{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T13:02:22Z","timestamp":1779714142753,"version":"3.53.1"},"reference-count":61,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Major Project of China","award":["2025D18043047"],"award-info":[{"award-number":["2025D18043047"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aristolochic acid (AA), a naturally occurring compound found in Aristolochia plants, is a well-established nephrotoxin and Group 1 carcinogen. Emerging evidence suggests a potential link between AA exposure and hepatocellular carcinoma (HCC), one of the leading causes of cancer-related mortality worldwide. This review critically evaluates current knowledge on AA\u2019s hepatic metabolism, its formation of persistent DNA adducts, and the induction of inflammatory responses in the liver. Based on preclinical and indirect human evidence, we propose a working hypothesis that AA may contribute to hepatocarcinogenesis through a dual mechanism: genotoxic (primarily via H-ras and p53 mutations resulting from AA-DNA adducts) and non-genotoxic (via chronic inflammation involving IL-6, TNF-\u03b1, and NF-\u03baB activation, as well as epithelial\u2013mesenchymal transition). We note, however, that these mechanisms remain to be validated in human cohorts and do not yet establish causality. Recent studies have identified novel mechanisms, including PDK4-mediated mitochondrial dysfunction, ferroptosis inhibition via p53 hijacking, and ARID1A deficiency as a susceptibility factor. A recent meta-analysis quantified a significantly increased risk of liver cancer following AA exposure in epidemiological studies. While direct causal evidence in humans remains limited, the high mutational burden observed in AA-exposed liver tissues warrants caution. Nevertheless, the primary public health priority pertains to the prevention of AA exposure. Further epidemiological and mechanistic studies are urgently needed.<\/jats:p>","DOI":"10.3390\/ijms27114746","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T11:57:44Z","timestamp":1779710264000},"page":"4746","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aristolochic Acid and Hepatocellular Carcinoma: A Critical Review of Genotoxic and Inflammatory Mechanisms"],"prefix":"10.3390","volume":"27","author":[{"given":"Yupeng","family":"Wang","sequence":"first","affiliation":[{"name":"Institute for Biological Product Control, National Institutes for Food and Drug Control, Beijing 102629, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8106-8820","authenticated-orcid":false,"given":"Yikun","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing 100176, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianqi","family":"Ren","sequence":"additional","affiliation":[{"name":"National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing 100176, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Institute for Biological Product Control, National Institutes for Food and Drug Control, Beijing 102629, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1605-2937","authenticated-orcid":false,"given":"Xingchao","family":"Geng","sequence":"additional","affiliation":[{"name":"Institute for Biological Product Control, National Institutes for Food and Drug Control, Beijing 102629, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.jep.2009.05.028","article-title":"Local uses of Aristolochia species and content of nephrotoxic aristolochic acid 1 and 2\u2014A global assessment based on bibliographic sources","volume":"125","author":"Heinrich","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1039\/c3np70114j","article-title":"Naturally occurring aristolochic acid analogues and their toxicities","volume":"31","author":"Michl","year":"2014","journal-title":"Nat. Prod. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3553","DOI":"10.1007\/s00204-025-04087-z","article-title":"Whether aristolochic acid directly drives hepatocarcinogenesis: Comprehensive investigations from mutational signatures to animal models","volume":"99","author":"Yang","year":"2025","journal-title":"Arch. Toxicol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"19860","DOI":"10.1038\/s41598-019-56394-y","article-title":"Reduction in the Incidence of Urological Cancers after the Ban on Chinese Herbal Products Containing Aristolochic Acid: An Interrupted Time-Series Analysis","volume":"9","author":"Jhuang","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_5","unstructured":"(1990, January 16\u201323). Occupational exposures in insecticide application, and some pesticides. Proceedings of the IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, Lyon, France."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1007\/s11684-024-1058-6","article-title":"Disparities in 36 cancers across 185 countries: Secondary analysis of global cancer statistics","volume":"18","author":"Li","year":"2024","journal-title":"Front. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"eaan6446","DOI":"10.1126\/scitranslmed.aan6446","article-title":"Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia","volume":"9","author":"Ng","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1002\/hep.30863","article-title":"The Mutational Features of Aristolochic Acid-Induced Mouse and Human Liver Cancers","volume":"71","author":"Lu","year":"2020","journal-title":"Hepatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"197ra101","DOI":"10.1126\/scitranslmed.3006086","article-title":"Genome-wide mutational signatures of aristolochic acid and its application as a screening tool","volume":"5","author":"Poon","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1080\/15376516.2025.2457340","article-title":"Clinical and safety outcomes associated with aristolochic acid exposure: A systematic review and meta-analysis","volume":"35","author":"Cui","year":"2025","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/path.6224","article-title":"New risk factors and molecular landscapes of hepatic angiosarcoma in the Taiwanese population","volume":"262","author":"Chung","year":"2024","journal-title":"J. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s13020-024-01003-y","article-title":"Unveiling correlations between aristolochic acids and liver cancer: Spatiotemporal heterogeneity phenomenon","volume":"19","author":"Li","year":"2024","journal-title":"Chin. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.fct.2016.03.014","article-title":"European medicinal and edible plants associated with subacute and chronic toxicity part II: Plants with hepato-, neuro-, nephro- and immunotoxic effects","volume":"92","author":"Kristanc","year":"2016","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1007\/BF00293699","article-title":"Tumour induction in mice following exposure to aristolochic acid","volume":"61","author":"Mengs","year":"1988","journal-title":"Arch. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1021\/tx010059z","article-title":"Human enzymes involved in the metabolic activation of carcinogenic aristolochic acids: Evidence for reductive activation by cytochromes P450 1A1 and 1A2","volume":"14","author":"Frei","year":"2001","journal-title":"Chem. Res. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1093\/toxsci\/kfr306","article-title":"Bioactivation versus detoxication of the urothelial carcinogen aristolochic acid I by human cytochrome P450 1A1 and 1A2","volume":"125","author":"Shi","year":"2012","journal-title":"Toxicol. Sci. Off. J. Soc. Toxicol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1093\/mutage\/17.4.265","article-title":"Aristolochic acid as a probable human cancer hazard in herbal remedies: A review","volume":"17","author":"Arlt","year":"2002","journal-title":"Mutagenesis"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e95978","DOI":"10.1172\/jci.insight.95978","article-title":"Human liver-kidney model elucidates the mechanisms of aristolochic acid nephrotoxicity","volume":"2","author":"Chang","year":"2017","journal-title":"JCI Insight"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1093\/toxsci\/kfr138","article-title":"Inhibition of renal NQO1 activity by dicoumarol suppresses nitroreduction of aristolochic acid I and attenuates its nephrotoxicity","volume":"122","author":"Chen","year":"2011","journal-title":"Toxicol. Sci. Off. J. Soc. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/ijc.20564","article-title":"Human hepatic and renal microsomes, cytochromes P450 1A1\/2, NADPH:cytochrome P450 reductase and prostaglandin H synthase mediate the formation of aristolochic acid-DNA adducts found in patients with urothelial cancer","volume":"113","author":"Frei","year":"2005","journal-title":"Int. J. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1021\/tx200333g","article-title":"Aristolochic acid I metabolism in the isolated perfused rat kidney","volume":"25","author":"Priestap","year":"2012","journal-title":"Chem. Res. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"107358","DOI":"10.1016\/j.jbc.2024.107358","article-title":"Structural and mechanistic insights into the transport of aristolochic acids and their active metabolites by human serum albumin","volume":"300","author":"Pomyalov","year":"2024","journal-title":"J. Biol. Chem."},{"key":"ref_23","first-page":"2025","article-title":"Detection of DNA adducts formed by aristolochic acid in renal tissue from patients with Chinese herbs nephropathy","volume":"56","author":"Schmeiser","year":"1996","journal-title":"Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1056\/NEJM200006083422301","article-title":"Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi)","volume":"342","author":"Nortier","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_25","first-page":"5464","article-title":"Aristolochic acid activates ras genes in rat tumors at deoxyadenosine residues","volume":"50","author":"Schmeiser","year":"1990","journal-title":"Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e11-7","DOI":"10.1053\/j.ajkd.2003.11.024","article-title":"DNA adducts and p53 mutations in a patient with aristolochic acid-associated nephropathy","volume":"43","author":"Lord","year":"2004","journal-title":"Am. J. Kidney Dis. Off. J. Natl. Kidney Found."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/978-1-4757-3230-6_20","article-title":"Carcinogen-DNA adducts as tools in risk assessment","volume":"472","author":"Airoldi","year":"1999","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.freeradbiomed.2023.05.005","article-title":"An unprecedented free radical mechanism for the formation of DNA adducts by the carcinogenic N-sulfonated metabolite of aristolochic acids","volume":"205","author":"Li","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1021\/acs.chemrestox.3c00255","article-title":"Tissue Organoid Cultures Metabolize Dietary Carcinogens Proficiently and Are Effective Models for DNA Adduct Formation","volume":"37","author":"Kucab","year":"2024","journal-title":"Chem. Res. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1093\/mutage\/geaf012","article-title":"Genotoxic effects of aristolochic acid I on functional human-induced hepatocyte-like cells","volume":"40","author":"Hu","year":"2025","journal-title":"Mutagenesis"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/sj.bjc.6602420","article-title":"Mutagenicity of comfrey (Symphytum Officinale) in rat liver","volume":"92","author":"Mei","year":"2005","journal-title":"Br. J. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chen, T., Guo, L., Zhang, L., Shi, L., Fang, H., Sun, Y., Fuscoe, J.C., and Mei, N. (2006). Gene expression profiles distinguish the carcinogenic effects of aristolochic acid in target (kidney) and non-target (liver) tissues in rats. BMC Bioinform., 7.","DOI":"10.1186\/1471-2105-7-S2-S20"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1038\/s41586-024-07054-3","article-title":"Deep whole-genome analysis of 494 hepatocellular carcinomas","volume":"627","author":"Chen","year":"2024","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Fang, Z., Wang, C., Niu, M., Liu, T., Ren, L., Li, Q., Li, Z., Wei, Z., Lin, L., and Mu, W. (2022). Integration of Transcriptomic and Metabolomic Data to Compare the Hepatotoxicity of Neonatal and Adult Mice Exposed to Aristolochic Acid I. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.840961"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/BF01973700","article-title":"Renal toxicity of aristolochic acid in rats as an example of nephrotoxicity testing in routine toxicology","volume":"67","author":"Mengs","year":"1993","journal-title":"Arch. Toxicol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1158\/1940-6207.CAPR-15-0339","article-title":"Hepatic Premalignant Alterations Triggered by Human Nephrotoxin Aristolochic Acid I in Canines","volume":"9","author":"Jin","year":"2016","journal-title":"Cancer Prev. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.jep.2011.03.054","article-title":"Kinetics of aristolochic acid I after oral administration of Radix Aristolochiae or Guanxinsuhe preparation in canines","volume":"135","author":"Yang","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1021\/acs.chemrestox.3c00333","article-title":"Screening DNA Damage in the Rat Kidney and Liver by Untargeted DNA Adductomics","volume":"37","author":"Ragi","year":"2024","journal-title":"Chem. Res. Toxicol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/nrc4017","article-title":"Functional and genetic deconstruction of the cellular origin in liver cancer","volume":"15","author":"Marquardt","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/em.21710","article-title":"ACB-PCR measurement of H-ras codon 61 CAA\u2192CTA mutation provides an early indication of aristolochic acid I carcinogenic effect in tumor target tissues","volume":"53","author":"Wang","year":"2012","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"10350","DOI":"10.1073\/pnas.91.22.10350","article-title":"Hepatitis B virus HBx protein activates Ras-GTP complex formation and establishes a Ras, Raf, MAP kinase signaling cascade","volume":"91","author":"Benn","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","first-page":"3347","article-title":"Activation of the Ha-, Ki-, and N-ras genes in chemically induced liver tumors from CD-1 mice","volume":"52","author":"Manam","year":"1992","journal-title":"Cancer Res."},{"key":"ref_43","first-page":"25","article-title":"Mutations at codon 249 of p53 gene in human hepatocellular carcinomas from Tongan, China","volume":"381","author":"Yang","year":"1997","journal-title":"Mutat. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1093\/carcin\/23.3.435","article-title":"Generation and characterization of p53 null transformed hepatic progenitor cells: Oval cells give rise to hepatocellular carcinoma","volume":"23","author":"Dumble","year":"2002","journal-title":"Carcinogenesis"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/jcb.23400","article-title":"Links between mutant p53 and genomic instability","volume":"113","author":"Hanel","year":"2012","journal-title":"J. Cell. Biochem."},{"key":"ref_46","first-page":"4003","article-title":"Effect of superoxide and inflammatory factor on aflatoxin B1 triggered hepatocellular carcinoma","volume":"8","author":"Qin","year":"2016","journal-title":"Am. J. Transl. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1093\/carcin\/bgg101","article-title":"Prospective detection of codon 249 mutations in plasma of hepatocellular carcinoma patients","volume":"24","author":"Jackson","year":"2003","journal-title":"Carcinogenesis"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/s41401-024-01354-0","article-title":"Aristolochic acids-hijacked p53 promotes liver cancer cell growth by inhibiting ferroptosis","volume":"46","author":"Hou","year":"2025","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.cell.2009.12.052","article-title":"Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression","volume":"140","author":"Park","year":"2010","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1007\/s00210-018-1538-9","article-title":"A comparison between the effects of ochratoxin A and aristolochic acid on the inflammation and oxidative stress in the liver and kidney of weanling piglets","volume":"391","author":"Marin","year":"2018","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_51","first-page":"302","article-title":"Molecular mechanisms controlling the phenotype and the EMT\/MET dynamics of hepatocyte","volume":"35","author":"Cicchini","year":"2015","journal-title":"Liver Int. Off. J. Int. Assoc. Study Liver"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Fabregat, I., and Caballero-D\u00edaz, D. (2018). Transforming Growth Factor-\u03b2-Induced Cell Plasticity in Liver Fibrosis and Hepatocarcinogenesis. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00357"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"115592","DOI":"10.1016\/j.fct.2025.115592","article-title":"Mechanisms of aristolochic acid I Hepatotoxicity: Central role of PDK4-Induced mitochondrial dysfunction and hepatic inflammation","volume":"203","author":"Wang","year":"2025","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Xing, S., Yu, W., Zhang, X., Luo, Y., Lei, Z., Huang, D., Lin, J., Huang, Y., Huang, S., and Nong, F. (2018). Isoviolanthin Extracted from Dendrobium officinale Reverses TGF-\u03b21-Mediated Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma Cells via Deactivating the TGF-\u03b2\/Smad and PI3K\/Akt\/mTOR Signaling Pathways. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061556"},{"key":"ref_55","first-page":"2956","article-title":"MiR-155 up-regulated by TGF-\u03b2 promotes epithelial-mesenchymal transition, invasion and metastasis of human hepatocellular carcinoma cells in vitro","volume":"9","author":"Li","year":"2017","journal-title":"Am. J. Transl. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/j.1365-2184.2006.00371.x","article-title":"Early induction of TGF-beta1 through a fasting-re-feeding regimen promotes liver carcinogenesis by a sub-initiating dose of diethylnitrosamine","volume":"39","author":"Tessitore","year":"2006","journal-title":"Cell Prolif."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e13981","DOI":"10.1002\/advs.202513981","article-title":"Arid1a Deficiency Drives Aristolochic Acid-Induced Liver Tumorigenesis through Ctnnb1 Mutation and Defective Nucleotide Excision Repair","volume":"13","author":"Wang","year":"2026","journal-title":"Adv. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1093\/mutage\/ger023","article-title":"Aristolochic acid-induced carcinogenesis examined by ACB-PCR quantification of H-Ras and K-Ras mutant fraction","volume":"26","author":"Wang","year":"2011","journal-title":"Mutagenesis"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.toxlet.2006.04.008","article-title":"Mutations induced by carcinogenic doses of aristolochic acid in kidney of Big Blue transgenic rats","volume":"165","author":"Chen","year":"2006","journal-title":"Toxicol. Lett."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1016\/j.apsb.2021.11.011","article-title":"Aristolochic acids exposure was not the main cause of liver tumorigenesis in adulthood","volume":"12","author":"Chen","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Teschke, R., and Andrade, R.J. (2016). Drug, Herb, and Dietary Supplement Hepatotoxicity. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17091488"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4746\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T12:03:22Z","timestamp":1779710602000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4746"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,25]]},"references-count":61,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27114746"],"URL":"https:\/\/doi.org\/10.3390\/ijms27114746","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,25]]}}}