{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T23:23:54Z","timestamp":1794266634513,"version":"4.9.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Vet Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Increasing evidence has confirmed that oxidative stress plays a nonnegligible role in the viral pathogenic process. In this study, we investigated the role of reactive oxygen species (ROS) in the replication of pseudorabies virus (PRV). Our data showed that PRV infection initially enhanced the contact between the endoplasmic reticulum (ER) and mitochondria, leading to an upsurge of mitochondrial Ca\n                    <jats:sup>2+<\/jats:sup>\n                    (mtCa\n                    <jats:sup>2+<\/jats:sup>\n                    ) concentration, which resulted in the loss of mitochondrial membrane potential (MMP) and excessive ROS production. Instead of translocating it to the nucleus, PRV infection concurrently sequestered Nrf2 in cytoplasm impeding the efficient scavenging of intracellular ROS. The excessive ROS production and failure in ROS clearance contributed to the persistently high ROS levels during PRV infection. Furthermore, elevated ROS levels elicited activation of the AMPK-ULK1 axis, initiating PINK1-Parkin-dependent mitophagy that selectively degraded damaged mitochondria along with mitochondrial-localized mitochondrial antiviral signaling protein (MAVS). This process suppressed MAVS-mediated type I interferon responses by eliminating both dysfunctional mitochondria and their associated antiviral signaling platforms, thereby creating a cellular environment permissive to viral replication. Overall, our findings elucidated the mechanism by which ROS enables the virus to resist the host interferon immune response and provided a theoretical basis for ROS-based antiviral strategies.\n                  <\/jats:p>","DOI":"10.1186\/s13567-025-01595-9","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T17:58:42Z","timestamp":1753120722000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Increased ROS levels activate AMPK-ULK1-mediated mitophagy to promote pseudorabies virus replication"],"prefix":"10.1186","volume":"56","author":[{"given":"Yuan","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenbang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4635-1602","authenticated-orcid":false,"given":"Xiangdong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"1595_CR1","doi-asserted-by":"publisher","first-page":"6035","DOI":"10.3748\/wjg.v16.i48.6035","volume":"16","author":"HL Ha","year":"2010","unstructured":"Ha HL, Shin HJ, Feitelson MA, Yu DY (2010) Oxidative stress and antioxidants in hepatic pathogenesis. World J Gastroenterol 16:6035\u20136043","journal-title":"World J Gastroenterol"},{"key":"1595_CR2","first-page":"367","volume":"30","author":"L Nencioni","year":"2007","unstructured":"Nencioni L, Sgarbanti R, De Chiara G, Garaci E, Palamara AT (2007) Influenza virus and redox mediated cell signaling: a complex network of virus\/host interaction. New Microbiol 30:367\u2013375","journal-title":"New Microbiol"},{"key":"1595_CR3","doi-asserted-by":"publisher","first-page":"972","DOI":"10.3390\/microorganisms8070972","volume":"8","author":"V Protto","year":"2020","unstructured":"Protto V, Tramutola A, Fabiani M, Marcocci ME, Napoletani G, Iavarone F, Vincenzoni F, Castagnola M, Perluigi M, Di Domenico F, De Chiara G, Palamara AT (2020) Multiple herpes simplex virus-1 (HSV-1) reactivations induce protein oxidative damage in mouse brain: novel mechanisms for Alzheimer\u2019s disease progression. Microorganisms 8:972","journal-title":"Microorganisms"},{"key":"1595_CR4","doi-asserted-by":"publisher","first-page":"1722","DOI":"10.1002\/ijc.30816","volume":"141","author":"J Hu","year":"2017","unstructured":"Hu J, Li H, Luo X, Li Y, Bode A, Cao Y (2017) The role of oxidative stress in EBV lytic reactivation, radioresistance and the potential preventive and therapeutic implications. Int J Cancer 141:1722\u20131729","journal-title":"Int J Cancer"},{"key":"1595_CR5","doi-asserted-by":"publisher","first-page":"23011","DOI":"10.1038\/s41598-023-50431-7","volume":"13","author":"W Sun","year":"2023","unstructured":"Sun W, Liu S, Yan Y, Wang Q, Fan Y, Okyere SK (2023) Pseudorabies virus causes splenic injury via inducing oxidative stress and apoptosis related factors in mice. Sci Rep 13:23011","journal-title":"Sci Rep"},{"key":"1595_CR6","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1159\/000502047","volume":"62","author":"IH Lai","year":"2019","unstructured":"Lai IH, Chang CD, Shih WL (2019) Apoptosis induction by pseudorabies virus via oxidative stress and subsequent DNA damage signaling. Intervirology 62:116\u2013123","journal-title":"Intervirology"},{"key":"1595_CR7","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1016\/j.ijbiomac.2022.03.041","volume":"207","author":"C Huan","year":"2022","unstructured":"Huan C, Xu Y, Zhang W, Pan H, Zhou Z, Yao J, Guo T, Ni B, Gao S (2022) Hippophae rhamnoides polysaccharides dampen pseudorabies virus infection through downregulating adsorption, entry and oxidative stress. Int J Biol Macromol 207:454\u2013463","journal-title":"Int J Biol Macromol"},{"key":"1595_CR8","doi-asserted-by":"publisher","first-page":"631","DOI":"10.3390\/antiox11040631","volume":"11","author":"Q Wang","year":"2022","unstructured":"Wang Q, Xie X, Chen Q, Yi S, Chen J, Xiao Q, Yu M, Wei Y, Hu T (2022) Effects of quercitrin on PRV-induced secretion of reactive oxygen species and prediction of lncRNA regulatory targets in 3D4\/2 cells. Antioxidants 11:631","journal-title":"Antioxidants"},{"key":"1595_CR9","doi-asserted-by":"publisher","first-page":"3691","DOI":"10.1016\/j.molcel.2021.08.018","volume":"81","author":"C Lennicke","year":"2021","unstructured":"Lennicke C, Cochem\u00e9 HM (2021) Redox metabolism: ROS as specific molecular regulators of cell signaling and function. Mol Cell 81:3691\u20133707","journal-title":"Mol Cell"},{"key":"1595_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102389","volume":"54","author":"S Liu","year":"2022","unstructured":"Liu S, Pi J, Zhang Q (2022) Signal amplification in the KEAP1-NRF2-ARE antioxidant response pathway. Redox Biol 54:102389","journal-title":"Redox Biol"},{"key":"1595_CR11","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1002\/hep.21679","volume":"46","author":"C Piccoli","year":"2007","unstructured":"Piccoli C, Scrima R, Quarato G, D\u2019Aprile A, Ripoli M, Lecce L, Boffoli D, Moradpour D, Capitanio N (2007) Hepatitis C virus protein expression causes calcium-mediated mitochondrial bioenergetic dysfunction and nitro-oxidative stress. Hepatology 46:58\u201365","journal-title":"Hepatology"},{"key":"1595_CR12","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2012.21","volume":"3","author":"H Lecoeur","year":"2012","unstructured":"Lecoeur H, Borgne-Sanchez A, Chaloin O, El-Khoury R, Brabant M, Langonn\u00e9 A, Porceddu M, Bri\u00e8re JJ, Buron N, Rebouillat D, P\u00e9choux C, Deniaud A, Brenner C, Briand JP, Muller S, Rustin P, Jacotot E (2012) HIV-1 Tat protein directly induces mitochondrial membrane permeabilization and inactivates cytochrome c oxidase. Cell Death Dis 3:e282","journal-title":"Cell Death Dis"},{"key":"1595_CR13","doi-asserted-by":"publisher","first-page":"597","DOI":"10.3390\/ijms20030597","volume":"20","author":"YM Choi","year":"2019","unstructured":"Choi YM, Lee SY, Kim BJ (2019) Naturally occurring hepatitis B virus mutations leading to endoplasmic reticulum stress and their contribution to the progression of hepatocellular carcinoma. Int J Mol Sci 20:597","journal-title":"Int J Mol Sci"},{"key":"1595_CR14","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1186\/s13567-021-00964-4","volume":"52","author":"PF Fu","year":"2021","unstructured":"Fu PF, Cheng X, Su BQ, Duan LF, Wang CR, Niu XR, Wang J, Yang GY, Chu BB (2021) CRISPR\/Cas9-based generation of a recombinant double-reporter pseudorabies virus and its characterization in vitro and in vivo. Vet Res 52:95","journal-title":"Vet Res"},{"key":"1595_CR15","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.3390\/v15091966","volume":"15","author":"Z Lian","year":"2023","unstructured":"Lian Z, Liu P, Zhu Z, Sun Z, Yu X, Deng J, Li R, Li X, Tian K (2023) Isolation and characterization of a novel recombinant classical pseudorabies virus in the context of the variant strains pandemic in China. Viruses 15:1966","journal-title":"Viruses"},{"key":"1595_CR16","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.tim.2021.12.011","volume":"30","author":"J Foo","year":"2022","unstructured":"Foo J, Bellot G, Pervaiz S, Alonso S (2022) Mitochondria-mediated oxidative stress during viral infection. Trends Microbiol 30:679\u2013692","journal-title":"Trends Microbiol"},{"key":"1595_CR17","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01048-24","volume":"98","author":"Y Zhao","year":"2024","unstructured":"Zhao Y, Ding C, Zhu Z, Wang W, Wen W, Favoreel HW, Li X (2024) Pseudorabies virus infection triggers mitophagy to dampen the interferon response and promote viral replication. J Virol 98:e0104824","journal-title":"J Virol"},{"key":"1595_CR18","doi-asserted-by":"publisher","first-page":"17208","DOI":"10.1074\/jbc.RA118.002579","volume":"293","author":"EC Hinchy","year":"2018","unstructured":"Hinchy EC, Gruszczyk AV, Willows R, Navaratnam N, Hall AR, Bates G, Bright TP, Krieg T, Carling D, Murphy MP (2018) Mitochondria-derived ROS activate AMP-activated protein kinase (AMPK) indirectly. J Biol Chem 293:17208\u201317217","journal-title":"J Biol Chem"},{"key":"1595_CR19","doi-asserted-by":"publisher","first-page":"30","DOI":"10.3390\/cells11010030","volume":"11","author":"R Iorio","year":"2021","unstructured":"Iorio R, Celenza G, Petricca S (2021) Mitophagy: molecular mechanisms, new concepts on Parkin activation and the emerging role of AMPK\/ULK1 Axis. Cells 11:30","journal-title":"Cells"},{"key":"1595_CR20","doi-asserted-by":"publisher","first-page":"4544","DOI":"10.1126\/sciadv.abg4544","volume":"7","author":"CM Hung","year":"2021","unstructured":"Hung CM, Lombardo PS, Malik N, Brun SN, Hellberg K, Van Nostrand JL, Garcia D, Baumgart J, Diffenderfer K, Asara JM, Shaw RJ (2021) AMPK\/ULK1-mediated phosphorylation of Parkin ACT domain mediates an early step in mitophagy. Sci Adv 7:4544","journal-title":"Sci Adv"},{"key":"1595_CR21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2025932118","volume":"118","author":"JC Drake","year":"2021","unstructured":"Drake JC, Wilson RJ, Laker RC, Guan Y, Spaulding HR, Nichenko AS, Shen W, Shang H, Dorn MV, Huang K, Zhang M, Bandara AB, Brisendine MH, Kashatus JA, Sharma PR, Young A, Gautam J, Cao R, Wallrabe H, Chang PA, Wong M, Desjardins EM, Hawley SA, Christ GJ, Kashatus DF, Miller CL, Wolf MJ, Periasamy A, Steinberg GR, Hardie DG, Yan Z (2021) Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy. Proc Natl Acad Sci USA 118:e2025932118","journal-title":"Proc Natl Acad Sci USA"},{"key":"1595_CR22","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/bs.ircmb.2021.02.015","volume":"362","author":"H Zhao","year":"2021","unstructured":"Zhao H, Pan X (2021) Mitochondrial Ca(2+) and cell cycle regulation. Int Rev Cell Mol Biol 362:171\u2013207","journal-title":"Int Rev Cell Mol Biol"},{"key":"1595_CR23","doi-asserted-by":"publisher","first-page":"6208067","DOI":"10.1155\/2018\/6208067","volume":"2018","author":"C Lee","year":"2018","unstructured":"Lee C (2018) Therapeutic modulation of virus-induced oxidative stress via the Nrf2-dependent antioxidative pathway. Oxid Med Cell Longev 2018:6208067","journal-title":"Oxid Med Cell Longev"},{"key":"1595_CR24","doi-asserted-by":"publisher","first-page":"4777","DOI":"10.3390\/ijms21134777","volume":"21","author":"F He","year":"2020","unstructured":"He F, Ru X, Wen T (2020) NRF2, a transcription factor for stress response and beyond. Int J Mol Sci 21:4777","journal-title":"Int J Mol Sci"},{"key":"1595_CR25","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.redox.2015.07.008","volume":"6","author":"C Espinosa-Diez","year":"2015","unstructured":"Espinosa-Diez C, Miguel V, Mennerich D, Kietzmann T, S\u00e1nchez-P\u00e9rez P, Cadenas S, Lamas S (2015) Antioxidant responses and cellular adjustments to oxidative stress. Redox Biol 6:183\u2013197","journal-title":"Redox Biol"},{"key":"1595_CR26","doi-asserted-by":"publisher","first-page":"2313","DOI":"10.1073\/pnas.0810619106","volume":"106","author":"B Gruhne","year":"2009","unstructured":"Gruhne B, Sompallae R, Marescotti D, Kamranvar SA, Gastaldello S, Masucci MG (2009) The Epstein-Barr virus nuclear antigen-1 promotes genomic instability via induction of reactive oxygen species. Proc Natl Acad Sci USA 106:2313\u20132318","journal-title":"Proc Natl Acad Sci USA"},{"key":"1595_CR27","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1016\/j.freeradbiomed.2024.10.304","volume":"225","author":"Y Zhang","year":"2024","unstructured":"Zhang Y, Chang L, Xin X, Qiao Y, Qiao W, Ping J, Xia J, Su J (2024) Influenza A virus-induced glycolysis facilitates virus replication by activating ROS\/HIF-1\u03b1 pathway. Free Radic Biol Med 225:910\u2013924","journal-title":"Free Radic Biol Med"},{"key":"1595_CR28","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02110-23","volume":"14","author":"LF Chen","year":"2023","unstructured":"Chen LF, Cai JX, Zhang JJ, Tang YJ, Chen JY, Xiong S, Li YL, Zhang H, Liu Z, Li MM (2023) Respiratory syncytial virus co-opts hypoxia-inducible factor-1\u03b1-mediated glycolysis to favor the production of infectious virus. MBio 14:e0211023","journal-title":"MBio"},{"key":"1595_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.136720","volume":"282","author":"YX Ma","year":"2024","unstructured":"Ma YX, Han YQ, Wang PZ, Wang MY, Yang GY, Li JL, Wang J, Chu BB (2024) Porcine reproductive and respiratory syndrome virus activates lipid synthesis through a ROS-dependent AKT\/PCK1\/INSIG\/SREBPs axis. Int J Biol Macromol 282:136720","journal-title":"Int J Biol Macromol"},{"key":"1595_CR30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002054","volume":"7","author":"F Ye","year":"2011","unstructured":"Ye F, Zhou F, Bedolla RG, Jones T, Lei X, Kang T, Guadalupe M, Gao SJ (2011) Reactive oxygen species hydrogen peroxide mediates Kaposi\u2019s sarcoma-associated herpesvirus reactivation from latency. PLoS Pathog 7:e1002054","journal-title":"PLoS Pathog"},{"key":"1595_CR31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002502","volume":"8","author":"J McArdle","year":"2012","unstructured":"McArdle J, Moorman NJ, Munger J (2012) HCMV targets the metabolic stress response through activation of AMPK whose activity is important for viral replication. PLoS Pathog 8:e1002502","journal-title":"PLoS Pathog"},{"key":"1595_CR32","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1080\/15548627.2021.1990515","volume":"18","author":"Y Gong","year":"2022","unstructured":"Gong Y, Tang N, Liu P, Sun Y, Lu S, Liu W, Tan L, Song C, Qiu X, Liao Y, Yu S, Liu X, Lin SH, Ding C (2022) Newcastle disease virus degrades SIRT3 via PINK1-PRKN-dependent mitophagy to reprogram energy metabolism in infected cells. Autophagy 18:1503\u20131521","journal-title":"Autophagy"},{"key":"1595_CR33","doi-asserted-by":"publisher","first-page":"e02193","DOI":"10.1128\/JVI.02193-17","volume":"92","author":"M Li","year":"2018","unstructured":"Li M, Li J, Zeng R, Yang J, Liu J, Zhang Z, Song X, Yao Z, Ma C, Li W, Wang K, Wei L (2018) Respiratory syncytial virus replication is promoted by autophagy-mediated inhibition of apoptosis. J Virol 92:e02193-e2217","journal-title":"J Virol"},{"key":"1595_CR34","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.yjmcc.2015.05.021","volume":"85","author":"W Xie","year":"2015","unstructured":"Xie W, Wang L, Dai Q, Yu H, He X, Xiong J, Sheng H, Zhang D, Xin R, Qi Y, Hu F, Guo S, Zhang K (2015) Activation of AMPK restricts coxsackievirus B3 replication by inhibiting lipid accumulation. J Mol Cell Cardiol 85:155\u2013167","journal-title":"J Mol Cell Cardiol"},{"key":"1595_CR35","doi-asserted-by":"publisher","first-page":"301","DOI":"10.3233\/JAD-140237","volume":"42","author":"C Martin","year":"2014","unstructured":"Martin C, Leyton L, Arancibia Y, Cuevas A, Zambrano A, Concha MI, Otth C (2014) Modulation of the AMPK\/Sirt1 axis during neuronal infection by herpes simplex virus type 1. J Alzheimers Dis 42:301\u2013312","journal-title":"J Alzheimers Dis"},{"key":"1595_CR36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033657","volume":"7","author":"CY Huang","year":"2012","unstructured":"Huang CY, Chiang SF, Lin TY, Chiou SH, Chow KC (2012) HIV-1 Vpr triggers mitochondrial destruction by impairing Mfn2-mediated ER-mitochondria interaction. PLoS One 7:e33657","journal-title":"PLoS One"},{"key":"1595_CR37","doi-asserted-by":"publisher","first-page":"2840","DOI":"10.1128\/JVI.74.6.2840-2846.2000","volume":"74","author":"Z Rahmani","year":"2000","unstructured":"Rahmani Z, Huh KW, Lasher R, Siddiqui A (2000) Hepatitis B virus X protein colocalizes to mitochondria with a human voltage-dependent anion channel, HVDAC3, and alters its transmembrane potential. J Virol 74:2840\u20132846","journal-title":"J Virol"},{"key":"1595_CR38","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02370-22","volume":"14","author":"XQ Xu","year":"2023","unstructured":"Xu XQ, Xu T, Ji W, Wang C, Ren Y, Xiong X, Zhou X, Lin SH, Xu Y, Qiu Y (2023) Herpes simplex virus 1-induced ferroptosis contributes to viral encephalitis. mBio 14:e0237022","journal-title":"mBio"},{"key":"1595_CR39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036216","volume":"7","author":"SJ Schachtele","year":"2012","unstructured":"Schachtele SJ, Hu S, Lokensgard JR (2012) Modulation of experimental herpes encephalitis-associated neurotoxicity through sulforaphane treatment. PLoS One 7:e36216","journal-title":"PLoS One"}],"container-title":["Veterinary Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13567-025-01595-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13567-025-01595-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13567-025-01595-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T17:43:06Z","timestamp":1757266986000},"score":1,"resource":{"primary":{"URL":"https:\/\/veterinaryresearch.biomedcentral.com\/articles\/10.1186\/s13567-025-01595-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,21]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1595"],"URL":"https:\/\/doi.org\/10.1186\/s13567-025-01595-9","relation":{},"ISSN":["1297-9716"],"issn-type":[{"value":"1297-9716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,21]]},"assertion":[{"value":"20 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"156"}}