{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T05:16:41Z","timestamp":1768540601224,"version":"3.49.0"},"reference-count":47,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MUR PNRR Extended Partnership initiative on Emerging Infectious Disease","award":["PE00000007, INF-ACT"],"award-info":[{"award-number":["PE00000007, INF-ACT"]}]},{"name":"MUR PNRR Extended Partnership initiative on Emerging Infectious Disease","award":["CUP E63C22002090006"],"award-info":[{"award-number":["CUP E63C22002090006"]}]},{"name":"National Research Project PRIN 2022","award":["CUP E53D23001300006"],"award-info":[{"award-number":["CUP E53D23001300006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Dental caries is a multifactorial chronic infectious disease that impacts healthcare costs globally, caused by alterations of the plaque microbiome and proliferation of cariogenic Streptococcus mutans. Treatments targeting S. mutans, such as alternative strategies using probiotics, might be effective in preventing the development of dental caries. In this study, the probiotic formulation of Lactobacillus reuteri SGL01, vitamin C, and acerola was tested against S. mutans DSM20523. Antimicrobial activity was assessed by deferred antagonism and spot-on-lawn assays for L. reuteri SGL01. MIC and MBC of L. reuteri SGL01 cell-free supernatant (CFS), vitamin C, and acerola were determined with the microdilution method. Time\u2013kill assays determined the bactericidal kinetics for each compound. The checkerboard method was used to evaluate the potential synergistic activity of CFS\u2013vitamin C or CFS\u2013acerola at scalar dilutions from 1 to 8X MIC. Lastly, antibiofilm activity was tested for each compound. Antimicrobial activity of L. reuteri SGL01 was first assessed by classic methods. MIC and MBC values differed for one dilution for all compounds, with values of 25% and 50% for CFS, 9.3 mg\/mL and 18.7 mg\/mL for vitamin C, and 18.7 mg\/mL and 37.5 mg\/mL for acerola, respectively. Moreover, time\u2013kill assays confirmed the bactericidal activity at different timepoints: 4 h for CFS, 6 h for vitamin C, and 24 h for acerola. The fractional inhibitory concentration index (FICI) showed indifference for all combinations, and for associations tested at 2, 4, and 8XMIC. S. mutans biofilm production was impaired for all components, with stronger activity by vitamin C and acerola at lower concentrations. The probiotic formulation containing L. reuteri SGl01, vitamin C, and acerola extract exerts a bactericidal effect, especially strong for the CFS, as well as antibiofilm activity. Thus, the combination of these three components could be advantageous for their complementary effects, with use as a novel treatment against the development of dental caries by S. mutans.<\/jats:p>","DOI":"10.3390\/biom16010158","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:13:21Z","timestamp":1768475601000},"page":"158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antimicrobial and Antibiofilm Activity of a Lactobacillus reuteri SGL01, Vitamin C and Acerola Probiotic Formulation Against Streptococcus mutans DSM20523"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7957-4351","authenticated-orcid":false,"given":"Adriana Antonina","family":"Tempesta","sequence":"first","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), Section of Microbiology, University of Catania, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4534-4176","authenticated-orcid":false,"given":"Gaia","family":"Vertillo Aluisio","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), Section of Microbiology, University of Catania, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Di Gregorio","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), Section of Microbiology, University of Catania, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9135-976X","authenticated-orcid":false,"given":"Roberta Lucia","family":"Pecora","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), Section of Microbiology, University of Catania, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0853-9564","authenticated-orcid":false,"given":"Maria Lina","family":"Mezzatesta","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), Section of Microbiology, University of Catania, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0785-7934","authenticated-orcid":false,"given":"Viviana","family":"Cafiso","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), Section of Microbiology, University of Catania, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5673-5048","authenticated-orcid":false,"given":"Eleonora","family":"Chines","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), Section of Microbiology, University of Catania, 95123 Catania, Italy"},{"name":"Department of Public Health, Experimental, and Forensic Medicine, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9006-7262","authenticated-orcid":false,"given":"Giovanni","family":"Barbagallo","sequence":"additional","affiliation":[{"name":"Centro Odontoiatrico Mediterraneo in Agreement with NHS, Private Dental Practice, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1491-4973","authenticated-orcid":false,"given":"Maria","family":"Santagati","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), Section of Microbiology, University of Catania, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10-1128","DOI":"10.1128\/microbiolspec.GPP3-0051-2018","article-title":"The biology of Streptococcus mutans","volume":"7","author":"Lemos","year":"2019","journal-title":"Microbiol. Spectr."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Fitri, D.K., Tuygunov, N., Harun, W.H.A.W., Purwasena, I.A., Cahyanto, A., and Zakaria, M.N. (2025). Key virulence genes associated with Streptococcus mutans biofilm formation: A systematic review. Front. Oral Health, 6.","DOI":"10.3389\/froh.2025.1654428"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1542576","DOI":"10.1155\/cjid\/1542576","article-title":"The Bacterial Biofilms: Formation, Impacts, and Possible Management Targets in the Healthcare System","volume":"2024","author":"Omwenga","year":"2024","journal-title":"Can. J. Infect. Dis. Med. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Almatroudi, A. (2025). Biofilm Resilience: Molecular Mechanisms Driving Antibiotic Resistance in Clinical Contexts. Biology, 14.","DOI":"10.3390\/biology14020165"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"178","DOI":"10.14219\/jada.archive.2008.0134","article-title":"Adverse events associated with chlorhexidine use","volume":"139","author":"McCoy","year":"2008","journal-title":"J. Am. Dent. Assoc."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Fedorowicz, Z., Pedrazzi, V., Oliveira-Neto, J.M., Shinkai, R., and Radhi, A. (2010). Chlorhexidine Treatment for the Prevention of Dental Caries in Children and Adolescents Cochrane Database of Systematic Reviews ed The Cochrane Collaboration, John Wiley & Sons, Ltd.","DOI":"10.1002\/14651858.CD008457"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1159\/000455377","article-title":"Chapter 10: Probiotic Bacteria and Dental Caries","volume":"28","year":"2020","journal-title":"Monogr. Oral Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1002\/cre2.740","article-title":"Oral Lactobacillus species and their probiotic capabilities in patients with periodontitis and periodontally healthy individuals","volume":"9","author":"Etebarian","year":"2023","journal-title":"Clin. Exp. Dent. Res."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Homayouni Rad, A., Pourjafar, H., and Mirzakhani, E. (2023). A comprehensive review of the application of probiotics and postbiotics in oral health. Front. Cell Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1120995"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1007\/s00203-014-0998-7","article-title":"A comparative study of the effect of probiotics on cariogenic biofilm model for preventing dental caries","volume":"196","author":"Lee","year":"2014","journal-title":"Arch. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e0243621","DOI":"10.1128\/aem.02436-21","article-title":"Inhibition of Streptococcus mutans Biofilm Formation by the Joint Action of Oxyresveratrol and Lactobacillus casei","volume":"88","author":"Wu","year":"2022","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1111\/jcmm.13496","article-title":"Probiotic Lactobacillus sp. inhibit growth, biofilm formation and gene expression of caries-inducing Streptococcus mutans","volume":"22","author":"Wasfi","year":"2018","journal-title":"J. Cell Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12602-014-9178-y","article-title":"Antimicrobial Effect of Lactobacillus reuteri on Cariogenic Bacteria Streptococcus gordonii, Streptococcus mutans, and micPeriodontal Diseases Actinomyces naeslundii and Tannerella forsythia","volume":"7","author":"Grondin","year":"2015","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Jones, S.E., and Versalovic, J. (2009). Probiotic Lactobacillus reuteri biofilms produce antimicrobial and anti-inflammatory factors. BMC Microbiol., 9.","DOI":"10.1186\/1471-2180-9-35"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mu, Q., Tavella, V.J., and Luo, X.M. (2018). Role of Lactobacillus reuteri in Human Health and Diseases. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.00757"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0168-1605(96)01180-4","article-title":"Production, purification and characterization of reutericin 6, a bacteriocin with lytic activity produced by Lactobacillus reuteri LA6","volume":"34","author":"Kabuki","year":"1997","journal-title":"Int. J. Food Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1089\/dna.2009.0868","article-title":"Bacterial and Host Interactions of Oral Streptococci","volume":"28","author":"Kreth","year":"2009","journal-title":"DNA Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/prd.12382","article-title":"2021 Probiotics for periodontal health\u2014Current molecular findings","volume":"87","author":"Nguyen","year":"2000","journal-title":"Periodontology"},{"key":"ref_19","first-page":"144","article-title":"Effectiveness of orally administered probiotic Lactobacillus reuteri in patients with peri-implant mucositis: A prospective clinical study","volume":"13","author":"Signorino","year":"2021","journal-title":"J. Osseointegr."},{"key":"ref_20","first-page":"79","article-title":"Clinical effectiveness of Lactobacillus reuteri in the treatment of peri-implant diseases: A systematic review and meta-analysis","volume":"35","author":"Panda","year":"2021","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1111\/jcpe.13191","article-title":"A double-blind, paralleled-arm, placebo-controlled and randomized clinical trial of the effectiveness of probiotics as an adjunct in periodontal care","volume":"46","author":"Pelekos","year":"2019","journal-title":"J. Clin. Periodontol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Dosed\u011bl, M., Jirkovsk\u00fd, E., Mac\u00e1kov\u00e1, K., Kr\u010dmov\u00e1, L., Javorsk\u00e1, L., Pourov\u00e1, J., Mercolini, L., Remi\u00e3o, F., Nov\u00e1kov\u00e1, L., and Mlad\u011bnka, P. (2021). Vitamin C\u2014Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination. Nutrients, 13.","DOI":"10.3390\/nu13020615"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Hassuna, N.A., Rabie, E.M., Mahd, W.K.M., Refaie, M.M.M., Yousef, R.K.M., and Abdelraheem, W.M. (2023). Antibacterial effect of vitamin C against uropathogenic E. coli in vitro and in vivo. BMC Microbiol., 23.","DOI":"10.1186\/s12866-023-02856-3"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1080\/09637486.2018.1498065","article-title":"Impact of combining acerola by-product with a probiotic strain on a gut microbiome model","volume":"70","author":"Bianchi","year":"2019","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Eydou, Z., Jad, B.N., Elsayed, Z., Ismail, A., Magaogao, M., and Hossain, A. (2020). Investigation on the effect of vitamin C on growth & biofilm-forming potential of Streptococcus mutans isolated from patients with dental caries. BMC Microbiol., 20.","DOI":"10.1186\/s12866-020-01914-4"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.jobcr.2024.09.011","article-title":"Microbiological evaluation of vitamin C rich acerola mediated silver and copperoxide nanogel in treatment of periodontitis with and without diabetes mellitus","volume":"14","author":"Kumari","year":"2024","journal-title":"J. Oral Biol. Craniofacial Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Comachio, F.M., Barichello, A., Kielb, G.G., Capoani, G.T., Colpani, G.L., Fiori, M.A., Guti\u00e9rrez, M.V., Corralo, V.D.S., Junior, W.A.R., and Zanetti, M. (2024). Chemical analysis and evaluation of the antimicrobial and antioxidant activities of a vitamin c concentrate obtained from Malpighia emarginata (acerola): Um estudo comparativo. Publica\u00e7\u00e3o Cont\u00ednua, 46.","DOI":"10.5902\/2179460X83711"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e1173","DOI":"10.1002\/mbo3.1173","article-title":"Antimicrobial properties of Lactobacillus cell-free supernatants against multidrug-resistant urogenital pathogens","volume":"10","author":"Scillato","year":"2021","journal-title":"Microbiologyopen"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Aluisio, G.V., Mezzatesta, M.L., Cafiso, V., Scuderi, R., Stefani, S., and Santagati, M. (2024). Cell-free supernatant of Lactobacillus gasseri 1A-TV shows a promising activity to eradicate carbapenem-resistant Klebsiella pneumoniae colonization. Front. Cell. Infect. Microbiol., 14.","DOI":"10.3389\/fcimb.2024.1471107"},{"key":"ref_30","unstructured":"Anon National Committee for Clinical Laboratory Standards (NCCLS) (1999). M21-A: Methodology for the Serum Bactericidal Test, NCCLS. Approved Guideline."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4678","DOI":"10.1128\/AAC.00497-10","article-title":"Synergy Testing by Etest, Microdilution Checkerboard, and Time-Kill Methods for Pan-Drug-Resistant Acinetobacter baumannii","volume":"54","author":"Sopirala","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13568-021-01232-6","article-title":"Biofilm formation by Streptococcus mutans and its inhibition by green tea extracts","volume":"11","author":"Zayed","year":"2021","journal-title":"AMB Express"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e250018","DOI":"10.1590\/1980-549720250018","article-title":"Impact of dental caries on the quality of life of adolescents: A systematic review and meta-analysis","volume":"28","author":"Bordin","year":"2025","journal-title":"Rev. Bras. Epidemiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100904","DOI":"10.1016\/j.identj.2025.100904","article-title":"Global Burden of Dental Caries from 1990 to 2021 and Future Projections","volume":"75","author":"Li","year":"2025","journal-title":"Int. Dent. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10476","DOI":"10.1038\/s41598-025-92523-6","article-title":"Investigating the link between oral health conditions and systemic diseases: A cross-sectional analysis","volume":"15","author":"Natarajan","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41522-024-00488-7","article-title":"How probiotics, prebiotics, synbiotics, and postbiotics prevent dental caries: An oral microbiota perspective","volume":"10","author":"Luo","year":"2024","journal-title":"npj Biofilms Microbiomes"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Liu, Z., Cao, Q., Wang, W., Wang, B., Yang, Y., Xian, C.J., Li, T., and Zhai, Y. (2024). The Impact of Lactobacillus reuteri on Oral and Systemic Health: A Comprehensive Review of Recent Research. Microorganisms, 13.","DOI":"10.3390\/microorganisms13010045"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Banakar, M., Pourhajibagher, M., Etemad-Moghadam, S., Mehran, M., Yazdi, M.H., Haghgoo, R., Alaeddini, M., and Frankenberger, R. (2023). Antimicrobial Effects of Postbiotic Mediators Derived from Lactobacillus rhamnosus GG and Lactobacillus reuteri on Streptococcus mutans. Front. Biosci., 28.","DOI":"10.31083\/j.fbl2805088"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"331","DOI":"10.17796\/1053-4625-42.5.2","article-title":"Effect of Probiotic Lactobacillus reuteri on Salivary Cariogenic Bacterial Counts among Groups of Preschool Children in Jeddah, Saudi Arabia: A Randomized Clinical Trial","volume":"42","author":"Alamoudi","year":"2018","journal-title":"J. Clin. Pediatr. Dent."},{"key":"ref_40","first-page":"35","article-title":"A probiotic lozenge administered medical device and its effect on salivary mutans streptococci and lactobacilli","volume":"18","author":"Kuscu","year":"2007","journal-title":"Int. J. Paediatr. Dent."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1038\/s41598-020-80921-x","article-title":"Lactobacillus reuteri AN417 cell-free culture supernatant as a novel antibacterial agent targeting oral pathogenic bacteria","volume":"11","author":"Yang","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"100136","DOI":"10.1016\/j.bioflm.2023.100136","article-title":"Limosilactobacillus reuteri inhibits the acid tolerance response in oral bacteria","volume":"6","author":"Boisen","year":"2023","journal-title":"Biofilm"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zanetta, P., Squarzanti, D.F., Coste Adi Rolla, R., Valletti, P.A., Garzaro, M., Dell\u2019Era, V., Amoruso, A., Pane, M., Azzimonti, B., and Zanetta, P. (2022). In Vitro Selection of Lactobacillus and Bifidobacterium Probiotic Strains for the Management of Oral Pathobiont Infections Associated to Systemic Diseases International. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232416163"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Liang, J., Zhou, Y., Tang, G., Wu, R., and Lin, H. (2023). Exploration of the Main Antibiofilm Substance of Lactobacillus plantarum ATCC 14917 and Its Effect against Streptococcus mutans. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24031986"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.1007\/s13197-018-3309-5","article-title":"Acerola, an untapped functional superfruit: A review on latest frontiers","volume":"55","author":"Prakash","year":"2018","journal-title":"J. Food Sci. Technol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1080\/1040841X.2021.1915959","article-title":"Inhibition of Streptococcus mutans biofilm formation by strategies targeting the metabolism of exopolysaccharides","volume":"47","author":"Lin","year":"2021","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jac\/dkg301","article-title":"Synergy, antagonism, and what the chequerboard puts between them","volume":"52","author":"Odds","year":"2003","journal-title":"J. Antimicrob. Chemother."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/1\/158\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T12:36:19Z","timestamp":1768480579000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/1\/158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,15]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["biom16010158"],"URL":"https:\/\/doi.org\/10.3390\/biom16010158","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,15]]}}}