{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:08:28Z","timestamp":1789013308837,"version":"build-2803163510"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Moyamoya disease (MMD) is a rare cerebrovascular disorder with unknown pathogenesis, partly due to limited access to human cerebral vascular tissue and suitable animal models. Using a large biobank of frozen serum samples, this study aimed to explore molecular signatures of ischemic and hemorrhagic MMD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">Serum from 30 patients with MMD (18 ischemic, 12 hemorrhagic) and 30 matched healthy controls underwent proteomic and metabolomic profiling. Data were analyzed for differential expression, pathway enrichment, and protein\u2013metabolite networks, with adjustment for age, sex, and body mass index.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      In a separate large Chinese cohort (n=6167), female patients had a higher proportion of hemorrhagic MMD (19.9% versus 16.9%) and a higher prevalence of anterior choroidal artery dilation (15.1% versus 13.2%) than male patients (both\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.05). At the molecular level, ischemic MMD showed complement C4\u2010B deficiency and disrupted natural killer cell cytotoxicity; both subtypes shared immunoglobulin perturbations (eg, decreased heavy\u2010chain variable regions). Sex\u2010specific alterations included anti\u2013folate\u2010binding protein, serum amyloid A2, glycolithocholic acid, and estradiol. All omics data are publicly accessible.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Integrated serum multiomics defines distinct immune\u2010related signatures for ischemic and hemorrhagic MMD and reveals sex\u2010dimorphic molecular pathways. These findings, together with clinical sex differences in disease subtype and vascular anatomy, provide a framework for personalized, sex\u2010aware management of MMD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.126.050737","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T10:30:38Z","timestamp":1784975438000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Serum Multiomics Reveal Subtype\u2010Specific Immune Dysregulation and Sex\u2010Dimorphic Pathophysiology in Moyamoya Disease"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6538-375X","authenticated-orcid":false,"given":"Qingbao","family":"Guo","sequence":"first","affiliation":[{"name":"XI'AN NO.9 HOSPITAL","place":["Xi\u2019an, China"]},{"name":"School of Medicine, Northwest University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1372-8135","authenticated-orcid":false,"given":"Manli","family":"Xie","sequence":"additional","affiliation":[{"name":"Xi'an Central Hospital","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0418-6143","authenticated-orcid":false,"given":"Cong","family":"Han","sequence":"additional","affiliation":[{"name":"Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2779-9954","authenticated-orcid":false,"given":"Jingjie","family":"Li","sequence":"additional","affiliation":[{"name":"Medical School of Chinese PLA","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6389-2347","authenticated-orcid":false,"given":"Qian\u2010Nan","family":"Wang","sequence":"additional","affiliation":[{"name":"Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7090-5583","authenticated-orcid":false,"given":"Gan","family":"Gao","sequence":"additional","affiliation":[{"name":"Medical School of Chinese PLA","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4093-3070","authenticated-orcid":false,"given":"Simeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical School of Chinese PLA","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5607-6926","authenticated-orcid":false,"given":"Fangbin","family":"Hao","sequence":"additional","affiliation":[{"name":"Medical School of Chinese PLA","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4620-4801","authenticated-orcid":false,"given":"Minjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical School of Chinese PLA","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5244-2586","authenticated-orcid":false,"given":"Xiaopeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical School of Chinese PLA","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1204-7386","authenticated-orcid":false,"given":"Xiangyang","family":"Bao","sequence":"additional","affiliation":[{"name":"Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7210-056X","authenticated-orcid":false,"given":"Lian","family":"Duan","sequence":"additional","affiliation":[{"name":"Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1969.00480090076012"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0804622"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad225"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(22)00165-X"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2022.08.009"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-025-00649-6"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201712120"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3109\/02688697.2014.976177"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036386"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.3171\/2017.9.JNS17576"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-025-03446-y"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/1844190"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.032297"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-7226764\/v1"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10143-025-04038-3"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10143-025-04026-7"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.2463\/mrms.mp.2025-0139"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013080816"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.12.065"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2011.65"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1932.sp002899"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2005.02.001"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.123.323284"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02481-14"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09922"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.03.546"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.049952"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13909"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-20942-w"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101733"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.3390\/ani12121497"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28155637"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-5-45"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.4.750"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13062-024-00522-w"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222413410"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1159\/000345957"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.513408"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-8467(97)00031-0"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.490714"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25010193"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep36362"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.030027"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1994.1052"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2023.100365"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000136819.93989.E1"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/nqz031"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izad080"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2023.02.023"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.48309\/AJCA.2024.462869.1555"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm500873e"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1021\/jf800651z"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.126.050737","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:41:07Z","timestamp":1789011667000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.126.050737"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":54,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2026,8,4]]}},"alternative-id":["10.1161\/JAHA.126.050737"],"URL":"https:\/\/doi.org\/10.1161\/jaha.126.050737","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]},"assertion":[{"value":"2026-03-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e050737"}}