Hyperlocal Air Pollution Mapping: A Scalable Transfer Learning LUR Approach for Mobile Monitoring.

Addressing the challenge of mapping hyperlocal air pollution in areas without local monitoring, we evaluated unsupervised transfer learning-based land-use regression (LUR) models developed using mobile monitoring data from other cities: CORrelation ALignment (Coral) and its inverse distance-weighted modification (IDW_Coral). These models mitigated domain shifts and transferred patterns learned from mobile air quality monitoring campaigns in Copenhagen and Rotterdam to estimate annual average air pollution levels in Amsterdam (50m road segments) without involving any Amsterdam measurements in model development. For nitrogen dioxide (NO2), IDW_Coral outperformed Copenhagen and Rotterdam LUR models directly applied to Amsterdam, achieving MAE (4.47 µg/m3) and RMSE (5.36 µg/m3) comparable to a locally fitted LUR model (AMS_SLR) developed using Amsterdam mobile measurements collected for 160 days. IDW_Coral yielded an R2 of 0.35, similar to that of the AMS_SLR based on 20 collection days, suggesting a minimum requirement of 20-day mobile monitoring to capture city-specific insights. For ultrafine particles (UFP), IDW_Coral's citywide predictions strongly correlated with previously published mixed-effect models fitted with 160-day Amsterdam measurements (Pearson correlation of 0.71 for UFP and 0.72 for NO2). IDW_Coral demands no direct measurements in the target area, showcasing its potential for large-scale applications and offering significant economic efficiencies in executing mobile monitoring campaigns.

Toward Cleaner Transport Alternatives: Reduction in Exposure to Air Pollutants in a Mass Public Transport.

Commuters are often exposed to higher concentrations of air pollutants due to its proximity to mobile sources. Despite recent trends in urban transport toward zero- and low-tailpipe emission alternatives, the assessments of the impact of these transformations on commuter exposure are limited by the low frequency of such studies. In this work, we use a unique data set of personal exposure concentration measurements collected over the span of 5 years to analyze changes due to the introduction of a new fleet for Bogotá's Bus Rapid Transit System. In that system, over a thousand Euro-II and -III diesel-powered buses were replaced with Euro-VI compressed natural gas and filter-equipped Euro-V diesel buses. We measured personal exposure concentrations of equivalent black carbon (eBC), fine particulate (PM2.5), and ultra fine particles (UFP) during and after the retirement of old buses and the introduction of new ones. Observations collected prior to the fleet renewal were used as baseline and later compared to data collected over two follow-up campaigns in 2019 and 2020. Significant reductions in the concentration of PM2.5 and eBC were observed during the 2019 campaign, with a 48% decrease for mean in-bus eBC (89.9 to 46.4 µg m-3) and PM2.5 (180.7 to 95.4 µg m-3) concentrations. Further reductions were observed during the 2020 follow-up, when the fleet renovation was completed, with mean in-bus eBC decreasing to 17.7 µg m-3 and PM2.5 to 42.3 µg m-3. These observations imply nearly a 5-fold reduction in eBC exposure and a 4-fold decrease in PM2.5. There was a much smaller reduction of in-bus UFP concentration between 2019 and 2020, indicating a persistent presence of high particle number concentrations in the near-road environment despite the fleet renovation process. In-bus UFP concentrations ranged between 65 000 and 104 500 cm-3 during the follow-up campaigns. The results in this work illustrate the immediate benefits of reducing personal exposure through the adoption of vehicles with more stringent emission standards.

Characterization of Annual Average Traffic-Related Air Pollution Concentrations in the Greater Seattle Area from a Year-Long Mobile Monitoring Campaign.

Growing evidence links traffic-related air pollution (TRAP) to adverse health effects. We designed an innovative and extensive mobile monitoring campaign to characterize TRAP exposure levels for the Adult Changes in Thought (ACT) study, a Seattle-based cohort. The campaign measured particle number concentration (PNC) to capture ultrafine particles (UFP), black carbon (BC), nitrogen dioxide (NO2), fine particulate matter (PM2.5), and carbon dioxide (CO2) at 309 roadside sites within a large, 1200 land km2 (463 mi2) area representative of the cohort. We collected about 29 two-minute measurements at each site during all seasons, days of the week, and most times of the day over a 1-year period. Validation showed good agreement between our BC, NO2, and PM2.5 measurements and monitoring agency sites (R2 = 0.68-0.73). Universal kriging-partial least squares models of annual average pollutant concentrations had cross-validated mean square error-based R2 (and root mean square error) values of 0.77 (1177 pt/cm3) for PNC, 0.60 (102 ng/m3) for BC, 0.77 (1.3 ppb) for NO2, 0.70 (0.3 µg/m3) for PM2.5, and 0.51 (4.2 ppm) for CO2. Overall, we found that the design of this extensive campaign captured the spatial pollutant variations well and these were explained by sensible land use features, including those related to traffic.

Nociceptin/orphanin FQ peptide receptor mediates inhibition of N-type calcium currents in vestibular afferent neurons of the rat.

The vestibular system is modulated by various neuromodulators including opioid peptides. The current study was conducted to determine whether activation of nociceptin/orphanin FQ peptide (NOP) receptors modulates voltage-gated calcium currents and action potential discharge of rat vestibular afferent neurons. We performed whole cell patch-clamp recordings on cultured vestibular afferent neurons from P7-P10 Long-Evans rats. Application of nociceptin/orphanin FQ (N/OFQ), a 17-amino acid neuropeptide that is the endogenous ligand for NOP receptor, inhibits the high-voltage activated (HVA) component of the calcium current in a concentration-dependent manner with a half inhibitory concentration of 26 nM. Said inhibitory action on the calcium current is voltage-dependent, which was made clear by the fact that it was reverted in 80% by a depolarizing prepulse. Furthermore, the effect of N/OFQ was blocked by application of the specific NOP-antagonist UFP101, by preincubation with G-protein blocker pertussis toxin, and by coapplication of the specific N-type calcium-current blocker ω-conotoxin-MVIIA. N/OFQ application causes an increase in the duration and maximum rate of repolarization of action potentials. It also decreases repetitive discharge and discharge elicited by sinusoidal stimulation. These results show that in vestibular afferents, NOP receptor activation inhibits N-type calcium current by activating G proteins, mostly through the Gßγ subunit. This suggests that NOP activation produces a presynaptic modulation of primary vestibular afferent neurons' output into the vestibular nuclei, thus taking part in the integration and gain setting of vestibular information in second-order vestibular nucleus neurons.NEW & NOTEWORTHY Our results show that in primary vestibular afferent neurons, activation of the nociceptin/orphanin FQ peptide receptor inhibits the N-type calcium current by a mechanism mediated by G proteins. We propose that calcium current inhibition modulates neurotransmitter release from vestibular afferents, producing a presynaptic modulation of vestibular input to vestibular nuclei, thus contributing to gain control in the vestibular afferent input.

Cardiovascular adaptations to particle inhalation exposure: molecular mechanisms of the toxicology.

Ambient air, occupational settings, and the use and distribution of consumer products all serve as conduits for toxicant exposure through inhalation. While the pulmonary system remains a primary target following inhalation exposure, cardiovascular implications are exceptionally culpable for increased morbidity and mortality. The epidemiological evidence for cardiovascular dysfunction resulting from acute or chronic inhalation exposure to particulate matter has been well documented, but the mechanisms driving the resulting disturbances remain elusive. In the current review, we aim to summarize the cellular and molecular mechanisms that are directly linked to cardiovascular health following exposure to a variety of inhaled toxicants. The purpose of this review is to provide a comprehensive overview of the biochemical changes in the cardiovascular system following particle inhalation exposure and to highlight potential biomarkers that exist across multiple exposure paradigms. We attempt to integrate these molecular signatures in an effort to provide direction for future investigations. This review also characterizes how molecular responses are modified in at-risk populations, specifically the impact of environmental exposure during critical windows of development. Maternal exposure to particulate matter during gestation can lead to fetal epigenetic reprogramming, resulting in long-term deficits to the cardiovascular system. In both direct and indirect (gestational) exposures, connecting the biochemical mechanisms with functional deficits outlines pathways that can be targeted for future therapeutic intervention. Ultimately, future investigations integrating "omics"-based approaches will better elucidate the mechanisms that are altered by xenobiotic inhalation exposure, identify biomarkers, and guide in clinical decision making.

Fifteen Years of Airborne Particulates in Vitro Toxicology in Milano: Lessons and Perspectives Learned.

Air pollution is one of the world's leading environmental causes of death. The epidemiological relationship between outdoor air pollution and the onset of health diseases associated with death is now well established. Relevant toxicological proofs are now dissecting the molecular processes that cause inflammation, reactive species generation, and DNA damage. In addition, new data are pointing out the role of airborne particulates in the modulation of genes and microRNAs potentially involved in the onset of human diseases. In the present review we collect the relevant findings on airborne particulates of one of the biggest hot spots of air pollution in Europe (i.e., the Po Valley), in the largest urban area of this region, Milan. The different aerodynamic fractions are discussed separately with a specific focus on fine and ultrafine particles that are now the main focus of several studies. Results are compared with more recent international findings. Possible future perspectives of research are proposed to create a new discussion among scientists working on the toxicological effects of airborne particles.

Variability of aerosol mass and number concentrations during taconite mining operations.

This study characterized concentration metrics of airborne nanoparticles and their time series across major operations of a taconite mine through monitoring respirable and ultrafine particle concentrations at four major processing departments of the mine: crushing, dry milling, wet milling, and pelletizing (United Taconite Mine, Iron Junction, MN, USA). We used three area stations of direct-reading instruments to estimate concentration metrics including PM1 (particles with an aerodynamic diameter <1 µm), respirable dust (particles sampled according to the respirable convention with a 50% sampling efficiency at an aerodynamic diameter of 4 µm), PN (total number concentration of particles), and lung-deposited surface area concentrations (LDSA) of particles smaller than 300 nm, on two different days. Results for each station were compared using bivariate correlation analysis to obtain insight into the spatial distribution, and intra-class correlation coefficients (ICCs) to evaluate the between-day repeatability between the measurements. Comparability of the LDSA concentrations measured by two different devices was also investigated using linear regression. Results revealed that the pelletizing operation produced the highest average LDSA concentration on both days (with a maximum concentration of 199 ± 48 µm2/cm3 in pelletizing, 141 ± 52 µm2/cm3 in crushing, 91 ± 9 µm2/cm3 in dry milling, and 85 ± 7 µm2/cm3 in wet milling). Concentrations in all operations showed a fair to excellent between-day repeatability but they were significantly different within stations of each operation. Measured LDSA concentrations did not show a linear correlation between different instruments, except for crushing.

(Ultra) Fine particle concentrations and exposure in different indoor and outdoor microenvironments during physical exercising.

Although regular exercise improves overall well-being, increased physical activity results in enhanced breathing which consequently leads to elevated exposure to a variety of air pollutants producing adverse effects. It is well-known that one of these ambient air contaminants is ultrafine particles (UFP). Thus, this study aimed to (1) examine exposure to particle number concentrations (PNC) in size ranging from N20-1000 nm in different sport environments and (2) estimate the respective inhalation doses across varying activity scenarios based upon the World Health Organization recommendations for physical activity. PNC were continuously monitored (TSI P-Trak™ condensation particle counter) outdoors (Out1-Out2) and indoors (Ind1-Ind2; fitness clubs) over 4 weeks. Outdoor PNC (total median 12 563 # cm-3; means of 20 367 # cm-3 at Out1 and 7 122 # cm-3 at Out2) were approximately 1.6-fold higher than indoors (total median 7 653 # cm-3; means of 11 861 # cm-3 at Ind1 and 14 200 # cm-3 at Ind2). The lowest doses were inhaled during holistic group classes (7.91 × 107-1.87 × 108 # per kg body weight) whereas exercising with mixed cardio and strength training led to approximately 1.8-fold higher levels. In order to optimize the health benefit of exercises, environmental characteristics of the locations at which physical activities are conducted need to be considered.

Ambient ultrafine particles activate human monocytes: Effect of dose, differentiation state and age of donors.

Exposure to ambient particulate matter (PM) has been linked to adverse pulmonary and cardiovascular health effects. Activation of both inflammatory and oxidative stress pathways has been observed and may be a probable cause of these outcomes. We tested the hypothesis that in human monocytes, PM-induced oxidative and inflammatory responses are interrelated. A human monocytic cell line (THP-1) was used to determine if dose and differentiation state plays a role in the cellular response after a 24hr exposure to particles. Primary human monocytes derived from eight female, non-smoker donors (aged: 21, 24, 27, 28, 48, 49, 54 & 60yo) were used to determine if the age of donors modulates the response. Cells were treated with aqueous suspensions of ambient ultrafine particles (UFP, defined as smaller than 0.2µm in size) or a media control for 24hr. After exposure, reactive oxygen species (ROS) formation was increased irrespective of dose or differentiation state of THP-1 cells. In the primary human monocytes, ROS formation was not significantly changed. The release of the proinflammatory cytokine, tumor necrosis factor alpha (TNF-α), was dose-dependent and greatest in differentiated compared to undifferentiated THP-1 cells exposed to UFP. In the Primary human monocytes, TNF-α secretion was increased irrespective of the age of the donor. Our results suggest that after a 24hr exposure to particles, general reactive oxygen species formation was nonspecific and uncorrelated to cytokine secretion which was consistently enhanced. Cytokines play an important role in orchestrating many immune responses and thus the ability of ambient particles to enhance robust secretion of a proinflammatory cytokine from primary human monocytes, and how this may influence the response to pathogens and alter disease states, needs to be further evaluated.

Enhanced cerebellar myelination with concomitant iron elevation and ultrastructural irregularities following prenatal exposure to ambient particulate matter in the mouse.

Accumulating evidence indicates the developing central nervous system (CNS) is a target of air pollution toxicity. Epidemiological reports increasingly demonstrate that exposure to the particulate matter (PM) fraction of air pollution during neurodevelopment is associated with an increased risk of neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD). These observations are supported by animal studies demonstrating prenatal exposure to concentrated ambient PM induces neuropathologies characteristic of ASD, including ventriculomegaly and aberrant corpus callosum (CC) myelination. Given the role of the CC and cerebellum in ASD etiology, this study tested whether prenatal exposure to concentrated ambient particles (CAPs) produced pathological features in offspring CC and cerebella consistent with ASD. Analysis of cerebellar myelin density revealed male-specific hypermyelination in CAPs-exposed offspring at postnatal days (PNDs) 11-15 without alteration of cerebellar area. Atomic absorption spectroscopy (AAS) revealed elevated iron (Fe) in the cerebellum of CAPs-exposed female offspring at PNDs 11-15, which connects with previously observed elevated Fe in the female CC. The presence of Fe inclusions, along with aluminum (Al) and silicon (Si) inclusions, were confirmed at nanoscale resolution in the CC along with ultrastructural myelin sheath damage. Furthermore, RNAseq and gene ontology (GO) enrichment analyses revealed cerebellar gene expression was significantly affected by sex and prenatal CAPs exposure with significant enrichment in inflammation and transmembrane transport processes that could underlie observed myelin and metal pathologies. Overall, this study highlights the ability of PM exposure to disrupt myelinogenesis and elucidates novel molecular targets of PM-induced developmental neurotoxicity.

Robustness of intra urban land-use regression models for ultrafine particles and black carbon based on mobile monitoring.

Land-use regression (LUR) models for ultrafine particles (UFP) and Black Carbon (BC) in urban areas have been developed using short-term stationary monitoring or mobile platforms in order to capture the high variability of these pollutants. However, little is known about the comparability of predictions of mobile and short-term stationary models and especially the validity of these models for assessing residential exposures and the robustness of model predictions developed in different campaigns. We used an electric car to collect mobile measurements (n = 5236 unique road segments) and short-term stationary measurements (3 × 30min, n = 240) of UFP and BC in three Dutch cities (Amsterdam, Utrecht, Maastricht) in 2014-2015. Predictions of LUR models based on mobile measurements were compared to (i) measured concentrations at the short-term stationary sites, (ii) LUR model predictions based on short-term stationary measurements at 1500 random addresses in the three cities, (iii) externally obtained home outdoor measurements (3 × 24h samples; n = 42) and (iv) predictions of a LUR model developed based upon a 2013 mobile campaign in two cities (Amsterdam, Rotterdam). Despite the poor model R2 of 15%, the ability of mobile UFP models to predict measurements with longer averaging time increased substantially from 36% for short-term stationary measurements to 57% for home outdoor measurements. In contrast, the mobile BC model only predicted 14% of the variation in the short-term stationary sites and also 14% of the home outdoor sites. Models based upon mobile and short-term stationary monitoring provided fairly high correlated predictions of UFP concentrations at 1500 randomly selected addresses in the three Dutch cities (R2 = 0.64). We found higher UFP predictions (of about 30%) based on mobile models opposed to short-term model predictions and home outdoor measurements with no clear geospatial patterns. The mobile model for UFP was stable over different settings as the model predicted concentration levels highly correlated to predictions made by a previously developed LUR model with another spatial extent and in a different year at the 1500 random addresses (R2 = 0.80). In conclusion, mobile monitoring provided robust LUR models for UFP, valid to use in epidemiological studies.

Ventilation dependence of concentration metrics of Ultra-fine Particles in a coagulating household smoke.

Role of Ultra-fine Particles (UFPs) in causing adverse health effects among large population across the world, attributable to household smoke, is being increasingly recognized. However, there is very little theoretical perspective available on the complex behavior of the UFP metrics with respect to controlling factors, such as ventilation rate and particle emission rate from the combustion sources. This numerical study examines through coagulation dynamics, the dependence of UFP metrics, viz., number (PN), mass (PM(0.1)) and surface area (PA(0.1)) concentrations below 0.1 µm diameter, on ventilation and the number emission rate from household smoke. For strong sources, the steady-state concentrations of these metrics are found to increase initially with increasing Air Exchange Rate (AER), reach a peak value and then decrease. Counter correlations are seen between UFP metric and PM(2.5) concentrations. The concepts of Critical Air Exchange Rate (CAER) and Half-Value Air Exchange Rate (HaVAER) have been introduced which indicate a feasibility of mitigation of PM(0.1) and PA(0.1), unlike PN, by ventilation techniques. The study clearly brings forth complex differential behavior of the three UFP metrics. The results are further discussed.

Combined toxicity of amorphous silica nanoparticles and methylmercury to human lung epithelial cells.

Exposure to the ambient particulate matters (PM) has been associated with the morbidity and mortality of cardiopulmonary diseases. Compared with coarse particles, ultrafine particles (UFP) absorb or condense higher concentration of toxic air pollutants and are easily inhaled into the lung. However, the combined effects of UFP and air pollutants on human health are still poorly understood. In this study, a co-exposure in vitro model of amorphous silica nanoparticles (nano-SiO2) and methyl mercury (MeHg) was established to investigate their combined effects and the potential joint action type. Lung adenocarcinoma cells (A549) were exposed to either nano-SiO2 or MeHg alone, or a combination of both. Factorial design was applied to analyze their potential joint action type. Higher interfacial energy was observed in the mixed solution of nano-SiO2 and MeHg. The intracellular content of both silicon and mercury in combination group were much higher than those in single exposure groups. In addition, the co-exposure of nano-SiO2 and MeHg enhanced the reactive oxygen species (ROS) generation, lipid peroxidation and reduced the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px). The excessive oxidative stress led to oxidative DNA damage as well as cellular apoptosis. Factorial design analysis demonstrated that additive and synergistic interactions were responsible for the combined toxicity of nano-SiO2 and MeHg.

Dynamics of ultrafine particles inside a roadway tunnel.

Size-segregated ultrafine particles from motor vehicles were investigated in the Craeybeckx tunnel (E19 motorway, Antwerp, Belgium) at two measurement sites, at 100 and 300 m inside the tunnel, respectively, during March 2008. It was observed that out of the three size modes, nucleation, Aitken, and accumulation, Aitken mode was the most dominant size fraction inside the tunnel. The diurnal variation in ultrafine particle (UFP) levels closely follows the vehicular traffic inside the tunnel, which was maximum during office rush hours, both in the morning and evening and minimum during night-time around 3 am. The tunnel data showed very high growth rates in comparison with free atmosphere. The average condensation sink during the growth period was 14.1-17.3 × 10(-2) s(-1). The average growth rate (GR) of geometric mean diameter was found to be 18.6 ± 2.45 nm h(-1). It was observed that increase in Aitken mode was related to the numbers of heavy-duty vehicles (HDV), as they emit mainly in the Aitken mode. The higher Aitken mode during traffic jams correlated well with HDV numbers. At the end of the tunnel, sudden dilution leading to fast coagulation was responsible for the sudden drop in the UFP number concentration.

Detection of mutations in the CYP21A2 gene: genotype-phenotype correlation in Slovenian couples with conceiving problems.

The objective of this study was to compare the CYP 21A2 genetic profiles of couples with unexplained fertility problems (UFP) with genetic profiles of healthy controls (HCs). Furthermore, we analyzed associations between mutations in the CYP21A2 gene and various clinical and laboratory parameters. Allele-specific polymerase chain reaction (PCR) was used in 638 probands with UFP and 200 HCs. Statistic analysis with χ2 was used to study the association of mutations with infertility. The effect of mutations on particular clinical and laboratory parameters was assessed with the analysis of variance (ANOVA) test. With regard to the CYP21A2 gene, 0.6% of probands with UFP and 0.5% of HCs were positive for the c.290-13A/C>G mutation; 0.6% of probands with UFP and 1.5% of HCs were positive for the p.I172N mutation; there were no probands with UFP positive for the p.P30L mutation, whereas 0.5% of HCs were; and 0.2% of probands with UFP and 0.5% of HCs were found to have the p.V281L mutation. We found a significant association between c.290-13A/C>G mutation and the frequency of significant hormone deviations (χ2 = 6.997, p = 0.008). Similar association was also observed between the c.29013A/C>G mutation and the frequency of polycystic ovary syndrome (PCOS) (χ2 = 16.775, p = 0.000). Our findings indicate that no significant difference in the prevalence of CYP 21A2 mutations can be found in probands with UFP when compared with HCs without infertility history. The results also imply the significant association of the c.290-13A/ C>G mutation in the CYP21A2 gene, not only with the frequency of PCOS, but also with the frequency of significant hormone deviations.

Source apportionment of fine and ultrafine particle number concentrations in a major city of the Eastern Mediterranean.

Ultrafine particles (UFP) are recognized as an emerging pollutant able to induce serious health effects. However, quantitative information regarding the contributions of UFP sources is generally limited. This study evaluates statistical (k-means clustering) and receptor models (Positive Matrix Factorization - PMF) using particle number size distributions (PNSD), along with chemical speciation data, measured at an urban background supersite in Athens, Greece, aiming to characterize their sources. PNSD measurements (10-487 nm) were performed during three distinct periods (warm, cold, and lockdown cold). Traffic and residential biomass burning (BB) produced high UFP number concentrations (NUFP) in the cold period (+107 % compared to summer), while the lockdown restrictions reduced NUFP (-42 %). The five groups produced by cluster analysis that were common among periods were linked to high- and low-traffic, new particle formation (NPF), urban background and regional aerosols. PMF source apportionment identified 5 and 6 factors during warm and cold periods, respectively, indicating that traffic particles dominated NUFP (64-78 % in all periods), while accumulation-mode particles and volume concentrations were controlled by processed aerosol, and especially in the cold periods by BB emissions. A nucleation factor linked to NPF contributed 7-11 % to NUFP. Comparing the two cold periods (business-as-usual, lockdown), important lockdown reductions (-46 %) were seen for fresh traffic contributions to total number concentration (Ntotal). The impact of the source attributed to NPF also eroded (-41 % for Ntotal). Due to the large reduction (-47 % for Ntotal) observed also for the BB source during the lockdown (reduced wood usage due to a milder winter), the relative contributions of all sources did not change considerably (fractional reductions <7 % for Ntotal). The quantitative results, bolstered by source apportionment combining PNSD and online chemical composition measurements, indicate the potential to constrain UFP levels by regulating traffic and residential emissions, with a large upside for population exposure control.

High-resolution spatial and spatiotemporal modelling of air pollution using fixed site and mobile monitoring in a Canadian city.

The development of high-resolution spatial and spatiotemporal models of air pollutants is essential for exposure science and epidemiological applications. While fixed-site sampling has conventionally provided input data for statistical predictive models, the evolving mobile monitoring method offers improved spatial resolution, ideal for measuring pollutants with high spatial variability such as ultrafine particles (UFP). The Quebec Air Pollution Exposure and Epidemiology (QAPEE) study measured and modelled the spatial and spatiotemporal distributions of understudied pollutants, such as UFPs, black carbon (BC), and brown carbon (BrC), along with fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) in Quebec City, Canada. We conducted a combined fixed-site (NO2 and O3) and mobile monitoring (PM2.5, BC, BrC, and UFPs) campaign over 10-months. Mobile monitoring routes were monitored on a weekly basis between 8am-10am and designed using location/allocation modelling. Seasonal fixed-site sampling campaigns captured continuous 24-h measurements over two-week periods. Generalized Additive Models (GAMs), which combined data on pollution concentrations with spatial, temporal, and spatiotemporal predictor variables were used to model and predict concentration surfaces. Annual models for PM2.5, NO2, O3 as well as seven of the smallest size fractions in the UFP range, had high out of sample predictive accuracy (range r2: 0.54-0.86). Varying spatial patterns were observed across UFP size ranges measured as Particle Number Counts (PNC). The monthly spatiotemporal models for PM2.5 (r2 = 0.49), BC (r2 = 0.27), BrC (r2 = 0.29), and PNC (r2 = 0.49) had moderate or moderate-low out of sample predictive accuracy. We conducted a sensitivity analysis and found that the minimum number of 'n visits' (mobile monitoring sessions) required to model annually representative air pollution concentrations was between 24 and 32 visits dependent on the pollutant. This study provides a single source of exposure models for a comprehensive set of air pollutants in Quebec City, Canada. These exposure models will feed into epidemiological research on the health impacts of ambient UFPs and other pollutants.

The Exposure Peaks of Traffic-Related Ultrafine Particles Associated with Inflammatory Biomarkers and Blood Lipid Profiles.

In this article, we explored the effects of ultrafine particle (UFP) peak exposure on inflammatory biomarkers and blood lipids using two novel metrics-the intensity of peaks and the frequency of peaks. We used data previously collected by the Community Assessment of Freeway Exposure and Health project from participants in the Greater Boston Area. The UFP exposure data were time-activity-adjusted hourly average concentration, estimated using land use regression models based on mobile-monitored ambient concentrations. The outcome data included C-reactive protein, interleukin-6 (IL-6), tumor necrosis factor-alpha receptor 2 (TNF-RII), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides and total cholesterol. For each health indicator, multivariate regression models were used to assess their associations with UFP peaks (N = 364-411). After adjusting for age, sex, body mass index, smoking status and education level, an increase in UFP peak exposure was significantly (p < 0.05) associated with an increase in TNF-RII and a decrease in HDL and triglycerides. Increases in UFP peaks were also significantly associated with increased IL-6 and decreased total cholesterol, while the same associations were not significant when annual average exposure was used. Our work suggests that analysis using peak exposure metrics could reveal more details about the effect of environmental exposures than the annual average metric.

Traffic-related ultrafine particles impair mitochondrial functions in human olfactory mucosa cells - Implications for Alzheimer's disease.

Constituents of air pollution, the ultrafine particles (UFP) with a diameter of ≤0.1 µm, are considerably related to traffic emissions. Several studies link air pollution to Alzheimer's disease (AD), yet the exact relationship between the two remains poorly understood. Mitochondria are known targets of environmental toxicants, and their dysfunction is associated with neurodegenerative diseases. The olfactory mucosa (OM), located at the rooftop of the nasal cavity, is directly exposed to the environment and in contact with the brain. Mounting evidence suggests that the UFPs can impact the brain directly through the olfactory tract. By using primary human OM cultures established from nasal biopsies of cognitively healthy controls and individuals diagnosed with AD, we aimed to decipher the effects of traffic-related UFPs on mitochondria. The UFP samples were collected from the exhausts of a modern heavy-duty diesel engine (HDE) without aftertreatment systems, run with renewable diesel (A0) and petroleum diesel (A20), and from an engine of a 2019 model diesel passenger car (DI-E6d) equipped with state-of-the-art aftertreatment devices and run with renewable diesel (Euro6). OM cells were exposed to three different UFPs for 24-h and 72-h, after which cellular processes were assessed on the functional and transcriptomic levels. Our results show that UFPs impair mitochondrial functions in primary human OM cells by hampering oxidative phosphorylation (OXPHOS) and redox balance, and the responses of AD cells differ from cognitively healthy controls. RNA-Seq and IPA® revealed inhibition of OXPHOS and mitochondrial dysfunction in response to UFPs A0 and A20. Functional validation confirmed that A0 and A20 impair cellular respiration, decrease ATP levels, and disturb redox balance by altering NAD and glutathione metabolism, leading to increased ROS and oxidative stress. RNA-Seq and functional assessment revealed the presence of AD-related alterations in human OM cells and that different fuels and engine technologies elicit differential effects.

Generation, characterization, and toxicological assessment of reference ultrafine soot particles with different organic content for inhalation toxicological studies.

Ultrafine particles (UFP) are the smallest atmospheric particulate matter linked to air pollution-related diseases. The extent to which UFP's physical and chemical properties contribute to its toxicity remains unclear. It is hypothesized that UFP act as carriers for chemicals that drive biological responses. This study explores robust methods for generating reference UFP to understand these mechanisms and perform toxicological tests. Two types of combustion-related UFP with similar elemental carbon cores and physical properties but different organic loads were generated and characterized. Human alveolar epithelial cells were exposed to these UFP at the air-liquid interface, and several toxicological endpoints were measured. UFP were generated using a miniCAST under fuel-rich conditions and immediately diluted to minimize agglomeration. A catalytic stripper and charcoal denuder removed volatile gases and semi-volatile particles from the surface. By adjusting the temperature of the catalytic stripper, UFP with high and low organic content was produced. These reference particles exhibited fractal structures with high reproducibility and stability over a year, maintaining similar mass and number concentrations (100 µg/m3, 2.0·105 #/cm3) and a mean particle diameter of about 40 nm. High organic content UFP had significant PAH levels, with benzo[a]pyrene at 0.2 % (m/m). Toxicological evaluations revealed that both UFP types similarly affected cytotoxicity and cell viability, regardless of organic load. Higher xenobiotic metabolism was noted for PAH-rich UFP, while reactive oxidation markers increased when semi-volatiles were stripped off. Both UFP types caused DNA strand breaks, but only the high organic content UFP induced DNA oxidation. This methodology allows modification of UFP's chemical properties while maintaining comparable physical properties, linking these variations to biological responses.