{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T06:35:57Z","timestamp":1762065357747,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordena\u00e7\u00e3o de Aperfeicoamento de Pessoal de N\u00edvel Superior","award":["CAPES-PRINT#88881.311044\/2018-00","CAPES-Finance Code 001","FAPESP#15\/03964-6","FAPERJ#E-26\/.010.002169\/2015"],"award-info":[{"award-number":["CAPES-PRINT#88881.311044\/2018-00","CAPES-Finance Code 001","FAPESP#15\/03964-6","FAPERJ#E-26\/.010.002169\/2015"]}]},{"name":"National Council for Scientific and Technological Development","award":["CAPES-PRINT#88881.311044\/2018-00","CAPES-Finance Code 001","FAPESP#15\/03964-6","FAPERJ#E-26\/.010.002169\/2015"],"award-info":[{"award-number":["CAPES-PRINT#88881.311044\/2018-00","CAPES-Finance Code 001","FAPESP#15\/03964-6","FAPERJ#E-26\/.010.002169\/2015"]}]},{"name":"S\u00e3o Paulo Re-search Foundation","award":["CAPES-PRINT#88881.311044\/2018-00","CAPES-Finance Code 001","FAPESP#15\/03964-6","FAPERJ#E-26\/.010.002169\/2015"],"award-info":[{"award-number":["CAPES-PRINT#88881.311044\/2018-00","CAPES-Finance Code 001","FAPESP#15\/03964-6","FAPERJ#E-26\/.010.002169\/2015"]}]},{"name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","award":["CAPES-PRINT#88881.311044\/2018-00","CAPES-Finance Code 001","FAPESP#15\/03964-6","FAPERJ#E-26\/.010.002169\/2015"],"award-info":[{"award-number":["CAPES-PRINT#88881.311044\/2018-00","CAPES-Finance Code 001","FAPESP#15\/03964-6","FAPERJ#E-26\/.010.002169\/2015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>We aimed to determine the biomarker performance of the proteolytic enzymes cathepsin B (Cat B) and plasma kallikrein (PKa) and transforming growth factor (TGF)-\u03b2 to detect hepatic fibrosis (HF) in chronic hepatitis C (CHC) patients. We studied 53 CHC patients and 71 healthy controls (HCs). Hepatic-disease stage was determined by liver biopsies, aminotransferase:platelet ratio index (APRI) and Fibrosis (FIB)4. Hepatic inflammation and HF in CHC patients were stratified using the METAVIR scoring system. Cat-B and PKa activities were monitored fluorometrically. Serum levels of TGF-\u03b2 (total and its active form) were determined using ELISA-like fluorometric methods. Increased serum levels of Cat B and PKa were found (p &lt; 0.0001) in CHC patients with clinically significant HF and hepatic inflammation compared with HCs. Levels of total TGF-\u03b2 (p &lt; 0.0001) and active TGF-\u03b2 (p &lt; 0.001) were increased in CHC patients compared with HCs. Cat-B levels correlated strongly with PKa levels (r = 0.903, p &lt; 0.0001) in CHC patients but did not correlate in HCs. Levels of Cat B, PKa and active TGF-\u03b2 increased with the METAVIR stage of HF. Based on analyses of receiver operating characteristic (ROC) curves, Cat B and PKa showed high diagnostic accuracy (area under ROC = 0.99 \u00b1 0.02 and 0.991 \u00b1 0.007, respectively) for distinguishing HF in CHC patients from HCs. Taken together, Cat B and PKa could be used as circulating biomarkers to detect HF in HCV-infected patients.<\/jats:p>","DOI":"10.3390\/microorganisms10091769","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:19:01Z","timestamp":1662077941000},"page":"1769","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cathepsin B and Plasma Kallikrein Are Reliable Biomarkers to Discriminate Clinically Significant Hepatic Fibrosis in Patients with Chronic Hepatitis-C Infection"],"prefix":"10.3390","volume":"10","author":[{"given":"Alexia de Cassia Oliveira","family":"Zanelatto","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04044-020, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilmar de Souza","family":"Lacerda","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Multiusu\u00e1rio de Apoio \u00e0 Pesquisa em Nefrologia e Ci\u00eancias M\u00e9dicas, Departamento de Medicina Cl\u00ednica\u2014LAMAP, Faculdade de Medicina, Universidade Federal Fluminense, Niter\u00f3i 24033-900, RJ, Brazil"},{"name":"Departamento de Patologia, Faculdade de Medicina, Universidade Federal Fluminense, Niter\u00f3i 24033-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila de Melo","family":"Accardo","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04044-020, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5109-085X","authenticated-orcid":false,"given":"Natalia Fonseca do","family":"Ros\u00e1rio","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Multiusu\u00e1rio de Apoio \u00e0 Pesquisa em Nefrologia e Ci\u00eancias M\u00e9dicas, Departamento de Medicina Cl\u00ednica\u2014LAMAP, Faculdade de Medicina, Universidade Federal Fluminense, Niter\u00f3i 24033-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5856-6128","authenticated-orcid":false,"given":"Andr\u00e9a Alice da","family":"Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Multiusu\u00e1rio de Apoio \u00e0 Pesquisa em Nefrologia e Ci\u00eancias M\u00e9dicas, Departamento de Medicina Cl\u00ednica\u2014LAMAP, Faculdade de Medicina, Universidade Federal Fluminense, Niter\u00f3i 24033-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5427-1795","authenticated-orcid":false,"given":"Guacyara","family":"Motta","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04044-020, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8399-4535","authenticated-orcid":false,"given":"Ivarne Luis dos Santos","family":"Tersariol","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04044-020, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4501-1857","authenticated-orcid":false,"given":"Analucia Rampazzo","family":"Xavier","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Multiusu\u00e1rio de Apoio \u00e0 Pesquisa em Nefrologia e Ci\u00eancias M\u00e9dicas, Departamento de Medicina Cl\u00ednica\u2014LAMAP, Faculdade de Medicina, Universidade Federal Fluminense, Niter\u00f3i 24033-900, RJ, Brazil"},{"name":"Departamento de Patologia, Faculdade de Medicina, Universidade Federal Fluminense, Niter\u00f3i 24033-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,1]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2020, January 29). Global Hepatitis Report 2018, Available online: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/273174\/9789241550345-eng.pdf?ua=1."},{"key":"ref_2","unstructured":"Ministry of Brazilian Health (2020, January 29). Clinical Protocol and Therapeutic Guidance for Hepatitis C and Coinfections, Available online: http:\/\/conitec.gov.br\/images\/Protocolos\/PCDT_HCV_2017.pdf."},{"key":"ref_3","unstructured":"Ministry of Brazilian Health (2020, January 29). Clinical Protocol and Therapeutic Guidance for Hepatitis C and Coinfections, Available online: http:\/\/www.aids.gov.br\/pt-br\/tags\/publicacoes\/protocolo-clinico-e-diretrizes-terapeuticas."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10299","DOI":"10.3748\/wjg.v21.i36.10299","article-title":"Chronic hepatitis C virus infection and lipoprotein metabolism","volume":"21","author":"Aizawa","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.tim.2015.07.007","article-title":"Roles of lipoproteins and apolipoproteins in particle formation of hepatitis C virus","volume":"23","author":"Fukuhara","year":"2015","journal-title":"Trends Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1080\/14789450.2017.1344102","article-title":"Hepatitis C virus\u2013apolipoprotein interactions: Molecular mechanisms and clinical impact","volume":"4","author":"Crouchet","year":"2017","journal-title":"Expert Rev. Proteom."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.tem.2009.07.005","article-title":"Hepatitis C Virus Hijacks Host Lipid Metabolism","volume":"21","author":"Syed","year":"2010","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/nm.3248","article-title":"Understanding the hepatitis C virus life cycle paves the way for highly effective therapies","volume":"19","author":"Scheel","year":"2013","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1053\/j.gastro.2014.07.005","article-title":"Signatures of Protective Memory Immune Responses During HCV Reinfection","volume":"147","author":"Murphy","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1136\/gutjnl-2014-306842","article-title":"Pathobiology of liver fibrosis: A translational success story","volume":"64","author":"Lee","year":"2015","journal-title":"Gut"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.mam.2018.09.002","article-title":"Liver fibrosis: Pathophysiology, pathogenic targets and clinical issues","volume":"65","author":"Parola","year":"2019","journal-title":"Mol. Asp. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e99","DOI":"10.1038\/ctg.2017.25","article-title":"Cathepsin L and B as Potential Markers for Liver Fibrosis: Insights From Patients and Experimental Models","volume":"8","author":"Manchanda","year":"2017","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1002\/hep.24784","article-title":"Protease-activated receptor 2 promotes experimental liver fibrosis in mice and activates human hepatic stellate cells","volume":"55","author":"Knight","year":"2012","journal-title":"Hepatology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1016\/j.jhep.2004.12.008","article-title":"Fibrosis in chronic liver diseases: Diagnosis and management","volume":"42","author":"Pinzani","year":"2005","journal-title":"J. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1111\/liv.12808","article-title":"Accuracy of transient elastography in assessing liver fibrosis in chronic viral hepatitis: A multicentre, retrospective study","volume":"35","author":"Seo","year":"2015","journal-title":"Liver Int."},{"key":"ref_16","first-page":"183","article-title":"Elastograf\u00eda hep\u00e1tica: \u00bfqu\u00e9 es, c\u00f3mo se hace y c\u00f3mo se interpreta?","volume":"60","author":"Romero","year":"2017","journal-title":"Radiolog\u00eda"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1590\/0074-0276130139","article-title":"Performance of diagnostic biomarkers in predicting liver fibrosis among hepatitis C virus-infected Egyptian children","volume":"108","author":"Nassef","year":"2013","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1053\/jhep.2003.50346","article-title":"A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C","volume":"38","author":"Wai","year":"2003","journal-title":"Hepatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1002\/hep.21178","article-title":"Development of a simple noninvasive index to predict significant fibrosis in patients with HIV\/HCV coinfection","volume":"43","author":"Sterling","year":"2006","journal-title":"Hepatology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1053\/j.gastro.2004.11.018","article-title":"Prospective comparison of transient elastography, fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C","volume":"128","author":"Vergniol","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/0014-5793(91)80318-W","article-title":"Novel epoxysuccinyl peptides: Selective inhibitors of cathepsin B., in vitro","volume":"280","author":"Murata","year":"1991","journal-title":"FEBS Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/978-1-4615-9546-5_5","article-title":"Highly selective synthetic inhibitors with regard to plasma-kallikrein activities","volume":"247","author":"Okamoto","year":"1989","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"124","DOI":"10.24171\/j.phrp.2017.8.2.04","article-title":"Quality of Life of Chronic Hepatitis C Patients and Its Associated factors","volume":"8","author":"Cho","year":"2017","journal-title":"Osong Public Health Res. Perspect."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14829","DOI":"10.1074\/jbc.M108180200","article-title":"Phorbol Ester Activation of a Proteolytic Cascade Capable of Activating Latent Transforming Growth Factor \u03b2","volume":"277","author":"Guo","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"47804","DOI":"10.1074\/jbc.M209778200","article-title":"Unusual Proteolytic Activation of Pro-hepatocyte Growth Factor by Plasma Kallikrein and Coagulation Factor XIa","volume":"277","author":"Peek","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1053\/gast.2002.34234","article-title":"Impaired liver regeneration in mice by lipopolysaccharide via TNF-alphakallikrein-mediated activation of latent TGF-beta","volume":"123","author":"Akita","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1172\/JCI200317740","article-title":"Cathepsin B inactivation attenuates hepatic injury and fibrosis during cholestasis","volume":"112","author":"Canbay","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00441-011-1246-y","article-title":"TGF-\u03b2 in progression of liver disease","volume":"347","author":"Dooley","year":"2012","journal-title":"Cell Tissue Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrgastro.2017.38","article-title":"Mechanisms of hepatic stellate cell activation","volume":"14","author":"Tsuchida","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jhep.2008.07.039","article-title":"Exceeding the limits of liver histology markers","volume":"50","author":"Mehta","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_31","unstructured":"Tagaya, N. (2012). Non-Invasive Evaluation of Liver Steatosis, Fibrosis and Cirrhosis in Hepatitis C Virus Infected Patients Using Unidimensional Transient Elastography (FibroscanR). Liver Biopsy: Indications, Procedures, Results, IntechOpen."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1002\/hep.21334","article-title":"FIB-4: A simple, inexpensive and accurate marker of fibrosis in HCV-infected patients","volume":"44","author":"Mallet","year":"2006","journal-title":"Hepatology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.jhep.2010.05.035","article-title":"Diagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: A multicenter prospective study (the FIBROSTIC study)","volume":"53","author":"Degos","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"357287","DOI":"10.1155\/2014\/357287","article-title":"Noninvasive Biomarkers of Liver Fibrosis: An Overview","volume":"2014","author":"Fallatah","year":"2014","journal-title":"Adv. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Xu, H., Kong, W., Liu, L., Chi, X., Wang, X., Wu, R., Gao, X., Wang, H., Qu, L., and Qi, Y. (2017). Accuracy of M2BPGi, compared with Fibro Scan\u00ae, in analysis of liver fibrosis in patients with hepatitis C. BMC Gastroenterol., 17.","DOI":"10.1186\/s12876-017-0618-5"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-pathol-011110-130246","article-title":"Pathogenesis of Liver Fibrosis","volume":"6","author":"Friedman","year":"2011","journal-title":"Annu. Rev. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.bpg.2011.02.005","article-title":"Mechanisms of Hepatic Fibrogenesis","volume":"25","author":"Lee","year":"2011","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1046\/j.1365-2893.1997.00124.x","article-title":"Transforming growth factor-\u00df1 in chronic hepatitis C","volume":"4","author":"Nelson","year":"1997","journal-title":"J. Viral Hepat."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.abb.2019.02.015","article-title":"The role of lysosomal cysteine cathepsins in NLRP3 inflammasome activation","volume":"670","author":"Campden","year":"2019","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"a021907","DOI":"10.1101\/cshperspect.a021907","article-title":"Regulation of the Bioavailability of TGF-\u03b2 and TGF-\u03b2-Related Proteins","volume":"8","author":"Robertson","year":"2016","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s13069-015-0034-9","article-title":"L59 TGF-\u03b2 LAP degradation products serve as a promising blood biomarker for liver fibrogenesis in mice","volume":"8","author":"Hara","year":"2015","journal-title":"Fibrogenesis Tissue Repair"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"H1821","DOI":"10.1152\/ajpheart.2001.280.4.H1821","article-title":"Assembly and activation of HK-PK complex on endothelial cells results in bradykinin liberation and NO formation","volume":"280","author":"Zhao","year":"2001","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/jnc.14793","article-title":"Plasma kallikrein-kinin system contributes to peripheral inflammation in temporal lobe epilepsy","volume":"150","author":"Zanelatto","year":"2019","journal-title":"J. Neurochem."},{"key":"ref_44","first-page":"551","article-title":"High Molecular Weight Kininogen as Substrate for Cathepsin B","volume":"385","author":"Barros","year":"2005","journal-title":"Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.3748\/wjg.15.2190","article-title":"Non-invasive assessment of liver fibrosis in chronic liver diseases: Implementation in clinical practice and decisional algorithms","volume":"15","author":"Sebastiani","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1136\/gut.2010.214650","article-title":"Biopsy and non-invasive methods for the diagnosis of liver fibrosis: Does it take two to tango?","volume":"59","author":"Castera","year":"2010","journal-title":"Gut"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1002\/hep.23584","article-title":"Diagnosis and management of autoimmune hepatitis","volume":"51","author":"Manns","year":"2010","journal-title":"Hepatology"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/10\/9\/1769\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:21:42Z","timestamp":1760142102000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/10\/9\/1769"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,1]]},"references-count":47,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["microorganisms10091769"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms10091769","relation":{},"ISSN":["2076-2607"],"issn-type":[{"type":"electronic","value":"2076-2607"}],"subject":[],"published":{"date-parts":[[2022,9,1]]}}}