{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T18:28:24Z","timestamp":1787336904449,"version":"build-2736575974"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"34","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471105"],"award-info":[{"award-number":["82471105"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471096"],"award-info":[{"award-number":["82471096"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271100"],"award-info":[{"award-number":["82271100"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018592","name":"\u201c333 Project\u201d of Jiangsu Province","doi-asserted-by":"publisher","award":["\/"],"award-info":[{"award-number":["\/"]}],"id":[{"id":"10.13039\/501100018592","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jiangsu Province Hospital High-level Talent Cultivation Program","award":["CZ0121002010037"],"award-info":[{"award-number":["CZ0121002010037"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,8,25]]},"abstract":"<jats:p>\n                    Diabetic microvasculopathy is a serious diabetes complication, with diabetic retinopathy (DR) being a leading cause of blindness worldwide due to immature, leaky neovessels. Antiangiogenic therapies merely suppress neovascularization, leaving the retina oxygen-starved and prone to regrowth. Thus, therapies that stabilize aberrant neovessels are needed. We identify the RNA demethylase ALKBH3 as an epitranscriptional driver of diabetic microvasculopathy. Upregulated ALKBH3 in diabetic vascular endothelial cells promoted a pathological shift to an unstable, pro-angiogenic phenotype, disrupting blood-retinal barrier and forming immature neovessels, which impaired vision. Conversely, removing ALKBH3 protected against this. Mechanistically, ALKBH3 demethylated\n                    <jats:italic toggle=\"yes\">BMP2<\/jats:italic>\n                    mRNA to increase its stability via YTHDF2. We further developed a neovasculature-targeting nanoparticle delivering the ALKBH3 inhibitor HUHS015, which normalized retinal neovascularization by simultaneously limiting growth and promoting maturation. It acted synergistically with vascular endothelial growth factor (VEGF) blockade, suggesting potential for anti-VEGF-resistant cases. Our work defines ALKBH3 as a key mediator of diabetic microvasculopathy and supports a VEGF-independent therapeutic paradigm that shifts the focus from vessel suppression to active normalization.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2602779123","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T17:35:51Z","timestamp":1787333751000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["ALKBH3 inhibition normalizes neovessels by reprogramming endothelial fate in diabetic microvasculopathy"],"prefix":"10.1073","volume":"123","author":[{"given":"Yi-Chen","family":"Zhang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04py1g812","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University","place":["Nanjing, 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Xu , Single-cell RNA sequencing identifies MMP11(+) cancer-associated fibroblasts as drivers of angiogenesis and bladder cancer progression. Adv. Sci. (Weinh.) 12, e02774 (2025).","journal-title":"Adv. Sci. (Weinh.)"},{"key":"e_1_3_4_52_2","unstructured":"Y. Zhang . ALKBH3 inhibition normalizes neovessels by reprogramming endothelial fate in diabetic microvasculopathy. NCBI Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE331464. Deposited 22 May 2026."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2602779123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T17:35:52Z","timestamp":1787333752000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2602779123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":52,"journal-issue":{"issue":"34","published-print":{"date-parts":[[2026,8,25]]}},"alternative-id":["10.1073\/pnas.2602779123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2602779123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]},"assertion":[{"value":"2026-01-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2602779123"}}