{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T19:51:10Z","timestamp":1782417070057,"version":"3.54.5"},"reference-count":53,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T00:00:00Z","timestamp":1638921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["209933838 - SFB-1052\/A9"],"award-info":[{"award-number":["209933838 - SFB-1052\/A9"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Plant sterols (PSs) cannot be synthesized in mammals and are exclusively diet-derived. PSs cross the blood-brain barrier and may have anti-neuroinflammatory effects. Obesity is linked to lower intestinal uptake and blood levels of PSs, but its effects in terms of neuroinflammation\u2014if any\u2014remain unknown. We investigated the effect of high-fat diet-induced obesity on PSs in the brain and the effects of the PSs campesterol and \u03b2-sitosterol on in vitro microglia activation. Sterols (cholesterol, precursors, PSs) and polyunsaturated fatty acid-derived lipid mediators were measured in the food, blood, liver and brain of C57BL\/6J mice. Under a PSs-poor high-fat diet, PSs levels decreased in the blood, liver and brain (&gt;50%). This effect was reversible after 2 weeks upon changing back to a chow diet. Inflammatory thromboxane B2 and prostaglandin D2 were inversely correlated to campesterol and \u03b2-sitosterol levels in all brain regions. PSs content was determined post mortem in human cortex samples as well. In vitro, PSs accumulate in lipid rafts isolated from SIM-A9 microglia cell membranes. In summary, PSs levels in the blood, liver and brain were associated directly with PSs food content and inversely with BMI. PSs dampen pro-inflammatory lipid mediators in the brain. The identification of PSs in the human cortex in comparable concentration ranges implies the relevance of our findings for humans.<\/jats:p>","DOI":"10.3390\/ijms222413207","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T02:07:18Z","timestamp":1639102038000},"page":"13207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Plant Sterol-Poor Diet Is Associated with Pro-Inflammatory Lipid Mediators in the Murine Brain"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3864-6424","authenticated-orcid":false,"given":"Madlen","family":"Reinicke","sequence":"first","affiliation":[{"name":"Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, Liebigstr. 27, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Leyh","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Leipzig University, Liebigstr. 13, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9644-8907","authenticated-orcid":false,"given":"Silke","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, Liebigstr. 27, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7150-1791","authenticated-orcid":false,"given":"Soroth","family":"Chey","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, Liebigstr. 27, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilijana Begcevic","family":"Brkovic","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, Liebigstr. 27, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christin","family":"Wassermann","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, Liebigstr. 27, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Landmann","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Leipzig University, Liebigstr. 13, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7941-8308","authenticated-orcid":false,"given":"Dieter","family":"L\u00fctjohann","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0714-6160","authenticated-orcid":false,"given":"Berend","family":"Isermann","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, Liebigstr. 27, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Bechmann","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Leipzig University, Liebigstr. 13, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uta","family":"Ceglarek","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, Liebigstr. 27, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1089\/ars.2016.6958","article-title":"Essential Dietary Bioactive Lipids in Neuroinflammatory Diseases","volume":"29","author":"Catani","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"E39","DOI":"10.1161\/CIR.0000000000000743","article-title":"Dietary cholesterol and cardiovascular risk: A science advisory from the American heart association","volume":"141","author":"Carson","year":"2020","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Wali, J.A., Jarzebska, N., Raubenheimer, D., Simpson, S.J., Rodionov, R.N., and Sullivan, J.F.O. (2020). Cardio-Metabolic Effects of High-Fat Diets and Their Underlying Mechanisms\u2014A Narrative Review. Nutrients, 12.","DOI":"10.3390\/nu12051505"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1900482","DOI":"10.1002\/mnfr.201900482","article-title":"Metabolic Inflammation in Obesity-At the Crossroads between Fatty Acid and Cholesterol Metabolism","volume":"65","author":"Curley","year":"2020","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"105215","DOI":"10.1016\/j.phrs.2020.105215","article-title":"Cholesterol homeostasis: Researching a dialogue between the brain and peripheral tissues","volume":"163","author":"Gliozzi","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1111\/j.1753-4887.2006.tb00224.x","article-title":"Plasma concentrations of plant sterols: Physiology and relationship with coronary heart disease","volume":"64","author":"Chan","year":"2006","journal-title":"Nutr. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1002\/jsfa.6174","article-title":"Key points for maximum effectiveness and safety for cholesterol-lowering properties of plant sterols and use in the treatment of metabolic syndrome","volume":"93","author":"Rondanelli","year":"2013","journal-title":"J. Sci. Food Agric."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/j.1753-4887.2011.00399.x","article-title":"Beyond cholesterol-lowering effects of plant sterols: Clinical and experimental evidence of anti-inflammatory properties","volume":"69","author":"Othman","year":"2011","journal-title":"Nutr. Rev."},{"key":"ref_9","first-page":"1","article-title":"Phytosterols and inflammation","volume":"25","author":"Vilahur","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0110758","article-title":"Protective role of plant sterol and stanol esters in liver inflammation: Insights from mice and humans","volume":"9","author":"Plat","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.jnutbio.2010.07.002","article-title":"Phytosterols differentially influence ABC transporter expression, cholesterol efflux and inflammatory cytokine secretion in macrophage foam cells","volume":"22","author":"Sabeva","year":"2011","journal-title":"J. Nutr. Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.plipres.2015.01.003","article-title":"Plant sterols: Friend or foe in CNS disorders?","volume":"58","author":"Vanmierlo","year":"2015","journal-title":"Prog. Lipid Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1093\/nutrit\/nuy032","article-title":"Progress and perspectives in plant sterol and plant stanol research","volume":"76","author":"Jones","year":"2018","journal-title":"Nutr. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2468","DOI":"10.1194\/jlr.M500272-JLR200","article-title":"Plant sterols and stanols: Effects on mixed micellar composition and LXR (target gene) activation","volume":"46","author":"Plat","year":"2005","journal-title":"J. Lipid Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.bbalip.2006.03.015","article-title":"Dietary plant sterols accumulate in the brain","volume":"1761","author":"Jansen","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1194\/jlr.M017244","article-title":"Dietary intake of plant sterols stably increases plant sterol levels in the murine brain","volume":"53","author":"Vanmierlo","year":"2012","journal-title":"J. Lipid Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1194\/jlr.M200071-JLR200","article-title":"Profile of cholesterol-related sterols in aged amyloid precursor protein transgenic mouse brain","volume":"43","author":"Brzezinka","year":"2002","journal-title":"J. Lipid Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1161\/01.ATV.0000120374.59826.1b","article-title":"Brain cholesterol: Long secret life behind a barrier","volume":"24","author":"Meaney","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.1016\/j.bbagen.2012.12.012","article-title":"Incorporation of beta-sitosterol into the membrane increases resistance to oxidative stress and lipid peroxidation via estrogen receptor-mediated PI3K\/GSK3beta signaling","volume":"1830","author":"Shi","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1096\/fj.06-7809com","article-title":"Plant sterols in \u201crafts\u201d: A better way to regulate membrane thermal shocks","volume":"21","author":"Beck","year":"2007","journal-title":"FASEB J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3262","DOI":"10.1523\/JNEUROSCI.23-08-03262.2003","article-title":"Lipid Rafts in the Maintenance of Synapses, Dendritic Spines, and Surface AMPA Receptor Stability","volume":"23","author":"Hering","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1194\/jlr.TR119000468","article-title":"Lipid rafts in glial cells: Role in neuroinflammation and pain processing","volume":"61","author":"Miller","year":"2020","journal-title":"J. Lipid Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1194\/jlr.TR119000427","article-title":"Lipid Rafts and Neurodegeneration: Structural and Functional Roles in Physiological Aging and Neurodegerative Diseases","volume":"61","author":"Grassi","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mesa-Herrera, F., Taoro-Gonz\u00e1lez, L., Vald\u00e9s-Baizabal, C., Diaz, M., and Mar\u00edn, R. (2019). Lipid and Lipid Raft Alteration in Aging and Neurodegenerative Diseases: A Window for the Development of New Biomarkers. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153810"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.neuropharm.2012.06.053","article-title":"Lipid rafts, synaptic transmission and plasticity: Impact in age-related neurodegenerative diseases","volume":"64","author":"Dias","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fncel.2019.00212","article-title":"Lipid metabolism crosstalk in the brain: Glia and neurons","volume":"13","author":"Barber","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1002\/mnfr.201300433","article-title":"\u03b2-Sitosterol attenuates high-fat diet-induced intestinal inflammation in mice by inhibiting the binding of lipopolysaccharide to toll-like receptor 4 in the NF-\u03baB pathway","volume":"58","author":"Kim","year":"2014","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1172\/JCI77487","article-title":"Prostaglandin signaling suppresses beneficial microglial function in Alzheimer\u2019s disease models","volume":"125","author":"Johansson","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s11130-011-0219-3","article-title":"Cerebral Accumulation of Dietary Derivable Plant Sterols does not Interfere with Memory and Anxiety Related Behavior in Abcg5\u2212\/\u2212 Mice","volume":"66","author":"Vanmierlo","year":"2011","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.cognition.2008.08.011","article-title":"Hierarchically organized behavior and its neural foundations: A reinforcement learning perspective","volume":"113","author":"Botvinick","year":"2009","journal-title":"Cognition"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/0166-2236(93)90073-U","article-title":"Movement and thought: Identical control mechanisms by the cerebellum","volume":"16","author":"Ito","year":"1993","journal-title":"Trends Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.clineuro.2008.05.013","article-title":"Cerebellar neurocognition: Insights into the bottom of the brain","volume":"110","author":"Baillieux","year":"2008","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_33","unstructured":"(2021, March 19). The Jackson Laboratory Mouse Genome Informatics. Available online: http:\/\/www.informatics.jax.org\/allele\/genoview\/MGI:2654709?counter=14."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1194\/jlr.D400041-JLR200","article-title":"A simplified method for the preparation of detergent-free lipid rafts","volume":"46","author":"Macdonald","year":"2005","journal-title":"J. Lipid Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4308","DOI":"10.1523\/JNEUROSCI.0003-06.2006","article-title":"Activated microglia contribute to the maintenance of chronic pain after spinal cord injury","volume":"26","author":"Hains","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0231597","article-title":"Characterization of the SIM-A9 cell line as a model of activated microglia in the context of neuropathic pain","volume":"15","author":"Dave","year":"2020","journal-title":"PLoS ONE"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12944-018-0703-y","article-title":"Associations of dietary phytosterols with blood lipid profiles and prevalence of obesity in Chinese adults, a cross-sectional study","volume":"17","author":"Li","year":"2018","journal-title":"Lipids Health Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1002\/ptr.6319","article-title":"Possible anti-obesity effects of phytosterols and phytostanols supplementation in humans: A systematic review and dose\u2013response meta-analysis of randomized controlled trials","volume":"33","author":"Ghaedi","year":"2019","journal-title":"Phyther. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/oby.2002.46","article-title":"Body weight modulates cholesterol metabolism in non-insulin dependent type 2 diabetics","volume":"10","author":"Simonen","year":"2002","journal-title":"Obes. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0009-8981(01)00734-3","article-title":"Acute effects of weight reduction on cholesterol metabolism in obese type 2 diabetes","volume":"316","author":"Simonen","year":"2002","journal-title":"Clin. Chim. Acta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.devbrainres.2003.09.015","article-title":"Ontogenesis and regulation of cholesterol metabolism in the central nervous system of the mouse","volume":"146","author":"Quan","year":"2003","journal-title":"Dev. Brain Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1002\/(SICI)1097-0010(20000515)80:7<939::AID-JSFA644>3.0.CO;2-C","article-title":"Review plant sterols: Biosynthesis, biological function and their importance to human nutrition","volume":"80","author":"Piironen","year":"2000","journal-title":"Sci. Food Agric."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1142\/S0192415X07004850","article-title":"Transgenic Panax ginseng Inhibits the Production of TNF-\u03b1, IL-6, and IL-8 as well as COX-2 Expression in Human Mast Cells","volume":"35","author":"Kim","year":"2007","journal-title":"Am. J. Chin. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"47148","DOI":"10.1074\/jbc.M408093200","article-title":"Guggulsterone inhibits NF-\u03baB and I\u03baB\u03b1 kinase activation, suppresses expression of anti-apoptotic gene products, and enhances apoptosis","volume":"279","author":"Shishodia","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1111\/j.1471-4159.2006.04371.x","article-title":"Modulation of inflammation in brain: A matter of fat","volume":"101","author":"Farooqui","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Leyh, J., Winter, K., Reinicke, M., Ceglarek, U., Bechmann, I., and Landmann, J. (2021). Long-Term Diet-Induced Obesity Does Not Lead to Learning And Memory Impairment in Adult Mice. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0257921"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.tips.2009.01.002","article-title":"The distinct roles of cyclooxygenase-1 and -2 in neuroinflammation: Implications for translational research","volume":"30","author":"Choi","year":"2009","journal-title":"Trends Pharm. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0306-4522(90)90229-W","article-title":"Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain","volume":"39","author":"Lawson","year":"1990","journal-title":"Neuroscience"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1016\/S0022-2275(20)34286-3","article-title":"Lethal atherosclerosis associated with abnormal plasma and tissue sterol composition in sitosterolemia with xanthomatosis","volume":"26","author":"Salen","year":"1985","journal-title":"J. Lipid Res."},{"key":"ref_50","first-page":"2211","article-title":"Tissue pretreatment for LC\u2013MS\/MS analysis of PUFA and eicosanoid distribution in mouse brain and liver","volume":"412","author":"Reinicke","year":"2020","journal-title":"ABC"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.jchromb.2013.03.012","article-title":"Fast liquid chromatography-quadrupole linear ion trap-mass spectrometry analysis of polyunsaturated fatty acids and eicosanoids in human plasma","volume":"927","author":"Kortz","year":"2013","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1194\/jlr.C400004-JLR200","article-title":"Rapid quantification of free and esterified phytosterols in human serum using APPI-LC-MS\/MS","volume":"46","author":"Lembcke","year":"2005","journal-title":"J. Lipid Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/978-1-0716-0814-2_2","article-title":"A detergent-free method for preparation of lipid rafts for the shotgun lipidomics study","volume":"2187","author":"Qin","year":"2021","journal-title":"Methods Mol. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13207\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:42:58Z","timestamp":1760168578000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,8]]},"references-count":53,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["ijms222413207"],"URL":"https:\/\/doi.org\/10.3390\/ijms222413207","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,8]]}}}