{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:31:12Z","timestamp":1787725872564,"version":"build-2784847793"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006196","name":"University of Oulu","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch Toxicol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Pregnane X receptor (PXR) is a nuclear receptor acting as a master xenobiotic receptor for many exogenous chemicals. Activation of PXR has been linked to liver growth in mice, usually via interaction with Yes-associated protein (YAP), but this adaptive response has not been observed in humans. We investigated the effect of human PXR agonist, rifampicin, on liver size in a controlled clinical trial in healthy volunteers. Moreover, we developed a novel protocol to reveal mechanisms of PXR-mediated liver growth in mice. One-week rifampicin treatment caused a 2.7% mean increase in liver volume-to-body weight ratio without affecting liver fat content in human volunteers (n=16). Pxr\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice were transduced with adenovirus carrying either murine PXR or green fluorescent protein and both groups were treated with pregnenolone\u221216\u03b1-carbonitrile (PCN) for 0 to 4 days. In this setup, activation of PXR with PCN significantly increased liver size in male mice already after 1-day PCN treatment and the liver growth was further enhanced after 4 days. No significant liver enlargement was observed in female mice. 4-day PCN treatment also improved glucose tolerance in the male mice. RNA-sequencing revealed upregulation of genes and pathways involved in proliferation. DigiWest protein profiling and immunoblotting revealed increased activity of AKT\u2013mammalian target of rapamycin (MTOR) pathway in the male mice. In contrast, we did not observe YAP activation. Our results indicate that PXR activation induces liver growth and activates proliferative AKT\u2013MTOR pathway in male mice and may also induce liver growth in humans.\n                  <\/jats:p>","DOI":"10.1007\/s00204-026-04526-5","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:02:55Z","timestamp":1787724175000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pregnane X receptor-mediated liver growth: a controlled clinical trial in healthy volunteers and identification of the role of AKT\u2013MTOR pathway in mouse"],"prefix":"10.1007","author":[{"given":"Piia","family":"Lassila","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikko","family":"Karpale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Outi","family":"Kummu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Stahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aki","family":"K\u00e4r\u00e4j\u00e4m\u00e4ki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eija","family":"P\u00e4\u00e4kk\u00f6","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen Sophie","family":"Hammer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Braeuning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"P\u00f6tz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Templin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janne","family":"Hukkanen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5048-4363","authenticated-orcid":false,"given":"Jukka","family":"Hakkola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"4526_CR1","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1124\/JPET.119.258632","volume":"371","author":"T Abe","year":"2019","unstructured":"Abe T, Shizu R, Sasaki T et al (2019) Functional interaction between pregnane X receptor and yes-associated protein in xenobiotic-dependent liver hypertrophy and drug metabolism. J Pharmacol Exp Ther 371:590\u2013601. https:\/\/doi.org\/10.1124\/JPET.119.258632","journal-title":"J Pharmacol Exp Ther"},{"key":"4526_CR2","doi-asserted-by":"publisher","unstructured":"Bartlett AQ, Vesco KK, Purnell JQ, et al (2021) Pregnancy and weaning regulate human maternal liver size and function. Proc Natl Acad Sci USA. https:\/\/doi.org\/10.1073\/PNAS.2107269118","DOI":"10.1073\/PNAS.2107269118"},{"key":"4526_CR3","doi-asserted-by":"publisher","first-page":"2089","DOI":"10.1007\/S00204-014-1348-X","volume":"89","author":"A Bitter","year":"2015","unstructured":"Bitter A, R\u00fcmmele P, Klein K et al (2015) Pregnane X receptor activation and silencing promote steatosis of human hepatic cells by distinct lipogenic mechanisms. Arch Toxicol 89:2089\u20132103. https:\/\/doi.org\/10.1007\/S00204-014-1348-X","journal-title":"Arch Toxicol"},{"key":"4526_CR4","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1002\/HEP.22129","volume":"47","author":"G Dai","year":"2008","unstructured":"Dai G, He L, Bu P, Wan YJY (2008) Pregnane X receptor is essential for normal progression of liver regeneration. Hepatology 47:1277\u20131287. https:\/\/doi.org\/10.1002\/HEP.22129","journal-title":"Hepatology"},{"key":"4526_CR5","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1111\/j.1365-2125.2010.03773.x","volume":"71","author":"U Diczfalusy","year":"2011","unstructured":"Diczfalusy U, Nyl\u00e9n H, Elander P, Bertilsson L (2011) 4\u03b2-hydroxycholesterol, an endogenous marker of CYP3A4\/5 activity in humans. Br J Clin Pharmacol 71:183\u2013189. https:\/\/doi.org\/10.1111\/j.1365-2125.2010.03773.x","journal-title":"Br J Clin Pharmacol"},{"key":"4526_CR6","doi-asserted-by":"publisher","first-page":"2821","DOI":"10.1172\/JCI44203","volume":"121","author":"C Espeillac","year":"2011","unstructured":"Espeillac C, Mitchell C, Celton-Morizur S et al (2011) S6 kinase 1 is required for rapamycin-sensitive liver proliferation after mouse hepatectomy. J Clin Investig 121:2821\u20132832. https:\/\/doi.org\/10.1172\/JCI44203","journal-title":"J Clin Investig"},{"key":"4526_CR7","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.jprot.2015.04.017","volume":"127","author":"N Groll","year":"2015","unstructured":"Groll N, Emele F, Poetz O, Rothbauer U (2015) Towards multiplexed protein-protein interaction analysis using protein tag-specific nanobodies. J Proteomics 127:289\u2013299. https:\/\/doi.org\/10.1016\/j.jprot.2015.04.017","journal-title":"J Proteomics"},{"key":"4526_CR8","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1016\/j.bbagrm.2016.03.012","volume":"1859","author":"J Hakkola","year":"2016","unstructured":"Hakkola J, Rys\u00e4 J, Hukkanen J (2016) Regulation of hepatic energy metabolism by the nuclear receptor PXR. Biochim Biophys Acta Gene Regul Mech 1859:1072\u20131082. https:\/\/doi.org\/10.1016\/j.bbagrm.2016.03.012","journal-title":"Biochim Biophys Acta Gene Regul Mech"},{"key":"4526_CR9","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1177\/0192623312448935","volume":"40","author":"AP Hall","year":"2012","unstructured":"Hall AP, Elcombe CR, Foster JR et al (2012) Liver hypertrophy: a review of adaptive (adverse and non-adverse) changes\u2013conclusions from the 3rd International ESTP expert workshop. Toxicol Pathol 40:971\u2013994. https:\/\/doi.org\/10.1177\/0192623312448935","journal-title":"Toxicol Pathol"},{"key":"4526_CR10","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1007\/s00204-020-02939-4","volume":"95","author":"H Hammer","year":"2021","unstructured":"Hammer H, Schmidt F, Marx-Stoelting P et al (2021) Cross-species analysis of hepatic cytochrome P450 and transport protein expression. Arch Toxicol 95:117\u2013133. https:\/\/doi.org\/10.1007\/s00204-020-02939-4","journal-title":"Arch Toxicol"},{"key":"4526_CR11","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.jchromb.2018.09.028","volume":"1100\u20131101","author":"H Hautaj\u00e4rvi","year":"2018","unstructured":"Hautaj\u00e4rvi H, Hukkanen J, Turpeinen M et al (2018) Quantitative analysis of 4\u03b2- and 4\u03b1-hydroxycholesterol in human plasma and serum by UHPLC\/ESI-HR-MS. J Chromatogr B Analyt Technol Biomed Life Sci 1100\u20131101:179\u2013186. https:\/\/doi.org\/10.1016\/j.jchromb.2018.09.028","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"4526_CR12","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1515\/dmdi-2013-0036","volume":"29","author":"J Hukkanen","year":"2014","unstructured":"Hukkanen J, Hakkola J, Rys\u00e4 J (2014) Pregnane X receptor (PXR)\u2014A contributor to the diabetes epidemic? Drug Metabol Drug Interact 29:3\u201315. https:\/\/doi.org\/10.1515\/dmdi-2013-0036","journal-title":"Drug Metabol Drug Interact"},{"key":"4526_CR13","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1002\/hep.30131","volume":"69","author":"Y Jiang","year":"2019","unstructured":"Jiang Y, Feng D, Ma X et al (2019) Pregnane X receptor regulates liver size and liver cell fate by yes-associated protein activation in mice. Hepatology 69:343\u2013358. https:\/\/doi.org\/10.1002\/hep.30131","journal-title":"Hepatology"},{"key":"4526_CR14","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1124\/dmd.120.000061","volume":"48","author":"T Jiao","year":"2020","unstructured":"Jiao T, Yao X, Zhao Y et al (2020) Dexamethasone-induced liver enlargement is related to PXR\/YAP activation and lipid accumulation but not hepatocyte proliferation. Drug Metab Dispos 48:830\u2013839. https:\/\/doi.org\/10.1124\/dmd.120.000061","journal-title":"Drug Metab Dispos"},{"key":"4526_CR15","doi-asserted-by":"publisher","unstructured":"Karpale M, Kummu O, K\u00e4rkk\u00e4inen O, et al (2023) Pregnane X receptor activation remodels glucose metabolism to promote NAFLD development in obese mice. Mol Metab. https:\/\/doi.org\/10.1016\/J.MOLMET.2023.101779","DOI":"10.1016\/J.MOLMET.2023.101779"},{"key":"4526_CR16","doi-asserted-by":"publisher","first-page":"7931","DOI":"10.1128\/MCB.24.18.7931-7940.2004","volume":"24","author":"S Kodama","year":"2004","unstructured":"Kodama S, Koike C, Negishi M, Yamamoto Y (2004) Nuclear receptors CAR and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes. Mol Cell Biol 24:7931\u20137940. https:\/\/doi.org\/10.1128\/MCB.24.18.7931-7940.2004","journal-title":"Mol Cell Biol"},{"key":"4526_CR17","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","volume":"30","author":"A Kr\u00e4mer","year":"2014","unstructured":"Kr\u00e4mer A, Green J, Pollard J, Tugendreich S (2014) Causal analysis approaches in ingenuity pathway analysis. Bioinformatics 30:523\u2013530. https:\/\/doi.org\/10.1093\/bioinformatics\/btt703","journal-title":"Bioinformatics"},{"key":"4526_CR18","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1093\/CARCIN\/BGG063","volume":"24","author":"GM Ledda-Columbano","year":"2003","unstructured":"Ledda-Columbano GM, Pibiri M, Concas D et al (2003) Sex difference in the proliferative response of mouse hepatocytes to treatment with the CAR ligand, TCPOBOP. Carcinogenesis 24:1059\u20131065. https:\/\/doi.org\/10.1093\/CARCIN\/BGG063","journal-title":"Carcinogenesis"},{"key":"4526_CR19","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1002\/HEP.23436","volume":"51","author":"G Lo Sasso","year":"2010","unstructured":"Lo Sasso G, Celli N, Caboni M et al (2010) Down-regulation of the LXR transcriptome provides the requisite cholesterol levels to proliferating hepatocytes. Hepatology 51:1334\u20131344. https:\/\/doi.org\/10.1002\/HEP.23436","journal-title":"Hepatology"},{"key":"4526_CR20","doi-asserted-by":"publisher","unstructured":"Luckert K, G\u00f6tschel F, Sorger PK, et al (2011) Snapshots of protein dynamics and post-translational modifications in one experiment - \u03b2-catenin and its functions. Mol Cell Proteom. https:\/\/doi.org\/10.1074\/mcp.M110.007377","DOI":"10.1074\/mcp.M110.007377"},{"key":"4526_CR21","doi-asserted-by":"publisher","unstructured":"Ma X, Huang T, Chen X, et al (2025) Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics. Signal Transduct Target Ther. https:\/\/doi.org\/10.1038\/S41392-024-02104-8","DOI":"10.1038\/S41392-024-02104-8"},{"key":"4526_CR22","doi-asserted-by":"publisher","unstructured":"Machitani M, Sakurai F, Wakabayashi K, et al (2016) NF-\u03baB promotes leaky expression of adenovirus genes in a replication-incompetent adenovirus vector. Sci Rep. https:\/\/doi.org\/10.1038\/SREP19922","DOI":"10.1038\/SREP19922"},{"key":"4526_CR23","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.jhep.2025.08.007","volume":"84","author":"M Matz-Soja","year":"2026","unstructured":"Matz-Soja M, Berg T, Kietzmann T (2026) Sex-related variations in liver homeostasis and disease: from zonation dynamics to clinical implications. J Hepatol 84:181\u2013193. https:\/\/doi.org\/10.1016\/j.jhep.2025.08.007","journal-title":"J Hepatol"},{"key":"4526_CR24","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1002\/HEP.28988","volume":"65","author":"GK Michalopoulos","year":"2017","unstructured":"Michalopoulos GK (2017) Hepatostat: liver regeneration and normal liver tissue maintenance. Hepatology 65:1384\u20131392. https:\/\/doi.org\/10.1002\/HEP.28988","journal-title":"Hepatology"},{"key":"4526_CR25","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/S41575-020-0342-4","volume":"18","author":"GK Michalopoulos","year":"2021","unstructured":"Michalopoulos GK, Bhushan B (2021) Liver regeneration: biological and pathological mechanisms and implications. Nat Rev Gastroenterol Hepatol 18:40\u201355. https:\/\/doi.org\/10.1038\/S41575-020-0342-4","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"4526_CR26","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1002\/HEP.28286","volume":"63","author":"M Pauta","year":"2016","unstructured":"Pauta M, Rotllan N, Fern\u00e1ndez-Hernando A et al (2016) Akt-mediated foxo1 inhibition is required for liver regeneration. Hepatology 63:1660\u20131674. https:\/\/doi.org\/10.1002\/HEP.28286","journal-title":"Hepatology"},{"key":"4526_CR27","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/s41575-018-0075-9","volume":"16","author":"MJ Perugorria","year":"2019","unstructured":"Perugorria MJ, Olaizola P, Labiano I et al (2019) Wnt\u2013\u03b2-catenin signalling in liver development, health and disease. Nat Rev Gastroenterol Hepatol 16:121\u2013136","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"4526_CR28","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1097\/00042737-199710000-00010","volume":"9","author":"C Reichel","year":"1997","unstructured":"Reichel C, Block W, Skodra T et al (1997) Relationship between cytochrome P450 induction by rifampicin, hepatic volume and portal blood flow in man. Eur J Gastroenterol Hepatol 9:975\u2013979","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"4526_CR29","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1210\/me.2002-0421","volume":"17","author":"JM Rosenfeld","year":"2003","unstructured":"Rosenfeld JM, Vargas R, Xie W, Evans RM (2003) Genetic profiling defines the xenobiotic gene network controlled by the nuclear receptor pregnane x receptor. Mol Endocrinol 17:1268\u20131282. https:\/\/doi.org\/10.1210\/me.2002-0421","journal-title":"Mol Endocrinol"},{"key":"4526_CR30","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1038\/CLPT.2013.48","volume":"93","author":"J Rys\u00e4","year":"2013","unstructured":"Rys\u00e4 J, Buler M, Savolainen MJ et al (2013) Pregnane X receptor agonists impair postprandial glucose tolerance. Clin Pharmacol Ther 93:556\u2013563. https:\/\/doi.org\/10.1038\/CLPT.2013.48","journal-title":"Clin Pharmacol Ther"},{"key":"4526_CR31","doi-asserted-by":"publisher","unstructured":"Sarkar A, Jin Y, Defelice BC, et al (2023) Intermittent fasting induces rapid hepatocyte proliferation to restore the hepatostat in the mouse liver. Elife. https:\/\/doi.org\/10.7554\/ELIFE.82311","DOI":"10.7554\/ELIFE.82311"},{"key":"4526_CR40","doi-asserted-by":"publisher","unstructured":"Shizu R, Abe T, Benoki S et al (2016) PXR stimulates growth factor-mediated hepatocyte proliferation by cross-talk with the FOXO transcription factor. Biochem J 473:257\u2013266. https:\/\/doi.org\/10.1042\/BJ20150734","DOI":"10.1042\/BJ20150734"},{"key":"4526_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2024.110970","volume":"393","author":"S Song","year":"2024","unstructured":"Song S, Peng H, Li Y et al (2024) Oleanolic acid promotes liver regeneration after partial hepatectomy via regulating pregnane X receptor signaling pathway in mice. Chem Biol Interact 393:110970. https:\/\/doi.org\/10.1016\/j.cbi.2024.110970","journal-title":"Chem Biol Interact"},{"key":"4526_CR33","doi-asserted-by":"publisher","first-page":"7847","DOI":"10.1038\/SJ.ONC.1204914","volume":"20","author":"B T\u00e4uber","year":"2001","unstructured":"T\u00e4uber B, Dobner T (2001) Adenovirus early E4 genes in viral oncogenesis. Oncogene 20:7847\u20137854. https:\/\/doi.org\/10.1038\/SJ.ONC.1204914","journal-title":"Oncogene"},{"key":"4526_CR34","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1111\/bcpt.13826","volume":"132","author":"H Tolonen","year":"2023","unstructured":"Tolonen H, Ranta S, H\u00e4m\u00e4l\u00e4inen E et al (2023) Effects of rifampicin on porphyrin metabolism in healthy volunteers. Basic Clin Pharmacol Toxicol 132:281\u2013291. https:\/\/doi.org\/10.1111\/bcpt.13826","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"4526_CR35","doi-asserted-by":"publisher","unstructured":"Treindl F, Ruprecht B, Beiter Y, et al (2016) A bead-based western for high-throughput cellular signal transduction analyses. Nat Commun. https:\/\/doi.org\/10.1038\/NCOMMS12852","DOI":"10.1038\/NCOMMS12852"},{"key":"4526_CR36","doi-asserted-by":"publisher","unstructured":"Tumaneng K, Russell RC, Guan KL (2012) Organ size control by Hippo and TOR pathways. Curr Biol. https:\/\/doi.org\/10.1016\/J.CUB.2012.03.003","DOI":"10.1016\/J.CUB.2012.03.003"},{"key":"4526_CR37","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1124\/dmd.117.078626","volume":"46","author":"F Wei\u00df","year":"2018","unstructured":"Wei\u00df F, Hammer HS, Klein K et al (2018) Direct quantification of cytochromes P450 and drug transporters - a rapid, targeted mass spectrometry-based immunoassay panel for tissues and cell culture lysates. Drug Metab Dispos 46:387\u2013396. https:\/\/doi.org\/10.1124\/dmd.117.078626","journal-title":"Drug Metab Dispos"},{"key":"4526_CR38","doi-asserted-by":"publisher","first-page":"2030","DOI":"10.1002\/HEP.27755","volume":"61","author":"L Zhang","year":"2015","unstructured":"Zhang L, Liu L, He Z et al (2015) Inhibition of wild-type p53-induced phosphatase 1 promotes liver regeneration in mice by direct activation of mammalian target of rapamycin. Hepatology 61:2030\u20132041. https:\/\/doi.org\/10.1002\/HEP.27755","journal-title":"Hepatology"},{"key":"4526_CR39","doi-asserted-by":"publisher","unstructured":"Zhang S, Guo M, Jiang X, et al (2023) PXR triggers YAP-TEAD binding and Sirt2-driven YAP deacetylation and polyubiquitination to promote liver enlargement and regeneration in mice. Pharmacol Res. https:\/\/doi.org\/10.1016\/J.PHRS.2023.106666","DOI":"10.1016\/J.PHRS.2023.106666"}],"container-title":["Archives of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-026-04526-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00204-026-04526-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-026-04526-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:02:57Z","timestamp":1787724177000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00204-026-04526-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":40,"alternative-id":["4526"],"URL":"https:\/\/doi.org\/10.1007\/s00204-026-04526-5","relation":{},"ISSN":["0340-5761","1432-0738"],"issn-type":[{"value":"0340-5761","type":"print"},{"value":"1432-0738","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]},"assertion":[{"value":"12 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The author OP declares the following competing financial interest(s): OP is shareholder of SIGNATOPE GmbH. SIGNATOPE offers assay development and service using MS-based immunoassay technology. The other authors have nothing to report.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}