{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T07:08:18Z","timestamp":1779001698635,"version":"3.51.4"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":35,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-40683-4","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T17:26:45Z","timestamp":1772040405000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Notch-1 in macrophages promoted the ischemia-reperfusion via modulating EZH2\/HSF1\/BRD4\/SIRP\u03b1\/SHP2 induced ROS and apoptosis in cardiomyocyte"],"prefix":"10.1038","volume":"16","author":[{"given":"Chengbi","family":"Tong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JiaWei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"YaJing","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"XiaoTong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ShaSha","family":"Zang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sha","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"40683_CR1","doi-asserted-by":"crossref","unstructured":"Neimark, M. I. [Ischemia-reperfusion syndrome][J]. Khirurgiia (Mosk), 9, 71\u201376 (2021).","DOI":"10.17116\/hirurgia202109171"},{"key":"40683_CR2","doi-asserted-by":"crossref","unstructured":"Weinberger, T. et al. Resident and recruited macrophages differentially contribute to cardiac healing after myocardial ischemia[J]. Elife, 12, RP89377 (2024).","DOI":"10.7554\/eLife.89377"},{"issue":"12","key":"40683_CR3","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1161\/CIRCRESAHA.124.325212","volume":"135","author":"J Wang","year":"2024","unstructured":"Wang, J. et al. CAR-Macrophage Therapy Alleviates Myocardial Ischemia-Reperfusion Injury[J]. Circ. Res. 135 (12), 1161\u20131174 (2024).","journal-title":"Circ. Res."},{"issue":"4","key":"40683_CR4","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1253\/circj.CJ-19-0959","volume":"84","author":"Y Yue","year":"2020","unstructured":"Yue, Y. et al. M2b Macrophages Regulate Cardiac Fibroblast Activation and Alleviate Cardiac Fibrosis After Reperfusion Injury[J]. Circ. J. 84 (4), 626\u2013635 (2020).","journal-title":"Circ. J."},{"issue":"5","key":"40683_CR5","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1002\/jcp.24872","volume":"230","author":"H Wang","year":"2015","unstructured":"Wang, H. et al. The role of Notch receptors in transcriptional regulation[J]. J. Cell. Physiol. 230 (5), 982\u2013988 (2015).","journal-title":"J. Cell. Physiol."},{"key":"40683_CR6","doi-asserted-by":"publisher","first-page":"695114","DOI":"10.3389\/fcell.2021.695114","volume":"9","author":"L Marracino","year":"2021","unstructured":"Marracino, L. et al. Adding a Notch to Cardiovascular Disease Therapeutics: A MicroRNA-Based Approach[J]. Front. Cell. Dev. Biol. 9, 695114 (2021).","journal-title":"Front. Cell. Dev. Biol."},{"issue":"11","key":"40683_CR7","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1161\/CIRCRESAHA.107.151381","volume":"101","author":"M Koyanagi","year":"2007","unstructured":"Koyanagi, M. et al. Notch signaling contributes to the expression of cardiac markers in human circulating progenitor cells[J]. Circ. Res. 101 (11), 1139\u20131145 (2007).","journal-title":"Circ. Res."},{"issue":"6","key":"40683_CR8","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1136\/annrheumdis-2012-201978","volume":"72","author":"W Gao","year":"2013","unstructured":"Gao, W. et al. Notch signalling pathways mediate synovial angiogenesis in response to vascular endothelial growth factor and angiopoietin 2[J]. Ann. Rheum. Dis. 72 (6), 1080\u20131088 (2013).","journal-title":"Ann. Rheum. Dis."},{"issue":"45","key":"40683_CR9","doi-asserted-by":"publisher","first-page":"eadi2167","DOI":"10.1126\/sciadv.adi2167","volume":"9","author":"R Guo","year":"2023","unstructured":"Guo, R. et al. Context-dependent regulation of Notch signaling in glial development and tumorigenesis[J]. Sci. Adv. 9 (45), eadi2167 (2023).","journal-title":"Sci. Adv."},{"key":"40683_CR10","doi-asserted-by":"crossref","unstructured":"Nakano, K. et al. Notch Signaling Affects Oral Neoplasm Cell Differentiation and Acquisition of Tumor-Specific Characteristics[J]. Int. J. Mol. Sci., 20(8), 1973 (2019).","DOI":"10.3390\/ijms20081973"},{"issue":"9","key":"40683_CR11","doi-asserted-by":"publisher","first-page":"2157","DOI":"10.7150\/ijbs.59648","volume":"17","author":"W Wang","year":"2021","unstructured":"Wang, W. et al. BMP and Notch Signaling Pathways differentially regulate Cardiomyocyte Proliferation during Ventricle Regeneration[J]. Int. J. Biol. Sci. 17 (9), 2157\u20132166 (2021).","journal-title":"Int. J. Biol. Sci."},{"issue":"2","key":"40683_CR12","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.tcm.2018.06.008","volume":"29","author":"OJ Harrison","year":"2019","unstructured":"Harrison, O. J. et al. Defective NOTCH signaling drives increased vascular smooth muscle cell apoptosis and contractile differentiation in bicuspid aortic valve aortopathy: A review of the evidence and future directions[J]. Trends Cardiovasc. Med. 29 (2), 61\u201368 (2019).","journal-title":"Trends Cardiovasc. Med."},{"key":"40683_CR13","doi-asserted-by":"publisher","first-page":"109452","DOI":"10.1016\/j.biopha.2019.109452","volume":"120","author":"Z Jin","year":"2019","unstructured":"Jin, Z. et al. Neuroprotective effects of irisin against cerebral ischemia\/ reperfusion injury via Notch signaling pathway[J]. Biomed. Pharmacother. 120, 109452 (2019).","journal-title":"Biomed. Pharmacother"},{"issue":"6","key":"40683_CR14","doi-asserted-by":"publisher","first-page":"1860","DOI":"10.7150\/thno.83353","volume":"13","author":"B Li","year":"2023","unstructured":"Li, B. et al. Histone H3K27 methyltransferase EZH2 regulates apoptotic and inflammatory responses in sepsis-induced AKI[J]. Theranostics 13 (6), 1860\u20131875 (2023).","journal-title":"Theranostics"},{"issue":"2","key":"40683_CR15","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1158\/1541-7786.MCR-15-0313","volume":"14","author":"H Xu","year":"2016","unstructured":"Xu, H. et al. Integrative Analysis Reveals the Transcriptional Collaboration between EZH2 and E2F1 in the Regulation of Cancer-Related Gene Expression[J]. Mol. Cancer Res. 14 (2), 163\u2013172 (2016).","journal-title":"Mol. Cancer Res."},{"issue":"2","key":"40683_CR16","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1097\/FJC.0000000000001062","volume":"78","author":"JL Yuan","year":"2021","unstructured":"Yuan, J. L. et al. EZH2 as an Epigenetic Regulator of Cardiovascular Development and Diseases[J]. J. Cardiovasc. Pharmacol. 78 (2), 192\u2013201 (2021).","journal-title":"J. Cardiovasc. Pharmacol."},{"issue":"2","key":"40683_CR17","doi-asserted-by":"publisher","first-page":"188700","DOI":"10.1016\/j.bbcan.2022.188700","volume":"1877","author":"S Sun","year":"2022","unstructured":"Sun, S. et al. EZH2, a prominent orchestrator of genetic and epigenetic regulation of solid tumor microenvironment and immunotherapy[J]. Biochim. Biophys. Acta Rev. Cancer. 1877 (2), 188700 (2022).","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"issue":"3","key":"40683_CR18","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.ccell.2025.01.013","volume":"43","author":"P Porazzi","year":"2025","unstructured":"Porazzi, P. et al. EZH1\/EZH2 inhibition enhances adoptive T cell immunotherapy against multiple cancer models[J]. Cancer Cell. 43 (3), 537\u2013551e537 (2025).","journal-title":"Cancer Cell."},{"issue":"9","key":"40683_CR19","doi-asserted-by":"publisher","first-page":"103104","DOI":"10.1016\/j.cpcardiol.2025.103104","volume":"50","author":"S Fang","year":"2025","unstructured":"Fang, S. et al. The dual functionality of EZH2 in cardiovascular disease: Bridging cancer biology and cardiac pathophysiology through epigenetic regulation, metabolic reprogramming, and novel therapeutic interventions[J]. Curr. Probl. Cardiol. 50 (9), 103104 (2025).","journal-title":"Curr. Probl. Cardiol."},{"issue":"6","key":"40683_CR20","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1016\/j.ccell.2024.04.009","volume":"42","author":"Y Liu","year":"2024","unstructured":"Liu, Y. et al. Understanding the complexity of p53 in a new era of tumor suppression[J]. Cancer Cell. 42 (6), 946\u2013967 (2024).","journal-title":"Cancer Cell."},{"key":"40683_CR21","doi-asserted-by":"crossref","unstructured":"Liu, Y. et al. Myeloid SHP2 attenuates myocardial ischemia\u2013reperfusion injury via regulation of BRD4\/SYK\/STING\/NOX4\/NLRP3 signaling[J]. Mol. Med. Rep. 31(6), 155 (2025).","DOI":"10.3892\/mmr.2025.13520"},{"key":"40683_CR22","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.yjmcc.2020.10.010","volume":"150","author":"N Wang","year":"2021","unstructured":"Wang, N. et al. HSF1 functions as a key defender against palmitic acid-induced ferroptosis in cardiomyocytes[J]. J. Mol. Cell. Cardiol. 150, 65\u201376 (2021).","journal-title":"J. Mol. Cell. Cardiol."},{"issue":"1","key":"40683_CR23","doi-asserted-by":"publisher","first-page":"29741","DOI":"10.1038\/s41598-025-13531-0","volume":"15","author":"X Liu","year":"2025","unstructured":"Liu, X. et al. HSF1 in macrophages suppressed the progression of asthma via modulating SIRP\u03b1\/SHP2-Dectin-1\/ SYK mediated ROS and inflammatory responses[J]. Sci. Rep. 15 (1), 29741 (2025).","journal-title":"Sci. Rep."},{"issue":"5","key":"40683_CR24","doi-asserted-by":"publisher","first-page":"2018","DOI":"10.1002\/anie.201912524","volume":"59","author":"W Nie","year":"2020","unstructured":"Nie, W. et al. Responsive Exosome Nano-bioconjugates for Synergistic Cancer Therapy[J]. Angew Chem. Int. Ed. Engl. 59 (5), 2018\u20132022 (2020).","journal-title":"Angew Chem. Int. Ed. Engl."},{"key":"40683_CR25","doi-asserted-by":"crossref","unstructured":"Li, Y. et al. SHP2 deneddylation mediates tumor immunosuppression in colon cancer via the CD47\/SIRP\u03b1 axis[J]. J. Clin. Invest. 133(4), e162870 (2023).","DOI":"10.1172\/JCI162870"},{"key":"40683_CR26","doi-asserted-by":"publisher","first-page":"867260","DOI":"10.3389\/fimmu.2022.867260","volume":"13","author":"M Cutolo","year":"2022","unstructured":"Cutolo, M. et al. The Role of M1\/M2 Macrophage Polarization in Rheumatoid Arthritis Synovitis[J]. Front. Immunol. 13, 867260 (2022).","journal-title":"Front. Immunol."},{"key":"40683_CR27","doi-asserted-by":"publisher","first-page":"1228962","DOI":"10.3389\/fphar.2023.1228962","volume":"14","author":"H Deng","year":"2023","unstructured":"Deng, H. et al. New hope for tumor immunotherapy: the macrophage-related do not eat me signaling pathway[J]. Front. Pharmacol. 14, 1228962 (2023).","journal-title":"Front. Pharmacol."},{"issue":"5","key":"40683_CR28","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1177\/10915818221105227","volume":"41","author":"D Wang","year":"2022","unstructured":"Wang, D. & Cao, Q. Shp2 in Alveolar Macrophages Regulates Macrophage I Phenotype in Acute Lung Injury[J]. Int. J. Toxicol. 41 (5), 412\u2013419 (2022).","journal-title":"Int. J. Toxicol."},{"issue":"7","key":"40683_CR29","doi-asserted-by":"publisher","first-page":"3894","DOI":"10.1074\/jbc.M114.614057","volume":"290","author":"XJ Li","year":"2015","unstructured":"Li, X. J. et al. Protein-tyrosine phosphatase Shp2 positively regulates macrophage oxidative burst[J]. J. Biol. Chem. 290 (7), 3894\u20133909 (2015).","journal-title":"J. Biol. Chem."},{"issue":"702","key":"40683_CR30","doi-asserted-by":"publisher","first-page":"eabb3966","DOI":"10.1126\/scisignal.abb3966","volume":"14","author":"L Shi","year":"2021","unstructured":"Shi, L. et al. SIRP\u03b1 sequesters SHP-2 to promote IL-4 and IL-13 signaling and the alternative activation of macrophages[J]. Sci. Signal. 14 (702), eabb3966 (2021).","journal-title":"Sci. Signal."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-40683-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-40683-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-40683-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T10:59:32Z","timestamp":1775041172000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-40683-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,25]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["40683"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-40683-4","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-6701664\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,25]]},"assertion":[{"value":"19 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study has been approved by the Medical Ethics Committee of Affiliated Hospital of Hebei Universit.(Approval number: HBDX202401040012).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"11020"}}