Associations of ultrafine and fine particles with childhood emergency room visits for respiratory diseases in a megacity.

BACKGROUND: Ambient fine particulate matter with aerodynamic diameter less than 2.5 µm (PM2.5) has been associated with deteriorated respiratory health, but evidence on particles in smaller sizes and childhood respiratory health has been limited. METHODS: We collected time-series data on daily respiratory emergency room visits (ERVs) among children under 14 years old in Beijing, China, during 2015-2017. Concurrently, size-fractioned number concentrations of particles in size ranges of 5-560 nm (PNC5-560) and mass concentrations of PM2.5, black carbon (BC) and nitrogen dioxide (NO2) were measured from a fixed-location monitoring station in the urban area of Beijing. Confounder-adjusted Poisson regression models were used to estimate excessive risks (ERs) of particle size fractions on childhood respiratory ERVs, and positive matrix factorisation models were applied to apportion the sources of PNC5-560. RESULTS: Among the 136 925 cases of all-respiratory ERVs, increased risks were associated with IQR increases in PNC25-100 (ER=5.4%, 95% CI 2.4% to 8.6%), PNC100-560 (4.9%, 95% CI 2.5% to 7.3%) and PM2.5 (1.3%, 95% CI 0.1% to 2.5%) at current and 1 prior days (lag0-1). Major sources of PNC5-560 were identified, including nucleation (36.5%), gasoline vehicle emissions (27.9%), diesel vehicle emissions (18.9%) and secondary aerosols (10.6%). Emissions from gasoline and diesel vehicles were found of significant associations with all-respiratory ERVs, with increased ERs of 6.0% (95% CI 2.5% to 9.7%) and 4.4% (95% CI 1.7% to 7.1%) at lag0-1 days, respectively. Exposures to other traffic-related pollutants (BC and NO2) were also associated with increased respiratory ERVs. CONCLUSION: Our findings suggest that exposures to higher levels of PNC5-560 from traffic emissions could be attributed to increased childhood respiratory morbidity, which supports traffic emission control priority in urban areas.

Combustion-Derived Particulate PAHs Associated with Small Airway Dysfunction in Elderly Patients with COPD.

Evidence of the respiratory effects of ambient organic aerosols (e.g., polycyclic aromatic hydrocarbons, PAHs) among patients with chronic diseases is limited. We aimed to assess whether exposure to ambient particle-bound PAHs could worsen small airway functions in patients with chronic obstructive pulmonary disease (COPD) and elucidate the underlying mechanisms involved. Forty-five COPD patients were recruited with four repeated visits in 2014-2015 in Beijing, China. Parameters of pulmonary function and pulmonary/systemic inflammation and oxidative stress were measured at each visit. Linear mixed-effect models were performed to evaluate the associations between PAHs and measurements. In this study, participants experienced an average PAH level of 61.7 ng/m3. Interquartile range increases in exposure to particulate PAHs at prior up to 7 days were associated with reduced small airway functions, namely, decreases of 17.7-35.5% in forced maximal mid-expiratory flow. Higher levels of particulate PAHs were also associated with heightened lung injury and inflammation and oxidative stress. Stronger overall effects were found for PAHs from traffic emissions and coal burning. Exposure to ambient particulate PAHs was capable of impairing small airway functions in elderly patients with COPD, potentially via inflammation and oxidative stress. These findings highlight the importance of control efforts on organic particulate matter from fossil fuel combustion emissions.

Extreme Levels of Air Pollution Associated With Changes in Biomarkers of Atherosclerotic Plaque Vulnerability and Thrombogenicity in Healthy Adults.

RATIONALE: The pathophysiologic mechanisms of air pollution-associated exacerbation of cardiovascular events remain incompletely understood. OBJECTIVE: To assess whether ambient air pollution can be a trigger of the vulnerable plaque and heightened thrombogenicity through systemic inflammatory pathways. METHODS AND RESULTS: In Beijing AIRCHD study (Air Pollution and Cardiovascular Dysfunctions in Healthy Adults Living in Beijing), 73 healthy adults (mean±SD, 23.3±5.4 years) were followed up in 2014 to 2016. We estimated associations between air pollutants and biomarkers relevant to atherosclerotic plaque vulnerability, thrombogenicity, and inflammation using linear mixed-effects models and elucidated the biological pathways involved using mediation analyses. Receiver operating characteristic analyses were conducted to assess the ability of each biomarker to predict ambient air pollution exposures. High average concentrations of particulate matter in diameter <2.5 µm (91.8±63.8 µg/m3) were observed during the study period. Significant increases in circulating biomarkers of plaque vulnerability, namely MMPs (matrix metalloproteinases; MMP-1, 2, 3, 7, 8, and 9), of 8.6% (95% CI, 0.1-17.8) to 141.4% (95% CI, 111.8-171.0) were associated with interquartile range increases in moving averages of particulate matter in diameter <2.5 µm, number concentrations of particles in sizes of 5 to 560 nm and black carbon, during the last 1 to 7 days before each participant's clinic visit. Higher air pollutant levels were also significantly associated with decreases in TIMP (tissue inhibitors of MMPs; TIMP-1 and 2), heightened thrombogenicity (shortened prothrombin time and increases in sCD40L [soluble CD40 ligand], sCD62P [soluble P-selectin], and fibrinogen/fibrin degradation products), and elevations in systemic inflammation (IL-1ß [interleukin-1ß], CRP [C-reactive protein], MIP-1α/ß [macrophage inflammatory protein-1α/ß], sRAGE [soluble receptor for advanced glycation end products], and IGFBP [insulin-like growth factor-binding protein]-1 and 3). Receiver operating characteristic curves showed that several biomarkers can serve as robust pollutant-specific predictors with high versus low black carbon exposure (area under the receiver operating characteristic curve of 0.974 [95% CI, 0.955-0.992] for MMP-8 and 0.962 [95% CI, 0.935-0.988] for sRAGE). Mediation analysis further showed that systemic inflammation can mediate ≤46% of the changes in MMPs and thrombogenicity associated with interquartile range increases in air pollutants. CONCLUSIONS: Our results suggest that air pollution may prompt cardiovascular events by triggering vulnerable plaque along with heightened thrombogenicity possibly through systemic inflammatory pathways.

Perturbation of amino acid metabolism mediates air pollution associated vascular dysfunction in healthy adults.

The molecular mechanisms of air pollution-associated adverse cardiovascular effects remain largely unknown. In the present study, we investigated the impacts of ambient air pollution on vascular function and the potential mediation effects of amino acids in a longitudinal follow-up of 73 healthy adults living in Beijing, China, between 2014 and 2016. We estimated associations between air pollutants and serum soluble intercellular adhesion molecule 1 (sICAM-1) and plasma levels of amino acids using linear mixed-effects models, and elucidated the biological pathways involved using mediation analyses. Higher air pollutant levels were significantly associated with increases in sICAM-1 levels. Metabolomics analysis showed that altered metabolites following short-term air pollution exposure were mainly involved in amino acid metabolism. Significant reductions in levels of plasma alanine, threonine and glutamic acid of 2.1 µM [95% confidence interval (CI): -3.8, -0.3] to 62.0 µM (95% CI: -76.1, -47.9) were associated with interquartile range increases in moving averages of PM2.5, BC, CO and SO2 in 1-7 days prior to clinical visits. Mediation analysis also showed that amino acids can mediate up to 48% of the changes in sICAM-1 associated with increased air pollution exposure. Our results indicated that air pollution may prompt vascular dysfunction through perturbing amino acid metabolism.

A review on reducing indoor particulate matter concentrations from personal-level air filtration intervention under real-world exposure situations.

Improving air quality in indoor environments where people live is of importance to protect human health. In this systematic review, we assessed the effectiveness of personal-level use of air filtration units in reducing indoor particulate matters (PM) concentrations under real-world situations following systematic review guidelines. A total of 54 articles were included in the review, in which 20 randomized controlled/crossover trials that reported the changes in indoor fine PM (PM2.5 ) concentrations were quantitatively assessed in meta-analysis. Standardized mean differences (SMDs) were calculated for changes in indoor PM concentrations following air filtration interventions. Moderate-to-large reductions of 11%-82% in indoor PM2.5  concentrations were observed with SMD of -1.19 (95% CI: -1.50, -0.88). The reductions in indoor PM concentrations varied by geographical locations, filtration technology employed, indoor environmental characteristics, and air pollution sources. Most studies were graded with low-to-moderate risk of bias; however, the overall certainty of evidence for indoor PM concentration reductions was graded at very low level. Considering the effectiveness of indoor air filtration under practical uses, socio-economic disparities across study populations, and costs of air filter replacement over time, our results highlight the importance of reducing air pollution exposure at the sources.

Ambient Air Pollution Is Associated With HDL (High-Density Lipoprotein) Dysfunction in Healthy Adults.

Objective- We aimed to assess whether exposure to higher levels of ambient air pollution impairs HDL (high-density lipoprotein) function and to elucidate the underlying biological mechanisms potentially involved. Approach and Results- In the Beijing AIRCHD study (Air Pollution and Cardiovascular Dysfunction in Healthy Adults), 73 healthy adults (23.3±5.4 years) were followed-up with 4 repeated study visits in 2014 to 2016. During each visit, ambient air pollution concentrations, HDL function metrics, and parameters of inflammation and oxidative stress were measured. Average daily concentrations of ambient particulate matter in diameter <2.5 µm were 62.9 µg/m3 (8.1-331.0 µg/m3). We observed significant decreases in HDL cholesterol efflux capacity of 2.3% (95% CI, -4.3 to -0.3) to 5.0% (95% CI, -7.6 to -2.4) associated with interquartile range increases in moving average concentrations of particulate matter in diameter <2.5 µm and traffic-related air pollutants (black carbon, nitrogen dioxide, and carbon monoxide) during the 1 to 7 days before each participant's clinic visit. Higher ambient air pollutant levels were also associated with significant reductions in circulating HDL cholesterol and apoA-I (apolipoprotein A-I), as well as elevations in HDL oxidation index, oxidized LDL (low-density lipoprotein), malondialdehyde, and high-sensitivity C-reactive protein. Conclusions- Higher ambient air pollution concentrations were associated with impairments in HDL functionality, potentially because of systemic inflammation and oxidative stress. These novel findings further our understanding of the mechanisms whereby air pollutants promote cardiometabolic disorders.

Ambient air pollution is associated with cardiac repolarization abnormalities in healthy adults.

BACKGROUND: Ambient air pollution has been associated with acute cardiovascular events; however, the underlying mechanisms remain incompletely understood. We aimed to examine the impacts of ambient air pollutants on cardiac ventricular repolarization in a highly polluted urban region. METHODS: Seventy-three healthy non-smoking young adults (66% female, mean age of 23.3 ±â€¯5.4 years) were followed with four repeated 24-h electrocardiogram recordings in 2014-2016 in Beijing, China. Continuous concentrations of ambient particulates in size fractions of 5-560 nm diameter, black carbon (BC), nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and ozone (O3) were measured at a fixed-location air pollution monitoring station. Generalized linear mixed models, with adjustment for individual risk factors, time-varying factors and meteorological parameters, were used to evaluate the effects of air pollution on 5-min segments of heart rate-corrected QT interval (QTc), an index of cardiac ventricular repolarization. RESULTS: During the study period, the mean levels of number concentrations of particulates in size range of 5-560 nm (PNC5-560) were 20,711 particles/cm3. Significant increases in QTc of 0.56% (95% CI: 0.27, 0.84) to 1.76% (95% CI: 0.73, 2.79) were associated with interquartile range increases in PNC50-560 at prior 1-5 moving average days. Significant increases in QTc were also associated with increases in exposures to traffic-related air pollutants (BC, NO2 and CO), a combustion pollutant SO2, and the secondary pollutant O3. The associations were stronger in participants who were male, overweight, with abdominal obesity, and with higher levels of high-sensitivity C-reactive protein. CONCLUSIONS: Our findings suggest that exposures to higher levels of ambient particulates in small size fractions and traffic pollutants were associated with cardiac repolarization abnormalities in healthy adults, and the cardio-metabolic risks may modify the adverse cardiac effects attributable to air pollution.

PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) in Beijing: Seasonal variations, sources, and risk assessment.

Polycyclic aromatic hydrocarbons (PAHs) have been of health concern due to its carcinogenesis and mutagenesis. In this study, we aimed to assess the variations, sources, and lifetime excessive cancer risk (ECR) attributable to PAHs bound to ambient particulate matters with aerodynamic diameter less than 2.5µm (PM2.5) in metropolitan Beijing, China. We collected 24-hour integrated PM2.5 samples on daily basis between November 2014 and June 2015 across both central heating (cold months) and non-heating (warm months) seasons, and further analyzed the PAH components in these daily PM2.5 samples. Our results showed that total concentrations of PM2.5-bound PAHs varied between (88.6±75.4)ng/m3 in the cold months and (11.0±5.9)ng/m3 in the warm months. Benzo[a]pyrene (BaP), the carcinogenic marker of PAHs, averaged at 5.7 and 0.4ng/m3 in the cold and warm months, respectively. Source apportionment analyses illustrated that gasoline, biomass burning, diesel, coal combustion and cooking were the major contributors, accounting for 12.9%, 17.8%, 24.7%, 24.3% and 6.4% of PM2.5-bound PAHs, respectively. The BaP equivalent lifetime ECR from inhalation of PM2.5-bound PAHs was 16.2 cases per million habitants. Our results suggested that ambient particulate reduction from energy reconstruction and adaption of clean fuels would result in reductions PM2.5-bound PAHs and its associated cancer risks. However, as only particulate phased PAHs was analyzed in the present study, the concentration of ambient PAHs could be underestimated.

A highly sensitive SPRi biosensing strategy for simultaneous detection of multiplex miRNAs based on strand displacement amplification and AuNP signal enhancement.

Herein, a dual channel surface plasmon resonance imaging (SPRi) biosensor has been developed for the simultaneous and highly sensitive detection of multiplex miRNAs based on strand displacement amplification (SDA) and DNA-functionalized AuNP signal enhancement. In the presence of target miRNAs (miR-21 or miR-192), the miRNAs could specifically hybridize with the corresponding hairpin probes (H) and initiate the SDA, resulting in massive triggers. Subsequently, the two parts of the released triggers could hybridize with capture probes (CP) and DNA-functionalized AuNPs, assembling DNA sandwiches with great mass on the chip surface. A significantly amplified SPR signal readout was achieved. This established biosensing method was capable of simultaneously detecting multiplex miRNAs with a limit of detection down to 0.15 pM for miR-21 and 0.22 pM for miR-192. This method exhibited good specificity and acceptable reproducibility. Moreover, the developed method was applied to the determination of target miRNAs in a complex matrix. Thus, this developed SPRi biosensing method may present a potential alternative tool for miRNA detection in biomedical research and clinical diagnosis.

Cardiovascular benefits of short-term indoor air filtration intervention in elderly living in Beijing: An extended analysis of BIAPSY study.

BACKGROUND: Adverse cardiovascular effects associated with air pollution exposure have been widely demonstrated. However, inconsistent cardiovascular responses were observed from reducing indoor air pollution exposure. We aimed to assess whether short-term air filtration intervention could benefit cardiovascular health in elderly living in high pollution area. METHODS: A randomized crossover intervention study of short-term indoor air filtration intervention on cardiovascular health was conducted among 35 non-smoking elderly participants living in Beijing in the winter of 2013, as part of Beijing Indoor Air Purifier StudY (BIAPSY). Portable air filtration units were randomly allocated to active filtration for 2 weeks and sham filtration for 2 weeks in the households. Twelve-hour daytime ambulatory heart rate variability (HRV) and blood pressure (ABP) were measured during active and sham filtration. Concurrently, real-time indoor and outdoor particulate matter with diameter less than 2.5 µm (PM2.5) and indoor black carbon (BC) concentrations were measured. We applied generalized additive mixed models to evaluate the associations of 1- to 10-h moving average (MA) exposures of indoor PM2.5 and BC with HRV and ABP indices, and to explore whether these associations could be modified by air filtration. RESULTS: We observed decreases of 34.8% in indoor PM2.5 and 35.3% in indoor BC concentrations during active filtration. Indoor PM2.5 and BC exposures were significantly associated with reduced HRV and increased ABP indices, and greater changes were observed during sham filtration. In specific, each 10 µg/m3 increase in indoor PM2.5 at MA8-h was associated with a significant reduction of 1.34% (95% CI: -2.42, -0.26) in SDNN during sham filtration, compared with a non-significant reduction of 0.81% (95% CI: -6.00, 4.68) during active filtration (Pinter< 0.001). Each 1 µg/m3 increase in indoor BC at MA8-h was associated with a significant increase of 2.41% (95% CI: 0.38, 4.47) in SBP during sham filtration, compared with a non-significant increase of -1.09% (95% CI: -4.06, 1.96) during active filtration (Pinter = 0.135). Nonlinear inverse exposure-response relationships of indoor air pollution exposures with predicted HRV and ABP indices also confirmed some cardiovascular benefits of short-term air filtration intervention. CONCLUSIONS: Our results suggested that short-term indoor air filtration intervention can be of some cardiovascular benefits in elderly living with high pollution episodes.

Are current Chinese national ambient air quality standards on 24-hour averages for particulate matter sufficient to protect public health?

With rapid economic development and urbanization in recent decades, China has experienced the worsening of ambient air quality. For better air quality management to protect human health, Chinese government revised national ambient air quality standards (NAAQS) for particulate matter (PM) in 2012 (GB3095-2012). To assess the effectiveness of current NAAQS for PM on public health in Chinese population, we conducted a meta-analysis on published studies examining the mortality risk of short-term exposure to PM with aerodynamic diameters less than 10 and 2.5µm (PM10 and PM2.5) in China. The reported 24-hour concentrations of PM10 and PM2.5 in studies ranged from 43.5 to 150.1µg/m3 and 37.5 to 176.7µg/m3. In the pooled excess, mortality risk estimates of short-term exposure to PM. In specific, per 10µg/m3 increase in PM10, we observed increases of 0.40% (95%CI: 0.33%, 0.47%), 0.57% (95%CI: 0.44%, 0.70%) and 0.49% (95%CI: 0.40%, 0.58%) in total, respiratory and cardiovascular mortality, per 10µg/m3 increase in PM2.5, we observed increases of 0.51% (95%CI: 0.38%, 0.63%), 0.62% (95%CI: 0.52%, 0.73%) and 0.75% (95%CI: 0.54%, 0.95%) in total, respiratory and cardiovascular mortality. Finally, we derived 125µg/m3 for PM10 and 62.5µg/m3 for PM2.5 as 24-hour recommendation values based on the pooled estimates. Our results indicated that current Chinese NAAQS for PM could be sufficient in mitigating the excess mortality risk from short-term exposure to ambient PM. However, future research on long-term exposure cohort studies in Chinese population is also essential in revising annual averages for PM in Chinese NAAQS.

Comprehensive analysis of serum metabolites in gestational diabetes mellitus by UPLC/Q-TOF-MS.

Gestational diabetes mellitus (GDM) refers to the first sign or onset of diabetes mellitus during pregnancy rather than progestation. In recent decades, more and more research has focused on the etiology and pathogenesis of GDM in order to further understand GDM progress and recovery. Using an advanced metabolomics platform based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS), we explored the changes in serum metabolites between women with GDM and healthy controls during and after pregnancy. Some significant differences were discovered using multivariate analysis including partial least-squares discriminant analysis (PLS-DA) and orthogonal PLS-DA (OPLS-DA). The dysregulated metabolites were further compared and verified in several databases to understand how these compounds might function as potential biomarkers. Analyses of the metabolic pathways associated with these potential biomarkers were subsequently explored. A total of 35 metabolites were identified, contributing to GDM progress to some extent. The identified biomarkers were involved in some important metabolic pathways including glycine, serine, and threonine metabolism; steroid hormone biosynthesis; tyrosine metabolism; glycerophospholipid metabolism; and fatty acid metabolism. The above mentioned metabolic pathways mainly participate in three major metabolic cycles in humans, including lipid metabolism, carbohydrate metabolism, and amino acid metabolism. In this pilot study, the valuable comprehensive analysis gave us further insight into the etiology and pathophysiology of GDM, which might benefit the feasibility of a rapid, accurate diagnosis and reasonable treatment as soon as possible but also prevent GDM and its related short- and long-term complications.

Association of CTLA4 gene polymorphism (rs5742909) with cervical cancer: a meta-analysis.

Previous studies suggested that CTLA4 polymorphism (rs5742909) is associated with susceptibility to cervical cancer. In the present study, we performed a meta-analysis to systematically summarize the possible association between rs5742909 and the risk for cervical cancer. We conducted a search of case­control studies on the associations of rs5742909 with susceptibility to cervical cancer in PubMed, EMBASE, ISI Web of Science, Cochrane Central Register of Controlled Trials, Wanfang database in China, and Chinese National Knowledge Infrastructure databases. We extracted the data from eligible studies for meta-analysis. The association of cervical cancer risk with rs5742909 was estimated by pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs). There were four studies on rs5742909 and cervical cancer in our meta-analysis. Our results suggested that both T allele frequency (OR = 1.63, 95 % CI 1.06-2.50; P = 0.03) and (TT + CT) genotype distribution (OR = 1.72, 95 % CI 1.07-2.77; P = 0.03) of the rs5742909 were associated with risk for cervical cancer. This meta-analysis suggests that rs5742909 is associated with the risk of cervical cancer. Well-designed studies with larger sample size and more ethnic groups are required to further validate the results.

Toward cleaner air and better health: Current state, challenges, and priorities.

The most up-to-date estimate of the global burden of disease indicates that ambient air pollution, including fine particulate matter and ozone, contributes to an estimated 5.2 million deaths each year. In this review, we highlight the challenges in estimating population exposure to air pollution and attributable health risks, particularly in low- and middle-income countries and among vulnerable populations. To protect public health, the evidence so far confirms urgent needs to prioritize interdisciplinary research on air pollution exposure and risk assessment and to develop evidence-based intervention policies and risk communication strategies. Here, we synthesize the emerging evidence supporting the monitoring and evaluation of the progress in implementation of the Global Air Quality Guidelines prepared by the World Health Organization.

Maternal preconceptional and prenatal exposure to El Niño Southern Oscillation levels and child mortality: a multi-country study.

El Niño Southern Oscillation (ENSO) has been shown to relate to the epidemiology of childhood infectious diseases, but evidence for whether they increase child deaths is limited. Here, we investigate the impact of mothers' ENSO exposure during and prior to delivery on child mortality by constructing a retrospective cohort study in 38 low- and middle-income countries. We find that high levels of ENSO indices cumulated over 0-12 lagged months before delivery are associated with significant increases in risks of under-five mortality; with the hazard ratio ranging from 1.33 (95% confidence interval [CI], 1.26, 1.40) to 1.89 (95% CI, 1.78, 2.00). Child mortality risks are particularly related to maternal exposure to El Niño-like conditions in the 0th-1st and 6th-12th lagged months. The El Niño effects are larger in rural populations and those with unsafe sources of drinking water and less education. Thus, preventive interventions are particularly warranted for the socio-economically disadvantaged.

Nonlinear impacts of climate anomalies on oil palm productivity.

Oil palm contributes to various global needs as one of the most productive oil crops, but there exist ongoing concerns regarding its yield reductions and associated environmental impacts resulting from land conversion. This is the first detailed report investigating the nonlinear threats to estate-level oil palm yields posed by El Niño Southern Oscillation (ENSO) in the equatorial Pacific Ocean, a major driver of climate variability. Using the Malaysian Palm Oil Board administrative records on monthly performances reported by oil palm estates through the e-submissions portal spanning from January 2015 to June 2023, we focused on elucidating the impacts of ENSO on fresh fruit bunch yield, oil extraction rate, and oil yield. We found that both El Niño and La Niña conditions, characterized by extreme levels of ENSO indices cumulated over lags of 0-23 months prior to harvest, were associated with statistically significant reductions in yields. Lag association patterns unveiled that production risks were linked to pre-harvest exposure to extreme ENSO indices in various time windows. Subgroup analyses further revealed that the effects were pronounced in labor-intensive estates and those lacking fertilizer investments. This study underscores the necessity for adaptation strategies in response to future climate anomalies.

Low-level ambient ozone exposure associated with neutrophil extracellular traps and pro-atherothrombotic biomarkers in healthy adults.

BACKGROUND AND AIMS: Uncertainty of the causality determinations for ambient ozone (O3) on cardiovascular events is heightened by the limited understanding of the mechanisms involved in humans. We aimed to examine the pro-atherothrombotic impacts of O3 exposure and to explore the potential mediating roles of dysfunctional neutrophils, focusing on neutrophil extracellular traps (NETs). METHODS: A longitudinal panel study of 152 healthy adults was conducted in the cool to cold months with relatively low levels of O3 between September 2019 and January 2020 in Beijing, China. Four repeated measurements of indicators reflecting atherothrombotic balance and NETs were performed for each participant. RESULTS: Daily average exposure levels of ambient O3 were 16.6 µg/m3 throughout the study period. Per interquartile range increase in average concentrations of O3 exposure at prior up to 7 days, we observed elevations of 200.1-276.3% in D-dimer, 27.2-36.8% in thrombin-antithrombin complex, 10.8-60.3% in plasminogen activator inhibitor 1, 13.9-21.8% in soluble P-selectin, 16.5-45.1% in matrix metalloproteinase-8, and 2.4-12.4% in lipoprotein-associated phospholipase A2. These pro-atherothrombotic changes were accompanied by endothelial activation, lung injury, and immune inflammation. O3 exposure was also positively associated with circulating NETs indicators, including citrullinated histone H3, neutrophil elastase, myeloperoxidase, and double-stranded DNA. Mediation analyses indicated that NETs could mediate O3-associated pro-atherothrombotic responses. The observational associations remained significant and robust after controlling for other pollutants, and were generally greater in participants with low levels of physical activity. CONCLUSIONS: Ambient O3 exposure was associated with significant increases in NETs and pro-atherothrombotic potential, even at exposure levels well below current air quality guidelines of the World Health Organization.

Short-Term Effects of Primary and Secondary Particulate Matter on Ceramide Metabolism, Pro-Inflammatory Response, and Blood Coagulation.

Evidence of the precise biological pathway responsible for acute cardiovascular events triggered by particulate matter (PM) exposure from anthropogenic emissions is sparse. We investigated the associations of biomarkers relevant to the pathophysiology of atherothrombosis (ceramide metabolism, pro-inflammatory response, and blood coagulation) with primary and secondary components in particulate matter with aerodynamic diameters less than 2.5 µm (PM2.5). A total of 152 healthy participants were followed with four repeated clinical visits between September 2019 and January 2020 in Beijing. Exposure to ambient inorganic aerosols (sulfate, nitrate, ammonium, and chloride), as well as organic aerosols (OA) in PM2.5, was measured by a real-time aerosol chemical speciation monitor, and sources of OA were performed by positive matrix factorization. We found significant increases of 101.9-397.9% in ceramide indicators associated with interquartile-range increases in inorganic aerosols and OA prior to 72 h of exposure. Higher levels of organic and inorganic aerosols in PM2.5 were associated with increases of 3.1-6.0% in normal T cells regulated upon activation and expressed and secreted relevant to the pro-inflammatory response; increases of 276.9-541.5% were observed in D-dimers relevant to coagulation. Detrimental effects were further observed following OA exposure from fossil fuel combustion. Mediation analyses indicated that ceramide metabolism could mediate the associations of PM2.5 components with pro-inflammatory responses. Our findings expand upon the current understanding of potential pathophysiological pathways of cardiovascular events posed by ambient particulates and highlight the importance of reducing primary and secondary PM from anthropogenic combustions.

Association between short-term air pollution exposure and perturbation in thyrotropin levels in 1.38 million Chinese women: A national longitudinal analysis, 2014-2019.

Prevalence of subclinical hypothyroidism substantially increased during the last decade in China, which has been commonly/clinically diagnosed as elevation in thyrotropin (thyroid-stimulating hormone [TSH]). Tobacco smoke containing toxic substances has been linked to thyroid dysfunction; however, data on perturbation of TSH following air pollution exposure in human has not been assessed at nationwide population level. We investigated the longitudinal impact of daily ambient air pollution estimated at residential level on serum TSH in 1.38 million women from China's 29 mainland provinces between 2014 and 2019. We observed that particulate matter with aerodynamic diameter ≤ 10 and ≤ 2.5 µm (PM10, PM2.5) and nitrogen dioxide (NO2) at cumulative lag 0-7 days of exposure were associated with percent elevations in TSH (0.88% [95% CI: 0.71, 1.05] per [interquartile range, IQR: 54.8 µg/m3] of PM10; 0.89% [95% CI, 0.71, 1.07] per IQR [40.3 µg/m3] of PM2.5; 2.01% [95% CI: 1.81, 2.22] per IQR [27.4 µg/m3] of NO2). Greater associations were observed in participants living in areas with ≥adequate iodine intake and those with low BMI levels and high inflammation status. Our results suggest that increased concentrations of recent ambient air pollutants at exposure ranges commonly encountered in Asia were associated with increases in TSH, supporting disturbing role of short-term air pollution exposure on the regulation of thyroid hormone homeostasis.

SIRT5 desuccinylates and activates SOD1 to eliminate ROS.

Cu/Zn superoxide dismutase (SOD1) is a key antioxidant enzyme. Deficiency of SOD1 is associated with various human diseases, including cancer. Here, we report that SOD1 is succinylated and that succinylation decreases its activity. SIRT5 binds to, desuccinylates and activates SOD1. SOD1-mediated ROS reduction is increased when SIRT5 is co-expressed. Furthermore, mutation of the SOD1 succinylation site inhibits the growth of lung tumor cells. These results reveal a novel post-translational regulation of SOD1 by means of succinylation and SIRT5-dependent desuccinylation, which is important for the growth of lung tumor cells.