{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:02:45Z","timestamp":1790071365439,"version":"4.0.1"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100010270","name":"Capital Health Research and Development of Special Fund","doi-asserted-by":"publisher","award":["2024\u20102\u20102015"],"award-info":[{"award-number":["2024\u20102\u20102015"]}],"id":[{"id":"10.13039\/501100010270","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Peripheral nerve injury (PNI) repair remains challenging, with metabolic regulation and neuronal senescence playing critical roles. This study explored whether intermittent hypoxia modulates injured dorsal root ganglion (DRG) neuron regeneration via lactate\u2010mediated mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      DRG neurons were subjected to impairment via acrylamide (ACR) to develop an in\u00a0vitro injury model, followed by the induction of intermittent hypoxia and lactate production inhibitors including 2\u2010deoxy\u2010\n                      <jats:sc>d<\/jats:sc>\n                      \u2010glucose (2\u2010DG) and oxamate. In\u00a0vivo experiments employed a rat PNI model exposed to intermittent hypoxia. Cellular evaluations comprised the CCK\u20108 assay to determine cell viability, \u03b2\u2010galactosidase staining to identify cellular senescence, and immunofluorescence for the detection of p21 and Lamin B1. The m5C\u2010RIP\u2010qPCR assay was used to assess m5C modification of SETD2 mRNA. The immunoprecipitation was applied to examine the lactylation of NSUN3 protein.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Intermittent hypoxia increased lactate production, improved ACR\u2010impaired DRG viability, reduced ROS and MDA levels, and promoted damaged neuron regeneration, effects reversed by 2\u2010DG or oxamate. Hypoxia inhibited ACR\u2010induced neuron senescence, which was abrogated by lactate inhibitors. Mechanistically, hypoxia\u2010induced lactate promoted NSUN3 lactylation, further enhanced m5C modification and stability of SETD2 mRNA. NSUN3 knockdown exacerbated senescence and suppressed mitochondrial biogenesis, while SETD2 overexpression reversed these impacts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Intermittent hypoxia facilitated the regeneration of injured DRG neurons through lactate\u2010mediated NSUN3 lactylation. This process was correlated with the stability of SETD2 mRNA via m5C modification, thereby mitigating cellular senescence and promoting mitochondrial function. These findings present novel targets for strategies aimed at nerve repair.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jns.70166","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T10:49:55Z","timestamp":1788173395000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hypoxia\u2010Induced Lactylation of\n                    <scp>NSUN3<\/scp>\n                    Promotes\n                    <scp>m5C<\/scp>\n                    Methylation of\n                    <scp>SETD2<\/scp>\n                    to Regulate Peripheral Nerve Injury Repair"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4234-2634","authenticated-orcid":false,"given":"Shuai","family":"An","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingfei","family":"Shi","sequence":"additional","affiliation":[{"name":"Cerebrovascular and Neuroscience Research Institute, Beijing Institute of Geriatrics, Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5664-1358","authenticated-orcid":false,"given":"Jingbo","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8935-3042","authenticated-orcid":false,"given":"Mingli","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23020918"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202404293"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/8868411"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibneur.2024.12.013"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25084465"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-024-03964-5"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13996"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-024-01624-8"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70269"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04842-9"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0563-24.2025"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202402133"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2022.04.003"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2025.1602112"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-025-01954-x"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26115349"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-022-00362-8"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.15582"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/17448069221089784"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2022.105455"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v28.i37.5420"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/15353702221098962"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnsyn.2022.859278"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-025-05342-8"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells14110832"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109334"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-023-00947-7"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes10020102"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.3724\/abbs.2024159"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.05.026"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.989109"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2021.08.020"}],"container-title":["Journal of the Peripheral Nervous System"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jns.70166","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jns.70166","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jns.70166","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:15:27Z","timestamp":1790068527000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jns.70166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,31]]},"references-count":32,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/jns.70166"],"URL":"https:\/\/doi.org\/10.1111\/jns.70166","archive":["Portico"],"relation":{},"ISSN":["1085-9489","1529-8027"],"issn-type":[{"value":"1085-9489","type":"print"},{"value":"1529-8027","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,31]]},"assertion":[{"value":"2026-04-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70166"}}