{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T18:07:46Z","timestamp":1785607666972,"version":"3.56.0"},"reference-count":60,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sanfilippo syndrome type B, also known as mucopolysaccharidosis type IIIB (MPS IIIB), is a rare autosomal recessive lysosomal storage disorder caused by mutations in the N-acetyl-\u03b1-D-glucosaminidase (NAGLU) gene, which encodes the enzyme \u03b1-N-acetylglucosaminidase. This enzyme is essential for degrading heparan sulfate. The deficiency leads to toxic accumulation within cells. To investigate the impact of NAGLU mutations, mutational data were retrieved from public databases including NCBI, UniProt, and HGMD. A total of 162 variants were evaluated using sequence-based prediction tools to identify deleterious mutations, followed by structure-based in silico analyses to assess changes in protein stability, biophysical properties, and ligand-binding potential. Among the analyzed mutations, the I154R variant was identified as the most deleterious, showing disease-associated characteristics, structural instability, and impaired functional properties. Molecular docking with N-acetylglucosamine (NAG) revealed binding affinities of \u22124.17 kcal\/mol for the native protein and \u22123.97 kcal\/mol for the I154R mutant, suggesting a retained yet slightly reduced binding potential. Molecular dynamics simulations supported these findings, indicating stable trajectories, favorable interaction profiles, and moderate flexibility for both complexes. These results enhance our understanding of NAGLU-related pathogenicity in MPS IIIB, contributing to improved health care strategies and offering a valuable foundation for future therapeutic developments targeting enzyme dysfunction in Sanfilippo syndrome type B.<\/jats:p>","DOI":"10.3390\/ijms27104404","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T08:50:12Z","timestamp":1778835012000},"page":"4404","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular Modeling of N-Acetylglucosamine Binding to the I154R Mutant of NAGLU: Pathogenic Insights into Sanfilippo Syndrome Type B"],"prefix":"10.3390","volume":"27","author":[{"given":"Priyanka","family":"Kannan","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Sri Ramachandra Institute of Higher Education and Research (DU), Porur, Chennai 600116, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhana","family":"Priya Nanda Kumar","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Sri Ramachandra Institute of Higher Education and Research (DU), Porur, Chennai 600116, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9202-2201","authenticated-orcid":false,"given":"Sidharth","family":"Kumar Nanda Kumar","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Sri Ramachandra Institute of Higher Education and Research (DU), Porur, Chennai 600116, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2277-0974","authenticated-orcid":false,"given":"Vasundra","family":"Vasudevan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Sri Ramachandra Institute of Higher Education and Research (DU), Porur, Chennai 600116, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuppan","family":"Kaviarasan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Sri Ramachandra Institute of Higher Education and Research (DU), Porur, Chennai 600116, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9508-8097","authenticated-orcid":false,"given":"Magesh","family":"Ramasamy","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Sri Ramachandra Institute of Higher Education and Research (DU), Porur, Chennai 600116, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"ref_1","first-page":"e30519","article-title":"A Novel Mutation in the NAGLU (N-Acetyl-Alpha-Glucosaminidase) Gene Associated with Mucopolysaccharidosis Type III-B in a Saudi Girl","volume":"14","author":"Albar","year":"2022","journal-title":"Cureus"},{"key":"ref_2","first-page":"173","article-title":"A Novel Pathogenic Variant in NAGLU (N-Acetyl-Alpha-Glucosaminidase) gene Identified by Targeted Next-Generation Sequencing Followed by in silico Analysis","volume":"13","author":"Khorrami","year":"2019","journal-title":"Iran. J. Child Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1086\/301685","article-title":"NAGLU mutations underlying Sanfilippo syndrome type B","volume":"62","author":"Schmidtchen","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s10038-005-0258-4","article-title":"Sanfilippo type B syndrome: Five patients with an R565P homozygous mutation in the alpha-N-acetylglucosaminidase gene from the Okinawa islands in Japan","volume":"50","author":"Chinen","year":"2005","journal-title":"J. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.jpeds.2004.01.046","article-title":"Enzyme replacement therapy for mucopolysaccharidosis I: A randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase)","volume":"144","author":"Wraith","year":"2004","journal-title":"J. Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100580","DOI":"10.1016\/j.mgene.2019.100580","article-title":"Identification of Three Novel Homozygous NAGLU Mutations in Egyptian Patients with Sanfilippo Syndrome B","volume":"21","author":"Mohammed","year":"2019","journal-title":"Meta Gene"},{"key":"ref_7","first-page":"28","article-title":"Identification of novel NAGLU mutations in Sanfilippo syndrome type B patients","volume":"36","author":"Bunge","year":"1999","journal-title":"Int. J. Mol. Sci."},{"key":"ref_8","first-page":"6101","article-title":"The molecular basis of Sanfilippo syndrome type B (a-N-acetylglucosaminidase\/mucopolysaccharidosis III B\/lysosomal storage disease)","volume":"93","author":"Zhao","year":"1996","journal-title":"Med. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Meikle, P.J., Fuller, M., and Hopwood, J.J. (2005). Lysosomal degradation of heparin and heparan sulfate. Chemistry and Biology of Heparin and Heparan Sulfate, Elsevier.","DOI":"10.1016\/B978-008044859-6\/50011-3"},{"key":"ref_10","first-page":"100732","article-title":"Clinical and genetic features of 13 patients with mucopolysaccarhidosis type IIIB: Description of two novel NAGLU gene mutations","volume":"27","author":"Ozkinay","year":"2021","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_11","unstructured":"Garg, U., Smith, L.D., and Yu, C. (2017). Lysosomal storage disorders: Mucopolysaccharidoses. Biomarkers in Inborn Errors of Metabolism, Elsevier."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s13023-018-0796-4","article-title":"Epidemiology of Sanfilippo syndrome: Results of a systematic literature review","volume":"13","author":"Zelei","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jsb.2019.02.005","article-title":"Structural characterization of the \u03b1-N-acetylglucosaminidase, a key enzyme in the pathogenesis of Sanfilippo syndrome B","volume":"205","author":"Birrane","year":"2019","journal-title":"J. Struct. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/S1474-4422(17)30169-2","article-title":"Intracerebral gene therapy in children with mucopolysaccharidosis type IIIB syndrome: An uncontrolled phase 1\/2 clinical trial","volume":"16","author":"Tardieu","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_15","first-page":"22","article-title":"Emerging Therapies for the Treatment of Mucopolysaccharidosis Type III","volume":"3","year":"2018","journal-title":"Turk. J. Mol. Biol. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1007\/s11030-023-10694-8","article-title":"Elucidating the functional impact of G137V and G144R variants in Maroteaux Lamy\u2019s Syndrome by Molecular Dynamics Simulation","volume":"28","author":"Priya","year":"2023","journal-title":"Mol. Divers."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s13023-017-0678-1","article-title":"Phenotype prediction for mucopolysaccharidosis type I by in silico analysis","volume":"12","author":"Ou","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1007\/s11011-019-00465-6","article-title":"Bioinformatics classification of mutations in patients with Mucopolysaccharidosis IIIA","volume":"34","author":"Tanwar","year":"2019","journal-title":"Metab. Brain Dis."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ugrinov, K.G., Freed, S.D., Thomas, C.L., and Lee, S.W. (2015). A multiparametric computational algorithm for comprehensive assessment of genetic mutations in mucopolysaccharidosis type IIIA (Sanfilippo Syndrome). PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0121511"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Doss, C.G.P., and Rajith, B. (2012). Computational refinement of functional single nucleotide polymorphisms associated with ATM gene. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034573"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Rajith, B., and Doss, C.G.P. (2011). Path to facilitate the prediction of functional amino acid substitutions in red blood cell disorders\u2014A computational approach. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024607"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s11011-020-00650-y","article-title":"A computational approach to analyse the amino acid variants of GLB1 protein causing GM1 gangliosidosis","volume":"36","author":"Priyanka","year":"2021","journal-title":"Metab. Brain Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8561","DOI":"10.1080\/07391102.2022.2135598","article-title":"Elucidating the mutational impact in causing Niemann\u2013Pick disease type C: An in silico approach","volume":"41","author":"Kannan","year":"2023","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4121","DOI":"10.1080\/07391102.2023.2218927","article-title":"Unravelling the relacatib activity against the CTSK proteins causing pycnodysostosis: A molecular docking and dynamics approach","volume":"42","author":"Kannan","year":"2024","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1002\/ccr3.1521","article-title":"A novel mutation in the NAGLU gene associated with Sanfilippo syndrome type B (mucopolysaccharidosis III B)","volume":"6","author":"Hettiarachchi","year":"2018","journal-title":"Clin. Case Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1007\/s100380200070","article-title":"Molecular analysis of the \u03b1-N-acetylglucosaminidase gene in seven Japanese patients from six unrelated families with mucopolysaccharidosis IIIB (Sanfilippo type B), including two novel mutations","volume":"47","author":"Tanaka","year":"2002","journal-title":"J. Hum. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Celik, B., Tomatsu, S.C., Tomatsu, S., and Khan, S.A. (2021). Epidemiology of Mucopolysaccharidoses Update. Diagnostics, 11.","DOI":"10.3390\/diagnostics11020273"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.ymgme.2007.09.011","article-title":"Clinical and genetic spectrum of Sanfilippo type C (MPS IIIC) disease in The Netherlands","volume":"93","author":"Ruijter","year":"2008","journal-title":"Mol. Genet. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"146","DOI":"10.2174\/157340911795677602","article-title":"Molecular Docking: A Powerful Approach for Structure-Based Drug Discovery","volume":"7","author":"Meng","year":"2011","journal-title":"Curr. Comput. Aided-Drug Des."},{"key":"ref_30","first-page":"13384","article-title":"Molecular Docking and Structure-Based Drug Design Strategies","volume":"20","author":"Ferreira","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Puglisi, R. (2022). Protein Mutations and Stability, a Link with Disease: The Case Study of Frataxin. Biomedicines, 10.","DOI":"10.3390\/biomedicines10020425"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"102498","DOI":"10.1016\/j.sbi.2022.102498","article-title":"Constant pH molecular dynamics simulations: Current status and recent applications","volume":"77","author":"Liu","year":"2022","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"111368","DOI":"10.1016\/j.isci.2024.111368","article-title":"Elucidating the Linagliptin and Fibroblast Activation Protein Binding Mechanism through Molecular Dynamics and Binding Free Energy Analysis","volume":"27","author":"Shi","year":"2024","journal-title":"iScience"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s11011-024-01341-8","article-title":"A computational approach to analyzing the functional and structural impacts of Tripeptidyl-Peptidase 1 missense mutations in neuronal ceroid lipofuscinosis","volume":"39","author":"Kannan","year":"2024","journal-title":"Metab. Brain Dis."},{"key":"ref_35","first-page":"1208","article-title":"Exploring the impact of variations in the mucolipin1 protein that result in mucolipidosis type 4 using the technique of molecular docking and dynamics simulation","volume":"44","author":"Kannan","year":"2024","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e04710","DOI":"10.1002\/slct.202504710","article-title":"Computational analysis of SMPD1 mutants and their binding affinity with desipramine: A therapeutic insight into Niemann\u2013Pick disease type A","volume":"10","author":"Kannan","year":"2025","journal-title":"ChemistrySelect"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1093\/nar\/gkg520","article-title":"SWISS-MODEL: An automated protein homology-modeling server","volume":"31","author":"Schwede","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"W344","DOI":"10.1093\/nar\/gkw408","article-title":"ConSurf2016: An improved methodology to estimate and visualize evolutionary conservation in macromolecules","volume":"44","author":"Ashkenazy","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Capriotti, E., Altman, R.B., and Bromberg, Y. (2013). Collective judgment predicts disease-associated single nucleotide variants. BMC Genom., 14.","DOI":"10.1186\/1471-2164-14-S3-S2"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Bendl, J., Stourac, J., Salanda, O., Pavelka, A., Wieben, E.D., Zendulka, J., Brezovsky, J., and Damborsky, J. (2014). PredictSNP: Robust and Accurate Consensus Classifier for Prediction of Disease-Related Mutations. PLoS Comput. Biol., 10.","DOI":"10.1371\/journal.pcbi.1003440"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1002\/humu.23553","article-title":"Improved, ACMG-compliant, in silico prediction of pathogenicity for missense substitutions encoded by TP53 variants","volume":"39","author":"Fortuno","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.csbj.2020.02.021","article-title":"iStable 2.0: Predicting protein thermal stability changes by integrating various characteristic modules","volume":"18","author":"Chen","year":"2020","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"W350","DOI":"10.1093\/nar\/gky300","article-title":"DynaMut: Predicting the impact of mutations on protein conformation, flexibility and stability","volume":"46","author":"Rodrigues","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"D527","DOI":"10.1093\/nar\/gki086","article-title":"SNPeffect: A database mapping molecular phenotypic effects of human non-synonymous coding SNPs","volume":"33","author":"Reumers","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1093\/nar\/gkr996","article-title":"SNPeffect 4.0: On-line prediction of molecular and structural effects of protein-coding variants","volume":"40","author":"Reumers","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Venselaar, H., Beek, T.A.H.T., Kuipers, R.K.P., Hekkelman, M.L., and Vriend, G. (2010). Protein structure analysis of mutations causing inheritable diseases. An e-Science approach with life scientist friendly interfaces. BMC Bioinform., 11.","DOI":"10.1186\/1471-2105-11-548"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1002\/jcb.25920","article-title":"Structural Analysis of G1691S Variant in the Human Filamin B Gene Responsible for Larsen Syndrome: A Comparative Computational Approach","volume":"118","author":"Sneha","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1007\/s11011-018-0278-3","article-title":"Computational approach to unravel the impact of missense mutations of proteins (D2HGDH and IDH2) causing D-2-hydroxyglutaric aciduria 2","volume":"33","author":"Kumar","year":"2018","journal-title":"Metab. Brain Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"W363","DOI":"10.1093\/nar\/gky473","article-title":"CASTp 3.0: Computed atlas of surface topography of proteins","volume":"46","author":"Tian","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"El-hachem, N., Haibe-kains, B., Khalil, A., Kobeissy, F.H., and Nemer, G. (2017). AutoDock and AutoDockTools for Protein-Ligand Docking: Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1(BACE1) as a Case Study. Neuroproteomics, Humana.","DOI":"10.1007\/978-1-4939-6952-4_20"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/978-1-59745-177-2_19","article-title":"Molecular docking","volume":"Volume 443","author":"Morris","year":"2008","journal-title":"Molecular Modeling of Proteins"},{"key":"ref_52","unstructured":"Dassault, R.M., Villacoublay, V., and Becard, N. (2026, March 15). Dassault Syst\u00e8mes Datafirst 78946. Available online: https:\/\/www.3ds.com\/."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/s00249-011-0700-9","article-title":"Definition and testing of the GROMOS force-field versions 54A7 and 54B7","volume":"40","author":"Schmid","year":"2011","journal-title":"Eur. Biophys. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1107\/S0907444904011679","article-title":"PRODRG: A tool for high-throughput crystallography of protein-ligand complexes","volume":"60","year":"2004","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1093\/protein\/gzm029","article-title":"Molecular dynamics studies of AChBP with nicotine and carbamylcholine: The role of water in the binding pocket","volume":"20","author":"Amiri","year":"2007","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1080\/07391102.2019.1605934","article-title":"Conformational insights into the inhibitory mechanism of phyto-compounds against Src kinase family members implicated in psoriasis","volume":"38","author":"Sundarrajan","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1021\/ci500020m","article-title":"g_mmpbsa\u2014A GROMACS tool for high-throughput MM-PBSA calculations","volume":"54","author":"Kumari","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s00894-021-04835-9","article-title":"Investigation of the reactivity properties of a thiourea derivative with anticancer activity by DFT and MD simulations","volume":"27","author":"Mary","year":"2021","journal-title":"J. Mol. Model."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Hassan, M., Shahzadi, S., Seo, S.Y., Alashwal, H., Zaki, N., and Moustafa, A.A. (2018). Molecular Docking and Dynamic Simulation of AZD3293 and Solanezumab Effects against BACE1 to Treat Alzheimer\u2019s Disease. Front. Comput. Neurosci., 12.","DOI":"10.3389\/fncom.2018.00034"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6849","DOI":"10.1038\/s41598-021-86211-4","article-title":"In silico studies reveal structural deviations of mutant profilin-1 and interaction with riluzole and edaravone in amyotrophic lateral sclerosis","volume":"11","author":"Sadr","year":"2021","journal-title":"Sci. Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4404\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T08:53:00Z","timestamp":1778835180000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4404"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,15]]},"references-count":60,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27104404"],"URL":"https:\/\/doi.org\/10.3390\/ijms27104404","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,15]]}}}