{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:06:39Z","timestamp":1791471999546,"version":"4.3.4"},"reference-count":53,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cerebral infarction, a leading cerebrovascular disease, often results in severe neurological impairments and high mortality. This study investigates a novel therapeutic approach involving small interfering RNA targeting Interferon Regulatory Factor 9 (si\u2010IRF9) delivered by RVG29\u2010functionalized poly(lactic\u2010co\u2010glycolic acid) nanoparticles (NPs) (RVG29\u2010PNPs@si\u2010IRF9), in combination with high\u2010frequency repetitive transcranial magnetic stimulation (rTMS), in promoting post\u2010stroke regeneration. Using a middle cerebral artery occlusion rat model and an in vitro oxygen\u2010glucose deprivation\/reoxygenation system, the regenerative efficacy of this combinatory therapy is evaluated on both neural and vascular recovery. Mechanistically, our results identify the IRF9\/Reticulon 4 (RTN4)\/Ras homolog family member A (RHOA)\/Rho\u2010associated coiled\u2010coil containing protein kinase (ROCK) pathway as a key mediator, which is effectively inhibited by RVG29\u2010PNPs@si\u2010IRF9. This inhibition enhances neurogenesis and angiogenesis, particularly when combined with rTMS. Moreover, the NP system demonstrates excellent biocompatibility and targeted delivery, highlighting its potential as a therapeutic platform for stroke rehabilitation. These findings provide a new perspective on integrating nanotechnology and neuromodulation to facilitate functional recovery after cerebral infarction.<\/jats:p>","DOI":"10.1002\/adhm.202501846","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T05:29:47Z","timestamp":1758259787000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Therapeutic Targeting of the IRF9\/RTN4\/RHOA\/ROCK Pathway via RVG29\u2010Modified PLGA Nanoparticles and rTMS for Neural and Vascular Regeneration Post\u2010Cerebral Infarction"],"prefix":"10.1002","volume":"15","author":[{"given":"Fangfang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Xiangya Hospital Central South University  Changsha 410000 China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha Hunan 410000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijin","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation The Second Affiliated Hospital of Xinjiang Medical University  Urumqi 830000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siting","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Xiangya Hospital Central South University, Jiangxi. (National Regional Center for Neurological Diseases)  Nanchang Jiangxi 330038 China"},{"name":"Jiangxi Provincial People's Hospital The First Affiliated Hospital of Nanchang Medical College  Nanchang 330038 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Xiangya Changde Hospital  Changde 415000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9803-7503","authenticated-orcid":false,"given":"Hongxing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Chongqing University Three Gorges Hospital\uff0cSchool of Medicine\uff0cChongqing University  Chongqing 404100 China"},{"name":"Xinjiang Key Laboratory of Neurological Disorder Research The Second Affiliated Hospital of Xinjiang Medical University  Urumqi 830000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.09.012"},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.264442"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21186718"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22168543"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2021.01.023"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.5b00345"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.1c00490"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.10264"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2022.02.036"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-024-02772-2"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15092322"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.121111"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2019.11.002"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02501-2"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.878345"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.389303"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01747-y"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e35339"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cortex.2021.02.024"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-022-01264-x"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2018.12.002"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/0963689719834870"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2047344"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2021.114559"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-03503-3"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.904875"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201601273"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2013.05.025"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2021.5070"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2020.02.010"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2019.03.022"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13561"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37150-3"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm7120490"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2020.08.017"},{"key":"e_1_2_11_36_1","volume":"26","author":"Guo M.","year":"2020","journal-title":"Med. Sci. Monitor"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13770-019-00233-8"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-181296"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2018.03.008"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.3c01622"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.51573"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X17666190726104139"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12020093"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-016-0447-9"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000160349.42665.0C"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110778"},{"key":"e_1_2_11_47_1","volume":"137","author":"Zhang D.\u2010M.","year":"2019","journal-title":"Free Rad. Biol. Med."},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18020455"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12061373"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2016.12.031"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2004.03.008"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-1727-6"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-019-0381-6"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202501846","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adhm.202501846","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202501846","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:41:31Z","timestamp":1768477291000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202501846"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,18]]},"references-count":53,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/adhm.202501846"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202501846","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,18]]},"assertion":[{"value":"2025-04-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01846"}}