The widespread application of zinc oxide nanoparticles (ZnO-NPs) brings convenience to our lives while also renders threats to public health and ecological environment. The lung has been recognized as a primary target of ZnO-NPs, however, the detrimental effects and mechanism of ZnO-NPs on the respiratory system have not been thoroughly characterized so far. To investigate the effect of ZnO-NPs on acute lung injury (ALI), Sprague Dawley rats were intratracheally instilled with ZnO-NPs suspension at doses of 1, 2, and 4 mg/kg/day for 3 consecutive days. Our study revealed that ZnO-NPs induced ALI in rats characterized by increased airway resistance, excessive inflammatory response and lung histological damage. In addition, we identified several molecular biomarkers related to the potential mechanism of ZnO-NP-induced ALI, including oxidative stress, mitochondrial damage, and NLRP3 inflammasome activation. The results of in vitro experiments showed that the viability of A549 cells decreased with the increase in ZnO-NPs concentration. Meanwhile, it was also found that ZnO-NP treatment induced the production of ROS, the decrease in mitochondrial membrane potential and activation of NLRP3 inflammasome in A549 cells. Furthermore, to explore the underlying molecular mechanisms of ZnO-NP-induced ALI, N-acetyl-L-cysteine (a ROS scavenger), Cyclosporin A (an inhibitor for mitochondrial depolarization) and Glibenclamide (an inhibitor for NLRP3 inflammasome activity) were used to pre-treat A549 cells before ZnO-NPs stimulation in the in vitro experiments, respectively. The results from this study suggested that ZnO-NP-induced ROS production triggered the accumulation of damaged mitochondria and assembly of NLRP3 inflammatory complex, leading to maturation and release of IL-1β. Moreover, ZnO-NP-induced NLRP3 inflammasome activation was partly mediated by mitochondrial damage. Taken together, our study suggested that ZnO-NPs induced ALI through oxidative stress-mediated mitochondrial damage and NLRP3 inflammasome activation and provided insight into the mechanisms of ZnO-NPs-induced ALI.

Engineered zinc oxide nanoparticles (ZnO-NPs) are currently being produced in high tonnage. Exposure to ZnO-NPs presents potential risks to cardiovascular system. Thus far, the toxicological effects of ZnO-NPs on cardiovascular system have not been well characterized. In this study, human coronary artery endothelial cells (HCAECs) were exposed to ZnO-NPs directly or indirectly using a transwell coculture system with human alveolar epithelial cell line A549 to mimic the lung/circulation interaction. It was shown that levels of proinflammatory mediators (interleukin-8 [IL-8] and tumor necrosis factor-α [TNF-α]) and biomarkers of atherosclerogenesis (heme oxygenase-1 [HO-1] and platelet endothelial cell adhesion molecules-1 [PECAM-1]) in the supernatants of culture media were significantly increased. Pretreatment of A549 cells on the apical side of the coculture system with the phagocytosis inhibitor cytochalasin B (CB) blocked ZnO-NP-induced HO-1 and PECAM-1 expression in HCAEC, indicating that endocytosis of ZnO-NPs by alveolar epithelial cells was involved in ZnO-NP-induced HO-1 or PECAM-1 expression in endothelial cells. Moreover, Wistar rats were intratracheally instilled with ZnO-NP suspension and high fat diet (positive control). ZnO-NP treatment induced lung and systemic inflammation, dyslipidemia, increased levels of serum HO-1 and PECAM-1, and aortic pathological damage. Taken together, exposure to ZnO-NPs could induce atherosclerotic alterations, which might involve phagocytosis of nanoparticles and inflammation in the lung.

To investigate the impact of high temperature (HT) exposure on cognitive function in humans and rats, focusing on the gut-brain axis as a potential mediating pathway. The study population was derived from the Guangzhou Nutrition and Health Study, with cognitive function assessed using the Addenbrooke's Cognitive Examination Revised (ACE-R) scale. HT exposure was defined as exposure for more than one year during the career. In animal experiments, 36 male Sprague Dawley rats were exposed to controlled temperatures (25°C, 30°C, 35°C, and 40°C) for four hours daily over 15 days. Cognitive function was evaluated using the Morris Water Maze (MWM) test. Neurodegeneration, glial activation, neuroinflammation, intestinal barrier function and inflammation were evaluated by Western blot, Elisa, immunohistochemistry and immunofluorescence staining. 16S rRNA sequencing was employed to profile the gut microbiota. Targeted metabolomics analysis was conducted using gas chromatography-mass spectrometry to quantify short-chain fatty acids (SCFAs) in fecal samples. Human participants in the HT group exhibited significantly lower ACE-R and memory scores compared to controls. Similarly, HT exposure in rats led to a notable decline in spatial learning and memory, accompanied by damage to hippocampal neurons. Further examinations revealed that HT exposure disrupted intestinal homeostasis, characterized by a reduced abundance of SCFA-producing bacteria and decreased SCFA levels in the intestines. This disruption was accompanied by intestinal inflammation, compromised intestinal barrier integrity, and neuroinflammation. This study suggests that HT exposure may negatively impact cognitive function through mechanisms potentially involving the gut-brain axis, offering insights into possible underlying biological pathways.

Scarce evidence exists on the impact of ozone (O₃) on atherosclerotic cardiovascular disease (ASCVD) morbidity in tropical urban settings, and whether temperature modifies this effect remains unclear. To bridge this gap, we assessed the association between ambient O₃ and ASCVD outpatient visits, and the potential effect modification by temperature, in Haikou, China. A time-series analysis was performed on data from 163,348 daily hospital outpatient visits for ASCVD collected between 1 January 2020 and 31 December 2022. The association between O₃ exposure and daily visits was evaluated with an over-dispersed Poisson generalized additive model (GAM), and the modifying effect of temperature was scrutinized using a nonparametric bivariate response surface model. A 10 μg/m³ increment in the daily maximum 8 h average concentration of O₃ was associated with a 1.35% (95% CI: 0.63, 2.07) increase in ASCVD outpatient visits at lag0. Stratified analyses revealed that the association between O₃ and ASCVD visits was only significant during the warm season, with stronger effects observed above 30 °C, peaking at 34 °C (lag06). The combined exposure to high temperature and O₃ concentrations significantly amplified ASCVD outpatient visits. Ambient O₃ exposure was associated with increased ASCVD outpatient visits in the tropical city, and this risk was enhanced under high temperatures. These results highlighted the importance of considering temperature interaction in O₃-related risk assessments.

Background: This study establishes the first molecular stratification framework for chronic obstructive pulmonary disease (COPD) based on oxeiptosis biology, exploring how this reactive oxygen species (ROS)-induced cell death pathway shapes disease heterogeneity. The precise role of oxeiptosis in COPD pathogenesis remains poorly understood. Methods: Transcriptomic profiles from two independent cohorts, GSE47460 (220 COPD cases and 108 controls) and GSE76925 (111 COPD cases and 40 controls), were systematically evaluated using a fully in silico computational pipeline. Oxeiptosis-related differentially expressed genes (ORDEGs) were identified through correlation and differential expression analyses, prioritized using machine learning, and then applied for unsupervised clustering. Subtypes were externally validated and functionally characterized through pathway enrichment and network analysis. Results: The support vector machine (SVM) model prioritized four of the seven ORDEGs for further analysis. Two reproducible subtypes were identified: C1, characterized by diminished ORDEGs activity and significantly worse pulmonary function (FEV₁% predicted: C1 vs. C2, 44% vs 59%, P < 0.05), and C2, marked by heightened activity and less severe dysfunction. Weighted gene coexpression network analysis (WGCNA) revealed a black module associated with subtype classification, enriched in cytokine signaling and extracellular matrix remodeling pathways. A predictive model was constructed to investigate clinical applicability. Conclusion: This computational discovery framework introduces an oxeiptosis-specific molecular taxonomy of COPD. The results underscore oxidative stress and the interaction between immune regulation and matrix remodeling as pivotal elements linked to disease heterogeneity, presenting potential pathways for precise diagnosis and treatment.