{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:17:43Z","timestamp":1760149063403,"version":"build-2065373602"},"reference-count":56,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:00:00Z","timestamp":1687910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"institutional grants of the University of Freiburg"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>(1) Background: Inflammatory bowel diseases are complex and multifactorial disorders of unknown etiology. The extravasation of activated leukocytes is a critical step in the pathogenesis of these diseases. Leukocyte integrin Mac-1 (\u03b1M\u03b22; CD11b\/CD18) is crucial for the extravasation of myeloid cells, and a novel activation-specific anti-Mac-1 Designed Ankyrin Repeat protein (DARPin F7) is a promising therapeutic agent for inflammatory diseases. In its activated conformation, Mac-1 expresses the high-affinity binding site I-domain, which the DARPin F7 selectively targets. In our study, we aimed to explore the therapeutic potential of anti-Mac-1 DARPin F7 in murine dextrane sodium sulfate (DSS)-induced colitis. (2) Methods: C57BL\/6J mice received 3% DSS drinking water for five days, followed by normal drinking water for one week. The mice were treated with DARPin F7 or a control substance daily via intraperitoneal injections. Disease activity index (DAI), colon length, myeloperoxidase (MPO) activity measurements, H&amp;E staining, and qRT-PCR were conducted after euthanizing the mice on day 12. (3) Results: Treatment with DARPin F7 resulted in less pronounced colon shortening and significantly lower histological scores. The DARPin F7-treated animals experienced substantially less disease and myeloperoxidase (MPO) activity. Animals that received DARPin F7 treatment suffered less weight loss and recovered from the weight loss more efficiently. Treatment with DARPin F7 also led to significantly reduced mRNA expression of inflammatory cytokines. (4) Conclusion: Anti-Mac-1 treatment markedly reduced disease activity and inflammatory reaction accompanying DSS-induced colitis in mice.<\/jats:p>","DOI":"10.3390\/life13071464","type":"journal-article","created":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:49:47Z","timestamp":1687999787000},"page":"1464","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Activation-Specific Anti-Mac-1 Designed-Ankyrin-Repeat-Protein Attenuates Colitis in Mice"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1009-084X","authenticated-orcid":false,"given":"Istvan","family":"Bojti","sequence":"first","affiliation":[{"name":"Department of Cardiology and Angiology, University Heart Center Freiburg\u2014Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology, University Heart Center Freiburg\u2014Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tibor","family":"Bojti","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology, University Heart Center Freiburg\u2014Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felicitas","family":"Bojti","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology, University Heart Center Freiburg\u2014Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick Malcolm","family":"Siegel","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology, University Heart Center Freiburg\u2014Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timo","family":"Heidt","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology, University Heart Center Freiburg\u2014Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Moser","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology, University Heart Center Freiburg\u2014Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Bode","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology, University Heart Center Freiburg\u2014Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Westermann","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology, University Heart Center Freiburg\u2014Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karlheinz","family":"Peter","sequence":"additional","affiliation":[{"name":"Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia"},{"name":"Department of Medicine, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia"},{"name":"Department of Cardiometabolic Health, University of Melbourne, Melbourne, VIC 3004, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Diehl","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology, University Heart Center Freiburg\u2014Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1146\/annurev-immunol-030409-101225","article-title":"Inflammatory Bowel Disease","volume":"28","author":"Kaser","year":"2010","journal-title":"Annu. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1056\/NEJMra2002697","article-title":"Pathophysiology of Inflammatory Bowel Diseases","volume":"383","author":"Chang","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/nrgastro.2015.150","article-title":"The global burden of IBD: From 2015 to 2025","volume":"12","author":"Kaplan","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1136\/gutjnl-2018-317977","article-title":"Immune cell trafficking and retention in inflammatory bowel disease: Mechanistic insights and therapeutic advances","volume":"68","author":"Zundler","year":"2019","journal-title":"Gut"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"405","DOI":"10.12998\/wjcc.v7.i4.405","article-title":"Immune checkpoint inhibitor-induced colitis: A comprehensive review","volume":"7","author":"Som","year":"2019","journal-title":"World J. Clin. Cases"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1001\/jamaoncol.2018.3923","article-title":"Fatal Toxic Effects Associated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis","volume":"4","author":"Wang","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nrgastro.2016.208","article-title":"Current and emerging therapeutic targets for IBD","volume":"14","author":"Neurath","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_8","first-page":"793","article-title":"Vedolizumab as a Treatment for Crohn\u2019s Disease and Ulcerative Colitis","volume":"10","author":"Ha","year":"2014","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.1111\/bph.15168","article-title":"Integrins meet complement: The evolutionary tip of an iceberg orchestrating metabolism and immunity","volume":"178","author":"Merle","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1093\/ibd\/izab212","article-title":"Noninfectious Pulmonary Complications Associated with Anti-Integrin Therapy: A Case Report and Systematic Review of the Literature","volume":"28","author":"Dulaney","year":"2022","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_11","unstructured":"Kelsey, R. (2018). The risk of natalizumab-associated PML is revealed. Nat. Res., Available online: https:\/\/www.nature.com\/articles\/d42859-018-00025-5."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1091\/mbc.10.4.861","article-title":"Specific activation of leukocyte beta2 integrins lymphocyte function-associated antigen-1 and Mac-1 by chemokines mediated by distinct pathways via the alpha subunit cytoplasmic domains","volume":"10","author":"Weber","year":"1999","journal-title":"Mol. Biol. Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"254","DOI":"10.3389\/fimmu.2019.00254","article-title":"Beta2-Integrins and Interacting Proteins in Leukocyte Trafficking, Immune Suppression, and Immunodeficiency Disease","volume":"10","author":"Fagerholm","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1136\/gut.51.1.30","article-title":"Double blind, placebo controlled trial of the remission inducing and steroid sparing properties of an ICAM-1 antisense oligodeoxynucleotide, alicaforsen (ISIS 2302), in active steroid dependent Crohn\u2019s disease","volume":"51","author":"Yacyshyn","year":"2002","journal-title":"Gut"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/nm0497-414","article-title":"Mac-1 (CD11b\/CD18) is an oligodeoxynucleotide-binding protein","volume":"3","author":"Benimetskaya","year":"1997","journal-title":"Nat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nri2156","article-title":"Getting to the site of inflammation: The leukocyte adhesion cascade updated","volume":"7","author":"Ley","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"662164","DOI":"10.3389\/fimmu.2021.662164","article-title":"The Promiscuous Profile of Complement Receptor 3 in Ligand Binding, Immune Modulation, and Pathophysiology","volume":"12","author":"Lamers","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3032","DOI":"10.4049\/jimmunol.2001208","article-title":"Complement Receptor 3 Forms a Compact High-Affinity Complex with iC3b","volume":"206","author":"Jensen","year":"2021","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1084\/jem.20060925","article-title":"Intraluminal crawling of neutrophils to emigration sites: A molecularly distinct process from adhesion in the recruitment cascade","volume":"203","author":"Phillipson","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s00395-021-00849-9","article-title":"A DARPin targeting activated Mac-1 is a novel diagnostic tool and potential anti-inflammatory agent in myocarditis, sepsis and myocardial infarction","volume":"116","author":"Siegel","year":"2021","journal-title":"Basic Res. Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1002\/pro.2312","article-title":"Design, construction, and characterization of a second-generation DARPin library with reduced hydrophobicity","volume":"22","author":"Seeger","year":"2013","journal-title":"Protein Sci."},{"key":"ref_22","unstructured":"(2010). DIRECTIVE 2010\/63\/EU OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 22 September 2010 on the Protection of Animals Used for Scientific Purposes, Official Journal of the European Union."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1538\/expanim.49.9","article-title":"Histological Analysis of Murine Colitis Induced by Dextran Sulfate Sodium of Different Molecular Weights","volume":"49","author":"Kitajima","year":"2000","journal-title":"Exp. Anim."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1136\/gutjnl-2011-300767","article-title":"Induction of dsRNA-activated protein kinase links mitochondrial unfolded protein response to the pathogenesis of intestinal inflammation","volume":"61","author":"Rath","year":"2012","journal-title":"Gut"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1056\/NEJMoa1905725","article-title":"Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis","volume":"381","author":"Sands","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1006\/clin.1997.4462","article-title":"Beta2 integrin\/ICAM expression in Crohn\u2019s disease","volume":"86","author":"Bernstein","year":"1998","journal-title":"Clin. Immunol. Immunopathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e54","DOI":"10.1016\/S1470-2045(18)30828-3","article-title":"New therapeutic perspectives to manage refractory immune checkpoint-related toxicities","volume":"20","author":"Martins","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1200\/JCO.2005.04.5716","article-title":"Enterocolitis in Patients with Cancer After Antibody Blockade of Cytotoxic T-Lymphocyte\u2013Associated Antigen 4","volume":"24","author":"Beck","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.lfs.2013.01.028","article-title":"Efficacy of drugs used in the treatment of IBD and combinations thereof in acute DSS-induced colitis in mice","volume":"92","author":"Sann","year":"2013","journal-title":"Life Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1046\/j.1365-2249.2000.01090.x","article-title":"Intercellular adhesion molecule-1 (ICAM-1) deficiency protects mice against severe forms of experimentally induced colitis","volume":"119","author":"Bendjelloul","year":"2000","journal-title":"Clin. Exp. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/labinvest.3700398","article-title":"Regulation of dextran sodium sulfate induced colitis by leukocyte beta 2 integrins","volume":"86","author":"Abdelbaqi","year":"2006","journal-title":"Lab. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Meers, G.K., Bohnenberger, H., Reichardt, H.M., L\u00fchder, F., and Reichardt, S.D. (2018). Impaired resolution of DSS-induced colitis in mice lacking the glucocorticoid receptor in myeloid cells. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0190846"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/mi.2012.24","article-title":"The role of neutrophils during intestinal inflammation","volume":"5","author":"Fournier","year":"2012","journal-title":"Mucosal Immunol."},{"key":"ref_34","first-page":"e1004","article-title":"Fecal Myeloperoxidase as a Biomarker for Inflammatory Bowel Disease","volume":"9","author":"Hansberry","year":"2017","journal-title":"Cureus"},{"key":"ref_35","first-page":"60","article-title":"Modulation of Neutrophil Apoptosis and the Resolution of Inflammation through \u03b22 Integrins","volume":"4","author":"Filep","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.abb.2018.01.004","article-title":"Myeloperoxidase: Its role for host defense, inflammation, and neutrophil function","volume":"640","author":"Aratani","year":"2018","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3924","DOI":"10.1038\/s41598-017-04041-9","article-title":"Uridine Ameliorates Dextran Sulfate Sodium (DSS)-Induced Colitis in Mice","volume":"7","author":"Jeengar","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1073\/pnas.0405193102","article-title":"Myeloperoxidase mediates neutrophil activation by association with CD11b\/CD18 integrins","volume":"102","author":"Lau","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6296","DOI":"10.1038\/s41598-022-10090-6","article-title":"An activation specific anti-Mac-1 designed ankyrin repeat protein improves survival in a mouse model of acute lung injury","volume":"12","author":"Siegel","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"23409","DOI":"10.1074\/jbc.R000004200","article-title":"The Leukocyte Integrins","volume":"275","author":"Harris","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1136\/gut.2009.197822","article-title":"Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome","volume":"59","author":"Bauer","year":"2010","journal-title":"Gut"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e003551","DOI":"10.1136\/jitc-2021-003551","article-title":"Potential therapies for immune-related adverse events associated with immune checkpoint inhibition: From monoclonal antibodies to kinase inhibition","volume":"10","author":"Miller","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1038\/mi.2013.103","article-title":"IL-10 modulates DSS-induced colitis through a macrophage\u2013ROS\u2013NO axis","volume":"7","author":"Li","year":"2014","journal-title":"Mucosal Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"400","DOI":"10.3389\/fimmu.2018.00400","article-title":"The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced Colitis","volume":"9","author":"Cardoso","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e20190418","DOI":"10.1084\/jem.20190418","article-title":"Biology and therapeutic potential of interleukin-10","volume":"217","author":"Saraiva","year":"2019","journal-title":"J. Exp. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"840313","DOI":"10.3389\/fimmu.2022.840313","article-title":"Interleukin-10 Is a Promising Marker for Immune-Related Adverse Events in Patients with Non-Small Cell Lung Cancer Receiving Immunotherapy","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1200\/JCO.18.02141","article-title":"Treatment Outcomes of Immune-Related Cutaneous Adverse Events","volume":"37","author":"Phillips","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/ibd.22974","article-title":"IL-10R Polymorphisms are Associated with Very Early-Onset Ulcerative Colitis","volume":"19","author":"Moran","year":"2013","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1161\/01.CIR.100.10.1102","article-title":"Treatment of Experimental Viral Myocarditis with Interleukin-10","volume":"100","author":"Nishio","year":"1999","journal-title":"Circulation"},{"key":"ref_50","first-page":"975","article-title":"Time course and cellular localization of interleukin-10 mRNA and protein expression in autoimmune inflammation of the rat central nervous system","volume":"152","author":"Jander","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jaut.2012.07.009","article-title":"Interleukin-6 Induces the Generation of IL-10-Producing Tr1 Cells and Suppresses Autoimmune Tissue Inflammation","volume":"40","author":"Jin","year":"2013","journal-title":"J. Autoimmun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"26252","DOI":"10.1038\/srep26252","article-title":"Integrin CD11b attenuates colitis by strengthening Src-Akt pathway to polarize anti-inflammatory IL-10 expression","volume":"6","author":"Hu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4691","DOI":"10.1172\/JCI124884","article-title":"IFN-\u03b3 drives inflammatory bowel disease pathogenesis through VE-cadherin\u2013directed vascular barrier disruption","volume":"129","author":"Langer","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nri3661","article-title":"Cytokines in inflammatory bowel disease","volume":"14","author":"Neurath","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1111\/j.1365-2249.2006.03214.x","article-title":"Interferon-gamma is causatively involved in experimental inflammatory bowel disease in mice","volume":"146","author":"Ito","year":"2006","journal-title":"Clin. Exp. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4572","DOI":"10.3389\/fimmu.2021.697725","article-title":"Intestinal CD11b+ B Cells Ameliorate Colitis by Secreting Immunoglobulin A","volume":"12","author":"Fu","year":"2021","journal-title":"Front. Immunol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/7\/1464\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:02:48Z","timestamp":1760126568000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/7\/1464"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,28]]},"references-count":56,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["life13071464"],"URL":"https:\/\/doi.org\/10.3390\/life13071464","relation":{},"ISSN":["2075-1729"],"issn-type":[{"type":"electronic","value":"2075-1729"}],"subject":[],"published":{"date-parts":[[2023,6,28]]}}}