{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T04:09:44Z","timestamp":1777954184041,"version":"3.51.4"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"General Programs of Natural Science Research of Anhui Provincial Education Department","award":["ZR2022B001"],"award-info":[{"award-number":["ZR2022B001"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Macrophage polarization correlates strongly with the progression and prognosis of spinal cord injury (SCI), yet the therapeutic potential of macrophage polarization-related genes (MPRGs) in SCI remains unexplored. This study identified hub genes associated with MPRGs for SCI diagnosis, prognosis, and therapy. Differentially expressed genes (DEGs) between SCI and control groups were intersected with MPRGs to identify six differentially expressed MPRGs (DE-MPRGs). Machine learning algorithms, including LASSO, RF, and XGBoost, selected three hub genes (\n                    <jats:italic>Soat1<\/jats:italic>\n                    ,\n                    <jats:italic>Comt<\/jats:italic>\n                    , and\n                    <jats:italic>Myo1f<\/jats:italic>\n                    ) with elevated expression in SCI samples. Functional enrichment analysis indicated involvement in immune-related pathways. Immune infiltration analysis revealed differences in 11 immune gene sets between SCI and controls, all positively correlated with the hub genes. In silico drug prediction identified 37 small molecules, including dexamethasone and atorvastatin, as potential modulators of macrophage polarization in SCI. Single-cell RNA sequencing showed significantly higher expression of all hub genes in M2 than in M1 macrophages. RT-qPCR validation confirmed upregulation of the hub genes in SCI models. These results highlight\n                    <jats:italic>Soat1<\/jats:italic>\n                    ,\n                    <jats:italic>Comt<\/jats:italic>\n                    , and\n                    <jats:italic>Myo1f<\/jats:italic>\n                    as novel hub genes in SCI, offering insights into macrophage polarization mechanisms and potential therapeutic targets.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0347599","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T17:30:19Z","timestamp":1777915819000},"page":"e0347599","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Screening macrophage polarization genes in spinal cord injury as therapeutic targets"],"prefix":"10.1371","volume":"21","author":[{"given":"Xiaowei","family":"Zha","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1285-1856","authenticated-orcid":true,"given":"Shen","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"issue":"1","key":"pone.0347599.ref001","doi-asserted-by":"crossref","first-page":"22344","DOI":"10.1038\/s41598-024-72947-2","article-title":"High mobility group box-1 protein promotes astrocytic CCL5 production through the MAPK\/NF-\u03baB pathway following spinal cord injury","volume":"14","author":"G Chi","year":"2024","journal-title":"Sci Rep"},{"key":"pone.0347599.ref002","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.pneurobio.2013.11.002","article-title":"From basics to clinical: a comprehensive review on spinal cord injury","volume":"114","author":"NA Silva","year":"2014","journal-title":"Prog Neurobiol"},{"issue":"1","key":"pone.0347599.ref003","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1310\/sci1901-1","article-title":"Causes of spinal cord injury","volume":"19","author":"Y Chen","year":"2013","journal-title":"Topics in spinal cord injury rehabilitation"},{"issue":"9304","key":"pone.0347599.ref004","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0140-6736(02)07603-1","article-title":"Spinal-cord injury","volume":"359","author":"JW McDonald","year":"2002","journal-title":"Lancet"},{"issue":"4","key":"pone.0347599.ref005","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1017\/S0317167100014530","article-title":"Global incidence and prevalence of traumatic spinal cord injury","volume":"40","author":"JC Furlan","year":"2013","journal-title":"Can J Neurol Sci"},{"issue":"5","key":"pone.0347599.ref006","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s00586-014-3424-6","article-title":"Incidence of traumatic spinal cord injury worldwide: a systematic review","volume":"24","author":"SB Jazayeri","year":"2015","journal-title":"Eur Spine J"},{"key":"pone.0347599.ref007","first-page":"309","article-title":"Global prevalence and incidence of traumatic spinal cord injury","volume":"6","author":"A Singh","year":"2014","journal-title":"Clin Epidemiol"},{"issue":"1","key":"pone.0347599.ref008","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s12974-019-1468-6","article-title":"Macrophage migration inhibitory factor facilitates prostaglandin E2 production of astrocytes to tune inflammatory milieu following spinal cord injury","volume":"16","author":"Y Zhang","year":"2019","journal-title":"J Neuroinflammation"},{"issue":"1","key":"pone.0347599.ref009","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/s12974-021-02186-z","article-title":"D-dopachrome tautomerase activates COX2\/PGE2 pathway of astrocytes to mediate inflammation following spinal cord injury","volume":"18","author":"H Ji","year":"2021","journal-title":"J Neuroinflammation"},{"issue":"2","key":"pone.0347599.ref010","doi-asserted-by":"crossref","first-page":"454","DOI":"10.4103\/NRR.NRR-D-23-02044","article-title":"Microglia: a promising therapeutic target in spinal cord injury","volume":"20","author":"X Zha","year":"2025","journal-title":"Neural Regen Res"},{"issue":"2","key":"pone.0347599.ref011","doi-asserted-by":"crossref","first-page":"108626","DOI":"10.1016\/j.celrep.2020.108626","article-title":"Dynamic Shifts in the Composition of Resident and Recruited Macrophages Influence Tissue Remodeling in NASH","volume":"34","author":"S Daemen","year":"2021","journal-title":"Cell Rep"},{"key":"pone.0347599.ref012","doi-asserted-by":"crossref","first-page":"1084101","DOI":"10.3389\/fimmu.2022.1084101","article-title":"Immune response following traumatic spinal cord injury: Pathophysiology and therapies","volume":"13","author":"RC Sterner","year":"2023","journal-title":"Front Immunol"},{"key":"pone.0347599.ref013","doi-asserted-by":"crossref","first-page":"1014013","DOI":"10.3389\/fimmu.2022.1014013","article-title":"Advances in the research of the role of macrophage\/microglia polarization-mediated inflammatory response in spinal cord injury","volume":"13","author":"S-P Fu","year":"2022","journal-title":"Front Immunol"},{"issue":"14","key":"pone.0347599.ref014","doi-asserted-by":"crossref","first-page":"8045","DOI":"10.1111\/jcmm.15436","article-title":"Resolvin D1 and D2 inhibit tumour growth and inflammation via modulating macrophage polarization","volume":"24","author":"K Shan","year":"2020","journal-title":"J Cell Mol Med"},{"issue":"8","key":"pone.0347599.ref015","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.3390\/cells10081943","article-title":"Activation of Neuroprotective Microglia and Astrocytes at the Lesion Site and in the Adjacent Segments Is Crucial for Spontaneous Locomotor Recovery after Spinal Cord Injury","volume":"10","author":"A Kisuck\u00e1","year":"2021","journal-title":"Cells"},{"issue":"1","key":"pone.0347599.ref016","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/s41392-023-01452-1","article-title":"Macrophages in immunoregulation and therapeutics","volume":"8","author":"S Chen","year":"2023","journal-title":"Signal Transduct Target Ther"},{"issue":"12","key":"pone.0347599.ref017","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1111\/febs.17305","article-title":"Macrophages and autophagy: partners in crime","volume":"292","author":"A Vitaliti","year":"2025","journal-title":"FEBS J"},{"issue":"2","key":"pone.0347599.ref018","doi-asserted-by":"crossref","DOI":"10.1172\/JCI175445","article-title":"Modulation of macrophage metabolism as an emerging immunotherapy strategy for cancer","volume":"134","author":"C Dussold","year":"2024","journal-title":"J Clin Invest"},{"key":"pone.0347599.ref019","doi-asserted-by":"crossref","first-page":"387090","DOI":"10.1155\/2015\/387090","article-title":"Transcriptional Pathways Associated with Skeletal Muscle Changes after Spinal Cord Injury and Treadmill Locomotor Training","volume":"2015","author":"C Baligand","year":"2015","journal-title":"Biomed Res Int"},{"issue":"8","key":"pone.0347599.ref020","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s00018-022-04494-w","article-title":"NPC transplantation rescues sci-driven cAMP\/EPAC2 alterations, leading to neuroprotection and microglial modulation","volume":"79","author":"B Mart\u00ednez-Rojas","year":"2022","journal-title":"Cell Mol Life Sci"},{"key":"pone.0347599.ref021","doi-asserted-by":"crossref","first-page":"9921012","DOI":"10.1155\/2021\/9921012","article-title":"Identification of Macrophage Polarization-Related Genes as Biomarkers of Chronic Obstructive Pulmonary Disease Based on Bioinformatics Analyses","volume":"2021","author":"Y Zhao","year":"2021","journal-title":"Biomed Res Int"},{"issue":"4","key":"pone.0347599.ref022","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/kjm2.12651","article-title":"S100A9 promotes tumor-associated macrophage for M2 macrophage polarization to drive human liver cancer progression: An in vitro study","volume":"39","author":"L-F Yang","year":"2023","journal-title":"Kaohsiung J Med Sci"},{"issue":"7","key":"pone.0347599.ref023","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"ME Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"pone.0347599.ref024","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"T Wu","year":"2021","journal-title":"Innovation (Camb)"},{"issue":"2","key":"pone.0347599.ref025","doi-asserted-by":"crossref","first-page":"100077","DOI":"10.1016\/j.neumar.2025.100077","article-title":"Identification of novel biomarkers and immune characteristics of spinal cord injury based on comprehensive bioinformatic analysis: A retrospective observational study","volume":"2","author":"X Zha","year":"2025","journal-title":"NeuroMarkers"},{"issue":"3","key":"pone.0347599.ref026","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"T Wu","year":"2021","journal-title":"The innovation"},{"key":"pone.0347599.ref027","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: gene set variation analysis for microarray and RNA-seq data","volume":"14","author":"S H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"pone.0347599.ref028","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/978-1-60761-175-2_12","article-title":"Cytoscape: a community-based framework for network modeling","volume":"563","author":"S Killcoyne","year":"2009","journal-title":"Methods Mol Biol"},{"key":"pone.0347599.ref029","doi-asserted-by":"crossref","first-page":"1068359","DOI":"10.3389\/fimmu.2023.1068359","article-title":"Combination of single-cell and bulk RNA seq reveals the immune infiltration landscape and targeted therapeutic drugs in spinal cord injury","volume":"14","author":"Q Zhang","year":"2023","journal-title":"Front Immunol"},{"key":"pone.0347599.ref030","doi-asserted-by":"crossref","first-page":"1128545","DOI":"10.3389\/fnmol.2023.1128545","article-title":"Effects of a neurokinin-1 receptor antagonist in the acute phase after thoracic spinal cord injury in a rat model","volume":"16","author":"G Zheng","year":"2023","journal-title":"Front Mol Neurosci"},{"issue":"1","key":"pone.0347599.ref031","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s12974-022-02449-3","article-title":"SU16f inhibits fibrotic scar formation and facilitates axon regeneration and locomotor function recovery after spinal cord injury by blocking the PDGFR\u03b2 pathway","volume":"19","author":"Z Li","year":"2022","journal-title":"J Neuroinflammation"},{"key":"pone.0347599.ref032","doi-asserted-by":"crossref","first-page":"5674921","DOI":"10.1155\/2020\/5674921","article-title":"Three Growth Factors Induce Proliferation and Differentiation of Neural Precursor Cells In Vitro and Support Cell-Transplantation after Spinal Cord Injury In Vivo","volume":"2020","author":"A Younsi","year":"2020","journal-title":"Stem Cells Int"},{"issue":"4","key":"pone.0347599.ref033","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"KJ Livak","year":"2001","journal-title":"Methods"},{"issue":"2","key":"pone.0347599.ref034","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/s41593-019-0566-1","article-title":"Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain","volume":"23","author":"J Marschallinger","year":"2020","journal-title":"Nat Neurosci"},{"issue":"7","key":"pone.0347599.ref035","doi-asserted-by":"crossref","first-page":"4197","DOI":"10.1007\/s11010-025-05246-7","article-title":"Macrophage polarization-related gene SOAT1 is involved in inflammatory response and functional recovery after spinal cord injury","volume":"480","author":"P Peng","year":"2025","journal-title":"Mol Cell Biochem"},{"issue":"17","key":"pone.0347599.ref036","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1182\/blood-2017-10-811851","article-title":"Myosin 1f is specifically required for neutrophil migration in 3D environments during acute inflammation","volume":"131","author":"M Salvermoser","year":"2018","journal-title":"Blood"},{"issue":"10","key":"pone.0347599.ref037","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1038\/s41419-021-03983-3","article-title":"Myosin 1f-mediated activation of microglia contributes to the photoreceptor degeneration in a mouse model of retinal detachment","volume":"12","author":"Y Wang","year":"2021","journal-title":"Cell Death Dis"},{"issue":"3","key":"pone.0347599.ref038","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2022.110695","article-title":"Oncogenic Vav1-Myo1f induces therapeutically targetable macrophage-rich tumor microenvironment in peripheral T cell lymphoma","volume":"39","author":"JR Cortes","year":"2022","journal-title":"Cell Rep"},{"issue":"1","key":"pone.0347599.ref039","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/s41536-023-00306-2","article-title":"DNA methyltransferase 1 deficiency improves macrophage motility and wound healing by ameliorating cholesterol accumulation","volume":"8","author":"C Zhao","year":"2023","journal-title":"NPJ Regen Med"},{"key":"pone.0347599.ref040","doi-asserted-by":"crossref","first-page":"3118","DOI":"10.3389\/fimmu.2018.03118","article-title":"Myosin 1F Regulates M1-Polarization by Stimulating Intercellular Adhesion in Macrophages","volume":"9","author":"ZL Piedra-Quintero","year":"2019","journal-title":"Front Immunol"},{"issue":"1","key":"pone.0347599.ref041","doi-asserted-by":"crossref","first-page":"15","DOI":"10.4014\/jmb.2104.04027","article-title":"A Newly Synthesized Flavone from Luteolin Escapes from COMT-Catalyzed Methylation and Inhibits Lipopolysaccharide-Induced Inflammation in RAW264.7 Macrophages via JNK, p38 and NF-\u03baB Signaling Pathways","volume":"32","author":"L Ye","year":"2022","journal-title":"J Microbiol Biotechnol"},{"issue":"1","key":"pone.0347599.ref042","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1186\/s12967-022-03662-7","article-title":"Genetic and epigenetic regulation of Catechol-O-methyltransferase in relation to inflammation in chronic fatigue syndrome and Fibromyalgia","volume":"20","author":"A Polli","year":"2022","journal-title":"J Transl Med"},{"issue":"12","key":"pone.0347599.ref043","article-title":"Acupuncture Resolves Persistent Pain and Neuroinflammation in a Mouse Model of Chronic Overlapping Pain Conditions","volume":"19","author":"S Kim","year":"2018","journal-title":"J Pain"},{"issue":"5","key":"pone.0347599.ref044","doi-asserted-by":"crossref","DOI":"10.1097\/QAI.0000000000002083","article-title":"COMT Val158Met Polymorphism, Cardiometabolic Risk, and Nadir CD4 Synergistically Increase Risk of Neurocognitive Impairment in Men Living With HIV","volume":"81","author":"R Saloner","year":"2019","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"2","key":"pone.0347599.ref045","doi-asserted-by":"crossref","first-page":"9902","DOI":"10.1080\/21655979.2021.1969195","article-title":"MicroRNA miR-27b-3p regulate microglial inflammation response and cell apoptosis by inhibiting A20 (TNF-\u03b1-induced protein 3)","volume":"12","author":"L Li","year":"2021","journal-title":"Bioengineered"},{"key":"pone.0347599.ref046","doi-asserted-by":"crossref","first-page":"101459","DOI":"10.1016\/j.tice.2020.101459","article-title":"MicroRNA-211-5p attenuates spinal cord injury via targeting of activating transcription factor 6","volume":"68","author":"H Zhang","year":"2021","journal-title":"Tissue Cell"},{"issue":"1","key":"pone.0347599.ref047","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12929-023-00991-7","article-title":"Inactivation of pentraxin 3 suppresses M2-like macrophage activity and immunosuppression in colon cancer","volume":"31","author":"F-W Chen","year":"2024","journal-title":"J Biomed Sci"},{"issue":"1","key":"pone.0347599.ref048","doi-asserted-by":"crossref","first-page":"10926","DOI":"10.1038\/s41598-019-47461-5","article-title":"Deletion of NFKB1 enhances canonical NF-\u03baB signaling and increases macrophage and myofibroblast content during tendon healing","volume":"9","author":"KT Best","year":"2019","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0347599.ref049","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s00210-020-01958-3","article-title":"Effect of nifedipine, a calcium channel blocker, on the generation of nitric oxide and interleukin-1\u03b2 by murine macrophages activated by lipopolysaccharide from Prevotella intermedia","volume":"394","author":"S-H Choe","year":"2021","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"pone.0347599.ref050","first-page":"83","article-title":"Effects of dexamethasone on apoptosis-related cell death after spinal cord injury","volume":"96","author":"M Zurita","year":"2002","journal-title":"J Neurosurg"},{"key":"pone.0347599.ref051","doi-asserted-by":"crossref","first-page":"1190261","DOI":"10.3389\/fimmu.2023.1190261","article-title":"Dexamethasone impairs the expression of antimicrobial mediators in lipopolysaccharide-activated primary macrophages by inhibiting both expression and function of interferon \u03b2","volume":"14","author":"JD O\u2019Neil","year":"2023","journal-title":"Front Immunol"},{"key":"pone.0347599.ref052","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.bcp.2017.05.022","article-title":"Testosterone regulates 3T3-L1 pre-adipocyte differentiation and epididymal fat accumulation in mice through modulating macrophage polarization","volume":"140","author":"X Ren","year":"2017","journal-title":"Biochem Pharmacol"},{"issue":"6","key":"pone.0347599.ref053","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.3390\/ijms19061701","article-title":"Activity-Based Physical Rehabilitation with Adjuvant Testosterone to Promote Neuromuscular Recovery after Spinal Cord Injury","volume":"19","author":"DM Otzel","year":"2018","journal-title":"Int J Mol Sci"},{"issue":"6","key":"pone.0347599.ref054","doi-asserted-by":"crossref","first-page":"977","DOI":"10.4103\/1673-5374.184498","article-title":"Atorvastatin activates autophagy and promotes neurological function recovery after spinal cord injury","volume":"11","author":"S Gao","year":"2016","journal-title":"Neural Regen Res"},{"issue":"4","key":"pone.0347599.ref055","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/1755-5922.12193","article-title":"Atorvastatin attenuates sympathetic hyperinnervation together with the augmentation of M2 macrophages in rats postmyocardial infarction","volume":"34","author":"N Yang","year":"2016","journal-title":"Cardiovasc Ther"},{"issue":"1","key":"pone.0347599.ref056","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/s12974-017-0934-2","article-title":"Anti-inflammatory and immunomodulatory mechanisms of atorvastatin in a murine model of traumatic brain injury","volume":"14","author":"X Xu","year":"2017","journal-title":"J Neuroinflammation"},{"key":"pone.0347599.ref057","doi-asserted-by":"crossref","first-page":"102148","DOI":"10.1016\/j.jchemneu.2022.102148","article-title":"Neuroprotective effects of lovastatin against traumatic spinal cord injury in rats","volume":"125","author":"J Mirzaie","year":"2022","journal-title":"J Chem Neuroanat"},{"key":"pone.0347599.ref058","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1089\/neu.2021.0355","article-title":"Fluvoxamine Confers Neuroprotection via Inhibiting Infiltration of Peripheral Leukocytes and M1 Polarization of Microglia\/Macrophages in a Mouse Model of Traumatic Brain Injury","volume":"39","author":"M Shi","year":"2022","journal-title":"J Neurotrauma"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0347599","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T17:30:31Z","timestamp":1777915831000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0347599"}},"subtitle":[],"editor":[{"given":"Sawar","family":"Khan","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,5,4]]},"references-count":58,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0347599","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,4]]}}}