{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T15:05:00Z","timestamp":1780067100073,"version":"3.54.0"},"reference-count":56,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"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":["82471412"],"award-info":[{"award-number":["82471412"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Peripheral nerve injury (PNI) remains a major regenerative challenge, in part because the post\u2010injury microenvironment can disrupt Schwann cell (SCs) homeostasis. Walnuts (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Juglans regia<\/jats:italic>\n                    <\/jats:styled-content>\n                    ) have long been used in ethnomedicine for perceived neurotrophic or neuroprotective benefits, a view historically linked to their resemblance to the brain. To examine whether this traditional concept can be leveraged as a nanotherapeutic approach, we isolated walnut\u2010derived extracellular vesicles (WEVs) and evaluated their effects on peripheral nerve repair. We found that WEVs are readily internalized by SCs and can help establish a \u201cpre\u2010regenerative niche,\u201d defined here as a permissive metabolic microenvironment that supports repair. Mechanistically, WEVs appear to engage a c\u2010Myc\u2010mediated transcriptional program that shifts SC metabolism toward aerobic glycolysis and increases lactate export, consistent with activation of a glia\u2010to\u2010neuron lactate shuttle. In parallel, WEVs may stabilize the glial bioenergetic hub by limiting stress\u2010induced mitophagy. In a rat sciatic nerve compression model, these changes were associated with preserved mitochondrial ultrastructure in the acute phase, followed by enhanced remyelination, improved motor and sensory outcomes, and attenuated muscle atrophy. Collectively, our findings suggest a mechanistic basis for the reported neuroprotective value of walnuts and identify WEVs as a niche\u2010modulating nanotherapeutic candidate that may promote regeneration by aligning glial metabolic plasticity with neuronal energy demands.\n                  <\/jats:p>","DOI":"10.1002\/glia.70168","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T10:42:16Z","timestamp":1779964936000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Walnut\u2010Derived Extracellular Vesicles Orchestrate a Pre\u2010Regenerative Niche via c\u2010Myc Mediated Metabolic Reprogramming"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3449-9144","authenticated-orcid":false,"given":"Junyang","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Zhengzhou University, Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4794-8244","authenticated-orcid":false,"given":"Genzhong","family":"Xu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Henan University of Traditional Chinese Medicine  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1541-3636","authenticated-orcid":false,"given":"Nianci","family":"Huo","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Zhengzhou University, Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6681-0072","authenticated-orcid":false,"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Zhengzhou University, Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3771-7155","authenticated-orcid":false,"given":"Hui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Zhengzhou University, Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5594-6732","authenticated-orcid":false,"given":"Jiaqi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Zhengzhou University, Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5319-0100","authenticated-orcid":false,"given":"Saichao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Preventive Dentistry and Orthodontics Institute of Dentistry, I.M. Sechenov First Moscow State Medical University (Sechenov University)  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2600-7887","authenticated-orcid":false,"given":"Siyao","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhongyuan University of Technology  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9010-2649","authenticated-orcid":false,"given":"Ningning","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Emergency The First Affiliated Hospital of Zhengzhou University, Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9869-1409","authenticated-orcid":false,"given":"Nan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Zhengzhou University, Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibneur.2022.10.015"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432\u20101033.1994.tb18989.x"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010020\u20100689\u20104"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2022.114173"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2020.03.005"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2022.105952"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201490441"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2025.110441"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753\u2010019\u201001113\u2010y"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fbio.2022.102327"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.70265"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.70071"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311401"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.665232"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202317907"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11007"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.22038\/ijbms.2024.79854.17302"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1453\u201017.2017"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12061256"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107062"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adm8454"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1201\/9781315152998-14"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23532"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom14101202"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.287045.116"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2023.0268"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010020\u20102458\u20104"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo14070383"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.98"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.08.015"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010021\u201003912\u20104"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23020918"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202402133"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.70037"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201012640\u20105"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.10.018"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201300729"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010020\u201003516\u20109"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/jox15020055"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.34133\/research.0825"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41536\u2010021\u201000163\u2010x"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2025.1602112"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010023\u201002815\u2010w"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12944\u2010025\u201002642\u20102"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2017.1319544"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom15081055"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/7864308"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2024.01.060"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010023\u201000634\u20103"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951\u2010024\u201002313\u2010x"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7295"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.05.004"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010024\u201006579\u20109"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v4.28713"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.62886"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom15081095"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.70168","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/glia.70168","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.70168","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T14:14:33Z","timestamp":1780064073000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.70168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,28]]},"references-count":56,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/glia.70168"],"URL":"https:\/\/doi.org\/10.1002\/glia.70168","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,28]]},"assertion":[{"value":"2026-03-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70168"}}