{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:22:19Z","timestamp":1792092139082,"version":"4.4.0"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"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":["82470290"],"award-info":[{"award-number":["82470290"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Cardiac repair after myocardial ischemia\u2013reperfusion (MIR) declines with aging. This study shows that Chromobox 7 (CBX7)\u00a0acts in an age\u2010dependent manner, in young hearts, it promotes cardiomyocyte proliferation, whereas in aged hearts, CBX7 forms liquid\u2013liquid phase separation (LLPS) with ATP7A, trapping ATP7A intracellularly, reducing membrane trafficking and copper efflux, and triggering cuproptosis. High\u2010throughput screening identifies \u03b4\u2010Amyrenone (\u03b4Ae) as a selective CBX7 inhibitor that disrupts CBX7\u2010ATP7A LLPS, restores ATP7A trafficking and copper efflux, and improves cardiac function while reducing fibrosis and arrhythmias. Single\u2010cell RNA\u2010seq shows MIR\u2010induced cuproptosis\u2010related loss is concentrated in NR4A3 positive cardiomyocytes and RGCC positive capillary endothelial cells in aged hearts. To enhance delivery, this study engineered a multifunctional conductive hydrogel with antioxidant, pro\u2010angiogenic, immunomodulatory, O\n                    <jats:sub>2<\/jats:sub>\n                    releasing and electrical properties. Loaded with \u03b4Ae, this single\u2010injection hydrogel provides controlled release, alleviates cuproptosis\u2010related mitochondrial injury, and pairs its intrinsic repair capacity with CBX7 inhibition to drive ATP7A trafficking, enhance copper efflux, and suppress cuproptosis. In aged mouse and Bama minipig MIR models, this strategy improves structural, functional, and electrophysiological outcomes, supporting translational potential.\n                  <\/jats:p>","DOI":"10.1002\/advs.202511630","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T09:08:04Z","timestamp":1761037684000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Engineered Multifunctional Hydrogel Delivering Novel CBX7 Inhibitor Modulates Cuproptosis Via Liquid\u2013Liquid Phase Separation to Restore Cardiac Function in Aged Myocardial Infarction"],"prefix":"10.1002","volume":"13","author":[{"given":"Jun","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Affiliated Hospital of North Sichuan Medical College  Nanchong 637000 China"},{"name":"School of Laboratory Medicine North Sichuan Medical College  Nanchong 637007 China"},{"name":"Translational Medicine Research Center North Sichuan Medical College  Nanchong 637007 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Affiliated Hospital of North Sichuan Medical College  Nanchong 637000 China"},{"name":"School of Laboratory Medicine North Sichuan Medical College  Nanchong 637007 China"},{"name":"Translational Medicine Research Center North Sichuan Medical College  Nanchong 637007 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Affiliated Hospital of North Sichuan Medical College  Nanchong 637000 China"},{"name":"School of Laboratory Medicine North Sichuan Medical College  Nanchong 637007 China"},{"name":"Translational Medicine Research Center North Sichuan Medical College  Nanchong 637007 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Liang","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Diseases &amp; Department of Cardiology Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China  Chengdu 610072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Affiliated Hospital of North Sichuan Medical College  Nanchong 637000 China"},{"name":"School of Laboratory Medicine North Sichuan Medical College  Nanchong 637007 China"},{"name":"Translational Medicine Research Center North Sichuan Medical College  Nanchong 637007 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Affiliated Hospital of North Sichuan Medical College  Nanchong 637000 China"},{"name":"School of Laboratory Medicine North Sichuan Medical College  Nanchong 637007 China"},{"name":"Translational Medicine Research Center North Sichuan Medical College  Nanchong 637007 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Mathematics Army Medical University  Chongqing 400038 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China  Chengdu 610072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feila","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Bioengineering Chongqing University of Technology  Chongqing 400050 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Affiliated Hospital of North Sichuan Medical College  Nanchong 637000 China"},{"name":"School of Laboratory Medicine North Sichuan Medical College  Nanchong 637007 China"},{"name":"Translational Medicine Research Center North Sichuan Medical College  Nanchong 637007 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1900-8358","authenticated-orcid":false,"given":"Panke","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Diseases &amp; Department of Cardiology Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China  Chengdu 610072 China"},{"name":"Ultrasound Medicine and Computational Cardiology Key Laboratory of Sichuan Province Chengdu 610072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China  Chengdu 610072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.026"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00413-2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867328666210914115411"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12012-024-09926-6"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.119.118018"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-020-00588-4"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.061131"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40203-2"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04924-6"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.054072"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2022.03.009"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-023-00622-3"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2022.100852"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf0529"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05639-w"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2023.07.004"},{"key":"e_1_2_9_17_1","first-page":"498","volume":"23","author":"Leake I.","year":"2024","journal-title":"Nat. Rev."},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.02.010"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202200990"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.1c16481"},{"key":"e_1_2_9_21_1","volume":"7","author":"Li Y.","year":"2021","journal-title":"Sci. Adv."},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2024.184306"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41540-024-00414-9"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13442-5"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-024-01337-5"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S483541"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2025.01.013"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02124-y"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.122.320246"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-023-00914-x"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202511630","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202511630","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202511630","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T13:00:39Z","timestamp":1774270839000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202511630"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,21]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/advs.202511630"],"URL":"https:\/\/doi.org\/10.1002\/advs.202511630","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,21]]},"assertion":[{"value":"2025-06-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e11630"}}