{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:57:51Z","timestamp":1790791071538,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"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                    <jats:bold>Background<\/jats:bold>\n                    : 14\u20103\u20103\u03b3 is implicated in neurodegeneration, yet its role in postoperative cognitive dysfunction (POCD) remains unclear.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods<\/jats:bold>\n                    : We performed CSF proteomic profiling using the SomaScan 7K platform in the Alzheimer's Disease Neuroimaging Initiative cohort (n = 237) to identify biomarkers associated with neurodegeneration\u2010enriched cognitive vulnerability (NECV). A prospective surgical cohort (n = 213) was used to evaluate circulating 14\u20103\u20103\u03b3 levels in relation to perioperative cognitive outcomes. Mechanistic studies were conducted using a murine surgery model, AAV\u2010mediated gene manipulation, neuronal cultures, pharmacological intervention, and molecular dynamics simulations.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    : CSF proteomics identified 14\u20103\u20103\u03b3 as a candidate biomarker associated with NECV and neurodegenerative progression. Plasma 14\u20103\u20103\u03b3 levels were associated with POCD and postoperative delirium. In mice, anesthesia and surgery reduced hippocampal 14\u20103\u20103\u03b3 expression, accompanied by increased Tau phosphorylation at Thr205 among examined sites, synaptic dysfunction, and cognitive impairment. Neuronal 14\u20103\u20103\u03b3 overexpression rescued these deficits. Mechanistically, 14\u20103\u20103\u03b3 interacted with Tau in a phosphorylation\u2010dependent manner and regulated Tau phosphorylation homeostasis. Pharmacological stabilization of the 14\u20103\u20103\u03b3\u2013Tau interaction using FC\u2010A reduced Tau Thr205 phosphorylation and improved cognition, whereas TauT205E expression diminished this rescue effect.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions<\/jats:bold>\n                    : 14\u20103\u20103\u03b3 represents a potential regulator of postoperative cognitive vulnerability and a candidate therapeutic target for POCD.\n                  <\/jats:p>","DOI":"10.1002\/advs.77480","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:00:31Z","timestamp":1790532031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["14\u20103\u20103\u03b3 Protects Against Postoperative Cognitive Dysfunction by Regulating Tau Thr205 Phosphorylation and Synaptic Integrity"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2021-5781","authenticated-orcid":false,"given":"Shouqiang","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing China"},{"name":"Medical School Nanjing University  Nanjing Jiangsu China"},{"name":"Jiangsu Key Laboratory of Molecular Medicine Nanjing University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7676-4651","authenticated-orcid":false,"given":"Tianjiao","family":"Xia","sequence":"additional","affiliation":[{"name":"Medical School Nanjing University  Nanjing Jiangsu China"},{"name":"Jiangsu Key Laboratory of Molecular Medicine Nanjing University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8218-7299","authenticated-orcid":false,"given":"Xiaoping","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing China"},{"name":"Medical School Nanjing University  Nanjing Jiangsu China"},{"name":"Jiangsu Key Laboratory of Molecular Medicine Nanjing University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/jmdh.S431168"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afae160"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e318195b569"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00391\u2010012\u20100326\u20102"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/aln.0000000000002334"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0000000000007316"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2025.1648161"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0284728"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40001\u2010025\u201003081\u20106"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.jvca.2021.05.016"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2026.111776"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102223"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787\u2010018\u201000559\u20100"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1145318"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.26355\/eurrev_201806_15184"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.900350"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e318298b077"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51499"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2025.102031"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1101\/2025.11.05.25339138"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41562\u2010024\u201001924\u20106"},{"issue":"2","key":"e_1_2_12_23_1","first-page":"152","article-title":"14\u20103\u20103 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