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Pollution caused by polyethylene microplastics (MP) has been reported for aquatic environments worldwide. However, despite recurrent research for several aquatic organisms, the effects of MP on the emergence stage of freshwater insects from tropical environments are little known. This study is the first to assess the emergence of the Brazilian native species Chironomus sancticaroli Strixino & Strixino, 1981 when exposed to primary polyethylene microplastics (size 40–48 µm). We performed two exposure scenarios, with a substrate (standard assays) and without substrate (as a stressful experience), and recorded emergence responses. The MP did not affect the species' emergence rate, but these rates were statistically different for the standard and stressful exposure scenarios. In bioassays without substrate, the high concentrations of MP caused anticipation of the insect's emergence (5–6 days). On the other hand, female emergence time was longer than males in standard bioassays. The substrate absence caused a slight increase in the left female wing's length and the potential female fecundity. These findings suggest that the polyethylene microplastics and substrate availability can affect the emergence dynamics of the tropical insect C. sancticaroli. [ABSTRACT FROM AUTHOR]

Our concerns have been raised about whether prolonged exposure to ammunition-related chemicals could correlate with genomic instability predisposing to lung carcinogenesis. The group of professional soldiers engaged in routine ammunition analysis and its explosive properties testing. To assess the presence of an innate genetic profile, DNA isolated from swabs was analyzed with LungCarta and HS Lung Panels and MassARRAY Analyzer 4 mass spectrometry. The presence of new somatic single nucleotide polymorphisms (SNPs) was detected with liquid biopsy technique and circulating cell-free DNA (ccfDNA) isolation, which was further analyzed with UltraSeek Lung Panel. Both genetic profiles obtained for each individual were compared. Genetic analysis revealed that in professional soldiers with long-term exposure to ammunition-related toxic chemicals, new SNPs in genes related to lung carcinogenesis are present. The preliminary data indicate that using modern molecular techniques could be a valuable tool for monitoring the genome instability in context of occupational risk of harmful volatile toxic compounds and improving personnel safety. The analyzed group will be further enlarged, and follow-up studies will be continued. [ABSTRACT FROM AUTHOR]

Human biomonitoring provides a scientific approach that systematically reveals exposure to phthalates through all possible routes. In this pilot study, fingernail was chosen as a non-destructive biospecimen to assess human exposure to nine phthalates. Concentrations of total phthalates ranged from 17.8 to 176 µg/g (median: 65.4 µg/g). Di(2-ethylhexyl) phthalate, dibutyl phthalate (DBP), and di-isobutyl phthalate were the major compounds found in fingernails, accounting for 64.3%, 19.4%, and 12.9% of the total phthalates, respectively. No significant difference in phthalates concentrations was found among genders and age-related distribution (p > 0.05). The concentration of DBP was positively correlated with participant's body mass index (r = 0.83). Our results suggested that fingernail can be used as a non-invasive biospecimen for the biomonitoring of human exposure to phthalates. Further studies are needed to investigate the relationship between phthalates or their metabolites in fingernail and other biological samples, such as urine and blood. [ABSTRACT FROM AUTHOR]

Since air pollution compromise the respiratory system and COVID-19 disease is caused by a respiratory virus, it is expected that air pollution plays an important role in the current COVID-19 pandemic. Exploratory studies have observed positive associations between air pollution and COVID-19 cases, deaths, fatality, and mortality rate. However, no study focused on Brazil, one of the most affected countries by the pandemic. Thus, this study aimed to understand how long-term exposure to PM10, PM2.5, and NO2 contributed to COVID-19 fatality and mortality rates in São Paulo state in 2020. Air quality data between 2015 and 2019 in 64 monitoring stations within 36 municipalities were considered. The COVID-19 fatality was calculated considering cases and deaths from the government’s official data and the mortality rate was calculated considering the 2020 population. Linear regression models were well-fitted for PM2.5 concentration and fatality (R2 = 0.416; p = 0.003), NO2 concentration and fatality (R2 = 0.232; p = 0.005), and NO2 concentration and mortality (R2 = 0.273; p = 0.002). This study corroborates other authors’ findings and enriches the discussion for having considered a longer time series to represent long-term exposure to the pollutants and for having considered one of the regions with the highest incidence of COVID-19 in the world. Thus, it reinforces measures to reduce the concentration of air pollutants which are essential for public health and will increase the chance to survive in future respiratory disease epidemics. [ABSTRACT FROM AUTHOR]

Abstract Background Exposure to particulate matter air pollution has been associated with cardiovascular disease (CVD) morbidity and mortality; however, most studies have focused on fine particulate matter (PM2.5) exposure and CVD. Coarse particulate matter (PM10–2.5) exposure has not been extensively studied, particularly for long-term exposure, and the biological mechanisms remain uncertain. Methods We examined the association between ambient concentrations of PM10–2.5 and inflammatory and hemostatic makers that have been linked to CVD. Annual questionnaire and clinical data were obtained from 1694 women (≥ 55 years old in 1999) enrolled in the longitudinal Study of Women’s Health Across the Nation (SWAN) at six study sites from 1999 to 2004. Residential locations and the USEPA air monitoring network measurements were used to assign exposure to one-year PM10–2.5, as well as co-pollutants. Linear mixed-effects regression models were used to describe the association between PM10–2.5 exposure and markers, including demographic, health and other covariates. Results Each interquartile (4 μg/m3) increase in one-year PM10–2.5 exposure was associated with a 5.5% (95% confidence interval [CI]: 1.8, 9.4%) increase in levels of plasminogen activator inhibitor-1 (PAI-1) and 4.1% (95% CI: − 0.1, 8.6%) increase in high-sensitivity C-creative Protein (hs-CRP). Stratified analyses suggested that the association with PAI-1 was particularly strong in some subgroups, including women who were peri-menopausal, were less educated, had a body mass index lower than 25, and reported low alcohol consumption. The association between PM10–2.5 and PAI-1 remained unchanged with adjustment for PM2.5, ozone, nitrogen dioxide, and carbon monoxide. Conclusions Long-term PM10–2.5 exposure may be associated with changes in coagulation independently from PM2.5, and thus, contribute to CVD risk in midlife women.

Abstract Background While many studies reported the association between long-term exposure to particulate matter air pollution (PM) and cardiovascular disease (CVD), few studies focused on incidence with relatively high-dose exposure using a nationwide cohort. This study aimed to investigate the association between long-term exposure to PM10 and PM2.5 and incidence of CVD in a nationwide and population-based cohort in South Korea where the annual average concentration of PM2.5 is above 20 μg/m3. Methods We selected 196,167 adults in the National Health Insurance Service-National Sample Cohort (NHIS-NSC) constructed based on the entire South Korean population. Incidence of four CVD subtypes including ischemic heart disease (IHD), myocardial infarction, heart failure, and stroke, and total CVD including all four was identified as the first diagnosis for 2007–2015. To assess individual exposures, we used annually-updated district-level residential addresses and district-specific PM concentrations predicted by a previously developed universal kriging prediction model. We computed individual-level long-term PM concentrations for four exposure windows: previous 1, 3, and 5 year(s) and 5 years before baseline. We applied time-dependent Cox proportional hazards models to estimate hazard ratios (HRs) of incident CVDs per 10 μg/m3 increase in PM10 and PM2.5 after adjusting for individual- and area-level characteristics. Results During 1,578,846 person-year, there were 33,580 cases of total incident CVD. Average PM10 and PM2.5 concentrations for the previous 5 years were 52.3 and 28.1 μg/m3, respectively. A 10 μg/m3 increase in PM2.5 exposed for the previous 5 years was associated with 4 and 10% increases in the incidence of total CVD (95% confidence interval: 0–9%) and IHD (4–16%), respectively. HRs tended to be higher with earlier exposure for IHD and more recent exposure for stroke. The estimated shape of the concentration-response relationship showed non-linear patterns. We did not find evidence of the association for PM10. Conclusions Using a population-based nationwide cohort exposed to relatively high PM concentration, this study confirmed the association between PM2.5 and CVD incidence that was reported in previous studies mostly with low-dose environments. The magnitude and the shape of the association were generally consistent with previous findings.

Abstract Background The association between long-term exposure to air pollutants, including nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), ozone (O3), and particulate matter 10 μm or less in diameter (PM10), and mortality by ischemic heart disease (IHD), cerebrovascular disease (CVD), pneumonia (PN), and chronic lower respiratory disease (CLRD) is unclear. We investigated whether living in an administrative district with heavy air pollution is associated with an increased risk of mortality by the diseases through an ecological study using South Korean administrative data over 19 years. Methods A total of 249 Si-Gun-Gus, unit of administrative districts in South Korea were studied. In each district, the daily concentrations of CO, SO2, NO2, O3, and PM10 were averaged over 19 years (2001–2018). Age-adjusted mortality rates by IHD, CVD, PN and CLRD for each district were averaged for the same study period. Multivariate beta-regression analysis was performed to estimate the associations between air pollutant concentrations and mortality rates, after adjusting for confounding factors including altitude, population density, higher education rate, smoking rate, obesity rate, and gross regional domestic product per capita. Associations were also estimated for two subgrouping schema: Capital and non-Capital areas (77:172 districts) and urban and rural areas (168:81 districts). Results For IHD, higher SO2 concentrations were significantly associated with a higher mortality rate, whereas other air pollutants had null associations. For CVD, SO2 and PM10 concentrations were significantly associated with a higher mortality rate. For PN, O3 concentrations had significant positive associations with a higher mortality rate, while SO2, NO2, and PM10 concentrations had significant negative associations. For CLRD, O3 concentrations were associated with an increased mortality rate, while CO, NO2, and PM10 concentrations had negative associations. In the subgroup analysis, positive associations between SO2 concentrations and IHD mortality were consistently observed in all subgroups, while other pollutant-disease pairs showed null, or mixed associations. Conclusion Long-term exposure to high SO2 concentration was significantly and consistently associated with a high mortality rate nationwide and in Capital and non-Capital areas, and in urban and rural areas. Associations between other air pollutants and disease-related mortalities need to be investigated in further studies.

Abstract Background Physical activity (PA) increases a person’s inhalation of air pollutants due to greater ventilation, possibly leading to larger adverse health effects. This study aims to investigate the combined effects of long-term exposure to fine particulate matter (PM2.5) and habitual PA on lung function in adults. Methods This was a longitudinal cohort study that included 278,065 Taiwan residents with an age of 20 years old or above who joined a standard medical screening programme between 2001 and 2014. Each participant received at least one medical examination (including spirometric, blood, and urinary tests and a standard self-administered questionnaire survey) during the study period. We estimated the 2-year average PM2.5 concentrations at each participant’s address using a new physical model based on observational data. Information on the participants’ PA was collected using the standard self-administrated questionnaire. Generalised linear mixed models were used to investigate the combined effects of PM2.5 and PA on pulmonary function. We also performed stratified analyses by different levels of PM2.5 exposure and habitual PA. Results Each 10 MET-h increase in PA was associated with a higher level of 0.20%, 0.16%, and 0.19% in forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and maximum mid-expiratory flow (MMEF), respectively, after adjusting for PM2.5 exposure and a wide range of covariates including age, sex education, body mass index, lifestyles, and health conditions. Each 10 μg/m3 increase in PM2.5 was associated with a lower FVC, FEV1, and MMEF (2.43%, 2.78% and 3.10%, respectively). Negative interactions were observed, and PM2.5 exposure was associated with a greater reduction in lung function among the participants with higher PA levels. Conclusions We found significant negative interaction effects between long-term exposure to PM2.5 and habitual PA, suggesting that the increased intake of PM2.5 due to PA may attenuate the benefits of habitual PA on lung function. However, the PA benefits generally remained stable at different stratum of PM2.5 in the stratified analyses, and habitual PA may still be recommended to people residing in relatively polluted regions.

Although PM2.5 mass varies in source and composition over time and space, most health effects assessment have made the inherent assumption that all PM2.5 mass has the same health implications, irrespective of composition. Nationwide estimates of source-specific PM2.5 mass and constituents at local-scale would allow for epidemiological studies and health effects assessments that consider the variability in PM2.5 characteristics in their health impact assessments. In response, we developed US models of annual exposures at the census tract level for five major PM2.5 sources (traffic, soil, coal, oil, and biomass combustion) and six trace elements (elemental carbon, sulfur, silicon, selenium, nickel, and non-soil potassium) for 2001 through 2014. We employed Absolute Factor Analysis (APCA) to derive the source-specific PM2.5 impacts at monitoring stations. Random forest algorithms that incorporated predictors derived from satellite, chemical transport model, and census tract resolution land-use data on traffic, meteorology, and emissions, which were rigorously tested by 10-fold cross-validation (CV), were then employed to estimate elemental and source-specific PM2.5 levels at non-monitoring site census-tracts over the study years. Model performances were moderate to good, with CV R2 ranging from 0.41 to 0.95. For PM2.5 sources, the highest CV R2 was attained for traffic PM2.5 (CV R2 = 0.73), followed by coal (CV R2 = 0.65), oil (CV R2 = 0.62), soil (CV R2 = 0.60), and biomass (CV R2 = 0.41). Among constituents, the CV was highest for sulfur (CV R2 = 0.95). Our analyses provided highly resolved spatial estimates of annual elemental and source-specific PM2.5 concentrations at the census-tract level, for 2001 through 2014. This dataset offers exposure estimates in support of future nationwide long-term health effects studies of source-specific PM2.5 mass and constituents, enabling epidemiological research that addresses the fact that not all particles are the same.

Growing evidence has linked long-term fine particulate matter (PM2.5) exposure to neurological disorders. Less is known about the individual effects of PM2.5 components. A population-based cohort study investigated the association between long-term (1-year average) exposure to PM2.5 components and dementia incidence among the elderly population (age, ≥65 years) in the United States. We used data from the Medicare Chronic Conditions Warehouse and a high-resolution PM2.5 components dataset of the northeastern United States (2000–2017). We identified dementia diagnoses from patients’ hospital and medical insurance records and carried out Cox proportional hazards regression to investigate their association with PM2.5 components. Among ∼2 million participants, 15.1% developed dementia. From the single-pollutant models, hazard ratios per interquartile range increase were 1.10 (95% confidence interval [CI]: 1.09–1.11) for black carbon, 1.08 (95% CI: 1.07, 1.10) for inorganic nitrate, 1.03 (95% CI: 1.02, 1.04) for organic matter, 1.13 (95% CI: 1.11, 1.15) for sulfate, 1.07 (95% CI: 1.06, 1.07) for soil particles, and 1.04 (95% CI: 1.03, 1.05) for sea salt. Increase in exposure to black carbon and sulfate per interquartile range had the strongest associations with dementia incidence. Penalized spline models indicated that dementia incidence increased linearly with elevated black carbon concentrations, whereas the incidence of dementia was only elevated significantly following sulfate concentrations above ∼2 μg/m3. Our study suggests that long-term exposure to PM2.5 components is significantly associated with increased dementia incidence and that different components have different neurotoxicity. Reduction of PM2.5 emissions, especially for main sources of black carbon and sulfate, may reduce the burden of dementia in the aging United States population.

Background: Previous studies about chronic effects of ozone (O 3 ) on cardiovascular mortality are scarce and inconclusive. We aimed to investigate the association between cardiovascular mortality and a broad range of long-term O 3 exposure levels., Methods: This analysis included 3,206,871 participants aged 35-75 years enrolled in the ChinaHEART study. Participants were recruited from the 31 provinces of the Chinese mainland between January 2015 and December 2020. The five-year average O 3 concentrations before baseline visits were calculated to represent long-term exposure., Findings: Over a median follow-up period of 4.7 (interquartile range: 3.7-6.2) years, 35,553 (1.1%) participants died from cardiovascular diseases (CVD). Following multivariable adjustment, nonlinear relationships were identified between O 3 concentrations and CVD and ischemic heart disease (IHD) mortality, with inflection points at 85.44 and 88.15 μg/m 3 , respectively. Above these points, a 10.0 μg/m 3 increase in the O 3 level was associated with a 13.9% (hazard ratio [HR]: 1.139, 95% confidence interval [CI]: 1.096-1.184) and 25.0% (HR: 1.250, 95% CI: 1.151-1.357) greater risk of CVD and IHD mortality, respectively. Conversely, O 3 exposure exhibited a linear relationship with ischemic stroke mortality. Moreover, the metabolic factors explained more than half of the association between O 3 exposure and CVD mortality., Interpretation: Substantial influences of long-term O 3 exposure on CVD mortality were identified, with notable mediation proportions attributed to metabolic factors. These findings could facilitate the air quality standard revisions and risk reduction strategy making in the future., Funding: This study was supported by the CAMS Innovation Fund for Medical Science (2021-1-I2M-011), the CAMS Innovation Fund for Medical Science (CIFMS, 2022-I2M-C&T-A-010), the National High Level Hospital Clinical Research Funding (2022-GSP-GG-4), the Ministry of Finance of China and National Health Commission of China, the 111 Project from the Ministry of Education of China (B16005)., Competing Interests: All authors declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© 2024 The Author(s).)

Ambient particulate matter pollution has been linked to impaired cognitive performance, but the effect of ambient ozone exposure on cognitive function remains largely unknown. We examined the association of long-term ozone exposure with the risk of cognitive impairment among a national representative cohort of 9,544 Chinese older adults (aged 65 years and over) with baseline normal cognition from the Chinese Longitudinal Healthy Longevity Survey (2005–2018). The ozone exposure of each participant was measured by annual mean ozone concentrations for the county of residence. Cognitive function was assessed by the Chinese version of the Mini-Mental State Examination (MMSE). We defined cognitive impairment as an MMSE score below 18 points accompanied by an MMSE score that declined ≥ 4 points from baseline. Cox proportional hazards models were applied to explore the association of ozone exposure with cognitive impairment. During the mean follow-up time of 6.5 years, 2,601 older adults developed cognitive impairment. Each 10-μg/m3 increase in annual mean ozone exposure was associated with a 10.4% increased risk of cognitive impairment. The exposure–response relationship between ozone exposure and risk of cognitive impairment showed a linear trend. Sensitivity analyses revealed the association to be robust. We found that older adults from Eastern, Central, and Southern China were particularly susceptible. Our results show that ozone is a risk factor for late-life cognitive decline. Reducing ambient ozone pollution may help delay the onset of cognitive impairment among older adults.

As the use of zinc oxide nanoparticles (ZnO NPs) in everyday products grows, so does concern about health risks. However, no findings on the gastrointestinal toxicity of ZnO NPs have been published. We investigated the possible malignant transformation of ZnO NPs in the mice’s colonic tissues using the APCmin/+ mouse model with a premalignant lesion in intestinal epithelial cells. Higher doses and long-term oral exposure to ZnO NPs were found to mildly promote colonic inflammation in WT mice, while they moderately or strongly exacerbated the severity of chronic inflammation and tumorigenesis in APCmin/+ mice with intestinal adenomatous polyposis. The ZnO NPs-induced inflammation and tumorigenesis in colonic epithelial cells was linked to the activation of CXCR2/NF-κB/STAT3/ERK and AKT pathways. Analysis of the ZnO NPs-exacerbated intestinal adenomatous polyposis in APCmin/+ mice revealed that ZnO NPs could activate the APC-driven Wnt/β-catenin signaling pathway, exacerbating intestinal tumorigenesis. In fact, ZnO NPs have been shown to increase intestinal inflammation and tumorigenesis in APCmin/+ mice by releasing free Zn2+. In WT mice, a low dose of ZnO NPs (26 mg/kg/day) did not cause intestinal inflammation. In conclusion, higher doses and prolonged exposure to ZnO NPs promote the malignant transformation of precancerous epithelial cells.

Background: Our understanding of the impact of long-term exposures to PM2.5 constituents and sources on mortality is limited. Objectives: To examine associations between long-term exposures to PM2.5 constituents and sources and cause-specific mortality in US older adults. Methods: We obtained demographic and mortality data for 15.4 million Medicare beneficiaries living within the conterminous United States (US) between 2000 and 2008. We assessed PM2.5 constituents exposures for each beneficiary and used factor analysis and residual-based methods to characterize PM2.5 sources and mixtures, respectively. In age-, sex-, race- and site- stratified Cox proportional hazard models adjusted for neighborhood socio-economic status (SES), we assessed associations of individual PM2.5 constituents, sources, and mixtures and cause-specific mortality and examined modification of these associations by participant demographics and location of residence. We assessed the robustness of our findings to additional adjustment for behavioral risk factors and to alternate exposure definitions and exposure windows. Results: Hazard ratios (HR) were highest for all causes of death, except COPD, for PM2.5 constituents and the coal combustion-related PM2.5 components, with no evidence of confounding by behavioral covariates. We further found Pb and metal-related PM2.5 components to be significantly associated with increased HR of all causes of death, except COPD and lung cancer mortality, and nitrate (NO3–) and silicon (Si) and associated source-related PM2.5 components (traffic and soil, respectively) to be significantly associated with increased all-cause, CVD, respiratory and all cancer-related mortality HR. Associations for other examined constituents and mortality were inconsistent or largely null. Our analyses of mixtures were generally consistent with these findings. Mortality HRs were greatest for minority, especially Black, low-income urban, younger, and male beneficiaries. Discussion: PM2.5 components related to coal combustion, traffic, and to a lesser extent, soil were strongly associated with mortality from CVD, respiratory disease, and cancer.

Rationale: It remains unknown whether long-term ozone exposure can impair lung function. Objectives: To investigate the associations between long-term ozone exposure and adult lung function in China. Methods: Lung function results and diagnosis of small airway dysfunction (SAD) were collected from a cross-sectional study, the China Pulmonary Health Study (N = 50,991). We used multivariable linear and logistic regression models to examine the associations of long-term ozone exposure with lung function parameters and SAD, respectively, adjusting for demographic characteristics, individual risk factors, and longitudinal trends. We then performed a stratification analysis by chronic obstructive pulmonary disease (COPD). Measurements and Main Results: We observed that each 1 SD (4.9 ppb) increase in warm-season ozone concentrations was associated with a 14.2 ml/s (95% confidence interval [CI], 8.8-19.6 ml/s] decrease in forced expiratory flow at the 75th percentile of vital capacity and a 29.5 ml/s (95% CI, 19.6-39.5 ml/s) decrease in mean forced expiratory flow between the 25th and 75th percentile of vital capacity. The odds ratio of SAD was 1.09 (95% CI, 1.06-1.11) for a 1 SD increase in warm-season ozone concentrations. Meanwhile, we observed a significant association with decreased FEV1/FVC but not with FEV1 or FVC. The association estimates were greater in the COPD group than in the non-COPD group. Conclusions: We found independent associations of long-term ozone exposure with impaired small airway function and higher SAD risks, while the associations with airflow obstruction were weak. Patients with COPD appear to be more vulnerable. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to assess the tolerability and safety of galcanezumab in patients with chronic cluster headache (CH) with up to 15 months of treatment. Background: Chronic CH is a highly debilitating disease with a substantial and unmet medical need. Methods: Patients were randomized to receive placebo or galcanezumab (300 mg) monthly for 12 weeks, followed by an optional 52‐week open‐label extension and 16‐week posttreatment follow‐up (washout). This is a secondary analysis and long‐term follow‐up of a previously conducted clinical trial. The safety analysis included patients who received galcanezumab at any time during the study. Outcomes included adverse events (AEs), discontinuations, laboratory values, vital signs, electrocardiograms (ECGs), and suicidality ratings. Results: A total of 233 patients received at least one galcanezumab dose. The mean exposure was 341 days. Galcanezumab‐treated patients were mostly male (n = 169/233; 72.5%) with a mean age of 44.9 (±10.9) years. Treatment‐emergent adverse events (TEAEs) were reported by 185 patients (n = 185/233; 79.4%), 23 patients (n = 23/233; 9.9%) reported serious adverse events (SAEs), and 18 patients (n = 18/233; 7.7%) discontinued due to AEs. The SAE CH was reported by three patients. The most common TEAEs (>10%) were nasopharyngitis (n = 41/233; 17.6%) and injection site pain (n = 33/233; 14.2%). 27.5% of patients (n = 64/233) had TEAEs related to injection sites. Likely hypersensitivity events, including injection site rash, injection site urticaria, and injection site hypersensitivity were reported (n = 14/233; 6.0%). There were past histories of suicidal ideation (n = 55/237; 23.2%) and suicidal behavior (n = 9/236; 3.8%). During the study, 15 patients (n = 15/230; 6.5%), seven with previous history, reported suicidal ideation. One patient had a nonfatal suicide attempt during the open‐label extension and an aborted attempt during the washout. There were no new safety findings compared with the placebo‐controlled treatment period in laboratory values, vital signs, or ECGs. Conclusions: Galcanezumab 300 mg monthly had a favorable tolerability and safety profile in patients with chronic CH with up to 15 months of treatment. [ABSTRACT FROM AUTHOR]

Natural waters are contaminated globally with pharmaceuticals including many antibiotics. In this study, we assessed the acquisition of antimicrobial resistance in the culturable intestinal microbiota of rainbow trout (Oncorhynchus mykiss) exposed for 6 months to sub-inhibitory concentrations of sulfamethoxazole (SMX), one of the most prevalent antibiotics in natural waters. SMX was tested at three concentrations: 3000 µg/L, a concentration that had no observed effect (NOEC) on the in vitro growth of fish intestinal microbiota; 3 µg/L, a theoretical predicted no effect concentration (PNEC) for long-term studies in natural environments; and 0.3 µg/L, a concentration detected in many surveys of surface waters from various countries including the USA. In two independent experiments, the emergence of phenotypic resistance and an increased prevalence of bacteria carrying a sulfonamide-resistance gene (sul1) were observed in SMX-exposed fish. The emergence of phenotypic resistance to1000 mg/L SMX was significant in fish exposed to 3 µg/L SMX and was in large part independent of sul resistance genes. The prevalence of bacteria carrying the sul1 resistance gene increased significantly in the culturable intestinal microbiota of SMX-exposed fish, but the sul1-positive population was in large part susceptible to 1000 mg/L SMX, suggesting that the gene confers a lower resistance level or a growth advantage. The increased prevalence of sul1 bacteria was observed in all groups of SMX-exposed fish. Overall, this study suggests that fish exposed long-term to waters contaminated with low levels of antibiotics serve as reservoir of antimicrobial resistant genes and of resistant bacteria, a potential threat to public health. [ABSTRACT FROM AUTHOR]

Background: The current evidence on health effects of long-term exposure to outdoor airborne black carbon (BC) exposure remains scarce. Objectives: To examine the association between long-term exposure to BC and mortality in a large population-based French cohort, with 28 years of follow-up. Methods: Data from the GAZEL cohort were collected between 1989 and 2017. Land use regression model with temporal extrapolation wa used to estimate yearly BC and PM2.5 exposure at the residential addresses from 1989 until censoring for 19,906 participants. Time-varying Cox models with attained age as time-scale was used to estimate the associations between BC and all-cause and cardiovascular mortality, after adjusting for individual and area-level covariates. To handle confounding by PM2.5, we used the residual of BC regressed on PM2.5 as an alternate exposure variable. For all-cause mortality, we also examined effect modification by sex, smoking status, BMI and fruit/vegetable intake. Results: The median of 20-year moving average of BC exposure was 2.02 10−5/m in study population. We found significant associations between BC exposure and all-cause mortality (n = 2357) using both 20-year moving average of BC and residual of BC, with corresponding hazard ratios (HR) of 1.14 (95 %CI: 1.07–1.22) and 1.17 (95 %CI: 1.10–1.24) for an inter-quartile range (IQR) increase (0.86 10−5/m for BC and 0.57 10−5/m for residual of BC). We found a similar association between BC and cardiovascular mortality (n = 277) with a HR of 1.15 (95 %CI: 0.95–1.38). The dose–response relationship between BC and all-cause mortality was monotonic but nonlinear with a steeper slope at high BC levels. In addition, the effect of BC was higher among never-smokers and among those having fruit/vegetables less than twice a week. Conclusions: There was a positive association between long-term exposure to BC and increased mortality risk, reinforcing the emerging evidence that BC is a harmful component of PM2.5.

Mounting evidence has linked air pollution with dementia and temperature modifies the association of air pollution with other disease. However, their interactions on dementia are unclear. We used a prospective cohort study (the UK Biobank) included 498 660 adults without cognitive impairment or dementia at baseline and followed up for 11.50 years (5734 907 person-years). We applied Cox proportional hazards regression with time-varying exposures to examine the effects of air pollutants [particulate matter (PM _2.5 , PM _10 ), nitrogen oxides (NO _2 , NO _X ) and sulphur dioxide (SO _2 )], the mean and variability of seasonal temperature, and their interactions on dementia. During the follow-up time, we ascertained 4119 cases of dementia. We observed a higher hazard of incident dementia for 1 μ g m ^−3 increase in SO _2 (hazard ratio [HR] = 1.11; 95% confidence interval [CI]: 1.08, 1.14), NO _2 (HR [95% CI] = 1.02 [1.01, 1.02]), NO _X (HR [95% CI] = 1.01 [1.00, 1.01]), PM _2.5 (HR [95% CI] = 1.03 [1.02, 1.05]), and PM _10 (HR HR [95% CI] = 1.02 [1.00, 1.03]). A lower risk of dementia in summertime temperature variability (HR for 1 °C increment above 1.27 °C = 0.61; 95% CI: 0.51, 0.72) was found. We observed a nonlinear relationship between higher risk of dementia and higher summer temperatures, and strong U-shaped relation of both wintertime temperature and wintertime temperature variability with dementia. We found the significantly synergistic effect between SO _2 and summertime temperature ( p < 0.001), the antagonistic effect between NO _2 ( p = 0.043), NO _X ( p = 0.026) and summertime temperature variability. Participants in a lower social economic position dominated susceptibility in temperature-air pollution interaction on dementia. In conclusion, some evidence of interactive effects between summer temperature and air pollutants was found, but no consistent interaction could be identified during the winter. Our study added weight to the evidence of air pollutants, temperature and their interaction on the onset of dementia.

The associations of long-term exposure to various constituents of fine particulate matter (≤2.5 μm in aerodynamic diameter, PM2.5) air pollution with lung function were not clearly elucidated in developing countries. The aim was to evaluate the associations of long-term exposure to main constituents of PM2.5 with lung function in China. This is a nationwide, cross-sectional analysis among 50,991 study participants from the China Pulmonary Health study. Multivariable linear regression models were used to obtain differences of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF), and forced expiratory flow at 25–75% of exhaled FVC (FEF25-75%) associated with an interquartile range (IQR) change of PM2.5 or its constituents. Residential annual PM2.5 levels varied from 26 μg/m3 to 92 μg/m3 (average: 53 μg/m3). An IQR increase of PM2.5 concentrations was associated with lower FEV1 (19.82 mL, 95% CI: 11.30–28.33), FVC (17.45 mL, 95% CI: 7.16–27.74), PEF (86.64 mL/s, 95% CI: 59.77–113.52), and FEF25-75% (31.93 mL/s, 95% CI: 16.64–47.22). Black carbon, organic matter, ammonium, sulfate, and nitrate were negatively associated with most lung function indicators, with organic matter and nitrate showing consistently larger magnitude of associations than PM2.5 mass. This large-scale study provides first-hand epidemiological evidence that long-term exposure to ambient PM2.5 and some constituents, especially organic matter and nitrate, were associated with lower large- and small- airway function.

Background: Triclosan (TCS) is a widely used antibacterial agent in personal care products and is ubiquitous in the environment. We aimed to examine whether TCS exposure affects microbiota in the gastrointestinal tract of zebrafish.Methods: After exposure to TCS 0 (Dimethyl Sulphoxide, DMSO control), 0.03, 0.3, 3, 30, 100, and 300ng/ml, respectively, from day 0 to 120days post fertilization (dpf), or for 7days in adult 4-month zebrafish, the long- and short-term impact of TCS exposure on the microbiome in the gastrointestinal tract was evaluated by analyzing 16S rRNA gene V3-V4 region sequencing.Results: The top two most dominant microbiota phyla were Proteobacteria and Fusobacteria phylum in all zebrafish groups. In TCS exposure 0–120 dpf, compared with DMSO control, the mean number of microbial operational taxonomic units (OTUs) was 54.46 lower (p

Uptake of most metal nanoparticles (NPs) in organisms is assumed to be mainly driven by the bioavailability of the released ions, as has been verified in controlled and short-term exposure tests. However, the changeability of NPs and the dynamic processes which NPs undergo in the soil environment, bring uncertainty regarding their interactions with soil organisms over a long period of time. To assess the potential impacts of long-term exposure scenarios on the toxicokinetic of metal NPs, earthworms Eisenia fetida were exposed to soils spiked with pristine Ag-NP, aged Ag-NP (Ag2S-NP) and ionic Ag for nine months, and results were compared to those from a similar short-term (28 days) experiment, conducted under similar conditions. Overall, there were no statistical differences between long-term accumulation patterns in earthworms exposed to pristine Ag-NP and AgNO3, while for Ag2S-NP, the amount of Ag internalized after 9 months was five times lower than for the other treatments. Average Ag concentrations in soil pore water in all treatments did not change over time, however the soil pH decreased and electrical conductivity increased in all treatments. Metallothionein concentrations in exposed earthworms were not statistically different from levels in untreated earthworms. Finally, the short-term toxicokinetic models predicted the bioaccumulation in earthworms exposed to Ag-NP, AgNO3 after nine months on the whole. Although the bioaccumulation for Ag2S-NPs was somewhat under-predicted, the rate of accumulation of Ag2S-NPs is much lower than that of Ag-NPs or AgNO3 and thus potentially of lower concern. Nevertheless, better understanding about the exposure kinetics of Ag2S-NP would help to address potential nano-specific toxicokinetic and toxicodynamics, also of other sulfidized metal NPs.

Atrazine (ATR) is a herbicide used widely worldwide. Because of its prolonged persistence in the environment and accumulation in the body, ATR exposure is a potential threat to human health. Our previous study showed that subacute exposure to ATR suppresses cellular immune function in mice. In this study, the effects of long-term exposure to ATR on rat immunological system function were measured. Four-week-old female Sprague-Dawley (SD) rats were treated with 0.4 μmol/L, 2 μmol/L and 10 μmol/L ATR for 24 weeks. The results showed that the spleen index increased, white blood cells decreased, and monocytes and eosinophils increased. No obvious changes were detected in the numbers of neutrophils and lymphocytes. Th1, Th2, and Th17 cells decreased significantly, while Treg cells increased after long-term ATR exposure. Moreover, serum levels of cytokines, including TNF-α, INF-γ, IL-6, and IL-12, decreased, while IL-1, IL-4, and IL-5 increased. Degenerative changes and cell apoptosis were found in the spleen; Caspase-3 and Caspase-9 were upregulated, and Bcl-2 was downregulated. These results suggested that long-term ATR exposure may inhibit immune system function.

Background: Triclosan (TCS) is a widely used antibacterial agent in personal care products and is ubiquitous in the environment. We aimed to examine whether TCS exposure affects microbiota in the gastrointestinal tract of zebrafish. Methods: After exposure to TCS 0 (Dimethyl Sulphoxide, DMSO control), 0.03, 0.3, 3, 30, 100, and 300ng/ml, respectively, from day 0 to 120days post fertilization (dpf), or for 7days in adult 4-month zebrafish, the long- and short-term impact of TCS exposure on the microbiome in the gastrointestinal tract was evaluated by analyzing 16S rRNA gene V3-V4 region sequencing. Results: The top two most dominant microbiota phyla were Proteobacteria and Fusobacteria phylum in all zebrafish groups. In TCS exposure 0–120 dpf, compared with DMSO control, the mean number of microbial operational taxonomic units (OTUs) was 54.46 lower (p <0.0001), Chao indice 41.40 lower (p =0.0004), and Ace indice 34.10 lower (p =0.0044) in TCS 300ng/ml group, but no change was observed in most of the other TCS concentrations. PCoA diagram showed that the microbial community in the long-term TCS 300ng/ml exposure group clustered differently from those in the DMSO control and other TCS exposure groups. A shorter body length of the zebrafish was observed in the long-term TCS exposure at 0.03, 100, and 300ng/ml. For 7-day short-term exposure in adult zebrafish, no difference was observed in alpha or beta diversity of microbiota nor the relative abundance of Proteobacteria or Fusobacteria phylum among DMSO control and any TCS levels, but a minor difference in microbial composition was observed for TCS exposure. Conclusions: Long-term exposure to high TCS concentration in a window from early embryonic life to early adulthood may reduce diversity and alter the composition of microbiota in the gastrointestinal tract. The effect of short-term TCS exposure was not observed on the diversity of microbiota but there was a minor change of microbial composition in adult zebrafish with TCS exposure. [ABSTRACT FROM AUTHOR]

Previous studies have proved that particulate air pollution was related to adverse cardiovascular effects. However, most studies focused on the acute effects of short-term fine particulate matter (PM2.5) exposure and the general population. Evidence from long-term cohort studies based on the cardiovascular disease (CVD) patients was scarce. Our study aimed to explore the impact of long-term exposure to PM2.5 on the mortality among post-CVD patients. This is a cohort study that involved 5143 post-CVD patients in Beijing, China. We collected records of CVD patients from hospitals in Beijing, China from 1 January 2012 to 31 December 2012 and followed up these patients from hospital admission until December 31, 2016. The vital status of the patients was determined using the National Death Surveillance Point System (DSPs). The PM2.5 concentrations were obtained from the Atmospheric Composition Analysis Group. The Cox regression models were used for data analyses. Our findings suggested that increased mortality of CVD patients with an HR of 1.43 (95% CI: 1.24, 1.63) was related to long-term exposure to PM2.5. The association was stronger for cardiovascular-related mortality, especially for mortality from myocardial infarction (MI). The HR for any CVD mortality was 1.57 (95% CI: 1.27, 1.94), HR for MI mortality was 1.82 (95% CI: 1.16, 2.83). Long-term PM2.5 exposure may significantly affect the survival of CVD patients. Compared with the general population, patients with CVD are more susceptible to PM2.5 exposure. Increased attention to the management of CVD patients is warranted. [ABSTRACT FROM AUTHOR]

Background: Much of the current evidence of associations between long-term PM2.5 and health outcomes relies on national or regional analyses using exposures derived directly from regulatory monitoring data. These findings could be affected by limited spatial coverage of monitoring data, particularly for time periods before spatially extensive monitoring began in the late 1990s. For instance, Pope et al. (2009) showed that between 1980 and 2000 a 10 μg/m3 reduction in PM2.5 was associated with an average 0.61 year (standard error (SE) = 0.20) longer life expectancy. That analysis used 1979-1983 averages of PM2.5 across 51 U.S. Metropolitan Statistical Areas (MSAs) computed from about 130 monitoring sites. Our reanalysis re-examines this association using modeled PM2.5 in order to assess population- or spatially-representative exposure. We hypothesized that modeled PM2.5 with finer spatial resolution provides more accurate health effect estimates compared to limited monitoring data.Methods: We used the same data for life expectancy and confounders, as well as the same analysis models, and investigated the same 211 continental U.S. counties, as Pope et al. (2009). For modeled PM2.5, we relied on a previously-developed point prediction model based on regulatory monitoring data for 1999-2015 and back-extrapolation to 1979. Using this model, we predicted annual average concentrations at centroids of all 72,271 census tracts and 12,501 25-km national grid cells covering the contiguous U.S., to represent population and space, respectively. We averaged these predictions to the county for the two time periods (1979-1983 and 1999-2000), whereas the original analysis used MSA averages given limited monitoring data. Finally, we estimated regression coefficients for PM2.5 reduction on life expectancy improvement over the two periods, adjusting for area-level confounders.Results: A 10 μg/m3 decrease in modeled PM2.5 based on census tract and national grid predictions was associated with 0.69 (standard error (SE) = 0.31) and 0.81 (0.29) -year increases in life expectancy. These estimates are higher than the estimate of Pope et al. (2009); they also have larger SEs likely because of smaller variability in exposure predictions, a standard property of regression. Two sets of effect estimates, however, had overlapping confidence intervals.Conclusions: Our approach for estimating population- and spatially-representative PM2.5 concentrations based on census tract and national grid predictions, respectively, provided generally consistent findings to the original findings using limited monitoring data. This finding lends additional support to the evidence that reduced fine particulate matter contributes to extended life expectancy. [ABSTRACT FROM AUTHOR]

Purpose: The etiology of Hodgkin lymphoma (HL) is obscure. Research on air pollution and risk of HL provides inconsistent results. We aimed to investigate the association between long-term residential exposure to air pollution and risk of adult Hodgkin lymphoma in Denmark. Methods: We performed a nationwide register-based case–control study, including all (n = 2,681) Hodgkin lymphoma cases registered in the nationwide Danish Cancer Registry between 1989 and 2014. We randomly selected 8,853 age- and sex-matched controls from the entire Danish population using the Civil Registration System, and identified 20-year residential address history for all cases and controls. We modeled outdoor air pollution concentrations at all these addresses using the high-resolution multiscale air pollution model system DEHM/UBM/AirGIS. We used conditional logistic regression to estimate odds ratios adjusted for individual and neighborhood level sociodemographic variables. Results: There was no association between 1, 5, 10, and 20 years' time-weighted average exposure to fine particles (PM2.5), O3, SO2, NO2, or the PM2.5 constituents OC, NH4, NO3, and SO4 and risk of Hodgkin lymphoma. Conclusion: Residential exposure to ambient air pollution does not seem to increase the risk of developing Hodgkin lymphoma. [ABSTRACT FROM AUTHOR]

The expected increments in the production/use of bioplastics, as an alternative to petroleum-based plastics, require a deep understanding of their potential environmental and health hazards, mainly as nanoplastics (NPLs). Since one important exposure route to NPLs is through inhalation, this study aims to determine the fate and effects of true-to-life polylactic acid nanoplastics (PLA-NPLs), using the in vitro Calu-3 model of bronchial epithelium, under air-liquid interphase exposure conditions. To determine the harmful effects of PLA-NPLs in a more realistic scenario, both acute (24 h) and long-term (1 and 2 weeks) exposures were used. Flow cytometry results indicated that PLA-NPLs internalized easily in the barrier (∼10 % at 24 h and ∼40 % after 2 weeks), which affected the expression of tight-junctions formation (∼50 % less vs control) and the mucus secretion (∼50 % more vs control), both measured by immunostaining. Interestingly, significant genotoxic effects (DNA breaks) were detected by using the comet assay, with long-term effects being more marked than acute ones (7.01 vs 4.54 % of DNA damage). When an array of cellular proteins including cytokines, chemokines, and growth factors were used, a significant over-expression was mainly found in long-term exposures (∼20 proteins vs 5 proteins after acute exposure). Overall, these results described the potential hazards posed by PLA-NPLs, under relevant long-term exposure scenarios, highlighting the advantages of the model used to study bronchial epithelium tissue damage, and signaling endpoints related to inflammation. [Display omitted] • An in vitro lung barrier containing Calu-3 cells has been set up. • PLA nanoplastics were tested under short and long-term exposures. • Easy internalization, tight-junctions, and mucus secretion effects were observed. • Genotoxicity was induced mainly after lon-term exposures. • Cellular proteins overexpression was induced mainly after long-term exposures [ABSTRACT FROM AUTHOR]

Long-term exposure to high-level ambient PM 2.5 was associated with increased risks of brain disorders, while the associations remain uncertain when the exposure is lower than current air quality standards in numerous countries. This study aimed to assess the effects of PM 2.5 exposure on the brain system in the population with annual mean concentrations ≤15 μg/m3. We analyzed data from 260,922 participants without preexisting brain diseases at baseline in the UK Biobank. The geographical distribution of PM 2.5 in 2010 was estimated by a land use regression model and linked with individual residential address. We investigated associations of ambient PM 2.5 with incident neurological (dementia, Parkinson's diseases [PD], epilepsy, and migraine) and psychiatric (major depressive disorder [MDD] and anxiety disorder) diseases through Cox proportional hazard models. We further estimated the links with brain imaging phenotypes by neuroimaging analysis. Results showed that in the population with PM 2.5 concentrations ≤15 μg/m3, each interquartile range (IQR, 1.28 μg/m3) increment in PM 2.5 was related to incidence risks of dementia, epilepsy, migraine, MDD, and anxiety disorder with hazard ratios of 1.08 (95% confidence interval [CI]: 1.03, 1.13), 1.12 (1.05, 1.20), 1.07 (1.00, 1.13), 1.06 (1.03, 1.09), and 1.05 (1.02, 1.08), respectively. We did not observe a significant association with PD. The association with dementia was stronger among the population with poor cardiovascular health (measured by Life's Essential 8) than the counterpart (P for interaction = 0.037). Likewise, per IQR increase was associated with specific brain imaging phenotypes, including volumes of total brain (β = −0.036; 95% CI: −0.050, −0.022), white matter (−0.030; −0.046, −0.014), grey matter (−0.030; −0.042, −0.017), respectively. The findings suggest long-term exposure to ambient PM 2.5 at low-level still has an adverse impact on the neuro-psychiatric systems. The brain-relevant epidemiological assessment suggests that each country should update the standard for ambient PM 2.5 following the World Health Organization Air Quality Guidelines 2021. [Display omitted] • Low-level PM 2.5 exposure was related to risks of dementia. • Low-level PM 2.5 exposure was associated with risks of mental illness. • Males were more vulnerable to the effect of PM 2.5 on major depressive disorder. • Low-level PM 2.5 was associated with shrunken volumes of brain imaging traits. [ABSTRACT FROM AUTHOR]

The causes of the physiological effects of microplastic pollution, potentially harming reef-building corals, are unclear. Reasons might include increased energy demands for handling particles and immune reactions. This study is among the first assessing the effects of long-term microplastic exposure on coral physiology at realistic concentrations (200 polyethylene particles L−1). The coral species Acropora muricata , Pocillopora verrucosa , Porites lutea , and Heliopora coerulea were exposed to microplastics for 11 months, and energy reserves, metabolites, growth, and photosymbiont state were analyzed. Results showed an overall low impact on coral physiology, yet species-specific effects occurred. Specifically, H. coerulea exhibited reduced growth, P. lutea and A. muricata showed changes in photosynthetic efficiency, and A. muricata variations in taurine levels. These findings suggest that corals may possess compensatory mechanisms mitigating the effects of microplastics. However, realistic microplastic concentrations only occasionally affected corals. Yet, corals exposed to increasing pollution scenarios will likely experience more negative impacts. • Coral physiology remained largely unaffected by long-term microplastic exposure. • Microplastics occasionally had subtle, species-specific effects on coral physiology. • Increased taurine levels may initiate the translocation of carbon fixation products. • Reduced growth may be a trade-off mitigating the increased energy needs. • Altered photosynthetic efficiency may provide additional energy for compensation. [ABSTRACT FROM AUTHOR]

Exposure to air pollutants has been associated with DNA damage and increases the risks of respiratory diseases, such as asthma and COPD; however short- and long-term effects of air pollutants on telomere dysfunction remain unclear. We investigated the impact of short- and long-term exposure to fine particulate matter with an aerodynamic diameter below 2.5 μm (PM 2.5) on telomere length in human bronchial epithelial BEAS-2B cells, and assessed the potential correlation between PM 2.5 exposure and telomere length in the LIGHTS childhood cohort study. We observed that long-term, but not short-term, PM 2.5 exposure was significantly associated with telomere shortening, along with the downregulation of human telomerase reverse transcriptase (hTERT) mRNA and protein levels. Moreover, long-term exposure to PM 2.5 induced proinflammatory cytokine secretion, notably interleukin 6 (IL-6) and IL-8, triggered subG1 cell cycle arrest, and ultimately caused cell death. Long-term exposure to PM 2.5 upregulated the LC3-II/ LC3-I ratio but led to p62 protein accumulation in BEAS-2B cells, suggesting a blockade of autophagic flux. Moreover, consistent with our in vitro findings, our epidemiological study found significant association between annual average exposure to higher PM 2.5 and shortening of leukocyte telomere length in children. However, no significant association between 7-day short-term exposure to PM 2.5 and leukocyte telomere length was observed in children. By combining in vitro experimental and epidemiological studies, our findings provide supportive evidence linking potential regulatory mechanisms to population level with respect to long-term PM 2.5 exposure to telomere shortening in humans. • Long-term PM 2.5 exposure shortens telomere length in cellular and cohort studies. • Short-term PM 2.5 exposure shows no association with telomere length. • hTERT mRNA and protein expression vary with different PM 2.5 exposure durations. • Long-term PM 2.5 exposure triggers inflammatory cytokine production. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the association between long-term exposure to fine particulate matter (PM 2.5) and its constituents (black carbon (BC), ammonium (NH 4 +), nitrate (NO 3 −), organic matter (OM), inorganic sulfate (SO 4 2−)) and incident female breast cancer in Beijing, China. Data from a prospective cohort comprising 85,504 women enrolled in the National Urban Cancer Screening Program in Beijing (2013–2019) and the Tracking Air Pollution in China dataset are used. Monthly exposures were aggregated to calculate 5-year average concentrations to indicate long-term exposure. Cox models and mixture exposure models (weighted quantile sum, quantile-based g-computation, and explanatory machine learning model) were employed to analyze the associations. Findings indicated increased levels of PM 2.5 and its constituents were associated with higher breast cancer risk, with hazard ratios per 1-μg/m3 increase of 1.02 (95% confidence interval (CI): 1.01, 1.03), 1.39 (95% CI: 1.16, 1.65), 1.28 (95% CI: 1.12, 1.46), 1.15 (95% CI: 1.05, 1.24), 1.05 (95% CI: 1.02, 1.08), and 1.15 (95% CI: 1.07, 1.23) for PM 2.5 , BC, NH 4 +, NO 3 −, OM, and SO 4 2−, respectively. Exposure-response curves demonstrated a monotonic risk increase without an evident threshold. Mixture exposure models highlighted BC and SO 4 2− as key factors, underscoring the importance of reducing emissions of these pollutants. [Display omitted] • Long-term exposure to PM 2.5 and its constituents was linked to higher female breast cancer risk in Beijing. • Key pollutants black carbon (BC) and sulfate (SO 4 2−) were identified as significant contributors to breast cancer risk. • Effective control measures are crucial in mitigating pollutants to reduce the risk of female breast cancer. [ABSTRACT FROM AUTHOR]

Despite the known link between air pollution and cause-specific mortality, its relation to chronic kidney disease (CKD)-associated mortality is understudied. Therefore, we investigated the association between long-term exposure to air pollution and CKD-related mortality in a large multicentre population-based European cohort. Cohort data were linked to local mortality registry data. CKD-death was defined as ICD10 codes N18–N19 or corresponding ICD9 codes. Mean annual exposure at participant's home address was determined with fine spatial resolution exposure models for nitrogen dioxide (NO 2), black carbon (BC), ozone (O 3), particulate matter ≤2.5 μm (PM 2.5) and several elemental constituents of PM 2.5. Cox regression models were adjusted for age, sex, cohort, calendar year of recruitment, smoking status, marital status, employment status and neighbourhood mean income. Over a mean follow-up time of 20.4 years, 313 of 289,564 persons died from CKD. Associations were positive for PM 2.5 (hazard ratio (HR) with 95% confidence interval (CI) of 1.31 (1.03–1.66) per 5 μg/m3, BC (1.26 (1.03–1.53) per 0.5 × 10− 5/m), NO 2 (1.13 (0.93–1.38) per 10 μg/m3) and inverse for O 3 (0.71 (0.54–0.93) per 10 μg/m3). Results were robust to further covariate adjustment. Exclusion of the largest sub-cohort contributing 226 cases, led to null associations. Among the elemental constituents, Cu, Fe, K, Ni, S and Zn, representing different sources including traffic, biomass and oil burning and secondary pollutants, were associated with CKD-related mortality. In conclusion, our results suggest an association between air pollution from different sources and CKD-related mortality. • Large population-based European cohort and fine-scale exposure resolution. • PM2.5 is positively associated with chronic kidney disease (CKD) mortality. • PM2.5 elemental constituents from different sources are related to CKD mortality. • The observed associations manifest below current European PM2.5 limit values. [ABSTRACT FROM AUTHOR]

The relationship of ozone (O 3), particularly the long-term exposure, with impacting metabolic homeostasis in population was understudied and under-recognised. Here, we used data from ChinaHEART, a nationwide, population-based cohort study, combined with O 3 and PM 2.5 concentration data with high spatiotemporal resolution, to explore the independent association of exposure to O 3 with the prevalence of insulin resistance (IR). Among the 271 540 participants included, the crude prevalence of IR was 39.1%, while the age and sex standardized prevalence stood at 33.0%. Higher IR prevalence was observed with each increase of 10.0 μg/m3 in long-term O 3 exposure, yielding adjusted odds ratios (OR) of 1.084 (95% CI: 1.079–1.089) in the one-pollutant model and 1.073 (95% CI: 1.067–1.079) in the two-pollutant model. Notably, a significant additive interaction between O 3 and PM 2.5 on the prevalence of IR was observed (P for additive interaction < 0.001). Our main findings remained consistent and robust in the sensitivity analyses. Our study suggests long-term exposure to O 3 was independently and positively associated with prevalence of IR. It emphasized the benefits of policy interventions to reduce O 3 and PM 2.5 exposure jointly, which could ultimately alleviate the health and economic burden related to DM. [Display omitted] • First study to investigate long-term ambient O 3 exposure and prevalence of IR. • Effects of O 3 exposure were greater in elderly, men, lower BMI, and rural areas. • We found a synergistic interaction between O 3 and PM 2.5 on IR. • This study extended our understanding of diabetogenic effects of ambient O 3. [ABSTRACT FROM AUTHOR]

The association between long-term exposure to ozone (O 3) and adult-onset asthma (AOA) remains inconclusive, and analysis of causality is lacking. To examine the causal association between long-term O 3 exposure and AOA. A prospective cohort study of 362,098 participants was conducted using the UK Biobank study. Incident cases of AOA were identified using health administrative data of the National Health Services. O 3 exposure at participants' residential addresses was estimated by a spatio-temporal model. Instrumental variable (IV) modelling was used to analyze the causal association between O 3 exposure and AOA, by incorporating wind speed and planetary boundary layer height as IVs into time-dependent Cox model. Negative control outcome (accidental injury) was also used to additionally evaluate unmeasured confounding. During a mean follow-up of 11.38 years, a total of 10,973 incident AOA cases were identified. A U-shaped concentration-response relationship was observed between O 3 exposure and AOA in the traditional Cox models with HR of 0.916 (95% CI: 0.888, 0.945) for O 3 at low levels (<38.17 ppb), and 1.204 (95% CI: 1.168, 1.242) for O 3 at high levels (≥38.17 ppb). However, in the IV analysis we only found a statistically significant association between high-level O 3 exposure and AOA risk, but not for low-level O 3 exposure. No significant associations between O 3 exposure and accidental injury were observed. Our findings suggest a potential causal relationship between long-term exposure to high-level ambient O 3 and increased risks of AOA. [Display omitted] • Causal association between long-term O 3 exposure and adult-onset asthma was assessed. • A U-shaped concentration-response curve was observed using traditional Cox models. • The association only remained for high-level O 3 in instrumental variable model. • High-level O 3 exposure could be causally associated with adult-onset asthma. [ABSTRACT FROM AUTHOR]

Little is known about the relationship between long-term joint exposure to mixtures of air pollutants and the prevalence of chronic obstructive pulmonary disease (COPD). We aimed to assess the joint impact of long-term exposure to ambient air pollution on the prevalence of COPD in Korea, especially in areas with high levels of air pollution. We included 22,387 participants who underwent spirometry tests in 2010–2019. The community multiscale air quality model was used to estimate the levels of ambient air pollution at residential addresses. The average exposure over the 5 years before the examination date was used to calculate the concentrations of air pollution. Forced expiratory volume in 1 s and forced vital capacity were used to define restrictive lung disease, COPD, and moderate-to-severe COPD. Quantile-based g-computation models were used to assess the joint impact of air pollution on COPD prevalence. A total of 2535 cases of restrictive lung disease, 2787 cases of COPD, and 1399 cases of moderate-to-severe COPD were identified. In the individual pollutant model, long-term exposure was significantly associated with both restrictive lung disease and COPD. In the mixture pollutant model, the odds ratios (ORs, 95% confidence intervals) for restrictive lung disease increased with each quartile increment in the 1- to 5-year average mixtures: 1.14 (1.02–1.28, 1 year), 1.25 (1.11–1.41, 2 years), 1.26 (1.11–1.42, 3 years), 1.32 (1.16–1.51, 4 years), and 1.37 (1.19–1.58, 5 years), respectively. The increase in ORs of restrictive lung disease accelerated over time. By contrast, the ORs of COPD showed a decreasing trend over time. Long-term exposure to air pollutants, both individually and jointly, was associated with an increased risk of developing COPD, particularly restrictive lung disease. Our findings highlight the importance of comprehensively assessing exposure to various air pollutants in relation to COPD. [Display omitted] • Ambient air pollutant mixture elevated restrictive lung disease and COPD prevalence. • Restrictive lung disease prevalence increased with higher level of mixture exposure. • NO 2 showed the strongest association with COPD, followed by O 3 and CO. • Comprehensively assessing air pollutants exposure is important in relation to COPD. [ABSTRACT FROM AUTHOR]

Evidence on the association between long-term ozone exposure and greenness exposure and hemorrhagic stroke (HS) is limited, with mixed results. One potential source of this inconsistency is the difference in exposure time metrics. This study aimed to investigate the association between long-term exposure to ambient ozone, greenness, and mortality from HS using exposure metrics at different times. We also examined whether greenness exposure modified the relationship between ozone exposure and mortality due to HS. The study population consisted of 45771 participants aged ≥40 y residing in 20 counties in Shandong Province who were followed up from 2013 to 2019. Ozone exposure metrics (annual mean and warm season) and the normalized difference a measure of greenness exposure, were calculated. The relationship between environmental exposures (ozone and greenness exposures) and mortality from HS was assessed using time-dependent Cox proportional hazards models, and the modification of greenness exposure was examined using stratified analysis with interaction terms. The person-years at the end of follow-up were 90,663. With full adjustments, the risk of death from hemorrhagic stroke increased by 5% per interquartile range increase in warm season ozone [hazard ratio =1.05; 95 % confidence interval: 1.01–1.08]. No clear association was observed between annual ozone and mortality HS. Both the annual and summer NDVI were found to reduce the risk of HS mortality. The relationships were influenced by age, sex, and residence (urban or rural). Furthermore, greenness exposure was shown to have a modifying effect on the relationship between ozone exposure and the occurrence of HS mortality (P for interaction = 0.001). Long-term exposure to warm season O 3 was positively associated with HS mortality, while greenness exposure was inversely associated with HS mortality. Greenness exposure may mitigate the negative effects of warm season ozone exposure on HS mortality. [Display omitted] • Warm season ozone positively associated with hemorrhagic stroke (HS) mortality. • Greenness exposure was negatively correlated with HS mortality. • Summer greenness attenuated the adverse effect of ozone on HS mortality. [ABSTRACT FROM AUTHOR]

Long-term ozone (O 3) exposure has been associated with cardiovascular disease (CVD) mortality in mounting cohort evidence, yet its relationship with incident CVD was poorly understood, especially in low- and middle-income countries (LMICs) experiencing high ambient air pollution. We carried out a nationwide perspective cohort study from 2010 through 2018 by dynamically enrolling 36948 participants across Chinese mainland. Warm-season (April–September) O 3 concentrations were estimated using satellite-based machine-learning models with national coverage. Cox proportional hazards model with time-varying exposures was employed to evaluate the association of long-term O 3 exposure with incident CVD (overall CVD, hypertension, stroke, and coronary heart disease [CHD]). Assuming causality, a counterfactual framework was employed to estimate O 3 -attributable CVD burden based on the exposure-response (E-R) relationship obtained from this study. Decomposition analysis was utilized to quantify the contributions of four key direct driving factors (O 3 exposure, population size, age structure, and incidence rate) to the net change of O 3 -related CVD cases between 2010 and 2018. A total of 4428 CVD, 2600 hypertension, 1174 stroke, and 337 CHD events were reported during 9-year follow-up. Each 10-μg/m³ increase in warm-season O 3 was associated with an incident risk of 1.078 (95% confidence interval [CI]: 1.050–1.106) for overall CVD, 1.098 (95% CI: 1.062–1.135) for hypertension, 1.073 (95% CI: 1.019–1.131) for stroke, and 1.150 (95% CI: 1.038–1.274) for CHD, respectively. We observed no departure from linear E-R relationships of O 3 exposure with overall CVD (P nonlinear = 0.22), hypertension (P nonlinear = 0.19), stroke (P nonlinear = 0.70), and CHD (P nonlinear = 0.44) at a broad concentration range of 60–160 µg/m3. Compared with rural dwellers, those residing in urban areas were at significantly greater O 3 -associated incident risks of overall CVD, hypertension, and stroke. We estimated 1.22 million (10.6% of overall CVD in 2018) incident CVD cases could be attributable to ambient O 3 pollution in 2018, representing an overall 40.9% growth (0.36 million) compared to 2010 (0.87 million, 9.7% of overall CVD in 2010). This remarkable rise in O 3 -attributable CVD cases was primary driven by population aging (+24.0%), followed by increase in O 3 concentration (+10.5%) and population size (+6.7%). Long-term O 3 exposure was associated with an elevated risk and burden of incident CVD in Chinese adults, especially among urban dwellers. Our findings underscored policy priorities of implementing joint control measures for fine particulate matter and O 3 in the context of accelerated urbanization and population aging in China. [Display omitted] • First nationwide study in China to evaluate the spatiotemporal patterns of O 3 -attributable CVD burden and quantify underlying driving factors. • Per 10 µg/m3 increase in long-term ozone exposure was associated with an HR of 1.078 (95% CI: 1.050–1.106) for overall CVD. • 1.22 million (95% CI: 0.64–2.26) CVD cases could be attributable to long-term ozone exposure in 2018. • Population aging was the leading driving factors of the rising ozone-attributable CVD burden between 2010 and 2018. [ABSTRACT FROM AUTHOR]

[Display omitted] We examined the associations between PM 2.5 exposure and Type 2 diabetes mellitus risk under the implementation of the Clean Air Act (CAA) among high-risk population for diabetes in Shanghai. A total of 10,499 subjects from the Shanghai High-Risk Diabetic Screen (SHiDS) project between 2002 and 2018, linked with remotely sensed PM 2.5 concentrations, were enrolled in this study. Ordinary least squares and logistic regression were applied to explore associations between PM 2.5 and diabetes risk in various exposure periods. In year 2002–2013 (before CAA), the diabetes risk increased 7.5 % (95 % CI: 1.018–1.137), 8.0 % (95 % CI: 1.022–1.142) and 7.9 % (95 % CI: 1.021–1.141) under each 10 μg/m3 increase of long-term (1, 2 and 3 years) PM 2.5 exposure, respectively. Elevated PM 2.5 exposure were also associated with a significant increase in glycemic parameters before CAA implementation. However, in the year 2014–2018 (after CAA), the associations between PM 2.5 exposure and diabetes risk were not significant after controlling for potential confounders. Our findings suggest that long-term and high-level exposure to PM 2.5 was associated with increased prevalence of diabetes. Moreover, the implementation of CAA might ameliorate PM 2.5 -related diabetes risk. [ABSTRACT FROM AUTHOR]

Rice consumption are a major cause of long-term exposure to arsenic. However, the exact mechanism of the neurotoxic action caused by arsenic exposure remain elusive. The purpose of this study was to investigate the effects of arsenic exposure on the behavior and neuronal structure of Caenorhabditis elegans , followed by the establishment of a 14-month mice model to simulate long-term effects. To elucidate the toxic effects of arsenic on brain metabolism, comprehensive analyses of neurotransmitter content and brain metabolomics were conducted. The findings demonstrated that arsenic exposure led to behavioral impairment, reduced levels of glutamatergic, GABAergic, dopaminergic and serotonergic neurotransmitters, as well as structural abnormalities. The majority of amino acid and fatty acid compounds were found to be upregulated in the hippocampus and cortical tissues. Respectively, an increase in nucleic acid and hydroxy acid-related compounds was observed in hippocampal tissues, while an upregulation of purine ribose-related compounds was detected in cortical tissues. The identified differential metabolites were primarily impacted by glutathione metabolism, arginine and proline metabolism, as well as alanine, aspartate, and glutamate metabolism. Correlation analysis of the hippocampus and cortex yielded compelling evidence of a strong association between glutamate and the majority of the presented metabolites. [Display omitted] [ABSTRACT FROM AUTHOR]

Long-term exposure to low doses of ionizing radiation may adversely affect human cells and tissues of hospital radiation workers, especially peripheral blood cell count. Blood cell count analysis is a useful screening test in a routine medical checkup. A high or low blood cells count even in a healthy-looking subject leads to the suspicion of disease and it should prompt further investigations. This study was aimed to assess the effects of ionizing radiation on the hematological parameters of radiation workers at several governmental hospitals in Indonesia and correlation between years of employment and equivalent dose on one hand and the hematological parameters on the other. It included 74 medical radiation workers occupationally exposed to low doses of ionizing radiation at the Unit of Radiology and Radiotherapy and 83 controls. Fourteen hematological parameters were measured by ABX Micros 60 Hematology analyzer and the correlation between years of employment and equivalent doseas well as hematological parameters on radiation-exposed workers were tested by linear regression analysis test. Our study reported that red blood cell and monocyte counts were significantly higher in radiation-exposed workers compared to controls, whereas white blood cells, hematocrit, mean corpuscular volume, and lymphocytes values were significantly lower in radiation-exposed workers. A significant correlation was observed between equivalent dose and red blood cells (RBCs) parameter (P=0.001) with a decline in RBC level of 0.541×106/µL per 1 mSv increase of radiation dose. The present study recommends that further studies shoulduse a larger sample size and include various independent variables (genetic polymorphism, chromosome aberration, micronucleus frequency) to study the long-term effects of low-dose radiation exposure on radiation-exposed workers.

Objectives: To evaluate the long- and short-term effects of air pollution on COVID-19 transmission simultaneously, especially in high air pollution level countries.Methods: Quasi-Poisson regression was applied to estimate the association between exposure to air pollution and daily new confirmed cases of COVID-19, with mutual adjustment for long- and short-term air quality index (AQI). The independent effects were also estimated and compared. We further assessed the modification effect of within-city migration (WM) index to the associations.Results: We found a significant 1.61% (95%CI: 0.51%, 2.72%) and 0.35% (95%CI: 0.24%, 0.46%) increase in daily confirmed cases per 1 unit increase in long- and short-term AQI. Higher estimates were observed for long-term impact. The stratifying result showed that the association was significant when the within-city migration index was low. A 1.25% (95%CI: 0.0.04%, 2.47%) and 0.41% (95%CI: 0.30%, 0.52%) increase for long- and short-term effect respectively in low within-city migration index was observed.Conclusions: There existed positive associations between long- and short-term AQI and COVID-19 transmission, and within-city migration index modified the association. Our findings will be of strategic significance for long-run COVID-19 control.

In the field of environmental health, the impact of air pollution on people's cognitive function is receiving increasing attention. Various air pollution exposures and different exposure periods result in different degrees of damage to cognition. This paper first used CFPS cognitive tests to evaluate the cognitive function of 15,163 adults in 25 provinces of China. Next, based on the geographical location of the population, the kriging interpolation method was applied to evaluate the different exposure periods for various air pollutants (PM2.5, NO2 and O3). Air pollution exposures lasting 3 years and more were referred to in this paper as long-term exposures, while those lasting

Background: Multi-walled carbon nanotube (MWCNT) is one of the most widely used manufactured nanomaterials, however, its potential harmful effect on human health is of great concern. Previously we have shown the acute and chronic exposure to MWCNT induced different responses in human mesothelial MeT-5A cells. In the current study, MeT-5A cells were continuously subjected to MWCNT exposure at 10 μg/cm2 for 48 h per passage, up to a whole year, to further clarify the carcinogesis and its potential mechanisms of MWCNT. Results: After one-year MWCNT treatment, MeT-5A cells exhibited neoplastic-like properties, including morphological changes, anchorage-independent growth, increased cell proliferation and cell migration. Further examination revealed the expression of microRNA 221 (miR221) was gradually decreased, while the annexin a1 expression was increased at both the mRNA and protein level during the exposure. Bioinformatic analysis indicated that annexin a1 is a target for miR221 regulation, and it was confirmed by transfecting cells with miR221 mimics, which resulted in the downregulation of annexin a1. Detailed analyses demonstrated miR221 was involved in the regulation of cell migration, e.g., downregulation of miR221 or overexpression of ANNEXIN A1, contributed to the increased cell migration. In contrast, overexpression of miR221 or downregulation of ANNEXIN A1 slowed cell migration. Conclusions: Taken together, these results point to a neoplastic-transforming property of MWCNT, and the miR221-annexin a1 axis is involved in the regulation of cell migration in the transformed cells. [ABSTRACT FROM AUTHOR]

Purpose: Increasingly epidemiological evidence supports that environmental factors are associated with breast cancer (BC) outcomes after a BC diagnosis. Although evidence suggests that air pollution exposure is associated with higher mortality in women with BC, studies investigating potential mechanisms have been lacking. Methods: We evaluated women with BC (N = 151) attended at the National Cancer Institute–Mexico from 2012 to 2015. We calculated 1-year average exposures to particulate matter < 2.5 μm (PM2.5) at home address before diagnosis. We used linear and logistic regression models to determine the associations between PM2.5 exposure and BC aggressiveness (tumor size, molecular phenotype). Results: Average annual PM2.5 exposure of this population was 23.0 μg/m3 [standard deviation (SD)]: 1.90 μg/m3]. PM2.5 levels were positively correlated with tumor size at diagnosis (r = 0.22; p = 0.007). Multivariable linear models had a similar inference [risk ratio (RR): 1.32; 95% confidence interval (95% CI): 1.04, 1.674]. We did not observe differences in this association by age or menopause status. Further, women with triple-negative BC (TNBC) had significantly higher PM2.5 levels compared with other phenotypes (p = 0.015). Multivariable-adjusted logistic regression models assessing the association between PM2.5 and tumor size had a similar inference (RR 1.41; 95% CI 1.05, 1.89) overall for all ages and also for women who were ≤ 50 years old at diagnosis (RR 1.63; 95% CI 1.036, 2.57). Conclusions: Our findings suggest a significant association between long-term PM2.5 exposure and BC aggressiveness based on tumor size and phenotype, as well as a worse outcome. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) originated in the People's Republic of China in December 2019. Thereafter, a global logarithmic expansion of cases occurred. Some countries have a higher rate of infections despite the early implementation of quarantine. Air pollution might be related to high susceptibility to the virus and associated case fatality rates (deaths/cases*100). Lima, Peru, has the second highest incidence of COVID-19 in Latin America and also has one the highest levels of air pollution in the region.Methods: This study investigated the association of levels of PM2.5 exposure in previous years (2010-2016) in 24 districts of Lima with cases, deaths and case fatality rates for COVID-19. Multiple linear regression was used to evaluate this association controlled by age, sex, population density and number of food markets per district. The study period was from March 6 to June 12, 2020.Results: There were 128,700 cases in Lima and 2382 deaths due to COVID-19. The case fatality rate was 1.93%. Previous exposure to PM2.5 (2010-2016) was associated with the number of COVID-19- cases (β = 0.07; 95% CI: 0.034-0.107) and deaths (β = 0.0014; 95% CI: 0.0006-0.0.0023) but not with the case fatality rate.Conclusions: After adjusting for age, sex and number of food markets, the higher rates of COVID-19 in Metropolitan Lima are attributable to the increased PM2.5 exposure in the previous years, among other reasons. Reduction in air pollution from a long-term perspective and social distancing are needed to prevent the spread of virus outbreaks. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Physical activity may increase a person's inhalation of air pollutants and exacerbate the adverse health effects. This study aimed to investigate the combined associations of chronic exposure to particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5) and habitual physical activity with the incidence of type 2 diabetes in Taiwan. Methods: We selected 156,314 non-diabetic adults (≥18 years old) who joined an ongoing longitudinal cohort between 2001 and 2016. Incident type 2 diabetes was identified at the follow-up medical examinations. Two-year mean PM2.5 exposure was estimated at each participant's address using a satellite-based spatiotemporal model. Information on physical activity and a wide range of covariates was collected using a standard self-administered questionnaire. We analysed the data using a Cox regression model with time-varying covariates. An interaction term between PM2.5 and physical activity was included to examine the overall interaction effects. Results: Compared with high physical activity, moderate and inactive/low physical activity were associated with a higher risk of diabetes (HR [95% CI] 1.31 [1.22, 1.41] and 1.56 [1.46, 1.68], respectively). Participants with moderate/high PM2.5 had a higher risk of type 2 diabetes than the participants exposed to low PM2.5 (HR 1.31 [1.22, 1.40] and 1.94 [1.76, 2.14], respectively). The participants with high physical activity and low PM2.5 had a 64% lower risk of type 2 diabetes than those with inactive/low physical activity and high PM2.5. Conclusions/interpretation: Higher physical activity and lower PM2.5 exposure are associated with lower risk of type 2 diabetes. Habitual physical activity can reduce the risk of diabetes regardless of the levels of PM2.5 exposure. Our results indicate that habitual physical activity is a safe diabetes prevention strategy for people residing in relatively polluted regions. [ABSTRACT FROM AUTHOR]

Hair is a unique biological matrix that adsorbs short-term exposures (e. g., environmental contaminants and personal care products) on its surface and also embeds endogenous metabolites and long-term exposures in its matrix. In this work, we developed an untargeted metabolomics workflow to profile both temporal exposure chemicals and endogenous metabolites in the same hair sample. This analytical workflow begins with the extraction of short-term exposures from hair surfaces through washing. Further development of mechanical homogenization extracts endogenous metabolites and long-term exposures from the cleaned hair. Both solutions of hair wash and hair extract were analyzed using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS)-based metabolomics for global-scale metabolic profiling. After analysis, raw data were processed using bioinformatic programs recently developed specifically for exposome research. Using optimized experimental conditions, we detected a total of 10,005 and 9,584 metabolic features from hair wash and extraction samples, respectively. Among them, 274 and 276 features can be definitively confirmed by MS2 spectral matching against spectral library, and an additional 3,356 and 3,079 features were tentatively confirmed as biotransformation metabolites. To demonstrate the performance of our hair metabolomics, we collected hair samples from three female volunteers and tested their hair metabolic changes before and after a 2-day exposure exercise. Our results show that 645 features from wash and 89 features from extract were significantly changed from the 2-day exposure. Altogether, this work provides a novel analytical approach to study the hair metabolome and exposome at a global scale, which can be implemented in a wide range of biological applications for a deeper understanding of the impact of environmental and genetic factors on human health.