{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:03:20Z","timestamp":1788926600784,"version":"build-2803163510"},"reference-count":55,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T00:00:00Z","timestamp":1671062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Singapore Ministry of Health\u2019s National Medical Research Council","award":["NMRC-OFYIRG16may012 and NMRC\/CG\/M003\/2017"],"award-info":[{"award-number":["NMRC-OFYIRG16may012 and NMRC\/CG\/M003\/2017"]}]},{"name":"Singapore Ministry of Health\u2019s National Medical Research Council","award":["NMRC\/MOH-000596-00 and NMRC\/CSA-SI-008-2016"],"award-info":[{"award-number":["NMRC\/MOH-000596-00 and NMRC\/CSA-SI-008-2016"]}]},{"name":"National Medical Research Council, Ministry of Health, Singapore","award":["NMRC-OFYIRG16may012 and NMRC\/CG\/M003\/2017"],"award-info":[{"award-number":["NMRC-OFYIRG16may012 and NMRC\/CG\/M003\/2017"]}]},{"name":"National Medical Research Council, Ministry of Health, Singapore","award":["NMRC\/MOH-000596-00 and NMRC\/CSA-SI-008-2016"],"award-info":[{"award-number":["NMRC\/MOH-000596-00 and NMRC\/CSA-SI-008-2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The retrograde flow of endometrial tissues deposited into the peritoneal cavity occurs in women during menstruation. Classically (M1) or alternatively (M2) activated macrophages partake in the removal of regurgitated menstrual tissue. The failure of macrophage egress from the peritoneal cavity through the mesothelium leads to chronic inflammation in endometriosis. To study the migration differences of macrophage phenotypes across mesothelial cells, an in vitro model of macrophage egress across a peritoneal mesothelial cell monolayer membrane was developed. M1 macrophages were more sessile, emigrating 2.9-fold less than M2 macrophages. The M1 macrophages displayed a pro-inflammatory cytokine signature, including IL-1\u03b1, IL-1\u03b2, TNF-\u03b1, TNF-\u03b2, and IL-12p70. Mass spectrometry sphingolipidomics revealed decreased levels of ceramide-1-phosphate (C1P), an inducer of migration in M1 macrophages, which correlated with its poor migration behavior. C1P is generated by ceramide kinase (CERK) from ceramide, and blocking C1P synthesis via the action of NVP231, a specific CERK chemical inhibitor, prohibited the emigration of M1 and M2 macrophages up to 6.7-fold. Incubation with exogenously added C1P rescued this effect. These results suggest that M1 macrophages are less mobile and have higher retention in the peritoneum due to lower C1P levels, which contributes to an altered peritoneal environment in endometriosis by generating a predominant pro-inflammatory cytokine environment.<\/jats:p>","DOI":"10.3390\/ijms232415977","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T01:46:51Z","timestamp":1671155211000},"page":"15977","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Decreased Innate Migration of Pro-Inflammatory M1 Macrophages through the Mesothelial Membrane Is Affected by Ceramide Kinase and Ceramide 1-P"],"prefix":"10.3390","volume":"23","author":[{"given":"Chee Wai","family":"Ku","sequence":"first","affiliation":[{"name":"Department of Reproductive Medicine, KK Women\u2019s and Children\u2019s Hospital, Singapore 229899, Singapore"},{"name":"Obstetrics and Gynaecology Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Yang","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynaecology Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"KK Research Centre, Singapore 229899, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Ying","family":"Tan","sequence":"additional","affiliation":[{"name":"Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry Kok Yen","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, KK Women\u2019s and Children\u2019s Hospital, Singapore 229899, Singapore"},{"name":"Obstetrics and Gynaecology Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yie Hou","family":"Lee","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynaecology Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"KK Research Centre, Singapore 229899, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3109\/01902149609074020","article-title":"Pleural Macrophages Differentially Alter Pleural Mesothelial Cell Glycosaminoglycan Production","volume":"22","author":"Baumann","year":"1996","journal-title":"Exp. Lung Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e180594","DOI":"10.1155\/2011\/180594","article-title":"Pathophysiology of the Peritoneal Membrane during Peritoneal Dialysis: The Role of Hyaluronan","volume":"2011","author":"Yung","year":"2011","journal-title":"BioMed Res. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1038\/ncomms2877","article-title":"Distinct Bone Marrow-Derived and Tissue-Resident Macrophage Lineages Proliferate at Key Stages during Inflammation","volume":"4","author":"Davies","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1530\/jrf.0.0820707","article-title":"Functional Aspects of Peritoneal Macrophages in Endometriosis of Women","volume":"82","author":"Dunselman","year":"1988","journal-title":"J. Reprod. Fertil."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1084\/jem.20011794","article-title":"Adhesion Molecule\u2013Dependent Mechanisms Regulate the Rate of Macrophage Clearance During the Resolution of Peritoneal Inflammation","volume":"196","author":"Bellingan","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3234","DOI":"10.1182\/blood-2005-03-1288","article-title":"A Specific Role of Integrin Mac-1 in Accelerated Macrophage Efflux to the Lymphatics","volume":"106","author":"Cao","year":"2005","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1126\/science.aam7928","article-title":"Inflammation and Metabolism in Tissue Repair and Regeneration","volume":"356","author":"Eming","year":"2017","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e2013776118","DOI":"10.1073\/pnas.2013776118","article-title":"Macrophages Inhibit and Enhance Endometriosis Depending on Their Origin","volume":"118","author":"Hogg","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1093\/humupd\/dmt024","article-title":"The Role of the Peritoneum in the Pathogenesis of Endometriosis","volume":"19","author":"Young","year":"2013","journal-title":"Hum. Reprod. Update"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ram\u00edrez-Pavez, T.N., Mart\u00ednez-Esparza, M., Ruiz-Alcaraz, A.J., Mar\u00edn-S\u00e1nchez, P., Machado-Linde, F., and Garc\u00eda-Pe\u00f1arrubia, P. (2021). The Role of Peritoneal Macrophages in Endometriosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910792"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.fertnstert.2012.06.029","article-title":"Pathogenesis and Pathophysiology of Endometriosis","volume":"98","author":"Burney","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.bbalip.2017.10.002","article-title":"Long-Chain Glucosylceramides Crosstalk with LYN Mediates Endometrial Cell Migration","volume":"1863","author":"Wimalachandra","year":"2018","journal-title":"Biochim. Et Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"26117","DOI":"10.1038\/srep26117","article-title":"Limited Value of Pro-Inflammatory Oxylipins and Cytokines as Circulating Biomarkers in Endometriosis\u2014A Targeted \u2018omics Study","volume":"6","author":"Lee","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_14","first-page":"349","article-title":"Endometriosis Still a Challenge","volume":"7","author":"Mehedintu","year":"2014","journal-title":"J. Med. Life"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1111\/jog.13938","article-title":"Eutopic Endometrium from Patients with Endometriosis Modulates the Expression of CD36 and SIRP-\u03b1 in Peritoneal Macrophages","volume":"45","author":"Xie","year":"2019","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zhou, J., Chern, B.S.M., Barton-Smith, P., Phoon, J.W.L., Tan, T.Y., Viardot-Foucault, V., Ku, C.W., Tan, H.H., Chan, J.K.Y., and Lee, Y.H. (2020). Peritoneal Fluid Cytokines Reveal New Insights of Endometriosis Subphenotypes. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103515"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3389\/fimmu.2013.00009","article-title":"Endometriosis, a Disease of the Macrophage","volume":"4","author":"Capobianco","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"817","DOI":"10.3727\/096504017X15130753659625","article-title":"The Peritoneal Macrophages in Inflammatory Diseases and Abdominal Cancers","volume":"26","author":"Liu","year":"2018","journal-title":"Oncol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"E1913","DOI":"10.1210\/jc.2014-1340","article-title":"Dysregulated Sphingolipid Metabolism in Endometriosis","volume":"99","author":"Lee","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.cellsig.2008.11.003","article-title":"Ceramide 1-Phosphate (C1P) Promotes Cell Migration Involvement of a Specific C1P Receptor","volume":"21","author":"Granado","year":"2009","journal-title":"Cell. Signal."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"109980","DOI":"10.1016\/j.cellsig.2021.109980","article-title":"Regulation of Cell Growth, Survival and Migration by Ceramide 1-Phosphate\u2014Implications in Lung Cancer Progression and Inflammation","volume":"83","author":"Ouro","year":"2021","journal-title":"Cell. Signal."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/nri3671","article-title":"Monocytes and Macrophages: Developmental Pathways and Tissue Homeostasis","volume":"14","author":"Ginhoux","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E1213","DOI":"10.1152\/ajpendo.00480.2012","article-title":"Ceramide 1-Phosphate Induces Macrophage Chemoattractant Protein-1 Release: Involvement in Ceramide 1-Phosphate-Stimulated Cell Migration","volume":"304","author":"Arana","year":"2013","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4349","DOI":"10.1210\/jc.2016-2391","article-title":"Role of Versican in the Pathogenesis of Peritoneal Endometriosis","volume":"101","author":"Tani","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_25","first-page":"1090","article-title":"Co-Cultured Endometrial Stromal Cells and Peritoneal Mesothelial Cells for an in Vitro Model of Endometriosis","volume":"4","author":"Chen","year":"2012","journal-title":"Integr. Biol. Quant. Biosci. Nano Macro"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S0015-0282(99)00292-7","article-title":"Effects of Peritoneal Macrophages from Women with Endometriosis on Endometrial Cellular Proliferation in an in Vitro Coculture Model","volume":"72","author":"Loh","year":"1999","journal-title":"Fertil. Steril."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/s41420-018-0075-0","article-title":"Targeting Sphingolipid Metabolism as an Approach for Combination Therapies in Haematological Malignancies","volume":"4","author":"Lewis","year":"2018","journal-title":"Cell Death Discov."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1515\/pp-2016-0009","article-title":"Diverse Properties of the Mesothelial Cells in Health and Disease","volume":"1","author":"Kawanishi","year":"2016","journal-title":"Pleura Peritoneum"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1038\/s41598-017-03780-z","article-title":"Image Based Machine Learning for Identification of Macrophage Subsets","volume":"7","author":"Rostam","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1016\/j.bbamcr.2011.06.019","article-title":"Signal Integration, Crosstalk Mechanisms and Networks in the Function of Inflammatory Cytokines","volume":"1813","author":"Schmitz","year":"2011","journal-title":"Biochim. Et Biophys. Acta (BBA) Mol. Cell Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7303","DOI":"10.4049\/jimmunol.177.10.7303","article-title":"Transcriptional Profiling of the Human Monocyte-to-Macrophage Differentiation and Polarization: New Molecules and Patterns of Gene Expression","volume":"177","author":"Martinez","year":"2006","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1124\/mol.108.048652","article-title":"Targeting Ceramide Metabolism with a Potent and Specific Ceramide Kinase Inhibitor","volume":"74","author":"Graf","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.rbmo.2013.09.020","article-title":"What Is the Societal Burden of Endometriosis-Associated Symptoms? A Prospective Belgian Study","volume":"28","author":"Klein","year":"2014","journal-title":"Reprod. BioMedicine Online"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3389\/fendo.2020.00007","article-title":"Endometriosis-Associated Macrophages: Origin, Phenotype, and Function","volume":"11","author":"Hogg","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.fertnstert.2007.02.057","article-title":"Endometrial and Peritoneal Expression of Aromatase, Cytokines, and Adhesion Factors in Women with Endometriosis","volume":"89","author":"Kyama","year":"2008","journal-title":"Fertil. Steril."},{"key":"ref_36","first-page":"491","article-title":"Macrophage Cytokines: Involvement in Immunity and Infectious Diseases","volume":"5","author":"Descoteaux","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.fertnstert.2008.02.093","article-title":"Pathogenic Mechanisms in Endometriosis-Associated Infertility","volume":"90","author":"Gupta","year":"2008","journal-title":"Fertil. Steril."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1111\/j.1600-0897.2008.00643.x","article-title":"REVIEW ARTICLE: Immunopathogenesis of Pelvic Endometriosis: Role of Hepatocyte Growth Factor, Macrophages and Ovarian Steroids","volume":"60","author":"Khan","year":"2008","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.2174\/092986708784049595","article-title":"Non-Steroidal Targets in the Diagnosis and Treatment of Endometriosis","volume":"15","author":"Kyama","year":"2008","journal-title":"CMC"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1002\/jcla.21944","article-title":"Association of the Precursor of Interleukin-1\u03b2 and Peritoneal Inflammation-Role in Pathogenesis of Endometriosis: ProIL-1\u03b2 in Endometriosis","volume":"30","author":"Sikora","year":"2016","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1034\/j.1600-0897.2003.01207.x","article-title":"The Role of Cytokines in Endometriosis *","volume":"49","author":"Wu","year":"2003","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_42","first-page":"332","article-title":"TNF-alpha secretion by peritoneal macrophages in endometriosis","volume":"120","author":"Richter","year":"1998","journal-title":"Zentralbl. Gynakol."},{"key":"ref_43","first-page":"824","article-title":"Tumor Necrosis Factor-\u03b1 Promotes Proliferation of Endometriotic Stromal Cells by Inducing Interleukin-8 Gene and Protein Expression","volume":"85","author":"Iwabe","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1016\/S0015-0282(16)55976-7","article-title":"Effect of Tumor Necrosis Factor-\u03b1 on Adhesion of Human Endometrial Stromal Cells to Peritoneal Mesothelial Cells: An in Vitro System *","volume":"59","author":"Zhang","year":"1993","journal-title":"Fertil. Steril."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1742-2094-11-23","article-title":"Macrophages Migrate in an Activation-Dependent Manner to Chemokines Involved in Neuroinflammation","volume":"11","author":"Vogel","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.3389\/fimmu.2018.02650","article-title":"Distinct Migratory Properties of M1, M2, and Resident Macrophages Are Regulated by AD\u03b22 and AM\u03b22 Integrin-Mediated Adhesion","volume":"9","author":"Cui","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"668","DOI":"10.4103\/1735-1995.166215","article-title":"Serum Anti-Inflammatory Cytokines for the Evaluation of Inflammatory Status in Endometriosis","volume":"20","author":"Drugan","year":"2015","journal-title":"J. Res. Med. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"96","DOI":"10.5114\/ceji.2015.50840","article-title":"Pro-Inflammatory Cytokines for Evaluation of Inflammatory Status in Endometriosis","volume":"40","author":"Malutan","year":"2015","journal-title":"Cent. Eur. J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Ahmad, T., Ishaq, M., Eapen, M., Singh, N., Park, A., Karpiniec, S., Stringer, D., Fitton, H., Caruso, V., and Eri, R. (2022). Fucoidan as an Inhibitor of Pro-Inflammatory Cytokines: Potential Candidate for Treating Inflammatory-Related Conditions. FASEB J., 36.","DOI":"10.1096\/fasebj.2022.36.S1.L7837"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1111\/aji.12592","article-title":"Alpha-7 Nicotinic Acetylcholine Receptor (NAChR) Agonist Inhibits the Development of Endometriosis by Regulating Inflammation","volume":"76","author":"Yoshino","year":"2016","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0165-0378(00)00073-5","article-title":"Ability of Recombinant Human TNF Binding Protein-1 (r-HTBP-1) to Inhibit the Development of Experimentally-Induced Endometriosis in Rats","volume":"48","author":"Martelli","year":"2000","journal-title":"J. Reprod. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/j.bbagen.2012.02.018","article-title":"Galectin-3 Endocytosis by Carbohydrate Independent and Dependent Pathways in Different Macrophage like Cell Types","volume":"1820","author":"Lepur","year":"2012","journal-title":"Biochim. Et Biophys. Acta (BBA) Gen. Subj."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1158\/1541-7786.MCR-11-0604","article-title":"Basal-like Breast Cancer Cells Induce Phenotypic and Genomic Changes in Macrophages","volume":"10","author":"Stewart","year":"2012","journal-title":"Mol. Cancer Res."},{"key":"ref_54","first-page":"478","article-title":"Deregulation of the Endometrial Stromal Cell Secretome Precedes Embryo Implantation Failure","volume":"23","author":"Aberkane","year":"2017","journal-title":"MHR: Basic Sci. Reprod. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"185","DOI":"10.4155\/bio-2018-0036","article-title":"Retention Time Bracketing for Targeted Sphingolipidomics by Liquid Chromatography\u2013Tandem Mass Spectrometry","volume":"11","author":"Zhu","year":"2019","journal-title":"Bioanalysis"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15977\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:42:01Z","timestamp":1760146921000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15977"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,15]]},"references-count":55,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232415977"],"URL":"https:\/\/doi.org\/10.3390\/ijms232415977","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,15]]}}}