{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:03:30Z","timestamp":1789193010033,"version":"build-2803163510"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"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>Background<\/jats:title>\n                    <jats:p>Psoriasis is a common autoimmune skin disease with high morbidity and associated complications, characterized by epidermal hyperplasia and cutaneous infiltration of immune cells. The role of S100A4, a key antimicrobial peptide, is highly expressed in psoriatic skin and has aroused considerable interest in recent years, yet its specific function and associated molecular mechanisms remain elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using CRISPR\/Cas9 to generate S100a4 gene knockout mice, imiquimod was continuously applied to the back skin to induce the psoriasis disease model. Single-cell RNA sequencing (scRNA-seq) was employed to investigate changes in epidermal cell composition and gene expression profiles in mice subjected to different treatments. Multiple bioinformatics analyses were conducted to elucidate the biological role of S100A4 in psoriasis pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We observed that S100a4 knockout mice exhibited significant pathological improvement in psoriasis-like lesions, including reduced inflammatory cell infiltration and decreased epidermal hyperplasia. The results of scRNA-seq revealed that after S100a4 knockout, the pathologically relevant keratinocyte subpopulation was significantly reduced, and the related tumor necrosis factor (TNF) and interleukin-17 (IL-17) signal transducers and activator of keratinization were downregulated. Moreover, S100a4 depletion moderated the abnormal proliferation and differentiation dynamics of keratinocytes. Additionally, Klf9-mediated transcriptional dysregulation of Krt15 in keratinocytes was identified as a key driver of hyperkeratosis, while S100a4 deficiency contributed to restoring cellular homeostasis in this process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings suggest a potential pathogenic role for S100A4 in psoriasis and highlight previously uncharacterized cell-specific transcriptional landscapes and regulatory mechanisms. Our results provide novel insights into the complex pathology of psoriasis and could offer important clues for the development of new targeted therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1744860","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T06:46:30Z","timestamp":1769150790000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Single-cell transcriptomics reveals keratinocyte dynamic processes associated with S100a4 expression in psoriasiform dermatitis"],"prefix":"10.3389","volume":"16","author":[{"given":"Huiqin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Dermatology and Venereology, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]},{"name":"Xinjiang Clinical Research Center for Dermatology and Venereology","place":["Urumqi, China"]},{"name":"Xinjiang Key Laboratory of Dermatology Research","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]},{"name":"Xinjiang Clinical Research Center for Dermatology and Venereology","place":["Urumqi, China"]},{"name":"Xinjiang Key Laboratory of Dermatology Research","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]},{"name":"Xinjiang Clinical Research Center for Dermatology and Venereology","place":["Urumqi, China"]},{"name":"Xinjiang Key Laboratory of Dermatology Research","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]},{"name":"Xinjiang Clinical Research Center for Dermatology and Venereology","place":["Urumqi, China"]},{"name":"Xinjiang Key Laboratory of Dermatology Research","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dezhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]},{"name":"Xinjiang Clinical Research Center for Dermatology and Venereology","place":["Urumqi, China"]},{"name":"Xinjiang Key Laboratory of Dermatology Research","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenqun","family":"Weng","sequence":"additional","affiliation":[{"name":"Teaching Department, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caying","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]},{"name":"Xinjiang Clinical Research Center for Dermatology and Venereology","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenrui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]},{"name":"Teaching Department, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]},{"name":"Teaching Department, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]},{"name":"Xinjiang Key Laboratory of Dermatology Research","place":["Urumqi, China"]},{"name":"Teaching Department, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32549-6","article-title":"Psoriasis","volume":"397","author":"Griffiths","year":"2021","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.7861\/clinmed.2021-0257","article-title":"Psoriasis: a brief overview","volume":"21","author":"Raharja","year":"2021","journal-title":"Clin Med (Lond)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.4006","article-title":"Pathophysiology, clinical presentation, and treatment of psoriasis: A review","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20061475","article-title":"Psoriasis pathogenesis and treatment","volume":"20","author":"Rendon","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207488","article-title":"New treatment addressing the pathogenesis of psoriasis","volume":"21","author":"Tokuyama","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241713313","article-title":"Challenges and future trends in the treatment of psoriasis","volume":"24","author":"Lee","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2022.102916","article-title":"Pathogenesis, multi-omics research, and clinical treatment of psoriasis","volume":"133","author":"Yu","year":"2022","journal-title":"J Autoimmun"},{"key":"B8","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/s41419-022-04523-3","article-title":"Advances in the pathogenesis of psoriasis: from keratinocyte perspective","volume":"13","author":"Zhou","year":"2022","journal-title":"Cell Death Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26020749","article-title":"Understanding the intricate pathophysiology of psoriasis and related skin disorders","volume":"26","author":"Orzan","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18122526","article-title":"The genetic basis of psoriasis","volume":"18","author":"Capon","year":"2017","journal-title":"Int J Mol Sci"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/jpm14050535","article-title":"Review: A contemporary, multifaced insight into psoriasis pathogenesis","volume":"14","author":"Dascalu","year":"2024","journal-title":"J Pers Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1191645","article-title":"Pathogenic role of S100 proteins in psoriasis","volume":"14","author":"Liang","year":"2023","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2009.206","article-title":"Significance of the S100A4 protein in psoriasis","volume":"130","author":"Zibert","year":"2010","journal-title":"J Invest Dermatol"},{"key":"B14","article-title":"Localization of S100A2, S100A4, S100A6, S100A7, and S100P in the human hair follicle","volume":"105","author":"Mitoma","year":"2014","journal-title":"Fukuoka Igaku Zasshi"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-9030-6_22","article-title":"The multifaceted S100A4 protein in cancer and inflammation","volume":"1929","author":"Ambartsumian","year":"2019","journal-title":"Methods Mol Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R500017200","article-title":"S100A4, a mediator of metastasis","volume":"281","author":"Garrett","year":"2006","journal-title":"J Biol Chem"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-007-0301-3","article-title":"S100A4: a common mediator of epithelial-mesenchymal transition, fibrosis and regeneration in diseases","volume":"86","author":"Schneider","year":"2008","journal-title":"J Mol Med (Berl)"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.matbio.2024.01.002","article-title":"S100A4 a classical DAMP as a therapeutic target in fibrosis","volume":"127","author":"O'Reilly","year":"2024","journal-title":"Matrix Biol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15259","article-title":"Extracellular S100A4 as a key player in fibrotic diseases","volume":"24","author":"Li","year":"2020","journal-title":"J Cell Mol Med"},{"key":"B20","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s13578-017-0191-1","article-title":"Role of metastasis-induced protein S100A4 in human non-tumor pathophysiologies","volume":"7","author":"Fei","year":"2017","journal-title":"Cell Biosci"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e09-07-0609","article-title":"S100A4 regulates macrophage chemotaxis","volume":"21","author":"Li","year":"2010","journal-title":"Mol Biol Cell"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1525567","article-title":"The multi-faceted immune modulatory role of S100A4 in cancer and chronic inflammatory disease","volume":"16","author":"Wong","year":"2025","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/s41584-024-01080-1","article-title":"S100A4 inhibition targets fibrosis in SSc","volume":"20","author":"McHugh","year":"2024","journal-title":"Nat Rev Rheumatol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2024.110242","article-title":"Single-cell technologies in psoriasis","volume":"264","author":"Cui","year":"2024","journal-title":"Clin Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000001085","article-title":"Understanding psoriatic disease at single-cell resolution: an update","volume":"37","author":"Do","year":"2025","journal-title":"Curr Opin Rheumatol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.7150\/thno.45614","article-title":"Single-cell RNA-Seq reveals the transcriptional landscape and heterogeneity of skin macrophages in Vsir(-\/-) murine psoriasis","volume":"10","author":"Qie","year":"2020","journal-title":"Theranostics"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2978","DOI":"10.1016\/j.jid.2022.04.014","article-title":"CHRNA5 is overexpressed in patients with psoriasis and promotes psoriasis-like inflammation in mouse models","volume":"142","author":"Wang","year":"2022","journal-title":"J Invest Dermatol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat Biotechnol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0","article-title":"Fast, sensitive and accurate integration of single-cell data with Harmony","volume":"16","author":"Korsunsky","year":"2019","journal-title":"Nat Methods"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1038\/s41467-022-28803-w","article-title":"Fully-automated and ultra-fast cell-type identification using specific marker combinations from single-cell transcriptomic data","volume":"13","author":"Ianevski","year":"2022","journal-title":"Nat Commun"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4402","article-title":"Reversed graph embedding resolves complex single-cell trajectories","volume":"14","author":"Qiu","year":"2017","journal-title":"Nat Methods"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4463","article-title":"SCENIC: single-cell regulatory network inference and clustering","volume":"14","author":"Aibar","year":"2017","journal-title":"Nat Methods"},{"key":"B34","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1016\/j.celrep.2018.10.045","article-title":"Revealing the critical regulators of cell identity in the mouse cell atlas","volume":"25","author":"Suo","year":"2018","journal-title":"Cell Rep"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and analysis of cell-cell communication using CellChat","volume":"12","author":"Jin","year":"2021","journal-title":"Nat Commun"},{"key":"B38","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.cels.2016.08.010","article-title":"Single-cell transcriptomics reveals that differentiation and spatial signatures shape epidermal and hair follicle heterogeneity","volume":"3","author":"Joost","year":"2016","journal-title":"Cell Syst"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.890624","article-title":"ILF2 contributes to hyperproliferation of keratinocytes and skin inflammation in a KLHDC7B-DT-dependent manner in psoriasis","volume":"13","author":"Yin","year":"2022","journal-title":"Front Genet"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e0316134","DOI":"10.1371\/journal.pone.0316134","article-title":"The involvement of Elf5 in regulating keratinocyte proliferation and differentiation processes in skin","volume":"20","author":"Hu","year":"2025","journal-title":"PloS One"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106689","article-title":"Hypoxia-inducible factor-1: A potential pharmacological target to manage psoriasis","volume":"86","author":"Zhu","year":"2020","journal-title":"Int Immunopharmacol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1118641109","article-title":"Kruppel-like factor 9 is a circadian transcription factor in human epidermis that controls proliferation of keratinocytes","volume":"109","author":"Sporl","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.22.6762","article-title":"The DBP gene is expressed according to a circadian rhythm in the suprachiasmatic nucleus and influences circadian behavior","volume":"16","author":"Lopez-Molina","year":"1997","journal-title":"EMBO J"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2021.06.019","article-title":"Mouse models of psoriasis: A comprehensive review","volume":"142","author":"Gangwar","year":"2022","journal-title":"J Invest Dermatol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111574","article-title":"Current concepts of psoriasis immunopathogenesis","volume":"22","author":"Vicic","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.2174\/1389202923666220527111037","article-title":"Etiopathogenesis of psoriasis from genetic perspective: an updated review","volume":"23","author":"Babaie","year":"2022","journal-title":"Curr Genomics"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.17023.1","article-title":"Tumour necrosis factor signalling in health and disease","volume":"8","author":"Holbrook","year":"2019","journal-title":"F1000Res"},{"key":"B48","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/s41419-024-06559-z","article-title":"Cellular heterogeneity in TNF\/TNFR1 signalling: live cell imaging of cell fate decisions in single cells","volume":"15","author":"Preedy","year":"2024","journal-title":"Cell Death Dis"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M004973200","article-title":"Opposite functions for E2F1 and E2F4 in human epidermal keratinocyte differentiation","volume":"275","author":"Paramio","year":"2000","journal-title":"J Biol Chem"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16272","article-title":"Hmga2 translocation induced in skin tumorigenesis","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"B51","article-title":"Ubiquitin\/proteasome pathway regulates levels of retinoic acid receptor gamma and retinoid X receptor alpha in human keratinocytes","volume":"60","author":"Boudjelal","year":"2000","journal-title":"Cancer Res"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2009.48","article-title":"Differential expression of stem-cell-associated markers in human hair follicle epithelial cells","volume":"89","author":"Inoue","year":"2009","journal-title":"Lab Invest"},{"key":"B53","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1186\/s12985-024-02514-8","article-title":"Upregulation of keratin 15 is required for varicella-zoster virus replication in keratinocytes and is attenuated in the live attenuated vOka vaccine strain","volume":"21","author":"Tommasi","year":"2024","journal-title":"Virol J"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3390\/ijms141019385","article-title":"Keratin k15 as a biomarker of epidermal stem cells","volume":"14","author":"Bose","year":"2013","journal-title":"Int J Mol Sci"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703623200","article-title":"Connexin levels regulate keratinocyte differentiation in the epidermis","volume":"282","author":"Langlois","year":"2007","journal-title":"J Biol Chem"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3892\/br.2017.903","article-title":"Connexin 43: Key roles in the skin","volume":"6","author":"Zhang","year":"2017","journal-title":"BioMed Rep"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22116060","article-title":"Dysregulation of connexin expression plays a pivotal role in psoriasis","volume":"22","author":"O'Shaughnessy","year":"2021","journal-title":"Int J Mol Sci"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1744860\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T06:46:31Z","timestamp":1769150791000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1744860\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,23]]},"references-count":57,"alternative-id":["10.3389\/fimmu.2025.1744860"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1744860","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,23]]},"article-number":"1744860"}}