{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:00:29Z","timestamp":1785128429908,"version":"3.55.0"},"reference-count":138,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"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. Physiol."],"abstract":"<jats:p>Pulmonary hypertension (PH) is a severe disorder characterized by progressive pulmonary vascular remodeling, increased pulmonary arterial pressure, and right heart failure. Beyond local abnormalities within the pulmonary vasculature, growing evidence suggests that PH is shaped by systemic inflammation, metabolic dysregulation, gut microbiota imbalance, and disruption of host circadian organization. In this review, we examine the circadian clock-gut microbiota-gut-lung axis as a time-dependent regulatory network in PH. We focus on core clock gene dysfunction, impaired intestinal barrier integrity, altered microbial metabolites, temporal monocyte and macrophage trafficking, NLRP3 inflammasome activation, and the feedback imposed by chronic hypoxia. The evidence is not equally strong across these mechanisms. Gut dysbiosis, altered microbial metabolites, and inflammatory monocyte activation have relatively direct PH-related support, whereas bile acid rhythmicity, engineered chronobiotic bacteria, and nanoparticle-mediated butyrate delivery remain more speculative. We therefore propose a hypoxia-circadian rhythm-gut microbiota-pulmonary vascular remodeling model as a testable framework rather than a proven causal pathway. This distinction matters: the next step for the field is not simply to identify different microbes, but to determine whether gut-derived inflammatory and metabolic signals lose their timing in PH and whether this loss of timing contributes to vascular remodeling.<\/jats:p>","DOI":"10.3389\/fphys.2026.1895249","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T04:25:01Z","timestamp":1785126301000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Circadian clock-gut microbiota axis in pulmonary hypertension: linking gut\u2013lung crosstalk, immune timing and vascular remodeling"],"prefix":"10.3389","volume":"17","author":[{"given":"Ruixian","family":"Wu","sequence":"first","affiliation":[{"name":"Guangzhou Laboratory, Guangzhou International Bio Island","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Fu","sequence":"additional","affiliation":[{"name":"Guangzhou Laboratory, Guangzhou International Bio Island","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangzhou Laboratory, Guangzhou International Bio Island","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Dong","sequence":"additional","affiliation":[{"name":"Guangzhou Laboratory, Guangzhou International Bio Island","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangzhou Laboratory, Guangzhou International Bio Island","place":["Guangzhou, Guangdong, China"]},{"name":"State Key Laboratory of Respiratory Diseases, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University","place":["Guangzhou, Guangdong, China"]},{"name":"Guangdong Key Laboratory of Vascular Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2747","DOI":"10.1161\/CIRCULATIONAHA.109.927681","article-title":"Formation of plexiform lesions in experimental severe pulmonary arterial hypertension","volume":"121","author":"Abe","year":"2010","journal-title":"Circulation"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1412502","article-title":"Effects of the ACE2-Ang-(1-7)-Mas axis on gut flora diversity and intestinal metabolites in SuHx mice","volume":"15","author":"Abudukeremu","year":"2024","journal-title":"Front. Microbiol."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2025.2563702","article-title":"Luminal LPS is transported across murine small intestine by a caveolin-1 dependent endocytic mechanism induced by chronic feeding of a Western-style diet","volume":"17","author":"Akiba","year":"2025","journal-title":"Gut Microbes"},{"key":"B4","doi-asserted-by":"publisher","first-page":"101128","DOI":"10.1128\/mSystems.00116-21","article-title":"Intermittent hypoxia and hypercapnia alter diurnal rhythms of luminal gut microbiome and metabolome","volume":"6","author":"Allaband","year":"2021","journal-title":"mSystems"},{"key":"B5","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1164\/rccm.202110-2274OC","article-title":"Macrophage-NLRP3 activation promotes right ventricle failure in pulmonary arterial hypertension","volume":"206","author":"Al-Qazazi","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3902","DOI":"10.1007\/s12325-025-03241-4","article-title":"Long-term mortality and morbidity impact on patients with pulmonary arterial hypertension (PAH) if access to sotatercept is delayed: A simulation model","volume":"42","author":"Alsumali","year":"2025","journal-title":"Adv. Ther."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1952","DOI":"10.1093\/cvr\/cvad057","article-title":"The circadian protein BMAL1 supports endothelial cell cycle during angiogenesis","volume":"119","author":"Astone","year":"2023","journal-title":"Cardiovasc. Res."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.107449","article-title":"The circadian clock protein Cryptochrome 1 is a direct target and feedback regulator of the Hippo pathway","volume":"26","author":"Azzi","year":"2023","journal-title":"iScience"},{"key":"B9","doi-asserted-by":"publisher","first-page":"10014","DOI":"10.1038\/s41467-024-53673-9","article-title":"Exposing 24-hour cycles in bile acids of male humans","volume":"15","author":"Bello","year":"2024","journal-title":"Nat. Commun."},{"key":"B10","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1016\/j.jacc.2025.07.026","article-title":"Association between anticoagulant therapy and survival in pulmonary arterial hypertension: A registry report and updated meta-analysis","volume":"86","author":"Bertoletti","year":"2025","journal-title":"J. Am. Coll. Cardiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1016\/j.bbi.2025.01.025","article-title":"Effects of kynurenine pathway metabolites on choroid plexus volume, hemodynamic response, and spontaneous neural activity: A new mechanism for disrupted neurovascular communication and impaired cognition in mood disorders","volume":"125","author":"Bravi","year":"2025","journal-title":"Brain Behav. Immun."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1016\/j.immuni.2024.05.023","article-title":"The tissue-resident regulatory T cell pool is shaped by transient multi-tissue migration and a conserved residency program","volume":"57","author":"Burton","year":"2024","journal-title":"Immunity"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2025.113183","article-title":"Colonic inflammation modulates the intestinal circadian landscape","volume":"28","author":"Butler","year":"2025","journal-title":"iScience"},{"key":"B14","doi-asserted-by":"publisher","first-page":"12326","DOI":"10.1038\/s41598-022-15039-3","article-title":"Kynurenine metabolites predict survival in pulmonary arterial hypertension: A role for IL-6\/IL-6Ralpha","volume":"12","author":"Cai","year":"2022","journal-title":"Sci. Rep."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.124.040896","article-title":"IDO-1 promotes pulmonary vascular remodeling via kynurenine pathway in pulmonary arterial hypertension","volume":"14","author":"Cai","year":"2025","journal-title":"J. Am. Heart Assoc."},{"key":"B16","doi-asserted-by":"publisher","first-page":"9681","DOI":"10.1038\/s41598-018-27682-w","article-title":"Pulmonary arterial hypertension affects the rat gut microbiome","volume":"8","author":"Callejo","year":"2018","journal-title":"Sci. Rep."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115868","article-title":"Rapid group-2 innate lymphoid cell mobilization from the intestine aids in early lung defense and repair","volume":"44","author":"Can","year":"2025","journal-title":"Cell Rep."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1022181","article-title":"Disease-associated gut microbiome and metabolome changes in rats with chronic hypoxia-induced pulmonary hypertension","volume":"12","author":"Cao","year":"2024","journal-title":"Front. Cell Dev. Biol."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adr3226","article-title":"Brain sensing of metabolic state regulates circulating monocytes","volume":"10","author":"Cavalcanti De Albuquerque","year":"2025","journal-title":"Sci. Immunol."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2025.105686","article-title":"Multi-kingdom gut microbiota dysbiosis is associated with the development of pulmonary arterial hypertension","volume":"115","author":"Chen","year":"2025","journal-title":"EBioMedicine"},{"key":"B21","doi-asserted-by":"publisher","first-page":"20356","DOI":"10.1038\/s41598-025-07068-5","article-title":"Transcription factor EB improves hypoxic pulmonary hypertension in fetal rats by suppressing NLRP3 inflammasome activation via induction of mitophagy","volume":"15","author":"Chen","year":"2025","journal-title":"Sci. Rep."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12954","article-title":"Gut microbially produced tryptophan metabolite melatonin ameliorates osteoporosis via modulating SCFA and TMAO metabolism","volume":"76","author":"Chen","year":"2024","journal-title":"J. Pineal Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1016\/j.neuron.2024.12.020","article-title":"Postprandial parasympathetic signals promote lung type 2 immunity","volume":"113","author":"Chen","year":"2025","journal-title":"Neuron"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2022.127205","article-title":"Microbiome and metabolome dysbiosis of the gut-lung axis in pulmonary hypertension","volume":"265","author":"Chen","year":"2022","journal-title":"Microbiol. Res."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2025.128375","article-title":"Circadian rhythm disturbance impairs intestinal mucus barrier and immune microenvironment via sebacic acid-mediated gut dysbiosis","volume":"303","author":"Cheng","year":"2026","journal-title":"Microbiol. Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.1093\/cvr\/cvaf146","article-title":"Mapping disease-specific vascular cell populations responsible for obliterative arterial remodelling during the development of pulmonary arterial hypertension","volume":"121","author":"Cober","year":"2025","journal-title":"Cardiovasc. Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2038","DOI":"10.1016\/j.cmet.2024.07.003","article-title":"Hepatic BMAL1 and HIF1alpha regulate a time-dependent hypoxic response and prevent hepatopulmonary-like syndrome","volume":"36","author":"Dandavate","year":"2024","journal-title":"Cell Metab."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111008","article-title":"Diet and feeding pattern modulate diurnal dynamics of the ileal microbiome and transcriptome","volume":"40","author":"Dantas MaChado","year":"2022","journal-title":"Cell Rep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/nature12820","article-title":"Diet rapidly and reproducibly alters the human gut microbiome","volume":"505","author":"David","year":"2014","journal-title":"Nature"},{"key":"B30","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.stem.2020.01.017","article-title":"C\/EBPbeta-dependent epigenetic memory induces trained immunity in hematopoietic stem cells","volume":"26","author":"De Laval","year":"2020","journal-title":"Cell Stem Cell"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1101\/2025.09.08.674931","article-title":"Genomic and phenotypic comparison of Saccharomyces cerevisiae and Saccharomyces boulardii","author":"Duffey","year":"2025","journal-title":"bioRxiv"},{"key":"B32","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1038\/s41418-022-00988-z","article-title":"Cell cycle regulation: p53-p21-RB signaling","volume":"29","author":"Engeland","year":"2022","journal-title":"Cell Death Differ."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.34133\/research.0673","article-title":"Isobutyrate confers resistance to inflammatory bowel disease through host-microbiota interactions in pigs","volume":"8","author":"Fang","year":"2025","journal-title":"Res. (Wash D. C)"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1053\/j.gastro.2022.07.051","article-title":"Histone deacetylase inhibition by gut microbe-generated short-chain fatty acids entrains intestinal epithelial circadian rhythms","volume":"163","author":"Fawad","year":"2022","journal-title":"Gastroenterology"},{"key":"B35","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1164\/rccm.202209-1761OC","article-title":"Single-cell imaging maps inflammatory cell subsets to pulmonary arterial hypertension vasculopathy","volume":"209","author":"Ferrian","year":"2024","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"3612","DOI":"10.4049\/jimmunol.1701287","article-title":"Inflammatory macrophage expansion in pulmonary hypertension depends upon mobilization of blood-borne monocytes","volume":"200","author":"Florentin","year":"2018","journal-title":"J. Immunol."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.826557","article-title":"Inflammasome activation in pulmonary arterial hypertension","volume":"8","author":"Foley","year":"2021","journal-title":"Front. Med. (Lausanne)"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.949563","article-title":"Genomic reconstruction of short-chain fatty acid production by the human gut microbiota","volume":"9","author":"Frolova","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1016\/j.bbrc.2013.12.022","article-title":"Clock upregulates intercellular adhesion molecule-1 expression and promotes mononuclear cells adhesion to endothelial cells","volume":"443","author":"Gao","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B40","doi-asserted-by":"publisher","first-page":"L363","DOI":"10.1152\/ajplung.00212.2011","article-title":"The monocrotaline model of pulmonary hypertension in perspective","volume":"302","author":"Gomez-Arroyo","year":"2012","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"13516","DOI":"10.1073\/pnas.1607984113","article-title":"Model-driven experimental approach reveals the complex regulatory distribution of p53 by the circadian factor Period 2","volume":"113","author":"Gotoh","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B42","doi-asserted-by":"publisher","first-page":"3081","DOI":"10.1091\/mbc.E14-05-0993","article-title":"The circadian factor Period 2 modulates p53 stability and transcriptional activity in unstressed cells","volume":"25","author":"Gotoh","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"B43","doi-asserted-by":"publisher","first-page":"3111","DOI":"10.1073\/pnas.0409734102","article-title":"Differential control of peripheral circadian rhythms by suprachiasmatic-dependent neural signals","volume":"102","author":"Guo","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2423","DOI":"10.1016\/j.cmet.2025.10.010","article-title":"Intestinal clock shapes sleep-wake cycle via sustaining glutamine homeostasis","volume":"37","author":"Guo","year":"2025","journal-title":"Cell Metab."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1854","DOI":"10.1016\/j.devcel.2025.02.001","article-title":"Innate immune training of osteoclastogenesis promotes inflammatory bone loss in mice","volume":"60","author":"Haacke","year":"2025","journal-title":"Dev. Cell"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.125.25832","article-title":"Targeting macrophage crosstalk to PASMC by blunting inflammatory phenotype via SerpinB1 protects against hypoxia-induced pulmonary hypertension","volume":"83","author":"Hao","year":"2026","journal-title":"Hypertension"},{"key":"B47","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1186\/s12931-025-03182-0","article-title":"Altered maturation and activation state of circulating monocytes is associated with their enhanced recruitment in pulmonary arterial hypertension","volume":"26","author":"Harper","year":"2025","journal-title":"Respir. Res."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14246191","article-title":"Regulation of chromatin accessibility by the Farnesoid X receptor is essential for circadian and bile acid homeostasis in vivo","volume":"14","author":"Hassan","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1016\/j.immuni.2018.10.007","article-title":"Circadian expression of migratory factors establishes lineage-specific signatures that guide the homing of leukocyte subsets to tissues","volume":"49","author":"He","year":"2018","journal-title":"Immunity"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2024.116574","article-title":"Ursodeoxycholic acid alleviates fat embolism syndrome-induced acute lung injury by inhibiting the p38 MAPK\/NF-kappaB signalling pathway through FXR","volume":"230","author":"He","year":"2024","journal-title":"Biochem. Pharmacol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"6068","DOI":"10.1038\/s41467-022-33609-x","article-title":"The intestinal clock drives the microbiome to maintain gastrointestinal homeostasis","volume":"13","author":"Heddes","year":"2022","journal-title":"Nat. Commun."},{"key":"B52","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1038\/nm.3589","article-title":"Chronic variable stress activates hematopoietic stem cells","volume":"20","author":"Heidt","year":"2014","journal-title":"Nat. Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"3138","DOI":"10.1038\/s44319-025-00464-y","article-title":"Genetic disruption of the circadian gene Bmal1 in the intestinal epithelium reduces colonic inflammation","volume":"26","author":"Hua","year":"2025","journal-title":"EMBO Rep."},{"key":"B54","doi-asserted-by":"publisher","first-page":"100944","DOI":"10.1016\/j.bj.2025.100944","article-title":"Anti-PD-L1 improves barrier function and reduces CD103(+) DC cell accumulation by regulating gut and lung microbiota and its metabolites to alleviate asthma in juvenile mice","author":"Huang","year":"2025","journal-title":"Biomed. J."},{"key":"B55","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/s12890-022-01932-0","article-title":"Altered gut microbiota and its association with inflammation in patients with chronic thromboembolic pulmonary hypertension: a single-center observational study in Japan","volume":"22","author":"Ikubo","year":"2022","journal-title":"BMC Pulm. Med."},{"key":"B56","doi-asserted-by":"publisher","first-page":"L183","DOI":"10.1152\/ajplung.00303.2024","article-title":"Activated factor X inhibition ameliorates NF-kappaB-IL-6-mediated perivascular inflammation and pulmonary hypertension","volume":"329","author":"Imakiire","year":"2025","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1101\/2025.07.23.666314","article-title":"Bidirectional crosstalk between sleep and pulmonary arterial hypertension","author":"Imani","year":"2025","journal-title":"bioRxiv"},{"key":"B58","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1136\/gutjnl-2015-310861","article-title":"Proton pump inhibitors alter the composition of the gut microbiota","volume":"65","author":"Jackson","year":"2016","journal-title":"Gut"},{"key":"B59","doi-asserted-by":"publisher","first-page":"27480","DOI":"10.1038\/s41598-025-10921-2","article-title":"Vitamin D and lipopolysaccharide jointly induce a distinct epigenetic and transcriptional program in human monocytes","volume":"15","author":"Jankowski","year":"2025","journal-title":"Sci. Rep."},{"key":"B60","doi-asserted-by":"publisher","first-page":"5029","DOI":"10.1038\/s41467-019-13036-1","article-title":"Evaluation of 16S rRNA gene sequencing for species and strain-level microbiome analysis","volume":"10","author":"Johnson","year":"2019","journal-title":"Nat. Commun."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1161\/HYPERTENSIONAHA.119.14294","article-title":"Altered gut microbiome profile in patients with pulmonary arterial hypertension","volume":"75","author":"Kim","year":"2020","journal-title":"Hypertension"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2024.114643","article-title":"Manipulation of feeding patterns in high fat diet fed rats improves microbiota composition dynamics, inflammation and gut-brain signaling","volume":"285","author":"Klingbeil","year":"2024","journal-title":"Physiol. Behav."},{"key":"B63","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1126\/science.1226339","article-title":"Transcriptional architecture and chromatin landscape of the core circadian clock in mammals","volume":"338","author":"Koike","year":"2012","journal-title":"Science"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1172\/JCI176865","article-title":"Monocytes and interstitial macrophages contribute to hypoxic pulmonary hypertension","volume":"135","author":"Kumar","year":"2025","journal-title":"J. Clin. Invest."},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3390\/nu17233663","article-title":"Short chain fatty acids lower inflammation and restore intestinal integrity and function markers in Mycobacterium paratuberculosis-infection in vitro model","volume":"17","author":"Lagod","year":"2025","journal-title":"Nutrients"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.116057","article-title":"Gut-lung axis: moxibustion's impact on short-chain fatty acids in various tissues of asthmatic rats","volume":"170","author":"Lai","year":"2026","journal-title":"Int. Immunopharmacol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1039\/d5mo00136f","article-title":"Cytokine-induced memory-like responses in endothelial cells link chronic inflammation to vascular disease risk","volume":"21","author":"Le","year":"2025","journal-title":"Mol. Omics"},{"key":"B68","doi-asserted-by":"publisher","first-page":"4839","DOI":"10.2147\/JIR.S321513","article-title":"Neutrophil extracellular traps augmented alveolar macrophage pyroptosis via AIM2 inflammasome activation in LPS-induced ALI\/ARDS","volume":"14","author":"Li","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1614768","article-title":"A high-calorie diet exacerbates lipopolysaccharide-induced pneumonia by promoting acetate-mediated macrophage polarization via the HDAC9\/10-HIF-1alpha-glycolysis axis","volume":"16","author":"Li","year":"2025","journal-title":"Front. Immunol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1038\/s41467-025-67680-x","article-title":"Genetic and dietary determinants of gut microbiome-bile acid interactions in the BXD genetic reference population","volume":"17","author":"Li","year":"2025","journal-title":"Nat. Commun."},{"key":"B71","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1093\/cvr\/cvm016","article-title":"FXR-mediated regulation of eNOS expression in vascular endothelial cells","volume":"77","author":"Li","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"B72","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1016\/j.immuni.2025.05.005","article-title":"A brain-to-lung signal from GABAergic neurons to ADRB2(+) interstitial macrophages promotes pulmonary inflammatory responses","volume":"58","author":"Li","year":"2025","journal-title":"Immunity"},{"key":"B73","doi-asserted-by":"publisher","first-page":"2218","DOI":"10.1038\/s41590-025-02328-y","article-title":"TSLP links intestinal nutrient sensing with amplification of the ILC2-tuft cell circuit","volume":"26","author":"Liao","year":"2025","journal-title":"Nat. Immunol."},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms11020472","article-title":"Gut microbiota and metabolome changes in three pulmonary hypertension rat models","volume":"11","author":"Luo","year":"2023","journal-title":"Microorganisms"},{"key":"B75","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1186\/s12974-025-03589-y","article-title":"Bone marrow-derived emergency monopoiesis drives brain-lung axis injury after traumatic brain injury via IL-1","volume":"22","author":"Ma","year":"2025","journal-title":"J. Neuroinflamm."},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202200699RR","article-title":"The HIF-1alpha\/miR-26a-5p\/PFKFB3\/ULK1\/2 axis regulates vascular remodeling in hypoxia-induced pulmonary hypertension by modulation of autophagy","volume":"37","author":"Ma","year":"2023","journal-title":"FASEB J."},{"key":"B77","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1073\/pnas.1914112117","article-title":"Hypoxia induces a time- and tissue-specific response that elicits intertissue circadian clock misalignment","volume":"117","author":"Manella","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B78","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1111\/nyas.70043","article-title":"Gut microbiota-derived lipopolysaccharides and short-chain fatty acids regulate immune responses via FFAR2\/FFAR3 in lung ischemia-reperfusion injury","volume":"1553","author":"Maruyama","year":"2025","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2025.2606486","article-title":"Gut microbiome-derived propionate reprograms alveolar macrophages metabolically and regulates lung injury responses in mice","volume":"18","author":"Maruyama","year":"2026","journal-title":"Gut Microbes"},{"key":"B80","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1038\/nature06685","article-title":"Haematopoietic stem cell release is regulated by circadian oscillations","volume":"452","author":"Mendez-Ferrer","year":"2008","journal-title":"Nature"},{"key":"B81","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1016\/j.stem.2024.09.010","article-title":"A distinct metabolic and epigenetic state drives trained immunity in HSC-derived macrophages from autoimmune mice","volume":"31","author":"Mills","year":"2024","journal-title":"Cell Stem Cell"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2024.106606","article-title":"Indole induces anxiety-like behaviour in mice mediated by brainstem locus coeruleus activation","volume":"200","author":"Mir","year":"2024","journal-title":"Neurobiol. Dis."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1194\/jlr.M087239","article-title":"Simultaneous inhibition of FXR and TGR5 exacerbates atherosclerotic formation","volume":"59","author":"Miyazaki-Anzai","year":"2018","journal-title":"J. Lipid Res."},{"key":"B84","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1164\/rccm.202203-0490OC","article-title":"Pulmonary arterial hypertension patients have a proinflammatory gut microbiome and altered circulating microbial metabolites","volume":"207","author":"Moutsoglou","year":"2023","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf1098","article-title":"Trained immunity: a program of innate immune memory in health and disease","volume":"352","author":"Netea","year":"2016","journal-title":"Science"},{"key":"B86","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1126\/science.1240636","article-title":"Circadian gene Bmal1 regulates diurnal oscillations of Ly6C(hi) inflammatory monocytes","volume":"341","author":"Nguyen","year":"2013","journal-title":"Science"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202400508RR","article-title":"Time-of-day control of mitochondria regulates NLRP3 inflammasome activation in macrophages","volume":"38","author":"O'siorain","year":"2024","journal-title":"FASEB J."},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.3390\/epigenomes9040052","article-title":"The exosome-mediated epigenome: non-coding RNA and mRNA-coding networks in microbiome-cellular communication, inflammation, and tumorigenesis along the oral-gut-lung axis","volume":"9","author":"Otalora-Otalora","year":"2025","journal-title":"Epigenomes"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.114095","article-title":"Phosphodiesterase 4B activation exacerbates pulmonary hypertension induced by intermittent hypoxia by regulating mitochondrial injury and cAMP\/PKA\/p-CREB\/PGC-1alpha signaling","volume":"158","author":"Pan","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"B90","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1172\/JCI93910","article-title":"Circadian clock component REV-ERBalpha controls homeostatic regulation of pulmonary inflammation","volume":"128","author":"Pariollaud","year":"2018","journal-title":"J. Clin. Invest."},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.3390\/nu15153292","article-title":"Adiposity reduction by Cucumis melo var. gaettongchamoe extract in high-fat diet-induced obese mice","volume":"15","author":"Park","year":"2023","journal-title":"Nutrients"},{"key":"B92","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1038\/s41467-020-15277-x","article-title":"Output from VIP cells of the mammalian central clock regulates daily physiological rhythms","volume":"11","author":"Paul","year":"2020","journal-title":"Nat. Commun."},{"key":"B93","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.cmet.2016.09.010","article-title":"Circadian clock interaction with HIF1alpha mediates oxygenic metabolism and anaerobic glycolysis in skeletal muscle","volume":"25","author":"Peek","year":"2017","journal-title":"Cell Metab."},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.124.012524","article-title":"Lactobacillus restructures the micro\/mycobiome to combat inflammation-mediated right ventricular dysfunction in pulmonary arterial hypertension","volume":"18","author":"Prisco","year":"2025","journal-title":"Circ. Heart Fail."},{"key":"B95","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.imlet.2014.11.014","article-title":"Overexpression of circadian clock protein cryptochrome (CRY) 1 alleviates sleep deprivation-induced vascular inflammation in a mouse model","volume":"163","author":"Qin","year":"2015","journal-title":"Immunol. Lett."},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-026-71189-2","article-title":"Targeting REV-ERBalpha\/BNIP3 axis attenuates pulmonary arterial hypertension by repressing mitophagy in mice","volume":"17","author":"Qiu","year":"2026","journal-title":"Nat. Commun."},{"key":"B97","doi-asserted-by":"publisher","first-page":"2772","DOI":"10.1016\/j.tjnut.2024.06.004","article-title":"Day and night reversed feeding aggravates high-fat diet-induced abnormalities in intestinal flora and lipid metabolism in adipose tissue of mice","volume":"154","author":"Qiu","year":"2024","journal-title":"J. Nutr."},{"key":"B98","doi-asserted-by":"publisher","first-page":"G527","DOI":"10.1152\/ajpgi.00388.2012","article-title":"Activation of G protein-coupled bile acid receptor, TGR5, induces smooth muscle relaxation via both Epac- and PKA-mediated inhibition of RhoA\/Rho kinase pathway","volume":"304","author":"Rajagopal","year":"2013","journal-title":"Am. J. Physiol. Gastrointest Liver Physiol."},{"key":"B99","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.immuni.2024.12.012","article-title":"Microbiota translocation following intestinal barrier disruption promotes Mincle-mediated training of myeloid progenitors in the bone marrow","volume":"58","author":"Robles-Vera","year":"2025","journal-title":"Immunity"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1093\/jleuko\/qiae240","article-title":"Interleukin-10 inhibits important components of trained immunity in human monocytes","volume":"117","author":"Roring","year":"2025","journal-title":"J. Leukoc. Biol."},{"key":"B101","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1038\/s41586-025-08898-z","article-title":"BMAL1-HIF2A heterodimer modulates circadian variations of myocardial injury","volume":"641","author":"Ruan","year":"2025","journal-title":"Nature"},{"key":"B102","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1186\/s12931-024-03046-z","article-title":"Intestinal IFNalpha4 promotes 15-HETE diet-induced pulmonary hypertension","volume":"25","author":"Ruffenach","year":"2024","journal-title":"Respir. Res."},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.158183","article-title":"Aorta- and liver-generated TMAO enhances trained immunity for increased inflammation via ER stress\/mitochondrial ROS\/glycolysis pathways","volume":"8","author":"Saaoud","year":"2023","journal-title":"JCI Insight"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1177\/2045894020929147","article-title":"Gut microbiota modification suppresses the development of pulmonary arterial hypertension in an SU5416\/hypoxia rat model","volume":"10","author":"Sanada","year":"2020","journal-title":"Pulm. Circ."},{"key":"B105","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1161\/ATVBAHA.117.309259","article-title":"Ly6C(high) monocytes oscillate in the heart during homeostasis and after myocardial infarction-brief report","volume":"37","author":"Schloss","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"B106","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1177\/07487304251363656","article-title":"Circadian control of pulmonary endothelial signaling occurs via the NADPH oxidase 2-NLRP3 pathway","volume":"40","author":"Sengupta","year":"2025","journal-title":"J. Biol. Rhythms"},{"key":"B107","doi-asserted-by":"publisher","first-page":"4472","DOI":"10.1002\/cam4.5129","article-title":"BMAL1 promotes colorectal cancer cell migration and invasion through ERK- and JNK-dependent c-Myc expression","volume":"12","author":"Shan","year":"2023","journal-title":"Cancer Med."},{"key":"B108","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1161\/HYPERTENSIONAHA.120.14931","article-title":"Gut pathology and its rescue by ACE2 (angiotensin-converting enzyme 2) in hypoxia-induced pulmonary hypertension","volume":"76","author":"Sharma","year":"2020","journal-title":"Hypertension"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00253-2019","article-title":"Pulmonary arterial hypertension-associated changes in gut pathology and microbiota","volume":"6","author":"Sharma","year":"2020","journal-title":"ERJ Open Res."},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009933","article-title":"NF-kappaB modifies the mammalian circadian clock through interaction with the core clock protein BMAL1","volume":"17","author":"Shen","year":"2021","journal-title":"PLoS Genet."},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1002\/imt2.272","article-title":"Cross-tissue multi-omics analyses reveal the gut microbiota's absence impacts organ morphology, immune homeostasis, bile acid and lipid metabolism","volume":"4","author":"Shen","year":"2025","journal-title":"Imeta"},{"key":"B112","doi-asserted-by":"publisher","first-page":"6925","DOI":"10.1039\/d5fo00772k","article-title":"Propionate alleviates ulcerative colitis by modulating the PI3K\/AKT signaling pathway and suppressing NLRP3 inflammasome activation","volume":"16","author":"Shi","year":"2025","journal-title":"Food Funct."},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2025.117111","article-title":"Dysregulated tryptophan metabolism and gut microbiota in chronic hypoxia-induced pulmonary hypertension rats","volume":"266","author":"Shuai","year":"2025","journal-title":"J. Pharm. Biomed. Anal."},{"key":"B114","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1038\/s41598-018-19836-7","article-title":"Gut microbiota-derived short chain fatty acids induce circadian clock entrainment in mouse peripheral tissue","volume":"8","author":"Tahara","year":"2018","journal-title":"Sci. Rep."},{"key":"B115","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s12987-025-00669-2","article-title":"Circadian misalignment potentiates blood-brain barrier disruption and mitochondria dysregulation in Zika virus infection","volume":"22","author":"Teglas","year":"2025","journal-title":"Fluids Barriers CNS"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2023.131499","article-title":"Exposure to polychlorinated biphenyls selectively dysregulates endothelial circadian clock and endothelial toxicity","volume":"454","author":"Teglas","year":"2023","journal-title":"J. Hazard. Mater."},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1408772","article-title":"The disrupted molecular circadian clock of monocytes and macrophages in allergic inflammation","volume":"15","author":"Teppan","year":"2024","journal-title":"Front. Immunol."},{"key":"B118","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1016\/j.cell.2016.11.003","article-title":"Microbiota diurnal rhythmicity programs host transcriptome oscillations","volume":"167","author":"Thaiss","year":"2016","journal-title":"Cell."},{"key":"B119","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.cell.2014.09.048","article-title":"Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis","volume":"159","author":"Thaiss","year":"2014","journal-title":"Cell."},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2025.2509281","article-title":"Impact of peripheral circadian misalignment and alcohol on the resiliency of intestinal barrier and microbiota","volume":"17","author":"Tran","year":"2025","journal-title":"Gut Microbes"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2023113527","article-title":"Hematopoietic stem cells undergo a lymphoid to myeloid switch in early stages of emergency granulopoiesis","volume":"42","author":"Vanickova","year":"2023","journal-title":"EMBO J."},{"key":"B122","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1038\/s41467-019-14177-z","article-title":"Impact of commonly used drugs on the composition and metabolic function of the gut microbiota","volume":"11","author":"Vich Vila","year":"2020","journal-title":"Nat. Commun."},{"key":"B123","doi-asserted-by":"publisher","first-page":"H765","DOI":"10.1152\/ajpheart.00131.2024","article-title":"Hypertension disrupts the vascular clock in both sexes","volume":"327","author":"Visniauskas","year":"2024","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B124","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1186\/s40104-025-01262-1","article-title":"Bacillus velezensis MZ09 alleviates DSS-induced colitis in piglets by remodeling the intestinal microbiota activating the SCFAs-GPR43-STAT3 pathway and suppressing NLRP3 inflammasome-mediated pyroptosis","volume":"16","author":"Wang","year":"2025","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"B125","doi-asserted-by":"publisher","first-page":"2690","DOI":"10.1016\/j.cell.2024.04.015","article-title":"Circadian tumor infiltration and function of CD8(+) T cells dictate immunotherapy efficacy","volume":"187","author":"Wang","year":"2024","journal-title":"Cell."},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2025.117515","article-title":"Tangeretin mitigates ulcerative colitis by improving BMAL1-mediated intestinal barrier function","volume":"243","author":"Weng","year":"2026","journal-title":"Biochem. Pharmacol."},{"key":"B127","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1159\/000532032","article-title":"Protease-activated receptor 2 controls vascular smooth muscle cell proliferation in cyclic AMP-dependent protein kinase\/mitogen-activated protein kinase kinase 1\/2-dependent manner","volume":"60","author":"Williams","year":"2023","journal-title":"J. Vasc. Res."},{"key":"B128","doi-asserted-by":"publisher","first-page":"111451","DOI":"10.1016\/j.yexcr.2019.05.032","article-title":"Regulation of circadian rhythms by NEAT1 mediated TMAO-induced endothelial proliferation: A protective role of asparagus extract","volume":"382","author":"Wu","year":"2019","journal-title":"Exp. Cell. Res."},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.812303","article-title":"Role of gut microbiota in pulmonary arterial hypertension","volume":"12","author":"Wu","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2025.111812","article-title":"The transcription factor BMAL1 inhibits endothelial cell apoptosis by targeting STAT6 to repress its expression","volume":"132","author":"Yang","year":"2025","journal-title":"Cell. Signal."},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2025.109310","article-title":"Development of a clinically relevant rat model of chronic thromboembolic pulmonary hypertension by combining splenectomy with pulmonary thromboembolism","volume":"249","author":"Zhang","year":"2025","journal-title":"Thromb. Res."},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.97130","article-title":"The microbiome interacts with the circadian clock and dietary composition to regulate metabolite cycling in the Drosophila gut","volume":"13","author":"Zhang","year":"2025","journal-title":"Elife"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2025.101776","article-title":"Elevated diurnal CD36 expression disrupts the bile acid synthesis rhythm leading to cholestatic liver injury and inflammation via the HMGCR\/CYP7A1 axis","volume":"13","author":"Zhang","year":"2026","journal-title":"Genes Dis."},{"key":"B134","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1124\/dmd.117.078105","article-title":"REV-ERBalpha regulates CYP7A1 through repression of liver receptor homolog-1","volume":"46","author":"Zhang","year":"2018","journal-title":"Drug Metab. Dispos."},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2025.1699748","article-title":"Gut microbiota dysbiosis aggravates sepsis-induced lung injury by promoting neutrophil extracellular traps and suppressing host integrin defense","volume":"16","author":"Zhao","year":"2025","journal-title":"Front. Microbiol."},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12892","article-title":"Homeostatic crosstalk among gut microbiome, hypothalamic and hepatic circadian clock oscillations, immunity and metabolism in response to different light-dark cycles: A multiomics study","volume":"75","author":"Zhen","year":"2023","journal-title":"J. Pineal Res."},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2025.1712516","article-title":"The molecular interplay between the gut microbiome and circadian rhythms: an integrated review","volume":"16","author":"Zheng","year":"2025","journal-title":"Front. Microbiol."},{"key":"B138","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1097\/HJH.0000000000004281","article-title":"Combined exposure of cold and hypoxia: a driver for hypertension and the underlying role of the microbiota-gut-brain axis","volume":"44","author":"Zhou","year":"2026","journal-title":"J. Hypertens."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2026.1895249\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T04:25:02Z","timestamp":1785126302000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2026.1895249\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":138,"alternative-id":["10.3389\/fphys.2026.1895249"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2026.1895249","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]},"article-number":"1895249"}}