{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:08:27Z","timestamp":1791590907393,"version":"4.3.4"},"reference-count":58,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T00:00:00Z","timestamp":1715644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences of the National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM152335"],"award-info":[{"award-number":["P20GM152335"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences of the National Institutes of Health","doi-asserted-by":"publisher","award":["1R56AG079224-01"],"award-info":[{"award-number":["1R56AG079224-01"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM152335"],"award-info":[{"award-number":["P20GM152335"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R56AG079224-01"],"award-info":[{"award-number":["1R56AG079224-01"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lipopolysaccharide-induced (LPS) inflammation is used as model to understand the role of inflammation in brain diseases. However, no studies have assessed the ability of peripheral low-level chronic LPS to induce neutrophil activation in the periphery and brain. Subclinical levels of LPS were injected intraperitoneally into mice to investigate its impacts on neutrophil frequency and activation. Neutrophil activation, as measured by CD11b expression, was higher in LPS-injected mice compared to saline-injected mice after 4 weeks but not 8 weeks of injections. Neutrophil frequency and activation increased in the periphery 4\u201312 h and 4\u20138 h after the fourth and final injection, respectively. Increased levels of G-CSF, TNFa, IL-6, and CXCL2 were observed in the plasma along with increased neutrophil elastase, a marker of neutrophil extracellular traps, peaking 4 h following the final injection. Neutrophil activation was increased in the brain of LPS-injected mice when compared to saline-injected mice 4\u20138 h after the final injection. These results indicate that subclinical levels of peripheral LPS induces neutrophil activation in the periphery and brain. This model of chronic low-level systemic inflammation could be used to understand how neutrophils may act as mediators of the periphery\u2013brain axis of inflammation with age and\/or in mouse models of neurodegenerative or neuroinflammatory disease.<\/jats:p>","DOI":"10.3390\/ijms25105357","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T08:59:37Z","timestamp":1715677177000},"page":"5357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Pilot Study to Investigate Peripheral Low-Level Chronic LPS Injection as a Model of Neutrophil Activation in the Periphery and Brain in Mice"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3398-3958","authenticated-orcid":false,"given":"Michelle","family":"Aries","sequence":"first","affiliation":[{"name":"McLaughlin Research Institute, Great Falls, MT 59405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makayla","family":"Cook","sequence":"additional","affiliation":[{"name":"McLaughlin Research Institute, Great Falls, MT 59405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6753-5622","authenticated-orcid":false,"given":"Tiffany","family":"Hensley-McBain","sequence":"additional","affiliation":[{"name":"McLaughlin Research Institute, Great Falls, MT 59405, USA"},{"name":"Department of Basic Sciences, Touro College of Osteopathic Medicine Montana, Great Falls, MT 59405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic inflammation in the etiology of disease across the life span","volume":"25","author":"Furman","year":"2019","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Rauf, A., Badoni, H., Abu-Izneid, T., Olatunde, A., Rahman, M.M., Painuli, S., Semwal, P., Wilairatana, P., and Mubarak, M.S. (2022). Neuroinflammatory Markers: Key Indicators in the Pathology of Neurodegenerative Diseases. Molecules, 27.","DOI":"10.3390\/molecules27103194"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Skrzypczak-Wiercioch, A., and Sa\u0142at, K. (2022). Lipopolysaccharide-Induced Model of Neuroinflammation: Mechanisms of Action, Research Application and Future Directions for Its Use. Molecules, 27.","DOI":"10.3390\/molecules27175481"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"796867","DOI":"10.3389\/fimmu.2021.796867","article-title":"The Impact of Systemic Inflammation on Alzheimer\u2019s Disease Pathology","volume":"12","author":"Xie","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.trci.2018.06.014","article-title":"Inflammation as a central mechanism in Alzheimer\u2019s disease","volume":"4","author":"Kinney","year":"2018","journal-title":"Alzheimer\u2019s Dement. Transl. Res. Clin. Interv."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"990","DOI":"10.3389\/fnins.2019.00990","article-title":"Myeloperoxidase Deficiency Inhibits Cognitive Decline in the 5XFAD Mouse Model of Alzheimer\u2019s Disease","volume":"13","author":"Volkman","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1123149","DOI":"10.3389\/fimmu.2023.1123149","article-title":"Neutrophils as a potential therapeutic target in Alzheimer\u2019s disease","volume":"14","author":"Aries","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.clim.2016.09.014","article-title":"Role of the JAK\/STAT signaling pathway in regulation of innate immunity in neuroinflammatory diseases","volume":"189","author":"Yan","year":"2018","journal-title":"Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/nm.3913","article-title":"Neutrophils promote Alzheimer\u2019s disease\u2013like pathology and cognitive decline via LFA-1 integrin","volume":"21","author":"Zenaro","year":"2015","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Song, L., Yang, Y.T., Guo, Q., the ZIB Consortium, and Zhao, X.-M. (2022). Cellular transcriptional alterations of peripheral blood in Alzheimer\u2019s disease. BMC Med., 20.","DOI":"10.1186\/s12916-022-02472-4"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"947781","DOI":"10.3389\/fneur.2022.947781","article-title":"Identification of genetic molecular markers and immune infiltration characteristics of Alzheimer\u2019s disease through weighted gene co-expression network analysis","volume":"13","author":"Duan","year":"2022","journal-title":"Front. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/ana.25159","article-title":"Neutrophil hyperactivation correlates with Alzheimer\u2019s disease progression: Neutrophil Hyperactivation in Alzheimer\u2019s Disease","volume":"83","author":"Dong","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1083928","DOI":"10.3389\/fnins.2023.1083928","article-title":"Novel diagnostic biomarkers related to immune infiltration in Parkinson\u2019s disease by bioinformatics analysis","volume":"17","author":"Zhang","year":"2023","journal-title":"Front. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/s41593-018-0329-4","article-title":"Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer\u2019s disease mouse models","volume":"22","author":"Bracko","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1177\/0271678X19873658","article-title":"Increasing cerebral blood flow improves cognition into late stages in Alzheimer\u2019s disease mice","volume":"40","author":"Bracko","year":"2020","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"104580","DOI":"10.1016\/j.phrs.2019.104580","article-title":"The role of neutrophils in neuro-immune modulation","volume":"151","author":"Kanashiro","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s40478-022-01347-2","article-title":"Neutrophil-vascular interactions drive myeloperoxidase accumulation in the brain in Alzheimer\u2019s disease","volume":"10","author":"Smyth","year":"2022","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Rossi, B., Constantin, G., and Zenaro, E. (2020). The emerging role of neutrophils in neurodegeneration. Immunobiology, 225.","DOI":"10.1016\/j.imbio.2019.10.014"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/nri.2016.49","article-title":"Neutrophil migration in infection and wound repair: Going forward in reverse","volume":"16","author":"Rosowski","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Manda-Handzlik, A., and Demkow, U. (2019). The Brain Entangled: The Contribution of Neutrophil Extracellular Traps to the Diseases of the Central Nervous System. Cells, 8.","DOI":"10.3390\/cells8121477"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.nbd.2016.07.007","article-title":"The blood-brain barrier in Alzheimer\u2019s disease","volume":"107","author":"Zenaro","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wu, Y.-C., Sonninen, T.-M., Peltonen, S., Koistinaho, J., and Lehtonen, \u0160. (2021). Blood-Brain Barrier and Neurodegenerative Diseases-Modeling with iPSC-Derived Brain Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147710"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1136\/thx.52.10.888","article-title":"Cryptogenic fibrosing alveolitis: Lack of association with Epstein-Barr virus infection","volume":"52","author":"Wangoo","year":"1997","journal-title":"Thorax"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e154225","DOI":"10.1172\/JCI154225","article-title":"Neutrophil extracellular traps regulate ischemic stroke brain injury","volume":"132","author":"Denorme","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.4110\/in.2023.23.e27","article-title":"NLRP3 Exacerbate NETosis-Associated Neuroinflammation in an LPS-Induced Inflamed Brain","volume":"23","author":"Byun","year":"2023","journal-title":"Immune Netw."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s12974-020-01759-8","article-title":"Sustained exposure to systemic endotoxin triggers chemokine induction in the brain followed by a rapid influx of leukocytes","volume":"17","author":"Thomson","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"27711","DOI":"10.1038\/srep27711","article-title":"NK cells promote neutrophil recruitment in the brain during sepsis-induced neuroinflammation","volume":"6","author":"He","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kim, Y.R., Kim, Y.M., Lee, J., Park, J., Lee, J.E., and Hyun, Y.-M. (2020). Neutrophils Return to Bloodstream through the Brain Blood Vessel after Crosstalk with Microglia During LPS-Induced Neuroinflammation. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.613733"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"823","DOI":"10.3858\/emm.2010.42.12.085","article-title":"Systemic LPS administration induces brain inflammation but not dopaminergic neuronal death in the substantia nigra","volume":"42","author":"Jeong","year":"2010","journal-title":"Exp. Mol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"96623","DOI":"10.3389\/fimmu.2014.00316","article-title":"A Comparative Review of Toll-Like Receptor 4 Expression and Functionality in Different Animal Species","volume":"5","author":"Vaure","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"175909141771920","DOI":"10.1177\/1759091417719201","article-title":"Peripheral Inflammation, Apolipoprotein E4, and Amyloid-\u03b2 Interact to Induce Cognitive and Cerebrovascular Dysfunction","volume":"9","author":"Marottoli","year":"2017","journal-title":"ASN Neuro"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"397","DOI":"10.3389\/fncel.2018.00397","article-title":"Diverse Protein Profiles in CNS Myeloid Cells and CNS Tissue from Lipopolysaccharide- and Vehicle-Injected APPSWE\/PS1\u0394E9 Transgenic Mice Implicate Cathepsin Z in Alzheimer\u2019s Disease","volume":"12","author":"Thygesen","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Batista, C.R.A., Gomes, G.F., Candelario-Jalil, E., Fiebich, B.L., and de Oliveira, A.C.P. (2019). Lipopolysaccharide-Induced Neuroinflammation as a Bridge to Understand Neurodegeneration. IJMS, 20.","DOI":"10.3390\/ijms20092293"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Chakraborty, S., Tabrizi, Z., Bhatt, N.N., Franciosa, S.A., and Bracko, O. (2023). A Brief Overview of Neutrophils in Neurological Diseases. Biomolecules, 13.","DOI":"10.3390\/biom13050743"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"228493","DOI":"10.3389\/fimmu.2017.00211","article-title":"NETosis in Alzheimer\u2019s Disease","volume":"8","author":"Pietronigro","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Hensley-McBain, T., Wu, M.C., Manuzak, J.A., Cheu, R.K., Gustin, A., Driscoll, C.B., Zevin, A.S., Miller, C.J., Coronado, E., and Smith, E. (2019). Increased mucosal neutrophil survival is associated with altered microbiota in HIV infection. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007672"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"L655","DOI":"10.1152\/ajplung.00327.2004","article-title":"LPS activation of Toll-like receptor 4 signals CD11b\/CD18 expression in neutrophils","volume":"288","author":"Zhou","year":"2005","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/S0197-4580(01)00346-3","article-title":"Neutrophils CD11b and fibroblasts PGE(2) are elevated in Alzheimer\u2019s disease","volume":"23","author":"Scali","year":"2002","journal-title":"Neurobiol. Aging"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"661838","DOI":"10.3389\/fncel.2021.661838","article-title":"Blood-Brain Barrier Dysfunction Amplifies the Development of Neuroinflammation: Understanding of Cellular Events in Brain Microvascular Endothelial Cells for Prevention and Treatment of BBB Dysfunction","volume":"15","author":"Takata","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S1074-7613(00)80278-2","article-title":"A Novel Role for the 2 Integrin CD11b\/CD18 in Neutrophil Apoptosis: A Homeostatic Mechanism in Inflammation","volume":"5","author":"Coxon","year":"1996","journal-title":"Immunity"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3476","DOI":"10.4049\/jimmunol.166.5.3476","article-title":"Promotion of Neutrophil Apoptosis by TNF-\u03b1","volume":"166","author":"Salamone","year":"2001","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s12264-016-0055-4","article-title":"Inflammatory Cytokines and Alzheimer\u2019s Disease: A Review from the Perspective of Genetic Polymorphisms","volume":"32","author":"Su","year":"2016","journal-title":"Neurosci. Bull."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/0304-3940(91)90490-K","article-title":"Elevated circulating tumor necrosis factor levels in Alzheimer\u2019s disease","volume":"129","author":"Fillit","year":"1991","journal-title":"Neurosci. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1002\/glia.20467","article-title":"Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration","volume":"55","author":"Qin","year":"2007","journal-title":"Glia"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1186\/1742-2094-9-101","article-title":"A single intraperitoneal injection of endotoxin in rats induces long-lasting modifications in behavior and brain protein levels of TNF-\u03b1 and IL-18","volume":"9","author":"Cutuli","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/imr.13153","article-title":"Neutrophils in aging and aging-related pathologies","volume":"314","author":"Strecker","year":"2023","journal-title":"Immunol. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/mi.2015.66","article-title":"Induction of human IL-10-producing neutrophils by LPS-stimulated Treg cells and IL-10","volume":"9","author":"Lewkowicz","year":"2016","journal-title":"Mucosal Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1258\/002367706778476370","article-title":"Effect of restraint and injection methods on heart rate and body temperature in mice","volume":"40","author":"Meijer","year":"2006","journal-title":"Lab. Anim."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1014296","DOI":"10.3389\/fimmu.2022.1014296","article-title":"Acute stress induces an inflammation dominated by innate immunity represented by neutrophils in mice","volume":"13","author":"Tang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1111\/bph.15203","article-title":"Repeated social defeat stress induces neutrophil mobilization in mice: Maintenance after cessation of stress and strain-dependent difference in response","volume":"178","author":"Ishikawa","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41586-022-04890-z","article-title":"Brain motor and fear circuits regulate leukocytes during acute stress","volume":"607","author":"Poller","year":"2022","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41586-018-0023-4","article-title":"Innate immune memory in the brain shapes neurological disease hallmarks","volume":"556","author":"Wendeln","year":"2018","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Wu, J., Cai, Y., Wu, X., Ying, Y., Tai, Y., and He, M. (2021). Transcardiac Perfusion of the Mouse for Brain Tissue Dissection and Fixation. Bio Protoc., 11.","DOI":"10.21769\/BioProtoc.3876"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1038\/s41385-018-0032-5","article-title":"Intestinal damage precedes mucosal immune dysfunction in SIV infection","volume":"11","author":"Berard","year":"2018","journal-title":"Mucosal Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"100537","DOI":"10.1016\/j.xpro.2021.100537","article-title":"Isolation of mouse brain-infiltrating leukocytes for single cell profiling of epitopes and transcriptomes","volume":"2","author":"Guldner","year":"2021","journal-title":"STAR Protoc."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1017976","DOI":"10.3389\/fncel.2022.1017976","article-title":"Proposed practical protocol for flow cytometry analysis of microglia from the healthy adult mouse brain: Systematic review and isolation methods\u2019 evaluation","volume":"16","year":"2022","journal-title":"Front. Cell. Neurosci."},{"key":"ref_57","unstructured":"National Research Council (US) Committee for the Update of the Guide for theCare and Use of Laboratory Animals (2024, April 09). Guide for the Care and Use of Laboratory Animals, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK54050\/."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Percie du Sert, N., Hurst, V., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., and Dirnagl, U. (2020). The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000410"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5357\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:42:11Z","timestamp":1760107331000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5357"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,14]]},"references-count":58,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["ijms25105357"],"URL":"https:\/\/doi.org\/10.3390\/ijms25105357","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,14]]}}}