{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:00:09Z","timestamp":1790744409009,"version":"4.1.0"},"reference-count":66,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"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":["82170320"],"award-info":[{"award-number":["82170320"]}],"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"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Atrial fibrillation (AF) is a common arrhythmia associated with calcium (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ) dysregulation. Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \/calmodulin\u2010dependent protein kinase II\u2010\u03b4 (CaMKII\u2010\u03b4) links Ca\n                    <jats:sup>2+<\/jats:sup>\n                    handling to arrhythmogenesis, but whether deubiquitination regulates its stability in AF remains unclear. We established an AF model by infusing angiotensin II (Ang II) for 3 weeks in atrial cardiomyocyte\u2010specific ubiquitin C\u2010terminal hydrolase L1 (UCHL1)\u2010knockout (CKO) and recombinant adeno\u2010associated virus serotype 9 (rAAV9)\u2010UCHL1\u2010overexpressing\u00a0mice. UCHL1 was markedly upregulated in atria from Ang II\u2010infused mice and patients with AF. UCHL1\u2010CKO attenuated Ang II\u2010induced atrial remodeling and AF susceptibility, reduced CaMKII\u2010\u03b4 stability, and improved Ca\n                    <jats:sup>2+<\/jats:sup>\n                    handling, whereas UCHL1 overexpression produced the opposite effects. Mechanistically, UCHL1 bound to and deubiquitinated CaMKII\u2010\u03b4 at K251, preventing proteasomal degradation and thereby enhancing ryanodine receptor type 2 (RyR2) phosphorylation and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    mishandling. The ubiquitination\u2010deficient CaMKII\u2010\u03b4\u2010K251R mutant aggravated AF, whereas CaMKII\u2010\u03b4 knockdown or inhibition reduced the proarrhythmic effects of UCHL1 overexpression. Furthermore, the UCHL1 inhibitor 6RK73 reduced AF inducibility in mice. These findings identify UCHL1\u2010mediated stabilization of the CaMKII\u2010\u03b4\u2013RyR2 axis as a mechanism of AF and support UCHL1 as a potential therapeutic target.\n                  <\/jats:p>","DOI":"10.1002\/advs.77855","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:39:37Z","timestamp":1790743177000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Deubiquitinase UCHL1 Drives Susceptibility to Atrial Fibrillation by Stabilizing CaMKII\u2010\u03b4"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9825-6973","authenticated-orcid":false,"given":"Hai\u2010Lian","family":"Bi","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular Diseases First Affiliated Hospital of Dalian Medical University  Dalian 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