{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T11:18:04Z","timestamp":1783423084977,"version":"3.54.6"},"reference-count":47,"publisher":"IMR Press","issue":"6","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University Research Project of Anhui Province","award":["KJ2020A0854"],"award-info":[{"award-number":["KJ2020A0854"]}]},{"name":"Scientific Research Project of Anhui Provincial Healthcare Commission","award":["2024AH050542"],"award-info":[{"award-number":["2024AH050542"]}]},{"name":"Scientific Research Project of Anhui Provincial Healthcare Commission","award":["AHWJ2023A20214"],"award-info":[{"award-number":["AHWJ2023A20214"]}]},{"name":"Scientific Research Project of Anhui Medical University","award":["2023XKJ116"],"award-info":[{"award-number":["2023XKJ116"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background:The molecular mechanisms underlying obstructive jaundice (OJ)-induced liver injury and subsequent repair after biliary recanalization (R-OJ) remain incompletely elucidated. This study aimed to identify and validate core gene involved in regulating OJ-related liver injury and repair via integrated in vitro and in vivo models.Methods:Animal models (OJ and R-OJ groups) and cell models (OJ serum (OJS) and OJ serum depletion (OJSD) groups) were established. Liver function and histopathologic changes were evaluated. Differentially expressed genes (DEGs) were screened by RNA sequencing (RNA-seq), and candidate genes were selected by intersecting DEGs with functional gene sets associated with \u201cinjury\u201d and \u201crepair\u201d. Key genes were identified via protein-protein interaction (PPI) network and pathway enrichment analyses. Fibroblast growth factor receptor 2 (FGFR2) expression was validated by quantitative reverse transcription PCR (qRT-PCR), Western blot, and immunohistochemistry (IHC). Functional involvement of FGFR2 was assessed by siRNA-mediated knockdown followed by assessment of downstream AKT signaling, proliferation (proliferating cell nuclear antigen, PCNA), and apoptosis maker cleaved caspase-3.Results:OJ induced significant liver dysfunction and tissue damage, which partially recovered after R-OJ. Bioinformatic analyses identified FGFR2 as a core regulatory gene among 20 candidates. FGFR2 was downregulated during injury (OJS vs. Con, p &lt; 0.05) and upregulated during repair (OJSD vs. OJS, p &lt; 0.05) both in vivo and in vitro. FGFR2 knockdown in BRL-3A cells markedly reduced p-AKT levels by approximately 50% under all serum conditions (p &lt; 0.01), significantly decreased PCNA expression, and altered cleaved caspase-3 levels, suggesting that FGFR2 may contribute to hepatocyte proliferation and survival, potentially through the phosphoinositide 3-kinase (PI3K)\/AKT signaling.Conclusion:FGFR2 exhibits a dynamic expression pattern of downregulation during cholestatic injury and upregulation during repair, and is associated with hepatocyte proliferation and apoptosis, potentially through AKT signaling. These findings suggest that FGFR2 may represent a potential therapeutic target for improving liver repair in obstructive jaundice.<\/jats:p>","DOI":"10.31083\/fbl49296","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:50:51Z","timestamp":1783421451000},"source":"Crossref","is-referenced-by-count":0,"title":["FGFR2 Regulates Liver Injury and Repair in a Model of Obstructive Jaundice"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0544-5393","authenticated-orcid":true,"given":"Weiwei","family":"Chu","sequence":"first","affiliation":[{"name":"Graduate School, Bengbu Medical University, 233000 Bengbu, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinshan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Anhui University of Chinese Medicine, 230031 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Anhui University of Chinese Medicine, 230031 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Xu","sequence":"additional","affiliation":[{"name":"Graduate School, Anhui Medical University, 230041 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanxuan","family":"Li","sequence":"additional","affiliation":[{"name":"Graduate School, Bengbu Medical University, 233000 Bengbu, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peilin","family":"Liu","sequence":"additional","affiliation":[{"name":"Graduate School, Anhui University of Science & Technology, 232001 Huainan, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongquan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Anhui University of Chinese Medicine, 230031 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Anhui University of Chinese Medicine, 230031 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoqiang","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Anhui University of Chinese Medicine, 230031 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8432-1369","authenticated-orcid":true,"given":"Jiaming","family":"Yao","sequence":"additional","affiliation":[{"name":"Graduate School, Bengbu Medical University, 233000 Bengbu, Anhui, China"},{"name":"Department of General Surgery, The First Affiliated Hospital of Anhui University of Chinese Medicine, 230031 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Pavlidis ET, Pavlidis TE. Pathophysiological consequences of obstructive jaundice and perioperative management. Hepatobiliary & Pancreatic Diseases International : HBPD INT. 2018; 17: 17\u201321.","DOI":"10.1016\/j.hbpd.2018.01.008"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Alshoabi SA, Binnuhaid AA, Muslem HF, Hamid AM, Alhazmi FH, Alrehily FA, et al. Demographic Profiles, Etiological Spectrum, and Anatomical Locations of the Post-Hepatic Obstructive Jaundice in Adult Population in Hadhramout Region in Yemen. Diseases (Basel, Switzerland). 2024; 12: 333.","DOI":"10.3390\/diseases12120333"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Kaomba L, Ng'ombe J, Mulwafu W. Clinicopathological features and management of obstructive jaundice at Queen Elizabeth Central Hospital, Malawi. A retrospective cohort analysis. Surgery Open Science. 2024; 20: 14\u201319.","DOI":"10.1016\/j.sopen.2024.05.004"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Kwak JY, Jeon H, Kim SJ, Han JH, Cha RR, Lee SS. Etiology and Outcomes of Patients with Extreme Hyperbilirubinemia in Korea: A Retrospective Cohort Study. The Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi. 2024; 84: 9\u201316.","DOI":"10.4166\/kjg.2024.038"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Kullak-Ublick GA, Meier PJ. Mechanisms of cholestasis. Clinics in Liver Disease. 2000; 4: 357\u2013385.","DOI":"10.1016\/s1089-3261(05)70114-8"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Pellicoro A, Ramachandran P, Iredale JP, Fallowfield JA. Liver fibrosis and repair: immune regulation of wound healing in a solid organ. Nature Reviews. Immunology. 2014; 14: 181\u2013194.","DOI":"10.1038\/nri3623"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Campana L, Esser H, Huch M, Forbes S. Liver regeneration and inflammation: from fundamental science to clinical applications. Nature Reviews. Molecular Cell Biology. 2021; 22: 608\u2013624.","DOI":"10.1038\/s41580-021-00373-7"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Seo E, Kang H, Choi H, Choi W, Jun HS. Reactive oxygen species-induced changes in glucose and lipid metabolism contribute to the accumulation of cholesterol in the liver during aging. Aging Cell. 2019; 18: e12895.","DOI":"10.1111\/acel.12895"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Liu J, Hu J, Xu H, Yan L, Yao J, Cao B. Role of VDAC1 in hepatocyte apoptosis during acute liver injury in rats induced by obstructive jaundice. Iranian Journal of Basic Medical Sciences. 2025; 28: 87\u201397.","DOI":"10.22038\/ijbms.2024.78454.16962"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Ren HM, Yang LQ, Liu ZQ, Chen CY, Cheung CW, Tao KM, et al. In vivo and ex vivo effects of propofol on myocardial performance in rats with obstructive jaundice. BMC Gastroenterology. 2011; 11: 144.","DOI":"10.1186\/1471-230X-11-144"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Acar S, Cetin R, Zihni I, Ozmen O, Sabuncuoglu MZ, Sozen I, et al. The effects of rose oil on liver damage in an experimental model of obstructive jaundice. Ulusal Travma Ve Acil Cerrahi Dergisi = Turkish Journal of Trauma & Emergency Surgery : TJTES. 2025; 31: 495\u2013504.","DOI":"10.14744\/tjtes.2025.96613"},{"key":"ref12","unstructured":"Ozozan OV, Dinc T, Vural V, Ozogul C, Ozmen MM, Coskun F. An electron microscopy study of liver and kidney damage in an experimental model of obstructive jaundice. Annali Italiani Di Chirurgia. 2020; 91: 122\u2013130."},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Wang Q, Li ZX, Liu BW, He ZG, Liu C, Chen M, et al. Altered expression of differential gene and lncRNA in the lower thoracic spinal cord on different time courses of experimental obstructive jaundice model accompanied with altered peripheral nociception in rats. Oncotarget. 2017; 8: 106098\u2013106112.","DOI":"10.18632\/oncotarget.22532"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Ramachandran P, Balamurali D, Peter JJ, Kumar MM, Safwan M, Vij M, et al. RNA-seq reveals outcome-specific gene expression of MMP7 and PCK1 in biliary atresia. Molecular Biology Reports. 2019; 46: 5123\u20135130.","DOI":"10.1007\/s11033-019-04969-3"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Tracey KJ, Cerami A. Tumor necrosis factor, other cytokines and disease. Annual Review of Cell Biology. 1993; 9: 317\u2013343.","DOI":"10.1146\/annurev.cb.09.110193.001533"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Diehl AM. Cytokine regulation of liver injury and repair. Immunological Reviews. 2000; 174: 160\u2013171.","DOI":"10.1034\/j.1600-0528.2002.017411.x"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Padrissa-Alt\u00e9s S, Bachofner M, Bogorad RL, Pohlmeier L, Rossolini T, B\u00f6hm F, et al. Control of hepatocyte proliferation and survival by Fgf receptors is essential for liver regeneration in mice. Gut. 2015; 64: 1444\u20131453.","DOI":"10.1136\/gutjnl-2014-307874"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Fang X, Yang D, Luo H, Wu S, Dong W, Xiao J, et al. SNORD126 promotes HCC and CRC cell growth by activating the PI3K-AKT pathway through FGFR2. Journal of Molecular Cell Biology. 2017; 9: 243\u2013255.","DOI":"10.1093\/jmcb\/mjw048"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Seitz T, Hellerbrand C. Role of fibroblast growth factor signalling in hepatic fibrosis. Liver International : Official Journal of the International Association for the Study of the Liver. 2021; 41: 1201\u20131215.","DOI":"10.1111\/liv.14863"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Hotta K, Kitamoto T, Kitamoto A, Ogawa Y, Honda Y, Kessoku T, et al. Identification of the genomic region under epigenetic regulation during non-alcoholic fatty liver disease progression. Hepatology Research : the Official Journal of the Japan Society of Hepatology. 2018; 48: E320\u2013E334.","DOI":"10.1111\/hepr.12992"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Geervliet E, Terstappen LWMM, Bansal R. Hepatocyte survival and proliferation by fibroblast growth factor 7 attenuates liver inflammation, and fibrogenesis during acute liver injury via paracrine mechanisms. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2023; 167: 115612.","DOI":"10.1016\/j.biopha.2023.115612"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Jeong A, Lim Y, Kook T, Kwon DH, Cho YK, Ryu J, et al. Circular RNA circSMAD4 regulates cardiac fibrosis by targeting miR-671-5p and FGFR2 in cardiac fibroblasts. Molecular Therapy. Nucleic Acids. 2023; 34: 102071.","DOI":"10.1016\/j.omtn.2023.102071"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Zou Y, Yue P, Cao H, Wu L, Xu L, Liu Z, et al. A novel ameliorated rat model of reversible obstructive jaundice. Journal of Zhejiang University. Science. B. 2023; 24: 345\u2013351.","DOI":"10.1631\/jzus.B2200421"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Sharma P. Value of Liver Function Tests in Cirrhosis. Journal of Clinical and Experimental Hepatology. 2022; 12: 948\u2013964.","DOI":"10.1016\/j.jceh.2021.11.004"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Cardiff RD, Miller CH, Munn RJ. Manual hematoxylin and eosin staining of mouse tissue sections. Cold Spring Harbor Protocols. 2014; 2014: 655\u2013658.","DOI":"10.1101\/pdb.prot073411"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Woolbright BL, Dorko K, Antoine DJ, Clarke JI, Gholami P, Li F, et al. Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis. Toxicology and Applied Pharmacology. 2015; 283: 168\u2013177.","DOI":"10.1016\/j.taap.2015.01.015"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Shen X, Zhang X, Li K, Huang G, Li X, Hou Y, et al. Combined bacterial translocation and cholestasis aggravates liver injury by activation pyroptosis in obstructive jaundice. Heliyon. 2024; 10: e35793.","DOI":"10.1016\/j.heliyon.2024.e35793"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Trovato FM, Zia R, Napoli S, Wolfer K, Huang X, Morgan PE, et al. Dysregulation of the Lysophosphatidylcholine\/Autotaxin\/Lysophosphatidic Acid Axis in Acute-on-Chronic Liver Failure Is Associated With Mortality and Systemic Inflammation by Lysophosphatidic Acid-Dependent Monocyte Activation. Hepatology (Baltimore, Md.). 2021; 74: 907\u2013925.","DOI":"10.1002\/hep.31738"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"de Carvalho TG, Pellenz FM, Laureano A, da Rocha Silla LM, Giugliani R, Baldo G, et al. A simple protocol for transfecting human mesenchymal stem cells. Biotechnology Letters. 2018; 40: 617\u2013622.","DOI":"10.1007\/s10529-018-2505-8"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biology. 2014; 15: 550.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Liu C, Yin Z, Feng T, Zhang M, Zhou Z, Zhou Y. An integrated network pharmacology and RNA-Seq approach for exploring the preventive effect of Lonicerae japonicae flos on LPS-induced acute lung injury. Journal of Ethnopharmacology. 2021; 264: 113364.","DOI":"10.1016\/j.jep.2020.113364"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Bustin SA, Ruijter JM, van den Hoff MJB, Kubista M, Pfaffl MW, Shipley GL, et al. MIQE 2.0: Revision of the Minimum Information for Publication of Quantitative Real-Time PCR Experiments Guidelines. Clinical Chemistry. 2025; 71: 634\u2013651.","DOI":"10.1093\/clinchem\/hvaf043"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Sule R, Rivera G, Gomes AV. Western blotting (immunoblotting): history, theory, uses, protocol and problems. BioTechniques. 2023; 75: 99\u2013114.","DOI":"10.2144\/btn-2022-0034"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Mebratie DY, Dagnaw GG. Review of immunohistochemistry techniques: Applications, current status, and future perspectives. Seminars in Diagnostic Pathology. 2024; 41: 154\u2013160.","DOI":"10.1053\/j.semdp.2024.05.001"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Liu JJ, Sun YM, Xu Y, Mei HW, Guo W, Li ZL. Pathophysiological consequences and treatment strategy of obstructive jaundice. World Journal of Gastrointestinal Surgery. 2023; 15: 1262\u20131276.","DOI":"10.4240\/wjgs.v15.i7.1262"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Santiago P, Scheinberg AR, Levy C. Cholestatic liver diseases: new targets, new therapies. Therapeutic Advances in Gastroenterology. 2018; 11: 1756284818787400.","DOI":"10.1177\/1756284818787400"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Li J, Zhu X, Zhang M, Zhang Y, Ye S, Leng Y, et al. Limb expression 1-like (LIX1L) protein promotes cholestatic liver injury by regulating bile acid metabolism. Journal of Hepatology. 2021; 75: 400\u2013413.","DOI":"10.1016\/j.jhep.2021.02.035"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Di HT, Wu XZ, Wang HQ, Chen M, Kong EL, Yu WF, et al. Involvement of the p38 MAPK-pHsp27 pathway in vascular hyporeactivity induced by obstructive jaundice in rats. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2020; 121: 109304.","DOI":"10.1016\/j.biopha.2019.109304"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Lin Y, Gil CH, Banno K, Yokoyama M, Wingo M, Go E, et al. ABCG2-Expressing Clonal Repopulating Endothelial Cells Serve to Form and Maintain Blood Vessels. Circulation. 2024; 150: 451\u2013465.","DOI":"10.1161\/CIRCULATIONAHA.122.061833"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Li Z, Solomonidis EG, Meloni M, Taylor RS, Duffin R, Dobie R, et al. Single-cell transcriptome analyses reveal novel targets modulating cardiac neovascularization by resident endothelial cells following myocardial infarction. European Heart Journal. 2019; 40: 2507\u20132520.","DOI":"10.1093\/eurheartj\/ehz305"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Meric-Bernstam F, Bahleda R, Hierro C, Sanson M, Bridgewater J, Arkenau HT, et al. Futibatinib, an Irreversible FGFR1-4 Inhibitor, in Patients with Advanced Solid Tumors Harboring FGF\/FGFR Aberrations: A Phase I Dose-Expansion Study. Cancer Discovery. 2022; 12: 402\u2013415.","DOI":"10.1158\/2159-8290.CD-21-0697"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Lau WM, Teng E, Huang KK, Tan JW, Das K, Zang Z, et al. Acquired Resistance to FGFR Inhibitor in Diffuse-Type Gastric Cancer through an AKT-Independent PKC-Mediated Phosphorylation of GSK3\u03b2. Molecular Cancer Therapeutics. 2018; 17: 232\u2013242.","DOI":"10.1158\/1535-7163.MCT-17-0367"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"DiPeri TP, Zhao M, Evans KW, Varadarajan K, Moss T, Scott S, et al. Convergent MAPK pathway alterations mediate acquired resistance to FGFR inhibitors in FGFR2 fusion-positive cholangiocarcinoma. Journal of Hepatology. 2024; 80: 322\u2013334.","DOI":"10.1016\/j.jhep.2023.10.041"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Zhang S, Yu J, Rao K, Cao J, Ma L, Yu Y, et al. Liver-derived extracellular vesicles from patients with hepatitis B virus-related acute-on-chronic liver failure impair hepatic regeneration by inhibiting on FGFR2 signaling via miR-218-5p. Hepatology International. 2023; 17: 833\u2013849.","DOI":"10.1007\/s12072-023-10513-0"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Tian C, Li Y, Wang L, Si J, Zheng Y, Kang J, et al. Blockade of FGF2\/FGFR2 partially overcomes bone marrow mesenchymal stromal cells mediated progression of T-cell acute lymphoblastic leukaemia. Cell Death & Disease. 2022; 13: 922.","DOI":"10.1038\/s41419-022-05377-5"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Meng Q, Luo L, Lei M, Chen Z, Sun Y, Chen X, et al. Inhibition of FGFR2 Signaling by Cynaroside Attenuates Liver Fibrosis. Pharmaceuticals (Basel, Switzerland). 2023; 16: 548.","DOI":"10.3390\/ph16040548"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Goyal L, Meric-Bernstam F, Hollebecque A, Valle JW, Morizane C, Karasic TB, et al. Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma. The New England Journal of Medicine. 2023; 388: 228\u2013239.","DOI":"10.1056\/NEJMoa2206834"}],"container-title":["Frontiers in Bioscience-Landmark"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/31\/6\/10.31083\/FBL49296","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:53:05Z","timestamp":1783421585000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/31\/6\/10.31083\/FBL49296"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":47,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026]]}},"alternative-id":["S2768-6701(26)02148-9"],"URL":"https:\/\/doi.org\/10.31083\/fbl49296","relation":{},"ISSN":["2768-6701","2768-6698"],"issn-type":[{"value":"2768-6701","type":"print"},{"value":"2768-6698","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,24]]},"article-number":"49296"}}