{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:05:52Z","timestamp":1789646752245,"version":"4.0.0"},"reference-count":58,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"20","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,5,16]]},"abstract":"<jats:p>\n                    Viral muscle soreness (VMS) is a common feature during acute viral infections, including those caused by enteroviruses, and it substantially diminishes patients\u2019 quality of life. At present, we aim to establish the \u201cbrain-muscle\u201d axis to explore the underlying mechanisms of VMS. We initially observed that diminished pain threshold occurred in enterovirus A71 (EV-A71)\u2013infected C57BL\/6J and AG6 mice. Subsequently, RNA sequencing data showed that lipocalin 2 (LCN2) was up-regulated during multiple viral infections, including EV-A71, Japanese encephalitis virus, vesicular stomatitis virus, and West Nile virus, which all caused VMS. As expected,\n                    <jats:italic toggle=\"yes\">Lcn2<\/jats:italic>\n                    -deficient C57BL\/6 J (\n                    <jats:italic toggle=\"yes\">Lcn2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice exhibited greater pain tolerance, as shown by stronger grip force and stable motor function after EV-A71 infection. Mechanistically, EV-A71\u2013induced high-mobility group 1 (HMGB1) stimulated astrocyte-derived LCN2 secreted into the circulatory system, which enhanced glycolysis and induced lactate buildup in muscle through increasing pyruvate dehydrogenase kinase 1 (PDK1) expression and decreasing pyruvate dehydrogenase (PDH) activity. Together, HMGB1\/LCN2\/PDK1\/lactate pathway in the brain-muscle axis promoted VMS development.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adt9837","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T13:58:50Z","timestamp":1747403930000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":6,"title":["Astrocytes-derived LCN2 triggers EV-A71\u2013induced muscle soreness via accumulating lactate"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6306-717X","authenticated-orcid":true,"given":"Qiao","family":"You","sequence":"first","affiliation":[{"name":"Center for Public Health Research, Medical School of Nanjing University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9111-3139","authenticated-orcid":true,"given":"Jing","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Public Health Research, Medical School of Nanjing University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3058-7634","authenticated-orcid":true,"given":"Chaoyong","family":"Wang","sequence":"additional","affiliation":[{"name":"Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, China."},{"name":"Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Public Health Research, Medical School of Nanjing University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiji","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4515-2484","authenticated-orcid":true,"given":"Yurong","family":"Cai","sequence":"additional","affiliation":[{"name":"Ningxia Institute of Clinical Medicine, Central Laboratory, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7345-2814","authenticated-orcid":true,"given":"Nan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruining","family":"Lyu","sequence":"additional","affiliation":[{"name":"Center for Public Health Research, Medical School of Nanjing University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajie","family":"Qian","sequence":"additional","affiliation":[{"name":"Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8095-4856","authenticated-orcid":true,"given":"Yi","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4000-0382","authenticated-orcid":true,"given":"Miao","family":"He","sequence":"additional","affiliation":[{"name":"Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&amp;D, College of Pharmacy, Dali University, Dali, Yunnan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0672-948X","authenticated-orcid":true,"given":"Zhiwei","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Public Health Research, Medical School of Nanjing University, Nanjing, China."},{"name":"Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&amp;D, College of Pharmacy, Dali University, Dali, Yunnan, China."},{"name":"State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.17219\/dmp\/80995"},{"key":"e_1_3_2_3_2","first-page":"204993612110093","article-title":"COVID-19 and post-infectious myalgic encephalomyelitis\/chronic fatigue syndrome: A narrative review","volume":"8","author":"Poenaru S.","year":"2021","unstructured":"S. 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