{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T02:24:35Z","timestamp":1777947875276,"version":"3.51.4"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intramural Research Program of the NIH"},{"DOI":"10.13039\/100000062","name":"The National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["DK043403"],"award-info":[{"award-number":["DK043403"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Clinical Center","award":["CL090096"],"award-info":[{"award-number":["CL090096"]}]},{"name":"Clinical Center","award":["CL090097"],"award-info":[{"award-number":["CL090097"]}]},{"name":"the Japan Society for the Promotion of Science Research Fellowship","award":["72207"],"award-info":[{"award-number":["72207"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Class B scavenger receptor BI splice variants (SR-BI) and BII (SR-BII) internalize lipoproteins but also bind and internalize bacteria. Their individual roles in sepsis are unknown. We overexpressed human SR-BI or BII in transgenic mice, primarily in the liver, but also in the kidney and in bone marrow-derived macrophages, and then performed cecal ligation and puncture (CLP) surgery. SR-BI and BII transgenic mice had significantly worse survival compared to WT mice. Twenty-four hours after CLP, liver injury markers and histological damage were elevated in both SR-BI and BII transgenic mice, whereas kidney damage was similar. Systemic inflammatory cytokines were markedly increased in SR-BI and BII transgenic mice; parallel increases were seen in liver mRNA expression, but not in the kidney. The highest degree of neutrophil infiltration was observed in the liver of SR-BI. Human SR-BI and BII dramatically decreased bacterial accumulation in the liver. Green fluorescent protein-labeled E. coli were efficiently phagocytosed in hepatic macrophages of SR-BI and BII transgenic mice; phagocytosis was more prominent in SR-BII transgenic mice. Finally, human SR-BI overexpression reduced systemic HDL-C levels, eliminated adrenal cortex lipid droplets, and dampened the systemic increase of corticosterone after CLP. Supplementation with glucocorticoid and mineralocorticoid improved survival in SR-BI but not in SR-BII transgenic mice after CLP. In summary, our findings suggest human SR-BI and BII overexpression contributes to higher mortality after CLP by different mechanisms: excessive inflammatory response due to adrenal insufficiency (SR-BI) or hyperactive phagocytosis (SR-BII) in the liver.<\/jats:p>","DOI":"10.3390\/biom16050670","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:54:07Z","timestamp":1777654447000},"page":"670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Different Functions of Human Scavenger Receptors BI and BII Overexpressed in a Murine Abdominal Sepsis Model"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7257-7670","authenticated-orcid":false,"given":"Naoki","family":"Hayase","sequence":"first","affiliation":[{"name":"Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1268, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatyana G.","family":"Vishnyakova","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina N.","family":"Baranova","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander V.","family":"Bocharov","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuzhen","family":"Hu","sequence":"additional","affiliation":[{"name":"Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1268, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy P.","family":"Patterson","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA"},{"name":"Office of the Director, Division of Program Coordination, Planning and Strategic Initiatives, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter S. T.","family":"Yuen","sequence":"additional","affiliation":[{"name":"Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1268, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas L.","family":"Eggerman","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA"},{"name":"Division of Diabetes, Endocrinology and Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0940-3079","authenticated-orcid":false,"given":"Robert A.","family":"Star","sequence":"additional","affiliation":[{"name":"Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1268, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S2213-2600(23)00330-2","article-title":"Profiling the dysregulated immune response in sepsis: Overcoming challenges to achieve the goal of precision medicine","volume":"12","author":"Cajander","year":"2024","journal-title":"Lancet Respir. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107909","DOI":"10.1016\/j.intimp.2021.107909","article-title":"Pattern recognition receptors as therapeutic targets for bacterial, viral and fungal sepsis","volume":"98","author":"Yuki","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1001\/jama.2013.2194","article-title":"Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: The ACCESS randomized trial","volume":"309","author":"Opal","year":"2013","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1097\/CCM.0b013e3181e7c5c9","article-title":"A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis","volume":"38","author":"Rice","year":"2010","journal-title":"Crit. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15241","DOI":"10.1074\/jbc.273.24.15241","article-title":"SR-BII, an isoform of the scavenger receptor BI containing an alternate cytoplasmic tail, mediates lipid transfer between high density lipoprotein and cells","volume":"273","author":"Webb","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/s41467-025-56223-z","article-title":"High-density lipoprotein nanoparticles spontaneously target to damaged renal tubules and alleviate renal fibrosis by remodeling the fibrotic niches","volume":"16","author":"He","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100616","DOI":"10.1016\/j.jbc.2021.100616","article-title":"The adaptor protein GIPC1 stabilizes the scavenger receptor SR-B1 and increases its cholesterol uptake","volume":"296","author":"Zhang","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1097\/MOL.0000000000000822","article-title":"Macrophage SR-B1 in atherosclerotic cardiovascular disease","volume":"33","author":"Huby","year":"2022","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Guo, L., Wang, Q., and Li, X.A. (2025). The Role of SR-BI in sepsis: Leveraging mechanistic insights to advance precision steroid therapy. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1643395"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s43556-025-00321-3","article-title":"Cholesterol metabolism: Molecular mechanisms, biological functions, diseases, and therapeutic targets","volume":"6","author":"Cui","year":"2025","journal-title":"Mol. Biomed."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.4049\/jimmunol.1100350","article-title":"Class B scavenger receptor types I and II and CD36 mediate bacterial recognition and proinflammatory signaling induced by Escherichia coli, lipopolysaccharide, and cytosolic chaperonin 60","volume":"188","author":"Baranova","year":"2012","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"16888","DOI":"10.1073\/pnas.0602126103","article-title":"CLA-1 and its splicing variant CLA-2 mediate bacterial adhesion and cytosolic bacterial invasion in mammalian cells","volume":"103","author":"Vishnyakova","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"19826","DOI":"10.1074\/jbc.M109.020933","article-title":"Scavenger Receptor BI Protects against Septic Death through Its Role in Modulating Inflammatory Response","volume":"284","author":"Guo","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.4049\/jimmunol.1003445","article-title":"Class B scavenger receptor types I and II and CD36 targeting improves sepsis survival and acute outcomes in mice","volume":"188","author":"Leelahavanichkul","year":"2012","journal-title":"J. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4555","DOI":"10.3748\/wjg.v27.i28.4555","article-title":"Cellular factors involved in the hepatitis C virus life cycle","volume":"27","author":"Li","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13509","DOI":"10.1038\/s41598-020-70468-2","article-title":"Molecular determinants of SR-B1-dependent Plasmodium sporozoite entry into hepatocytes","volume":"10","author":"Langlois","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.4049\/jimmunol.1501709","article-title":"Human SR-BI and SR-BII Potentiate Lipopolysaccharide-Induced Inflammation and Acute Liver and Kidney Injury in Mice","volume":"196","author":"Baranova","year":"2016","journal-title":"J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8221","DOI":"10.1016\/S0021-9258(18)53085-4","article-title":"A far-downstream hepatocyte-specific control region directs expression of the linked human apolipoprotein E and C-I genes in transgenic mice","volume":"268","author":"Simonet","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.neurobiolaging.2004.08.004","article-title":"Quantification of apolipoprotein E receptors in human brain-derived cell lines by real-time polymerase chain reaction","volume":"26","author":"Thilakawardhana","year":"2005","journal-title":"Neurobiol. Aging"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e110","DOI":"10.1002\/cpim.110","article-title":"Inducing Experimental Polymicrobial Sepsis by Cecal Ligation and Puncture","volume":"131","author":"Sjaastad","year":"2020","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Shrum, B., Anantha, R.V., Xu, S.X., Donnelly, M., Haeryfar, S.M., McCormick, J.K., and Mele, T. (2014). A robust scoring system to evaluate sepsis severity in an animal model. BMC Res. Notes, 7.","DOI":"10.1186\/1756-0500-7-233"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e490","DOI":"10.1097\/CCM.0000000000001264","article-title":"Corticosteroid Therapy Benefits Septic Mice With Adrenal Insufficiency But Harms Septic Mice Without Adrenal Insufficiency","volume":"43","author":"Ai","year":"2015","journal-title":"Crit. Care Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Stasi, A., Franzin, R., Fiorentino, M., Squiccimarro, E., Castellano, G., and Gesualdo, L. (2021). Multifaced Roles of HDL in Sepsis and SARS-CoV-2 Infection: Renal Implications. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115980"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1161\/ATVBAHA.121.315882","article-title":"Hepatic Scavenger Receptor Class B Type 1 Knockdown Reduces Atherosclerosis and Enhances the Antiatherosclerotic Effect of Brown Fat Activation in APOE*3-Leiden.CETP Mice","volume":"41","author":"Zhou","year":"2021","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Aderhold, A., and Alexaki, V.I. (2025). Lipid metabolism in the adrenal gland. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1577505"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1172\/JCI31539","article-title":"SR-BI protects against endotoxemia in mice through its roles in glucocorticoid production and hepatic clearance","volume":"118","author":"Cai","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1161\/ATVBAHA.111.234716","article-title":"Deficiency of scavenger receptor BI leads to impaired lymphocyte homeostasis and autoimmune disorders in mice","volume":"31","author":"Feng","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Yang, F., Lu, J.C., Shen, T., Jin, Y.H., and Liang, Y.J. (2023). Effect of hyperlipidemia on the outcome of in vitro fertilization in non-obese patients with polycystic ovary syndrome. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1281794"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/s13613-024-01377-0","article-title":"Organ crosstalk and dysfunction in sepsis","volume":"14","author":"Borges","year":"2024","journal-title":"Ann. Intensive Care"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1097\/SHK.0000000000002648","article-title":"Continuous antithrombin III infusion in a clinically relevant sepsis model","volume":"65","author":"Hayase","year":"2026","journal-title":"Shock"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/s41419-025-07637-6","article-title":"The role of heme in sepsis induced Kupffer cell PANoptosis and senescence","volume":"16","author":"Li","year":"2025","journal-title":"Cell Death Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.mce.2006.01.007","article-title":"Adrenal deficiency alters mechanisms of neutrophil mobilization","volume":"249","author":"Cavalcanti","year":"2006","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/s13613-025-01535-y","article-title":"Renal perfusion pressure: Role and implications in critical illness","volume":"15","author":"Panwar","year":"2025","journal-title":"Ann. Intensive Care"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e14025","DOI":"10.1111\/apha.14025","article-title":"Renal arterial infusion of tempol prevents medullary hypoperfusion, hypoxia, and acute kidney injury in ovine Gram-negative sepsis","volume":"239","author":"Betrie","year":"2023","journal-title":"Acta Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1210\/en.2005-1286","article-title":"Effects of hepatic expression of the high-density lipoprotein receptor SR-BI on lipoprotein metabolism and female fertility","volume":"147","author":"Yesilaltay","year":"2006","journal-title":"Endocrinology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1210\/jc.2008-1223","article-title":"Scavenger receptor class B type I protein as an independent predictor of high-density lipoprotein cholesterol levels in subjects with hyperalphalipoproteinemia","volume":"94","author":"West","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1172\/JCI30060","article-title":"Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe","volume":"117","author":"Temel","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1161\/ATVBAHA.120.314506","article-title":"SR-BI (Scavenger Receptor BI), Not LDL (Low-Density Lipoprotein) Receptor, Mediates Adrenal Stress Response-Brief Report","volume":"40","author":"Ito","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1016\/S0022-2275(20)33380-0","article-title":"Polyunsaturated fatty acids up-regulate hepatic scavenger receptor B1 (SR-BI) expression and HDL cholesteryl ester uptake in the hamster","volume":"40","author":"Spady","year":"1999","journal-title":"J. Lipid Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Chiba-Falek, O., Nichols, M., Suchindran, S., Guyton, J., Ginsburg, G.S., Barrett-Connor, E., and McCarthy, J.J. (2010). Impact of gene variants on sex-specific regulation of human Scavenger receptor class B type 1 (SR-BI) expression in liver and association with lipid levels in a population-based study. BMC Med. Genet., 11.","DOI":"10.1186\/1471-2350-11-9"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"172","DOI":"10.4236\/jdm.2013.34027","article-title":"Hyperglycemia promotes overexpression of SR-BII isoform of the scavenger receptor class B type I in type 2 diabetes mellitus: A study in Juana Koslay City, San Luis, Argentina","volume":"3","author":"Mendoza","year":"2013","journal-title":"J. Diabetes Mellit."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Vandewalle, J., and Libert, C. (2020). Glucocorticoids in Sepsis: To Be or Not to Be. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01318"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"104981","DOI":"10.1016\/j.ebiom.2024.104981","article-title":"Low circulatory levels of total cholesterol, HDL-C and LDL-C are associated with death of patients with sepsis and critical illness: Systematic review, meta-analysis, and perspective of observational studies","volume":"100","author":"Taylor","year":"2024","journal-title":"EBioMedicine"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Zhao, J., Zhang, X., Li, Y., Yu, J., Chen, Z., Niu, Y., Ran, S., Wang, S., Ye, W., and Luo, Z. (2023). Interorgan communication with the liver: Novel mechanisms and therapeutic targets. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1314123"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1113\/expphysiol.2012.070524","article-title":"Adrenal hormone deprivation affects macrophage catecholamine metabolism and beta2-adrenoceptor density, but not propranolol stimulation of tumour necrosis factor-alpha production","volume":"98","author":"Stanojevic","year":"2013","journal-title":"Exp. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e0030121","DOI":"10.1128\/IAI.00301-21","article-title":"Class B Scavenger Receptors BI and BII Protect against LPS-Induced Acute Lung Injury in Mice by Mediating LPS","volume":"89","author":"Baranova","year":"2021","journal-title":"Infect. Immun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1677\/joe.0.1750663","article-title":"Effect of estrogen on scavenger receptor BI expression in the rat","volume":"175","author":"Stangl","year":"2002","journal-title":"J. Endocrinol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5295","DOI":"10.1210\/en.2007-0376","article-title":"Regulation of alternative splicing of liver scavenger receptor class B gene by estrogen and the involved regulatory splicing factors","volume":"148","author":"Zhang","year":"2007","journal-title":"Endocrinology"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Wang, N., Lu, Y., Zheng, J., and Liu, X. (2022). Of mice and men: Laboratory murine models for recapitulating the immunosuppression of human sepsis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.956448"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1128\/IAI.01213-09","article-title":"Characterization and modulation of the immunosuppressive phase of sepsis","volume":"78","author":"Muenzer","year":"2010","journal-title":"Infect. Immun."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/5\/670\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T04:18:38Z","timestamp":1777781918000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/5\/670"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,1]]},"references-count":50,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["biom16050670"],"URL":"https:\/\/doi.org\/10.3390\/biom16050670","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,1]]}}}