{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T19:11:25Z","timestamp":1783537885207,"version":"3.55.0"},"posted":{"date-parts":[[2023,10,17]]},"group-title":"Immunology","reference-count":121,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,10,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The airway epithelium plays a central role in the pathogenesis of chronic respiratory diseases such as asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), but the mechanisms by which airway epithelial cells (EpCs) maintain inflammation are poorly understood.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We hypothesized that transcriptomic assessment of sorted airway EpCs across the spectrum of differentiation would allow us to define mechanisms by which EpCs perpetuate airway inflammation.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Ethmoid sinus EpCs from adult patients with CRS were sorted into 3 subsets, bulk RNA sequenced, and analyzed for differentially expressed genes and pathways. Single cell RNA-seq (scRNA-seq) datasets from eosinophilic and non-eosinophilic CRSwNP and bulk RNA-seq of EpCs from mild\/moderate and severe asthma were assessed. Immunofluorescent staining and\n                    <jats:italic>ex vivo<\/jats:italic>\n                    functional analysis of sinus EpCs were used to validate our findings.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Analysis within and across purified EpC subsets revealed an enrichment in glycolytic programming in CRSwNP vs CRSsNP. Correlation analysis identified mammalian target of rapamycin complex 1 (mTORC1) as a potential regulator of the glycolytic program and identified EpC expression of cytokines and wound healing genes as potential sequelae. mTORC1 activity was upregulated in CRSwNP, and\n                    <jats:italic>ex vivo<\/jats:italic>\n                    inhibition demonstrated that mTOR is critical for EpC generation of CXCL8, IL-33, and CXCL2. Across patient samples, the degree of glycolytic activity was associated with T2 inflammation in CRSwNP, and with both T2 and non-T2 inflammation in severe asthma.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Together, these findings highlight a metabolic axis required to support epithelial generation of cytokines critical to both chronic T2 and non-T2 inflammation in CRSwNP and asthma.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>KEY MESSAGES<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Epithelial mTORC1 activity is upregulated in CRSwNP.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>mTOR regulates EpC cytokine generation.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Epithelial metabolic reprograming correlates with T2 inflammation in CRSwNP, and with both T2 and non-T2 inflammation in asthma.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>CAPSULE SUMMARY<\/jats:title>\n                  <jats:p>mTORC1 mediates EpC cytokine generation in CRSwNP.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.10.13.562288","type":"posted-content","created":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T12:35:23Z","timestamp":1697546123000},"source":"Crossref","is-referenced-by-count":6,"title":["Increased epithelial mTORC1 activity in chronic rhinosinusitis with nasal polyps"],"prefix":"10.64898","author":[{"given":"George X.","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils R.","family":"Hallen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minkyu","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael V.","family":"Mandanas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Djeddi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Fernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Hacker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regan W.","family":"Bergmark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Bhattacharyya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice Z.","family":"Maxfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel E.","family":"Roditi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M.","family":"Buchheit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya M.","family":"Laidlaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Gern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teal S.","family":"Hallstrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuradha","family":"Ray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally E.","family":"Wenzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua A.","family":"Boyce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gutierrez-Arcelus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora A.","family":"Barrett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2023102008000677000_2023.10.13.562288v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/S41591-019-0468-5"},{"issue":"13","key":"2023102008000677000_2023.10.13.562288v1.2","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1056\/NEJMoa0906312","article-title":"Consortium-Based Genomewide Association Study of Asthma","volume":"363","year":"2010","journal-title":"N Engl J Med [Internet"},{"issue":"9","key":"2023102008000677000_2023.10.13.562288v1.3","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/ng.888","article-title":"Meta-analysis of Genome-wide Association Studies of Asthma In Ethnically Diverse North American Populations","volume":"43","year":"2011","journal-title":"Nat Genet [Internet"},{"key":"2023102008000677000_2023.10.13.562288v1.4","doi-asserted-by":"crossref","unstructured":"Kristjansson RP , Benonisdottir S , Davidsson OB , Oddsson A , Tragante V , Sigurdsson JK , et al. A loss-of-function variant in ALOX15 protects against nasal polyps and chronic rhinosinusitis. Nature Genetics 2019 51:2 [Internet]. 2019 Jan 14 [cited 2022 Nov 3];51(2):267\u201376. Available from: https:\/\/www-nature-com.ezp-prod1.hul.harvard.edu\/articles\/s41588-018-0314-6","DOI":"10.1038\/s41588-018-0314-6"},{"issue":"10209","key":"2023102008000677000_2023.10.13.562288v1.5","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1016\/S0140-6736(19)31881-1","article-title":"Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials","volume":"394","year":"2019","journal-title":"Lancet [Internet"},{"issue":"26","key":"2023102008000677000_2023.10.13.562288v1.6","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1056\/NEJMoa1804092","article-title":"Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma","volume":"378","year":"2018","journal-title":"New England Journal of Medicine [Internet"},{"issue":"10","key":"2023102008000677000_2023.10.13.562288v1.7","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/S2213-2600(21)00097-7","article-title":"Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"9","year":"2021","journal-title":"Lancet Respir Med [Internet"},{"issue":"13","key":"2023102008000677000_2023.10.13.562288v1.8","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1056\/NEJMoa1403290","article-title":"Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma","volume":"371","year":"2014","journal-title":"New England Journal of Medicine [Internet"},{"issue":"10056","key":"2023102008000677000_2023.10.13.562288v1.9","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1016\/S0140-6736(16)31324-1","article-title":"Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting \u03b22-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial","volume":"388","year":"2016","journal-title":"The Lancet [Internet"},{"issue":"5","key":"2023102008000677000_2023.10.13.562288v1.10","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1164\/rccm.200903-0392OC","article-title":"T-helper Type 2\u2013driven Inflammation Defines Major Subphenotypes of Asthma","volume":"180","year":"2009","journal-title":"Am J Respir Crit Care Med [Internet"},{"key":"2023102008000677000_2023.10.13.562288v1.11","first-page":"7720","article-title":"Allergic inflammatory memory in human respiratory epithelial progenitor cells","volume":"560","year":"2018","journal-title":"Nature"},{"issue":"2","key":"2023102008000677000_2023.10.13.562288v1.12","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.jaci.2020.04.031","article-title":"Activation of the 15-lipoxygenase pathway in aspirin-exacerbated respiratory disease","volume":"147","year":"2021","journal-title":"J Allergy Clin Immunol [Internet"},{"key":"2023102008000677000_2023.10.13.562288v1.13","doi-asserted-by":"publisher","DOI":"10.1172\/jci"},{"issue":"10","key":"2023102008000677000_2023.10.13.562288v1.14","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1038\/s41590-022-01312-0","article-title":"Single-cell profiling identifies mechanisms of inflammatory heterogeneity in chronic rhinosinusitis","volume":"23","year":"2022","journal-title":"Nat Immunol [Internet"},{"key":"2023102008000677000_2023.10.13.562288v1.15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI155884"},{"key":"2023102008000677000_2023.10.13.562288v1.16","doi-asserted-by":"crossref","unstructured":"Wenzel SE , Tyurina YY , Zhao J , St. Croix CM , Dar HH , Mao G , et al. PEBP1 Wardens Ferroptosis by Enabling Lipoxygenase Generation of Lipid Death Signals. Cell. 2017;171(3).","DOI":"10.1016\/j.cell.2017.09.044"},{"key":"2023102008000677000_2023.10.13.562288v1.17","doi-asserted-by":"crossref","unstructured":"Zhao J , Minami Y , Etling E , Coleman JM , Lauder SN , Tyrrell V , et al. Preferential generation of 15-HETE-PE induced by IL-13 regulates goblet cell differentiation in human airway epithelial cells. Am J Respir Cell Mol Biol. 2017;57(6).","DOI":"10.1165\/rcmb.2017-0031OC"},{"issue":"5","key":"2023102008000677000_2023.10.13.562288v1.18","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1016\/j.jaci.2019.06.037","article-title":"15-Lipoxygenase 1 in nasal polyps promotes CCL26\/eotaxin 3 expression through extracellular signal-regulated kinase activation","volume":"144","year":"2019","journal-title":"J Allergy Clin Immunol [Internet"},{"issue":"6","key":"2023102008000677000_2023.10.13.562288v1.19","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1016\/j.jaci.2023.01.030","article-title":"Type 2 inflammation drives an airway basal stem cell program through insulin receptor substrate signaling","volume":"151","year":"2023","journal-title":"J Allergy Clin Immunol [Internet"},{"key":"2023102008000677000_2023.10.13.562288v1.20","doi-asserted-by":"crossref","unstructured":"Cao PP , Li H Bin , Wang BF , Wang S Bin , You XJ , Cui YH , et al. Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese. Journal of Allergy and Clinical Immunology. 2009;124(3).","DOI":"10.1016\/j.jaci.2009.05.017"},{"key":"2023102008000677000_2023.10.13.562288v1.21","doi-asserted-by":"crossref","unstructured":"Tu Y , Liu J , Li T , Zhou X , Tan K Sen , Ong HH , et al. Mucus composition abnormalities in sinonasal mucosa of chronic rhinosinusitis with and without nasal polyps. Inflammation. 2021;44(5).","DOI":"10.1007\/s10753-021-01471-6"},{"issue":"4","key":"2023102008000677000_2023.10.13.562288v1.22","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1165\/rcmb.2021-0364OC","article-title":"The Type 2 Asthma Mediator IL-13 Inhibits Severe Acute Respiratory Syndrome Coronavirus 2 Infection of Bronchial Epithelium","volume":"66","year":"2022","journal-title":"Am J Respir Cell Mol Biol [Internet"},{"key":"2023102008000677000_2023.10.13.562288v1.23","unstructured":"Andrews S. FastQC: A Quality Control Tool for High Throughput Sequence Data. http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/. 2010."},{"key":"2023102008000677000_2023.10.13.562288v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3519"},{"key":"2023102008000677000_2023.10.13.562288v1.25","doi-asserted-by":"crossref","unstructured":"Soneson C , Love MI , Robinson MD. Differential analyses for RNA-seq: Transcript-level estimates improve gene-level inferences. F1000Res [Internet]. 2016 [cited 2023 Jul 19];4. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/26925227\/","DOI":"10.12688\/f1000research.7563.2"},{"key":"2023102008000677000_2023.10.13.562288v1.26","doi-asserted-by":"crossref","unstructured":"Anders S , Huber W . Differential expression analysis for sequence count data. Genome Biol. 2010;11(10).","DOI":"10.1186\/gb-2010-11-10-r106"},{"issue":"12","key":"2023102008000677000_2023.10.13.562288v1.27","first-page":"1","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","year":"2014","journal-title":"Genome Biol [Internet"},{"issue":"1","key":"2023102008000677000_2023.10.13.562288v1.28","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","year":"1995","journal-title":"Journal of the Royal Statistical Society: Series B (Methodological) [Internet"},{"issue":"43","key":"2023102008000677000_2023.10.13.562288v1.29","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","year":"2005","journal-title":"Proc Natl Acad Sci U S A [Internet"},{"key":"2023102008000677000_2023.10.13.562288v1.30","doi-asserted-by":"crossref","unstructured":"Yu G , Wang LG , Han Y , He QY . ClusterProfiler: An R package for comparing biological themes among gene clusters. OMICS. 2012;16(5).","DOI":"10.1089\/omi.2011.0118"},{"key":"2023102008000677000_2023.10.13.562288v1.31","doi-asserted-by":"crossref","unstructured":"Liberzon A , Subramanian A , Pinchback R , Thorvaldsd\u00f3ttir H , Tamayo P , Mesirov JP . Molecular signatures database (MSigDB) 3.0. Bioinformatics. 2011;27(12).","DOI":"10.1093\/bioinformatics\/btr260"},{"issue":"6","key":"2023102008000677000_2023.10.13.562288v1.32","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection","volume":"1","year":"2015","journal-title":"Cell Syst [Internet"},{"issue":"1","key":"2023102008000677000_2023.10.13.562288v1.33","first-page":"1","article-title":"GSVA: Gene set variation analysis for microarray and RNA-Seq data","volume":"14","year":"2013","journal-title":"BMC Bioinformatics [Internet"},{"issue":"7","key":"2023102008000677000_2023.10.13.562288v1.34","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","year":"2015","journal-title":"Nucleic Acids Res [Internet"},{"key":"2023102008000677000_2023.10.13.562288v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELL.2021.04.048"},{"issue":"5","key":"2023102008000677000_2023.10.13.562288v1.36","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","year":"2018","journal-title":"Nat Biotechnol [Internet"},{"key":"2023102008000677000_2023.10.13.562288v1.37","doi-asserted-by":"crossref","unstructured":"Zheng GXY , Terry JM , Belgrader P , Ryvkin P , Bent ZW , Wilson R , et al. Massively parallel digital transcriptional profiling of single cells. Nat Commun. 2017;8.","DOI":"10.1038\/ncomms14049"},{"issue":"12","key":"2023102008000677000_2023.10.13.562288v1.38","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","article-title":"Fast, sensitive and accurate integration of single-cell data with Harmony","volume":"16","year":"2019","journal-title":"Nature Methods"},{"key":"2023102008000677000_2023.10.13.562288v1.39","doi-asserted-by":"publisher","DOI":"10.1172\/jci"},{"issue":"2","key":"2023102008000677000_2023.10.13.562288v1.40","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.jaci.2020.05.051","article-title":"Expression of SARS-CoV-2 receptor ACE2 and coincident host response signature varies by asthma inflammatory phenotype","volume":"146","year":"2020","journal-title":"J Allergy Clin Immunol [Internet"},{"key":"2023102008000677000_2023.10.13.562288v1.41","doi-asserted-by":"crossref","unstructured":"Schneider CA , Rasband WS , Eliceiri KW . NIH Image to ImageJ: 25 years of image analysis. Vol. 9, Nature Methods. 2012.","DOI":"10.1038\/nmeth.2089"},{"key":"2023102008000677000_2023.10.13.562288v1.42","unstructured":"Rstudio Team. RStudio: Integrated development for R. RStudio, Inc., Boston MA. RStudio. 2019."},{"issue":"7718","key":"2023102008000677000_2023.10.13.562288v1.43","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41586-018-0394-6","article-title":"A single cell atlas of the tracheal epithelium reveals the CFTR-rich pulmonary ionocyte","volume":"560","year":"2018","journal-title":"Nature [Internet"},{"key":"2023102008000677000_2023.10.13.562288v1.44","doi-asserted-by":"crossref","unstructured":"Buchheit KM , Sohail A , Hacker J , Maurer R , Gakpo D , Bensko JC , et al. Rapid and sustained effect of dupilumab on clinical and mechanistic outcomes in aspirin-exacerbated respiratory disease. J Allergy Clin Immunol [Internet]. 2022 Aug 1 [cited 2022 Nov 29];150(2):415\u201324. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/35460728\/","DOI":"10.1016\/j.jaci.2022.04.007"},{"issue":"5","key":"2023102008000677000_2023.10.13.562288v1.45","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1038\/mi.2016.120","article-title":"Cadherin 26 is an alpha integrin-binding epithelial receptor regulated during allergic inflammation","volume":"10","year":"2017","journal-title":"Mucosal Immunol [Internet"},{"key":"2023102008000677000_2023.10.13.562288v1.46","doi-asserted-by":"crossref","unstructured":"Rochman M , Travers J , Abonia JP , Caldwell JM , Rothenberg ME . Synaptopodin is upregulated by IL-13 in eosinophilic esophagitis and regulates esophageal epithelial cell motility and barrier integrity. JCI Insight. 2017;2(20).","DOI":"10.1172\/jci.insight.96789"},{"key":"2023102008000677000_2023.10.13.562288v1.47","doi-asserted-by":"crossref","unstructured":"Zeng C , Vanoni S , Wu D , Caldwell JM , Wheeler JC , Arora K , et al. Solute carrier family 9, subfamily A, member 3 (SLC9A3)\/sodium-hydrogen exchanger member 3 (NHE3) dysregulation and dilated intercellular spaces in patients with eosinophilic esophagitis. Journal of Allergy and Clinical Immunology. 2018;142(6).","DOI":"10.1016\/j.jaci.2018.03.017"},{"key":"2023102008000677000_2023.10.13.562288v1.48","doi-asserted-by":"crossref","unstructured":"Van Es JH , Sato T , Van De Wetering M , Lyubimova A , Yee Nee AN , Gregorieff A , et al. Dll1 + secretory progenitor cells revert to stem cells upon crypt damage. Nat Cell Biol. 2012;14(10).","DOI":"10.1038\/ncb2581"},{"key":"2023102008000677000_2023.10.13.562288v1.49","doi-asserted-by":"crossref","unstructured":"Sidney LE , Branch MJ , Dunphy SE , Dua HS , Hopkinson A . Concise review: Evidence for CD34 as a common marker for diverse progenitors. Vol. 32, Stem Cells. 2014.","DOI":"10.1002\/stem.1661"},{"key":"2023102008000677000_2023.10.13.562288v1.50","doi-asserted-by":"crossref","unstructured":"Radu P , Zurzu M , Paic V , Bratucu M , Garofil D , Tigora A , et al. CD34\u2014Structure, Functions and Relationship with Cancer Stem Cells. Medicina (B Aires) [Internet]. 2023 May 1 [cited 2023 Jul 19];59(5). Available from: \/pmc\/articles\/PMC10220851\/","DOI":"10.3390\/medicina59050938"},{"key":"2023102008000677000_2023.10.13.562288v1.51","doi-asserted-by":"crossref","unstructured":"Cui Z , Mu C , Wu Z , Pan S , Cheng Z , Zhang Z qing , et al. The sodium\/myo-inositol co-transporter SLC5A3 promotes non-small cell lung cancer cell growth. Cell Death Dis. 2022;13(6).","DOI":"10.1038\/s41419-022-05017-y"},{"key":"2023102008000677000_2023.10.13.562288v1.52","doi-asserted-by":"crossref","unstructured":"Zheng H , Long G , Zheng Y , Yang X , Cai W , He S , et al. Glycolysis-Related SLC2A1 Is a Potential Pan-Cancer Biomarker for Prognosis and Immunotherapy. Cancers (Basel). 2022;14(21).","DOI":"10.3390\/cancers14215344"},{"key":"2023102008000677000_2023.10.13.562288v1.53","unstructured":"Chen CL , Ma J , Lu RY , Wang YT , Zhao JF , Kang YF , et al. Perturbated glucose metabolism augments epithelial cell proinflammatory function in chronic rhinosinusitis. Journal of Allergy and Clinical Immunology. 2022 Oct 28;"},{"key":"2023102008000677000_2023.10.13.562288v1.54","doi-asserted-by":"crossref","unstructured":"Chen C , Zhang X . Glycolysis regulator PFKP induces human melanoma cell proliferation and tumor growth. Clinical and Translational Oncology. 2023;25(7).","DOI":"10.1007\/s12094-023-03096-7"},{"key":"2023102008000677000_2023.10.13.562288v1.55","doi-asserted-by":"crossref","unstructured":"Wang F , Li L , Zhang Z . Platelet isoform of phosphofructokinase promotes aerobic glycolysis and the progression of non-small cell lung cancer. Mol Med Rep. 2021;23(1).","DOI":"10.3892\/mmr.2020.11712"},{"key":"2023102008000677000_2023.10.13.562288v1.56","doi-asserted-by":"crossref","unstructured":"Ivan M , Kaelin WG . The EGLN-HIF O2-Sensing System: Multiple Inputs and Feedbacks. Vol. 66, Molecular Cell. 2017.","DOI":"10.1016\/j.molcel.2017.06.002"},{"key":"2023102008000677000_2023.10.13.562288v1.57","doi-asserted-by":"crossref","unstructured":"Luczak SE , Glatt SJ , Wall TJ . Meta-analyses of ALDH2 and ADH1B with alcohol dependence in asians. Psychol Bull. 2006;132(4).","DOI":"10.1037\/0033-2909.132.4.607"},{"key":"2023102008000677000_2023.10.13.562288v1.58","doi-asserted-by":"crossref","unstructured":"Matsumura Y , Stiles KM , Reid J , Frenk EZ , Cronin S , Pagovich OE , et al. Gene Therapy Correction of Aldehyde Dehydrogenase 2 Deficiency. Mol Ther Methods Clin Dev. 2019;15.","DOI":"10.1016\/j.omtm.2019.08.004"},{"key":"2023102008000677000_2023.10.13.562288v1.59","doi-asserted-by":"crossref","unstructured":"Chang JS , Hsiao JR , Chen CH . ALDH2 polymorphism and alcohol-related cancers in Asians: A public health perspective Tse-Hua Tan. Vol. 24, Journal of Biomedical Science. 2017.","DOI":"10.1186\/s12929-017-0327-y"},{"key":"2023102008000677000_2023.10.13.562288v1.60","doi-asserted-by":"crossref","unstructured":"Cardet JC , White AA , Barrett NA , Feldweg AM , Wickner PG , Savage J , et al. Alcohol-induced respiratory symptoms are common in patients with aspirin exacerbated respiratory disease. Journal of Allergy and Clinical Immunology: In Practice. 2014;2(2).","DOI":"10.1016\/j.jaip.2013.12.003"},{"issue":"8","key":"2023102008000677000_2023.10.13.562288v1.61","first-page":"1713","article-title":"Regulation of mTORC1 and its impact on gene expression at a glance","volume":"126","year":"2013","journal-title":"J Cell Sci [Internet"},{"key":"2023102008000677000_2023.10.13.562288v1.62","doi-asserted-by":"crossref","unstructured":"Liu GY , Sabatini DM . mTOR at the nexus of nutrition, growth, ageing and disease. Vol. 21, Nature Reviews Molecular Cell Biology. 2020.","DOI":"10.1038\/s41580-019-0199-y"},{"key":"2023102008000677000_2023.10.13.562288v1.63","doi-asserted-by":"crossref","unstructured":"Baffi TR , Lorden G , Wozniak JM , Feichtner A , Yeung W , Kornev AP , et al. TORC2 controls the activity of PKC and Akt by phosphorylating a conserved TOR interaction motif. Sci Signal. 2021;14(678).","DOI":"10.1126\/scisignal.abe4509"},{"key":"2023102008000677000_2023.10.13.562288v1.64","doi-asserted-by":"crossref","unstructured":"Su\u00e1rez H , Andreu Z , Mazzeo C , Toribio V , P\u00e9rez-Rivera AE , L\u00f3pez-Mart\u00edn S , et al. CD9 inhibition reveals a functional connection of extracellular vesicle secretion with mitophagy in melanoma cells. J Extracell Vesicles. 2021;10(7).","DOI":"10.1002\/jev2.12082"},{"key":"2023102008000677000_2023.10.13.562288v1.65","doi-asserted-by":"crossref","unstructured":"Cho JH , Kim EC , Son Y , Lee DW , Park YS , Choi JH , et al. CD9 induces cellular senescence and aggravates atherosclerotic plaque formation. Cell Death Differ. 2020;27(9).","DOI":"10.1038\/s41418-020-0537-9"},{"key":"2023102008000677000_2023.10.13.562288v1.66","doi-asserted-by":"crossref","unstructured":"Zeng Y , Zhang J , Xu M , Chen F , Zi R , Yue J , et al. Roles of mitochondrial serine hydroxymethyltransferase 2 (SHMT2) in human carcinogenesis. J Cancer. 2021;12(19).","DOI":"10.7150\/jca.60170"},{"key":"2023102008000677000_2023.10.13.562288v1.67","doi-asserted-by":"crossref","unstructured":"Cayrol C , Girard JP . Interleukin-33 (IL-33): A nuclear cytokine from the IL-1 family. Vol. 281, Immunological Reviews. 2018.","DOI":"10.1111\/imr.12619"},{"key":"2023102008000677000_2023.10.13.562288v1.68","doi-asserted-by":"crossref","unstructured":"Russo RC , Garcia CC , Teixeira MM , Amaral FA . The CXCL8\/IL-8 chemokine family and its receptors in inflammatory diseases. Vol. 10, Expert Review of Clinical Immunology. 2014.","DOI":"10.1586\/1744666X.2014.894886"},{"key":"2023102008000677000_2023.10.13.562288v1.69","doi-asserted-by":"crossref","unstructured":"Gschwandtner M , Derler R , Midwood KS . More Than Just Attractive: How CCL2 Influences Myeloid Cell Behavior Beyond Chemotaxis. Vol. 10, Frontiers in Immunology. 2019.","DOI":"10.3389\/fimmu.2019.02759"},{"key":"2023102008000677000_2023.10.13.562288v1.70","doi-asserted-by":"crossref","unstructured":"Jacobsen EA , Jackson DJ , Heffler E , Mathur SK , Bredenoord AJ , Pavord ID , et al. Eosinophil Knockout Humans: Uncovering the Role of Eosinophils through Eosinophil-Directed Biological Therapies. Vol. 39, Annual Review of Immunology. 2021.","DOI":"10.1146\/annurev-immunol-093019-125918"},{"key":"2023102008000677000_2023.10.13.562288v1.71","doi-asserted-by":"crossref","unstructured":"Gougousis S , Domvri K , Porpodis K , Besli I , Karkos P , Vliagoftis H , et al. CD4+ and CD8+ T cells infiltration of the polyp tissue in a series of Greek patients with chronic rhinosinusitis with nasal polyps. Eur J Inflamm. 2021;19.","DOI":"10.1177\/20587392211028733"},{"key":"2023102008000677000_2023.10.13.562288v1.72","doi-asserted-by":"crossref","unstructured":"Pant H , Hughes A , Miljkovic D , Schembri M , Wormald P , Macardle P , et al. Accumulation of effector memory CD8+ T cells in nasal polyps. Am J Rhinol Allergy. 2013;27(5).","DOI":"10.2500\/ajra.2013.27.3958"},{"key":"2023102008000677000_2023.10.13.562288v1.73","doi-asserted-by":"crossref","unstructured":"Ickrath P , Kleinsasser N , Ding X , Ginzkey C , Beyersdorf N , Hagen R , et al. Characterization of T-cell Subpopulations in Patients with Chronic Rhinosinusitis with Nasal Polyposis. Allergy and Rhinology. 2017;8(3).","DOI":"10.2500\/ar.2017.8.0214"},{"key":"2023102008000677000_2023.10.13.562288v1.74","doi-asserted-by":"crossref","unstructured":"Steinke JW , Liu L , Huyett P , Negri J , Payne SC , Borish L . Prominent role of IFN-\u03b3 in patients with aspirin-exacerbated respiratory disease. Journal of Allergy and Clinical Immunology. 2013;132(4).","DOI":"10.1016\/j.jaci.2013.05.008"},{"key":"2023102008000677000_2023.10.13.562288v1.75","doi-asserted-by":"crossref","unstructured":"Ochiai K , Tanabe E , Ishihara C , Kagami M , Sugiyama T , Sueishi M , et al. Role of JAK2 signal transductional pathway in activation and survival of human peripheral eosinophils by interferon-gamma (IFN-\u03b3). Clin Exp Immunol. 1999;118(3).","DOI":"10.1046\/j.1365-2249.1999.01068.x"},{"key":"2023102008000677000_2023.10.13.562288v1.76","doi-asserted-by":"crossref","unstructured":"Chiarella E , Lombardo N , Lobello N , Aloisio A , Aragona T , Pelaia C , et al. Nasal polyposis: Insights in epithelial-mesenchymal transition and differentiation of polyp mesenchymal stem cells. Vol. 21, International Journal of Molecular Sciences. 2020.","DOI":"10.20944\/preprints202008.0087.v1"},{"key":"2023102008000677000_2023.10.13.562288v1.77","doi-asserted-by":"crossref","unstructured":"Xia Y , Wang H , Yin J . The Role of Epithelial-Mesenchymal Transition in Chronic Rhinosinusitis. Vol. 183, International Archives of Allergy and Immunology. 2022.","DOI":"10.1159\/000524950"},{"issue":"2","key":"2023102008000677000_2023.10.13.562288v1.78","first-page":"AB39","article-title":"Switching of Glucose Metabolism from Oxidative Phosphorylation to Aerobic Glycolysis (the Warburg Effect) in T-Cells from Patients with Asthma","volume":"125","year":"2010","journal-title":"Journal of Allergy and Clinical Immunology [Internet"},{"issue":"7","key":"2023102008000677000_2023.10.13.562288v1.79","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1084\/jem.20110278","article-title":"HIF1\u03b1\u2013dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells","volume":"208","year":"2011","journal-title":"Journal of Experimental Medicine [Internet"},{"issue":"6","key":"2023102008000677000_2023.10.13.562288v1.80","doi-asserted-by":"crossref","first-page":"3299","DOI":"10.4049\/jimmunol.1003613","article-title":"Cutting Edge: Distinct Glycolytic and Lipid Oxidative Metabolic Programs Are Essential for Effector and Regulatory CD4+ T Cell Subsets","volume":"186","year":"2011","journal-title":"The Journal of Immunology [Internet"},{"key":"2023102008000677000_2023.10.13.562288v1.81","doi-asserted-by":"crossref","unstructured":"Peng M , Yin N , Chhangawala S , Xu K , Leslie CS , Li MO . Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism. Science (1979). 2016;354(6311).","DOI":"10.1126\/science.aaf6284"},{"issue":"2","key":"2023102008000677000_2023.10.13.562288v1.82","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.jaci.2017.08.043","article-title":"IL-1\/inhibitory \u03baB kinase \u03b5\u2013 induced glycolysis augment epithelial effector function and promote allergic airways disease","volume":"142","year":"2018","journal-title":"Journal of Allergy and Clinical Immunology [Internet"},{"issue":"3","key":"2023102008000677000_2023.10.13.562288v1.83","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1111\/all.15074","article-title":"Endotypes of chronic rhinosinusitis: Relationships to disease phenotypes, pathogenesis, clinical findings, and treatment approaches","volume":"77","year":"2022","journal-title":"Allergy [Internet"},{"key":"2023102008000677000_2023.10.13.562288v1.84","unstructured":"Fokkens WJ , Lund VJ , Hopkins C , Hellings PW , Kern R , Reitsma S , et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology [Internet]. 2020 Feb 20 [cited 2022 Nov 29];58(Suppl S29):1\u2013464. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/32077450\/"},{"key":"2023102008000677000_2023.10.13.562288v1.85","doi-asserted-by":"crossref","unstructured":"Delemarre T , Holtappels G , De Ruyck N , Zhang N , Nauwynck H , Bachert C , et al. A substantial neutrophilic inflammation as regular part of severe type 2 chronic rhinosinusitis with nasal polyps. Journal of Allergy and Clinical Immunology. 2021;147(1).","DOI":"10.1016\/j.jaci.2020.08.036"},{"key":"2023102008000677000_2023.10.13.562288v1.86","doi-asserted-by":"crossref","unstructured":"Montoro DT , Haber AL , Biton M , Vinarsky V , Lin B , Birket SE , et al. A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature. 2018;560(7718).","DOI":"10.1038\/s41586-018-0393-7"},{"key":"2023102008000677000_2023.10.13.562288v1.87","doi-asserted-by":"crossref","unstructured":"Zhou Y , Yang Y , Guo L , Qian J , Ge J , Sinner D , et al. Airway Basal Cells Show Regionally: Distinct Potential to Undergo Metaplastic Differentiation. Elife. 2022;11.","DOI":"10.7554\/eLife.80083"},{"key":"2023102008000677000_2023.10.13.562288v1.88","doi-asserted-by":"crossref","unstructured":"Ruysseveldt E , Martens K , Steelant B. Airway Basal Cells, Protectors of Epithelial Walls in Health and Respiratory Diseases. Vol. 2, Frontiers in Allergy. 2021.","DOI":"10.3389\/falgy.2021.787128"},{"issue":"4","key":"2023102008000677000_2023.10.13.562288v1.89","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1164\/rccm.201512-2452OC","article-title":"A transcriptome-driven analysis of epithelial brushings and bronchial biopsies to define asthma phenotypes in U-BIOPRED","volume":"195","year":"2017","journal-title":"Am J Respir Crit Care Med [Internet"},{"key":"2023102008000677000_2023.10.13.562288v1.90","doi-asserted-by":"crossref","unstructured":"Kuo CHS , Pavlidis S , Loza M , Baribaud F , Rowe A , Pandis I , et al. T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED. Eur Respir J. 2017;49(2).","DOI":"10.1183\/13993003.02135-2016"},{"issue":"2","key":"2023102008000677000_2023.10.13.562288v1.91","doi-asserted-by":"crossref","first-page":"108974","DOI":"10.1016\/j.celrep.2021.108974","article-title":"High-dimensional profiling clusters asthma severity by lymphoid and non-lymphoid status","volume":"35","year":"2021","journal-title":"Cell Rep [Internet"},{"issue":"4","key":"2023102008000677000_2023.10.13.562288v1.92","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.immuni.2023.03.007","article-title":"Metabolism in type 2 immune responses","volume":"56","year":"2023","journal-title":"Immunity"},{"key":"2023102008000677000_2023.10.13.562288v1.93","doi-asserted-by":"crossref","unstructured":"Raval F . The Bidirectional Relationship between Metabolism and Immune Responses. Discoveries. 2013;","DOI":"10.15190\/d.2013.6"},{"key":"2023102008000677000_2023.10.13.562288v1.94","doi-asserted-by":"crossref","unstructured":"Queener AM , Chiarella SE , Cuervo-Pardo L , Coden ME , Abdala-Valencia H , Berdnikovs S . Metabolism of Epithelial Cells in Health and Allergic Disease: Collegium Internationale Allergologicum Update 2021. Vol. 182, International Archives of Allergy and Immunology. 2021.","DOI":"10.1159\/000516809"},{"key":"2023102008000677000_2023.10.13.562288v1.95","doi-asserted-by":"crossref","unstructured":"Chen JYF , Hour TC , Yang SF , Chien CY , Chen HR , Tsai KL , et al. Autophagy is deficient in nasal polyps: Implications for the pathogenesis of the disease. Int Forum Allergy Rhinol. 2015;5(2).","DOI":"10.1002\/alr.21456"},{"key":"2023102008000677000_2023.10.13.562288v1.96","doi-asserted-by":"crossref","unstructured":"Wang C , Zhou ML , Liu YC , Cheng KJ . The Roles of Autophagy, Mitophagy, and the Akt\/mTOR Pathway in the Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps. J Immunol Res. 2022;2022.","DOI":"10.1155\/2022\/2273121"},{"key":"2023102008000677000_2023.10.13.562288v1.97","doi-asserted-by":"crossref","unstructured":"Fredriksson K , Fielhaber JA , Lam JK , Yao X , Meyer KS , Keeran KJ , et al. Paradoxical effects of Rapamycin on experimental house dust mite-induced asthma. PLoS One. 2012;7(5).","DOI":"10.1371\/journal.pone.0033984"},{"key":"2023102008000677000_2023.10.13.562288v1.98","doi-asserted-by":"crossref","unstructured":"Mushaben EM , Kramer EL , Brandt EB , Khurana Hershey GK , Le Cras TD . Rapamycin Attenuates Airway Hyperreactivity, Goblet Cells, and IgE in Experimental Allergic Asthma. The Journal of Immunology. 2011;187(11).","DOI":"10.4049\/jimmunol.1102133"},{"key":"2023102008000677000_2023.10.13.562288v1.99","doi-asserted-by":"crossref","unstructured":"Zhang Y , Jing Y , Qiao J , Luan B , Wang X , Wang L , et al. Activation of the mTOR signaling pathway is required for asthma onset. Sci Rep. 2017;7(1).","DOI":"10.1038\/s41598-017-04826-y"},{"key":"2023102008000677000_2023.10.13.562288v1.100","doi-asserted-by":"crossref","unstructured":"Sarbassov DD , Guertin DA , Ali SM , Sabatini DM . Phosphorylation and regulation of Akt\/PKB by the rictor-mTOR complex. Science (1979). 2005;307(5712).","DOI":"10.1126\/science.1106148"},{"key":"2023102008000677000_2023.10.13.562288v1.101","doi-asserted-by":"crossref","unstructured":"Mushaben EM , Brandt EB , Hershey GKK , Le Cras TD . Differential Effects of Rapamycin and Dexamethasone in Mouse Models of Established Allergic Asthma. PLoS One. 2013;8(1).","DOI":"10.1371\/journal.pone.0054426"},{"key":"2023102008000677000_2023.10.13.562288v1.102","doi-asserted-by":"crossref","unstructured":"Wu J , Zhong W , Zhang H , Yin Y . Mammalian Target of Rapamycin Signaling Enhances Ovalbumin-Induced Neutrophilic Airway Inflammation by Promoting Th17 Cell Polarization in Murine Noneosinophilic Asthma Model. Pediatr Allergy Immunol Pulmonol. 2020;33(1).","DOI":"10.1089\/ped.2019.1088"},{"key":"2023102008000677000_2023.10.13.562288v1.103","doi-asserted-by":"crossref","unstructured":"Ma B , Athari SS , Mehrabi Nasab E , Zhao L . PI3K\/AKT\/mTOR and TLR4\/MyD88\/NF-\u03baB Signaling Inhibitors Attenuate Pathological Mechanisms of Allergic Asthma. Inflammation. 2021;44(5).","DOI":"10.1007\/s10753-021-01466-3"},{"key":"2023102008000677000_2023.10.13.562288v1.104","doi-asserted-by":"crossref","unstructured":"Li W , Wu Y , Zhao Y , Li Z , Chen H , Dong L , et al. MTOR suppresses autophagy-mediated production of IL25 in allergic airway inflammation. Thorax. 2020;75(12).","DOI":"10.1136\/thoraxjnl-2019-213771"},{"key":"2023102008000677000_2023.10.13.562288v1.105","doi-asserted-by":"crossref","unstructured":"Aladegbami B , Barron L , Bao J , Colasanti J , Erwin CR , Warner BW , et al. Epithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine. Sci Rep. 2017;7(1).","DOI":"10.1038\/s41598-017-06070-w"},{"key":"2023102008000677000_2023.10.13.562288v1.106","doi-asserted-by":"crossref","unstructured":"Squarize CH , Castilho RM , Bugge TH , Gutkind JS . Accelerated wound healing by mTOR activation in genetically defined mouse models. PLoS One. 2010;5(5).","DOI":"10.1371\/journal.pone.0010643"},{"key":"2023102008000677000_2023.10.13.562288v1.107","doi-asserted-by":"crossref","unstructured":"Kaur H , Moreau R . Role of mTORC1 in intestinal epithelial repair and tumorigenesis. Cellular and Molecular Life Sciences. 2019.","DOI":"10.1007\/s00018-019-03085-6"},{"key":"2023102008000677000_2023.10.13.562288v1.108","doi-asserted-by":"crossref","unstructured":"Sampson LL , Davis AK , Grogg MW , Zheng Y . MTOR disruption causes intestinal epithelial cell defects and intestinal atrophy postinjury in mice. FASEB Journal. 2016;30(3).","DOI":"10.1096\/fj.15-278606"},{"key":"2023102008000677000_2023.10.13.562288v1.109","doi-asserted-by":"crossref","unstructured":"Barron L , Sun RC , Aladegbami B , Erwin CR , Warner BW , Guo J . Intestinal Epithelial-Specific mTORC1 Activation Enhances Intestinal Adaptation After Small Bowel Resection. CMGH. 2017;3(2).","DOI":"10.1016\/j.jcmgh.2016.10.006"},{"key":"2023102008000677000_2023.10.13.562288v1.110","doi-asserted-by":"publisher","DOI":"10.1164\/rccm201109-1706OC"},{"key":"2023102008000677000_2023.10.13.562288v1.111","doi-asserted-by":"crossref","unstructured":"K\u00f6nnecke M , Burmeister M , Pries R , B\u00f6scke R , Bruchhage KL , Ungefroren H , et al. Epithelial\u2013Mesenchymal Transition in Chronic Rhinosinusitis: Differences Revealed Between Epithelial Cells from Nasal Polyps and Inferior Turbinates. Arch Immunol Ther Exp (Warsz). 2017;65(2).","DOI":"10.1007\/s00005-016-0409-7"},{"key":"2023102008000677000_2023.10.13.562288v1.112","doi-asserted-by":"crossref","unstructured":"Kicic A , Hallstrand TS , Sutanto EN , Stevens PT , Kobor MS , Taplin C , et al. Decreased fibronectin production significantly contributes to dysregulated repair of asthmatic epithelium. Am J Respir Crit Care Med. 2010;181(9).","DOI":"10.1164\/rccm.200907-1071OC"},{"key":"2023102008000677000_2023.10.13.562288v1.113","doi-asserted-by":"crossref","unstructured":"Stevens PT , Kicic A , Sutanto EN , Knight DA , Stick SM . Dysregulated repair in asthmatic paediatric airway epithelial cells: The role of plasminogen activator inhibitor-1. Clinical and Experimental Allergy. 2008;38(12).","DOI":"10.1111\/j.1365-2222.2008.03093.x"},{"key":"2023102008000677000_2023.10.13.562288v1.114","doi-asserted-by":"crossref","unstructured":"Kierans SJ , Taylor CT . Regulation of glycolysis by the hypoxia-inducible factor (HIF): implications for cellular physiology. Vol. 599, Journal of Physiology. 2021.","DOI":"10.1113\/JP280572"},{"key":"2023102008000677000_2023.10.13.562288v1.115","doi-asserted-by":"crossref","unstructured":"Pescador N , Cuevas Y , Naranjo S , Alcaide M , Villar D , Land\u00e1zuri MO , et al. Identification of a functional hypoxia-responsive element that regulates the expression of the egl nine homologue 3 (egln3\/phd3) gene. Biochemical Journal. 2005;390(1).","DOI":"10.1042\/BJ20042121"},{"key":"2023102008000677000_2023.10.13.562288v1.116","doi-asserted-by":"crossref","unstructured":"Konieczny P , Xing Y , Sidhu I , Subudhi I , Mansfield KP , Hsieh B , et al. Interleukin-17 governs hypoxic adaptation of injured epithelium. Science (1979). 2022;377(6602).","DOI":"10.1126\/science.abg9302"},{"key":"2023102008000677000_2023.10.13.562288v1.117","doi-asserted-by":"crossref","unstructured":"Hu Y , Lou J , Mao YY , Lai TW , Liu LY , Zhu C , et al. Activation of MTOR in pulmonary epithelium promotes LPS-induced acute lung injury. Autophagy. 2016;12(12).","DOI":"10.1080\/15548627.2016.1230584"},{"key":"2023102008000677000_2023.10.13.562288v1.118","doi-asserted-by":"crossref","unstructured":"Ramirez-Moral I , Yu X , Butler JM , van Weeghel M , Otto NA , Ferreira BL , et al. mTOR-driven glycolysis governs induction of innate immune responses by bronchial epithelial cells exposed to the bacterial component flagellin. Mucosal Immunol. 2021;14(3).","DOI":"10.1038\/s41385-021-00377-8"},{"key":"2023102008000677000_2023.10.13.562288v1.119","doi-asserted-by":"crossref","unstructured":"Song W , He X , Gong P , Yang Y , Huang S , Zeng Y , et al. Glycolysis-Related Gene Expression Profiling Screen for Prognostic Risk Signature of Pancreatic Ductal Adenocarcinoma. Front Genet. 2021;12.","DOI":"10.3389\/fgene.2021.639246"},{"key":"2023102008000677000_2023.10.13.562288v1.120","doi-asserted-by":"crossref","unstructured":"Wei J , Huang K , Chen Z , Hu M , Bai Y , Lin S , et al. Characterization of glycolysis-associated molecules in the tumor microenvironment revealed by pan-cancer tissues and lung cancer single cell data. Cancers (Basel). 2020;12(7).","DOI":"10.3390\/cancers12071788"},{"key":"2023102008000677000_2023.10.13.562288v1.121","doi-asserted-by":"crossref","unstructured":"Bi G , Bian Y , Liang J , Yin J , Li R , Zhao M , et al. Pan-cancer characterization of metabolism-related biomarkers identifies potential therapeutic targets. J Transl Med. 2021;19(1).","DOI":"10.1186\/s12967-021-02889-0"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.10.13.562288","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:23:21Z","timestamp":1768454601000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.10.13.562288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,17]]},"references-count":121,"URL":"https:\/\/doi.org\/10.1101\/2023.10.13.562288","relation":{},"subject":[],"published":{"date-parts":[[2023,10,17]]},"subtype":"preprint"}}