{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:49:33Z","timestamp":1788353373894,"version":"build-2803163510"},"reference-count":58,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T00:00:00Z","timestamp":1665273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["22K10606"],"award-info":[{"award-number":["22K10606"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["18K19670"],"award-info":[{"award-number":["18K19670"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Contraction band necrosis (CBN) is a common abnormality found in the myocardium of cocaine abusers, but is rarely reported in experimental models of cocaine abuse. Connexin 43 (Cx43) is essential for cardiac intercellular communication and the propagation of CBN. Under stress or injury, cardiac Cx43 is dephosphorylated, which is related to cardiomyocyte dysfunction and pathogenesis, whereas adiponectin exerts beneficial effects in the myocardium. In this study, we explore the effects of cocaine on cardiac Cx43 in vivo. Rats were administered cocaine via the tail vein at 20 mg\/kg\/day for 14 days, and showed widespread CBN, microfocal myocarditis and myocardial fibrosis, corresponding to a dysfunction of cardiac mitochondria under increased oxidative stress. The increase in dephosphorylated cardiac Cx43 and its negative correlation with the myocardial distribution of CBN after cocaine administration were determined. In addition, apoptosis and necroptosis, as well as increased adiponectin levels, were observed in the myocardium after cocaine exposure. Accordingly, we found altered profiles of cardiac Cx43, CBN and its negative correlation with dephosphorylated cardiac Cx43, and the possible involvement of adiponectin in the myocardium after 14 days of cocaine administration. The latter might play a protective role in the cardiotoxicity of cocaine. The current findings would be beneficial for establishing novel therapeutic strategies in cocaine-induced cardiac consequences.<\/jats:p>","DOI":"10.3390\/ijms231911978","type":"journal-article","created":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T20:49:31Z","timestamp":1665348571000},"page":"11978","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Contraction Band Necrosis with Dephosphorylated Connexin 43 in Rat Myocardium after Daily Cocaine Administration"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5913-8720","authenticated-orcid":false,"given":"Shuheng","family":"Wen","sequence":"first","affiliation":[{"name":"Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kana","family":"Unuma","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Funakoshi","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Aki","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Uemura","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1056\/NEJM198612043152302","article-title":"Acute Cardiac Events Temporally Related to Cocaine Abuse","volume":"315","author":"Isner","year":"1986","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1161\/01.CIR.85.2.407","article-title":"The Effects of Acute and Chronic Cocaine Use on the Heart","volume":"85","author":"Kloner","year":"1992","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/BF03256574","article-title":"Cocaine Cardiotoxicity: A Review of the Pathophysiology, Pathology, and Treatment Options","volume":"9","author":"Phillips","year":"2009","journal-title":"Am. J. Cardiovasc. Drugs"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/S0006-3495(90)82574-1","article-title":"Characterization of Cocaine-Induced Block of Cardiac Sodium Channels","volume":"57","author":"Crumb","year":"1990","journal-title":"Biophys. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0033-0620(97)80023-0","article-title":"Cocaine-Induced Myocardial Ischemia and Infarction: Pathophysiology, Recognition, and Management","volume":"40","author":"Pitts","year":"1997","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Georgieva, E., Karamalakova, Y., Miteva, R., Abrashev, H., and Nikolova, G. (2021). Oxidative Stress and Cocaine Intoxication as Start Points in the Pathology of Cocaine-Induced Cardiotoxicity. Toxics, 9.","DOI":"10.21203\/rs.3.rs-194166\/v1"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s004140050066","article-title":"Myocardial Necrosis and Cocaine. A Quantitative Morphologic Study in 26 Cocaine-Associated Deaths","volume":"110","author":"Fineschi","year":"1997","journal-title":"Int. J. Leg. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0046-8177(87)80338-6","article-title":"Cocaine and the Heart","volume":"18","author":"Tazelaar","year":"1987","journal-title":"Hum. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0046-8177(86)80150-2","article-title":"Myocardial Contraction Bands Revisited","volume":"17","author":"Karch","year":"1986","journal-title":"Hum. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S0022-2828(85)80132-2","article-title":"Experimental Catecholamine-Induced Myocardial Necrosis. I. Morphology, Quantification and Regional Distribution of Acute Contraction Band Lesions","volume":"17","author":"Todd","year":"1985","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/0002-8703(75)90189-1","article-title":"Different Types of Myocardial Necrosis in Coronary Heart Disease: A Pathophysiologic Review of Their Functional Significance","volume":"89","author":"Baroldi","year":"1975","journal-title":"Am. Heart J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1097\/00000433-198703000-00002","article-title":"Resuscitation-Induced Myocardial Necrosis. Catecholamines and Defibrillation","volume":"8","author":"Karch","year":"1987","journal-title":"Am. J. Forensic. Med. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3579","DOI":"10.1161\/01.CIR.96.10.3579","article-title":"Gap Junction Uncoupler Heptanol Prevents Cell-to-Cell Progression of Hypercontracture and Limits Necrosis During Myocardial Reperfusion","volume":"96","author":"Inserte","year":"1997","journal-title":"Circulation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1161\/01.RES.85.3.280","article-title":"Propagation of Cardiomyocyte Hypercontracture by Passage of Na(+) through Gap Junctions","volume":"85","author":"Hofstaetter","year":"1999","journal-title":"Circ. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1253\/circj.CJ-09-0079","article-title":"Ischemia Enhances Translocation of Connexin43 and Gap Junction Intercellular Communication, Thereby Propagating Contraction Band Necrosis after Reperfusion","volume":"73","author":"Unuma","year":"2009","journal-title":"Circ. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1093\/cvr\/cvn133","article-title":"Remodelling of Gap Junctions and Connexin Expression in Diseased Myocardium","volume":"80","author":"Severs","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.pharmthera.2015.06.005","article-title":"Connexin 43 Is an Emerging Therapeutic Target in Ischemia\/Reperfusion Injury, Cardioprotection and Neuroprotection","volume":"153","author":"Schulz","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3435","DOI":"10.1242\/jcs.03089","article-title":"Analysis of Connexin43 Phosphorylated at S325, S328 and S330 in Normoxic and Ischemic Heart","volume":"119","author":"Lampe","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1083\/jcb.200707060","article-title":"Phosphorylation at S365 Is a Gatekeeper Event That Changes the Structure of Cx43 and Prevents Down-Regulation by Pkc","volume":"179","author":"Solan","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4858","DOI":"10.1172\/JCI134682","article-title":"Auxiliary Trafficking Subunit Gja1-20k Protects Connexin-43 from Degradation and Limits Ventricular Arrhythmias","volume":"130","author":"Xiao","year":"2020","journal-title":"J. Clin. Invest."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1161\/01.RES.87.8.656","article-title":"Dephosphorylation and Intracellular Redistribution of Ventricular Connexin43 During Electrical Uncoupling Induced by Ischemia","volume":"87","author":"Beardslee","year":"2000","journal-title":"Circ. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1038\/s41418-019-0277-x","article-title":"Connexin43 Dephosphorylation at Serine 282 Is Associated with Connexin43-Mediated Cardiomyocyte Apoptosis","volume":"26","author":"Yang","year":"2019","journal-title":"Cell Death Differ."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1161\/01.RES.87.5.346","article-title":"Role of Gap Junctions in Cardiac Conduction and Development: Insights from the Connexin Knockout Mice","volume":"87","author":"Lo","year":"2000","journal-title":"Circ Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S62","DOI":"10.1016\/j.hrthm.2009.03.003","article-title":"Arrhythmogenic Cardiomyopathy and Abnormalities of Cell-to-Cell Coupling","volume":"6","author":"Saffitz","year":"2009","journal-title":"Heart Rhythm"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1111\/j.1476-5381.2011.01395.x","article-title":"Adiponectin and Cardiovascular Health: An Update","volume":"165","author":"Hui","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1007\/s10067-014-2540-3","article-title":"Mean Platelet Volume as an Indicator of Disease Activity in Juvenile Sle","volume":"33","author":"Yavuz","year":"2014","journal-title":"Clin. Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1002\/cphy.c170046","article-title":"Adiponectin Regulation and Function","volume":"8","author":"Fang","year":"2018","journal-title":"Compr. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.phrs.2014.03.003","article-title":"Back to the heart: The protective role of adiponectin","volume":"82","author":"Caselli","year":"2014","journal-title":"Pharmacol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/FJC.0000000000000789","article-title":"Restoration of Adiponectin-Connexin43 Signaling Mitigates Myocardial Inflammation and Dysfunction in Diabetic Female Rats","volume":"75","author":"Leffler","year":"2020","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"644225","DOI":"10.3389\/fphar.2021.644225","article-title":"Adiponectin Attenuates Lipopolysaccharide-Induced Apoptosis by Regulating the Cx43\/Pi3k\/Akt Pathway","volume":"12","author":"Liu","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/S0008-6363(03)00499-1","article-title":"Role of Reactive Oxygen Species in Cocaine-Induced Cardiac Dysfunction","volume":"59","author":"Moritz","year":"2003","journal-title":"Cardiovasc. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s004140000194","article-title":"Markers of Cardiac Oxidative Stress and Altered Morphology after Intraperitoneal Cocaine Injection in a Rat Model","volume":"114","author":"Fineschi","year":"2001","journal-title":"Int. J. Leg. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0014-4800(80)90006-4","article-title":"Isoproterenol-Induced Myocardial Necrosis and Membrane Permeability Alterations in the Isolated Perfused Rabbit Heart","volume":"33","author":"Todd","year":"1980","journal-title":"Exp. Mol. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1016\/j.freeradbiomed.2012.07.021","article-title":"Cytochrome C Oxidase Dysfunction in Oxidative Stress","volume":"53","author":"Srinivasan","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1046\/j.0022-3042.2002.00744.x","article-title":"Generation of reactive oxygen species by the mitochondrial electron transport chain","volume":"80","author":"Liu","year":"2002","journal-title":"J. Neurochem."},{"key":"ref_36","first-page":"842","article-title":"Direct cocaine cardiotoxicity demonstrated by endomyocardial biopsy","volume":"113","author":"Peng","year":"1989","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1083\/jcb.151.3.483","article-title":"Akt Regulates Cell Survival and Apoptosis at a Postmitochondrial Level","volume":"151","author":"Zhou","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1073\/pnas.97.2.529","article-title":"Bax-induced apoptotic cell death","volume":"97","author":"Pawlowski","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/ni.3206","article-title":"The Diverse Role of Rip Kinases in Necroptosis and Inflammation","volume":"16","author":"Silke","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1536\/ihj.52.139","article-title":"Enhanced Inflammation in Epicardial Fat in Patients with Coronary Artery Disease","volume":"52","author":"Hirata","year":"2011","journal-title":"Int. Heart J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5163","DOI":"10.1016\/j.febslet.2005.07.098","article-title":"Adiponectin is synthesized and secreted by human and murine cardiomyocytes","volume":"579","author":"Iglesias","year":"2005","journal-title":"FEBS Lett."},{"key":"ref_42","first-page":"389","article-title":"Cardiomyopathy in a Rat Model of Pheochromocytoma. Morphological and Functional Alterations","volume":"1","author":"Rosenbaum","year":"1988","journal-title":"Am. J. Cardiovasc. Pathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/0002-8703(88)90078-6","article-title":"Cardiovascular Effects of Cocaine: An Autopsy Study of 40 Patients","volume":"115","author":"Virmani","year":"1988","journal-title":"Am. Heart J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1161\/01.RES.83.6.629","article-title":"Rapid Turnover of Connexin43 in the Adult Rat Heart","volume":"83","author":"Beardslee","year":"1998","journal-title":"Circ. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"H1907","DOI":"10.1152\/ajpheart.01242.2010","article-title":"Cholesterol diet leads to attenuation of ischemic preconditioning-induced cardiac protection: The role of connexin 43","volume":"300","author":"Varga","year":"2011","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1042\/BJ20082319","article-title":"Connexin43 phosphorylation: Structural changes and biological effects","volume":"419","author":"Solan","year":"2009","journal-title":"Biochem. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.tcb.2019.07.001","article-title":"Biological Functions of Connexin43 Beyond Intercellular Communication","volume":"29","author":"Aasen","year":"2019","journal-title":"Trends Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"H1453","DOI":"10.1152\/ajpheart.00554.2015","article-title":"Drug-induced mitochondrial dysfunction and cardiotoxicity","volume":"309","author":"Varga","year":"2015","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00395-019-0759-5","article-title":"Mitochondrial connexin 43 in sex-dependent myocardial responses and estrogen-mediated cardiac protection following acute ischemia\/reperfusion injury","volume":"115","author":"Wang","year":"2019","journal-title":"Basic Res. Cardiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1038\/nm1295","article-title":"Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2\u2013dependent mechanisms","volume":"11","author":"Shibata","year":"2005","journal-title":"Nat. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"H984","DOI":"10.1152\/ajpheart.00428.2011","article-title":"Adiponectin mediates cardioprotection in oxidative stress-induced cardiac myocyte remodeling","volume":"301","author":"Essick","year":"2011","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1038\/nm1137","article-title":"Adiponectin-mediated modulation of hypertrophic signals in the heart","volume":"10","author":"Shibata","year":"2004","journal-title":"Nat. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.pbb.2018.11.001","article-title":"Cocaine and Cocaine Expectancy Increase Growth Hormone, Ghrelin, Glp-1, Igf-1, Adiponectin, and Corticosterone While Decreasing Leptin, Insulin, Gip, and Prolactin","volume":"176","author":"You","year":"2019","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"24129","DOI":"10.1038\/s41598-021-03631-y","article-title":"Altered cardiac mitochondrial dynamics and biogenesis in rat after short-term cocaine administration","volume":"11","author":"Wen","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.2337\/db05-1525","article-title":"Comparison of Serum High-Molecular Weight (Hmw) Adiponectin with Total Adiponectin Concentrations in Type 2 Diabetic Patients with Coronary Artery Disease Using a Novel Enzyme-Linked Immunosorbent Assay to Detect Hmw Adiponectin","volume":"55","author":"Aso","year":"2006","journal-title":"Diabetes"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"70","DOI":"10.2174\/1874143600802010070","article-title":"Mechanisms of Acute Cocaine Toxicity","volume":"2","author":"Heard","year":"2008","journal-title":"Open Pharmacol. J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.neuro.2019.09.001","article-title":"Repeated exposure of cocaine alters mitochondrial dynamics in mouse neuroblastoma Neuro2a","volume":"75","author":"Funakoshi","year":"2019","journal-title":"NeuroToxicology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11978\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:48:36Z","timestamp":1760143716000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11978"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,9]]},"references-count":58,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231911978"],"URL":"https:\/\/doi.org\/10.3390\/ijms231911978","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,9]]}}}