},{"key":"80780_CR92","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1093\/bioinformatics\/btm554","volume":"24","author":"Y Assenov","year":"2008","unstructured":"Assenov, Y., Ramirez, F., Schelhorn, S. E., Lengauer, T. & Albrecht, M. Computing topological parameters of biological networks. Bioinformatics 24, 282\u2013284 (2008).","journal-title":"Bioinformatics"},{"key":"80780_CR93","doi-asserted-by":"publisher","first-page":"D447","DOI":"10.1093\/nar\/gku1003","volume":"43","author":"D Szklarczyk","year":"2015","unstructured":"Szklarczyk, D. et al. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 43, D447-452 (2015).","journal-title":"Nucleic Acids Res."},{"key":"80780_CR94","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.biosystems.2014.11.005","volume":"127","author":"Y Tang","year":"2015","unstructured":"Tang, Y., Li, M., Wang, J., Pan, Y. & Wu, F. X. CytoNCA: a cytoscape plugin for centrality analysis and evaluation of protein interaction networks. Biosystems 127, 67\u201372 (2015).","journal-title":"Biosystems"},{"key":"80780_CR95","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-35791-9","volume":"8","author":"W Song","year":"2018","unstructured":"Song, W., Ni, S., Fu, Y. & Wang, Y. Uncovering the mechanism of Maxing Ganshi Decoction on asthma from a systematic perspective: A network pharmacology study. Sci. Rep. 8, 1\u201311 (2018).","journal-title":"Sci. Rep."},{"key":"80780_CR96","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1471-2105-4-2","volume":"4","author":"GD Bader","year":"2003","unstructured":"Bader, G. D. & Hogue, C. W. An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinform. 4, 2\u201329 (2003).","journal-title":"BMC Bioinform."},{"key":"80780_CR97","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.compbiolchem.2015.08.008","volume":"59","author":"HA Ahmed","year":"2015","unstructured":"Ahmed, H. A., Bhattacharyya, D. K. & Kalita, J. K. Core and peripheral connectivity based cluster analysis over PPI network. Comput. Biol. Chem. 59, 32\u201341 (2015).","journal-title":"Comput. Biol. Chem."},{"key":"80780_CR98","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/nmeth.3252","volume":"12","author":"W Huber","year":"2015","unstructured":"Huber, W. et al. Orchestrating high-throughput genomic analysis with bioconductor. Nat. Methods 12, 115\u2013121 (2015).","journal-title":"Nat. Methods"},{"key":"80780_CR99","doi-asserted-by":"publisher","first-page":"D331","DOI":"10.1093\/nar\/gkw1108","volume":"45","author":"The Gene Ontology, C","year":"2017","unstructured":"The Gene Ontology, C. Expansion of the gene ontology knowledgebase and resources. Nucleic Acids Res. 45, D331\u2013D338 (2017).","journal-title":"Nucleic Acids Res."},{"key":"80780_CR100","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa, M. & Goto, S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27\u201330 (2000).","journal-title":"Nucleic Acids Res."},{"key":"80780_CR101","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1002\/pro.3715","volume":"28","author":"M Kanehisa","year":"2019","unstructured":"Kanehisa, M. Toward understanding the origin and evolution of cellular organisms. Protein Sci. 28, 1947\u20131951 (2019).","journal-title":"Protein Sci."},{"key":"80780_CR102","first-page":"gkaa970","volume":"20","author":"M Kanehisa","year":"2021","unstructured":"Kanehisa, M., Furumichi, M., Sato, Y., Ishiguro-Watanabe, M. & Tanabe, M. KEGG: Integrating viruses and cellular organisms. Nucleic Acids Res. 20, gkaa970 (2021).","journal-title":"Nucleic Acids Res."},{"key":"80780_CR103","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/nar\/28.1.235","volume":"28","author":"HM Berman","year":"2000","unstructured":"Berman, H. M. et al. The protein data bank. Nucleic Acids Res. 28, 235\u2013242 (2000).","journal-title":"Nucleic Acids Res."},{"key":"80780_CR104","doi-asserted-by":"publisher","first-page":"2041","DOI":"10.1016\/j.str.2016.11.012","volume":"24","author":"S Yuan","year":"2016","unstructured":"Yuan, S., Chan, H. C. S., Filipek, S. & Vogel, H. PyMOL and inkscape bridge the data and the data visualization. Structure 24, 2041\u20132042 (2016).","journal-title":"Structure"},{"key":"80780_CR105","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2010","unstructured":"Trott, O. & Olson, A. J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31, 455\u2013461 (2010).","journal-title":"J. Comput. Chem."},{"key":"80780_CR106","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1080\/03639045.2020.1788070","volume":"46","author":"Q Tao","year":"2020","unstructured":"Tao, Q. et al. Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Huashi Baidu formula in the treatment of COVID-19. Drug Dev. Ind. Pharm. 46, 1345\u20131353 (2020).","journal-title":"Drug Dev. Ind. Pharm."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-80780-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-80780-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-80780-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:35:12Z","timestamp":1724373312000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-80780-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,26]]},"references-count":106,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["80780"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-80780-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,26]]},"assertion":[{"value":"14 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2220"}}