{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:15:25Z","timestamp":1792631725416,"version":"4.5.0"},"reference-count":71,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC3601200"],"award-info":[{"award-number":["2022YFC3601200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871847"],"award-info":[{"award-number":["81871847"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172546"],"award-info":[{"award-number":["82172546"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272609"],"award-info":[{"award-number":["82272609"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82402954"],"award-info":[{"award-number":["82402954"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A151512137"],"award-info":[{"award-number":["2022A151512137"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515012695"],"award-info":[{"award-number":["2023A1515012695"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Circular RNA (circRNA) plays a pivotal role in regulating neurological damage post\u2010ischemic stroke. Previous researches demonstrated that exercise mitigates neurological dysfunction after ischemic stroke, yet the specific contributions of circRNAs to exercise\u2010induced neuroprotection remain unclear. This study reveals that mmu_circ_0001113 (circFndc3b) is markedly downregulated in the penumbral cortex of a mouse model subjected to middle cerebral artery occlusion (MCAO). However, exercise increased circFndc3b expression in microglia\/macrophages, alleviating pyroptosis, reducing infarct volume, and enhancing neurological recovery in MCAO mice. Mechanistically, circFndc3b interacted with Enolase 1 (ENO1), facilitating ENO1's binding to the 3' Untranslated Region (3'UTR) of Kr\u00fcppel\u2010like Factor 2 (Klf2) mRNA, thereby stabilizing Klf2 mRNA and increasing its protein expression, which suppressed NOD\u2010like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome\u2010mediated microglial\/macrophage pyroptosis. Additionally, circFndc3b enhanced ENO1's interaction with the 3\u2032UTR of Fused in Sarcoma (FUS) mRNA, leading to increased FUS protein levels and promoting circFndc3b cyclization. These results suggest that circFndc3b mediates exercise\u2010induced anti\u2010pyroptotic effects via the ENO1\/Klf2 axis, and a circFndc3b\/ENO1\/FUS positive feedback loop may potentiate exercise's neuroprotective effects. This study unveils a novel mechanism underlying exercise\u2010induced neuroprotection in ischemic stroke and positions circFndc3b as a promising therapeutic target for stroke management, mimicking the beneficial effects of exercise.<\/jats:p>","DOI":"10.1002\/advs.202403818","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T15:39:08Z","timestamp":1730129948000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["CircFndc3b Mediates Exercise\u2010Induced Neuroprotection by Mitigating Microglial\/Macrophage Pyroptosis via the ENO1\/KLF2 Axis in Stroke Mice"],"prefix":"10.1002","volume":"12","author":[{"given":"Yun","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine The Third Affiliated Hospital Sun Yat\u2010sen University  600 Tianhe Road Guangzhou Guangdong 510630 China"},{"name":"Department of Rehabilitation Zhujiang Hospital Southern Medical University  253 Industrial Middle Road Guangzhou Guangdong 510282 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"He","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine The Third Affiliated Hospital Sun Yat\u2010sen University  600 Tianhe Road Guangzhou Guangdong 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine The Third Affiliated Hospital Sun Yat\u2010sen University  600 Tianhe Road Guangzhou Guangdong 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongqiu","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine The Third Affiliated Hospital Sun Yat\u2010sen University  600 Tianhe Road Guangzhou Guangdong 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Zhujiang Hospital Southern Medical University  253 Industrial Middle Road Guangzhou Guangdong 510282 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghui","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine The Third Affiliated Hospital Sun Yat\u2010sen University  600 Tianhe Road Guangzhou Guangdong 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine The Third Affiliated Hospital Sun Yat\u2010sen University  600 Tianhe Road Guangzhou Guangdong 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine The Third Affiliated Hospital Sun Yat\u2010sen University  600 Tianhe Road Guangzhou Guangdong 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zejie","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine The Third Affiliated Hospital Sun Yat\u2010sen University  600 Tianhe Road Guangzhou Guangdong 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5554-6903","authenticated-orcid":false,"given":"Xiquan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine The Third Affiliated Hospital Sun Yat\u2010sen University  600 Tianhe Road Guangzhou Guangdong 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,28]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz8110"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-02-769026"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21186454"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X19836118"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30078-X"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abe0917"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2019.11.005"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0270-8"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S239546"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.242"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.00153"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13620"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21239086"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-021-02317-5"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2023.114380"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S213994"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-0653-4"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2021.1113"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.045765"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00067.2020"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-020-00258-z"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11777-7"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.9b00103"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2021.135662"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-021-00299-1"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-489"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab393"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky967"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-021-00872-2"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14741"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.08.019"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3230"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-019-00388-3"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101522"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-021-00817-w"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2023.106253"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11729"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24385"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-019-08586-y"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.319412"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2018.1458173"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.889855"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2020.09.032"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-04569-9"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.39854"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.63556"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-021-02033-8"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1707-x"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-023-01391-6"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2017.15"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1162607"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10258"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2007.07.018"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevEukaryotGeneExpr.2019029018"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-022-00813-z"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232113477"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.314402"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2020.109843"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1093"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01184-8"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0243-y"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-219969"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-04054-8"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-021-01739-z"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00144"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119033"},{"key":"e_1_2_9_68_1","volume":"5","author":"Young K.","year":"2018","journal-title":"J. Vis. Exp."},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12185"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa322"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01547-7"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202403818","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T21:08:25Z","timestamp":1767042505000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202403818"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,28]]},"references-count":71,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/advs.202403818"],"URL":"https:\/\/doi.org\/10.1002\/advs.202403818","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,28]]},"assertion":[{"value":"2024-04-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2403818"}}