{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,14]],"date-time":"2026-11-14T08:39:32Z","timestamp":1794645572436,"version":"4.9.1"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/s41467-025-65852-3","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T12:14:00Z","timestamp":1764591240000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Extracellular activation of HCN4 by a subtype-specific nanobody"],"prefix":"10.1038","volume":"16","author":[{"given":"Atiyeh Sadat","family":"Sharifzadeh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6773-7486","authenticated-orcid":false,"given":"Roberta","family":"Castelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4845-6165","authenticated-orcid":false,"given":"Alessandro","family":"Porro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9538-3096","authenticated-orcid":false,"given":"Pietro","family":"Mesirca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2229-4700","authenticated-orcid":false,"given":"Romain","family":"Perrier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0009-2884","authenticated-orcid":false,"given":"Ana M.","family":"G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Mekrane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Benoit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albano C.","family":"Meli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca M. G.","family":"Palloni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7322-1790","authenticated-orcid":false,"given":"Dario","family":"DiFrancesco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8892-3373","authenticated-orcid":false,"given":"Matteo E.","family":"Mangoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Thiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5035-5174","authenticated-orcid":false,"given":"Andrea","family":"Saponaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1860-406X","authenticated-orcid":false,"given":"Anna","family":"Moroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"65852_CR1","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1146\/annurev.physiol.65.092101.142734","volume":"65","author":"RB Robinson","year":"2003","unstructured":"Robinson, R. B. & Siegelbaum, S. A. Hyperpolarization-activated cation currents: from molecules to physiological function. Annu. Rev. Physiol. 65, 453\u2013480 (2003).","journal-title":"Annu. Rev. Physiol."},{"key":"65852_CR2","doi-asserted-by":"publisher","first-page":"3160","DOI":"10.1093\/brain\/awy263","volume":"141","author":"C Marini","year":"2018","unstructured":"Marini, C. et al. HCN1 mutation spectrum: from neonatal epileptic encephalopathy to benign generalized epilepsy and beyond. Brain 141, 3160\u20133178 (2018).","journal-title":"Brain"},{"key":"65852_CR3","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.tips.2012.04.004","volume":"33","author":"EC Emery","year":"2012","unstructured":"Emery, E. C., Young, G. T. & McNaughton, P. A. HCN2 ion channels: an emerging role as the pacemakers of pain. Trends Pharm. Sci. 33, 456\u2013463 (2012).","journal-title":"Trends Pharm. Sci."},{"key":"65852_CR4","doi-asserted-by":"publisher","first-page":"4117","DOI":"10.1113\/jphysiol.2013.253765","volume":"591","author":"D DiFrancesco","year":"2013","unstructured":"DiFrancesco, D. Funny channel gene mutations associated with arrhythmias. J. Physiol. 591, 4117\u20134124 (2013).","journal-title":"J. Physiol."},{"key":"65852_CR5","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.2165\/00003495-200464160-00003","volume":"64","author":"D DiFrancesco","year":"2004","unstructured":"DiFrancesco, D. & Camm, J. A. Heart rate lowering by specific and selective If current inhibition with ivabradine. Drugs 64, 1757\u20131765 (2004).","journal-title":"Drugs"},{"key":"65852_CR6","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.1016\/j.pain.2014.05.021","volume":"155","author":"GT Young","year":"2014","unstructured":"Young, G. T., Emery, E. C., Mooney, E. R., Tsantoulas, C. & McNaughton, P. A. Inflammatory and neuropathic pain are rapidly suppressed by peripheral block of hyperpolarisation-activated cyclic nucleotide-gated ion channels. Pain 155, 1708\u20131719 (2014).","journal-title":"Pain"},{"key":"65852_CR7","doi-asserted-by":"crossref","unstructured":"Saponaro, A. et al. Structural determinants of ivabradine block of the open pore of HCN4. Proc. Natl. Acad. Sci. USA 121, e2402259121 (2024).","DOI":"10.1073\/pnas.2402259121"},{"key":"65852_CR8","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1146\/annurev-biochem-063011-092449","volume":"82","author":"S Muyldermans","year":"2013","unstructured":"Muyldermans, S. Nanobodies: natural single-domain antibodies. Annu Rev. Biochem 82, 775\u2013797 (2013).","journal-title":"Annu Rev. Biochem"},{"key":"65852_CR9","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.coi.2018.02.003","volume":"52","author":"C Stortelers","year":"2018","unstructured":"Stortelers, C., Pinto-Espinoza, C., Van Hoorick, D. & Koch-Nolte, F. Modulating ion channel function with antibodies and nanobodies. Curr. Opin. Immunol. 52, 18\u201326 (2018).","journal-title":"Curr. Opin. Immunol."},{"key":"65852_CR10","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/s41594-018-0028-6","volume":"25","author":"C McMahon","year":"2018","unstructured":"McMahon, C. et al. Yeast surface display platform for rapid discovery of conformationally selective nanobodies. Nat. Struct. Mol. Biol. 25, 289\u2013296 (2018).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"65852_CR11","doi-asserted-by":"publisher","first-page":"2929","DOI":"10.1016\/j.molcel.2021.05.033","volume":"81","author":"A Saponaro","year":"2021","unstructured":"Saponaro, A. et al. Gating movements and ion permeation in HCN4 pacemaker channels. Mol. Cell 81, 2929\u20132943.e6 (2021).","journal-title":"Mol. Cell"},{"key":"65852_CR12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45136-y","volume":"15","author":"A Porro","year":"2024","unstructured":"Porro, A. et al. A high affinity switch for cAMP in the HCN pacemaker channels. Nat. Commun. 15, 843 (2024).","journal-title":"Nat. Commun."},{"key":"65852_CR13","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1152\/physrev.00036.2011","volume":"92","author":"JI Vandenberg","year":"2012","unstructured":"Vandenberg, J. I. et al. hERG K + channels: structure, function, and clinical significance. Physiol. Rev. 92, 1393\u20131478 (2012).","journal-title":"Physiol. Rev."},{"key":"65852_CR14","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1038\/351145a0","volume":"351","author":"D DiFrancesco","year":"1991","unstructured":"DiFrancesco, D. & Tortora, P. Direct activation of cardiac pacemaker channels by intracellular cyclic AMP. Nature 351, 145\u2013147 (1991).","journal-title":"Nature"},{"key":"65852_CR15","doi-asserted-by":"crossref","unstructured":"Porro, A. et al. The HCN domain couples voltage gating and cAMP response in hyperpolarization-activated cyclic nucleotide-gated channels. Elife 8, e49672 (2019).","DOI":"10.7554\/eLife.49672"},{"key":"65852_CR16","doi-asserted-by":"crossref","unstructured":"Page, D. A. & Ruben, P. C. Cannabidiol potentiates hyperpolarization-activated cyclic nucleotide\u2013gated (HCN4) channels. J. Gen. Physiol. 156, e202313505 (2024).","DOI":"10.1085\/jgp.202313505"},{"key":"65852_CR17","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1113\/jphysiol.2002.027698","volume":"549","author":"C Altomare","year":"2003","unstructured":"Altomare, C. et al. Heteromeric HCN1-HCN4 channels: a comparison with native pacemaker channels from the rabbit sinoatrial node. J. Physiol. 549, 347\u2013359 (2003).","journal-title":"J. Physiol."},{"key":"65852_CR18","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1002\/jcsm.13411","volume":"15","author":"M Souidi","year":"2024","unstructured":"Souidi, M. et al. Ryanodine receptor dysfunction causes senescence and fibrosis in Duchenne dilated cardiomyopathy. J. Cachexia Sarcopenia Muscle 15, 536\u2013551 (2024).","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"65852_CR19","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1056\/NEJMoa052475","volume":"354","author":"R Milanesi","year":"2006","unstructured":"Milanesi, R., Baruscotti, M., Gnecchi-Ruscone, T. & DiFrancesco, D. Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel. N. Engl. J. Med. 354, 151\u2013157 (2006).","journal-title":"N. Engl. J. Med."},{"key":"65852_CR20","doi-asserted-by":"publisher","first-page":"9","DOI":"10.15420\/aer.2015.4.1.9","volume":"4","author":"D DiFrancesco","year":"2015","unstructured":"DiFrancesco, D. HCN4, sinus bradycardia and atrial fibrillation. Arrhythm. Electrophysiol. Rev. 4, 9\u201313 (2015).","journal-title":"Arrhythm. Electrophysiol. Rev."},{"key":"65852_CR21","doi-asserted-by":"publisher","first-page":"2768","DOI":"10.1093\/eurheartj\/ehs391","volume":"34","author":"N Duhme","year":"2013","unstructured":"Duhme, N. et al. Altered HCN4 channel C-linker interaction is associated with familial tachycardia-bradycardia syndrome and atrial fibrillation. Eur. Heart J. 34, 2768\u20132775 (2013).","journal-title":"Eur. Heart J."},{"key":"65852_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.101763","volume":"298","author":"L Srinivasan","year":"2022","unstructured":"Srinivasan, L. et al. Development of high-affinity nanobodies specific for NaV1.4 and NaV1.5 voltage-gated sodium channel isoforms. J. Biol. Chem. 298, 101763 (2022).","journal-title":"J. Biol. Chem."},{"key":"65852_CR23","doi-asserted-by":"crossref","unstructured":"Hartung, F. et al. A novel anti-Kv10.1 nanobody fused to single-chain TRAIL enhances apoptosis induction in cancer cells. Front. Pharmacol. 11, 686 (2020).","DOI":"10.3389\/fphar.2020.00686"},{"key":"65852_CR24","doi-asserted-by":"crossref","unstructured":"Chandy, K. G., Sanches, K. & Norton, R. S. Structure of the voltage-gated potassium channel K V 1.3: insights into the inactivated conformation and binding to therapeutic leads. Channels 17, 2253104 (2023).","DOI":"10.1080\/19336950.2023.2253104"},{"key":"65852_CR25","doi-asserted-by":"crossref","unstructured":"Morgenstern, T. J., Park, J., Fan, Q. R. & Colecraft, H. M. A potent voltage-gated calcium channel inhibitor engineered from a nanobody targeted to auxiliary CaV\u03b2 subunits. Elife 8, e49253 (2019).","DOI":"10.7554\/eLife.49253"},{"key":"65852_CR26","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/j.synbio.2025.02.005","volume":"10","author":"S Ali","year":"2025","unstructured":"Ali, S., Suris, A., Huang, Y. & Zhou, Y. Modulating ion channels with nanobodies. Synth. Syst. Biotechnol. 10, 593\u2013599 (2025).","journal-title":"Synth. Syst. Biotechnol."},{"key":"65852_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48536-2","volume":"15","author":"KEJ R\u00f6dstr\u00f6m","year":"2024","unstructured":"R\u00f6dstr\u00f6m, K. E. J. et al. Extracellular modulation of TREK-2 activity with nanobodies provides insight into the mechanisms of K2P channel regulation. Nat. Commun. 15, 4173 (2024).","journal-title":"Nat. Commun."},{"key":"65852_CR28","doi-asserted-by":"publisher","first-page":"2084","DOI":"10.1111\/febs.15515","volume":"288","author":"S Muyldermans","year":"2021","unstructured":"Muyldermans, S. A guide to: generation and design of nanobodies. FEBS J. 288, 2084\u20132102 (2021).","journal-title":"FEBS J."},{"key":"65852_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.103024","volume":"60","author":"Y Sleiman","year":"2020","unstructured":"Sleiman, Y. et al. Modeling polymorphic ventricular tachycardia at rest using patient-specific induced pluripotent stem cell-derived cardiomyocytes. EBioMedicine 60, 103024 (2020).","journal-title":"EBioMedicine"},{"key":"65852_CR30","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1007\/978-1-0716-1484-6_14","volume":"2320","author":"M Nakanishi-Koakutsu","year":"2021","unstructured":"Nakanishi-Koakutsu, M., Takaki, T., Miki, K. & Yoshida, Y. Characterization of ventricular and atrial cardiomyocyte subtypes from human-induced pluripotent stem cells. Methods Mol. Biol. 2320, 135\u2013149 (2021).","journal-title":"Methods Mol. Biol."},{"key":"65852_CR31","doi-asserted-by":"crossref","unstructured":"Larsson, J. E., Larsson, H. P. & Liin, S. I. KCNE1 tunes the sensitivity of KV7.1 to polyunsaturated fatty acids by moving turret residues close to the binding site. Elife 7, e37257 (2018).","DOI":"10.7554\/eLife.37257"},{"key":"65852_CR32","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46813-8","volume":"15","author":"Q Liang","year":"2024","unstructured":"Liang, Q. et al. The binding and mechanism of a positive allosteric modulator of Kv3 channels. Nat. Commun. 15, 2533 (2024).","journal-title":"Nat. Commun."},{"key":"65852_CR33","doi-asserted-by":"publisher","first-page":"2307","DOI":"10.1529\/biophysj.107.104349","volume":"93","author":"A Broomand","year":"2007","unstructured":"Broomand, A., \u00d6sterberg, F., Wardi, T. & Elinder, F. Electrostatic domino effect in the shaker K channel turret. Biophys. J. 93, 2307\u20132314 (2007).","journal-title":"Biophys. J."},{"key":"65852_CR34","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/s41586-024-07743-z","volume":"632","author":"ED Kim","year":"2024","unstructured":"Kim, E. D. et al. Propofol rescues voltage-dependent gating of HCN1 channel epilepsy mutants. Nature 632, 451\u2013459 (2024).","journal-title":"Nature"},{"key":"65852_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36730-7","volume":"14","author":"CAZ Bassetto","year":"2023","unstructured":"Bassetto, C. A. Z., Costa, F., Guardiani, C., Bezanilla, F. & Giacomello, A. Noncanonical electromechanical coupling paths in cardiac hERG potassium channel. Nat. Commun. 14, 1110 (2023).","journal-title":"Nat. Commun."},{"key":"65852_CR36","doi-asserted-by":"crossref","unstructured":"Bassetto, C. A., Carvalho-de-Souza, J. L. & Bezanilla, F. Molecular basis for functional connectivity between the voltage sensor and the selectivity filter gate in Shaker K+ channels. Elife 10, e63077 (2021).","DOI":"10.7554\/eLife.63077"},{"key":"65852_CR37","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11545-7","volume":"10","author":"JL Carvalho-de-Souza","year":"2019","unstructured":"Carvalho-de-Souza, J. L. & Bezanilla, F. Noncanonical mechanism of voltage sensor coupling to pore revealed by tandem dimers of shaker. Nat. Commun. 10, 3584 (2019).","journal-title":"Nat. Commun."},{"key":"65852_CR38","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/j.jacc.2014.05.045","volume":"64","author":"A Milano","year":"2014","unstructured":"Milano, A. et al. HCN4 mutations in multiple families with bradycardia and left ventricular noncompaction cardiomyopathy. J. Am. Coll. Cardiol. 64, 745\u2013756 (2014).","journal-title":"J. Am. Coll. Cardiol."},{"key":"65852_CR39","doi-asserted-by":"publisher","first-page":"18011","DOI":"10.1073\/pnas.1308477110","volume":"110","author":"ED Larson","year":"2013","unstructured":"Larson, E. D., St Clair, J. R., Sumner, W. A., Bannister, R. A. & Proenza, C. Depressed pacemaker activity of sinoatrial node myocytes contributes to the age-dependent decline in maximum heart rate. Proc. Natl. Acad. Sci. USA 110, 18011\u201318016 (2013).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"65852_CR40","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.cger.2012.07.003","volume":"28","author":"GV Chow","year":"2012","unstructured":"Chow, G. V., Marine, J. E. & Fleg, J. L. Epidemiology of arrhythmias and conduction disorders in older adults. Clin. Geriatr. Med. 28, 539\u2013553 (2012).","journal-title":"Clin. Geriatr. Med."},{"key":"65852_CR41","doi-asserted-by":"publisher","first-page":"147","DOI":"10.2147\/OAEM.S351548","volume":"ume 14","author":"S Rujichanuntakul","year":"2022","unstructured":"Rujichanuntakul, S. et al. Bradycardia in older patients in a single-center emergency department: incidence, characteristics and outcomes. Open Access Emerg. Med. ume 14, 147\u2013153 (2022).","journal-title":"Open Access Emerg. Med."},{"key":"65852_CR42","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s40259-019-00392-z","volume":"34","author":"I Jov\u010devska","year":"2020","unstructured":"Jov\u010devska, I. & Muyldermans, S. The therapeutic potential of nanobodies. BioDrugs 34, 11\u201326 (2020).","journal-title":"BioDrugs"},{"key":"65852_CR43","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1038\/s41587-020-0687-9","volume":"38","author":"A Gray","year":"2020","unstructured":"Gray, A. et al. Animal-free alternatives and the antibody iceberg. Nat. Biotechnol. 38, 1234\u20131239 (2020).","journal-title":"Nat. Biotechnol."},{"key":"65852_CR44","doi-asserted-by":"publisher","unstructured":"Saponaro, A., Sharifzadeh, A. S. & Moroni, A. Detection of ligand binding to purified HCN channels using fluorescence-based size exclusion chromatography. 105\u2013123 https:\/\/doi.org\/10.1016\/bs.mie.2021.01.043 (2021).","DOI":"10.1016\/bs.mie.2021.01.043"},{"key":"65852_CR45","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1113\/jphysiol.1986.sp016177","volume":"377","author":"D DiFrancesco","year":"1986","unstructured":"DiFrancesco, D., Ferroni, A., Mazzanti, M. & Tromba, C. Properties of the hyperpolarizing-activated current (if) in cells isolated from the rabbit sino-atrial node. J. Physiol. 377, 61\u201388 (1986).","journal-title":"J. Physiol."},{"key":"65852_CR46","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-76049-7","volume":"10","author":"M Baudot","year":"2020","unstructured":"Baudot, M. et al. Concomitant genetic ablation of L-type Cav1.3 (\u03b11D) and T-type Cav3.1 (\u03b11G) Ca2+ channels disrupts heart automaticity. Sci. Rep. 10, 18906 (2020).","journal-title":"Sci. Rep."},{"key":"65852_CR47","doi-asserted-by":"crossref","unstructured":"Bernardin, A. A. et al. Impact of neurons on patient-derived cardiomyocytes using organ-on-a-chip and iPSC biotechnologies. Cells 11, 3764 (2022).","DOI":"10.3390\/cells11233764"},{"key":"65852_CR48","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.biomaterials.2015.01.067","volume":"51","author":"MC Ribeiro","year":"2015","unstructured":"Ribeiro, M. C. et al. Functional maturation of human pluripotent stem cell derived cardiomyocytes in vitro-correlation between contraction force and electrophysiology. Biomaterials 51, 138\u2013150 (2015).","journal-title":"Biomaterials"},{"key":"65852_CR49","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/j.stem.2020.05.004","volume":"26","author":"E Giacomelli","year":"2020","unstructured":"Giacomelli, E. et al. Human-iPSC-derived cardiac stromal cells enhance maturation in 3D cardiac microtissues and reveal non-cardiomyocyte contributions to heart disease. Cell Stem Cell 26, 862\u2013879.e11 (2020).","journal-title":"Cell Stem Cell"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-65852-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-65852-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-65852-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T12:14:02Z","timestamp":1764591242000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-65852-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,1]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["65852"],"URL":"https:\/\/doi.org\/10.1038\/s41467-025-65852-3","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,1]]},"assertion":[{"value":"12 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10804"}}