{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:35:10Z","timestamp":1791894910324,"version":"4.3.4"},"reference-count":89,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021ZD0202900"],"award-info":[{"award-number":["2021ZD0202900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2017YFA0104303"],"award-info":[{"award-number":["2017YFA0104303"]}],"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":["81761138048"],"award-info":[{"award-number":["81761138048"]}],"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":["81673410"],"award-info":[{"award-number":["81673410"]}],"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":["81973304"],"award-info":[{"award-number":["81973304"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20191265"],"award-info":[{"award-number":["BK20191265"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2020 ZX09201015"],"award-info":[{"award-number":["2020 ZX09201015"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2242021R41098"],"award-info":[{"award-number":["2242021R41098"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Major depressive disorder (MDD) is the most prevalent psychiatric disorder worldwide and severely limits psychosocial function and quality of life, but no effective medication is currently available. Circular RNAs (circRNAs) have been revealed to participate in the MDD pathological process. Targeted delivery of circRNAs without blood\u2010brain barrier (BBB) restriction for remission of MDD represents a promising approach for antidepressant therapy. In this study, RVG\u2010circDYM\u2010extracellular vesicles (RVG\u2010circDYM\u2010EVs) were engineered to target and preferentially transfer circDYM to the brain, and the effect on the pathological process in a chronic unpredictable stress (CUS) mouse model of depression was investigated. The results showed that RVG\u2010circDYM\u2010EVs were successfully purified by ultracentrifugation from overexpressed circDYM HEK 293T cells, and the characterization of RVG\u2010circDYM\u2010EVs was successfully demonstrated in terms of size, morphology and specific markers. Beyond demonstrating proof\u2010of\u2010concept for an RNA drug delivery technology, we observed that systemic administration of RVG\u2010circDYM\u2010EVs efficiently delivered circDYM to the brain, and alleviated CUS\u2010induced depressive\u2010like behaviours, and we discovered that RVG\u2010circDYM\u2010EVs notably inhibited microglial activation, BBB leakiness and peripheral immune cells infiltration, and attenuated astrocyte disfunction induced by CUS. CircDYM can bind mechanistically to the transcription factor TAF1 (TATA\u2010box binding protein associated factor 1), resulting in the decreased expression of its downstream target genes with consequently suppressed neuroinflammation. Taken together, our findings suggest that extracellular vesicle\u2010mediated delivery of circDYM is effective for MDD treatment and promising for clinical applications.<\/jats:p>","DOI":"10.1002\/jev2.12185","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T23:39:58Z","timestamp":1642117198000},"source":"Crossref","is-referenced-by-count":137,"title":["Extracellular vesicle\u2010mediated delivery of circDYM alleviates CUS\u2010induced depressive\u2010like behaviours"],"prefix":"10.1002","volume":"11","author":[{"given":"Xiaoyu","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Medicine Southeast University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine Southeast University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine Southeast University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minzi","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine Southeast University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianci","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine Southeast University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine Southeast University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine Southeast University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine Southeast University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica &amp; Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoku","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Medicine Southeast University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine Southeast University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghong","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine Southeast University  Nanjing Jiangsu China"},{"name":"Jiangsu Provincial Key Laboratory of Critical Care Medicine Southeast University  Nanjing Jiangsu China"},{"name":"Co\u2010innovation Center of Neuroregeneration Nantong University  Nantong Jiangsu China"},{"name":"Institute of Life Sciences Key Laboratory of Developmental Genes and Human Disease Southeast University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2009.07.030"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1807"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2015.14020181"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.4304"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15423-5"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1116848108"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3162"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)30934-1"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12651-2"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00573"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.2217\/bmm-2016-0130"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(19)30215-9"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22960"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2020.1795362"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2013.00146"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2018.09.028"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881106075588"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.06.034"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.120.265058"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2019.105416"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-46632-8"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI35700"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1088547"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa150"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2020.02.018"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.038361"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-1098-8"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.621383"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v4.26238"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.105006"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700984RR"},{"key":"e_1_2_7_33_1","article-title":"Microglia in depression: Current perspectives","author":"Jia X.","year":"2018","journal-title":"Science China Life Science"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2773-4"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(82)90056-9"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1017\/S003329170400265X"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.27"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03733-8"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0158-7"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx765"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v4.30087"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21197084"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2020.1722385"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.03.046"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17394"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31948-2"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad8670"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2018.08.019"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31551-4"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-017-0010-3"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2015.5"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8NR07755J"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.16"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15432"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2018.03.013"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2019.01.012"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61139-3"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.03.005"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103337"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.1c00068"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2019.1582237"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/515180a"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2014.12.013"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01848-8"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.9b00287"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2020.05.109"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-017-2123-5"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2017.1388731"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2018.1535750"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.20"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.11.083"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.14.6649"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.065"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2019.1599680"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.38198"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02794-5"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1054-3"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav8521"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v4.26316"},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00427414"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.05.026"},{"key":"e_1_2_7_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0090-3"},{"key":"e_1_2_7_83_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2019.1580494"},{"key":"e_1_2_7_84_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1100"},{"key":"e_1_2_7_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12735-z"},{"key":"e_1_2_7_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2017.31"},{"key":"e_1_2_7_87_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11718-4"},{"key":"e_1_2_7_88_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.1127"},{"key":"e_1_2_7_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0285-0"},{"key":"e_1_2_7_90_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-019-0733-3"}],"container-title":["Journal of Extracellular Vesicles"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jev2.12185","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jev2.12185","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jev2.12185","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T17:26:41Z","timestamp":1760635601000},"score":1,"resource":{"primary":{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/10.1002\/jev2.12185"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":89,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1002\/jev2.12185"],"URL":"https:\/\/doi.org\/10.1002\/jev2.12185","archive":["Portico"],"relation":{},"ISSN":["2001-3078","2001-3078"],"issn-type":[{"value":"2001-3078","type":"print"},{"value":"2001-3078","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1]]},"article-number":"e12185"}}