{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:13:16Z","timestamp":1790730796684,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T00:00:00Z","timestamp":1602115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","award":["2017"],"award-info":[{"award-number":["2017"]}],"id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Janus kinase (JAK) inhibitors have been developed as novel immunomodulatory drugs and primarily used for treating rheumatoid arthritis and other inflammatory diseases. Recent studies have suggested that this category of anti-inflammatory drugs could be potentially useful for the control of inflammation \u201cstorms\u201d in respiratory virus infections. In addition to their role in regulating immune cell functions, JAK1 and JAK2 have been recently identified as crucial cellular factors involved in influenza A virus (IAV) replication and could be potentially targeted for antiviral therapy. Gingerenone A (Gin A) is a compound derived from ginger roots and a dual inhibitor of JAK2 and p70 S6 kinase (S6K1). Our present study aimed to determine the antiviral activity of Gin A on influenza A virus (IAV) and to understand its mechanisms of action. Here, we reported that Gin A suppressed the replication of three IAV subtypes (H1N1, H5N1, H9N2) in four cell lines. IAV replication was also inhibited by Ruxolitinib (Rux), a JAK inhibitor, but not by PF-4708671, an S6K1 inhibitor. JAK2 overexpression enhanced H5N1 virus replication and attenuated Gin A-mediated antiviral activity. In vivo experiments revealed that Gin A treatment suppressed IAV replication in the lungs of H5N1 virus-infected mice, alleviated their body weight loss, and prolonged their survival. Our study suggests that Gin A restricts IAV replication by inhibiting JAK2 activity; Gin A could be potentially useful for the control of influenza virus infections.<\/jats:p>","DOI":"10.3390\/v12101141","type":"journal-article","created":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T08:52:41Z","timestamp":1602147161000},"page":"1141","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["In Vitro and In Vivo Antiviral Activity of Gingerenone A on Influenza A Virus Is Mediated by Targeting Janus Kinase 2"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6140-5173","authenticated-orcid":false,"given":"Jiongjiong","family":"Wang","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Prinz","sequence":"additional","affiliation":[{"name":"Department of Surgery, Northshore University HealthSystem, Evanston, IL 60201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufan","family":"Liu","sequence":"additional","affiliation":[{"name":"Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou 225009, China"},{"name":"Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiulong","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou 225009, China"},{"name":"Institutes of Agricultural Science and Technology Development, Yangzhou University Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/S0140-6736(17)30129-0","article-title":"Influenza","volume":"390","author":"Paules","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S1473-3099(12)70121-4","article-title":"Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: A modelling study","volume":"12","author":"Dawood","year":"2012","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMra1000449","article-title":"Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection","volume":"362","author":"Bautista","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1016\/S1473-3099(14)70821-7","article-title":"International severe acute respiratory and emerging infection consortium (ISARIC) antiviral combinations for severe influenza","volume":"14","author":"Dunning","year":"2014","journal-title":"Lancet Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41579-018-0115-z","article-title":"Host and viral determinants of influenza A virus species specificity","volume":"17","author":"Long","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sutton, T. (2018). The pandemic threat of emerging H5 and H7 avian influenza viruses. Viruses, 10.","DOI":"10.3390\/v10090461"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.antiviral.2013.09.015","article-title":"Favipiravir (T-705), a novel viral RNA polymerase inhibitor","volume":"100","author":"Furuta","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Abraham, G.M., Morton, J.B., and Saravolatz, L.D. (2020). Baloxavir: A novel antiviral agent in the treatment of influenza. Clin. Infect. Dis.","DOI":"10.1093\/cid\/ciaa107"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1016\/S1473-3099(14)70828-X","article-title":"Emerging novel and antimicrobial-resistant respiratory tract infections: New drug development and therapeutic options","volume":"14","author":"Zumla","year":"2014","journal-title":"Lancet Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3659","DOI":"10.1007\/s00018-014-1615-2","article-title":"Antiviral strategies against influenza virus: Towards new therapeutic approaches","volume":"71","author":"Loregian","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3058","DOI":"10.1128\/JVI.02082-06","article-title":"Influenza A virus NS1 protein activates the PI3K\/Akt pathway to mediate antiapoptotic signaling responses","volume":"81","author":"Ehrhardt","year":"2007","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"205","DOI":"10.3851\/IMP2080","article-title":"Inhibition of influenza a virus replication by antagonism of a PI3K-AKT-mTOR pathway member identified by gene-trap insertional mutagenesis","volume":"22","author":"Murray","year":"2012","journal-title":"Antivir. Chem. Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.1128\/AAC.02798-13","article-title":"Akt inhibitor MK2206 prevents influenza pH1N1 virus infection in vitro","volume":"58","author":"Denisova","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.chom.2014.11.002","article-title":"Influenza virus-host interactome screen as a platform for antiviral drug development","volume":"16","author":"Watanabe","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.celrep.2018.03.045","article-title":"Genome-wide CRISPR\/Cas9 screen identifies host factors essential for influenza virus replication","volume":"23","author":"Han","year":"2018","journal-title":"Cell Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.fct.2007.09.085","article-title":"Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): A review of recent research","volume":"46","author":"Ali","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.phymed.2004.07.009","article-title":"Zingiberis rhizoma: A comprehensive review on the ginger effect and efficacy profiles","volume":"12","author":"Chrubasik","year":"2005","journal-title":"Phytomedicine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.jep.2012.10.043","article-title":"Fresh ginger (Zingiber officinale) has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines","volume":"145","author":"Chang","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"23553","DOI":"10.1074\/jbc.M115.662445","article-title":"Identification of a dual inhibitor of Janus kinase 2 (JAK2) and p70 ribosomal S6 kinase1 (S6K1) pathways","volume":"290","author":"Byun","year":"2015","journal-title":"J. Boil. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1007\/s00705-013-1771-y","article-title":"Isolation and characterization of two H5N1 influenza viruses from swine in Jiangsu Province of China","volume":"158","author":"He","year":"2013","journal-title":"Arch. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3102","DOI":"10.1099\/vir.0.2008\/005652-0","article-title":"Characterization of H9N2 influenza viruses isolated from vaccinated flocks in an integrated broiler chicken operation in eastern China during a 5 year period (1998\u20132002)","volume":"89","author":"Zhang","year":"2008","journal-title":"J. Gen. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"30015","DOI":"10.1038\/srep30015","article-title":"Detection of influenza A virus from live-bird market poultry swab samples in China by a pan-IAV, one-step reverse-transcription FRET-PCR","volume":"6","author":"Luan","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.vetmic.2014.12.011","article-title":"Hemagglutinin glycosylation modulates the pathogenicity and antigenicity of the H5N1 avian influenza virus","volume":"175","author":"Zhang","year":"2015","journal-title":"Veter- Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.celrep.2015.06.044","article-title":"Wild-Type N-Ras, overexpressed in basal-like breast cancer, promotes tumor formation by inducing IL-8 secretion via JAK2 activation","volume":"12","author":"Zheng","year":"2015","journal-title":"Cell Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"28593","DOI":"10.1038\/srep28593","article-title":"Highly pathogenic avian influenza H5N1 virus delays apoptotic responses via activation of STAT3","volume":"6","author":"Hui","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1042\/BJ20101024","article-title":"Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1)","volume":"431","author":"Pearce","year":"2010","journal-title":"Biochem. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e1800709","DOI":"10.1002\/mnfr.201800709","article-title":"Gingerenone A sensitizes the insulin receptor and increases glucose uptake by inhibiting the activity of p70 S6 kinase","volume":"62","author":"Chen","year":"2018","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_28","first-page":"813","article-title":"Human host factors required for influenza virus replication","volume":"463","author":"Stertz","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6182","DOI":"10.1128\/JVI.03024-12","article-title":"Tyrosine 132 Phosphorylation of influenza A virus M1 protein is crucial for virus replication by controlling the nuclear import of M1","volume":"87","author":"Wang","year":"2013","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.coph.2012.06.008","article-title":"Jakinibs: A new class of kinase inhibitors in cancer and autoimmune disease","volume":"12","author":"Kontzias","year":"2012","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.2174\/092986709788682065","article-title":"Antiviral and virucidal activities of natural products","volume":"16","author":"Arakawa","year":"2009","journal-title":"Curr. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1039\/C4NP00085D","article-title":"Antiviral drug discovery: Broad-spectrum drugs from nature","volume":"32","author":"Martinez","year":"2015","journal-title":"Nat. Prod. Rep."},{"key":"ref_33","first-page":"123ra24","article-title":"Productive replication of Ebola virus is regulated by the c-Abl1 tyrosine kinase","volume":"4","author":"Cooper","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gavegnano, C., Brehm, J.H., Dupuy, F.P., Talla, A., Ribeiro, S.P., Kulpa, D.A., Cameron, C., Santos, S., Hurwitz, S.J., and Marconi, V.C. (2017). Novel mechanisms to inhibit HIV reservoir seeding using Jak inhibitors. PLOS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006740"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1128\/AAC.02496-13","article-title":"Ruxolitinib and tofacitinib are potent and selective inhibitors of HIV-1 replication and virus reactivation in vitro","volume":"58","author":"Gavegnano","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e00075-17","DOI":"10.1128\/JVI.00075-17","article-title":"JAK-STAT Signaling Pathways and Inhibitors Affect Reversion of Envelope-Mutated HIV-1","volume":"91","author":"Quan","year":"2017","journal-title":"J. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1700139","DOI":"10.1002\/mnfr.201700139","article-title":"Gingerenone A, a polyphenol present in ginger, suppresses obesity and adipose tissue inflammation in high-fat diet-fed mice","volume":"61","author":"Suk","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.virol.2019.08.023","article-title":"p-STAT1 regulates the influenza A virus replication and inflammatory response in vitro and vivo","volume":"537","author":"Zhang","year":"2019","journal-title":"Virology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.virol.2018.10.017","article-title":"Lack of IFNgamma signaling attenuates spread of influenza A virus in vivo and leads to reduced pathogenesis","volume":"526","author":"Nicol","year":"2019","journal-title":"Virology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cytogfr.2016.05.001","article-title":"STAT3 signaling in immunity","volume":"31","author":"Hillmer","year":"2016","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Suarez, A.A.R., Van Renne, N., Baumert, T.F., and Lupberger, J. (2018). Viral manipulation of STAT3: Evade, exploit, and injure. PLOS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006839"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/s41568-018-0090-8","article-title":"Therapeutically exploiting STAT3 activity in cancer \u2014 using tissue repair as a road map","volume":"19","author":"Huynh","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1073\/pnas.1114232109","article-title":"Signal transducer and activator of transcription 3 (STAT3) and survivin induction by varicella-zoster virus promote replication and skin pathogenesis","volume":"109","author":"Sen","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1002\/hep.26496","article-title":"Signal transducer and activator of transcription 3 is a proviral host factor for hepatitis C virus","volume":"58","author":"McCartney","year":"2013","journal-title":"Hepatology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1093\/jac\/dkv077","article-title":"A novel small-molecule inhibitor of hepatitis C virus replication acts by suppressing signal transducer and activator of transcription 3","volume":"70","author":"Niu","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_46","first-page":"1755","article-title":"A novel anti-viral role for STAT3 in IFN-\u03b1 signalling responses","volume":"74","author":"Stevenson","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.3389\/fimmu.2019.01843","article-title":"Influenza Virus-Induced Robust Expression of SOCS3 Contributes to Excessive Production of IL-6","volume":"10","author":"Liu","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.jep.2011.11.018","article-title":"Ge-Gen-Tang has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines","volume":"139","author":"Chang","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.jep.2011.03.058","article-title":"Sheng-Ma-Ge-Gen-Tang (Shoma-kakkon-to) inhibited cytopathic effect of human respiratory syncytial virus in cell lines of human respiratory tract","volume":"135","author":"Wang","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1142\/S0192415X06003722","article-title":"Macrophage-mediated inhibitory effect of Zingiber officinale Rosc, a traditional oriental herbal medicine, on the growth of influenza A\/Aichi\/2\/68 virus","volume":"34","author":"Imanishi","year":"2006","journal-title":"Am. J. Chin. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.vetmic.2019.02.001","article-title":"Virucidal activity of ginger essential oil against caprine alphaherpesvirus-1","volume":"230","author":"Camero","year":"2019","journal-title":"Vet. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1128\/AAC.00426-06","article-title":"Susceptibility of Drug-Resistant Clinical Herpes Simplex Virus Type 1 Strains to Essential Oils of Ginger, Thyme, Hyssop, and Sandalwood","volume":"51","author":"Schnitzler","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.phymed.2007.09.003","article-title":"Inhibitory effect of essential oils against herpes simplex virus type 2","volume":"15","author":"Koch","year":"2008","journal-title":"Phytomedicine"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/nrd.2017.201","article-title":"JAK inhibition as a therapeutic strategy for immune and inflammatory diseases","volume":"16","author":"Schwartz","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S0140-6736(20)30628-0","article-title":"COVID-19: Consider cytokine storm syndromes and immunosuppression","volume":"395","author":"Mehta","year":"2020","journal-title":"Lancet"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e30","DOI":"10.1016\/S0140-6736(20)30304-4","article-title":"Baricitinib as potential treatment for 2019-nCoV acute respiratory disease","volume":"395","author":"Richardson","year":"2020","journal-title":"Lancet"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Wang, J., Sun, J., Hu, J., Wang, C., Prinz, R.A., Peng, D., Liu, X., and Xu, X. (2020). A77 1726, the active metabolite of the anti-rheumatoid arthritis drug leflunomide, inhibits influenza A virus replication in vitro and in vivo by inhibiting the activity of Janus kinases. FASEB J.","DOI":"10.1096\/fj.201902793RR"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Li, X., Sun, J., Prinz, R.A., Liu, X., and Xu, X. (2020). Inhibition of porcine epidemic diarrhea virus (PEDV) replication by A77 1726 through targeting JAK and Src tyrosine kinases. Virology.","DOI":"10.1016\/j.virol.2020.06.009"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Hu, K., Wang, M., Zhao, Y., Zhang, Y., Wang, T., Zheng, Z., Li, X., Zeng, S., Zhao, D., and Li, H. (2020). A Small-Scale Medication of Leflunomide as a Treatment of COVID-19 in an Open-Label Blank-Controlled Clinical Trial. Virol. Sin., 1\u20139.","DOI":"10.1007\/s12250-020-00258-7"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/10\/1141\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:17:21Z","timestamp":1760177841000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/10\/1141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,8]]},"references-count":59,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["v12101141"],"URL":"https:\/\/doi.org\/10.3390\/v12101141","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,8]]}}}