{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:50:05Z","timestamp":1791877805504,"version":"4.3.4"},"reference-count":80,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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":["82173262"],"award-info":[{"award-number":["82173262"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012542","name":"Sichuan Provincial Science and Technology Support Program","doi-asserted-by":"publisher","award":["2024NSFSC1536"],"award-info":[{"award-number":["2024NSFSC1536"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sepsis survivors face an elevated long\u2010term risk of Alzheimer's disease (AD), yet the peripheral pathways linking systemic immune activation to chronic neurodegeneration remain undefined. We mapped peripheral immune reprogramming across sepsis and AD and tested a candidate regulatory node.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A single\u2010cell atlas of peripheral immunity was built by integrating scRNA\u2010seq from human sepsis and AD cohorts, using clustering, SCENIC regulatory\u2010network inference and an exploratory pseudotime ordering. The resulting signature was validated in two clinical cohorts (ROC and survival analysis). MAFG\u2010associated subpopulations and redox status were profiled in APP\/PS1, cecal ligation and puncture (CLP) and composite models, and causality was tested by lentiviral MAFG knockdown and adoptive transfer into APP\/PS1 recipients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Peripheral immunity was myeloid\u2010skewed in sepsis and lymphoid\u2010dominated in AD, with APP\u2010expressing common myeloid progenitors (CMPs), dendritic cells (DCs), and platelets forming an APP\u2010enriched compartment. A core transcription\u2010factor network differed between disease states, yielding a four\u2010gene signature (MAFG, NFIL3, RGS10, FOXO3) with cross\u2010cohort diagnostic and prognostic value. MAFG was upregulated in septic patients and associated with poorer survival, subpopulation expansion, and systemic oxidative stress. Superimposed CLP aggravated amyloid deposition, microglial activation, and memory deficits in APP\/PS1 mice, whereas MAFG silencing restored A\u03b2 uptake and, on adoptive transfer, reduced amyloid burden, attenuated microgliosis, and preserved cognition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Peripheral immune states differ across the sepsis\u2010to\u2010AD spectrum and are captured by a MAFG\u2010centered signature. Independent of any trajectory assumption, loss\u2010of\u2010function and adoptive\u2010transfer experiments identify MAFG as a causal, redox\u2010sensitive node constraining peripheral A\u03b2 clearance and a candidate biomarker and therapeutic target in sepsis survivors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71201","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:34:24Z","timestamp":1791876864000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>MAFG<\/scp>\n                    as a Redox\u2010Sensitive Node Linking Peripheral Immune Reprogramming to Cognitive Risk in the Sepsis\u2010to\u2010Alzheimer's Disease Continuum: Single\u2010Cell Dissection and Adoptive\u2010Transfer Validation"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2213-0714","authenticated-orcid":false,"given":"Xiaoyu","family":"Xiang","sequence":"first","affiliation":[{"name":"Institute of Critical Care Medicine, West China Hospital Sichuan University  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Critical Care Medicine, West China Hospital Sichuan University  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongxue","family":"Feng","sequence":"additional","affiliation":[{"name":"Institute of Critical Care Medicine, West China Hospital Sichuan University  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital Sichuan University  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwen","family":"Gong","sequence":"additional","affiliation":[{"name":"Institute of Critical Care Medicine, West China Hospital Sichuan University  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0186-2173","authenticated-orcid":false,"given":"Lietao","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Critical Care Medicine, West China Hospital Sichuan University  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9595-1156","authenticated-orcid":false,"given":"Lijun","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Critical Care Medicine, West China Hospital Sichuan University  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7588-7249","authenticated-orcid":false,"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Critical Care Medicine, West China Hospital Sichuan University  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2025.108971","article-title":"Sepsis\u2010Associated Encephalopathy: Unraveling Molecular Mechanisms, Emerging Therapeutics, and Translational Frontiers","volume":"278","author":"Zhang X.","year":"2026","journal-title":"Pharmacology & Therapeutics"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"4463","DOI":"10.1038\/s41380-023-02172-2","article-title":"Sepsis Exacerbates Alzheimer's Disease Pathophysiology, Modulates the Gut Microbiome, Increases Neuroinflammation and Amyloid Burden","volume":"28","author":"Giridharan V. 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