{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T07:59:56Z","timestamp":1793260796942,"version":"4.5.0"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100012165","name":"Key Technologies Research and Development Program","doi-asserted-by":"publisher","award":["2023YFA1800600"],"award-info":[{"award-number":["2023YFA1800600"]}],"id":[{"id":"10.13039\/501100012165","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004147","name":"Tsinghua University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004147","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007937","name":"Peking University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007937","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["gpyc20240020"],"award-info":[{"award-number":["gpyc20240020"]}],"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":["32230032"],"award-info":[{"award-number":["32230032"]}],"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":["82400316"],"award-info":[{"award-number":["82400316"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFA0800501"],"award-info":[{"award-number":["2018YFA0800501"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jmmc-online.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Molecular and Cellular Cardiology"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.yjmcc.2026.04.002","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T06:58:35Z","timestamp":1776668315000},"page":"20-35","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Small-molecule cocktail 5SM induces heart regeneration by upregulating TGF\u03b2\/BMP signaling"],"prefix":"10.1016","volume":"215","author":[{"given":"Yuanyuan","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye-Guang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Wei","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.yjmcc.2026.04.002_bb0005","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1016\/j.jacc.2019.10.009","article-title":"The global burden of cardiovascular diseases and risk factors: 2020 and beyond","volume":"74","author":"Mensah","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0010","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/j.chembiol.2016.07.007","article-title":"Chemical modulation of cell fate in stem cell therapeutics and regenerative medicine","volume":"23","author":"Liu","year":"2016","journal-title":"Cell Chem. Biol."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0015","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.stem.2022.03.009","article-title":"A small-molecule cocktail promotes mammalian cardiomyocyte proliferation and heart regeneration","volume":"29","author":"Du","year":"2022","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0020","doi-asserted-by":"crossref","DOI":"10.1093\/jmcb\/mjad034","article-title":"Effective therapy of the small-molecule cocktail 5SM on adult rat heart after ischemia-reperfusion injury","volume":"15","author":"Zheng","year":"2023","journal-title":"J. Mol. Cell Biol."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0025","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a021865","article-title":"The discovery and early days of TGF-\u03b2: a historical perspective","volume":"8","author":"Moses","year":"2016","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0030","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13619-024-00194-x","article-title":"New progress in roles of TGF-\u03b2 signaling crosstalks in cellular functions, immunity and diseases","volume":"13","author":"Gu","year":"2024","journal-title":"Cell Regener."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0035","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1471-2148-9-28","article-title":"Emergence, development and diversification of the TGF-beta signalling pathway within the animal kingdom","volume":"9","author":"Huminiecki","year":"2009","journal-title":"BMC Evol. Biol."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0040","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a022186","article-title":"TGF-\u03b2 family signaling in embryonic and somatic stem-cell renewal and differentiation","volume":"9","author":"Mullen","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0045","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/nrd3810","article-title":"Targeting the TGF\u03b2 signalling pathway in disease","volume":"11","author":"Akhurst","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0050","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1146\/annurev.biochem.67.1.753","article-title":"TGF-beta signal transduction","volume":"67","author":"Massagu\u00e9","year":"1998","journal-title":"Annu. Rev. Biochem."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0055","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/nrm3434","article-title":"TGF\u03b2 signalling in context","volume":"13","author":"Massagu\u00e9","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0060","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a022053","article-title":"Signaling receptors for TGF-\u03b2 family members","volume":"8","author":"Heldin","year":"2016","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0065","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jcp.10066","article-title":"Regulation of cell proliferation by Smad proteins","volume":"191","author":"Ten Dijke","year":"2002","journal-title":"J. Cell. Physiol."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0070","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2022.104139","article-title":"Inhibition of DYRK1A, via histone modification, promotes cardiomyocyte cell cycle activation and cardiac repair after myocardial infarction","volume":"82","author":"Lan","year":"2022","journal-title":"EBioMedicine"},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0075","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1158\/2159-8290.CD-14-0275","article-title":"Active CREB1 promotes a malignant TGF\u03b22 autocrine loop in glioblastoma","volume":"4","author":"Rod\u00f3n","year":"2014","journal-title":"Cancer Discov."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0080","doi-asserted-by":"crossref","first-page":"29479","DOI":"10.1074\/jbc.M600579200","article-title":"Requirement of smad3 and CREB-1 in mediating transforming growth factor-beta (TGF beta) induction of TGF beta 3 secretion","volume":"281","author":"Liu","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0085","article-title":"Transcriptional regulation of BMP2 expression by the PTH-CREB signaling pathway in osteoblasts","volume":"6","author":"Zhang","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0090","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1172\/JCI59466","article-title":"Administration of BMP2\/7 in utero partially reverses Rubinstein-Taybi syndrome-like skeletal defects induced by pdk1 or Cbp mutations in mice","volume":"122","author":"Shim","year":"2012","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0095","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1111\/j.1474-9726.2011.00735.x","article-title":"Age-related decline in osteoblastogenesis and 1\u03b1-hydroxylase\/CYP27B1 in human mesenchymal stem cells: stimulation by parathyroid hormone","volume":"10","author":"Geng","year":"2011","journal-title":"Aging Cell"},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0100","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/s41401-020-0469-4","article-title":"Oral administration of curcumin ameliorates pulmonary fibrosis in mice through 15d-PGJ2-mediated induction of hepatocyte growth factor in the colon","volume":"42","author":"Miao","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0105","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1038\/s41467-024-46365-x","article-title":"Targeting P2Y(14)R protects against necroptosis of intestinal epithelial cells through PKA\/CREB\/RIPK1 axis in ulcerative colitis","volume":"15","author":"Liu","year":"2024","journal-title":"Nat. Commun."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0110","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1749-6632.2002.tb04327.x","article-title":"Role of the PKA-regulated transcription factor CREB in development and tumorigenesis of endocrine tissues","volume":"968","author":"Rosenberg","year":"2002","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0115","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/36362","article-title":"Switching of the coupling of the beta2-adrenergic receptor to different g proteins by protein kinase a","volume":"390","author":"Daaka","year":"1997","journal-title":"Nature"},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0120","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1161\/01.CIR.101.19.2302","article-title":"Dopamine as a novel antioxidative agent for rat vascular smooth muscle cells through dopamine d(1)-like receptors","volume":"101","author":"Yasunari","year":"2000","journal-title":"Circulation"},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0125","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.cell.2007.12.033","article-title":"Visualizing spatiotemporal dynamics of multicellular cell-cycle progression","volume":"132","author":"Sakaue-Sawano","year":"2008","journal-title":"Cell"},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0130","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.devcel.2015.12.010","article-title":"Spatially resolved genome-wide transcriptional profiling identifies BMP signaling as essential regulator of zebrafish cardiomyocyte regeneration","volume":"36","author":"Wu","year":"2016","journal-title":"Dev. Cell"},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0135","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.stem.2012.04.025","article-title":"Small molecule-mediated TGF-\u03b2 type II receptor degradation promotes cardiomyogenesis in embryonic stem cells","volume":"11","author":"Willems","year":"2012","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0140","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1038\/nm.1888","article-title":"BMP type i receptor inhibition reduces heterotopic [corrected] ossification","volume":"14","author":"Yu","year":"2008","journal-title":"Nat. Med."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0145","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1161\/CIRCULATIONAHA.116.024692","article-title":"Chemical enhancement of in vitro and in vivo direct cardiac reprogramming","volume":"135","author":"Mohamed","year":"2017","journal-title":"Circulation"},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0150","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a033274","article-title":"TGF-\u03b2 family signaling in early vertebrate development","volume":"10","author":"Zinski","year":"2018","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0155","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ceb.2019.07.007","article-title":"TGF-\u03b2 signaling in cell fate control and cancer","volume":"61","author":"Yu","year":"2019","journal-title":"Curr. Opin. Cell Biol."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0160","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1161\/01.CIR.0000165066.71481.8E","article-title":"Postinfarction gene therapy against transforming growth factor-beta signal modulates infarct tissue dynamics and attenuates left ventricular remodeling and heart failure","volume":"111","author":"Okada","year":"2005","journal-title":"Circulation"},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0165","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.4049\/jimmunol.1800322","article-title":"Conventional dendritic cells impair recovery after myocardial infarction","volume":"201","author":"Lee","year":"2018","journal-title":"J. Immunol."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0170","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1093\/cvr\/cvaa287","article-title":"Angiogenesis after acute myocardial infarction","volume":"117","author":"Wu","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0175","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1126\/science.2164258","article-title":"Mediation of cardioprotection by transforming growth factor-beta","volume":"249","author":"Lefer","year":"1990","journal-title":"Science (New York, N.Y.)"},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0180","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s00395-010-0108-1","article-title":"TGF-beta1 improves cardiac performance via up-regulation of laminin receptor 37\/67 in adult ventricular cardiomyocytes","volume":"105","author":"Wenzel","year":"2010","journal-title":"Basic Res. Cardiol."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0185","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nm.3820","article-title":"A high-throughput chemical screen reveals that Harmine-mediated inhibition of DYRK1A increases human pancreatic beta cell replication","volume":"21","author":"Wang","year":"2015","journal-title":"Nat. Med."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0190","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1172\/JCI63623","article-title":"Inhibition of DYRK1A destabilizes EGFR and reduces EGFR-dependent glioblastoma growth","volume":"123","author":"Pozo","year":"2013","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0195","doi-asserted-by":"crossref","first-page":"17320","DOI":"10.1074\/jbc.M109.006759","article-title":"DYRK1A is a novel negative regulator of cardiomyocyte hypertrophy","volume":"284","author":"Kuhn","year":"2009","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0200","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1161\/CIRCULATIONAHA.121.055727","article-title":"DYRK1B-STAT3 drives cardiac hypertrophy and heart failure by impairing mitochondrial bioenergetics","volume":"145","author":"Zhuang","year":"2022","journal-title":"Circulation"},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0205","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1038\/s41467-025-56993-6","article-title":"BMP signaling promotes zebrafish heart regeneration via alleviation of replication stress","volume":"16","author":"Vasudevarao","year":"2025","journal-title":"Nat. Commun."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0210","doi-asserted-by":"crossref","DOI":"10.1242\/dev.164194","article-title":"In vivo analysis of cardiomyocyte proliferation during trabeculation","volume":"145","author":"Uribe","year":"2018","journal-title":"Development"},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0215","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.cardiores.2007.02.023","article-title":"Developmental expression of myostatin in cardiomyocytes and its effect on foetal and neonatal rat cardiomyocyte proliferation","volume":"74","author":"McKoy","year":"2007","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0220","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.diff.2016.06.005","article-title":"Smad4 is required for the development of cardiac and skeletal muscle in zebrafish","volume":"92","author":"Yang","year":"2016","journal-title":"Differentiation"},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0225","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.ydbio.2007.08.022","article-title":"Essential role of smad4 in maintaining cardiomyocyte proliferation during murine embryonic heart development","volume":"311","author":"Qi","year":"2007","journal-title":"Dev. Biol."},{"key":"10.1016\/j.yjmcc.2026.04.002_bb0230","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13619-023-00170-x","article-title":"Chemical screening links disulfiram with cardiac protection after ischemic injury","volume":"12","author":"Chen","year":"2023","journal-title":"Cell Regener."}],"container-title":["Journal of Molecular and Cellular Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022282826000532?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022282826000532?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T12:48:29Z","timestamp":1783169309000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022282826000532"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":46,"alternative-id":["S0022282826000532"],"URL":"https:\/\/doi.org\/10.1016\/j.yjmcc.2026.04.002","relation":{},"ISSN":["0022-2828"],"issn-type":[{"value":"0022-2828","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Small-molecule cocktail 5SM induces heart regeneration by upregulating TGF\u03b2\/BMP signaling","name":"articletitle","label":"Article Title"},{"value":"Journal of Molecular and Cellular Cardiology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.yjmcc.2026.04.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}