{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T10:51:59Z","timestamp":1785927119843,"version":"3.56.0"},"reference-count":53,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"publisher","award":["ARUK PG2013A-003"],"award-info":[{"award-number":["ARUK PG2013A-003"]}],"id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"publisher"}]},{"award":["ARUK PG2013A-003"],"award-info":[{"award-number":["ARUK PG2013A-003"]}],"id":[{"id":"https:\/\/ror.org\/02ymzm013","id-type":"ROR","asserted-by":"publisher"}]},{"name":"MRC","award":["MRC\/G9901400"],"award-info":[{"award-number":["MRC\/G9901400"]}]},{"name":"MRC","award":["U.1052.00.0013"],"award-info":[{"award-number":["U.1052.00.0013"]}]},{"name":"MRC","award":["G0900582"],"award-info":[{"award-number":["G0900582"]}]},{"award":["MRC\/G9901400"],"award-info":[{"award-number":["MRC\/G9901400"]}],"id":[{"id":"https:\/\/ror.org\/03x94j517","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U.1052.00.0013"],"award-info":[{"award-number":["U.1052.00.0013"]}],"id":[{"id":"https:\/\/ror.org\/03x94j517","id-type":"ROR","asserted-by":"publisher"}]},{"award":["G0900582"],"award-info":[{"award-number":["G0900582"]}],"id":[{"id":"https:\/\/ror.org\/03x94j517","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/0187kwz08","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Cellular senescence may affect the post-mitotic cells of the brain. We examined the expression of senescence markers, including p16, p21, \u03b3H2Ax and H3K9me3, in the frontal cortex of brain donations from the Cognitive Function and Ageing Study to assess their relationship to Alzheimer\u2019s disease neuropathological change (ADNC) and dementia. p21, \u03b3H2Ax and H3K9me3 were expressed in pyramidal neurons and glia, whilst p16 was confined to glial cells. p21 and \u03b3H2Ax were correlated in neurons, and with p16 in glia. They did not increase with ADNC, tending to be higher at early Braak neurofibrillary tangle stages. Transcriptomic profiling of pyramidal neuron-enriched samples at low Braak stages showed that higher neuronal p21 expression was associated with altered pathways for neuronal function, neurodegeneration, protein homeostasis, mitochondrial dysfunction and synaptic signalling. In conclusion, the different expression profile of senescence markers in neurons and glia suggest possible differences in senescence-related mechanisms. Expression at lower ADNC stages suggests senescence may be important at earlier stages of Alzheimer\u2019s pathogenesis, whilst transcriptomic changes suggest an impact on neuronal function. The lack of association of senescence markers with dementia status indicates that more work is needed to determine the value of senescence as a therapeutic target for dementia.<\/jats:p>","DOI":"10.3390\/ijms27156964","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:57:56Z","timestamp":1785761876000},"page":"6964","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Senescence Markers and Associated Transcriptomic Changes Are Expressed at Early Stages of Alzheimer\u2019s Neuropathology but Are Not Independently Related to Dementia"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1668-7797","authenticated-orcid":false,"given":"Irina","family":"Vazquez-Villase\u00f1or","sequence":"first","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget","family":"Benson","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor D.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne NE1 7RU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5815-8829","authenticated-orcid":false,"given":"Rachel","family":"Waller","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia M.","family":"Castelli","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3753-4271","authenticated-orcid":false,"given":"Julie E.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1728-2388","authenticated-orcid":false,"given":"Fiona E.","family":"Matthews","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Applied Research, University of Hull, Hull HU6 7RX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Brayne","sequence":"additional","affiliation":[{"name":"Cambridge Public Health, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2785-333X","authenticated-orcid":false,"given":"Stephen B.","family":"Wharton","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e115","DOI":"10.1016\/S2666-7568(23)00019-3","article-title":"The prevalence, correlation, and co-occurrence of neuropathology in old age: Harmonisation of 12 measures across six community-based autopsy studies of dementia","volume":"4","author":"Nichols","year":"2023","journal-title":"Lancet Healthy Longev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s00401-017-1717-7","article-title":"Impact of multiple pathologies on the threshold for clinically overt dementia","volume":"134","author":"Kapasi","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study(MRC CFAS) (2001). Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Lancet, 357, 169\u2013175.","DOI":"10.1016\/S0140-6736(00)03589-3"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Matthews, F., Brayne, C., Lowe, J., McKeith, I., Wharton, S., and Ince, P. (2009). Epidemiological pathology of dementia: Attributable-risks at death in the MRC Cognitive Function and Ageing Study. PLoS Med., 6.","DOI":"10.1371\/journal.pmed.1000180"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s00401-022-02444-1","article-title":"Frequency of LATE neuropathologic change across the spectrum of Alzheimer\u2019s disease neuropathology: Combined data from 13 community-based or population-based autopsy cohorts","volume":"144","author":"Nelson","year":"2022","journal-title":"Acta Neuropathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s00401-015-1509-x","article-title":"Aging-related tau astrogliopathy (ARTAG): Harmonized evaluation strategy","volume":"131","author":"Kovacs","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s00401-018-1872-5","article-title":"Non-Alzheimer\u2019s contributions to dementia and cognitive resilience in the 90+ study","volume":"136","author":"Robinson","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1056\/NEJMoa0806142","article-title":"For the Medical Research Council Cognitive Function and Ageing Study. Age, neuropathology, and dementia","volume":"360","author":"Savva","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1002\/ana.24125","article-title":"Mild to moderate Alzheimer dementia with insufficient neuropathological changes","volume":"75","author":"Qian","year":"2014","journal-title":"Ann. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1002\/ana.23964","article-title":"Much of late life cognitive decline is not due to common neurodegenerative pathologies","volume":"74","author":"Boyle","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Maarouf, C.L., Daugs, I.D., Kokjohn, T.A., Walker, D.G., Hunter, J.M., Kruchowsky, J.C., Woltjer, R., Kaye, J., Casta\u00f1o, E.M., and Sabbagh, M.N. (2011). Alzheimer\u2019s disease and non-demented high pathology control nonagenarians: Comparing and contrasting the biochemistry of successful aging. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027291"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s40478-018-0558-5","article-title":"Neuropathology and cognitive performance in self-reported cognitively healthy centenarians","volume":"6","author":"Ganz","year":"2018","journal-title":"Acta Neuropathol. Comm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/S0140-6736(13)61570-6","article-title":"A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: Results of the Cognitive Function and Ageing Study I and II","volume":"382","author":"Matthews","year":"2013","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of ageing","volume":"153","author":"Blasco","year":"2013","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Sah, E., Krishnamurthy, S., Ahmidouch, M.Y., Gillispie, G.J., Milligan, C., and Orr, M.E. (2021). The Cellular Senescence Stress Response in Post-Mitotic Brain Cells: Cell Survival at the Expense of Tissue Degeneration. Life, 11.","DOI":"10.3390\/life11030229"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/nan.12689","article-title":"Cell senescence in neuropathology: A focus on neurodegeneration and tumours","volume":"47","author":"Carreno","year":"2021","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1136\/jnnp-2022-330743","article-title":"Molecules of senescent glial cells differentiate Alzheimer\u2019s disease from ageing","volume":"94","author":"Dai","year":"2023","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/nan.12559","article-title":"Expression of p16 and p21 in the frontal association cortex of ALS\/MND brains suggests neuronal cell cycle dysregulation and astrocyte senescence in early stages of the disease","volume":"46","author":"Garwood","year":"2020","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e12840","DOI":"10.1111\/acel.12840","article-title":"Tau protein aggregation is associated with cellular senescence in the brain","volume":"17","author":"Musi","year":"2018","journal-title":"Aging Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1111\/j.1474-9726.2012.00870.x","article-title":"Postmitotic neurons develop a p21-dependent senescence-like phenotype driven by a DNA damage response","volume":"11","author":"Jurk","year":"2012","journal-title":"Ageing Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/s41593-019-0372-9","article-title":"Senolytic therapy alleviates Ab-associated oligodendroglial progenitor cell senescence and cognitive defects in an Alzheimer\u2019s disease model","volume":"22","author":"Zhang","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41586-018-0543-y","article-title":"Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline","volume":"562","author":"Bussian","year":"2018","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e12923","DOI":"10.1111\/nan.12923","article-title":"Insights into the Pathological Basis of Dementia from Population Based Neuropathology Studies","volume":"49","author":"Wharton","year":"2023","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1038\/cdd.2009.221","article-title":"Cyclin-C-dependent cell-cycle entry is required for activation of non-homologous end joining DNA repair in postmitotic neurons","volume":"17","author":"Tomashevski","year":"2010","journal-title":"Cell Death Differ."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S0896-6273(04)00017-0","article-title":"Cell cycle activation linked to neuronal cell death initiated by DNA damage","volume":"41","author":"Kruman","year":"2004","journal-title":"Neuron"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1038\/s12276-025-01480-7","article-title":"Hallmarks of cellular senescence: Biology, mechanisms, regulations","volume":"57","author":"Ajoolabady","year":"2025","journal-title":"Exp. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.cell.2019.10.005","article-title":"Cellular Senescence: Defining a Path Forward","volume":"179","author":"Gorgoulis","year":"2019","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S0092-8674(03)00401-X","article-title":"Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence","volume":"113","author":"Narita","year":"2003","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"23","DOI":"10.4161\/nucl.23189","article-title":"High-order chromatin structure and the epigenome in SAHFs","volume":"4","author":"Chandra","year":"2013","journal-title":"Nucleus"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nrg3673","article-title":"Every amino acid matters: Essential contributions of histone variants to mammalian development and disease","volume":"15","author":"Maze","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nn.3639","article-title":"Tau promotes neurodegeneration through global chromatin relaxation","volume":"17","author":"Frost","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/nature14252","article-title":"Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer\u2019s disease","volume":"518","author":"Gjoneska","year":"2015","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1111\/acel.12580","article-title":"Detecting senescence: A new method for an old pigment","volume":"16","author":"Salmonowicz","year":"2017","journal-title":"Ageing Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"81099","DOI":"10.18632\/oncotarget.12752","article-title":"Is senescence-associated beta-galactosidase a marker of neuronal senescence?","volume":"7","author":"Piechota","year":"2016","journal-title":"Oncotarget"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kalisperati, P., Spanou, E., Pateras, I.S., Evangelou, K., Thymara, I., Korkolopoulou, P., Kotsinas, A., Vlachoyiannopoulos, P.G., Tzioufas, A.G., and Kanellopoulos, C. (2024). Helicobacter pylori Eradication Reverses DNA Damage Response Pathway but Not Senescence in Human Gastric Epithelium. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25073888"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/nan.12202","article-title":"A neuronal DNA damage response is detected at the earliest stages of Alzheimer\u2019s neuropathology and correlates with cognitive impairment in the MRC-CFAS ageing brain cohort","volume":"41","author":"Simpson","year":"2015","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1093\/jnen\/60.8.759","article-title":"Oxidative damage is the earliest event in Alzheimer Disease","volume":"60","author":"Nunomura","year":"2001","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1111\/j.1471-4159.2005.03615.x","article-title":"Increased oxidative damage in nuclear and mitochondrial DNA in mild cognitive impairment","volume":"96","author":"Wang","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1038\/s43587-021-00142-3","article-title":"Profiling senescent cells in human brains reveals neurons with CDKN2D\/p19 and tau neuropathology","volume":"1","author":"Dehkordi","year":"2021","journal-title":"Nat. Aging"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/s00401-024-02727-9","article-title":"Characterisation of premature cell senescence in Alzheimer\u2019s disease using single nuclear transcriptomics","volume":"147","author":"Fancy","year":"2024","journal-title":"Acta Neuropathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.4103\/0366-6999.186646","article-title":"Amyloid beta Protein Aggravates Neuronal Senescence and Cognitive Deficits in 5XFAD Mouse Model of Alzheimer\u2019s Disease","volume":"129","author":"Wei","year":"2016","journal-title":"Chin. Med. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1016\/j.neuron.2025.04.020","article-title":"p16-expressing microglia and endothelial cells promote tauopathy and neurovascular abnormalities in PS19 mice","volume":"113","author":"Graves","year":"2025","journal-title":"Neuron"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1002\/bies.20634","article-title":"Mitochondria and ageing: Winning and losing in the numbers game","volume":"29","author":"Passos","year":"2007","journal-title":"Bioessays"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"724","DOI":"10.15252\/embj.201592862","article-title":"Mitochondria are required for pro-ageing features of the senescent phenotype","volume":"35","author":"Marques","year":"2016","journal-title":"EMBO J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.cmet.2015.11.011","article-title":"Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype","volume":"23","author":"Wiley","year":"2016","journal-title":"Cell Metab."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Klepacki, H., Kowalczuk, K., Lepkowska, N., and Hermanowicz, J.M. (2025). Molecular Regulation of SASP in Cellular Senescence: Therapeutic Implications and Translational Challenges. Cells, 14.","DOI":"10.3390\/cells14130942"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.tcb.2018.02.001","article-title":"Hallmarks of Cellular Senescence","volume":"28","author":"Nehme","year":"2018","journal-title":"Trends Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1212\/WNL.41.4.479","article-title":"The Consortium to Establish a Registry for Alzheimer\u2019s Disease (CERAD). Part II. Standardisation of the neuropathologic assessment of Alzheimer\u2019s disease","volume":"41","author":"Mirra","year":"1991","journal-title":"Neurology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological stageing of Alzheimer-related changes","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1186\/s40478-019-0858-4","article-title":"Epidemiological pathology of Ab deposition in the ageing brain in CFAS: Addition of multiple Ab-derived measures does not improve dementia assessment using logistic regression and machine learning approaches","volume":"7","author":"Wharton","year":"2019","journal-title":"Acta Neuropathol. Comm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1212\/WNL.58.12.1791","article-title":"Phases of Ab-deposition in the human brain and its relevance for the development of AD","volume":"58","author":"Thal","year":"2002","journal-title":"Neurology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1111\/j.1365-2990.2010.01130.x","article-title":"Association between APOE genotype, neuropathology and dementia in the older population of England and Wales","volume":"37","author":"Nicoll","year":"2011","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"16878","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: Open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci. Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6964\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T10:42:00Z","timestamp":1785926520000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6964"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,3]]},"references-count":53,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156964"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156964","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,3]]}}}