{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T12:54:43Z","timestamp":1770555283775,"version":"3.49.0"},"reference-count":55,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T00:00:00Z","timestamp":1653523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU Seventh Framework Programme","award":["FP7\/2007-2013"],"award-info":[{"award-number":["FP7\/2007-2013"]}]},{"name":"EU Seventh Framework Programme","award":["NFR 204341\/H10"],"award-info":[{"award-number":["NFR 204341\/H10"]}]},{"name":"EU Seventh Framework Programme","award":["Nano-cancer 19\/0274"],"award-info":[{"award-number":["Nano-cancer 19\/0274"]}]},{"name":"Research Council of Norway","award":["FP7\/2007-2013"],"award-info":[{"award-number":["FP7\/2007-2013"]}]},{"name":"Research Council of Norway","award":["NFR 204341\/H10"],"award-info":[{"award-number":["NFR 204341\/H10"]}]},{"name":"Research Council of Norway","award":["Nano-cancer 19\/0274"],"award-info":[{"award-number":["Nano-cancer 19\/0274"]}]},{"name":"National Institute of Occupational Health, Norway","award":["FP7\/2007-2013"],"award-info":[{"award-number":["FP7\/2007-2013"]}]},{"name":"National Institute of Occupational Health, Norway","award":["NFR 204341\/H10"],"award-info":[{"award-number":["NFR 204341\/H10"]}]},{"name":"National Institute of Occupational Health, Norway","award":["Nano-cancer 19\/0274"],"award-info":[{"award-number":["Nano-cancer 19\/0274"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Telomere shortening can result in cellular senescence and in increased level of genome instability, which are key events in numerous of cancer types. Despite this, few studies have focused on the effect of nanomaterial exposure on telomere length as a possible mechanism involved in nanomaterial-induced carcinogenesis. In this study, effects of exposure to multiwalled carbon nanotubes (MWCNT) on telomere length were investigated in mice exposed by intrapleural injection, as well as in human lung epithelial and mesothelial cell lines. In addition, cell cycle, apoptosis, and regulation of genes involved in DNA damage repair were assessed. Exposure to MWCNT led to severe fibrosis, infiltration of inflammatory cells in pleura, and mesothelial cell hyperplasia. These histological alterations were accompanied by deregulation of genes involved in fibrosis and immune cell recruitment, as well as a significant shortening of telomeres in the pleura and the lung. Assessment of key carcinogenic mechanisms in vitro confirmed that long-term exposure to the long MWCNT led to a prominent telomere shortening in epithelial cells, which coincided with G1-phase arrest and enhanced apoptosis. Altogether, our data show that telomere shortening resulting in cell cycle arrest and apoptosis may be an important mechanism in long MWCNT-induced inflammation and fibrosis.<\/jats:p>","DOI":"10.3390\/ijms23116005","type":"journal-article","created":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T07:05:07Z","timestamp":1653635107000},"page":"6005","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Multiwalled Carbon Nanotubes Induce Fibrosis and Telomere Length Alterations"],"prefix":"10.3390","volume":"23","author":[{"given":"Mayes","family":"Alswady-Hoff","sequence":"first","affiliation":[{"name":"National Institute of Occupational Health, 0033 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna Samulin","family":"Erdem","sequence":"additional","affiliation":[{"name":"National Institute of Occupational Health, 0033 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona","family":"Aleksandersen","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Norwegian University of Life Sciences, 1432 As, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristine Haugen","family":"Anmarkrud","sequence":"additional","affiliation":[{"name":"National Institute of Occupational Health, 0033 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8043-2820","authenticated-orcid":false,"given":"\u00d8ivind","family":"Skare","sequence":"additional","affiliation":[{"name":"National Institute of Occupational Health, 0033 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0534-9469","authenticated-orcid":false,"given":"Fang-Chin","family":"Lin","sequence":"additional","affiliation":[{"name":"National Institute of Occupational Health, 0033 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Simensen","sequence":"additional","affiliation":[{"name":"National Institute of Occupational Health, 0033 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yke Jildouw","family":"Arnoldussen","sequence":"additional","affiliation":[{"name":"National Institute of Occupational Health, 0033 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vidar","family":"Skaug","sequence":"additional","affiliation":[{"name":"National Institute of Occupational Health, 0033 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Ropstad","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Norwegian University of Life Sciences, 1432 As, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9747-9625","authenticated-orcid":false,"given":"Shanbeh","family":"Zienolddiny-Narui","sequence":"additional","affiliation":[{"name":"National Institute of Occupational Health, 0033 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,26]]},"reference":[{"key":"ref_1","unstructured":"Tran, C.L., Hankin, S.M., Ross, B., Aitken, R.J., Jones, A.D., Donaldson, K., Stone, V., and Trantra, R. (2008). An Outline Scoping Study to Determine Whether High Aspect Ratio Nanoparticles (Harn) Should Raise the Same Concerns as Do Asbestos Fibres. Report on Project CB0406, IOM."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1743-8977-7-5","article-title":"Asbestos, Carbon Nanotubes and the Pleural Mesothelium: A Review of the Hypothesis Regarding the Role of Long Fibre Retention in the Parietal Pleura, Inflammation and Mesothelioma","volume":"7","author":"Donaldson","year":"2010","journal-title":"Part. Fibre Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Barbarino, M., and Giordano, A. (2021). Assessment of the Carcinogenicity of Carbon Nanotubes in the Respiratory System. Cancers, 13.","DOI":"10.3390\/cancers13061318"},{"key":"ref_4","unstructured":"IARC (2017, May 19). Some Nanomaterials and Some Fibres: Iarc Monographs on the Evaluation of Carcinogenic Risks to Humans. Available online: https:\/\/publications.iarc.fr\/Book-And-Report-Series\/Iarc-Monographs-On-The-Identification-Of-Carcinogenic-Hazards-To-Humans\/Some-Nanomaterials-And-Some-Fibres-2017."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1080\/17435390.2016.1202351","article-title":"Multi-walled carbon nanotube physicochemical properties predict pulmonary inflammation and genotoxicity","volume":"10","author":"Poulsen","year":"2016","journal-title":"Nanotoxicology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1743-8977-11-3","article-title":"Promotion of lung adenocarcinoma following inhalation exposure to multi-walled carbon nanotubes","volume":"11","author":"Sargent","year":"2014","journal-title":"Part. Fibre Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1080\/17435390.2018.1465139","article-title":"Inflammation in the pleural cavity following injection of multi-walled carbon nanotubes is dependent on their characteristics and the presence of IL-1 genes","volume":"12","author":"Arnoldussen","year":"2018","journal-title":"Nanotoxicology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1007\/s00204-014-1356-x","article-title":"Role of oxidative stress in carbon nanotube-generated health effects","volume":"88","author":"Jensen","year":"2014","journal-title":"Arch. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10408444.2016.1206061","article-title":"Evaluating the Mechanistic Evidence and Key Data Gaps in Assessing the Potential Carcinogenicity of Carbon Nanotubes and Nanofibers in Humans","volume":"47","author":"Kuempel","year":"2017","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1021\/acs.chemrestox.0c00172","article-title":"Toxicity of Carbon Nanotubes: Molecular Mechanisms, Signaling Cascades, and Remedies in Biomedical Applications","volume":"34","author":"Saleemi","year":"2020","journal-title":"Chem. Res. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"14532","DOI":"10.1038\/ncomms14532","article-title":"Cellular senescence mediates fibrotic pulmonary disease","volume":"8","author":"Schafer","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ebiom.2017.03.027","article-title":"Telomeres and Cell Senescence\u2014Size Matters Not","volume":"21","author":"Victorelli","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1126\/science.277.5328.955","article-title":"Telomerase Catalytic Subunit Homologs from Fission Yeast and Human","volume":"277","author":"Nakamura","year":"1997","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/345458a0","article-title":"Telomeres shorten during ageing of human fibroblasts","volume":"345","author":"Harley","year":"1990","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1152\/physrev.00026.2007","article-title":"Telomeres and Aging","volume":"88","author":"Aubert","year":"2008","journal-title":"Physiol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.mrfmmm.2011.10.013","article-title":"Telomerase and idiopathic pulmonary fibrosis","volume":"730","author":"Armanios","year":"2012","journal-title":"Mutat. Res. Mol. Mech. Mutagen."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"107742","DOI":"10.1016\/j.pharmthera.2020.107742","article-title":"Telomeres in Toxicology: Occupational Health","volume":"220","author":"Shoeb","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1093\/mutage\/gew036","article-title":"Repair activity of oxidatively damaged DNA and telomere length in human lung epithelial cells after exposure to multi-walled carbon nanotubes","volume":"32","author":"Borghini","year":"2016","journal-title":"Mutagenesis"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1080\/17435390.2021.1910359","article-title":"Reactive Oxygen Species Production, Genotoxicity and Telomere Length in Fe1-Muta\u2122Mouse Lung Epithelial Cells Exposed to Carbon Nanotubes","volume":"15","author":"Wils","year":"2021","journal-title":"Nanotoxicology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"122569","DOI":"10.1016\/j.jhazmat.2020.122569","article-title":"Increased telomere length and mtDNA copy number induced by multi-walled carbon nanotube exposure in the workplace","volume":"394","author":"Ghosh","year":"2020","journal-title":"J. Hazard. Mater."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1016\/j.ajpath.2011.02.040","article-title":"Length-Dependent Retention of Carbon Nanotubes in the Pleural Space of Mice Initiates Sustained Inflammation and Progressive Fibrosis on the Parietal Pleura","volume":"178","author":"Murphy","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1002\/ijc.2910500620","article-title":"Mesothelioma in rats following intrapleural injection of chrysotile and phosphorylated chrysotile (chrysophosphate)","volume":"50","author":"Fleury","year":"1992","journal-title":"Int. J. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/1097-0142(197501)35:1<165::AID-CNCR2820350122>3.0.CO;2-U","article-title":"Nodular mesothelial hyperplasia in hernia sacs.A benign reactive condition simulating a neoplastic process","volume":"35","author":"Rosai","year":"1975","journal-title":"Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12989-021-00413-2","article-title":"In Vitro-in Vivo Correlations of Pulmonary Inflammogenicity and Genotoxicity of Mwcnt","volume":"18","author":"Erdem","year":"2021","journal-title":"Part. Fibre Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.mrgentox.2017.08.005","article-title":"Multi-walled carbon nanotube-induced genotoxic, inflammatory and pro-fibrotic responses in mice: Investigating the mechanisms of pulmonary carcinogenesis","volume":"823","author":"Rahman","year":"2017","journal-title":"Mutat. Res. Toxicol. Environ. Mutagen."},{"key":"ref_27","first-page":"111412","article-title":"Cellular senescence as a response to multiwalled carbon nanotube (MWCNT) exposure in human mesothelial cells","volume":"193","author":"Hackbarth","year":"2020","journal-title":"Mech. Ageing Dev."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lucas, J., Wang, Q., Muthumalage, T., and Rahman, I. (2021). Multi-Walled Carbon Nanotubes (MWCNTs) Cause Cellular Senescence in TGF-\u03b2 Stimulated Lung Epithelial Cells. Toxics, 9.","DOI":"10.20944\/preprints202105.0354.v1"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1038\/nature05976","article-title":"Replication and protection of telomeres","volume":"447","author":"Verdun","year":"2007","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Turner, K., Vasu, V., and Griffin, D. (2019). Telomere Biology and Human Phenotype. Cells, 8.","DOI":"10.3390\/cells8010073"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1111\/pin.12710","article-title":"Measurement of telomere length in cells from pleural effusion: Asbestos exposure causes telomere shortening in pleural mesothelial cells","volume":"68","author":"Aida","year":"2018","journal-title":"Pathol. Int."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Alswady-Hoff, M., Erdem, J.S., Phuyal, S., Knittelfelder, O., Sharma, A., Fonseca, D.D.M., Skare, \u00d8., Slupphaug, G., and Zienolddiny, S. (2021). Long-Term Exposure to Nanosized TiO2 Triggers Stress Responses and Cell Death Pathways in Pulmonary Epithelial Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105349"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1093\/mutage\/gez003","article-title":"Telomere length and genotoxicity in the lung of rats following intragastric exposure to food-grade titanium dioxide and vegetable carbon particles","volume":"34","author":"Jensen","year":"2019","journal-title":"Mutagenesis"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1016\/S0960-9822(03)00542-6","article-title":"DNA Damage Foci at Dysfunctional Telomeres","volume":"13","author":"Takai","year":"2003","journal-title":"Curr. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"794","DOI":"10.3109\/17435390.2015.1132345","article-title":"In vitro and in vivo genotoxic effects of straight versus tangled multi-walled carbon nanotubes","volume":"10","author":"Siivola","year":"2016","journal-title":"Nanotoxicology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1080\/17435390.2018.1425500","article-title":"Characterization of the proteome and lipidome profiles of human lung cells after low dose and chronic exposure to multiwalled carbon nanotubes","volume":"12","author":"Phuyal","year":"2018","journal-title":"Nanotoxicology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.exger.2014.07.010","article-title":"Dietary restriction ameliorates haematopoietic ageing independent of telomerase, whilst lack of telomerase and short telomeres exacerbates the ageing phenotype","volume":"58","author":"Saretzki","year":"2014","journal-title":"Exp. Gerontol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/ng0296-200","article-title":"Differential regulation of telomerase activity and telomerase RNA during multi-stage tumorigenesis","volume":"12","author":"Blasco","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/S0960-9822(00)00805-8","article-title":"The telomerase reverse transcriptase is limiting and necessary for telomerase function in vivo","volume":"10","author":"Harrington","year":"2000","journal-title":"Curr. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3754","DOI":"10.1038\/sj.onc.1211037","article-title":"TERT promotes cellular and organismal survival independently of telomerase activity","volume":"27","author":"Lee","year":"2008","journal-title":"Oncogene"},{"key":"ref_41","first-page":"3088","article-title":"Reversible cellular senescence: Implications for immortalization of normal human diploid fibroblasts","volume":"9","author":"Wright","year":"1989","journal-title":"Mol. Cell. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1038\/ncb1744","article-title":"Opposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiency","volume":"10","author":"Baker","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.gde.2010.10.005","article-title":"Cellular senescence: Putting the paradoxes in perspective","volume":"21","author":"Campisi","year":"2011","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nrc3773","article-title":"Inside and out: The activities of senescence in cancer","volume":"14","author":"Young","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41556-018-0249-2","article-title":"The dynamic nature of senescence in cancer","volume":"21","author":"Lee","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1097\/MCO.0b013e32834121b1","article-title":"Telomeres, Lifestyle, Cancer, and Aging","volume":"14","author":"Shammas","year":"2011","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"ra67","DOI":"10.1126\/scisignal.2005309","article-title":"The E3 ligase PARC mediates the degradation of cytosolic cytochrome c to promote survival in neurons and cancer cells","volume":"7","author":"Gama","year":"2014","journal-title":"Sci. Signal."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.cyto.2015.01.032","article-title":"Involvement of IL-1 genes in the cellular responses to carbon nanotube exposure","volume":"73","author":"Arnoldussen","year":"2015","journal-title":"Cytokine"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.tiv.2017.07.016","article-title":"Effects on human bronchial epithelial cells following low-dose chronic exposure to nanomaterials: A 6-month transformation study","volume":"44","author":"Phuyal","year":"2017","journal-title":"Toxicol. Vitro"},{"key":"ref_50","unstructured":"Rasmussen, K., Cotogno, G., and Gaillard, C. (2014, August 29). Multi-Walled Carbon Nanotubes, Nm-400, Nm-401, Nm-402, Nm-403: Characterisation and Physico-Chemical Properties. Available online: https:\/\/publications.jrc.ec.europa.eu\/repository\/bitstream\/JRC91205\/mwcnt-online.pdf."},{"key":"ref_51","unstructured":"Jensen, K.A. (2013, March 26). Deliverable 4.1: Summary Report on Primary Physicochemical Properties of Manufactured Nanomaterials Used in Nanogenotox. Available online: https:\/\/www.anses.fr\/en\/system\/files\/nanogenotox_deliverable.1.pdf."},{"key":"ref_52","unstructured":"Jensen, K.A. (2014). The Nanogenotox Dispersion Protocol for Nanoreg, National Research Centre for the Working Environment."},{"key":"ref_53","unstructured":"NIOSH (2013, April 01). Occupational Exposure to Carbon Nanotubes and Nanofibers, Available online: https:\/\/www.cdc.gov\/niosh\/docs\/2013-145\/pdfs\/2013-145.pdf?id=10.26616\/NIOSHPUB2013145."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1080\/17435390.2020.1814439","article-title":"Quantitative measurement of carbon nanotubes in rat lung","volume":"14","author":"Devoy","year":"2020","journal-title":"Nanotoxicology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1480-9222-13-3","article-title":"A quantitative PCR method for measuring absolute telomere length","volume":"13","author":"Fenech","year":"2011","journal-title":"Biol. Proced. Online"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/11\/6005\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:19:24Z","timestamp":1760138364000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/11\/6005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,26]]},"references-count":55,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["ijms23116005"],"URL":"https:\/\/doi.org\/10.3390\/ijms23116005","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,26]]}}}