{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:33:17Z","timestamp":1791657197855,"version":"4.3.4"},"reference-count":59,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2022LZY021"],"award-info":[{"award-number":["ZR2022LZY021"]}],"id":[{"id":"10.13039\/501100007129","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":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Ras\u2010GTPase\u2010activating protein SH3 domain\u2010binding protein 1 (G3BP1) mediates stress granules (SGs) via phase separation. However, there is limited understanding of the allosteric mechanism and the identification of regulatory molecules. Here, we identify icariin (ICA), a small\u2010molecule inducer that promotes G3BP1\u2010driven biomolecular condensate formation, which effectively restructures SGs architecture. Moreover, we demonstrate that ICA interacts with the N\u2010terminal nuclear transport factor 2\u2010like (NTF2L) domain of G3BP1, inducing a conformational switch from \u201cclosed\u2010to\u2010open\u201d that facilitates G3BP1 oligomerization and phase separation. Crucially, G3BP1 condensates recruit N\n                    <jats:sup>6<\/jats:sup>\n                    \u2010methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) reader insulin\u2010like growth factor 2 mRNA\u2010binding protein 1 (IGF2BP1)\u00a0through topology\u2010selective scaffolding, establishing epitranscriptomic hubs that resolve proteotoxic stress via m\n                    <jats:sup>6<\/jats:sup>\n                    A\u2010dependent AMP\u2010activated protein kinase (AMPK)\u2010mitogen\u2010activated protein kinase (MAPK)\u2010glutathione peroxidase 4 (GPX4) signaling pathways. Strikingly, this chemical intervention shows translational potential, as ICA reduces cerebral infarct volume in ischemia models via G3BP1\u2010dependent SGs remodeling. Additionally, single\u2010nucleus transcriptomics identify\n                    <jats:italic>Fezf2<\/jats:italic>\n                    ,\n                    <jats:italic>Pou3f1<\/jats:italic>\n                    , and\n                    <jats:italic>Kcnn2<\/jats:italic>\n                    neuronal subpopulations as mechanistically aligned responders. Furthermore, ischemic stroke patients reveal G3BP1\u2013IGF2BP1\u2013m\n                    <jats:sup>6<\/jats:sup>\n                    A axis within peripheral blood mononuclear cells. Taken together, this study redefines SGs as dynamically druggable epitranscriptomic processors for precision neuroprotection. In particular, a framework for leveraging biomolecular condensate topology in the development of next\u2010generation neurological therapeutics is offered.\n                  <\/jats:p>","DOI":"10.1002\/advs.202514703","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T09:23:52Z","timestamp":1763630632000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Targeting G3BP1 Condensate Topology Promotes Stress Granule Assembly via m\n                    <sup>6<\/sup>\n                    A\u2010IGF2BP1 for Ischemic Stroke Rescue"],"prefix":"10.1002","volume":"13","author":[{"given":"Ling","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2010Dong","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Immunology School of Basic Medical Sciences Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Yong","family":"Du","sequence":"additional","affiliation":[{"name":"Key Laboratory of Remodeling\u2010Related Cardiovascular Diseases Ministry of Education National Clinical Research Center for Cardiovascular Diseases Beijing Institute of Heart Lung and Blood Vessel Disease Beijing Anzhen Hospital Capital Medical University Beijing 100029 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian\u2010Wei","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang\u2010Fang","family":"Zhuo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian\u2010Tian","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng\u2010Ping","family":"Liu","sequence":"additional","affiliation":[{"name":"Shandong Engineering Research Center of New Sustained and Controlled Release Formulations and Drug Targeted Delivery Systems Shandong Academy of Pharmaceutical Sciences  Jinan 250101 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Han","sequence":"additional","affiliation":[{"name":"School of Pharmacy\/Key Laboratory of Xinjiang Phytomedicine Resource and Utilization Shihezi University  Shihezi 832003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Pharmacy\/Key Laboratory of Xinjiang Phytomedicine Resource and Utilization Shihezi University  Shihezi 832003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei\u2010Pei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Peking University Health Science Center  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines School of Traditional Chinese Pharmacy China Pharmaceutical University Nanjing 211198 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Yuan","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences &amp; Institute of Materia Medica Shandong First Medical University &amp; Shandong Academy of Medical Sciences Jinan 250117 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng\u2010Fei","family":"Tu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Hong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Immunology School of Basic Medical Sciences Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1082-6327","authenticated-orcid":false,"given":"Ke\u2010Wu","family":"Zeng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.115.16.3227"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncrna.2021.04.003"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2016.05.004"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.03.046"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201801214"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.739573"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf6548"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0262-4"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-021-00306-w"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/1061186X.2018.1523415"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.11.003"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2023.188885"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2022.146294"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200212128"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.6.2561"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1744309110042156"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080947"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12104-022-10067-6"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202308083"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3724\/abbs.2023106"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2024.149497"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2402847121"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.606111"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apha.2019.10.004"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23073747"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-022-01151-y"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19211-z"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1CC00392E"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biophys.37.032807.125842"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.38483"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/mas.20082"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202206533"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.9b03647"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0SC05330A"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00763-12"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chmed.2023.09.003"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00052-19"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0045-z"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2023.2181575"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-017-2537-6"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2020.00103"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2024.102472"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11070923"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-27293-5"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adg1323"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00036"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-019-0222-5"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.559384"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1138864"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms251910571"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2013.07.004"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33079-1"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.220369"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204553"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.97228"},{"key":"e_1_2_9_56_1","doi-asserted-by":"crossref","unstructured":"C. C.Chang C. C.Chow L. C.Tellier S.Vattikuti S. M.Purcell J. J.Lee Gigascience2015 4 s13742\u201013015\u201010047\u201013748.","DOI":"10.1186\/s13742-015-0047-8"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.134492"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.20.1.84"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2023.133038"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202514703","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202514703","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202514703","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T07:46:17Z","timestamp":1775979977000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202514703"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,20]]},"references-count":59,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/advs.202514703"],"URL":"https:\/\/doi.org\/10.1002\/advs.202514703","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,20]]},"assertion":[{"value":"2025-08-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14703"}}