{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:58:07Z","timestamp":1790668687205,"version":"4.1.0"},"reference-count":53,"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":["82202721"],"award-info":[{"award-number":["82202721"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY23H060005"],"award-info":[{"award-number":["LY23H060005"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY23H060006"],"award-info":[{"award-number":["LY23H060006"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007194","name":"Wenzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["GY20250281"],"award-info":[{"award-number":["GY20250281"]}],"id":[{"id":"10.13039\/501100007194","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>Microglial polarization toward the pro\u2010inflammatory state drives secondary injury following spinal cord injury (SCI), yet the mechanisms of metabolic reprogramming governing this phenotypic shift remain elusive. Here, we identify a lactate\u2010dependent signaling axis linking histone lactylation to mitochondrial reverse electron transport (RET) that sustains neuroinflammation. We demonstrate that SCI\u2010induced accumulation of lactate promotes histone H4 lysine 12 lactylation (H4K12la), which directly upregulates NDUFS7, a core subunit of mitochondrial Complex I. Elevated NDUFS7 triggers mitochondrial hyperactivity and RET, resulting in a reactive oxygen species (ROS) burst that enforces pro\u2010inflammatory polarization. To intervene in this cascade, we engineered a biomimetic nanotherapeutic, MM@mPTC, comprising an LDHA\u2010targeting PROTAC encapsulated within ROS\u2010responsive micelles and coated with microglial membranes (MM). The biomimetic MM@mPTC system actively targets activated microglia and undergoes ROS\u2010responsive payload release to specifically degrade LDHA. This targeted degradation dismantles the pathogenic \u201cLDHA\u2010H4K12la\u2010NDUFS7\u2010RET\u201d axis, halting RET\u2010driven ROS production and reprogramming microglia toward a reparative phenotype. Consequently, this intervention significantly mitigates neuroinflammation, preserves neuronal tissue, and promotes robust locomotor recovery, presenting a precise metabolic\u2010epigenetic therapeutic paradigm for central nervous system trauma.<\/jats:p>","DOI":"10.1002\/advs.78057","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:44:41Z","timestamp":1790667881000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["H4K12 Lactylation Regulates NDUFS7 to Drive Microglia Reverse Electron Transport in Spinal Cord Injury"],"prefix":"10.1002","author":[{"given":"Chenglong","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Orthopaedics  Wenzhou China"},{"name":"The Second Clinical Medical College of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhichen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Orthopaedics  Wenzhou China"},{"name":"The Second Clinical Medical College of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhouwei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Orthopaedics  Wenzhou China"},{"name":"The Second Clinical Medical College of Wenzhou Medical University  Wenzhou 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaijie","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Orthopaedics  Wenzhou China"},{"name":"The Second Clinical Medical College of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihui","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Orthopaedics  Wenzhou China"},{"name":"The Second Clinical Medical College of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaobo","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Orthopaedics  Wenzhou China"},{"name":"The Second Clinical Medical College of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Jin","sequence":"additional","affiliation":[{"name":"The Second Clinical Medical College of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Orthopaedics  Wenzhou China"},{"name":"The Second Clinical Medical College of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Orthopaedics  Wenzhou China"},{"name":"The Second Clinical Medical College of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunren","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated 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