{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:42:55Z","timestamp":1791513775663,"version":"4.3.4"},"reference-count":61,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"the National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["7R01NS110370"],"award-info":[{"award-number":["7R01NS110370"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"award":["7R01NS110370"],"award-info":[{"award-number":["7R01NS110370"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Division of Biomedical Sciences, School of Medicine at the University of California, Riverside"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ischemic stroke promotes monocyte recruitment to the injured brain and their differentiation into monocyte-derived macrophages (MDMs). These cells contribute to debris clearance but may also exacerbate neuroinflammation. However, the heterogeneity of MDM subsets and the phenotypic transitions that shape MDM functional states during the subacute phase of stroke remain incompletely characterized. To address this, we first performed single-cell RNA sequencing (scRNA-seq) to define the transcriptional landscape of the mouse brain 48 h after transient middle cerebral artery occlusion\/reperfusion compared with sham controls. Reclustering of macrophage-lineage cells identified multiple MDM subsets, including a distinct Cd68hi\/Ctsdhi MDM subset enriched for lysosomal and lipid-processing gene expression programs. Cell trajectory inference supported a transition from early recruited MDMs toward the Cd68hi\/Ctsdhi state, accompanied by induction of transcriptomic networks that drive MDM function to favor a clearance-competent phenotype in response to ischemic stroke. Complementary single-cell ATAC sequencing (scATAC-seq) demonstrated cell type-specific chromatin remodeling after stroke and revealed MDM subclusters with accessibility at key loci regulating lysosomal function and lipid metabolism. Together, our findings define a cellular and regulatory framework of the subacute post-stroke brain and identify a lysosome-enriched Cd68hi\/Ctsdhi MDM trajectory, highlighting endolysosomal and lipid-processing programs during early stroke recovery.<\/jats:p>","DOI":"10.3390\/ijms27083657","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T09:37:42Z","timestamp":1776677862000},"page":"3657","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Multimodal Single-Cell Transcriptomic and Chromatin Accessibility Profiling Reveals Monocyte-Derived Macrophage Dynamics Following Ischemic Stroke"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8538-4841","authenticated-orcid":false,"given":"Milton H.","family":"Hamblin","sequence":"first","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA 92521, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5297-8307","authenticated-orcid":false,"given":"Rabi","family":"Murad","sequence":"additional","affiliation":[{"name":"NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin C.","family":"Boese","sequence":"additional","affiliation":[{"name":"School of Medicine, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2471-8351","authenticated-orcid":false,"given":"Huijie","family":"Huang","sequence":"additional","affiliation":[{"name":"Center for Neurological Diseases, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A.","family":"Porritt","sequence":"additional","affiliation":[{"name":"NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7966-3186","authenticated-orcid":false,"given":"Tanvi","family":"Bobba","sequence":"additional","affiliation":[{"name":"Health Sciences Center, Tulane University, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pyo","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA 92521, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e139","DOI":"10.1161\/CIR.0000000000000757","article-title":"Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association","volume":"141","author":"Virani","year":"2020","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.neuron.2010.07.002","article-title":"The Science of Stroke: Mechanisms in Search of Treatments","volume":"67","author":"Moskowitz","year":"2010","journal-title":"Neuron"},{"key":"ref_3","first-page":"e85","article-title":"Heart disease and stroke statistics\u20142006 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee","volume":"113","author":"Thom","year":"2006","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/nm.2399","article-title":"The immunology of stroke: From mechanisms to translation","volume":"17","author":"Iadecola","year":"2011","journal-title":"Nat. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nrneurol.2012.98","article-title":"The immunology of acute stroke","volume":"8","author":"Chamorro","year":"2012","journal-title":"Nat. Rev. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1161\/STROKEAHA.108.534503","article-title":"Temporal and Spatial Dynamics of Cerebral Immune Cell Accumulation in Stroke","volume":"40","author":"Gelderblom","year":"2009","journal-title":"Stroke"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1161\/STROKEAHA.114.008608","article-title":"The Functional Role of Regulatory Lymphocytes in Stroke: Facts and Controversies","volume":"46","author":"Liesz","year":"2015","journal-title":"Stroke"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1038\/nn.2887","article-title":"Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool","volume":"14","author":"Ajami","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1002\/ana.23529","article-title":"Macrophages prevent hemorrhagic infarct transformation in murine stroke models","volume":"71","author":"Gliem","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.cell.2019.08.053","article-title":"Microglia Biology: One Century of Evolving Concepts","volume":"179","author":"Prinz","year":"2019","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1182\/blood.2021011671","article-title":"Donor bone marrow-derived macrophage MHC II drives neuroinflammation and altered behavior during chronic GVHD in mice","volume":"139","author":"Adams","year":"2022","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1182\/blood.2023022040","article-title":"CSF1R inhibition promotes neuroinflammation and behavioral deficits during graft-versus-host disease in mice","volume":"143","author":"Adams","year":"2024","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1038\/nri1733","article-title":"Monocyte and macrophage heterogeneity","volume":"5","author":"Gordon","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3095","DOI":"10.1161\/STROKEAHA.120.029827","article-title":"Reciprocal Interaction Between Pericytes and Macrophage in Poststroke Tissue Repair and Functional Recovery","volume":"51","author":"Shibahara","year":"2020","journal-title":"Stroke"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1161\/STROKEAHA.119.027315","article-title":"Brain Cleanup as a Potential Target for Poststroke Recovery: The Role of RXR (Retinoic X Receptor) in Phagocytes","volume":"51","author":"Ting","year":"2020","journal-title":"Stroke"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4182","DOI":"10.1523\/JNEUROSCI.4317-15.2016","article-title":"Monocyte-Derived Macrophages Contribute to Spontaneous Long-Term Functional Recovery after Stroke in Mice","volume":"36","author":"Wattananit","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S98","DOI":"10.1177\/0271678X20909055","article-title":"CCR2 deficiency in monocytes impairs angiogenesis and functional recovery after ischemic stroke in mice","volume":"40","author":"Pedragosa","year":"2020","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e131355","DOI":"10.1172\/jci.insight.131355","article-title":"STAT6\/Arg1 promotes microglia\/macrophage efferocytosis and inflammation resolution in stroke mice","volume":"4","author":"Cai","year":"2019","journal-title":"JCI Insight"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/s41590-023-01711-x","article-title":"Analysis of brain and blood single-cell transcriptomics in acute and subacute phases after experimental stroke","volume":"25","author":"Shahanoor","year":"2024","journal-title":"Nat. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/1742-2094-11-64","article-title":"Enhanced uptake of multiple sclerosis-derived myelin by THP-1 macrophages and primary human microglia","volume":"11","author":"Hendrickx","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1097\/MOL.0000000000000213","article-title":"Degradation and beyond: The macrophage lysosome as a nexus for nutrient sensing and processing in atherosclerosis","volume":"26","author":"Sergin","year":"2015","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1038\/emboj.2012.32","article-title":"A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB","volume":"31","author":"Settembre","year":"2012","journal-title":"Embo J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1126\/science.1174447","article-title":"A gene network regulating lysosomal biogenesis and function","volume":"325","author":"Sardiello","year":"2009","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nrm2745","article-title":"Lysosome biogenesis and lysosomal membrane proteins: Trafficking meets function","volume":"10","author":"Saftig","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3852","DOI":"10.1093\/hmg\/ddr306","article-title":"Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways","volume":"20","author":"Palmieri","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.tcb.2017.07.006","article-title":"Emerging Roles for the Lysosome in Lipid Metabolism","volume":"27","author":"Thelen","year":"2017","journal-title":"Trends Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1177\/0271678X231205078","article-title":"Growth arrest specific protein 6 alleviated white matter injury after experimental ischemic stroke","volume":"44","author":"Jia","year":"2024","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1111\/cns.13256","article-title":"Macrophages reprogram after ischemic stroke and promote efferocytosis and inflammation resolution in the mouse brain","volume":"25","author":"Zhang","year":"2019","journal-title":"CNS Neurosci. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"102186","DOI":"10.1016\/j.isci.2021.102186","article-title":"Single-cell RNA-seq analysis reveals compartment-specific heterogeneity and plasticity of microglia","volume":"24","author":"Zheng","year":"2021","journal-title":"iScience"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"eabe7915","DOI":"10.1126\/sciimmunol.abe7915","article-title":"CD300a blockade enhances efferocytosis by infiltrating myeloid cells and ameliorates neuronal deficit after ischemic stroke","volume":"6","author":"Fujiyama","year":"2021","journal-title":"Sci. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.14336\/AD.2022.0212","article-title":"Cell Heterogeneity Uncovered by Single-Cell RNA Sequencing Offers Potential Therapeutic Targets for Ischemic Stroke","volume":"13","author":"Qiu","year":"2022","journal-title":"Aging Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1038\/s41467-022-28593-1","article-title":"Stroke induces disease-specific myeloid cells in the brain parenchyma and pia","volume":"13","author":"Beuker","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1016\/j.cell.2014.11.018","article-title":"Tissue-Resident Macrophage Enhancer Landscapes Are Shaped by the Local Microenvironment","volume":"159","author":"Lavin","year":"2014","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.cell.2014.11.023","article-title":"Environment drives selection and function of enhancers controlling tissue-specific macrophage identities","volume":"159","author":"Gosselin","year":"2014","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1251086","DOI":"10.1126\/science.1251086","article-title":"Epigenetic programming during monocyte to macrophage differentiation and trained innate immunity","volume":"345","author":"Saeed","year":"2014","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s12974-022-02447-5","article-title":"Single-cell transcriptomic analysis of the immune cell landscape in the aged mouse brain after ischemic stroke","volume":"19","author":"Li","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"346","DOI":"10.4103\/NRR.NRR-D-24-01092","article-title":"Changes in border-associated macrophages after stroke: Single-cell sequencing analysis","volume":"21","author":"Yu","year":"2026","journal-title":"Neural Regen. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.immuni.2014.06.008","article-title":"Macrophage activation and polarization: Nomenclature and experimental guidelines","volume":"41","author":"Murray","year":"2014","journal-title":"Immunity"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1182\/blood.V81.6.1607.1607","article-title":"Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins","volume":"81","author":"Holness","year":"1993","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1080\/15548627.2020.1761219","article-title":"Restoration of CTSD (cathepsin D) and lysosomal function in stroke is neuroprotective","volume":"17","author":"Hossain","year":"2021","journal-title":"Autophagy"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/ni.2956","article-title":"Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages","volume":"15","author":"Huang","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/nm.1927","article-title":"Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke","volume":"15","author":"Liesz","year":"2009","journal-title":"Nat. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1093\/brain\/awn109","article-title":"Debris clearance by microglia: An essential link between degeneration and regeneration","volume":"132","author":"Neumann","year":"2009","journal-title":"Brain"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.immuni.2019.03.016","article-title":"Immune Signaling in Neurodegeneration","volume":"50","author":"Hammond","year":"2019","journal-title":"Immunity"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3330","DOI":"10.1091\/mbc.e14-05-0967","article-title":"Contrasting phagosome pH regulation and maturation in human M1 and M2 macrophages","volume":"25","author":"Canton","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1126\/science.277.5323.228","article-title":"Niemann-Pick C1 Disease Gene: Homology to Mediators of Cholesterol Homeostasis","volume":"277","author":"Carstea","year":"1997","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1126\/science.aan4183","article-title":"Defective cholesterol clearance limits remyelination in the aged central nervous system","volume":"359","author":"Fitzner","year":"2018","journal-title":"Science"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/s41593-019-0566-1","article-title":"Lipid droplet accumulating microglia represent a dysfunctional and pro-inflammatory state in the aging brain","volume":"23","author":"Marschallinger","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.it.2018.01.012","article-title":"Lipid Droplets as Immune Modulators in Myeloid Cells","volume":"39","author":"Raaijmakers","year":"2018","journal-title":"Trends Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1194\/jlr.R009761","article-title":"Lipid metabolism in myelinating glial cells: Lessons from human inherited disorders and mouse models","volume":"52","author":"Chrast","year":"2011","journal-title":"J. Lipid Res."},{"key":"ref_51","first-page":"1083","article-title":"Cholesterol in myelin biogenesis and hypomyelinating disorders","volume":"1851","author":"Saher","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Biol. Lipids"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00018-023-04786-9","article-title":"TREM2 promotes cholesterol uptake and foam cell formation in atherosclerosis","volume":"80","author":"Guo","year":"2023","journal-title":"Cell Mol. Life Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1080\/01616412.1997.11740874","article-title":"Monofilament intraluminal middle cerebral artery occlusion in the mouse","volume":"19","author":"Clark","year":"1997","journal-title":"Neurol. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/scrt519","article-title":"Human neural stem cells rapidly ameliorate symptomatic inflammation in early-stage ischemic-reperfusion cerebral injury","volume":"5","author":"Huang","year":"2014","journal-title":"Stem Cell Res. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"841","DOI":"10.5966\/sctm.2014-0184","article-title":"Bystander Effect Fuels Human Induced Pluripotent Stem Cell-Derived Neural Stem Cells to Quickly Attenuate Early Stage Neurological Deficits After Stroke","volume":"4","author":"Eckert","year":"2015","journal-title":"Stem Cells Transl. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"113275","DOI":"10.1016\/j.expneurol.2020.113275","article-title":"Human neural stem cells improve early stage stroke outcome in delayed tissue plasminogen activator-treated aged stroke brains","volume":"329","author":"Boese","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Hamblin, M.H., Boese, A.C., Murad, R., and Lee, J.P. (2024). MMP-3 Knockout Induces Global Transcriptional Changes and Reduces Cerebral Infarction in Both Male and Female Models of Ischemic Stroke. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137383"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Hamblin, M.H., Boese, A.C., Murad, R., and Lee, J.P. (2025). PPAR\u03b1 Genetic Deletion Reveals Global Transcriptional Changes in the Brain and Exacerbates Cerebral Infarction in a Mouse Model of Stroke. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26094082"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1093\/bioinformatics\/btz698","article-title":"scds: Computational annotation of doublets in single-cell RNA sequencing data","volume":"36","author":"Bais","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","article-title":"Dictionary learning for integrative, multimodal and scalable single-cell analysis","volume":"42","author":"Hao","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/nbt.2859","article-title":"The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells","volume":"32","author":"Trapnell","year":"2014","journal-title":"Nat. Biotechnol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3657\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T09:40:14Z","timestamp":1776678014000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3657"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,20]]},"references-count":61,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27083657"],"URL":"https:\/\/doi.org\/10.3390\/ijms27083657","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,20]]}}}