{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T14:15:52Z","timestamp":1793196952480,"version":"4.5.0"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"39","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"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":["82301557"],"award-info":[{"award-number":["82301557"]}],"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":["82171373"],"award-info":[{"award-number":["82171373"]}],"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":["32170958"],"award-info":[{"award-number":["32170958"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,9,30]]},"abstract":"<jats:p>\n                    Microglia\/macrophage-induced neuroinflammation plays a crucial role in the progression of traumatic brain injury (TBI). However, the involvement of N6-methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) RNA modifications in this process remains elusive. Single-cell RNA sequencing (scRNA-seq) and m\n                    <jats:sup>6<\/jats:sup>\n                    A RNA immunoprecipitation sequencing (MeRIP-seq) across multiple time points postinjury revealed a strong correlation between m\n                    <jats:sup>6<\/jats:sup>\n                    A modifications and genes enriched in microglia\/macrophages. Furthermore, the m\n                    <jats:sup>6<\/jats:sup>\n                    A demethylase ALKBH5 was identified as a key regulator of dynamic m\n                    <jats:sup>6<\/jats:sup>\n                    A patterns at the injury site. ALKBH5 suppression in microglia\/macrophages exacerbated neuroinflammation in vitro and worsened neurological deficits in controlled cortical impact (CCI) models. MeRIP-qPCR and RNA pull-down assays revealed SOCS3 was a downstream target of ALKBH5-mediated m\n                    <jats:sup>6<\/jats:sup>\n                    A demethylation. This demethylation stabilized\n                    <jats:italic toggle=\"yes\">Socs3<\/jats:italic>\n                    mRNA and enhanced its protein expression, which in turn suppressed neuroinflammation via inhibiting the JAK2-STAT3 pathway. Conversely, SOCS3 depletion impaired functional recovery after injury. These findings unveiled a critical ALKBH5\u2013m\n                    <jats:sup>6<\/jats:sup>\n                    A\u2013SOCS3 regulatory axis that mitigated microglia\/macrophage-driven neuroinflammation after TBI, underscoring its potential as a therapeutic intervention target for TBI progression.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2504697122","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T15:49:17Z","timestamp":1758642557000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":22,"title":["ALKBH5 demethylates the m\n                    <sup>6<\/sup>\n                    A modification of SOCS3 in microglia\/macrophages and alleviates neuroinflammation after brain injury"],"prefix":"10.1073","volume":"122","author":[{"given":"Lin","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Department of Neurology, Zhongshan Hospital, Laboratory Animal Center, Ministry of Education Frontiers Center for Brain Science, Fudan University","place":["Shanghai, China"]},{"name":"National Children\u2019s Medical Center, Children\u2019s Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, Ministry of Education Frontiers Center for Brain Science, Ministry of Education Innovative Center for New Drug Development of Immune Inflammatory Diseases, Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases, Fudan University","place":["Shanghai, China"]},{"name":"Department of Neurosurgery, Huashan Hospital, Fudan University","place":["Shanghai, 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