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.

Association of fine particulate matter and residential green space with rheumatoid arthritis.

BACKGROUND: Fine particulate matter (PM2.5) is a recognized risk factor for respiratory and cardiovascular diseases, but the association between PM2.5 and rheumatoid arthritis (RA) is still controversial. Additionally, evidence on the relationship of green space with RA is scarce. This study aimed to investigate the separate and combined associations of PM2.5 and green space with risk of RA. METHODS: Our study involved 30,684 participants from the Yinzhou cohort in Ningbo, China. PM2.5 concentrations were determined using a land-use regression model. Residential green space was assessed using the Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) from satellite images. We employed the Cox proportional hazard model to evaluate the relationships of PM2.5 and green space with RA. RESULTS: During the 176,894 person-years of follow-up period, 354 cases of RA were identified. Hazard ratio (HR) and the corresponding 95% confidence interval (95% CI) for every interquartile range (IQR) increase in PM2.5 were 1.23 (95% CI: 1.02, 1.49). Compared with lower exposure to residential green space, individuals living in areas with more green space had a decreased risk of RA (HR was 0.80 (95% CI: 0.70, 0.92), 0.80 (95% CI: 0.70, 0.92), and 0.79 (95% CI: 0.70, 0.89) for 250m, 500m, and 1000m NDVI buffers, respectively). Similar results were observed for the association between EVI and RA. Furthermore, a significant multiplicative interaction was observed between PM2.5 and green space (NDVI 250m and EVI 250m). No mediating effect of PM2.5 on the relationship between green space and RA was observed. CONCLUSION: Our findings indicated that living in areas with higher green space was linked to a reduced risk of RA, whereas living in areas with higher PM2.5 was associated with an increased risk of RA. The beneficial effect of high green space may be offset by exposure to PM2.5.

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.

An investigation of inequalities in exposure to PM2.5 air pollution across small areas in Ireland.

The link between exposure to air pollution and adverse effects on human health is well documented. Yet, in a European context, research on the spatial distribution of air pollution and the characteristics of areas is relatively scarce, and there is a need for research using different spatial scales, a wider variety of socioeconomic indicators (such as ethnicity) and new methodologies to assess these relationships. This study uses comprehensive data on a wide range of demographic and socioeconomic indicators, matched to data on PM2.5 concentrations for small areas in Ireland, to assess the relationship between social vulnerability and PM2.5 air pollution. Examining a wide range of socioeconomic indicators revealed some differentials in PM2.5 concentration levels by measure and by rural and urban classification. However, statistical modelling using concentration curves and concentration indices did not present substantial evidence of inequalities in PM2.5 concentrations across small areas. In common with other western European countries, an overall decline in the levels of PM2.5 between 2011 and 2016 was observed in Ireland, though the data indicates that almost all small areas in Ireland were found to have exceeded the World Health Organization (WHO)'s PM2.5 annual guideline (of 5 µg/m3), calling for greater policy efforts to reduce air pollution in Ireland. The recent Clean Air Strategy contains a commitment to achieve the WHO guideline limits for PM2.5 by 2040, with interim targets at various points over the next two decades. Achieving these targets will require policy measures to decarbonise home heating, promote active travel and the transition to electric vehicles, and further regulations on burning fossil fuels and enforcing environmental regulations more tightly. From a research and information-gathering perspective, installing more monitoring stations at key points could improve the quality and spatial dimension of the data collected and facilitate the assessment of the implementation of the measures in the Clean Air Strategy.

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.

Hidden health effects and economic burden of stroke and coronary heart disease attributed to ambient air pollution (PM2.5) in Tehran, Iran: Evidence from an assessment and forecast up to 2030.

Air pollution is one of the main causes of global disease burden, especially in low-income and middle-income countries. Estimation of the current situation and prediction of the future health effects of death and incidence of stroke and coronary heart disease (CHD) attributed to PM2.5 were done using BenMAP-CE software. Estimating and forecasting the economic burden of these diseases were done in 4 scenarios: Stability of the current PM2.5 concentration, annual 10 % reduction of PM2.5 concentration, reduction to 5 µg/m3, and reduction to 12 µg/m3, with three approaches for calculating the economic burden in mortality costs, including the human capital(HC), years of life lost(YLL) and value of statistical life(VSL) was performed. With the stability of the PM2.5 concentration, the economic burden of stroke attributed to PM2.5 with the approach of calculating the cost of death with the HC, the YLL, and VSL will reach from 64, 82 and 172 million USD in 2020-849, 1120 and 2703 million USD in 2030 and these costs for CHD in the mentioned approaches of calculating the cost of death will reach respectively from 499, 568 and 898 million USD in 2020-7096, 8088, and 13,621 million USD in 2030. We find that the morbidity economic burden (including direct, indirect, and intangible costs) of stroke compared to the cost of death with the HC, and YLL approaches are 67.58 times, 3.15 times respectively, and in the VSL approach is 47.32 % of stroke death cost. Also, the costs of CHD morbidity economic burden compared to the cost of death in the method of calculating the cost of death with the HC, YLL, and VSL approaches are 42.09, 7.25, and 1.16 times, respectively. This study provides comprehensive baseline information for health policymakers to understand the benefits of air pollution control policies globally, especially in LMICs.

A longitudinal study on the effect of PM2.5 components on blood pressure in the hypertensive patients from 2011 to 2019.

Extensive research has established the link between PM2.5 exposure and blood pressure (BP) levels among normal individuals. However, the association between PM2.5 components and BP levels in hypertensive patients has not been fully explored. In this study, 12 971 hypertensive cases from Jinchang cohort (in Jinchang City, China) with nearly 9 years of follow-up were enrolled. Based on the linear mixed-effect model, the effects of fine particulate matter (PM2.5) and five major components [sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), black carbon (BC) and organic matter (OM)]on BP [systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP)]were evaluated by single-component model, component-joint model and component-residual model, respectively. A positive correlation was found between PM2.5 as well as its components (SO42-, NO3-, NH4+, BC and OM) exposure and BP levels. The effects of SO42-, BC and OM on BP were observed to be the most robust among the three models. Based on the results of interaction effects and stratified analysis, the effect of BC exposure on SBP, and the effect of PM2.5 and its five components on PP were greater in female than in males. Compared with elderly hypertensive patients, OM had more significant effects on SBP, DBP and MAP in young and (or) middle-aged hypertensive patients. During the heating season, the effect of PM2.5 and its components on BP was grater compared to the non-heating season. Meanwhile, PM2.5 and its components have a greater influence on BP in patients with hypertension combined with diabetes. Therefore, the findings suggested that both PM2.5 exposure and its components had a significant effect on BP in patients with hypertension. Women and young and middle-aged hypertensive patient were the sensitive population. The implementation of source control and reduction of PM2.5 emission (mainly for SO42-, BC and OM) may be of great significance to control BP level and could reduce the risk of cardiovascular disease in patients with hypertension.

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.

Satellite or ground-based measurements for air pollutants (PM2.5, PM10, SO2, NO2, O3) data and their health hazards: which is most accurate and why?

Air pollution is growing at alarming rates on regional and global levels, with significant consequences for human health, ecosystems, and change in climatic conditions. The present 12 weeks (4 October 2021, to 26 December 2021) study revealed the different ambient air quality parameters, i.e., PM2.5, PM10, SO2, NO2, and O3 over four different sampling stations of Delhi-NCR region (Dwarka, Knowledge park III, Sector 125, and Vivek Vihar), India, by using satellite remote sensing data (MERRA-2, OMI, and Aura Satellite) and different ground-based instruments. The ground-based observation revealed the mean concentration of PM2.5 in Dwarka, Knowledge park III, Sector 125, and Vivek Vihar as 279 µg m-3, 274 µg m-3, 294 µg m-3, and 365 µg m-3, respectively. The ground-based instrumental concentration of PM2.5 was greater than that of satellite observations, while as for SO2 and NO2, the mean concentration of satellite-based monitoring was higher as compared to other contaminants. Negative and positive correlations were observed among particulate matter, trace gases, and various meteorological parameters. The wind direction proved to be one of the prominent parameter to alter the variation of these pollutants. The current study provides a perception into an observable behavior of particulate matter, trace gases, their variation with meteorological parameters, their health hazards, and the gap between the measurements of satellite remote sensing and ground-based measurements.

Exposure to ambient fine particulate matter components during pregnancy and early childhood and its association with asthma, allergies, and sensitization in school-age children.

BACKGROUND: Exposure to fine particulate matter (PM2.5) has been associated with allergic diseases, including asthma. However, information about the effects of specific PM2.5 components is limited. This study aimed to investigate the relationship of exposure to chemical components of PM2.5 during pregnancy and early childhood with the development of asthma, allergies, and sensitization in school-age children. METHODS: This study included 2,408 children in the second grade of elementary school. Questionnaire surveys of respiratory/allergic symptoms and measurements of serum total IgE and specific IgE levels to house dust mite (HDM) and animal proteins were conducted. Exposures to ambient PM2.5 mass, sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), elemental carbon (EC), and organic carbon (OC) of PM2.5 in participants' residences from conception to age six were estimated using predictive models. Multiple logistic regression analysis was used to analyze the association of respiratory/allergic symptoms and allergen sensitization with estimated exposure concentrations, after adjustment for survey year, sex, season of birth, feeding method during infancy, presence of siblings, history of lower respiratory tract infection, use of childcare facilities, passive smoking, presence of pets, mother's age, history of allergic diseases, smoking during pregnancy, and annual household income. RESULTS: No significant association was found between PM2.5 and its component concentrations and asthma. However, wheezing significantly increased with mean NO3- concentrations during pregnancy (odds ratio of 1.64 [95% confidence interval: 1.10, 2.47] for an interquartile range increase). Significant associations were also found between EC in the second trimester of pregnancy and PM2.5, NO3-, EC, and OC concentrations in early childhood. Higher PM2.5, SO4-, and NH4+ concentrations during the second trimester increased the risk of rhinitis. Sensitizations to HDM and animal proteins were significantly associated with exposure to components such as SO42- and NH4+ during pregnancy but not with postnatal exposure. CONCLUSIONS: Exposures to NO3-, EC, and OC during pregnancy and early childhood were associated with wheezing. SO42- and NH4+ exposures during pregnancy were associated with sensitization to HDM and animal proteins. Asthma was not associated with exposure to PM2.5 and its main components at any period.

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.

Short-term exposure to ambient fine particulate pollution aggravates ventilator-associated pneumonia in pediatric intensive care patients undergoing cardiovascular surgeries.

BACKGROUND: Ambient air pollutants can be hazardous to human health, especially for vulnerable children. The impact of ambient air pollutant exposure before and during intensive care unit (ICU) stays on the development of ventilator-associated pneumonia (VAP) in critically ill children has not been established. We aimed to determine the correlations between short-term exposures to ambient fine particulate matter (PM2.5) and VAP in pediatric cardiac surgery patients in the ICU, and explore the effect of delayed exposure. METHODS: The medical record of 1755 child patients requiring artificial ventilation in the ICU between December 2013 to December 2020, were analyzed. The daily average concentrations of particulate matters (PM2.5 and PM10), sulfur dioxide (SO2), and ozone (O3) were calculated from public data. Interactions between these pollutants and VAP were simulated with the distributed lag non-linear model. RESULTS: Three hundred forty-eight cases (19.829%) of VAP were identified in this study, while the average concentrations of PM2.5, PM10, O3 and SO2 were 58, 118, 98 and 26 µg/m3, respectively. Exposure to increased levels of PM2.5 two days prior (lag 2-day) to VAP diagnosis is significantly correlated with an enhanced risk for VAP development. Even a slight increase of 10 µg/m3 in PM2.5 can translate to a 5.4% increase in VAP incidence (95% CI: 1.4%-9.5%) while the VAP incidence increased to 11.1% (95%CI: 4.5-19.5%) when PM2.5 concentration is well below the National Ambient Air Quality standard (NAAQS) of 50 µg/m3. The association was more pronounced in those aged below 3-months, with low body mass index or suffered from pulmonary arterial hypertension. CONCLUSION: Short-term PM2.5 exposure is a significant risk for development of VAP in pediatric patients. This risk is present even with PM2.5 levels below the NAAQS. Ambient PM2.5 may represent a previously unrecognized risk factor for pneumonia and the current environmental pollution standards need to be reevaluated to consider susceptible populations. TRIAL REGISTRATION: The trial was registered with the National Clinical Trial Center: The correlation between ambient air pollution and the complications in ICU underwent cardiac surgery. TRIAL REGISTRATION NUMBER: ChiCTR2000030507. Date of registration: March 5, 2020. URL of trial registry record: http://www.chictr.org.cn/index.aspx .

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.

PM2.5-Attributable Mortality Burden Variability in the Continental U.S.

Epidemiologic studies have consistently observed associations between fine particulate matter (PM2.5) exposure and premature mortality. These studies use air quality concentration information from a combination of sources to estimate pollutant exposures and then assess how mortality varies as a result of differing exposures. Health impact assessments then typically use a single log-linear hazard ratio (HR) per health outcome to estimate counts of avoided human health effects resulting from air quality improvements. This paper estimates the total PM2.5-attributable premature mortality burden using a variety of methods for estimating exposures and quantifying PM2.5-attributable deaths in 2011 and 2028. We use: 1) several exposure models that apply a wide range of methods, and 2) a variety of HRs from the epidemiologic literature that relate long-term PM2.5 exposures to mortality among the U.S. population. We then further evaluate the variability of aggregated national premature mortality estimates to stratification by race and/or ethnicity or exposure level (e.g., below the current annual PM2.5 National Ambient Air Quality Standards). We find that unstratified annual adult mortality burden incidence estimates vary more (e.g., ~3-fold) by HR than by exposure model (e.g., <10%). In addition, future mortality burden estimates stratified by race/ethnicity are larger than the unstratified estimates of the entire population, and studies that stratify PM2.5-attributable mortality HRs by an exposure concentration threshold led to substantially higher estimates. These results are intended to provide transparency regarding the sensitivity of mortality estimates to upstream input choices.

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.