{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T19:54:11Z","timestamp":1784231651832,"version":"3.55.0"},"reference-count":49,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T00:00:00Z","timestamp":1703635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swedish Medical Research Council","award":["no. 2019-01052"],"award-info":[{"award-number":["no. 2019-01052"]}]},{"name":"Swedish Medical Research Council","award":["ALFGBG-723921"],"award-info":[{"award-number":["ALFGBG-723921"]}]},{"name":"Swedish Medical Research Council","award":["ALFGBG-965619"],"award-info":[{"award-number":["ALFGBG-965619"]}]},{"name":"Swedish Medical Research Council","award":["no. VGFOUREG-931919"],"award-info":[{"award-number":["no. 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VGFOUREG-940815"]}]},{"name":"Regional Executive Board, Region V\u00e4stra G\u00f6taland","award":["no. 2019-01052"],"award-info":[{"award-number":["no. 2019-01052"]}]},{"name":"Regional Executive Board, Region V\u00e4stra G\u00f6taland","award":["ALFGBG-723921"],"award-info":[{"award-number":["ALFGBG-723921"]}]},{"name":"Regional Executive Board, Region V\u00e4stra G\u00f6taland","award":["ALFGBG-965619"],"award-info":[{"award-number":["ALFGBG-965619"]}]},{"name":"Regional Executive Board, Region V\u00e4stra G\u00f6taland","award":["no. VGFOUREG-931919"],"award-info":[{"award-number":["no. VGFOUREG-931919"]}]},{"name":"Regional Executive Board, Region V\u00e4stra G\u00f6taland","award":["no. VGFOUREG-940815"],"award-info":[{"award-number":["no. VGFOUREG-940815"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Intestinal macrophages and fibroblasts act as microenvironmental sentinels mediating inflammation and disease progression in Crohn\u2019s disease (CD). We aimed to establish the effects of fecal supernatants (FSs) from patients with CD on macrophage and fibroblast phenotype and function. FS were obtained by ultracentrifugation, and the metabolites were analyzed. Monocyte-derived M2 macrophages and fibroblasts were conditioned with FS, and secreted proteins, surface proteins and gene expression were analyzed. M2 macrophage efferocytosis was evaluated. Patients with CD (n = 15) had a skewed fecal metabolite profile compared to healthy subjects (HS, n = 10). FS from CD patients (CD-FS) induced an anti-inflammatory response in M2 macrophages with higher expression of IL-10, IL1RA and CD206 as compared to healthy FS (HS-FS) while the efferocytotic capacity was unaltered. CD-FS did not affect extracellular matrix production from fibroblasts, but increased expression of the pro-inflammatory proteins IL-6 and MCP-1. Conditioned media from M2 macrophages treated with CD-FS modulated gene expression in fibroblasts for TGF\u03b2 superfamily members and reduced IL-4 expression compared to HS-FS. We show that M2 macrophages and fibroblasts react abnormally to the fecal microenvironment of CD patients, resulting in altered protein expression related to inflammation but not fibrosis. This implies that the gut microbiota and its metabolites have an important role in the generation and\/or perpetuation of inflammation in CD.<\/jats:p>","DOI":"10.3390\/cells13010060","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T10:23:54Z","timestamp":1703672634000},"page":"60","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Fecal Supernatants from Patients with Crohn\u2019s Disease Induce Inflammatory Alterations in M2 Macrophages and Fibroblasts"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3548-4618","authenticated-orcid":false,"given":"Frida","family":"Gorreja","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia","family":"Bendix","sequence":"additional","affiliation":[{"name":"Medical Department, Randers Regional Hospital, 8930 Randers, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen T. A.","family":"Rush","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2944-5700","authenticated-orcid":false,"given":"Lujain","family":"Maasfeh","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otto","family":"Savolainen","sequence":"additional","affiliation":[{"name":"Chalmers Mass Spectrometry Infrastructure, Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Dige","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Aarhus University Hospital, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorgen","family":"Agnholt","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Aarhus University Hospital, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8142-2106","authenticated-orcid":false,"given":"Lena","family":"\u00d6hman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8888-4968","authenticated-orcid":false,"given":"Maria K.","family":"Magnusson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1136\/gutjnl-2017-315568","article-title":"Natural disease course of Crohn\u2019s disease during the first 5 years after diagnosis in a European population-based inception cohort: An Epi-IBD study","volume":"68","author":"Burisch","year":"2019","journal-title":"Gut"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1093\/ecco-jcc\/jjaa227","article-title":"Metabolomic Analysis in Inflammatory Bowel Disease: A Systematic Review","volume":"15","author":"Gallagher","year":"2021","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1136\/gutjnl-2016-313235","article-title":"A microbial signature for Crohn\u2019s disease","volume":"66","author":"Pascal","year":"2017","journal-title":"Gut"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/s41586-019-1237-9","article-title":"Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases","volume":"569","author":"Arze","year":"2019","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1093\/ecco-jcc\/jjz049","article-title":"Faecal Microbiota Dynamics and their Relation to Disease Course in Crohn\u2019s Disease","volume":"13","author":"Galazzo","year":"2019","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Str\u00f6mbeck, A., Lasson, A., Strid, H., Sundin, J., Stotzer, P.-O., Simr\u00e9n, M., Magnusson, M.K., and \u00d6hman, L. (2020). Fecal microbiota composition is linked to the postoperative disease course in patients with Crohn\u2019s disease. BMC Gastroenterol., 20.","DOI":"10.1186\/s12876-020-01281-4"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1111\/imm.12930","article-title":"Immune regulation by microbiome metabolites","volume":"154","author":"Kim","year":"2018","journal-title":"Immunology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1007\/s10753-022-01647-8","article-title":"MEFV and NLRP3 Inflammasome Expression Is Attributed to Immature Macrophages and Correlates with Serum Inflammatory Proteins in Crohn\u00b4s Disease Patients","volume":"45","author":"Gorreja","year":"2022","journal-title":"Inflammation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/s41385-018-0126-0","article-title":"Two distinct colonic CD14+ subsets characterized by single-cell RNA profiling in Crohn\u2019s disease","volume":"12","author":"Chapuy","year":"2019","journal-title":"Mucosal Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1093\/ibd\/izab029","article-title":"Human Intestinal Macrophages Are Involved in the Pathology of Both Ulcerative Colitis and Crohn Disease","volume":"27","author":"Dharmasiri","year":"2021","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/s41575-019-0172-4","article-title":"Macrophages in intestinal inflammation and resolution: A potential therapeutic target in IBD","volume":"16","author":"Na","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/nature08296","article-title":"Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance","volume":"461","author":"Elliott","year":"2009","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3389\/fmed.2020.00167","article-title":"Pathology of Fibrosis in Crohn\u2019s Disease\u2014Contribution to Understanding Its Pathogenesis","volume":"7","author":"Zidar","year":"2020","journal-title":"Front. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/s41385-019-0146-4","article-title":"Induction of autophagy in Cx3cr1+ mononuclear cells limits IL-23\/IL-22 axis-mediated intestinal fibrosis","volume":"12","author":"Mathur","year":"2019","journal-title":"Mucosal Immunol."},{"key":"ref_15","first-page":"631","article-title":"Interleukin (IL)-4 and IL-17 synergistically stimulate IL-6 secretion in human colonic myofibroblasts","volume":"10","author":"Andoh","year":"2002","journal-title":"Int. J. Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1038\/s41591-021-01520-5","article-title":"IL-1-driven stromal\u2013neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies","volume":"27","author":"Friedrich","year":"2021","journal-title":"Nat. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1097\/00054725-200102000-00003","article-title":"Inflammation location, but not type, determines the increase in TGF-beta1 and IGF-1 expression and collagen deposition in IBD intestine","volume":"7","author":"Lawrance","year":"2001","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Bendix, M., Dige, A., J\u00f8rgensen, S.P., Dahlerup, J.F., Bibby, B.M., Deleuran, B., and Agnholt, J. (2020). Decrease in Mucosal IL17A, IFN\u03b3 and IL10 Expressions in Active Crohn\u2019s Disease Patients Treated with High-Dose Vitamin D Alone or Combined with Infliximab. Nutrients, 12.","DOI":"10.3390\/nu12123699"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1007\/s00394-017-1531-y","article-title":"High-dose vitamin D3 supplementation decreases the number of colonic CD103+ dendritic cells in healthy subjects","volume":"57","author":"Bak","year":"2018","journal-title":"Eur. J. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/j.jcmgh.2021.06.004","article-title":"Impaired Luminal Control of Intestinal Macrophage Maturation in Patients With Ulcerative Colitis During Remission","volume":"12","author":"Maasfeh","year":"2021","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1021\/acs.jproteome.5b00790","article-title":"A Simultaneous Metabolic Profiling and Quantitative Multimetabolite Metabolomic Method for Human Plasma Using Gas-Chromatography Tandem Mass Spectrometry","volume":"15","author":"Savolainen","year":"2016","journal-title":"J. Proteome Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8086","DOI":"10.1021\/ac051211v","article-title":"Extraction and GC\/MS analysis of the human blood plasma metabolome","volume":"77","author":"Jiye","year":"2005","journal-title":"Anal. Chem."},{"key":"ref_23","unstructured":"R Core Team (2022). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: https:\/\/www.R-project.org\/."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1038\/s41596-022-00710-w","article-title":"Using MetaboAnalyst 5.0 for LC\u2013HRMS spectra processing, multi-omics integration and covariate adjustment of global metabolomics data","volume":"17","author":"Pang","year":"2022","journal-title":"Nat. Protoc."},{"key":"ref_25","unstructured":"Lenth, R. (2023, September 12). Emmeans: Estimated Marginal Means, Aka Least-Squares Means. R Package Version 1.4.1. Available online: https:\/\/CRAN.R-project.org\/package=emmeans."},{"key":"ref_26","unstructured":"Vu, V.Q. (2023, September 12). Ggbiplot: A Ggplot2 Based Biplot. R Package Version 0.55. Available online: http:\/\/github.com\/vqv\/ggbiplot."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1097\/MIB.0000000000000081","article-title":"Impaired innate immune function associated with fecal supernatant from crohn\u2019s disease patients","volume":"20","author":"Meelu","year":"2014","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11306-017-1311-y","article-title":"Alterations in Lipid, Amino Acid, and Energy Metabolism Distinguish Crohn\u2019s Disease from Ulcerative Colitis and Control Subjects by Serum Metabolomic Profiling","volume":"14","author":"Scoville","year":"2018","journal-title":"Metabolomics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1054\/clnu.2001.0469","article-title":"Effect of L-arginine on the course of experimental colitis","volume":"20","author":"Ojanguren","year":"2001","journal-title":"Clin. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1093\/nutrit\/nuac070","article-title":"Arginine metabolism regulates the pathogenesis of inflammatory bowel disease","volume":"81","author":"Li","year":"2023","journal-title":"Nutr. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.immuni.2010.05.007","article-title":"Alternative activation of macrophages: Mechanism and functions","volume":"32","author":"Gordon","year":"2010","journal-title":"Immunity"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.humimm.2018.03.006","article-title":"HLA-G is expressed in intestinal samples of ulcerative colitis and Crohn\u2019s disease patients and HLA-G5 expression is differentially correlated with TNF and IL-10 cytokine expression","volume":"79","author":"Gomes","year":"2018","journal-title":"Hum. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3510","DOI":"10.1172\/JCI90229","article-title":"Macrophage-derived IL-10 mediates mucosal repair by epithelial WISP-1 signaling","volume":"127","author":"Quiros","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"19616","DOI":"10.1038\/s41598-021-98611-7","article-title":"The mannose receptor (CD206) identifies a population of colonic macrophages in health and inflammatory bowel disease","volume":"11","author":"Wright","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1038\/s41385-018-0030-7","article-title":"Human intestinal pro-inflammatory CD11chighCCR2+CX3CR1+ macrophages, but not their tolerogenic CD11c\u2212CCR2\u2212CX3CR1\u2212 counterparts, are expanded in inflammatory bowel disease","volume":"11","author":"Bernardo","year":"2018","journal-title":"Mucosal Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1038\/ni.3796","article-title":"\u03b1-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming","volume":"18","author":"Liu","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1096\/fj.08-121228","article-title":"Macrophage phagocytosis of apoptotic neutrophils is critically regulated by the opposing actions of pro-inflammatory and anti-inflammatory agents: Key role for TNF-\u03b1","volume":"23","author":"Michlewska","year":"2009","journal-title":"FASEB J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1084\/jem.20060370","article-title":"Oxidized phosphatidylserine\u2013CD36 interactions play an essential role in macrophage-dependent phagocytosis of apoptotic cells","volume":"203","author":"Greenberg","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1016\/j.cell.2019.08.008","article-title":"Single-Cell Analysis of Crohn\u2019s Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy","volume":"178","author":"Martin","year":"2019","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1002\/ibd.21552","article-title":"Oxidative state and IL-6 production in intestinal myofibroblasts of Crohn\u2019s disease patients","volume":"17","author":"Catarzi","year":"2011","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1038\/ni1496","article-title":"Interleukins 1\u03b2 and 6 but not transforming growth factor-\u03b2 are essential for the differentiation of interleukin 17\u2013producing human T helper cells","volume":"8","author":"Napolitani","year":"2007","journal-title":"Nat. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1093\/ibd\/izx008","article-title":"Inhibition of Fibroblast Activation Protein Restores a Balanced Extracellular Matrix and Reduces Fibrosis in Crohn\u2019s Disease Strictures Ex Vivo","volume":"24","author":"Truffi","year":"2018","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40169-015-0046-5","article-title":"Hallmarks of epithelial to mesenchymal transition are detectable in Crohn\u2019s disease associated intestinal fibrosis","volume":"4","author":"Scharl","year":"2015","journal-title":"Clin. Transl. Med."},{"key":"ref_44","first-page":"e87680","article-title":"Heterogeneous fibroblasts underlie age-dependent tertiary lymphoid tissues in the kidney","volume":"1","author":"Sato","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_45","first-page":"e125326","article-title":"PD-L1 on invasive fibroblasts drives fibrosis in a humanized model of idiopathic pulmonary fibrosis","volume":"4","author":"Geng","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.micpath.2018.05.009","article-title":"Fecal bacteria from Crohn\u2019s disease patients more potently activated NOD-like receptors and Toll-like receptors in macrophages, in an IL-4-repressible fashion","volume":"121","author":"Gu","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.yexcr.2017.10.011","article-title":"Fecal bacteria from treatment-naive Crohn\u2019s disease patients can skew helper T cell responses","volume":"361","author":"Ma","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Holst, L.M., Iribarren, C., Sapnara, M., Savolainen, O., T\u00f6rnblom, H., Wettergren, Y., Strid, H., Simr\u00e9n, M., Magnusson, M.K., and \u00d6hman, L. (2022). Fecal Luminal Factors from Patients with Gastrointestinal Diseases Alter Gene Expression Profiles in Caco-2 Cells and Colonoids. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415505"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1093\/ecco-jcc\/jjab022","article-title":"TREM-1+ Macrophages Define a Pathogenic Cell Subset in the Intestine of Crohn\u2019s Disease Patients","volume":"15","author":"Gorreja","year":"2021","journal-title":"J. Crohn\u2019s Colitis"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/1\/60\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:42:56Z","timestamp":1760132576000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/1\/60"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,27]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["cells13010060"],"URL":"https:\/\/doi.org\/10.3390\/cells13010060","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,27]]}}}