{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:12:18Z","timestamp":1785420738941,"version":"3.56.0"},"reference-count":59,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T00:00:00Z","timestamp":1775347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"crossref","award":["770528"],"award-info":[{"award-number":["770528"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003141","name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"crossref","award":["4003403"],"award-info":[{"award-number":["4003403"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"crossref"}]},{"award":["770528"],"award-info":[{"award-number":["770528"]}],"id":[{"id":"https:\/\/ror.org\/059ex5q34","id-type":"ROR","asserted-by":"publisher"}]},{"award":["4003403"],"award-info":[{"award-number":["4003403"]}],"id":[{"id":"https:\/\/ror.org\/059ex5q34","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>For a protein to perform its biological functions, it must adopt a specific three-dimensional conformation. In addition, many proteins require the assistance of other protein complexes known as chaperonins to fold \u2014i.e., to acquire such a specific conformation\u2014, although the exact mechanisms whereby the chaperonins act and assist the folding process have not been completely determined. In this work, we characterize the physical environment at the interior of the chaperonin HSP60\/HSP10 via Molecular Dynamics Simulations. We found that, inside the cavity of the chaperonin (within a region covering much of the cavity\u2019s volume), the long-range electrostatic potential presents a structured pattern that, except for small fluctuations, does not change in time. The electrostatic potential generates an electric field that can be modeled, as a first approximation, as constant and unidirectional (E\/(V\u00b7\u00c5\u22121)\u2248\u22120.0054\ud835\udea4^+0.010\ud835\udea5^\u22120.162k^, here the chaperonin\u2019s main axis is aligned along k^), which can produce large deformations in the structure of a heated protein (Rhodanese); the long-range approximated E(r) can in fact unfold the Rhodanese, when applied as an external field. Finally, we discuss the possible implications of such an electric field for the protein folding problem, within the context of proteins whose folding is assisted by chaperones. The existence and effects of the electric field are consistent with several theories and experimental observations related to the protein folding problem, in particular with the foldon view.<\/jats:p>","DOI":"10.3390\/ijms27073297","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T02:06:21Z","timestamp":1775441181000},"page":"3297","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Proteins Inside the HSP60\/HSP10 Fold Under a Constant Electric Field: Potential Implications for the Protein Folding Problem"],"prefix":"10.3390","volume":"27","author":[{"given":"Luc\u00eda J.","family":"Pe\u00f1a-Ortiz","sequence":"first","affiliation":[{"name":"Posgrado en Ciencias Qu\u00edmicas, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, 14 Sur y Av. San Claudio, Col. San Manuel, Puebla C. P. 72570, Puebla, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1178-2146","authenticated-orcid":false,"given":"Julio Manuel","family":"Hern\u00e1ndez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas, Benem\u00e9rita Unversidad Aut\u00f3noma de Puebla, 14 Sur y Av. San Claudio, Col. San Manuel, Puebla C. P. 72570, Puebla, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8041-9404","authenticated-orcid":false,"given":"Bertha Alicia","family":"Le\u00f3n-Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas, Benem\u00e9rita Unversidad Aut\u00f3noma de Puebla, 14 Sur y Av. San Claudio, Col. San Manuel, Puebla C. P. 72570, Puebla, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6594-1141","authenticated-orcid":false,"given":"Jose R.","family":"Eguibar","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda, Benem\u00e9rita Unversidad Aut\u00f3noma de Puebla, 14 Sur #6301, Col. San Manuel, Puebla C. P. 72570, Puebla, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8773-4215","authenticated-orcid":false,"given":"Juan Manuel","family":"Solano-Altamirano","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas, Benem\u00e9rita Unversidad Aut\u00f3noma de Puebla, 14 Sur y Av. San Claudio, Col. San Manuel, Puebla C. P. 72570, Puebla, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1626-9357","authenticated-orcid":false,"given":"Viridiana","family":"Vargas-Castro","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas, Benem\u00e9rita Unversidad Aut\u00f3noma de Puebla, 14 Sur y Av. San Claudio, Col. San Manuel, Puebla C. P. 72570, Puebla, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1126\/science.181.4096.223","article-title":"Principles that govern the folding of protein chains","volume":"181","author":"Anfinsen","year":"1973","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1126\/science.abj8754","article-title":"Accurate prediction of protein structures and interactions using a three-track neural network","volume":"373","author":"Baek","year":"2021","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e2214423119","DOI":"10.1073\/pnas.2214423119","article-title":"Protein folds vs. protein folding: Differing questions, different challenges","volume":"120","author":"Chen","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1126\/science.abn9422","article-title":"The protein-folding problem: Not yet solved","volume":"375","author":"Moore","year":"2022","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1007\/s10930-020-09925-w","article-title":"The Last Secret of Protein Folding: The Real Relationship Between Long-Range Interactions and Local Structures","volume":"39","author":"Cao","year":"2020","journal-title":"Protein J."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kikuchi, T. (2022). Decoding an Amino Acid Sequence to Extract Information on Protein Folding. Molecules, 27.","DOI":"10.3390\/molecules27093020"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1021\/acs.biochem.4c00321","article-title":"Slow Conformational Exchange between Partially Folded and Near-Native States of Ubiquitin: Evidence for a Multistate Folding Model","volume":"63","author":"Adhada","year":"2024","journal-title":"Biochemistry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"014402","DOI":"10.1103\/PhysRevE.104.014402","article-title":"Building blocks of protein structures: Physics meets biology","volume":"104","author":"Maritan","year":"2021","journal-title":"Phys. Rev. E"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/377754a0","article-title":"Initial hydrophobic collapse in the folding of barstar","volume":"377","author":"Agashe","year":"1995","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8911","DOI":"10.1021\/acs.chemrev.1c00704","article-title":"Heterogeneity in Protein Folding and Unfolding Reactions","volume":"122","author":"Bhatia","year":"2022","journal-title":"Chem. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"15873","DOI":"10.1073\/pnas.1411798111","article-title":"The nature of protein folding pathways","volume":"111","author":"Englander","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8253","DOI":"10.1073\/pnas.1706196114","article-title":"The case for defined protein folding pathways","volume":"114","author":"Englander","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"16623","DOI":"10.1073\/pnas.0606843103","article-title":"A backbone-based theory of protein folding","volume":"103","author":"Rose","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1146\/annurev.biochem.77.061306.131357","article-title":"Structure and Energetics of the Hydrogen-Bonded Backbone in Protein Folding","volume":"77","author":"Bolen","year":"2008","journal-title":"Annu. Rev. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1073\/pnas.70.3.697","article-title":"Nucleation, Rapid Folding, and Globular Intrachain Regions in Proteins","volume":"70","author":"Wetlaufer","year":"1973","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/BF00208801","article-title":"The nature of protein folding pathways: The classical versus the new view","volume":"5","author":"Baldwin","year":"1995","journal-title":"J. Biomol. NMR"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/nsb0197-10","article-title":"From Levinthal to pathways to funnels","volume":"4","author":"Dill","year":"1997","journal-title":"Nat. Struct. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"167126","DOI":"10.1016\/j.jmb.2021.167126","article-title":"The protein folding problem: The role of theory","volume":"433","author":"Nassar","year":"2021","journal-title":"J. Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"E9759","DOI":"10.1073\/pnas.1716444114","article-title":"Theory, simulations, and experiments show that proteins fold by multiple pathways","volume":"114","author":"Eaton","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1051\/jcp\/1968650044","article-title":"Are there pathways for protein folding?","volume":"65","author":"Levinthal","year":"1968","journal-title":"J. Chim. Phys."},{"key":"ref_22","first-page":"22","article-title":"How to fold graciously","volume":"67","author":"Levinthal","year":"1969","journal-title":"Mossbauer Spectrosc. Biol. Syst."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1126\/science.7618079","article-title":"Protein Folding Intermediates: Native-State Hydrogen Exchange","volume":"269","author":"Bai","year":"1995","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/(SICI)1097-0134(199602)24:2<145::AID-PROT1>3.0.CO;2-I","article-title":"Future directions in folding: The multi-state nature of protein structure","volume":"24","author":"Bai","year":"1996","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1006\/jmbi.1997.1205","article-title":"The foldon universe: A survey of structural similarity and self-recognition of independently folding units 11Edited by F. E. Cohen","volume":"272","author":"Panchenko","year":"1997","journal-title":"J. Mol. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1080\/07391102.2012.748536","article-title":"The free energy landscape of protein folding and dynamics: A global view","volume":"31","author":"Yang","year":"2013","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/S0959-440X(97)80003-6","article-title":"Submillisecond kinetics of protein folding","volume":"7","author":"Eaton","year":"1997","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4770","DOI":"10.1016\/j.cell.2022.11.014","article-title":"Structural visualization of the tubulin folding pathway directed by human chaperonin TRiC\/CCT","volume":"185","author":"Gestaut","year":"2022","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.tibs.2015.07.009","article-title":"The GroEL-GroES Chaperonin Machine: A Nano-Cage for Protein Folding","volume":"41","author":"Bracher","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e2118465119","DOI":"10.1073\/pnas.2118465119","article-title":"Conserved and divergent chaperoning effects of Hsp60\/10 chaperonins on protein folding landscapes","volume":"119","author":"Sadat","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.cell.2006.04.027","article-title":"Structural Features of the GroEL-GroES Nano-Cage Required for Rapid Folding of Encapsulated Protein","volume":"125","author":"Tang","year":"2006","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1038\/s41467-020-15698-8","article-title":"Structural basis for active single and double ring complexes in human mitochondrial Hsp60-Hsp10 chaperonin","volume":"11","author":"Jebara","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s12192-020-01080-6","article-title":"An inventory of interactors of the human HSP60\/HSP10 chaperonin in the mitochondrial matrix space","volume":"25","author":"Bie","year":"2020","journal-title":"Cell Stress Chaperones"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/S0092-8674(00)81446-4","article-title":"Prefoldin, a Chaperone that Delivers Unfolded Proteins to Cytosolic Chaperonin","volume":"93","author":"Vainberg","year":"1998","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1083\/jcb.145.2.265","article-title":"Prefoldin-Nascent Chain Complexes in the Folding of Cytoskeletal Proteins","volume":"145","author":"Hansen","year":"1999","journal-title":"J. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD\u2014Visual Molecular Dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1080\/07391102.2012.674286","article-title":"Levinthal\u2019s question revisited, and answered","volume":"30","year":"2012","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6719","DOI":"10.1073\/pnas.092686399","article-title":"Molecular dynamics simulations of protein folding from the transition state","volume":"99","author":"Gsponer","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4702","DOI":"10.1021\/ja908369h","article-title":"Unfolded-State Dynamics and Structure of Protein L Characterized by Simulation and Experiment","volume":"132","author":"Voelz","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1093\/nar\/gkz1235","article-title":"Pre-folded structures govern folding pathways of human telomeric G-quadruplexes","volume":"48","author":"Frelih","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e23020","DOI":"10.1002\/bip.23020","article-title":"Hydrophobic-hydrophilic forces in protein folding","volume":"107","author":"Durell","year":"2017","journal-title":"Biopolymers"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11367","DOI":"10.1073\/pnas.1831920100","article-title":"How protein thermodynamics and folding mechanisms are altered by the chaperonin cage: Molecular simulations","volume":"100","author":"Takagi","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11838","DOI":"10.1021\/ja802248m","article-title":"A Role for Confined Water in Chaperonin Function","volume":"130","author":"England","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.sbi.2007.12.013","article-title":"Rattling the cage: Computational models of chaperonin-mediated protein folding","volume":"18","author":"England","year":"2008","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"E4758","DOI":"10.1073\/pnas.1800690115","article-title":"Developing a molecular dynamics force field for both folded and disordered protein states","volume":"115","author":"Robustelli","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3772","DOI":"10.1016\/j.bpj.2009.02.033","article-title":"Force Field Bias in Protein Folding Simulations","volume":"96","author":"Freddolino","year":"2009","journal-title":"Biophys. J."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Roterman, I., Stapor, K., and Konieczny, L. (2024). Model of the external force field for the protein folding process\u2014The role of prefoldin. Front. Chem., 12.","DOI":"10.3389\/fchem.2024.1342434"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1021\/acs.jctc.3c01106","article-title":"The Role of Force Fields and Water Models in Protein Folding and Unfolding Dynamics","volume":"20","author":"Fischer","year":"2024","journal-title":"J. Chem. Theory Comput."},{"key":"ref_49","first-page":"375","article-title":"Statistical mechamics of protein folding: Some outstanding problems","volume":"Volume 23","author":"Attig","year":"2004","journal-title":"Computational Soft Matter: From Synthetic Polymers to Proteins"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6474","DOI":"10.1021\/jp003919d","article-title":"Evaluation and Reparametrization of the OPLS-AA Force Field for Proteins via Comparison with Accurate Quantum Chemical Calculations on Peptides","volume":"105","author":"Kaminski","year":"2001","journal-title":"J. Phys. Chem. B"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Berendsen, H.J.C., Postma, J.P.M., van Gunsteren, W.F., and Hermans, J. (1981). Interaction Models for Water in Relation to Protein Hydration. Intermolecular Forces: Proceedings of the Fourteenth Jerusalem Symposium on Quantum Chemistry and Biochemistry Held in Jerusalem, Israel, Springer.","DOI":"10.1007\/978-94-015-7658-1_21"},{"key":"ref_53","unstructured":"(2026, February 16). VMD PMEPot Plugin. Available online: https:\/\/www.ks.uiuc.edu\/Research\/vmd\/plugins\/pmepot\/."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3745","DOI":"10.1529\/biophysj.104.058727","article-title":"Imaging \u03b1-Hemolysin with Molecular Dynamics: Ionic Conductance, Osmotic Permeability, and the Electrostatic Potential Map","volume":"88","author":"Aksimentiev","year":"2005","journal-title":"Biophys. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"W665","DOI":"10.1093\/nar\/gkh381","article-title":"PDB2PQR: An automated pipeline for the setup of Poisson-Boltzmann electrostatics calculations","volume":"32","author":"Dolinsky","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"W522","DOI":"10.1093\/nar\/gkm276","article-title":"PDB2PQR: Expanding and upgrading automated preparation of biomolecular structures for molecular simulations","volume":"35","author":"Dolinsky","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1021\/j100058a043","article-title":"Accurate Calculation of Hydration Free Energies Using Macroscopic Solvent Models","volume":"98","author":"Sitkoff","year":"1994","journal-title":"J. Phys. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/j.jmb.2006.12.001","article-title":"Calculation of pKas in RNA: On the Structural Origins and Functional Roles of Protonated Nucleotides","volume":"366","author":"Tang","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_59","unstructured":"Pe\u00f1a-Ortiz, L. (2022). Caracterizaci\u00f3n del Potencial Electrost\u00e1tico de Largo Alcance en el Interior de la Chaperonina HSP60-HSP10 y su Posible Efecto Sobre el Plegamiento de Prote\u00ednas. [Master\u2019s Thesis, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla]."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3297\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T04:14:40Z","timestamp":1775535280000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3297"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,5]]},"references-count":59,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27073297"],"URL":"https:\/\/doi.org\/10.3390\/ijms27073297","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,5]]}}}