{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:31:04Z","timestamp":1787725864710,"version":"build-2784847793"},"reference-count":105,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Pneumocystis<\/jats:italic>\n                      pneumonia (PCP) remains a major cause of morbidity and mortality in immunocompromised individuals. Although baicalin (Ba), a natural bioactive flavonoid, has demonstrated protective and therapeutic effects against PCP, its molecular mechanisms remain undefined. We employed dual RNA sequencing (dual RNA-seq) to characterize host and pathogen transcriptional responses to Ba treatment in an immunosuppressed rat model of PCP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Comparative transcriptomic analyses identified differentially expressed genes in both the host and\n                      <jats:italic>Pneumocystis<\/jats:italic>\n                      , followed by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analyses. Candidate targets were further investigated using network pharmacology, protein\u2013protein interaction analysis, molecular docking, and molecular dynamics simulations. Key findings were validated by immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative PCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ba markedly remodeled host and pathogen transcriptomes. Host transcriptomic analyses showed that Ba attenuated inflammatory and oxidative stress responses by modulating immune-related pathways, including Toll-like receptor, NF-\u03baB, cytokine-cytokine receptor interaction, chemokine signaling, Th17 cell differentiation, and antigen processing and presentation. Experimental validation demonstrated that Ba reduced pulmonary expression of indoleamine 2,3-dioxygenase 1 (IDO1), Toll-like receptor 2 (TLR2), and TLR4 while increasing nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant enzyme heme oxygenase-1 (HO-1). Pathogen transcriptomic analysis identified\n                      <jats:italic>Pneumocystis Rtt109<\/jats:italic>\n                      (\n                      <jats:italic>PcRtt109<\/jats:italic>\n                      ), a fungal histone acetyltransferase, as a potential pathogen-specific target that was significantly downregulated after Ba treatment. Molecular docking and molecular dynamics simulations supported stable interactions between Ba and IDO1, Nrf2, TLR2, TLR4, and\n                      <jats:italic>PcRtt109<\/jats:italic>\n                      , with the strongest predicted binding observed for\n                      <jats:italic>PcRtt109<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Dual RNA-seq revealed that Ba exerts anti-PCP activity through coordinated modulation of host and pathogen molecular networks. Its therapeutic effects are associated with suppression of inflammatory signaling, enhancement of antioxidant defenses, and inhibition of a fungal virulence-associated target. These findings provide mechanistic insights into host-pathogen interactions during PCP and support Ba as a potential therapeutic candidate for PCP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1923465","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:02:26Z","timestamp":1787724146000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated dual transcriptome sequencing and experimental validation reveal potential mechanisms of baicalin against pneumocystis pneumonia in immunosuppressed rats"],"prefix":"10.3389","volume":"17","author":[{"given":"Ting","family":"Xue","sequence":"first","affiliation":[{"name":"State Key Laboratory for Pneumoconiosis of National Health Commission, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]},{"name":"Key Laboratory of Prevention and Treatment of Chronic Respiratory Diseases and Pneumoconiosis in Shanxi Province, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]},{"name":"Department of Respiratory and Critical Care Medicine, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]},{"name":"Department of Clinical Laboratory, The First People\u2019s Hospital of Lvliang","place":["Lvliang, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Fan","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Pneumoconiosis of National Health Commission, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]},{"name":"Key Laboratory of Prevention and Treatment of Chronic Respiratory Diseases and Pneumoconiosis in Shanxi Province, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]},{"name":"Department of Respiratory and Critical Care Medicine, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqin","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First People\u2019s Hospital of Lvliang","place":["Lvliang, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaofeng","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Pneumoconiosis of National Health Commission, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]},{"name":"Key Laboratory of Prevention and Treatment of Chronic Respiratory Diseases and Pneumoconiosis in Shanxi Province, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]},{"name":"Department of Respiratory and Critical Care Medicine, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Dai","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Pneumoconiosis of National Health Commission, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]},{"name":"Key Laboratory of Prevention and Treatment of Chronic Respiratory Diseases and Pneumoconiosis in Shanxi Province, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]},{"name":"Department of Respiratory and Critical Care Medicine, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Xu","sequence":"additional","affiliation":[{"name":"Clinical Practice Teaching Center, Shenyang Medical College","place":["Shenyang, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lufeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouan","family":"Ren","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Pneumoconiosis of National Health Commission, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]},{"name":"Key Laboratory of Prevention and Treatment of Chronic Respiratory Diseases and Pneumoconiosis in Shanxi Province, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]},{"name":"Department of Respiratory and Critical Care Medicine, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1080\/17476348.2022.2152332","article-title":"A comprehensive clinical guide for Pneumocystis jirovecii pneumonia: a missing therapeutic target in HIV-uninfected patients","volume":"16","author":"Alsayed","year":"2022","journal-title":"Expert Rev. Respir. Med."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1177\/1060028016650107","article-title":"Pneumocystis jirovecii pneumonia in the non-HIV-infected population","volume":"50","author":"Avino","year":"2016","journal-title":"Ann. Pharmacother."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"3605","DOI":"10.1098\/rstb.2011.0069","article-title":"Structural insights into anaphase-promoting complex function and mechanism","volume":"366","author":"Barford","year":"","journal-title":"Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1017\/S0033583510000259","article-title":"Structure, function and mechanism of the anaphase promoting complex (APC\/C)","volume":"44","author":"Barford","year":"","journal-title":"Q. Rev. Biophys."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"101544","DOI":"10.1016\/j.redox.2020.101544","article-title":"Oxidative stress-based therapeutics in COPD","volume":"33","author":"Barnes","year":"2020","journal-title":"Redox Biol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/s0022-2143(96)90044-x","article-title":"Role of CD8+ lymphocytes in host defense against Pneumocystis carinii in mice","volume":"128","author":"Beck","year":"1996","journal-title":"J. Lab. Clin. Med."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1165\/ajrcmb\/5.2.186","article-title":"Inflammatory responses to Pneumocystis carinii in mice selectively depleted of helper T lymphocytes","volume":"5","author":"Beck","year":"1991","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"9012","DOI":"10.1093\/nar\/gkac687","article-title":"Prp43\/DHX15 exemplify RNA helicase multifunctionality in the gene expression network","volume":"50","author":"Bohnsack","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/s12890-020-1142-x","article-title":"The dietary antioxidant quercetin reduces hallmarks of bleomycin-induced lung fibrogenesis in mice","volume":"20","author":"Boots","year":"2020","journal-title":"BMC Pulm. Med."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.intimp.2015.07.011","article-title":"Forsythiaside inhibits cigarette smoke-induced lung inflammation by activation of Nrf2 and inhibition of NF-kappaB","volume":"28","author":"Cheng","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.taap.2018.12.004","article-title":"Sulforaphane enriched transcriptome of lung mitochondrial energy metabolism and provided pulmonary injury protection via Nrf2 in mice","volume":"364","author":"Cho","year":"2019","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1761361","DOI":"10.3389\/fimmu.2026.1761361","article-title":"Taking its TOLL: the role of toll-like receptor 4 in human health and disease, and its potential as a therapeutic target","volume":"17","author":"Crammond","year":"2026","journal-title":"Front. Immunol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"2046","DOI":"10.1128\/MCB.01609-13","article-title":"The Mi-2 homolog Mit1 actively positions nucleosomes within heterochromatin to suppress transcription","volume":"34","author":"Creamer","year":"2014","journal-title":"Mol. Cell. Biol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1016\/j.tips.2020.07.003","article-title":"Can activation of Nrf2 be a strategy against COVID-19?","volume":"41","author":"Cuadrado","year":"2020","journal-title":"Trends Pharmacol. Sci."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"3650","DOI":"10.1128\/AAC.02637-14","article-title":"Pneumocystis jirovecii Rtt109, a novel drug target for Pneumocystis pneumonia in immunosuppressed humans","volume":"58","author":"Dahlin","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1042\/BST20200652","article-title":"Unlocking immune-mediated disease mechanisms with transcriptomics","volume":"49","author":"de Jong","year":"2021","journal-title":"Biochem. Soc. Trans."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"856","DOI":"10.3390\/jof7100856","article-title":"Update on dihydropteroate synthase (DHPS) mutations in Pneumocystis jirovecii","volume":"7","author":"de la Horra","year":"2021","journal-title":"J Fungi (Basel)"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"jcs216895","DOI":"10.1242\/jcs.216895","article-title":"Involvement of the septation initiation network in events during cytokinesis in fission yeast","volume":"131","author":"Dey","year":"2018","journal-title":"J. Cell Sci."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1007\/s10529-017-2319-0","article-title":"Transcriptomics as a tool to discover new antibacterial targets","volume":"39","author":"Dominguez","year":"2017","journal-title":"Biotechnol. Lett."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1126\/science.1135862","article-title":"Yeast Rtt109 promotes genome stability by acetylating histone H3 on lysine 56","volume":"315","author":"Driscoll","year":"2007","journal-title":"Science"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/s00281-014-0459-z","article-title":"Pathological and protective immunity to Pneumocystis infection","volume":"37","author":"Eddens","year":"2015","journal-title":"Semin. Immunopathol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1534\/genetics.112.140467","article-title":"The ubiquitin-proteasome system of Saccharomyces cerevisiae","volume":"192","author":"Finley","year":"2012","journal-title":"Genetics"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/s41401-020-0411-9","article-title":"Baicalin prevents LPS-induced activation of TLR4\/NF-kappaB p65 pathway and inflammation in mice via inhibiting the expression of CD14","volume":"42","author":"Fu","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"118385","DOI":"10.1016\/j.jep.2024.118385","article-title":"Beneficial effects of oxymatrine from Sophora flavescens on alleviating ulcerative colitis by improving inflammation and ferroptosis","volume":"332","author":"Gao","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"4246255","DOI":"10.1155\/2021\/4246255","article-title":"Emerging pathological engagement of ferroptosis in gut diseases","volume":"2021","author":"Gao","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/nrg.2016.49","article-title":"Coming of age: ten years of next-generation sequencing technologies","volume":"17","author":"Goodwin","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1111\/bph.12054","article-title":"Andrographolide protects against cigarette smoke-induced oxidative lung injury via augmentation of Nrf2 activity","volume":"168","author":"Guan","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"2598","DOI":"10.1080\/15384101.2019.1652471","article-title":"IDO1 depletion induces an anti-inflammatory response in macrophages in mice with chronic viral myocarditis","volume":"18","author":"Guo","year":"2019","journal-title":"Cell Cycle"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/S0966-842X(97)01204-3","article-title":"Pneumocystis carinii and the immune response in disease","volume":"6","author":"Hanano","year":"1998","journal-title":"Trends Microbiol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"2833","DOI":"10.3390\/ijerph19052833","article-title":"Trimethoprim-sulfamethoxazole (bactrim) dose optimization in Pneumocystis jirovecii pneumonia (PCP) management: a systematic review","volume":"19","author":"Haseeb","year":"2022","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1016\/S0140-6736(99)03320-6","article-title":"Effects of mutations in Pneumocystis carinii dihydropteroate synthase gene on outcome of AIDS-associated P. Carinii pneumonia","volume":"354","author":"Helweg-Larsen","year":"1999","journal-title":"Lancet"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1186\/s13045-020-01005-x","article-title":"RNA sequencing: new technologies and applications in cancer research","volume":"13","author":"Hong","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1080\/14787210.2017.1364991","article-title":"Treatment of Pneumocystis jirovecii pneumonia in HIV-infected patients: a review","volume":"15","author":"Huang","year":"2017","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"107566","DOI":"10.1016\/j.intimp.2021.107566","article-title":"Taxifolin ameliorates benzo[a]pyrene-induced lung injury possibly via stimulating the Nrf2 signalling pathway","volume":"96","author":"Islam","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"150423","DOI":"10.1016\/j.bbrc.2024.150423","article-title":"The ubiquitin-proteasome system degrades fatty acid synthase under nitrogen starvation when autophagy is dysfunctional in Saccharomyces cerevisiae","volume":"733","author":"Jang","year":"2024","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"104890","DOI":"10.1016\/j.phrs.2020.104890","article-title":"Immunological regulatory effect of flavonoid baicalin on innate immune toll-like receptors","volume":"158","author":"Jiang","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.3892\/mmr.2017.6700","article-title":"Sulforaphane increases Nrf2 expression and protects alveolar epithelial cells against injury caused by cigarette smoke extract","volume":"16","author":"Jiao","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"11624","DOI":"10.1038\/ncomms11624","article-title":"Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription","volume":"7","author":"Kobayashi","year":"2016","journal-title":"Nat. Commun."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"e01210-20","DOI":"10.1128\/AAC.01210-20","article-title":"Targeting CARD9 with small-molecule therapeutics inhibits innate immune signaling and inflammatory response to Pneumocystis carinii beta-glucans","volume":"64","author":"Kottom","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1165\/rcmb.2009-0443OC","article-title":"Pneumocystis carinii expresses an active Rtt109 histone acetyltransferase","volume":"44","author":"Kottom","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s40268-022-00389-0","article-title":"Preclinical and toxicology studies of BRD5529, a selective inhibitor of CARD9","volume":"22","author":"Kottom","year":"2022","journal-title":"Drugs R D"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"2882","DOI":"10.1242\/jcs.03025","article-title":"The Schizosaccharomyces pombe septation initiation network (SIN) is required for spore formation in meiosis","volume":"119","author":"Krapp","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1042\/BST0360411","article-title":"An overview of the fission yeast septation initiation network (SIN)","volume":"36","author":"Krapp","year":"2008","journal-title":"Biochem. Soc. Trans."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1002\/jcc.23899","article-title":"New ways to boost molecular dynamics simulations","volume":"36","author":"Krieger","year":"2015","journal-title":"J. Comput. Chem."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"673","DOI":"10.3390\/md17120673","article-title":"Astaxanthin suppresses cigarette smoke-induced emphysema through Nrf2 activation in mice","volume":"17","author":"Kubo","year":"2019","journal-title":"Mar. Drugs"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1128\/EC.00345-07","article-title":"Pneumocystis encodes a functional S-adenosylmethionine synthetase gene","volume":"7","author":"Kutty","year":"2008","journal-title":"Eukaryot. Cell"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1046\/j.1365-2958.2001.02620.x","article-title":"Characterization of the expression site of the major surface glycoprotein of human-derived Pneumocystis carinii","volume":"42","author":"Kutty","year":"2001","journal-title":"Mol. Microbiol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1249098","DOI":"10.3389\/fimmu.2023.1249098","article-title":"Role of toll-like receptors and nod-like receptors in acute lung infection","volume":"14","author":"Le","year":"2023","journal-title":"Front. Immunol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1002\/iub.2811","article-title":"Evolution and variation in amide aminoacyl-tRNA synthesis","volume":"76","author":"Lewis","year":"2024","journal-title":"IUBMB Life"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.intimp.2017.03.024","article-title":"IDO1: an important immunotherapy target in cancer treatment","volume":"47","author":"Li","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1007\/s00408-020-00321-w","article-title":"Resveratrol attenuates intermittent hypoxia-induced lung injury by activating the Nrf2\/ARE pathway","volume":"198","author":"Lian","year":"2020","journal-title":"Lung"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"7090534","DOI":"10.1155\/2019\/7090534","article-title":"Role of Nrf2 and its activators in respiratory diseases","volume":"2019","author":"Liu","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"6603","DOI":"10.1002\/jsfa.12027","article-title":"Curcumin alleviated lipopolysaccharide-induced lung injury via regulating the Nrf2-ARE and NF-kappaB signaling pathways in ducks","volume":"102","author":"Liu","year":"2022","journal-title":"J. Sci. Food Agric."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"101766","DOI":"10.1016\/j.redox.2020.101766","article-title":"The NRF2-LOC344887 signaling axis suppresses pulmonary fibrosis","volume":"38","author":"Liu","year":"2021","journal-title":"Redox Biol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"e681","DOI":"10.1097\/MD.0000000000000681","article-title":"Epidemiology and long-term survival in HIV-infected patients with Pneumocystis jirovecii pneumonia in the HAART era: experience in a university hospital and review of the literature","volume":"94","author":"Lopez-Sanchez","year":"2015","journal-title":"Medicine"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"e02878-19","DOI":"10.1128\/mBio.02878-19","article-title":"Diversity and complexity of the large surface protein family in the compacted genomes of multiple Pneumocystis species","volume":"11","author":"Ma","year":"2020","journal-title":"mBio"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"10740","DOI":"10.1038\/ncomms10740","article-title":"Genome analysis of three Pneumocystis species reveals adaptation mechanisms to life exclusively in mammalian hosts","volume":"7","author":"Ma","year":"2016","journal-title":"Nat. Commun."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"e00009-18","DOI":"10.1128\/CMR.00009-18","article-title":"A molecular window into the biology and epidemiology of Pneumocystis spp","volume":"31","author":"Ma","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"17743","DOI":"10.1074\/jbc.M200762200","article-title":"Prp43 is an essential RNA-dependent ATPase required for release of lariat-intron from the spliceosome","volume":"277","author":"Martin","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"e0010122","DOI":"10.1128\/cmr.00101-22","article-title":"Pneumocystis jirovecii pneumonia in people living with HIV: a review","volume":"37","author":"McDonald","year":"2024","journal-title":"Clin. Microbiol. Rev."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.femsle.2004.06.039","article-title":"S-adenosylmethionine and Pneumocystis","volume":"237","author":"Merali","year":"2004","journal-title":"FEMS Microbiol. Lett."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41392-025-02178-y","article-title":"Deep insight into cytokine storm: from pathogenesis to treatment","volume":"10","author":"Nie","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1186\/gb-2010-11-12-220","article-title":"From RNA-seq reads to differential expression results","volume":"11","author":"Oshlack","year":"2010","journal-title":"Genome Biol."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"2175","DOI":"10.1091\/mbc.E11-01-0031","article-title":"Anaphase promoting complex-dependent degradation of transcriptional repressors Nrm1 and Yhp1 in Saccharomyces cerevisiae","volume":"22","author":"Ostapenko","year":"2011","journal-title":"Mol. Biol. 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