{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T21:13:31Z","timestamp":1760044411660},"reference-count":47,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T00:00:00Z","timestamp":1578614400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81703149","81874251"],"award-info":[{"award-number":["81703149","81874251"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Key Technology R&D Program of Hunan Provincial Project of Hunan","award":["2018SK2087"],"award-info":[{"award-number":["2018SK2087"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>The <jats:italic>Haplopelma hainanum<\/jats:italic> is a species of theraphosid spider from China. Its large size and charming appearance make this species a popular pet. According to a previous study, theraphosid spider bites can induce pain, erythema, and edema in humans and can present more severely in domestic animals. The pathological consequences of envenomation by <jats:italic>H. hainanum<\/jats:italic> remain unclear. In this study, we investigated the effects and mechanisms of <jats:italic>H. hainanum<\/jats:italic> envenomation in mice. We showed that the venom induced slight swelling, intense inflammatory response, and increased the microvascular density in mice skin. Moreover, we found that 50 \u00b5g\/ml of the spider\u2019s venom induced IL-1\u03b2 expression in both HaCaT cells and fibroblast cells, but repressed CXCL10 expression in fibroblasts. The venom significantly induced cell senescence and repressed cell proliferation and migration in both HaCaT cells and fibroblast cells. Finally, we examined the expression of Nav channel in HaCaT and fibroblast cells and found that <jats:italic>H. hainanum<\/jats:italic> venom effectively inhibited Na<jats:sup>+<\/jats:sup> currents in HaCaT cells. Our study calls for further investigation of the pathological consequences and potential mechanisms of <jats:italic>H. hainanum<\/jats:italic> envenomation. This information might assist in the development of suitable therapy.<\/jats:p>","DOI":"10.7717\/peerj.8264","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T09:27:19Z","timestamp":1578648439000},"page":"e8264","source":"Crossref","is-referenced-by-count":1,"title":["<i>Haplopelma hainanum<\/i> venom induces inflammatory skin lesions"],"prefix":"10.7717","volume":"8","author":[{"given":"Zhili","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China"},{"name":"Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Central South University, Changsha, China"},{"name":"Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China"},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University,  Changsha, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaling","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China"},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University,  Changsha, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"San","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China"},{"name":"Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Central South University, Changsha, China"},{"name":"Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China"},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University,  Changsha, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China"},{"name":"Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Central South University, Changsha, China"},{"name":"Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China"},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University,  Changsha, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiya","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China"},{"name":"Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Central South University, Changsha, China"},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University,  Changsha, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2020,1,10]]},"reference":[{"key":"10.7717\/peerj.8264\/ref-1","first-page":"862","article-title":"Spider bites\u2014assessment and management","volume":"38","author":"Braitberg","year":"2009","journal-title":"Australian Family Physician"},{"key":"10.7717\/peerj.8264\/ref-2","doi-asserted-by":"publisher","first-page":"14644","DOI":"10.1038\/ncomms14644","article-title":"Potassium channels Kv1.3 and KCa3.1 cooperatively and compensatorily regulate antigen-specific memory T cell functions","volume":"8","author":"Chiang","year":"2017","journal-title":"Nature Communications"},{"key":"10.7717\/peerj.8264\/ref-3","doi-asserted-by":"publisher","first-page":"e0153090","DOI":"10.1371\/journal.pone.0153090","article-title":"Sphingomyelinase D from Loxosceles laeta venom induces the expression of MMP7 in Human Keratinocytes: contribution to Dermonecrosis","volume":"11","author":"Correa","year":"2016","journal-title":"PLOS ONE"},{"key":"10.7717\/peerj.8264\/ref-4","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.toxicon.2014.04.002","article-title":"Whole venom of Loxosceles similis activates caspases-3, -6, -7, and -9 in human primary skin fibroblasts","volume":"84","author":"Dantas","year":"2014","journal-title":"Toxicon"},{"key":"10.7717\/peerj.8264\/ref-5","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.toxicon.2016.07.011","article-title":"Characterization of ion channels on subesophageal ganglion neurons from Chinese tarantula Ornithoctonus huwena: exploring the myth of the spider insensitive to its venom","volume":"120","author":"Deng","year":"2016","journal-title":"Toxicon"},{"key":"10.7717\/peerj.8264\/ref-6","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1081\/CLT-100102435","article-title":"Loxosceles deserta spider venom induces NF-kappaB-dependent chemokine production by endothelial cells","volume":"37","author":"Desai","year":"1999","journal-title":"Journal of Toxicology. Clinical Toxicology"},{"key":"10.7717\/peerj.8264\/ref-7","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1038\/sj.jid.5700644","article-title":"Upregulation of IL-6, IL-8, CXCL1, and CXCL2 dominates gene expression in human fibroblast cells exposed to Loxosceles reclusa sphingomyelinase D: insights into spider venom dermonecrosis","volume":"127","author":"Dragulev","year":"2007","journal-title":"Journal of Investigative Dermatology"},{"key":"10.7717\/peerj.8264\/ref-8","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12964-015-0112-z","article-title":"Orai\/CRACM1 and KCa3.1 ion channels interact in the human lung mast cell plasma membrane","volume":"13","author":"Duffy","year":"2015","journal-title":"Cell Communication and Signaling"},{"key":"10.7717\/peerj.8264\/ref-9","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1080\/15563650.2017.1393084","article-title":"Envenomation by the noble false widow spider Steatoda nobilis (Thorell, 1875)\u2014five new cases of steatodism from Ireland and Great Britain","volume":"56","author":"Dunbar","year":"2018","journal-title":"Clinical Toxicology"},{"key":"10.7717\/peerj.8264\/ref-10","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1080\/15563650.2019.1578367","article-title":"The kiss of (cell) death: can venom-induced immune response contribute to dermal necrosis following arthropod envenomations?","volume":"57","author":"Dunbar","year":"2019","journal-title":"Clinical Toxicology"},{"key":"10.7717\/peerj.8264\/ref-11","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.toxicon.2008.10.016","article-title":"Inflammatory oedema induced by Lachesis muta muta (Surucucu) venom and LmTX-I in the rat paw and dorsal skin","volume":"53","author":"Ferreira","year":"2009","journal-title":"Toxicon"},{"key":"10.7717\/peerj.8264\/ref-12","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.toxicon.2013.10.032","article-title":"A verified spider bite and a review of the literature confirm Indian ornamental tree spiders (Poecilotheria species) as underestimated theraphosids of medical importance","volume":"77","author":"Fuchs","year":"2014","journal-title":"Toxicon"},{"key":"10.7717\/peerj.8264\/ref-13","first-page":"207","article-title":"Loxosceles spider venom induces the production of alpha and beta chemokines: implications for the pathogenesis of dermonecrotic arachnidism","volume":"23","author":"Gomez","year":"1999","journal-title":"Inflammation"},{"key":"10.7717\/peerj.8264\/ref-14","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/S0014-2999(98)00276-3","article-title":"Vespula vulgaris venom: role of kinins and release of 5-hydroxytryptamine from skin mast cells","volume":"351","author":"Griesbacher","year":"1998","journal-title":"European Journal of Pharmacology"},{"key":"10.7717\/peerj.8264\/ref-15","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1016\/j.jid.2017.05.012","article-title":"miR-146b probably assists miRNA-146a in the suppression of keratinocyte proliferation and inflammatory responses in psoriasis","volume":"137","author":"Hermann","year":"2017","journal-title":"Journal of Investigative Dermatology"},{"issue":"6","key":"10.7717\/peerj.8264\/ref-16","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1111\/jdv.15472","article-title":"Innate immune response of human epidermal keratinocytes and dermal fibroblast to in vitro incubation of Trichophyton benhamiae DSM 6916","volume":"33","author":"Hesse-Macabata","year":"2019","journal-title":"The Journal of the European Academy of Dermatology and Venereology"},{"key":"10.7717\/peerj.8264\/ref-17","doi-asserted-by":"publisher","first-page":"988","DOI":"10.3390\/toxins6030988","article-title":"The venom of the spider Selenocosmia jiafu contains various neurotoxins acting on voltage-gated ion channels in rat dorsal root ganglion neurons","volume":"6","author":"Hu","year":"2014","journal-title":"Toxins"},{"key":"10.7717\/peerj.8264\/ref-18","doi-asserted-by":"publisher","first-page":"2568","DOI":"10.3390\/toxins6082568","article-title":"The activation effect of hainantoxin-I, a peptide toxin from the Chinese spider, Ornithoctonus hainana, on intermediate-conductance Ca2+-activated K+ channels","volume":"6","author":"Huang","year":"2014","journal-title":"Toxins"},{"key":"10.7717\/peerj.8264\/ref-19","doi-asserted-by":"publisher","first-page":"2039","DOI":"10.1016\/s0140-6736(10)62230-1","article-title":"Spider bite","volume":"378","author":"Isbister","year":"2011","journal-title":"Lancet"},{"key":"10.7717\/peerj.8264\/ref-20","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/S0041-0101(02)00395-1","article-title":"Bites by spiders of the family Theraphosidae in humans and canines","volume":"41","author":"Isbister","year":"2003","journal-title":"Toxicon"},{"key":"10.7717\/peerj.8264\/ref-21","doi-asserted-by":"publisher","first-page":"2421","DOI":"10.1038\/jid.2008.118","article-title":"Skin pathology induced by snake venom metalloproteinase: acute damage, revascularization, and re-epithelization in a mouse ear model","volume":"128","author":"Jimenez","year":"2008","journal-title":"Journal of Investigative Dermatology"},{"key":"10.7717\/peerj.8264\/ref-22","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41577-018-0084-5","article-title":"The immunological anatomy of the skin","volume":"19","author":"Kabashima","year":"2019","journal-title":"Nature Reviews Immunology"},{"key":"10.7717\/peerj.8264\/ref-23","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1111\/j.1440-0960.2010.00629.x","article-title":"Aquaporin-3 gene and protein expression in sun-protected human skin decreases with skin ageing","volume":"51","author":"Li","year":"2010","journal-title":"Australasian Journal of Dermatology"},{"key":"10.7717\/peerj.8264\/ref-24","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.intimp.2018.12.031","article-title":"Tranexamic acid ameliorates rosacea symptoms through regulating immune response and angiogenesis","volume":"67","author":"Li","year":"2019","journal-title":"International Immunopharmacology"},{"key":"10.7717\/peerj.8264\/ref-25","doi-asserted-by":"publisher","first-page":"e2394","DOI":"10.1371\/journal.pntd.0002394","article-title":"Venom of the Brazilian spider Sicarius ornatus (Araneae, Sicariidae) contains active sphingomyelinase D: potential for toxicity after envenomation","volume":"7","author":"Lopes","year":"2013","journal-title":"PLOS Neglected Tropical Diseases"},{"key":"10.7717\/peerj.8264\/ref-26","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.it.2012.11.005","article-title":"The IL-23\/T17 pathogenic axis in psoriasis is amplified by keratinocyte responses","volume":"34","author":"Lowes","year":"2013","journal-title":"Trends in Immunology"},{"key":"10.7717\/peerj.8264\/ref-27","first-page":"101","article-title":"Pathogenic action and specificity of venom from the spider Loxosceles laeta (Nicolet)","volume":"47","author":"Mackinnon","year":"1954","journal-title":"Bulletin de la Societe de Pathologie Exotique et de ses Filiales"},{"key":"10.7717\/peerj.8264\/ref-28","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.molimm.2017.12.009","article-title":"Loxosceles venom Sphingomyelinase D activates human blood leukocytes: Role of the complement system","volume":"94","author":"Manzoni-de Almeida","year":"2018","journal-title":"Molecular Immunology"},{"issue":"10","key":"10.7717\/peerj.8264\/ref-29","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19102942","article-title":"Histone deacetylases enhance Ca(2+)-activated K(+) channel KCa31 expression in murine inflammatory CD4(+) T cells","volume":"19","author":"Matsui","year":"2018","journal-title":"International Journal of Molecular Sciences"},{"issue":"3","key":"10.7717\/peerj.8264\/ref-30","doi-asserted-by":"publisher","DOI":"10.3390\/toxins9030090","article-title":"Tetracycline reduces kidney damage induced by loxosceles spider venom","volume":"9","author":"Okamoto","year":"2017","journal-title":"Toxins"},{"key":"10.7717\/peerj.8264\/ref-31","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/sj.jid.5700049","article-title":"Role of matrix metalloproteinases in HaCaT keratinocytes apoptosis induced by loxosceles venom sphingomyelinase D","volume":"126","author":"Paixao-Cavalcante","year":"2006","journal-title":"Journal of Investigative Dermatology"},{"key":"10.7717\/peerj.8264\/ref-32","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1038\/sj.jid.5700688","article-title":"Tetracycline protects against dermonecrosis induced by Loxosceles spider venom","volume":"127","author":"Paixao-Cavalcante","year":"2007","journal-title":"Journal of Investigative Dermatology"},{"key":"10.7717\/peerj.8264\/ref-33","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1172\/jci117379","article-title":"The necrotic venom of the brown recluse spider induces dysregulated endothelial cell-dependent neutrophil activation. Differential induction of GM-CSF, IL-8, and E-selectin expression","volume":"94","author":"Patel","year":"1994","journal-title":"Journal of Clinical Investigation"},{"key":"10.7717\/peerj.8264\/ref-34","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.toxicon.2015.01.008","article-title":"Pattern of inflammatory response to Loxosceles intermedia venom in distinct mouse strains: a key element to understand skin lesions and dermonecrosis by poisoning","volume":"96","author":"Ribeiro","year":"2015","journal-title":"Toxicon"},{"key":"10.7717\/peerj.8264\/ref-35","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1124\/jpet.115.226787","article-title":"Pharmacological characterization of the edema caused by vitalius dubius (theraphosidae, mygalomorphae) spider venom in rats","volume":"356","author":"Rocha","year":"2016","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"issue":"4","key":"10.7717\/peerj.8264\/ref-36","doi-asserted-by":"publisher","DOI":"10.3390\/toxins9040125","article-title":"Phospholipase D from loxosceles laeta spider venom induces IL-6, IL-8, CXCL1\/GRO-alpha, and CCL2\/MCP-1 production in human skin fibroblasts and stimulates monocytes migration","volume":"9","author":"Rojas","year":"2017","journal-title":"Toxins"},{"issue":"9","key":"10.7717\/peerj.8264\/ref-37","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1016\/j.biopsych.2018.12.008","article-title":"MicroRNA-26a\/death-associated protein kinase 1 signaling induces synucleinopathy and dopaminergic neuron degeneration in Parkinson\u2019s disease","volume":"85","author":"Su","year":"2018","journal-title":"Biological Psychiatry"},{"key":"10.7717\/peerj.8264\/ref-38","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1111\/j.0022-202X.2005.23654.x","article-title":"Loxosceles sphingomyelinase induces complement-dependent dermonecrosis, neutrophil infiltration, and endogenous gelatinase expression","volume":"124","author":"Tambourgi","year":"2005","journal-title":"Journal of Investigative Dermatology"},{"key":"10.7717\/peerj.8264\/ref-39","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1111\/j.1538-7836.2007.02382.x","article-title":"Loxosceles spider venom induces the release of thrombomodulin and endothelial protein C receptor: implications for the pathogenesis of intravascular coagulation as observed in loxoscelism","volume":"5","author":"Van den Berg","year":"2007","journal-title":"Journal of Thrombosis and Haemostasis"},{"key":"10.7717\/peerj.8264\/ref-40","doi-asserted-by":"publisher","first-page":"191","DOI":"10.3390\/toxins4030191","article-title":"Spider-venom peptides as bioinsecticides","volume":"4","author":"Windley","year":"2012","journal-title":"Toxins"},{"key":"10.7717\/peerj.8264\/ref-41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0014-2999(03)02190-3","article-title":"Inhibition of neuronal tetrodotoxin-sensitive Na+ channels by two spider toxins: hainantoxin-III and hainantoxin-IV","volume":"477","author":"Xiao","year":"2003","journal-title":"European Journal of Pharmacology"},{"key":"10.7717\/peerj.8264\/ref-42","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1007\/s00403-013-1324-y","article-title":"Protective role of AQP3 in UVA-induced NHSFs apoptosis via Bcl2 up-regulation","volume":"305","author":"Xie","year":"2013","journal-title":"Archives of Dermatological Research"},{"key":"10.7717\/peerj.8264\/ref-43","doi-asserted-by":"publisher","first-page":"e2663","DOI":"10.1038\/cddis.2017.75","article-title":"miR-377 induces senescence in human skin fibroblasts by targeting DNA methyltransferase 1","volume":"8","author":"Xie","year":"2017","journal-title":"Cell Death & Disease"},{"key":"10.7717\/peerj.8264\/ref-44","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1080\/19336950.2018.1449497","article-title":"The Venom of Ornithoctonus huwena affect the electrophysiological stability of neonatal rat ventricular myocytes by inhibiting sodium, potassium and calcium current","volume":"12","author":"Yan","year":"2018","journal-title":"Channels"},{"key":"10.7717\/peerj.8264\/ref-45","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.immuni.2016.06.021","article-title":"Antimicrobial peptide LL37 and MAVS signaling drive interferon-beta production by epidermal keratinocytes during skin injury","volume":"45","author":"Zhang","year":"2016","journal-title":"Immunity"},{"key":"10.7717\/peerj.8264\/ref-46","doi-asserted-by":"publisher","first-page":"14192","DOI":"10.1074\/jbc.M114.635458","article-title":"Structural and functional diversity of peptide toxins from tarantula haplopelma hainanum (ornithoctonus hainana) venom revealed by transcriptomic, peptidomic, and patch clamp approaches","volume":"290","author":"Zhang","year":"2015","journal-title":"Journal of Biological Chemistry"},{"key":"10.7717\/peerj.8264\/ref-47","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.pain.2008.03.016","article-title":"Voltage-gated sodium channel expression in rat and human epidermal keratinocytes: evidence for a role in pain","volume":"139","author":"Zhao","year":"2008","journal-title":"Pain"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/8264.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/8264.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/8264.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/8264.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T09:27:24Z","timestamp":1578648444000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/8264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,10]]},"references-count":47,"alternative-id":["10.7717\/peerj.8264"],"URL":"https:\/\/doi.org\/10.7717\/peerj.8264","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,10]]},"article-number":"e8264"}}