{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T14:09:57Z","timestamp":1781014197873,"version":"3.54.1"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":76,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470303"],"award-info":[{"award-number":["82470303"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82570354"],"award-info":[{"award-number":["82570354"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270300"],"award-info":[{"award-number":["82270300"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Myocardial infarction (MI) remains a predominant contributor to global cardiovascular disease death, with apoptosis playing a pivotal yet incompletely characterized role in adverse cardiac remodeling. Despite advances in bulk RNA sequence analyses, the single\u2010cell level analyses of apoptotic signaling of MI progression remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Multiomics data integration was synthesized through single\u2010nucleus RNA\u2010seq (snRNA\u2010seq) (GSE270788) and bulk RNA\u2010seq (GSE21610). Three hundred ninety\u2010seven ARGs (apoptosis\u2010related genes) were downloaded from GeneCards (relevance score &gt;\u20097), followed by identification of candidate genes through AUCell scoring and correlation analysis. Random Forest, Boruta, and LASSO algorithms were employed to refine hub genes. Hub genes were validated by animal and cell experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Single\u2010nucleus sequence analysis reveals dramatic variation in ARGs activity across cardiac cells after MI, with fibroblasts demonstrating significantly elevated apoptotic activity compared with other cell types. Integration of single\u2010nucleus and bulk sequence confirms TNFRSF12A as the major molecule regulating ARGs activation in MI. Experiment validation confirmed that upregulation of TNFRSF12A in the MI model and TGF\u2010\n                      <jats:italic>\u03b2<\/jats:italic>\n                      induced NIH3T3.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study revealed that fibroblast dominates apoptotic activity post\u2010MI. We identified TNFRSF12A as a key regulator in MI through multiomics analysis, with potential as a diagnostic biomarker and therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/cdr\/5553167","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T06:29:08Z","timestamp":1773901748000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Machine Learning Integrates Bulk and Single\u2010Nucleus RNA Sequence to Explore Apoptosis\u2010Related Gene in Myocardial Infarction"],"prefix":"10.1155","volume":"2026","author":[{"given":"Bin","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shude","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panting","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghui","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dali","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9040-2200","authenticated-orcid":false,"given":"Dan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4569-6737","authenticated-orcid":false,"given":"Yaling","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.042157"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/CD9.0000000000000106"},{"key":"e_1_2_13_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn285"},{"key":"e_1_2_13_4_2","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1161\/01.CIR.0000085658.98621.49","article-title":"Ventricular Remodeling After Infarction and the Extracellular Collagen Matrix: When Is Enough Enough?","volume":"108","author":"Jugdutt B. I.","year":"2003","journal-title":"Circulation"},{"key":"e_1_2_13_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00310.2009"},{"key":"e_1_2_13_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/hh1501.094115"},{"key":"e_1_2_13_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-025-02075-3"},{"key":"e_1_2_13_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16329"},{"key":"e_1_2_13_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000074225.62168.68"},{"key":"e_1_2_13_10_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060547"},{"key":"e_1_2_13_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.104.3.253"},{"key":"e_1_2_13_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_2_13_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4463"},{"key":"e_1_2_13_14_2","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_2_13_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_2_13_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-022-03364-0"},{"key":"e_1_2_13_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11517-019-02079-7"},{"key":"e_1_2_13_18_2","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v033.i01"},{"key":"e_1_2_13_19_2","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: Gene Set Variation Analysis for Microarray and RNA-Seq Data","volume":"14","author":"H\u00e4nzelmann S.","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"e_1_2_13_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07767-w"},{"key":"e_1_2_13_21_2","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2105-12-77","article-title":"pROC: An Open-Source Package for R and S+ to Analyze and Compare ROC Curves","volume":"12","author":"Robin X.","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"e_1_2_13_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"e_1_2_13_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.223925"},{"key":"e_1_2_13_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115083"},{"key":"e_1_2_13_25_2","doi-asserted-by":"publisher","DOI":"10.3791\/1738-v"},{"key":"e_1_2_13_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.115220"},{"key":"e_1_2_13_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-012-0325-x"},{"key":"e_1_2_13_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2013.05.009"},{"key":"e_1_2_13_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2024.05.006"},{"key":"e_1_2_13_30_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.47180"},{"key":"e_1_2_13_31_2","article-title":"HDAC Class I Inhibitor, Mocetinostat, Reverses Cardiac Fibrosis in Heart Failure and Diminishes CD90+ Cardiac Myofibroblast Activation","volume":"7","author":"Nural-Guvener H. F.","year":"2014","journal-title":"Fibrogenesis & Tissue Repair"},{"key":"e_1_2_13_32_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.113825"},{"key":"e_1_2_13_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.320157"},{"key":"e_1_2_13_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-025-02946-8"},{"key":"e_1_2_13_35_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-024-02342-8"},{"key":"e_1_2_13_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.837286"},{"key":"e_1_2_13_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105414"},{"key":"e_1_2_13_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05403-6"}],"container-title":["Cardiovascular Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/cdr\/5553167","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/cdr\/5553167","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/cdr\/5553167","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T06:29:09Z","timestamp":1773901749000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/cdr\/5553167"}},"subtitle":[],"editor":[{"given":"Baohui","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/cdr\/5553167"],"URL":"https:\/\/doi.org\/10.1155\/cdr\/5553167","archive":["Portico"],"relation":{},"ISSN":["1755-5914","1755-5922"],"issn-type":[{"value":"1755-5914","type":"print"},{"value":"1755-5922","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-09-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"5553167"}}