{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T16:12:44Z","timestamp":1785341564131,"version":"3.55.0"},"reference-count":44,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P42ES05948"],"award-info":[{"award-number":["P42ES05948"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30ES10126"],"award-info":[{"award-number":["P30ES10126"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1ES06721"],"award-info":[{"award-number":["RO1ES06721"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P42ES04705"],"award-info":[{"award-number":["P42ES04705"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P42ES05948"],"award-info":[{"award-number":["P42ES05948"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30ES10126"],"award-info":[{"award-number":["P30ES10126"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1ES06721"],"award-info":[{"award-number":["RO1ES06721"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P42ES04705"],"award-info":[{"award-number":["P42ES04705"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P42ES05948"],"award-info":[{"award-number":["P42ES05948"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30ES10126"],"award-info":[{"award-number":["P30ES10126"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1ES06721"],"award-info":[{"award-number":["RO1ES06721"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P42ES04705"],"award-info":[{"award-number":["P42ES04705"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P42ES05948"],"award-info":[{"award-number":["P42ES05948"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30ES10126"],"award-info":[{"award-number":["P30ES10126"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1ES06721"],"award-info":[{"award-number":["RO1ES06721"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P42ES04705"],"award-info":[{"award-number":["P42ES04705"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Cancer Institute","award":["P42ES05948"],"award-info":[{"award-number":["P42ES05948"]}]},{"name":"National Cancer Institute","award":["P30ES10126"],"award-info":[{"award-number":["P30ES10126"]}]},{"name":"National Cancer Institute","award":["RO1ES06721"],"award-info":[{"award-number":["RO1ES06721"]}]},{"name":"National Cancer Institute","award":["P42ES04705"],"award-info":[{"award-number":["P42ES04705"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Benzene is a ubiquitous environmental pollutant that induces blood cancers via its complex metabolism. Since cancer risks to the general public involve toxic benzene metabolites derived from the inhalation of benzene at ppb air concentrations, questions remain regarding low-dose metabolism. Using previously published data from 389 Chinese workers, we fit Michaelis\u2013Menten-like models to predict urinary concentrations of E,E-muconic acid (the most discriminating urinary metabolite) as functions of urinary benzene levels between 0.0001 \u03bcM and 54 \u03bcM, equivalent to benzene air concentrations between 0.1 ppb and more than 100 ppm. When we compared models having either one or two metabolic pathways, weights of evidence favoring two pathways were essentially 100 percent for nonsmoking males and females and 58 percent for smoking males. At ppb exposure levels, metabolic rates for the high-affinity pathway were 43-fold greater than those for the low-affinity pathway in nonsmoking males, 6.5-fold greater in nonsmoking females, and 4.9-fold greater in smoking males. Thus, the high-affinity pathway is most efficient in nonsmoking males and is inhibited by smoking. The characteristics of the two-pathway model implicate lung metabolism of benzene via CYP2A13 and\/or CYP2F1 at ppb air levels and liver metabolism by CYP2E1 above one ppm. Since ambient benzene concentrations are typically less than 10 ppb, blood-cancer risks predicted from workers exposed to above 1 ppm likely underestimate risks to the general public by many fold, and these risks may be modulated by smoking. Also, since the lung is the site of initial metabolism upon inhalation, the respiratory bioactivation of benzene could contribute to lung-cancer incidence, including that for lung adenomas in never smokers.<\/jats:p>","DOI":"10.3390\/ijms26178550","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T08:08:46Z","timestamp":1756973326000},"page":"8550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Benzene Metabolism Is Dominated by a High-Affinity Pathway at Ambient Exposures with Implications for Cancer Risks"],"prefix":"10.3390","volume":"26","author":[{"given":"Reuben","family":"Thomas","sequence":"first","affiliation":[{"name":"J. David Gladstone Institutes, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1378-8795","authenticated-orcid":false,"given":"Sungkyoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul 08826, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Lan","sequence":"additional","affiliation":[{"name":"Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Service, Rockville, MD 20850, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4082-8163","authenticated-orcid":false,"given":"Roel","family":"Vermeulen","sequence":"additional","affiliation":[{"name":"Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, 3508 TD Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7866-8391","authenticated-orcid":false,"given":"Luoping","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, University of California, Berkeley, CA 94720, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel","family":"Rothman","sequence":"additional","affiliation":[{"name":"Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Service, Rockville, MD 20850, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martyn T.","family":"Smith","sequence":"additional","affiliation":[{"name":"School of Public Health, University of California, Berkeley, CA 94720, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Rappaport","sequence":"additional","affiliation":[{"name":"School of Public Health, University of California, Berkeley, CA 94720, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"ref_1","unstructured":"IARC (2018). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Benzene, International Agency for Research on Cancer."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1097\/01.ede.0000082001.05563.e0","article-title":"Leukemia risk associated with low-level benzene exposure","volume":"14","author":"Glass","year":"2003","journal-title":"Epidemiology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1002\/ijc.29591","article-title":"A retrospective cohort study of cause-specific mortality and incidence of hematopoietic malignancies in Chinese benzene-exposed workers","volume":"137","author":"Linet","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1081\/DMR-200033445","article-title":"Xenobiotic metabolism and the mechanism(s) of benzene toxicity","volume":"36","author":"Snyder","year":"2004","journal-title":"Drug Metab. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1080\/00984100050166361","article-title":"The role of metabolism and specific metabolites in benzene-induced toxicity: Evidence and issues","volume":"61","author":"Ross","year":"2000","journal-title":"J. Toxicol. Environ. Health A"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.toxlet.2014.10.007","article-title":"Metabolic polymorphisms and biomarkers of effect in the biomonitoring of occupational exposure to low-levels of benzene: State of the art","volume":"231","author":"Manno","year":"2014","journal-title":"Toxicol. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/carcin\/bgi297","article-title":"Using urinary biomarkers to elucidate dose-related patterns of human benzene metabolism","volume":"27","author":"Kim","year":"2006","journal-title":"Carcinogenesis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.1002\/ijc.32202","article-title":"Residential ambient benzene exposure in the United States and subsequent risk of hematologic malignancies","volume":"145","author":"Teras","year":"2019","journal-title":"Int. J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1093\/jnci\/djs411","article-title":"Myelodysplastic syndrome and benzene exposure among petroleum workers: An international pooled analysis","volume":"104","author":"Schnatter","year":"2012","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/aje\/kwv120","article-title":"Parental, In Utero, and Early-Life Exposure to Benzene and the Risk of Childhood Leukemia: A Meta-Analysis","volume":"183","author":"Zhang","year":"2016","journal-title":"Am. J. Epidemiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"46002","DOI":"10.1289\/EHP4381","article-title":"Association between Outdoor Air Pollution and Childhood Leukemia: A Systematic Review and Dose-Response Meta-Analysis","volume":"127","author":"Filippini","year":"2019","journal-title":"Environ. Health Perspect."},{"key":"ref_12","first-page":"1330","article-title":"Albumin adducts of benzene oxide and 1,4-benzoquinone as measures of human benzene metabolism","volume":"62","author":"Rappaport","year":"2002","journal-title":"Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1158\/1055-9965.EPI-06-0262","article-title":"Modeling human metabolism of benzene following occupational and environmental exposures","volume":"15","author":"Kim","year":"2006","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1097\/FPC.0b013e3280128f77","article-title":"Genetic polymorphisms and benzene metabolism in humans exposed to a wide Range of air concentrations","volume":"17","author":"Kim","year":"2007","journal-title":"Pharmacogenet Genom."},{"key":"ref_15","unstructured":"Burnham, K.P., and Anderson, D.R. (2002). Model Selection and Multimodel Inference: A Practical Information-Theoretic Approach, Springer. [2nd ed.]."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1289\/ehp.0800510","article-title":"Evidence that humans metabolize benzene via two pathways","volume":"117","author":"Rappaport","year":"2009","journal-title":"Environ. Health Perspect."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1093\/carcin\/bgs257","article-title":"A reanalysis of the evidence for increased efficiency in benzene metabolism at airborne exposure levels below 3 p.p.m","volume":"33","author":"Price","year":"2012","journal-title":"Carcinogenesis"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1093\/carcin\/bgs382","article-title":"Low-dose metabolism of benzene in humans: Science and obfuscation","volume":"34","author":"Rappaport","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1093\/carcin\/bgt101","article-title":"Letter to the editor in response to \u2018Low-dose metabolism of benzene in humans: Science and obfuscation\u2019 Rappaport et al. (2013)","volume":"34","author":"Price","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1093\/carcin\/bgt100","article-title":"Ignoring and adding errors do not improve the science","volume":"34","author":"Rappaport","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.cbi.2017.09.002","article-title":"Evidence for non-linear metabolism at low benzene exposures? A reanalysis of data","volume":"278","author":"McNally","year":"2017","journal-title":"Chem. Biol. Interact."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.cbi.2017.08.007","article-title":"Non-parametric estimation of low-concentration benzene metabolism","volume":"278","author":"Cox","year":"2017","journal-title":"Chem. Biol. Interact."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.cbi.2009.12.017","article-title":"Human benzene metabolism following occupational and environmental exposures","volume":"184","author":"Rappaport","year":"2010","journal-title":"Chem. Biol. Interact."},{"key":"ref_24","first-page":"261","article-title":"Accounting for heteroscedasticity in the transform both sides regression model","volume":"40","author":"Kettl","year":"1991","journal-title":"J. R. Stat. Soc. Ser. C Appl. Stat."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s004200050143","article-title":"trans,trans-muconic acid as a biomarker of non-occupational environmental exposure to benzene","volume":"69","author":"Ruppert","year":"1997","journal-title":"Int. Arch. Occup. Environ. Health"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1136\/oem.55.4.249","article-title":"Evaluation of personal exposure to monoaromatic hydrocarbons","volume":"55","author":"Leung","year":"1998","journal-title":"Occup. Environ. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/sj.jea.7500084","article-title":"The German Environmental Survey 1990\/92 (GerES II): Sources of personal exposure to volatile organic compounds","volume":"10","author":"Hoffmann","year":"2000","journal-title":"J. Expo. Anal. Environ. Epidemiol."},{"key":"ref_28","unstructured":"Wallace, L.A. (1987). The Total Exposure Assessment Methodology (TEAM) Study: Summary and Analysis: Volume I, EPA\/600\/6-87\/002a."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s002040050583","article-title":"Metabolism of benzene in human liver microsomes: Individual variations in relation to CYP2E1 expression","volume":"73","author":"Nedelcheva","year":"1999","journal-title":"Arch. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0041-008X(96)80026-3","article-title":"Reduction of benzene metabolism and toxicity in mice that lack CYP2E1 expression","volume":"141","author":"Valentine","year":"1996","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/1099-0461(2000)14:6<303::AID-JBT2>3.0.CO;2-8","article-title":"Cytochromes P450 involved with benzene metabolism in hepatic and pulmonary microsomes","volume":"14","author":"Powley","year":"2000","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1146\/annurev.pharmtox.43.100901.140251","article-title":"Human extrahepatic cytochromes P450: Function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts","volume":"43","author":"Ding","year":"2003","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"067004","DOI":"10.1289\/EHP844","article-title":"Human CYP2A13 and CYP2F1 Mediate Naphthalene Toxicity in the Lung and Nasal Mucosa of CYP2A13\/2F1-Humanized Mice","volume":"125","author":"Li","year":"2017","journal-title":"Environ. Health Perspect."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1002\/jbt.20010","article-title":"Benzene metabolism in human lung cell lines BEAS-2B and A549 and cells overexpressing CYP2F1","volume":"18","author":"Sheets","year":"2004","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1021\/tx700325f","article-title":"Human cytochrome P450 2A13 efficiently metabolizes chemicals in air pollutants: Naphthalene, styrene, and toluene","volume":"21","author":"Fukami","year":"2008","journal-title":"Chem. Res. Toxicol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1124\/dmd.112.044826","article-title":"Generation and characterization of a CYP2A13\/2B6\/2F1-transgenic mouse model","volume":"40","author":"Wei","year":"2012","journal-title":"Drug Metab. Dispos."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Vrzal, R. (2021). Genetic and Enzymatic Characteristics of CYP2A13 in Relation to Lung Damage. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212306"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1124\/jpet.105.091306","article-title":"Inactivation of CYP2A6 and CYP2A13 during nicotine metabolism","volume":"316","author":"Brown","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1039\/C6TX00016A","article-title":"The inhibition of cytochrome P450 2A13-catalyzed NNK metabolism by NAT, NAB and nicotine","volume":"5","author":"Liu","year":"2016","journal-title":"Toxicol. Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Chiavarini, M., Rosignoli, P., Sorbara, B., Giacchetta, I., and Fabiani, R. (2024). Benzene Exposure and Lung Cancer Risk: A Systematic Review and Meta-Analysis of Human Studies. Int. J. Environ. Res. Public Health, 21.","DOI":"10.3390\/ijerph21020205"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/s41571-023-00844-0","article-title":"Lung cancer in patients who have never smoked\u2014An emerging disease","volume":"21","author":"LoPiccolo","year":"2024","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1021\/tx970122d","article-title":"Dimethyldioxirane converts benzene oxide\/oxepin into (Z,Z)-muconaldehyde and sym-oxepin oxide: Modeling the metabolism of benzene and its photooxidative degradation","volume":"10","author":"Bleasdale","year":"1997","journal-title":"Chem. Res. Toxicol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Effron, B., and Tibshirani, R. (1994). An Introduction to the Bootstrap, Chapman and Hall\/CRC.","DOI":"10.1201\/9780429246593"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1467-9868.2010.00749.x","article-title":"Fast stable restricted maximum likelihood and marginal likelihood estimation of semiparametric generalized linear models","volume":"73","author":"Wood","year":"2011","journal-title":"J. R. Stat. Soc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8550\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:38:31Z","timestamp":1760035111000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8550"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,3]]},"references-count":44,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26178550"],"URL":"https:\/\/doi.org\/10.3390\/ijms26178550","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,3]]}}}