Pre-pregnancy ozone and ultrafine particulate matter exposure during second year of life associated with decreased cognitive and adaptive functioning at aged 2-5 years.

BACKGROUND: This study sought to investigate the association of prenatal and early life exposure to a mixture of air pollutants on cognitive and adaptive outcomes separately in children with or without autism spectrum disorder (ASD). METHODS: Utilizing data from the CHARGE case-control study (birth years: 2000-2016), we predicted daily air concentrations of NO2, O3, and particulate matter <0.1 µm (PM0.1), between 0.1 and 2.5 µm (PM0.1-2.5), and between 2.5 and 10 µm (PM2.5-10) using chemical transport models with ground-based monitor adjustments. Exposures were evaluated for pre-pregnancy, each trimester, and the first two years of life. Individual and combined effects of pollutants were assessed with Vineland Adaptive Behavior Scales (VABS) and Mullen Scales of Early Learning (MSEL), separately for children with ASD (n = 660) and children without ASD (typically developing (TD) and developmentally delayed (DD) combined; n = 753) using hierarchical Bayesian Kernel Machine Regression (BKMR) models with three groups: PM size fractions (PM0.1, PM0.1-2.5, PM2.5-10), NO2, and O3. RESULTS: Pre-pregnancy Ozone was strongly negatively associated with all scores in the non-ASD group (group posterior inclusion probability (gPIP) = 0.83-1.00). The PM group during year 2 was also strongly negatively associated with all scores in the non-ASD group (gPIP = 0.59-0.93), with PM0.1 driving the group association (conditional PIP (cPIP) = 0.73-0.96). Weaker and less consistent associations were observed between PM0.1-2.5 during pre-pregnancy and ozone during year 1 and VABS scores in the ASD group. CONCLUSIONS: These findings prompt further investigation into ozone and ultrafine PM as potential environmental risk factors for neurodevelopment.

Ultrafine particulate matter exposure during second year of life, but not before, associated with increased risk of autism spectrum disorder in BKMR mixtures model of multiple air pollutants.

Prenatal and early postnatal air pollution exposures have been shown to be associated with autism spectrum disorder (ASD) risk but results regarding specific air pollutants and exposure timing are mixed and no study has investigated the effects of combined exposure to multiple air pollutants using a mixtures approach. We aimed to evaluate prenatal and early life multipollutant mixtures for the drivers of associations of air pollution with ASD. This study examined 484 typically developing (TD) and 660 ASD children from the CHARGE case-control study. Daily air concentrations for NO2, O3, ultrafine (PM0.1), fine (PM0.1-2.5), and coarse (PM2.5-10) particles were predicted from chemical transport models with statistical bias adjustment based on ground-based monitors. Daily averages were calculated for each exposure period (pre-pregnancy, each trimester of pregnancy, first and second year of life) between 2000 and 2016. Air pollution variables were natural log-transformed and then standardized. Individual and joint effects of pollutant exposure with ASD, and potential interactions, were evaluated for each period using hierarchical Bayesian Kernel Machine Regression (BKMR) models, with three groups: PM size fractions (PM0.1, PM0.1-2.5, PM2.5-10), NO2, and O3. In BKMR models, the PM group was associated with ASD in year 2 (group posterior inclusion probability (gPIP) = 0.75), and marginally associated in year 1 (gPIP = 0.497). PM2.5-10 appeared to drive the association (conditional PIP (cPIP) = 0.64) in year 1, while PM0.1 appeared to drive the association in year 2 (cPIP = 0.76), with both showing a moderately strong increased risk. Pre-pregnancy O3 showed a slight J-shaped risk of ASD (gPIP = 0.55). No associations were observed for exposures during pregnancy. Pre-pregnancy O3 and year 2 p.m.0.1 exposures appear to be associated with an increased risk of ASD. Future research should examine ultrafine particulate matter in relation to ASD.

The contributions of neonatal inhalation of copper to air pollution-induced neurodevelopmental outcomes in mice.

Exposures to ambient ultrafine particle (UFP) air pollution (AP) during the early postnatal period in mice (equivalent to human third trimester brain development) produce male-biased changes in brain structure, including ventriculomegaly, reduced brain myelination, alterations in neurotransmitters and glial activation, as well as impulsive-like behavioral characteristics, all of which are also features characteristic of male-biased neurodevelopmental disorders (NDDs). The purpose of this study was to ascertain the extent to which inhaled Cu, a common contaminant of AP that is also dysregulated across multiple NDDs, might contribute to these phenotypes. For this purpose, C57BL/6J mice were exposed from postnatal days 4-7 and 10-13 for 4 hr/day to inhaled copper oxide (CuxOy) nanoparticles at an environmentally relevant concentration averaging 171.9 ng/m3. Changes in brain metal homeostasis and neurotransmitter levels were determined following termination of exposure (postnatal day 14), while behavioral changes were assessed in adulthood. CuxOy inhalation modified cortical metal homeostasis and produced male-biased disruption of striatal neurotransmitters, with marked increases in dopaminergic function, as well as excitatory/inhibitory imbalance and reductions in serotonergic function. Impulsive-like behaviors in a fixed ratio (FR) waiting-for-reward schedule and a fixed interval (FI) schedule of food reward occurred in both sexes, but more prominently in males, effects which could not be attributed to altered locomotor activity or short-term memory. Inhaled Cu as from AP exposures, at environmentally relevant levels experienced during development, may contribute to impaired brain function, as shown by its ability to disrupt brain metal homeostasis and striatal neurotransmission. In addition, its ability to evoke impulsive-like behavior, particularly in male offspring, may be related to striatal dopaminergic dysfunction that is known to mediate such behaviors. As such, regulation of air Cu levels may be protective of public health.

Disruption of phosphofructokinase activity and aerobic glycolysis in human bronchial epithelial cells by atmospheric ultrafine particulate matter.

Exposure to ambient ultrafine particulate matter (UPM) causes respiratory disorders; however, the underlying molecular mechanisms remain unclear. In this study, we synthesized simulated UPM (sUPM) with controlled physicochemical properties using the spark-discharge method. Subsequently, we investigated the biological effects of sUPM using BEAS-2B human bronchial epithelial cells (HBECs) and a mouse intratracheal instillation model. High throughput RNA-sequencing and bioinformatics analyses revealed that dysregulation of the glycolytic metabolism is involved in the inhibited proliferation and survival of HBECs by sUPM treatment. Furthermore, signaling pathway and enzymatic analyses showed that the treatment of BEAS-2B cells with sUPM induces the inactivation of extracellular signal-regulated kinase (ERK) and protein kinase B (PKB, also known as AKT), resulting in the downregulation of phosphofructokinase 2 (PFK2) S483 phosphorylation, PFK enzyme activity, and aerobic glycolysis in HBECs in an oxidative stress-independent manner. Additionally, intratracheal instillation of sUPM reduced the phosphorylation of ERK, AKT, and PFK2, decreased proliferation, and increased the apoptosis of bronchial epithelial cells in mice. The findings of this study imply that UPM induces pulmonary toxicity by disrupting aerobic glycolytic metabolism in lung epithelial cells, which can provide novel insights into the toxicity mechanisms of UPM and strategies to prevent their toxic effects.

Ambient Ultrafine Particulate Matter and Clinical Outcomes in Fibrotic Interstitial Lung Disease.

RATIONALE: Particulate matter ≤2.5µm (PM2.5) is associated with adverse outcomes in fibrotic interstitial lung disease (fILD), but the impact of ultrafine particulates (UFPs; aerodynamic diameter ≤100nm) remains unknown. OBJECTIVE: To evaluate UFP associations with clinical outcomes in fILD. METHODS: Multicenter, prospective cohort study enrolling patients with fILD from the University of Pittsburgh Simmons Center and Pulmonary Fibrosis Foundation Patient Registry (PFF-PR). Using a national-scale UFP model, we linked exposures using three approaches in Simmons (residential address geocoordinates, zip centroid geocoordinates, zip average) and two in PFF-PR where only 5-digit zip code was available (zip centroid, zip average). We tested UFP associations with transplant-free survival using multivariable Cox, baseline percent predicted forced vital capacity (FVC) and diffusion capacity of the lung (DLCO) using multivariable linear regressions, and decline in FVC and DLCO using linear mixed models, adjusting for age, sex, smoking, race, socioeconomic status, site, PM2.5, and nitrogen dioxide. RESULTS: Annual mean outdoor UFP levels for 2017 were estimated for 1416 Simmons and 1919 PFF-PR patients. Increased UFP level was associated with transplant-free survival in fully-adjusted Simmons residential address models (HR=1.08 per 1000 particles/cm3, 95%CI 1.01-1.15, p=0.02), but not PFF-PR models, which used less precise linkage approaches. Higher UFP was associated with lower baseline FVC and more rapid FVC decline in Simmons. CONCLUSIONS: Increased UFP exposure was associated with transplant-free survival and lung function in the cohort with precise residential location linkage. This work highlights the need for more robust regulatory networks to study the health effects of UFPs nationwide.

Exposure to ultrafine particles and cognitive decline among older people in the United States.

BACKGROUND: Some studies suggest that ambient particulate air pollution is associated with cognitive decline. However, the findings are mixed, and there is no relevant research examining the influences of ultrafine particles (UFP), which may have more toxicity than larger particles. We therefore conducted this study to investigate whether residential UFP exposure is associated with cognitive decline using data from the Alzheimer's Disease Research Centers in the United States. METHODS: This is a longitudinal study of participants who were aged 65 years and older and had normal cognitive status at baseline. Residential UFP exposure, expressed as particle number concentrations (PNC), was assessed in 2016-2017 using a nationwide land use regression model, and was assigned to each participant using their 3-digit residential ZIP codes. Cognitive functions including memory, attention, language, executive function, and global function were assessed annually using 15 neuropsychological tests from March 2015 to February 2022. Linear mixed-effects models were used to examine the associations after adjustment for covariates including baseline age, sex, APOE ε4 status, race, education, smoking status, history of diabetes, quartiles of neighborhood median household income, and interaction terms of follow-up time with each covariate. RESULTS: This study included 5646 participants (mean age 76 years, 65% female). On average, each participant had 4 annual visits. When PNC was treated as a continuous variable, there were no statistically or clinically significant changes in annual decline of each cognitive function in relation to an interquartile range elevation in PNC (4026 particles/cm3). Similarly, when PNC was treated as a categorical variable including five exposure groups, there were no linear exposure-response trends in annual decline of each cognitive function across the five exposure groups. CONCLUSIONS: This study found no meaningful associations between residential UFP exposure and cognitive decline in global and domain-specific functions. There is a need for further research that assigns UFP exposure at a finer geographic scale.

Size fraction of hazardous particulate matter governing the respiratory deposition and inhalation risk in the highly polluted city Delhi.

Delhi has been identified as one of the highly polluted cities in the world and recently associated with the highest population weighted PM2.5 concentration. However, the unavailability of the health risk estimations using long-term data for Indian cities has been pointed out as a hurdle in performing the correct assessment. The present work estimated deposition of particles in different regions of respiratory systems (head airway = 67% deposition for 2.5 µm particles; tracheo-bronchiolar (TB) = 73% deposition for 1.0 µm particles; alveolar (AL) = 17% deposition for 0.5 µm, 0.25 µm, and < 0.25 µm particles) using PM samples collected at a breathing height of 1.5 m near the major ring road in New Delhi (India). The calculated risk index (RI) varied considerably between winter (1.21 ± 0.26 to 1.33 ± 0.50) and pre-monsoon-southwest monsoon months (0.34 ± 0.08 to 0.96 ± 0.27). Respiratory deposition dose of nanosized particles (≤ 500 nm) in the alveoli region of the lung was found to be considerable (35%) indicating the need for understanding the role of these particles in posing health risk. Although the calculated values of risk metric for exposures of PM-associated metals indicated no risk to IIT Delhi population (hazard quotient < 1 and excess risk of getting cancer < 10-6-10-9), continuous monitoring for particles of different sizes at inhalation height are required for protecting human health.

The potential involvement of inhaled iron (Fe) in the neurotoxic effects of ultrafine particulate matter air pollution exposure on brain development in mice.

BACKGROUND: Air pollution has been associated with neurodevelopmental disorders in epidemiological studies. In our studies in mice, developmental exposures to ambient ultrafine particulate (UFP) matter either postnatally or gestationally results in neurotoxic consequences that include brain metal dyshomeostasis, including significant increases in brain Fe. Since Fe is redox active and neurotoxic to brain in excess, this study examined the extent to which postnatal Fe inhalation exposure, might contribute to the observed neurotoxicity of UFPs. Mice were exposed to 1 µg/m3 Fe oxide nanoparticles alone, or in conjunction with sulfur dioxide (Fe (1 µg/m3) + SO2 (SO2 at 1.31 mg/m3, 500 ppb) from postnatal days 4-7 and 10-13 for 4 h/day. RESULTS: Overarching results included the observations that Fe + SO2 produced greater neurotoxicity than did Fe alone, that females appeared to show greater vulnerability to these exposures than did males, and that profiles of effects differed by sex. Consistent with metal dyshomeostasis, both Fe only and Fe + SO2 exposures altered correlations of Fe and of sulfur (S) with other metals in a sex and tissue-specific manner. Specifically, altered metal levels in lung, but particularly in frontal cortex were found, with reductions produced by Fe in females, but increases produced by Fe + SO2 in males. At PND14, marked changes in brain frontal cortex and striatal neurotransmitter systems were observed, particularly in response to combined Fe + SO2 as compared to Fe only, in glutamatergic and dopaminergic functions that were of opposite directions by sex. Changes in markers of trans-sulfuration in frontal cortex likewise differed in females as compared to males. Residual neurotransmitter changes were limited at PND60. Increases in serum glutathione and Il-1a were female-specific effects of combined Fe + SO2. CONCLUSIONS: Collectively, these findings suggest a role for the Fe contamination in air pollution in the observed neurotoxicity of ambient UFPs and that such involvement may be different by chemical mixture. Translation of such results to humans requires verification, and, if found, would suggest a need for regulation of Fe in air for public health protection.

In Utero Ultrafine Particulate Exposure Yields Sex- and Dose-Specific Responses to Neonatal Respiratory Syncytial Virus Infection.

Exposure to particulate matter (PM) is associated with lower respiratory tract infections. The role of ultrafine particles (UFPs, ≤0.1 µm) in respiratory disease is not fully elucidated, especially in models of immunologically immature populations. To characterize the effects of maternal UFP exposure on neonatal infection, we exposed time-mated C57Bl/6n mice to filtered air or UFPs at a low dose (LD, ∼55 µg/m3) and high dose (HD, ∼275 µg/m3) throughout gestation. At 5 days of age, offspring were infected with a respiratory syncytial virus (RSV) strain known to mimic infant infection or sham control. Offspring body weights were significantly reduced in response to infection in the LD RSV group, particularly females. Pulmonary gene expression analysis demonstrated significantly increased levels of oxidative stress- and inflammation-related genes in HD-exposed male offspring in sham and RSV-infected groups. In males, the highest grade of inflammation was observed in the HD RSV group, whereas in females, the LD RSV group showed the most marked inflammation. Overall, findings highlight neonatal responses are dependent on offspring sex and maternal UFP dose. Importantly, infant RSV pathology may be enhanced following even low dose UFP exposure signifying the importance of preventing maternal exposure.

Particle emissions from mobile sources: Discussion of ultrafine particle emissions and definition.

There is no universally agreed upon definition for ultrafine particles (UFP). Commonly used definitions for UFP are either particle number below 100 nm or total particle number, but without an agreed upon lower cut point. For example, a lower cut point of 3 nm compared to 10 nm could result in a substantially higher count. Another definition for UFP is total particle mass but without a commonly agreed upon aerodynamic diameter upper cut point, e.g., below 100 nm, 200 nm, 300 nm, etc. Yet another definition is lung deposited surface area weighted by lung deposition fraction, found mainly in the particle mobility diameter range from 20 to 400 nm. It is clear from these definitions that there are inconsistencies in the way UFP is used and defined in the literature. Sometimes these metrics are well correlated, sometimes not. In this paper we suggest three exposure metrics: UFP-N, UFP-M, and UFP-S, that we believe will add clarity. These metrics represent total number, mass, and surface area below 500 nm, respectively. For surface area and mass, the 500 nm cut point can be either aerodynamic or mobility diameter depending upon measurement methodology. For all metrics, this cut point captures nearly all of the primary particle emissions from mobile sources. Furthermore, UFP-N would include a lower cut point of 3-6 nm and would not require an upper size cut point because there is very little particle number above 500 nm or even above 100 nm. Thus, our definition of UFP-N is consistent with the current definition of ultrafine number except for, importantly, the specification of a lower cut point. These exposure metrics can help facilitate consistency in the characterization of both short- and long-term UFP ambient exposures and associated health effects in epidemiological studies.

NRF2 Protects against Altered Pulmonary T Cell Differentiation in Neonates Following In Utero Ultrafine Particulate Matter Exposure.

Early life exposure to particulate matter (PM) air pollution negatively impacts neonatal health. The underlying mechanisms following prenatal exposure, particularly to ultrafine particles (UFP, diameter ≤ 0.1 µm), are not fully understood; To evaluate the role of Nrf2 in response to in utero UFP exposure, we exposed time-mated Nrf2-deficient (Nrf2-/-) or wildtype (WT) mice to filtered air (FA) or 100 µg/m3 ultrafine PM daily throughout pregnancy. Offspring were evaluated for pulmonary immunophenotypes and pulmonary/systemic oxidative stress on postnatal day 5, a timepoint at which we previously demonstrated viral respiratory infection susceptibility; Nrf2-/- offspring exposed to FA had significantly lower average body weights compared to FA-exposed WT pups. Moreover, PM-exposed Nrf2-/- offspring weighed significantly less than PM-exposed WT pups. Notably, PM-exposed Nrf2-/- offspring showed a decreased pulmonary Th1/Th2 ratio, indicating a Th2 bias. Th17 cells were increased in FA-exposed Nrf2-/- neonates yet decreased in PM-exposed Nrf2-/- neonates. Analysis of oxidative stress-related genes in lung and oxidative stress biomarkers in liver tissues did not vary significantly across exposure groups or genotypes. Collectively, these findings indicate that the lack of Nrf2 causes growth inhibitory effects in general and in response to gestational UFP exposure. Prenatal UFP exposure skews CD4+ T lymphocyte differentiation toward Th2 in neonates lacking Nrf2, signifying its importance in maternal exposure and infant immune responses.

NRF2-Dependent Placental Effects Vary by Sex and Dose following Gestational Exposure to Ultrafine Particles.

Exposure to ultrafine particles (UFPs, PM0.1) during pregnancy triggers placental oxidative stress and inflammation, similar to fine PM (PM2.5). The Nrf2 gene encodes a redox-sensitive transcription factor that is a major regulator of antioxidant and anti-inflammatory responses. Disruption of NRF2 is known to substantially enhance PM2.5-driven oxidant and inflammatory responses; however, specific responses to UFP exposure, especially during critical windows of susceptibility such as pregnancy, are not fully characterized; To investigate the role of NRF2 in regulating maternal antioxidant defenses and placental responses to UFP exposure, wildtype (WT) and Nrf2-/- pregnant mice were exposed to either low dose (LD, 100 µg/m3) or high dose (HD, 500 µg/m3) UFP mixture or filtered air (FA, control) throughout gestation; Nrf2-/- HD-exposed female offspring exhibited significantly reduced fetal and placental weights. Placental morphology changes appeared most pronounced in Nrf2-/- LD-exposed offspring of both sexes. Glutathione (GSH) redox analysis revealed significant increases in the GSH/GSSG ratio (reduced/oxidized) in WT female placental tissue exposed to HD in comparison with Nrf2-/- HD-exposed mice. The expression of inflammatory cytokine genes (Il1ß, Tnfα) was significantly increased in Nrf2-/- placentas from male and female offspring across all exposure groups. Genes related to bile acid metabolism and transport were differentially altered in Nrf2-/- mice across sex and exposure groups. Notably, the group with the most marked phenotypic effects (Nrf2-/- HD-exposed females) corresponded to significantly higher placental Apoa1 and Apob expression suggesting a link between placental lipid transport and NRF2 in response to high dose UFP exposure; Disruption of NRF2 exacerbates adverse developmental outcomes in response to high dose UFP exposure in female offspring. Morphological effects in placenta from male and female offspring exposed to low dose UFPs also signify the importance of NRF2 in maternal-fetal response to UFPs.

Gestational Exposure to Ultrafine Particles Reveals Sex- and Dose-Specific Changes in Offspring Birth Outcomes, Placental Morphology, and Gene Networks.

Particulate matter (PM) causes adverse developmental outcomes following prenatal exposure, but the underlying biological mechanisms remain uncertain. Here we elucidate the effects of diesel exhaust ultrafine particle (UFP) exposure during pregnancy on placental and fetal development. Time-mated C57Bl/6n mice were gestationally exposed to UFPs at a low dose (LD, 100 µg/m3) or high dose (HD, 500 µg/m3) for 6 h daily. Phenotypic effects on fetuses and placental morphology at gestational day (GD) of 18.5 were evaluated, and RNA sequencing was characterized for transcriptomic changes in placental tissue from male and female offspring. A significant decrease in average placental weights and crown to rump lengths was observed in female offspring in the LD exposure group. Gestational UFP exposure altered placental morphology in a dose- and sex-specific manner. Average female decidua areas were significantly greater in the LD and HD groups. Maternal lacunae mean areas were increased in the female LD group, whereas fetal blood vessel mean areas were significantly greater in the male LD and HD groups. RNA sequencing indicated several disturbed cellular functions related to lipid metabolism, which were most pronounced in the LD group and especially in female placental tissue. Our findings demonstrate the vulnerability of offspring exposed to UFPs during pregnancy, highlighting sex-specific effects and emphasizing the importance of mitigating PM exposure to prevent adverse health outcomes.

Effectual removal of indoor ultrafine PM using submicron water droplets.

Exposure to ultrafine airborne particulate matter (PM1.0) poses a significant risk to human health and well-being. Examining the effect of submicron water droplets on the removal of ultrafine PM is timely and important for mitigating indoor ultrafine PM, which is difficult to filter out from incoming air. In this study, submicron water droplets were made by using a nanoporous membrane and an ultrasonic module of a commercial household ultrasonic humidifier (UH) for effectual ultrafine PM removal. The effect of water droplet size on indoor PM removal was experimentally investigated. Variations in the normalized PM concentration, removal efficiency and deposition constants were evaluated by analyzing the temporal variation in PM concentration inside a test chamber. The measured PM deposition constants were compared with the results of other previous studies. As a result, submicron water droplets of 800 nm in mean diameter were generated by ultrasonic module combined passive nanoporous membrane, and PM1.0 concentration decreased by 30% in the initial 30 min. Compared with micron-sized water droplets, PM1.0 removal efficiency improved by approximately two times higher. Moreover, the substitution of the experimental results into a theoretical model ascertained that PM collection efficiency is increased by approximately 103 levels as the size of water droplets decreases. These results would be utilized in the development and implementation of effective strategies for indoor PM removal.

A Systematic Review of The Impact of Commercial Aircraft Activity on Air Quality Near Airports.

Commercial airport activity can adversely impact air quality in the vicinity of airports, and millions of people live close to major airports in the United States. Because of these potential impacts, a systematic literature review was conducted to identify peer reviewed literature on air quality near commercial airports and assess the quality of the studies. The systematic review included reference database searches in PubMed, Web of Science, and Google Scholar, inclusive of years 2000 through 2020. We identified 3,301 articles, and based on the inclusion and exclusion criteria developed, seventy studies were identified for extraction and evaluation using a combination of supervised machine learning and manual screening techniques. These studies consistently showed that ultrafine particulate matter (UFP) is elevated in and around airports. Furthermore, many studies show elevated levels of particulate matter under 2.5 microns in diameter (PM2.5), black carbon, criteria pollutants, and polycyclic aromatic hydrocarbons as well. Finally, the systematic review, while not focused on health effects, identified a limited number of on-topic references reporting adverse health effects impacts, including increased rates of premature death, pre-term births, decreased lung function, oxidative DNA damage and childhood leukemia. More research is needed linking particle size distributions to specific airport activities, and proximity to airports, characterizing relationships between different pollutants, evaluating long-term impacts, and improving our understanding of health effects.

Pulmonary toxicity of actual alveolar deposition concentrations of ultrafine particulate matters in human normal bronchial epithelial cell.

Air pollution is a major worldwide concern, and exposure to particulate matter (PM) can increase the risks of pulmonary diseases. Normal human bronchial epithelial cells were applied to clarify the role of ultrafine PM (UFPM) in the pathogenesis of pulmonary toxic effects with realistic alveolar deposition doses. The UFPM used in this research originated from vehicular emissions and coal combustion. UFPM exposure of up to 72 h was found to induce significant time- and concentration-dependent decreases in cell viability. Exposure to UFPM increased reactive oxygen species (ROS) accumulation through heme oxygenase-1 (HO-1) inhibition and induced massive oxidative stress that increased the interleukin-8 (IL-8) expression. UFPM also reduced the pulmonary trans-epithelial electrical resistance through the depletion of zonula occludens (ZO) proteins. Finally, UFPM decreased the α1-antitrypsin (A1AT) expression, which implies high risk of chronic obstructive pulmonary disease (COPD). The evidence demonstrates that exposure to UFPM, even at very low concentrations, may affect the functions of the respiratory system.

Urban Air Pollution Nanoparticles from Los Angeles: Recently Decreased Neurotoxicity.

BACKGROUND: Air pollution is widely associated with accelerated cognitive decline at later ages and risk of Alzheimer's disease (AD). Correspondingly, rodent models demonstrate the neurotoxicity of ambient air pollution and its components. Our studies with nano-sized particulate matter (nPM) from urban Los Angeles collected since 2009 have shown pro-amyloidogenic and pro-inflammatory responses. However, recent batches of nPM have diminished induction of the glutamate receptor GluA1 subunit, Iba1, TNFα, Aß42 peptide, and white matter damage. The same methods, materials, and mouse genotypes were used throughout. OBJECTIVE: Expand the nPM batch comparisons and evaluate archived brain samples to identify the earliest change in nPM potency. METHODS: Batches of nPM were analyzed by in vitro cell assays for NF-κB and Nrf2 induction for comparison with in vivo responses of mouse brain regions from mice exposed to these batches, analyzed by PCR and western blot. RESULTS: Five older nPM batches (2009-2017) and four recent nPM batches (2018, 2019) for NF-κB and Nrf2 induction showed declines in nPM potency after 2017 that paralleled declines of in vivo activity from independent exposures in different years. CONCLUSION: Transcription-based in vitro assays of nPM corresponded to the loss of in vivo potency for inflammatory and oxidative responses. These recent decreases of nPM neurotoxicity give a rationale for evaluating possible benefits to the risk of dementia and stroke in Los Angeles populations.

The Protective Effects of Shengmai Formula Against Myocardial Injury Induced by Ultrafine Particulate Matter Exposure and Myocardial Ischemia are Mediated by the PI3K/AKT/p38 MAPK/Nrf2 Pathway.

Background and Purpose: Ultrafine particulate matter (UFPM) induces oxidative stress (OS) and is considered to be a risk factor of myocardial ischemia (MI). Shengmai formula (SMF) is a traditional Chinese medicine with antioxidant properties and has been used to treat cardiovascular diseases for a long time. The aim of this study was to explore the protective role of SMF and the mechanism by which it prevents myocardial injury in UFPM-exposed rats with MI. Methods: An MI rat model was established. Animals were randomly divided into five groups: sham, UFPM + MI, SMF (1.08 mg/kg⋅d) + UFPM + MI, SMF (2.16 mg/kg⋅d) + UFPM + MI, and SMF (4.32 mg/kg⋅d) + UFPM + MI. SMF or saline was administrated 7 days before UFPM instillation (100 µg/kg), followed by 24 h of ischemia. Physiological and biochemical parameters were measured, and histopathological examinations were conducted to evaluate myocardial damage. We also explored the potential mechanism of the protective role of SMF using a system pharmacology approach and an in vitro myoblast cell model with small molecule inhibitors. Results: UFPM produced myocardial injuries on myocardial infarct size; serum levels of LDH, CK-MB, and cardiac troponin; and OS responses in the rats with MI. Pretreatment with SMF significantly attenuated these damages via reversing the biomarkers. SMF also improved histopathology induced by UFPM and significantly altered the PI3K/AKT/MAPK and OS signaling pathways. The expression patterns of Cat, Gstk1, and Cyba in the UFPM model group were reversed in the SMF-treated group. In in vitro studies, SMF attenuated UFPM-induced reactive oxygen species production, mitochondrial damage, and OS responses. The PI3K/AKT/p38 MAPK/Nrf2 pathway was significantly changed in the SMF group compared with that in the UFPM group, whereas opposite results were obtained for pathway inhibition. Conclusion: These findings indicate that SMF prevents OS responses and exerts beneficial effects against myocardial injury induced by UFPM + MI in rats. Furthermore, the PI3K/AKT/p38 MAPK/Nrf2 signaling pathway might be involved in the protective effects of SMF.

Associations between socioeconomic status and ultrafine particulate exposure in the school commute: An environmental inequality study for Toronto, Canada.

Ultrafine particulate matter (UFP) air pollution is unevenly distributed across urban environments. Disparities in routine activity patterns, such as the exposure risk we face at work or on the commute, can contribute to chronic exposure-related health outcomes that place excess burdening on vulnerable population groups. In Canada, there is disagreement in the literature on the nature of these exposure-related inequalities, and our understanding of disparities associated with specific activity patterns such as commuting is limited. In the context of UFP specific exposure, these relationships are almost entirely unexplored in the environmental inequality literature. Our study presents an exploratory analysis of UFP exposure patterns in Toronto, Canada. We examined UFP dosage disparities experienced by children during routine school commutes. We estimated single trip dosages that accounted for variation in ambient UFP concentration, route morphology (distance, slope) and their effect on inhalation rate and trip duration. We aggregated these values at the dissemination-area level and collected socioeconomic status descriptors from the 2016 census. Our OLS model showed significant spatial autocorrelation (MI = 0.59, p < 0.001), and we instead applied a spatial error model to account for spatial effects in our dataset. We identified significant associations related to median income (ß = -0.087, p < 0.05), government transfer dependence (ß = -0.107, p < 0.005), immigration status (ß = 0.119, p < 0.001), and education rates (ß = -0.059, p < 0.05). Our results diverged from other pollutants in Toronto-based literature and could indicate that UFPs exhibit unique patterns of inequality. Our findings suggest a need to further study UFP dosage from an environmental inequality perspective.

Emission factors of ultrafine particulate matter (PM<0.1 µm) and particle-bound polycyclic aromatic hydrocarbons from biomass combustion for source apportionment.

Data for source apportionment estimation was obtained from combustion of 11 types of biomass (rubber wood, palm kernel, palm fiber, sugarcane bagasse, sugarcane leaves, maize residue, rice stubble, rice straw, Xylocarpus moluccensis, Avicennia alba Blume and Rhizophora mucronata) and bituminous coal. Combustion was carried out in a tube furnace and emitted particulate matter (PM) was collected using a nanosampler that segregated particle sizes down to 0.1 µm. Emission factors of PM < 0.1 µm were in the range of 0.11-0.28 g kg-1 (∼1-8% of total PM), except in the case of Rhizophora mucronata, which had an emission factor of 0.071 ± 0.004 g kg-1 (∼18% of total PM). The dominant polycyclic aromatic hydrocarbons (PAHs) found on PM < 0.1 µm were chrysene from combustion of rubber wood, palm kernel, palm fiber, maize residue, Xylocarpus moluccensis, Avicennia alba Blume, Rhizophora mucronata and bituminous coal; benzo[b]fluoranthene from combustion of rice straw, sugarcane bagasse and sugarcane leaves; and benzo[k]fluoranthene from rice stubble combustion. The emission factors of PAHs bound to PM < 0.1 µm from biomass combustion ranged from 0.005 to 0.044 mg kg-1 and the emission factor from bituminous coal combustion was 0.1411 ± 0.0004 mg kg-1. The carcinogenic potency equivalent or benzo[a]pyrene equivalent was highest from bituminous coal combustion (0.1252 mg kg-1) and between 0.0019 and 0.0192 mg kg-1 from biomass combustion. However, emission factors of both PM and particle-bound PAHs from biomass combustion were affected by moisture content of biomass and moisture contents of biomass used in this study were quite low, ranging from 0.165 to 0.863%.