{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T18:10:07Z","timestamp":1776363007954,"version":"3.51.2"},"reference-count":58,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T00:00:00Z","timestamp":1636761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Merck Serono KGaA","award":["GMSI 2017"],"award-info":[{"award-number":["GMSI 2017"]}]},{"name":"Spanish Ministry of Science","award":["CTQ2017-89832-P"],"award-info":[{"award-number":["CTQ2017-89832-P"]}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/QUI-QOR\/29967\/2017"],"award-info":[{"award-number":["PTDC\/QUI-QOR\/29967\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["LISBOA-01-0145-FEDER-029967"],"award-info":[{"award-number":["LISBOA-01-0145-FEDER-029967"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04138\/2020 and UIDP\/04138\/2020"],"award-info":[{"award-number":["UIDB\/04138\/2020 and UIDP\/04138\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that is characterized by the presence of demyelinated regions with accumulated myelin lipid debris. Importantly, to allow effective remyelination, such debris must be cleared by microglia. Therefore, the study of microglial activity with sensitive tools is of great interest to better monitor the MS clinical course. Using a boronic acid-based (BASHY) fluorophore, specific for nonpolar lipid aggregates, we aimed to address BASHY\u2019s ability to label nonpolar myelin debris and image myelin clearance in the context of demyelination. Demyelinated ex vivo organotypic cultures (OCSCs) and primary microglia cells were immunostained to evaluate BASHY\u2019s co-localization with myelin debris and also to evaluate BASHY\u2019s specificity for phagocytosing cells. Additionally, mice induced with experimental autoimmune encephalomyelitis (EAE) were injected with BASHY and posteriorly analyzed to evaluate BASHY+ microglia within demyelinated lesions. Indeed, in our in vitro and ex vivo studies, we showed a significant increase in BASHY labeling in demyelinated OCSCs, mostly co-localized with Iba1-expressing amoeboid\/phagocytic microglia. Most importantly, BASHY\u2019s presence was also found within demyelinated areas of EAE mice, essentially co-localizing with lesion-associated Iba1+ cells, evidencing BASHY\u2019s potential for the in vivo bioimaging of myelin clearance and myelin-carrying microglia in regions of active demyelination.<\/jats:p>","DOI":"10.3390\/cells10113163","type":"journal-article","created":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T20:48:36Z","timestamp":1636922916000},"page":"3163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["BASHY Dye Platform Enables the Fluorescence Bioimaging of Myelin Debris Phagocytosis by Microglia during Demyelination"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4972-7369","authenticated-orcid":false,"given":"Maria V.","family":"Pinto","sequence":"first","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"given":"F\u00e1bio M. F.","family":"Santos","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"given":"Catarina","family":"Barros","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"given":"Ana Rita","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"given":"Uwe","family":"Pischel","sequence":"additional","affiliation":[{"name":"CIQSO (Centro de Investigaci\u00f3n en Qu\u00edmica Sostenible)\u2014Centre for Research in Sustainable Chemistry and Department of Chemistry, University of Huelva, 21071 Huelva, Spain"}]},{"given":"Pedro M. P.","family":"Gois","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-003 Lisbon, Portugal"},{"name":"Department of Pharmaceutical Sciences and Medicines, Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2782-9519","authenticated-orcid":false,"given":"Adelaide","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-003 Lisbon, Portugal"},{"name":"Department of Pharmaceutical Sciences and Medicines, Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,13]]},"reference":[{"key":"ref_1","unstructured":"WHO (2008). Atlas Multiple Sclerosis resources In The World 2008, WHO."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1055\/s-0038-1649502","article-title":"Multiple Sclerosis","volume":"38","author":"Yamout","year":"2018","journal-title":"Semin. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1084\/jem.20141656","article-title":"Inefficient clearance of myelin debris by microglia impairs remyelinating processes","volume":"212","author":"Lampron","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/35000219","article-title":"Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1","volume":"403","author":"Chen","year":"2000","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1002\/glia.22535","article-title":"Myelin inhibits oligodendroglial maturation and regulates oligodendrocytic transcription factor expression","volume":"61","author":"Plemel","year":"2013","journal-title":"Glia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/s41593-021-00829-1","article-title":"Microglia clean up toxic lipids in multiple sclerosis","volume":"24","author":"Monroe","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/0896-6273(94)90247-X","article-title":"identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth","volume":"13","author":"McKerracher","year":"1994","journal-title":"Neuron"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1038\/nn.3168","article-title":"Animal models of multiple sclerosis: The good, the bad and the bottom line","volume":"15","author":"Ransohoff","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/S0140-6736(08)61620-7","article-title":"Multiple Sclerosis","volume":"372","year":"2008","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1002\/jmri.22441","article-title":"Is the magnetization transfer ratio a marker for myelin in multiple sclerosis?","volume":"33","author":"Vavasour","year":"2011","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1536012118785471","DOI":"10.1177\/1536012118785471","article-title":"Detecting Demyelination by PET: The Lesion as Imaging Target","volume":"17","author":"Brugarolas","year":"2018","journal-title":"Mol. Imaging"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1002\/ana.23965","article-title":"Longitudinal positron emission tomography imaging for monitoring myelin repair in the spinal cord","volume":"74","author":"Wu","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"14663","DOI":"10.1523\/JNEUROSCI.4082-08.2009","article-title":"In vivo quantification of myelin changes in the vertebrate nervous system","volume":"29","author":"Wang","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Sahraian MA, R.E. (2008). Gadolinium enhancing lesions in multiple sclerosis. MRI Atlas of MS Lesions, Springer.","DOI":"10.1007\/978-3-540-71372-2_3"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tronel, C., Largeau, B., Santiago Ribeiro, M.J., Guilloteau, D., Dupont, A.C., and Arlicot, N. (2017). Molecular Targets for PET Imaging of Activated Microglia: The Current Situation and Future Expectations. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18040802"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3389\/fneur.2018.00181","article-title":"Evaluation of Microglial Activation in Multiple Sclerosis Patients Using Positron Emission Tomography","volume":"9","author":"Airas","year":"2018","journal-title":"Front. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1038\/s41467-019-08990-9","article-title":"Imaging inflammation using an activated macrophage probe with Slc18b1 as the activation-selective gating target","volume":"10","author":"Park","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1002\/glia.24052","article-title":"Activated microglia do not increase 18 kDa translocator protein (TSPO) expression in the multiple sclerosis brain","volume":"69","author":"Nutma","year":"2021","journal-title":"Glia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1002\/chem.201503943","article-title":"A Three-Component Assembly Promoted by Boronic Acids Delivers a Modular Fluorophore Platform (BASHY Dyes)","volume":"22","author":"Santos","year":"2016","journal-title":"Chem. Eur. J."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rasband, M.N., and Macklin, W.B. (2012). Myelin Structure and Biochemistry. Basic Neurochemistry: Principles of Molecular, Cellular, and Medical Neurobiology, Elsevier.","DOI":"10.1016\/B978-0-12-374947-5.00010-9"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1084\/jem.20132477","article-title":"Differential roles of microglia and monocytes in the inflamed central nervous system","volume":"211","author":"Yamasaki","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s40478-018-0628-8","article-title":"The physiology of foamy phagocytes in multiple sclerosis","volume":"6","author":"Grajchen","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2682","DOI":"10.2353\/ajpath.2010.091234","article-title":"Fingolimod (FTY720) enhances remyelination following demyelination of organotypic cerebellar slices","volume":"176","author":"Miron","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/jnr.20248","article-title":"Lysolecithin Induces Demyelination In Vitro in a Cerebellar Slice Culture System","volume":"78","author":"Birgbauer","year":"2004","journal-title":"J. Neurosci. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/jnr.20857","article-title":"Unconjugated bilirubin activates and damages microglia","volume":"84","author":"Gordo","year":"2006","journal-title":"J. Neurosci. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/glia.10274","article-title":"High-yield isolation of murine microglia by mild trypsinization","volume":"44","author":"Saura","year":"2003","journal-title":"Glia"},{"key":"ref_27","first-page":"56322","article-title":"In Vitro Phagocytosis of Myelin Debris by Bone Marrow-Derived Macrophages","volume":"130","author":"Rolfe","year":"2017","journal-title":"J. Vis. Exp."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.4049\/jimmunol.1201269","article-title":"T cell apoptosis and induction of Foxp3+ regulatory T cells underlie the therapeutic efficacy of CD4 blockade in experimental autoimmune encephalomyelitis","volume":"189","author":"Duarte","year":"2012","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1039\/C6CC08671C","article-title":"Site-selective installation of BASHY fluorescent dyes to Annexin V for targeted detection of apoptotic cells","volume":"53","author":"Cal","year":"2016","journal-title":"Chem. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"14064","DOI":"10.1002\/chem.202001623","article-title":"Cyanine-Like Boronic Acid-Derived Salicylidenehydrazone Complexes (Cy-BASHY) for Bioimaging Applications","volume":"26","author":"Santos","year":"2020","journal-title":"Chem. Eur. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.celrep.2016.06.008","article-title":"Loss of Myelin Basic Protein Function Triggers Myelin Breakdown in Models of Demyelinating Diseases","volume":"16","author":"Weil","year":"2016","journal-title":"Cell Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cellimm.2018.01.020","article-title":"Macrophages and lipid metabolism","volume":"330","author":"Remmerie","year":"2018","journal-title":"Cell Immunol"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00401-016-1653-y","article-title":"An updated histological classification system for multiple sclerosis lesions","volume":"133","author":"Kuhlmann","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3389\/fncel.2018.00215","article-title":"Microglia Responses to Pro-inflammatory Stimuli (LPS, IFNgamma+TNFalpha) and Reprogramming by Resolving Cytokines (IL-4, IL-10)","volume":"12","author":"Lively","year":"2018","journal-title":"Front. Cell Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1038\/s41593-019-0418-z","article-title":"Central nervous system regeneration is driven by microglia necroptosis and repopulation","volume":"22","author":"Lloyd","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1186\/s12974-016-0730-4","article-title":"Nogo receptor complex expression dynamics in the inflammatory foci of central nervous system experimental autoimmune demyelination","volume":"13","author":"Theotokis","year":"2016","journal-title":"J. Neuroinflam."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.neuroimage.2006.05.006","article-title":"Cerebellar cortical atrophy in experimental autoimmune encephalomyelitis","volume":"32","author":"Tinsley","year":"2006","journal-title":"Neuroimage"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1093\/brain\/awz144","article-title":"Assessment of lesions on magnetic resonance imaging in multiple sclerosis: Practical guidelines","volume":"142","author":"Filippi","year":"2019","journal-title":"Brain A J. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Lavi, E., and Constantinescu, C.S. (2005). Histopathology of EAE. Experimental Models of Multiple Sclerosis, Springer US.","DOI":"10.1007\/b135502"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/B978-0-444-52001-2.00008-X","article-title":"The experimental autoimmune encephalomyelitis (EAE) model of MS: Utility for understanding disease pathophysiology and treatment","volume":"122","author":"Robinson","year":"2014","journal-title":"Handb. Clin. Neurol"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Sloka, S., Zhornitsky, S., Silva, C., Metz, L.M., and Yong, V.W. (2015). 1,25-Dihydroxyvitamin D3 Protects against Immune-Mediated Killing of Neurons in Culture and in Experimental Autoimmune Encephalomyelitis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0144084"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jneumeth.2017.04.003","article-title":"Consistent induction of chronic experimental autoimmune encephalomyelitis in C57BL\/6 mice for the longitudinal study of pathology and repair","volume":"284","author":"Hasselmann","year":"2017","journal-title":"J. Neurosci. Methods"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"255","DOI":"10.3389\/fimmu.2018.00255","article-title":"Significance and In Vivo Detection of Iron-Laden Microglia in White Matter Multiple Sclerosis Lesions","volume":"9","author":"Gillen","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1002\/1098-1136(200103)33:3<256::AID-GLIA1024>3.0.CO;2-J","article-title":"Dynamics of microglial activation: A confocal time-lapse analysis in hippocampal slices","volume":"33","author":"Stence","year":"2001","journal-title":"Glia"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.4103\/1673-5374.145358","article-title":"The occurrence of diffuse axonal injury in the brain: Associated with the accumulation and clearance of myelin debris","volume":"9","author":"Wen","year":"2014","journal-title":"Neural Regen. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1038\/nprot.2013.055","article-title":"Imaging of neutral lipids by oil red O for analyzing the metabolic status in health and disease","volume":"8","author":"Mehlem","year":"2013","journal-title":"Nat. Protoc."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.1111\/jcmm.16274","article-title":"Basic fibroblast growth factor accelerates myelin debris clearance through activating autophagy to facilitate early peripheral nerve regeneration","volume":"25","author":"Jiang","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Wulin Teo, A.V.C., MeMorgan, g.L., Luchicchi, A., Schenk, G.J., Joseph, J.T., Geurts, J.J.G., and Stys, P.K. (2021). Nile Red fluorescence spectroscopy reports early physicochemical changes in myelin with high sensitivity. Proc. Natl. Acad. Sci. USA, 118.","DOI":"10.1073\/pnas.2016897118"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1093\/brain\/aws262","article-title":"Astrocytes regulate myelin clearance through recruitment of microglia during cuprizone-induced demyelination","volume":"136","author":"Skripuletz","year":"2013","journal-title":"Brain"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1093\/brain\/aww298","article-title":"Myelin phagocytosis by astrocytes after myelin damage promotes lesion pathology","volume":"140","author":"Ponath","year":"2017","journal-title":"Brain"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41593-020-00757-6","article-title":"Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis","volume":"24","author":"Berghoff","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1002\/glia.20815","article-title":"Lysophosphatidylcholine induces glial cell activation: Role of rho kinase","volume":"57","author":"Sheikh","year":"2009","journal-title":"Glia"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1159\/000026329","article-title":"Transgenic models to study the actions of cytokines in the central nervous system","volume":"5","author":"Campbell","year":"1998","journal-title":"Neuroimmunomodulation"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1038\/nn.3469","article-title":"M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination","volume":"16","author":"Miron","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"8488","DOI":"10.1038\/s41598-019-44682-6","article-title":"Central nervous system targeted autoimmunity causes regional atrophy: A 9.4T MRI study of the EAE mouse model of Multiple Sclerosis","volume":"9","author":"Hamilton","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jneuroim.2014.09.016","article-title":"Mapping the accumulation of co-infiltrating CNS dendritic cells and encephalitogenic T cells during EAE","volume":"277","author":"Clarkson","year":"2014","journal-title":"J. Neuroimmunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1093\/intimm\/dxt044","article-title":"Early pathological alterations of lower lumbar cords detected by ultrahigh-field MRI in a mouse multiple sclerosis model","volume":"26","author":"Mori","year":"2014","journal-title":"Int. Immunol."},{"key":"ref_58","first-page":"600","article-title":"Administration of Substances to Laboratory Animals: Routes of Administration and Factors to Consider","volume":"50","author":"Patricia","year":"2011","journal-title":"J. Am. Assoc. Lab. Anim. Sci."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/11\/3163\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:29:56Z","timestamp":1760167796000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/11\/3163"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,13]]},"references-count":58,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["cells10113163"],"URL":"https:\/\/doi.org\/10.3390\/cells10113163","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,13]]}}}