{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:10:38Z","timestamp":1778217038170,"version":"3.51.4"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Inflammatory monocyte (MC) subset polarization is a hallmark of systemic and tissue inflammatory feature in diabetes. The underlying molecular mechanism remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      Blood pro-inflammatory Ly6C\n                      <jats:sup>high<\/jats:sup>\n                      and anti-inflammatory Ly6C\n                      <jats:sup>low<\/jats:sup>\n                      MC subsets were isolated from control (C57\/BL6), type 1 diabetes mellitus (T1DM), and type 2 diabetes mellitus (T2DM) mice by flow cytometry sorting and subjected to bulk high-throughput RNA-sequencing. Intensive and integrative functional bioinformatic studies were performed by analyzing the transcriptome through seven pairs of comparison between Ly6C\n                      <jats:sup>high<\/jats:sup>\n                      and Ly6C\n                      <jats:sup>low<\/jats:sup>\n                      MC subsets and between different mouse groups. We examined molecular features of three key immune activation signals in innate and adaptive immune responses, including signal 1 antigen (Ag)-presenting, signal 2 immune checkpoint, and signal 3 cytokine, and their upstream transcription factors (TF). A total of 10 differentially expressed genes (DEG) of MHC-II molecules (signal 1) presented a low expression profile in Ly6C\n                      <jats:sup>high<\/jats:sup>\n                      MCs from all mice and mostly further reduced in T2DM Ly6C\n                      <jats:sup>high<\/jats:sup>\n                      MC. Ly6C\n                      <jats:sup>high<\/jats:sup>\n                      MCs show high intercellular inflammatory propagation based on immune checkpoint\/cytokine-ligand expression but low intracellular inflammatory capacity based on immune checkpoint\/cytokine-receptor expression, both further enhanced in T1\/T2DM. In contrast, Ly6C\n                      <jats:sup>low<\/jats:sup>\n                      MCs exhibit low intercellular propagation but high intracellular inflammatory capacity; both also increased in T1\/T2DM. Furthermore, 921 upstream DEG transcription factors and 17 transcriptional axes were recognized in diabetic Ly6C\n                      <jats:sup>high<\/jats:sup>\n                      MCs by IPA upstream regulator analysis. Finally, three critical transcriptional axes that drove the altered immunological phenotype in Ly6C\n                      <jats:sup>high<\/jats:sup>\n                      MCs were recognized: \u2193PAX5-\u2193CIITA-\u2193Cd74\/H2-Eb2 for reduced Ag-presenting power, \u2193MYC-\u2191Sema4a for elevated intercellular inflammatory propagation capacity, and \u2191CEBPA\/E-\u2191Csf2ra\/3r for enhanced intracellular inflammatory propagation capacity in MC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We have three major discoveries: 1) Ly6C\n                      <jats:sup>high<\/jats:sup>\n                      MCs exhibit lower Ag-presenting power, which was further suppressed in T2DM, mostly via \u2193PAX5-\u2193CIITA-\u2193CD74 regulation. 2) Ly6C\n                      <jats:sup>high<\/jats:sup>\n                      MCs display high intercellular inflammatory propagation but low intracellular inflammatory capacity, both further enhanced in T1\/T2DM, mostly via \u2193MYC-\u2191Sema4a and \u2191CEBPA\/E-\u2191Csf2ra\/3r regulation. 3) Ly6C\n                      <jats:sup>low<\/jats:sup>\n                      MCs acquired additional intercellular and intracellular inflammatory capacity in T1\/T2DM.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1794704","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T04:35:52Z","timestamp":1778214952000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Empowered pro-inflammatory features in Ly6C monocytes and altered antigen-presenting capacity in Ly6Chigh monocytes in diabetic mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Pingping","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University","place":["Nanchang, Jiangxi, China"]},{"name":"Center for Metabolic Disease Research, Department of Cardiovascular Science, Lewis Kats School of Medicine, Temple University","place":["Philadelphia, PA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pu","family":"Fang","sequence":"additional","affiliation":[{"name":"Center for Metabolic Disease Research, Department of Cardiovascular Science, Lewis Kats School of Medicine, Temple University","place":["Philadelphia, PA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lizhe","family":"Sun","sequence":"additional","affiliation":[{"name":"Center for Metabolic Disease Research, Department of Cardiovascular Science, Lewis Kats School of Medicine, Temple University","place":["Philadelphia, PA, United States"]},{"name":"Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi\u2019an Jiaotong University","place":["Xi\u2019an, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Metabolic Disease Research, Department of Cardiovascular Science, Lewis Kats School of Medicine, Temple University","place":["Philadelphia, PA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linghua","family":"Fu","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Xi","sequence":"additional","affiliation":[{"name":"Center for Metabolic Disease Research, Department of Cardiovascular Science, Lewis Kats School of Medicine, Temple University","place":["Philadelphia, PA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Metabolic Disease Research, Department of Cardiovascular Science, Lewis Kats School of Medicine, Temple University","place":["Philadelphia, PA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rihab","family":"Bouchareb","sequence":"additional","affiliation":[{"name":"Center for Metabolic Disease Research, Department of Cardiovascular Science, Lewis Kats School of Medicine, Temple University","place":["Philadelphia, PA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shengjing Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinghua","family":"Wu","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Ji","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Harbin Medical University","place":["Harbin, Heilongjiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Metabolic Disease Research, Department of Cardiovascular Science, Lewis Kats School of Medicine, Temple University","place":["Philadelphia, PA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Metabolic Disease Research, Department of Cardiovascular Science, Lewis Kats School of Medicine, Temple University","place":["Philadelphia, PA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1038\/nri3671","article-title":"Monocytes and macrophages: developmental pathways and tissue homeostasis","volume":"14","author":"Ginhoux","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1146\/annurev-pathmechdis-012418-013058","article-title":"Monocytes in the tumor microenvironment","volume":"16","author":"Ugel","year":"2021","journal-title":"Annu Rev Pathol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1186\/s13045-017-0504-1","article-title":"Metabolism-associated danger signal-induced immune response and reverse immune checkpoint-activated CD40(+) monocyte differentiation","volume":"10","author":"Dai","year":"2017","journal-title":"J Hematol Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1186\/2050-7771-2-1","article-title":"Monocyte and macrophage differentiation: circulation inflammatory monocyte as biomarker for inflammatory diseases","volume":"2","author":"Yang","year":"2014","journal-title":"biomark Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.119.313138","article-title":"Ly6C(+) inflammatory monocyte differentiation partially mediates hyperhomocysteinemia-induced vascular dysfunction in type 2 diabetic db\/db mice","volume":"39","author":"Fang","year":"2019","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01430-3","article-title":"CD40 signal rewires fatty acid and glutamine metabolism for stimulating macrophage anti-tumorigenic functions","volume":"24","author":"Liu","year":"2023","journal-title":"Nat Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107709","article-title":"Molecular basis and therapeutic implications of CD40\/CD40L immune checkpoint","volume":"219","author":"Tang","year":"2021","journal-title":"Pharmacol Ther"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.116.308750","article-title":"Chronic kidney disease\u00a0induces\u00a0inflammatory CD40+ monocyte differentiation via homocysteine elevation and DNA hypomethylation","volume":"119","author":"Yang","year":"2016","journal-title":"Circ Res"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aat0207","article-title":"Emergence of immunoregulatory Ym1(+)Ly6C(hi) monocytes during recovery phase of tissue injury","volume":"3","author":"Ikeda","year":"2018","journal-title":"Sci Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s10456-015-9489-y","article-title":"Inflammation is associated with a reduced number of pro-angiogenic Tie-2 monocytes and endothelial progenitor cells in patients with critical limb ischemia","volume":"19","author":"Dopheide","year":"2016","journal-title":"Angiogenesis"},{"key":"B11","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s40779-023-00462-y","article-title":"Single-cell transcriptome profiling of sepsis identifies HLA-DR(low)S100A(high) monocytes with immunosuppressive function","volume":"10","author":"Yao","year":"2023","journal-title":"Mil Med Res"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1111600109","article-title":"Diabetes promotes an inflammatory macrophage phenotype and atherosclerosis through acyl-CoA synthetase 1","volume":"109","author":"Kanter","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.118.310703","article-title":"Ly6C(Hi) blood monocyte\/macrophage drive chronic inflammation and impair wound healing in diabetes mellitus","volume":"38","author":"Kimball","year":"2018","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adn2136","article-title":"Monocytes in type 1 diabetes families exhibit high cytolytic activity and subset abundances that correlate with clinical progression","volume":"10","author":"Pant","year":"2024","journal-title":"Sci Adv"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-024-06098-4","article-title":"A novel subpopulation of monocytes with a strong interferon signature indicated by SIGLEC-1 is present in patients with in recent-onset type 1 diabetes","volume":"67","author":"Guo","year":"2024","journal-title":"Diabetologia"},{"key":"B16","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1007\/s00125-022-05860-w","article-title":"CCR2-positive monocytes contribute to the pathogenesis of early diabetic retinopathy in mice","volume":"66","author":"Saadane","year":"2023","journal-title":"Diabetologia"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.632333","article-title":"Immunological feature and transcriptional signaling of Ly6C monocyte subsets from transcriptome analysis in control and hyperhomocysteinemic mice","volume":"12","author":"Yang","year":"2021","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.809208","article-title":"Adaptive immune response signaling is suppressed in Ly6C(high) monocyte but upregulated in monocyte subsets of ApoE(-\/-) mice - functional implication in atherosclerosis","volume":"12","author":"Yang","year":"2021","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101759","article-title":"Innate-adaptive immunity interplay and redox regulation in immune response","volume":"37","author":"Sun","year":"2020","journal-title":"Redox Biol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.109.866889","article-title":"Hyperhomocysteinemia promotes inflammatory monocyte generation and accelerates atherosclerosis in transgenic cystathionine beta-synthase-deficient mice","volume":"120","author":"Zhang","year":"2009","journal-title":"Circulation"},{"key":"B21","doi-asserted-by":"publisher","first-page":"3964","DOI":"10.1038\/s41467-019-11843-0","article-title":"Non-classical tissue monocytes and two functionally distinct populations of interstitial macrophages populate the mouse lung","volume":"10","author":"Schyns","year":"2019","journal-title":"Nat Commun"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2009.21","article-title":"The role of inflammation in insulitis and beta-cell loss in type 1 diabetes","volume":"5","author":"Eizirik","year":"2009","journal-title":"Nat Rev Endocrinol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.ccell.2020.09.001","article-title":"The PD-1\/PD-L1-checkpoint restrains T cell immunity in tumor-draining lymph nodes","volume":"38","author":"Dammeijer","year":"2020","journal-title":"Cancer Cell"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-024-00945-0","article-title":"Targeting pro-inflammatory T cells as a novel therapeutic approach to potentially resolve atherosclerosis in humans","volume":"34","author":"Fan","year":"2024","journal-title":"Cell Res"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.156330","article-title":"Immune cells and their inflammatory mediators modify \u03b2 cells and cause checkpoint inhibitor-induced diabetes","volume":"7","author":"Perdigoto","year":"2022","journal-title":"JCI Insight"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201907692","article-title":"Engineered PD-L1-expressing platelets reverse new-onset type 1 diabetes","volume":"32","author":"Zhang","year":"2020","journal-title":"Adv Mater"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.114052","article-title":"Wounds under diabetic milieu: the role of immune cellar components and signaling pathways","volume":"157","author":"Lin","year":"2023","journal-title":"BioMed Pharmacother"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2020.104257","article-title":"Usefulness of IL-21, IL-7, and IL-15 conditioned media for expansion of antigen-specific CD8+ T cells from healthy donor-PBMCs suitable for immunotherapy","volume":"360","author":"Chamucero-Millares","year":"2021","journal-title":"Cell Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2020.11.005","article-title":"Hyperglycemia and dyslipidemia: reduced HLA-DR expression in monocyte subpopulations from diabetes patients","volume":"82","author":"Restrepo","year":"2021","journal-title":"Hum Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02035","article-title":"Human monocyte subsets and phenotypes in major chronic inflammatory diseases","volume":"10","author":"Kapellos","year":"2019","journal-title":"Front Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-326827","article-title":"SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset","volume":"118","author":"Zawada","year":"2011","journal-title":"Blood"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05309-5","article-title":"Novel antigen-presenting cell imparts Treg-dependent tolerance to gut microbiota","volume":"610","author":"Akagbosu","year":"2022","journal-title":"Nature"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.09.011","article-title":"Antigen-presenting cells as specialized drivers of intestinal T\u00a0cell functions","volume":"57","author":"Kedmi","year":"2024","journal-title":"Immunity"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.5A0416-182R","article-title":"Antigen-presenting human B cells are expanded in inflammatory conditions","volume":"101","author":"Shimabukuro-Vornhagen","year":"2017","journal-title":"J Leukoc Biol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3390\/cells12020314","article-title":"MHC class II presentation in autoimmunity","volume":"12","author":"Ishina","year":"2023","journal-title":"Cells"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.120.314330","article-title":"Vascular endothelial cells and innate immunity","volume":"40","author":"Shao","year":"2020","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.03225","article-title":"Trained immunity carried by non-immune cells","volume":"9","author":"Hamada","year":"2018","journal-title":"Front Microbiol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"988","DOI":"10.2337\/db18-0686","article-title":"HLA class II antigen processing and presentation pathway components demonstrated by transcriptome and protein analyses of islet \u03b2-cells from donors with type 1 diabetes","volume":"68","author":"Russell","year":"2019","journal-title":"Diabetes"},{"key":"B39","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1007\/s00125-021-05619-9","article-title":"Upregulation of HLA class II in pancreatic beta cells from organ donors with type 1 diabetes","volume":"65","author":"Quesada-Masachs","year":"2022","journal-title":"Diabetologia"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2009.02.005","article-title":"Differential CD74 (major histocompatibility complex class II invariant chain) expression in mouse and human intestinal adenomas","volume":"45","author":"Cuthbert","year":"2009","journal-title":"Eur J Cancer"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2016.03.026","article-title":"The multifaceted roles of the invariant chain CD74--more than just a chaperone","volume":"1863","author":"Schr\u00f6der","year":"2016","journal-title":"Biochim Biophys Acta"},{"key":"B42","doi-asserted-by":"publisher","first-page":"2860","DOI":"10.1038\/s41467-020-16447-7","article-title":"MYC functions as a switch for natural killer cell-mediated immune surveillance of lymphoid Malignancies","volume":"11","author":"Swaminathan","year":"2020","journal-title":"Nat Commun"},{"key":"B43","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/s13045-022-01306-3","article-title":"Long noncoding RNA Smyca coactivates TGF-\u03b2\/Smad and Myc pathways to drive tumor progression","volume":"15","author":"Chen","year":"2022","journal-title":"J Hematol Oncol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.024","article-title":"Transforming growth factor-\u03b2 signaling in immunity and cancer","volume":"50","author":"Batlle","year":"2019","journal-title":"Immunity"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021005459","article-title":"M-CSFR\/CSF1R signaling regulates myeloid fates in zebrafish via distinct action of its receptors and ligands","volume":"6","author":"Hason","year":"2022","journal-title":"Blood Adv"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023010830","article-title":"Enhanced MAPK signaling induced by CSF3R mutants confers dependence to DUSP1 for leukemic transformation","volume":"8","author":"Kesarwani","year":"2024","journal-title":"Blood Adv"},{"key":"B47","doi-asserted-by":"publisher","first-page":"994","DOI":"10.21037\/atm-20-5363","article-title":"Genomic analysis of the prognostic value of colony-stimulating factors (CSFs) and colony-stimulating factor receptors (CSFRs) across 24 solid cancer types","volume":"8","author":"Huang","year":"2020","journal-title":"Ann Transl Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1794704\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T04:35:57Z","timestamp":1778214957000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1794704\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":47,"alternative-id":["10.3389\/fimmu.2026.1794704"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1794704","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,8]]},"article-number":"1794704"}}