Analysis of PM2.5 inorganic and organic constituents to resolve contributing sources in Seoul, South Korea and Beijing, China and their possible associations with cytokine IL-8.

China and South Korea are the most polluted countries in East Asia due to significant urbanization and extensive industrial activities. As neighboring countries, collaborative management plans to maximize public health in both countries can be helpful in reducing transboundary air pollution. To support such planning, PM2.5 inorganic and organic species were determined in simultaneously collected PM2.5 integrated filters. The resulting data were used as inputs to positive matrix factorization, which identified nine sources at the ambient air monitoring sites in both sites. Secondary nitrate, secondary sulfate/oil combustion, soil, mobile, incinerator, biomass burning, and secondary organic carbon (SOC) were found to be sources at both sampling sites. Industry I and II were only identified in Seoul, whereas combustion and road dust sources were only identified in Beijing. A subset of samples was selected for exposure assessment. The expression levels of IL-8 were significantly higher in Beijing (167.7 pg/mL) than in Seoul (72.7 pg/mL). The associations between the PM2.5 chemical constituents and its contributing sources with PM2.5-induced inflammatory cytokine (interleukin-8, IL-8) levels in human bronchial epithelial cells were investigated. For Seoul, the soil followed by the secondary nitrate and the biomass burning showed increase with IL-8 production. However, for the Beijing, the secondary nitrate exhibited the highest association with IL-8 production and SOC and biomass burning showed modest increase with IL-8. As one of the highest contributing sources in both cities, secondary nitrate showed an association with IL-8 production. The soil source having the strongest association with IL-8 production was found only for Seoul, whereas SOC showed a modest association only for Beijing. This study can provide the scientific basis for identifying the sources to be prioritized for control to provide effective mitigation of particulate air pollution in each city and thereby improve public health.

Long-term exposure to ambient fine particulate matter constituents and mortality from total and site-specific gastrointestinal cancer.

BACKGROUND: Ambient fine particulate matter (PM2.5) exposure has been associated with an increased risk of gastrointestinal cancer mortality, but the attributable constituents remain unclear. OBJECTIVES: To investigate the association of long-term exposure to PM2.5 constituents with total and site-specific gastrointestinal cancer mortality using a difference-in-differences approach in Jiangsu province, China during 2015-2020. METHODS: We split Jiangsu into 53 spatial units and computed their yearly death number of total gastrointestinal, esophagus, stomach, colorectum, liver, and pancreas cancer. Utilizing a high-quality grid dataset on PM2.5 constituents, we estimated 10-year population-weighted exposure to black carbon (BC), organic carbon (OC), sulfate, nitrate, ammonium, and chloride in each spatial unit. The effect of constituents on gastrointestinal cancer mortality was assessed by controlling time trends, spatial differences, gross domestic product (GDP), and seasonal temperatures. RESULTS: Overall, 524,019 gastrointestinal cancer deaths were ascertained in 84.77 million population. Each interquartile range increment of BC (0.46 µg/m3), OC (4.56 µg/m3), and nitrate (1.41 µg/m3) was significantly associated with a 27%, 26%, and 34% increased risk of total gastrointestinal cancer mortality, respectively, and these associations remained significant in PM2.5-adjusted models and constituent-residual models. We also identified robust associations of BC, OC, and nitrate exposures with site-specific gastrointestinal cancer mortality. The mortality risk generally displayed increased trends across the total exposure range and rose steeper at higher levels. We did not identify robust associations for sulfate, ammonium, or chlorine exposure. Higher mortality risk ascribed to constituent exposures was identified in total gastrointestinal and liver cancer among women, stomach cancer among men, and total gastrointestinal and stomach cancer among low-GDP regions. CONCLUSIONS: This study offers consistent evidence that long-term exposure to PM2.5-bound BC, OC, and nitrate is associated with total and site-specific gastrointestinal cancer mortality, indicating that these constituents need to be controlled to mitigate the adverse effect of PM2.5 on gastrointestinal cancer mortality.

Interleukin-37 relieves PM2.5-triggered lung injury by inhibiting autophagy through the AKT/mTOR signaling pathway in vivo and in vitro.

Autophagy mediates PM2.5-related lung injury (LI) and is tightly linked to inflammation and apoptosis processes. IL-37 has been demonstrated to regulate autophagy. This research aimed to examine the involvement of IL-37 in the progression of PM2.5-related LI and assess whether autophagy serves as a mediator for its effects.To create a model of PM2.5-related LI, this research employed a nose-only PM2.5 exposure system and utilized both human IL-37 transgenic mice and wild-type mice. The hIL-37tg mice demonstrated remarkable reductions in pulmonary inflammation and pathological LI compared to the WT mice. Additionally, they exhibited activation of the AKT/mTOR signaling pathway, which served to regulate the levels of autophagy and apoptosis.Furthermore, in vitro experiments revealed a dose-dependent upregulation of autophagy and apoptotic proteins following exposure to PM2.5 DMSO extraction. Simultaneously, p-AKT and p-mTOR expression was found to decrease. However, pretreatment with IL-37 demonstrated a remarkable reduction in the levels of autophagy and apoptotic proteins, along with an elevation of p-AKT and p-mTOR. Interestingly, pretreatment with rapamycin, an autophagy inducer, weakened the therapeutic impact of IL-37. Conversely, the therapeutic impact of IL-37 was enhanced when treated with 3-MA, a potent autophagy inhibitor. Moreover, the inhibitory effect of IL-37 on autophagy was successfully reversed by administering AKT inhibitor MK2206. The findings suggest that IL-37 can inhibit both the inflammatory response and autophagy, leading to the alleviation of PM2.5-related LI. At the molecular level, IL-37 may exert its anti autophagy and anti apoptosis effects by activating the AKT/mTOR signaling pathway.

PM2.5 associates with blood pressure: a Mendelian randomization analysis.

The relationship between fine particulate matter (PM2.5) and blood pressure (BP) is a controversial issue. We conducted a two-sample Mendelian randomization (MR) analysis and identified 58 genome-wide significant single-nucleotide polymorphisms associated with PM2.5 as instrument variables. Inverse-variance weighted (IVW) was used as the primary analysis approach. MR-Egger, weighted median, simple model, and weighted model methods were selected for quality control. We found a significant negative causal association of higher genetically predicted PM2.5 levels with lower systolic BP (SBP), while no causal relationship was identified between PM2.5 and diastolic BP (DBP). For each 1 standard deviation increase in genetically predicted PM2.5 levels, the beta value (95% CI) of SBP was -0.14 (-0.25, -0.03) for IVW (p=0.02), and -0.13 (-0.22, -0.04) for weighted median (p=0.005). Increased PM2.5 concentrations can lead to decreased SBP levels. Our findings provided novel insights into the controversial topic on the causal relationship between PM2.5 and BP.

The Exosome-Mediated Cascade Reactions for the Transfer and Inflammatory Responses of Fine Atmospheric Particulate Matter in Macrophages.

Exposure to atmospheric particulate matter (PM) is a frequent occurrence to humans, and their adverse outcomes have become a global concern. Although PM-induced inflammation is a common phenomenon, a clear picture of the mechanisms underlying exosome-mediated inflammation of PM has not yet emerged. Here, we show that exosomes can mediate the cascade reactions for the transfer of PM and inflammatory responses of macrophages. Specifically, two fine PM2.5, namely F1 (<0.49 µm) and F2 (0.95-1.5 µm), stimulated a substantial release of exosomes from macrophages (THP-1 cells) with the order of F1 > F2, via regulation of the P2X7 receptor (P2X7R). Inhibiting P2X7R with a specific inhibitor largely prevented the secretion of exosomes. In particular, we found that exosomes served as a mediator for the transfer of PM2.5 to the recipient macrophages and activated NF-κB signaling through toll-like receptor 4 (TLR-4), thereby stimulating inflammatory cytokine release and altering the inflammatory phenotype of recipients. Importantly, the exosomes derived from PM2.5-treated macrophages induced the inflammatory responses of lung in mice. Our results highlight that exosomes undergo a secretion-particle transfer-adverse outcome chain in macrophages treated with PM2.5. Given the ubiquitous atmospheric particulate matter, these new findings underscore an urgent need for assessing the secretion of exosomes and their impact on human health via exosome-centric physiological pathways.

Polar Nitrated Aromatic Compounds in Urban Fine Particulate Matter: A Focus on Formation via an Aqueous-Phase Radical Mechanism.

Polar nitrated aromatic compounds (pNACs) are key ambient brown carbon chromophores; however, their formation mechanisms, especially in the aqueous phase, remain unclear. We developed an advanced technique for pNACs and measured 1764 compounds in atmospheric fine particulate matter sampled in urban Beijing, China. Molecular formulas were derived for 433 compounds, of which 17 were confirmed using reference standards. Potential novel species with up to four aromatic rings and a maximum of five functional groups were found. Higher concentrations were detected in the heating season, with a median of 82.6 ng m-3 for Σ17pNACs. Non-negative matrix factorization analysis indicated that primary emissions particularly coal combustion were dominant in the heating season. While in the non-heating season, aqueous-phase nitration could generate abundant pNACs with the carboxyl group, which was confirmed by their significant association with the aerosol liquid water content. Aqueous-phase formation of 3- and 5-nitrosalicylic acids instead of their isomer of 4-hydroxy-3-nitrobenzoic acid suggests the existence of an intermediate where the intramolecular hydrogen bond favors kinetics-controlled NO2• nitration. This study provides not only a promising technique for the pNAC measurement but also evidence for their atmospheric aqueous-phase formation, facilitating further evaluation of pNACs' climatic effects.

Prenatal PM2.5 exposure impairs spatial learning and memory in male mice offspring: from transcriptional regulation to neuronal morphogenesis.

BACKGROUND: As one of the environmental risk factors for human health, atmospheric fine particulate matter (PM2.5) contributes to cognitive deterioration in addition to respiratory and cardiovascular injuries. Recently, increasing evidence implicates that PM2.5 inhalation can affect neurological functions in offspring, but the sex-specific outcomes and the underlying biological processes are largely unknown. OBJECTIVES: To observe the influence of prenatal PM2.5 exposure on cognitive performance in offspring, to elucidate the neuronal morphological alterations and possible transcriptional regulation based on mRNA-sequencing (mRNA-Seq) data after birth, and to determine the key components of PM2.5 contributing to the adverse effects. METHODS: Pregnant C57BL/6J mice were exposed to sterile saline or PM2.5 suspension. Morris water maze test was used to assess the cognitive function in weanling offspring. Microscopic observation was applied to detect neuronal morphogenesis in vivo and in vitro. The cortex tissues from male offspring were collected on postnatal days (PNDs) 1, 7, and 21 for mRNA-Seq analysis. The organic and inorganic components of PM2.5 were separated to assess their contributions using primary cultured neurons. RESULTS: Prenatal PM2.5 exposure impaired spatial learning and memory in weanling male mice, but not female mice. The sex-specific outcomes were associated with mRNA expression profiles of the cortex during postnatal critical windows, and the annotations in Gene Ontology (GO) of differentially expressed genes (DEGs) revealed that the exposure persistently disrupted the expression of genes involved in neuronal features in male offspring. Consistently, axonal growth impairment and dendritic complexity reduction were observed. Importantly, Homeobox A5 (Hoxa5), a critical transcription factor regulating all of the neuronal morphogenesis-associated hub genes on PNDs 1, 7, and 21, significantly decreased in the cortex of male offspring following PM2.5 exposure. In addition, both inorganic and organic components were harmful to axonal and dendritic growth, with organic components exhibiting stronger inhibition than inorganic ones. CONCLUSION: Prenatal PM2.5 exposure affected spatial learning and memory in male mice by disrupting Hoxa5-mediated neuronal morphogenesis, and the organic components, including polycyclic aromatic hydrocarbons (PAHs), posed more adverse effects than the inorganic components.

High glucose enhances the activation of NLRP3 inflammasome by ambient fine particulate matter in alveolar macrophages.

BACKGROUND: Epidemiological studies have demonstrated that individuals with preexisting conditions, including diabetes mellitus (DM), are more susceptible to air pollution. However, the underlying mechanisms remain unclear. In this study, we proposed that a high glucose setting enhances ambient fine particulate matter (PM2.5)-induced macrophage activation and secretion of the proinflammatory cytokine, IL-1ß, through activation of the NLRP3 inflammasome, altering the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). RESULTS: Exposure of mouse alveolar macrophages to non-cytotoxic doses of PM2.5 led to upregulation of IL-1ß, activation of the NLRP3 inflammasome, increased nuclear translocation of the transcription factor NF-κB, increased generation of reactive oxygen species (ROS), and increased expression and enzymatic activity of MMP-9; these effects were enhanced when cells were pretreated with high glucose. However, pretreatment in a high glucose setting alone did not induce significant changes. ROS generation following PM2.5 exposure was abolished when cells were pretreated with ROS scavengers such as Trolox and superoxide dismutase (SOD), or with an NADPH oxidase inhibitor, DPI. Pretreatment of cells with DPI attenuated the effects of a high glucose setting on PM2.5-induced upregulation of IL-1ß, activation of the NLRP3 inflammasome, and nuclear translocation of NF-κB. In addition, enhancement of PM2.5-induced expression and enzymatic activity of MMP-9 following high glucose pretreatment was not observed in primary alveolar macrophages obtained from NLRP3 or IL-1R1 knockout (KO) mice, where pro-IL-1ß cannot be cleaved to IL-1ß or cells are insensitive to IL-1ß, respectively. CONCLUSIONS: This study demonstrated that exposure of mouse alveolar macrophages to PM2.5 in a high glucose setting enhanced PM2.5-induced production of IL-1ß through activation of the NLRP3 inflammasome and nuclear translocation of NF-κB due to PM2.5-induced oxidative stress, leading to MMP-9 upregulation. The key role of NADPH oxidase in PM2.5-induced ROS generation and activation of the IL-1ß secretion pathway and the importance of IL-1ß secretion and signaling in PM2.5-induced increases in MMP-9 enzymatic activity were also demonstrated. This study provides a further understanding of the potential mechanisms underlying the susceptibility of individuals with DM to air pollution and suggests potential therapeutic targets.

The pathophysiological and molecular mechanisms of atmospheric PM2.5 affecting cardiovascular health: A review.

BACKGROUND: Exposure to ambient fine particulate matter (PM2.5, with aerodynamic diameter less than 2.5 µm) is a leading environmental risk factor for global cardiovascular health concern. OBJECTIVE: To provide a roadmap for those new to this field, we reviewed the new insights into the pathophysiological and cellular/molecular mechanisms of PM2.5 responsible for cardiovascular health. MAIN FINDINGS: PM2.5 is able to disrupt multiple physiological barriers integrity and translocate into the systemic circulation and get access to a range of secondary target organs. An ever-growing body of epidemiological and controlled exposure studies has evidenced a causal relationship between PM2.5 exposure and cardiovascular morbidity and mortality. A variety of cellular and molecular biology mechanisms responsible for the detrimental cardiovascular outcomes attributable to PM2.5 exposure have been described, including metabolic activation, oxidative stress, genotoxicity, inflammation, dysregulation of Ca2+ signaling, disturbance of autophagy, and induction of apoptosis, by which PM2.5 exposure impacts the functions and fates of multiple target cells in cardiovascular system or related organs and further alters a series of pathophysiological processes, such as cardiac autonomic nervous system imbalance, increasing blood pressure, metabolic disorder, accelerated atherosclerosis and plaque vulnerability, platelet aggregation and thrombosis, and disruption in cardiac structure and function, ultimately leading to cardiovascular events and death. Therein, oxidative stress and inflammation were suggested to play pivotal roles in those pathophysiological processes. CONCLUSION: Those biology mechanisms have deepen insights into the etiology, course, prevention and treatment of this public health concern, although the underlying mechanisms have not yet been entirely clarified.

Maternal exposure to PM2.5 induces cognitive impairment in offspring via cerebellar neuroinflammation and oxidative stress.

Available evidence suggest that exposure to PM2.5 during pregnancy is associated with reduced cognitive function in offspring. This study aimed to investigate the effects of maternal exposure to PM2.5 on offspring cognitive function and to elucidate the underlying mechanisms. In this work, pregnant C57BL/6 female mice were exposed to concentrated ambient PM2.5 or filtered air from day 0.5 (=vaginal plug) to day 15.5 in the Shanghai Meteorological and Environmental Animal Exposure System, and offspring cerebellar tissues were collected on embryonic day 15.5, as well as postnatal days 0, 10 and 42. The mean PM2.5 concentrations exposed to the pregnant mice were 73.06 ± 4.90 µg/m3 and 11.15 ± 2.71 µg/m3 in the concentrated ambient PM2.5 and filtered air chambers, respectively. Maternal concentrated PM2.5 exposure was negatively correlated with offspring spatial memory significantly as assessed by the Morris water maze. Compared with the filtered air group, PM2.5-exposed offspring mice had reduced cerebellar microglia. Both RNA and protein levels of IL-8 and TNF-α were elevated in the concentrated ambient PM2.5 group. PM2.5 exposure increased the level of 8-OHG in miRNA of microglia and Purkinje cells in 6-week-old offspring. The level of prostaglandin F2α (8-iso-PGF2Aα) in the cerebellum was increased at different growing stages of offspring after gestational exposure of PM2.5. These results suggested that maternal air pollution exposure might cause inflammatory damage and oxidative stress to the cerebellum, contributing to reduced cognitive performance in mice offspring.

Assessing traffic-related air pollution-induced fiber-specific white matter degradation associated with motor performance declines in aged rats.

Fine particulate matter (PM2.5) is thought to exacerbate Parkinson's disease (PD) in the elderly, and early detection of PD progression may prevent further irreversible damage. Therefore, we used diffusion tensor imaging (DTI) for probing microstructural changes after late-life chronic traffic-related PM2.5 exposure. Herein, 1.5-year-old Fischer 344 rats were exposed to clean air (control), high-efficiency particulate air (HEPA)-filtered ambient air (HEPA group), and ambient traffic-related PM2.5 (PM2.5 group, 9.933 ± 1.021 µg/m3) for 3 months. Rotarod test, DTI tractographic analysis, and immunohistochemistry were performed in the end of study period. Aged rats exposed to PM2.5 exhibited motor impairment with decreased fractional anisotropy and tyrosine hydroxylase expression in olfactory and nigrostriatal circuits, indicating disrupted white matter integrity and dopaminergic (DA) neuronal loss. Additionally, increased radial diffusivity and lower expression of myelin basic protein in PM2.5 group suggested ageing progression of demyelination exacerbated by PM2.5 exposure. Significant production of tumor necrosis factor-α was also observed after PM2.5 exposure, revealing potential inflammation of injury to multiple fiber tracts of DA pathways. Microstructural changes demonstrated potential links between PM2.5-induced inflammatory white matter demyelination and behavioral performance, with indication of pre-manifestation of DTI-based biomarkers for early detection of PD progression in the elderly.

Spatiotemporally continuous estimates of daily 1-km PM2.5 concentrations and their long-term exposure in China from 2000 to 2020.

Monitoring long-term variations in fine particulate matter (PM2.5) is essential for environmental management and epidemiological studies. While satellite-based statistical/machine-learning methods can be used for estimating high-resolution ground-level PM2.5 concentration data, their applications have been hindered by limited accuracy in daily estimates during years without PM2.5 measurements and massive missing values due to satellite retrieval data. To address these issues, we developed a new spatiotemporal high-resolution PM2.5 hindcast modeling framework to generate the full-coverage, daily, 1-km PM2.5 data for China for the period 2000-2020 with improved accuracy. Our modeling framework incorporated information on changes in observation variables between periods with and without monitoring data and filled gaps in PM2.5 estimates induced by satellite data using imputed high-resolution aerosol data. Compared to previous hindcast studies, our method achieved superior overall cross-validation (CV) R2 and root-mean-square error (RMSE) of 0.90 and 12.94 µg/m3 and significantly improved the model performance in years without PM2.5 measurements, raising the leave-one-year-out CV R2 [RMSE] to 0.83 [12.10 µg/m3] at a monthly scale (0.65 [23.29 µg/m3] at a daily scale). Our long-term PM2.5 estimates show a sharp decline in PM2.5 exposure in recent years, but the national exposure level in 2020 still exceeded the first annual interim target of the 2021 World Health Organization air quality guidelines. The proposed hindcast framework represents a new strategy to improve air quality hindcast modeling and can be applied to other regions with limited air quality monitoring periods. These high-quality estimates can support both long- and short-term scientific research and environmental management of PM2.5 in China.

Association of Long-term Ambient Fine Particulate Matter (PM2.5) and Incident CKD: A Prospective Cohort Study in China.

RATIONALE & OBJECTIVE: Increasing evidence has linked ambient fine particulate matter (ie, particulate matter no larger than 2.5 µm [PM2.5]) to chronic kidney disease (CKD), but their association has not been fully elucidated, especially in regions with high levels of PM2.5 pollution. This study aimed to investigate the long-term association of high PM2.5 exposure with incident CKD in mainland China. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 72,425 participants (age ≥18 years) without CKD were recruited from 121 counties in Hunan Province, China. EXPOSURE: Annual mean PM2.5 concentration at the residence of each participant derived from a long-term, full-coverage, high-resolution (1 × 1 km2), high-quality dataset of ground-level air pollutants in China. OUTCOMES: Incident CKD during the interval between the baseline examination of each participant (2005-2017) and the end of follow-up through 2018. ANALYTICAL APPROACH: Cox proportional hazards models were used to estimate the independent association of PM2.5 with incident CKD and the joint association of PM2.5 with temperature or humidity on the development of PM2.5-related CKD. Restricted cubic splines were used to model exposure-response relationships. RESULTS: Over a median follow-up of 3.79 (IQR, 2.03-5.48) years, a total of 2,188 participants with incident CKD were identified. PM2.5 exposure was associated with incident CKD with an adjusted hazard ratio of 1.71 (95% CI, 1.58-1.85) per 10-µg/m3 greater long-term exposure. Multiplicative interactions between PM2.5 and humidity or temperature on incident CKD were detected (all P < 0.001 for interaction), whereas an additive interaction was detected only for humidity (relative risk due to interaction, 3.59 [95% CI, 0.97-6.21]). LIMITATIONS: Lack of information on participants' activity patterns such as time spent outdoors. CONCLUSIONS: Greater long-term ambient PM2.5 pollution is associated with incident CKD in environments with high PM2.5 exposure. Ambient humidity has a potentially synergetic effect on the association of PM2.5 with the development of CKD. PLAIN-LANGUAGE SUMMARY: Exposure to a form of air pollution known as fine particulate matter (ie, particulate matter ≤2.5 µm [PM2.5]) has been linked to an increased risk of chronic kidney disease (CKD), but little is known about how PM2.5 affects CKD in regions with extremely high levels of PM2.5 pollution. This longitudinal cohort study in China investigates the effect of PM2.5 on the incidence of CKD and whether temperature or humidity interact with PM2.5. Our findings suggest that long-term exposure to high levels of ambient PM2.5 significantly increased the risk of CKD in mainland China, especially in terms of cumulative average PM2.5. The associations of PM2.5 and incident CKD were greater in high-humidity environments. These findings support the recommendation that reducing PM2.5 pollution should be a priority to decrease the burden of associated health risks, including CKD.

Long-Term Exposure to Source-Specific Fine Particles and Mortality─A Pooled Analysis of 14 European Cohorts within the ELAPSE Project.

We assessed mortality risks associated with source-specific fine particles (PM2.5) in a pooled European cohort of 323,782 participants. Cox proportional hazard models were applied to estimate mortality hazard ratios (HRs) for source-specific PM2.5 identified through a source apportionment analysis. Exposure to 2010 annual average concentrations of source-specific PM2.5 components was assessed at baseline residential addresses. The source apportionment resulted in the identification of five sources: traffic, residual oil combustion, soil, biomass and agriculture, and industry. In single-source analysis, all identified sources were significantly positively associated with increased natural mortality risks. In multisource analysis, associations with all sources attenuated but remained statistically significant with traffic, oil, and biomass and agriculture. The highest association per interquartile increase was observed for the traffic component (HR: 1.06; 95% CI: 1.04 and 1.08 per 2.86 µg/m3 increase) across five identified sources. On a 1 µg/m3 basis, the residual oil-related PM2.5 had the strongest association (HR: 1.13; 95% CI: 1.05 and 1.22), which was substantially higher than that for generic PM2.5 mass, suggesting that past estimates using the generic PM2.5 exposure response function have underestimated the potential clean air health benefits of reducing fossil-fuel combustion. Source-specific associations with cause-specific mortality were in general consistent with findings of natural mortality.

Effect of a solar lighting intervention on fuel-based lighting use and exposure to household air pollution in rural Uganda: A randomized controlled trial.

Solar lighting is an alternative to polluting kerosene and other fuel-based lighting devices relied upon by millions of families in resource-limited settings. Whether solar lighting provides sustained displacement of fuel-based lighting sources and reductions in personal exposure to fine particulate matter (PM2 .5 ) and black carbon (BC) has not been examined in randomized controlled trials. Eighty adult women living in rural Uganda who utilized fuel-based (candles and kerosene lamps) and/or clean (solar, grid, and battery-powered devices) lighting were randomized in a 1:1 ratio to receive a home solar lighting system at no cost to study participants (ClinicalTrials.gov NCT03351504). Among intervention group participants, kerosene lamps were completely displaced in 92% of households using them. The intervention led to an average exposure reduction of 36.1 µg/m3 (95% CI -70.3 to -2.0) in PM2 .5 and 10.8 µg/m3 (95% CI -17.6 to -4.1) in BC, corresponding to a reduction from baseline of 37% and 91%, respectively. Reductions were greatest among participants using kerosene lamps. Displacement of kerosene lamps and personal exposure reductions were sustained over 12 months of follow-up. Solar lighting presents an immediate opportunity for achieving sustained reductions in personal exposure to PM2.5 and BC and should be considered in household air pollution intervention packages.

PM2.5 exposure triggers cell death through lysosomal membrane permeabilization and leads to ferroptosis insensitivity via the autophagy dysfunction/p62-KEAP1-NRF2 activation in neuronal cells.

PM2.5 exposure can be associated with the onset of neurodegenerative diseases, with oxidative stress-induced cellular homeostasis disruption and cell death as one of the main mechanisms. However, the exact cellular and molecular processes are still rarely investigated. Autophagy and KEAP1-NRF2 (Kelch-like ECH-Associating protein 1-nuclear factor erythroid 2 related factor 2) signaling pathway are two main cellular defense systems for maintaining cellular homeostasis and resisting oxidative stress. In this study, we primarily investigated the role of autophagy and KEAP1-NRF2 in regulating cell death resulting from PM2.5 exposure in mouse neuroblastoma N2a cells. Our results showed that PM2.5 exposure disrupted autophagic flux by impairing lysosomal function, including lysosomal alkalinization, increased lysosome membrane permeabilization (LMP), and Cathepsin B release. Furthermore, dysregulated autophagy enhances NRF2 activity in a p62-dependent manner, which then initiates the expression of a series of antioxidant genes and increases cellular insensitivity to ferroptosis. Meanwhile, autophagy dysfunction impairs the intracellular degradation of ferroptosis related proteins such as GPX4 and ferritin. As these proteins accumulate, cells also become less sensitive to ferroptosis. LMP-associated cell death may be the main mechanism of PM2.5-induced N2a cytotoxicity. Our results may provide insights into the mechanisms of PM2.5-induced neurotoxicity and predict effective prevention and treatment strategies.

Endothelial progenitor cells as critical mediators of environmental air pollution-induced cardiovascular toxicity.

Environmental air pollution exposure is a leading cause of death worldwide, and with increasing industrialization and urbanization, its disease burden is expected to rise even further. The majority of air pollution exposure-associated deaths are linked to cardiovascular disease (CVD). Although ample research demonstrates a strong correlation between air pollution exposure and CVD risk, the mechanisms by which inhalation of polluted air affects cardiovascular health are not completely understood. Inhalation of environmental air pollution has been associated with endothelial dysfunction, which suggests that air pollution exposure impacts CVD health by inducing endothelial injury. Interestingly, recent studies demonstrate that air pollution exposure affects the number and function of endothelial progenitor cells (EPCs), subpopulations of bone marrow-derived proangiogenic cells that have been shown to play an essential role in maintaining cardiovascular health. In line with their beneficial function, chronically low levels of circulating EPCs and EPC dysfunction (e.g., in diabetic patients) have been associated with vascular dysfunction, poor cardiovascular health, and increases in the severity of cardiovascular outcomes. In contrast, treatments that improve EPC number and function (e.g., exercise) have been found to attenuate cardiovascular dysfunction. Considering the critical, nonredundant role of EPCs in maintaining vascular health, air pollution exposure-induced impairments in EPC number and function could lead to endothelial dysfunction, consequently increasing the risk for CVD. This review article covers novel aspects and new mechanistic insights of the adverse effects of air pollution exposure on cardiovascular health associated with changes in EPC number and function.

Organic Components of Personal PM2.5 Exposure Associated with Inflammation: Evidence from an Untargeted Exposomic Approach.

Fine particulate matter (PM2.5) can promote chronic diseases through the fundamental mechanism of inflammation; however, systemic information is lacking on the inflammatory PM2.5 components. To decipher organic components from personal PM2.5 exposure that were associated with respiratory and circulatory inflammatory responses in older adults, we developed an exposomic approach using trace amounts of particles and applied it on 424 personal PM2.5 samples collected in a panel study in Beijing. Applying an integrated multivariate and univariate untargeted strategy, a total of 267 organic compounds were filtered and then chemically identified according to their association with exhaled nitric oxide (eNO)/interleukin (IL)-6 or serum IL-1ß/IL-6, with monocyclic and polycyclic aromatic compounds (i.e., MACs and PACs) as the representatives. Indoor-derived species with medium volatility including MACs were mainly associated with systemic inflammation, while low-volatile ambient components that originate from combustion sources, such as PACs, were mostly associated with airway inflammation. Following ambient component exposure, we found an inverted U-shaped relationship on change of eNO with insulin resistance, suggesting a higher risk of cardiopulmonary dysfunction for individuals with homeostatic model assessment for insulin resistance (HOMA-IR) levels > 2.3. Overall, this study provided a practical untargeted strategy for the systemic investigation of PM2.5 components and proposed source-specific inflammatory effects.

Effects of ambient air pollution on childhood asthma exacerbation in the Philadelphia metropolitan Region, 2011-2014.

Fine particulate matter (PM2.5) and ozone (O3) air pollutants are known risk factors for asthma exacerbation. We studied the association of these air pollutants with pediatric asthma exacerbation in the Philadelphia metropolitan region, and evaluated potential effect modification by children's characteristics (e.g., race/ethnicity, atopic conditions) and environmental factors (e.g., neighborhood tree canopy, meteorological factors, aeroallergens). We conducted a time-stratified case-crossover study of 54,632 pediatric (age ≤18 years) asthma exacerbation cases occurring from 2011 to 2014, identified through electronic health records (EHR) of the Children's Hospital of Philadelphia (CHOP) health system. We applied conditional logistic regression to estimate associations between air pollution and asthma exacerbation, using daily census-tract level pollutant concentrations estimated from the EPA Fused Air Quality Surface Using Downscaling (FAQSD) files. The associations were estimated within warm (Apr-Sep) and cold (Oct-Mar) months for unlagged exposure and for cumulative effects up to 5 days after exposure, with adjustment for temperature, relative humidity, and holidays. We found small increases in odds of asthma exacerbation with higher pollutant concentrations, with positive associations (OR, comparing concentrations of 75th to 25th percentile) observed for PM2.5 during both warm (1.03, 95% CI: 0.98-1.08) and cold months (1.05, 95% CI: 1.02-1.07), and for O3 during cold months (1.08, 95% CI: 1.02-1.14). The exposure-response relationship with PM2.5 during the cold months was essentially linear, whereas thresholds of effect were observed for the other associations at low-medium pollutant concentrations. Results were robust to multi-pollutant modeling and adjustment for additional covariates. We found no effect modification by most children's characteristics, while effect sizes were higher on days with detected tree and grass pollens during warm months. Our results suggest that even small decreases in pollutant concentrations could potentially reduce risk of childhood asthma exacerbation - an important finding, given the high burden of childhood asthma and known disparities in asthma control.

Suspended fine particulate matter (PM2.5), microplastics (MPs), and polycyclic aromatic hydrocarbons (PAHs) in air: Their possible relationships and health implications.

Exposure to fine particulate matter (PM2.5) and their associated microcontaminants have been linked to increased harmful effects on the human health. In this study, the possible relationships between PM2.5, microplastics (MPs), and polycyclic aromatic hydrocarbons (PAHs) were analyzed in an urban area of Bushehr port, in the northern part of the Persian Gulf. Presence, sources, and health risks of MPs and PAHs in both normal and dusty days were also investigated. The median of PM2.5 and Æ©PAHs were 52.8 µg/m3 and 14.1 ng/m3, respectively, indicating high pollution levels especially in dusty days. The mean level of MPs in urban suspended PM2.5 was 5.2 items/m3. Fragments were the most abundant shape of identified MPs and polyethylene terephthalate (PET) was the most plastic types in urban dust of Bushehr port. The results revealed that PM2.5 and MPs may possibly act as a carrier for airborne MPs and PAHs, respectively. In addition, the significant positive relationships between MPs, wind speed and wind direction, confirmed that the MPs transportation were highly controlled by atmospheric condition. Moreover, the source identification methods and trajectory analyses indicated that petrogenic sources from both proximal and distal origins play an important role in the level of PAHs. The results of chronic health risk evaluation via inhalation revealed that PM2.5-bound PAHs had high potential cancer risk in winter, while, the estimated risks for non-carcinogenic PAHs were not considerable. In the case of MPs, the assessment of human intake of MPs via inhalation highlighted the possible risks for habitants.