{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:10:09Z","timestamp":1788930609212,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"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":["82072204"],"award-info":[{"award-number":["82072204"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010722","name":"Harbin Medical University","doi-asserted-by":"publisher","award":["HDHY2025032"],"award-info":[{"award-number":["HDHY2025032"]}],"id":[{"id":"10.13039\/100010722","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                    Intestinal ischemia\/reperfusion (I\/R) disrupts the gut vascular barrier (GVB), causing bacterial translocation and organ injury. Dexmedetomidine can protect the GVB, but its clinical use is limited by dose\u2011dependent cardiorespiratory depression. To address this, we develop reactive oxygen species (ROS)\u2011responsive nanoparticles for targeted intestinal delivery and evaluate the efficacy and mechanism of dexmedetomidine\u2011loaded nanoparticles (Dex\u2011NPs) against intestinal I\/R\u2011induced GVB damage. We observe that GVB disruption in clinical and experimental specimens is associated with reduced expression of Claudin5 and VE\u2011cadherin. Dex\u2011NPs preferentially accumulate in the ischemic intestine and release the drug upon ROS stimulation. Low\u2011dose Dex\u2011NPs (dexmedetomidine 5\u00a0\u00b5g\/kg) confer GVB and hepatic protection comparable to high\u2011dose free dexmedetomidine, without detectable acute cardiorespiratory depression under the conditions tested. Mechanistically, dexmedetomidine inhibits histone deacetylase (HDAC), enhances H3K27 acetylation, and upregulates T\u2010cell factor 4 (TCF4, encoded by\n                    <jats:italic>TCF7L2<\/jats:italic>\n                    ), which directly binds and activates\n                    <jats:italic>CLDN5<\/jats:italic>\n                    and\n                    <jats:italic>CDH5<\/jats:italic>\n                    promoters, thereby restoring Claudin5\/VE\u2011cadherin expression and GVB integrity; TCF4 knockdown largely abolishes these protective effects. In summary, ROS\u2011responsive Dex\u2011NPs enable low\u2011dose dexmedetomidine to preserve GVB integrity and mitigate post\u2011I\/R liver injury via HDAC inhibition and TCF4 upregulation, circumventing dose\u2011limiting toxicity and suggesting TCF4 as a potential therapeutic target in oxidative stress\u2011associated gut endothelial barrier dysfunction.\n                  <\/jats:p>","DOI":"10.1002\/advs.77702","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:55:42Z","timestamp":1788929742000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ROS\u2010Responsive Nanoparticle Delivery of Dexmedetomidine Protects the Gut Vascular Barrier After Intestinal Ischemia\/Reperfusion via the HDAC\u2010H3K27ac\u2010TCF4 Axis"],"prefix":"10.1002","author":[{"given":"Hu\u2010Fei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5831-8906","authenticated-orcid":false,"given":"Jian\u2010Tong","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua\u2010Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Chemistry and Materials Science Jinan University  Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si\u2010Qi","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital of Jinan University  Guangzhou People's Republic of 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