From Inhalation to Neurodegeneration: Air Pollution as a Modifiable Risk Factor for Alzheimer's Disease.

Air pollution, a growing concern for public health, has been linked to various respiratory and cardiovascular diseases. Emerging evidence also suggests a link between exposure to air pollutants and neurodegenerative diseases, particularly Alzheimer's disease (AD). This review explores the composition and sources of air pollutants, including particulate matter, gases, persistent organic pollutants, and heavy metals. The pathophysiology of AD is briefly discussed, highlighting the role of beta-amyloid plaques, neurofibrillary tangles, and genetic factors. This article also examines how air pollutants reach the brain and exert their detrimental effects, delving into the neurotoxicity of air pollutants. The molecular mechanisms linking air pollution to neurodegeneration are explored in detail, focusing on oxidative stress, neuroinflammation, and protein aggregation. Preclinical studies, including in vitro experiments and animal models, provide evidence for the direct effects of pollutants on neuronal cells, glial cells, and the blood-brain barrier. Epidemiological studies have reported associations between exposure to air pollution and an increased risk of AD and cognitive decline. The growing body of evidence supporting air pollution as a modifiable risk factor for AD underscores the importance of considering environmental factors in the etiology and progression of neurodegenerative diseases, in the face of worsening global air quality.

Genetic evidence supports a causal relationship between air pollution and brain imaging-derived phenotypes.

BACKGROUND: Observational studies have reported associations between air pollutants and brain imaging-derived phenotypes (IDPs); however, whether this relationship is causal remains uncertain. METHODS: We conducted bidirectional two-sample Mendelian randomization (MR) analyses to explore the causal relationships between 5 types of air pollutants (N=423,796 to 456,380 individuals) and 587 reliable IDPs (N=33,224 individuals). Two-step MR was also conducted to assess whether the identified effects are mediated through the modulation of circulating cytokines (N=8293). RESULTS: We found genetic evidence supporting the association of nitrogen oxides (NOx) with mean intra-cellular volume fraction (ICVF) in the left uncinate fasciculus (IVW ß=-0.42, 95 % CI -0.62 to -0.23, P=1.51×10-5) and mean fractional anisotropy (FA) in the left uncinate fasciculus (IVW ß=-0.42, 95 % CI -0.62 to -0.21, P=4.89×10-5). In further two-step MR analyses, we did not find evidence that genetic predictions of any circulating cytokines mediated the association between NOx and IDPs. CONCLUSION: This study provides evidence for the association between air pollutants and brain IDPs, emphasizing the importance of controlling air pollution to improve brain health.

Differential effects of long- and short-term exposure to PM2.5 on accelerating telomere shortening: from in vitro to epidemiological studies.

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 (PM2.5) on telomere length in human bronchial epithelial BEAS-2B cells, and assessed the potential correlation between PM2.5 exposure and telomere length in the LIGHTS childhood cohort study. We observed that long-term, but not short-term, PM2.5 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 PM2.5 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 PM2.5 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 PM2.5 and shortening of leukocyte telomere length in children. However, no significant association between 7-day short-term exposure to PM2.5 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 PM2.5 exposure to telomere shortening in humans.

Air pollution disproportionately impairs beneficial invertebrates: a meta-analysis.

Air pollution has the potential to disrupt ecologically- and economically-beneficial services provided by invertebrates, including pollination and natural pest regulation. To effectively predict and mitigate this disruption requires an understanding of how the impacts of air pollution vary between invertebrate groups. Here we conduct a global meta-analysis of 120 publications comparing the performance of different invertebrate functional groups in unpolluted and polluted atmospheres. We focus on the pollutants ozone, nitrogen oxides, sulfur dioxide and particulate matter. We show that beneficial invertebrate performance is reduced by air pollution, whereas the performance of plant pest invertebrates is not significantly affected. Ozone pollution has the most detrimental impacts, and these occur at concentrations below national and international air quality standards. Changes in invertebrate performance are not dependent on air pollutant concentrations, indicating that even low levels of pollution are damaging. Predicted increases in tropospheric ozone could result in unintended consequences to global invertebrate populations and their valuable ecological services.

Evaluating the properties that affect the quality of the charcoal product, determining the limits of toxic emissions during combustion, and studying their impact on human health.

This research focuses on examining the potential impact of charcoal briquettes and lumps on human health due to the emissions they release, and verifying their quality standards. Quality assessment was conducted using a device capable of measuring toxic gases to identify contaminants from various sources such as biomass, synthetic resins, coal, metals, and mineral matter. Toxicity assessments were carried out on five types of briquettes and two varieties of lump charcoal. All charcoal samples were subjected to elemental analysis (SEM/EDAX), including the examination of Ca, Al, Cr, V, Cu, Fe, S, Sr, Si, Ba, Pb, P, Mn, Rb, K, Ti, and Zn. The results showed that burning lump charcoal had toxicity indexes ranging from 2.5 to 5, primarily due to NOx emissions. Briquettes, on the other hand, exhibited higher toxicity indices between 3.5 and 6.0, with CO2 being the main contributor to toxicity. The average 24-h CO content of all charcoal samples exceeded the World Health Organization's 24-h Air Quality Guideline of 6.34 ppm, with a measurement of 37 ppm. The data indicates that most of the products tested did not meet the prevailing quality standard (EN 1860-2:2005 (E) in Appliances, solid fuels and firelighters for barbecuing-Part 2: Barbecue charcoal and barbecue charcoal briquettes-Requirements and test method, 2005), which specifies a maximum of 1% contaminants, with some products containing as much as 21% impurities. The SEM analysis revealed irregularly shaped grains with an uneven distribution of particles, and the average particle size distribution is quite broad at 5 µm. Malaysia Charcoal had the highest calorific value at 32.80 MJ/Kg, with the value being influenced by the fixed carbon content-higher carbon content resulting in a higher calorific value.

Causal relationship and shared genes between air pollutants and amyotrophic lateral sclerosis: A large-scale genetic analysis.

OBJECTIVE: Air pollutants have been reported to have a potential relationship with amyotrophic lateral sclerosis (ALS). The causality and underlying mechanism remained unknown despite several existing observational studies. We aimed to investigate the potential causality between air pollutants (PM2.5, NOX, and NO2) and the risk of ALS and elucidate the underlying mechanisms associated with this relationship. METHODS: The data utilized in our study were obtained from publicly available genome-wide association study data sets, in which single nucleotide polymorphisms (SNPs) were employed as the instrumental variantswith three principles. Two-sample Mendelian randomization and transcriptome-wide association (TWAS) analyses were conducted to evaluate the effects of air pollutants on ALS and identify genes associated with both pollutants and ALS, followed by regulatory network prediction. RESULTS: We observed that exposure to a high level of PM2.5 (OR: 2.40 [95% CI: 1.26-4.57], p = 7.46E-3) and NOx (OR: 2.35 [95% CI: 1.32-4.17], p = 3.65E-3) genetically increased the incidence of ALS in MR analysis, while the effects of NO2 showed a similar trend but without sufficient significance. In the TWAS analysis, TMEM175 and USP35 turned out to be the genes shared between PM2.5 and ALS in the same direction. CONCLUSION: Higher exposure to PM2.5 and NOX might causally increase the risk of ALS. Avoiding exposure to air pollutants and air cleaning might be necessary for ALS prevention.

Effect of nitrogen oxides and sulfur oxides to triphenyl phosphate degradation and cytotoxicity on surface of different transition metal salts.

Nitrogen oxides and sulfur oxides, as the dominant toxic gases in the atmosphere, can induce severe human health problems under the composite pollutant conditions. Currently the effect of nitrogen or sulfur oxides in atmospheric environment to the degradation and cytotoxicity of triphenyl phosphate (TPhP) on atmospheric particle surfaces still remain poorly understood. Hence, laboratory simulation methods were used in this study to investigate the effect and related mechanism. First, particle samples were prepared with the TPhP coated on MnSO4, CuSO4, FeSO4 and Fe2(SO4)3 surface. The results showed that, when nitrogen or sulfur oxides were present, more significant TPhP degradation on all samples can be observed under both light and dark conditions. The results proved nitrogen oxides and sulfur oxides were the vital influence factors to the degradation of TPhP, which mainly promoted the OH generation in the polluted atmosphere. The mechanism study indicated that diphenyl hydrogen phosphate (DPhP) and OH-DPhP were two main stable degradation products. These degradation products originated from the phenoxy bond cleavage and hydroxylation of TPhP caused by hydroxyl radicals. In addition, no TPhP related organosulfates (OSs) or organic nitrates (ON) formation were observed. Regarding the cytotoxicity, all the particles can induce more significant cellular injury and apoptosis of A549 cells, which may be relevant to the adsorbed nitrogen oxides or sulfur oxides on particles surfaces. The superfluous reactive oxygen species (ROS) generation was the possible reason of cytotoxicity. This research can supply a comprehensive understanding of the promoting effect of nitrogen and sulfur oxides to TPhP degradation and the composite cytotoxicity of atmospheric particles.

Prenatal exposure to ambient air pollution and risk of fetal overgrowth: Systematic review of cohort studies.

OBJECTIVES: Fetal overgrowth has detrimental effects on both the mother and the fetus. The global issue of ambient air pollution has been found to contribute to fetal overgrowth through various pathways. This study aimed to identify the association between prenatal exposure to ambient air pollution and the risk of fetal overgrowth. METHODS: We identified articles between January 2013 and February 2024 by searching the Web of Sciences(WoS), PubMed, Proquest, Scopus, and Google Scholar databases. Quality assessment was performed using the Newcastle Ottawa scale. This review was provided based on the PRISMA guideline and registered with PROSPERO, "CRD42023488936". RESULTS: The search generated 1719 studies, of which 22 cohort studies were included involving 3,480,041 participants. Results on the effects of air pollutants on fetal overgrowth are inconsistent because they vary in population and geographic region. But in general, the results indicate that prenatal exposure to air pollutants, specifically PM2.5, NO2, and SO2, is linked to a higher likelihood of fetal overgrowth(macrosomia and large for gestational age). Nevertheless, the relationship between CO and O3 pollution and fetal overgrowth remains uncertain. Furthermore, PM10 has a limited effect on fetal overgrowth. It is essential to consider the time that reproductive-age women are exposed to air pollution. Exposure to air pollutants before conception and throughout pregnancy has a substantial impact on the fetus's vulnerability to overgrowth. CONCLUSIONS: Fetal overgrowth has implications for the health of both mother and fetus. fetal overgrowth can cause cardiovascular diseases, obesity, type 2 diabetes, and other diseases in adulthood, so it is considered an important issue for the health of the future generation. Contrary to popular belief that air pollution leads to intrauterine growth restriction and low birth weight, this study highlights that one of the adverse consequences of air pollution is macrosomia or LGA during pregnancy. Therefore governments must focus on implementing initiatives that aim to reduce pregnant women's exposure to ambient air pollution to ensure the health of future generations.

How long-term PM exposure may affect all-site cancer mortality: Evidence from a large cohort in southern China.

BACKGROUND: Evidence of a potential causal link between long-term exposure to particulate matter (PM) and all-site cancer mortality from large population cohorts remained limited and suffered from residual confounding issues with traditional statistical methods. AIMS: We aimed to examine the potential causal relationship between long-term PM exposure and all-site cancer mortality in South China using causal inference methods. METHODS: We used a cohort in southern China that recruited 580,757 participants from 2009 through 2015 and tracked until 2020. Annual averages of PM1, PM2.5, and PM10 concentrations were generated with validated spatiotemporal models. We employed a causal inference approach, the Marginal Structural Cox model, based on observational data to evaluate the association between long-term exposure to PM and all-site cancer mortality. RESULTS: With an increase of 1 µg/m³ in PM1, PM2.5, and PM10, the hazard ratios (HRs) and 95% confidence interval (CI) for all-site cancer were 1.033 (95% CI: 1.025-1.041), 1.032 (95% CI: 1.027-1.038), and 1.020 (95% CI: 1.016-1.025), respectively. The HRs (95% CI) for digestive system and respiratory system cancer mortality associated with each 1 µg/m³ increase in PM1 were 1.022 (1.009-1.035) and 1.053 (1.038-1.068), respectively. In addition, inactive participants, who never smoked, or who lived in areas of low surrounding greenness were more susceptible to the effects of PM exposure, the HRs (95% CI) for all-site cancer mortality were 1.042 (1.031-1.053), 1.041 (1.032-1.050), and 1.0473 (1.025-1.070) for every 1 µg/m³ increase in PM1, respectively. The effect of PM1 tended to be more pronounced in the low-exposure group than in the general population, and multiple sensitivity analyses confirmed the robustness of the results. CONCLUSION: This study provided evidence that long-term exposure to PM may elevate the risk of all-site cancer mortality, emphasizing the potential health benefits of improving air quality for cancer prevention.

Mixed effects of ambient air pollutants on oocyte-related outcomes: A novel insight from women undergoing assisted reproductive technology.

Air pollution is widely acknowledged as a significant risk factor for human health, especially reproductive health. Nevertheless, many studies have disregarded the potentially mixed effects of air pollutants on reproductive outcomes. We performed a retrospective cohort study involving 8048 women with 9445 cycles undergoing In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI) in China, from 2017 to 2021. A land-use random forest model was applied to estimate daily residential exposure to air pollutants, including sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and fine particulate matter (PM2.5). Individual and joint associations between air pollutants and oocyte-related outcomes of ART were evaluated. In 90 days prior to oocyte pick-up to oocyte pick-up (period A), NO2, O3 and CO was negatively associated with total oocyte yield. In the 90 days prior to oocyte pick-up to start of gonadotropin medication (Gn start, period B), there was a negative dose-dependent association of exposure to five air pollutants with total oocyte yield and mature oocyte yield. In Qgcomp analysis, increasing the multiple air pollutants mixtures by one quartile was related to reducing the number of oocyte pick-ups by -2.00 % (95 %CI: -2.78 %, -1.22 %) in period A, -2.62 % (95 %CI: -3.40 %, -1.84 %) in period B, and -0.98 % (95 %CI: -1.75 %, -0.21 %) in period C. During period B, a 1-unit increase in the WQS index of multiple air pollutants exposure was associated with fewer number of total oocyte (-1.27 %, 95 %CI: -2.16 %, -0.36 %) and mature oocyte (-1.42 %, 95 %CI: -2.41 %, -0.43 %). O3 and NO2 were major contributors with adverse effects on the mixed associations. Additionally, period B appears to be the susceptible window. Our study implies that exposure to air pollution adversely affects oocyte-related outcomes, which raises concerns about the potential adverse impact of air pollution on women's reproductive health.

Exposure memory and susceptibility to ambient PM2.5: A perspective from hepatic cholesterol and bile acid metabolism.

Both epidemiological and experimental studies increasingly show that exposure to ambient fine particulate matter (PM2.5) is related to the occurrence and development of chronic diseases, such as metabolic diseases. However, whether PM2.5 has "exposure memory" and how these memories affect chronic disease development like hepatic metabolic homeostasis are unknown. Therefore, we aimed to explore the effects of exposure transition on liver cholesterol and bile acids (BAs) metabolism in mice. In this study, C57BL/6 mice were exposed to concentrated ambient PM2.5 or filtered air (FA) in a whole-body exposure facility for an initial period of 10 weeks, followed by another 8 weeks of exposure switch (PM2.5 to FA and FA to PM2.5) comparing to non-switch groups (FA to FA and PM2.5 to PM2.5), which were finally divided into four groups (FF of FA to FA, PP of PM2.5 to PM2.5, PF of PM2.5 to FA, and FP of FA to PM2.5). Our results showed no significant difference in food intake, body composition, glucose homeostasis, and lipid metabolism between FA and PM2.5 groups after the initial exposure before the exposure switch. At the end of the exposure switch, the mice switched from FA to PM2.5 exposure exhibited a high sensitivity to late-onset PM2.5 exposure, as indicated by significantly elevated hepatic cholesterol levels and disturbed BAs metabolism. However, the mice switched from PM2.5 to FA exposure retained a certain memorial effects of previous PM2.5 exposure in hepatic cholesterol levels, cholesterol metabolism, and BAs metabolism. Furthermore, 18-week PM2.5 exposure significantly increased hepatic free BAs levels, which were completely reversed by the FA exposure switch. Finally, the changes in small heterodimeric partner (SHP) and nuclear receptor subfamily 5 group A member 2 (LRH1) in response to exposure switch mechanistically explained the above alterations. Therefore, mice switching from PM2.5 exposure to FA showed only a weak memory of prior PM2.5 exposure. In contrast, the early FA caused mice to be more susceptible to subsequent PM2.5 exposure.

Global associations between long-term exposure to PM2.5 constituents and health: A systematic review and meta-analysis of cohort studies.

Existing studies on the most impactful component remain controversial, hindering the optimization of future air quality standards that concerns particle composition. We aimed to summarize the health risk associated with PM2.5 components and identify those components with the greatest health risk. We performed a meta-analysis to quantify the combined health effects of PM2.5 components, and used the meta-smoothing to produce the pooled concentration-response (C-R) curves. Out of 8954 initial articles, 80 cohort studies met the inclusion criteria, including a total of 198.08 million population. The pooled C-R curves demonstrated approximately J-shaped association between total mortality and exposure to BC, and NO3-, but U-shaped and inverted U-shaped relationship withSO42- and OC, respectively. In addition, this study found that exposure to various elements, including BC,SO42-NO3-, NH4+, Zn, Ni, and Si, were significantly associated with an increased risk of total mortality, with Ni presenting the largest estimate. And exposure to NO3-, Zn, and Si was positively associated with an increased risk of respiratory mortality, while exposure to BC, SO42-, and NO3- showed a positive association with risk of cardiovascular mortality. For health outcome of morbidity, BC was notably associated with a higher incidence of asthma, type 2 diabetes and stroke. Subgroup analysis revealed a higher susceptibility to PM2.5 components in Asia compared to Europe and North America, and females showed a higher vulnerability. Given the significant health effects of PM2.5 components, governments are advised to introduce them in regional monitoring and air quality control guidelines. ENVIRONMENTAL IMPLICATION: PM2.5 is a complex mixture of chemical components from various sources, and each component has unique physicochemical properties and uncertain toxicity, posing significant threat to public health. This study systematically reviewed cohort studies on the association between long-term exposure to 13 PM2.5 components and the risk of morbidity and mortality. And we applied the meta-smoothing approach to establish the pooled concentration-response associations between PM2.5 components and mortality globally. Our findings will provide strong support for PM2.5 components monitoring and the improvement of air quality-related regulations. This will aid in helping to enhance health intervention strategies and mitigating public exposure to detrimental particulate matter.

The Impact of Fine Particulate Matter on Embryonic Development.

Airborne fine particulate matter (PM2.5) in air pollution has become a significant global public health concern related to allergic diseases. Previous research indicates that PM2.5 not only affects the respiratory system but may also induce systemic inflammation in various tissues. Moreover, its impact may vary among different populations, with potential consequences during pregnancy and in newborns. However, the precise mechanisms through which PM2.5 induces inflammatory reactions remain unclear. This study aims to explore potential pathways of inflammatory responses induced by PM2.5 through animal models and zebrafish embryo experiments. In this study, zebrafish embryo experiments were conducted to analyze the effects of PM2.5 on embryo development and survival, and mouse experimental models were employed to assess the impact of PM2.5 stimulation on various aspects of mice. Wild-type zebrafish embryos were exposed to a PM2.5 environment of 25-400 µg/mL starting at 6 h after fertilization (6 hpf). At 6 days post-fertilization, the survival rates of the 25, 50, 100, and 200 µg/mL groups were 100%, 80, 40%, and 40%, respectively. Zebrafish embryos stimulated with 25 µg/mL of PM2.5 still exhibited successful development and hatching. Additionally, zebrafish subjected to doses of 25-200 µg/mL displayed abnormalities such as spinal curvature and internal swelling after hatching, indicating a significant impact of PM2.5 stimulation on embryo development. In the mouse model, mice exposed to PM2.5 exhibited apparent respiratory overreaction, infiltration of inflammatory cells into the lungs, elevated levels of inflammatory response-related cytokines, and inflammation in various organs, including the liver, lungs, and uterus. Blood tests on experimental mice revealed increased expression of inflammatory and chemotactic cytokines, and GSEA indicated the induction of various inflammatory responses and an upregulation of the TNF-α/NFκB pathway by PM2.5. Our results provide insights into the harmful effects of PM2.5 on embryos and organs. The induced inflammatory responses by PM2.5 may be mediated through the TNF-α/NFκB pathway, leading to systemic organ inflammation. However, whether PM2.5-induced inflammatory responses in various organs and abnormal embryo development are generated through different pathways requires further study to comprehensively clarify and identify potential treatment and prevention methods.

Dissecting heritability, environmental risk, and air pollution causal effects using > 50 million individuals in MarketScan.

Large national-level electronic health record (EHR) datasets offer new opportunities for disentangling the role of genes and environment through deep phenotype information and approximate pedigree structures. Here we use the approximate geographical locations of patients as a proxy for spatially correlated community-level environmental risk factors. We develop a spatial mixed linear effect (SMILE) model that incorporates both genetics and environmental contribution. We extract EHR and geographical locations from 257,620 nuclear families and compile 1083 disease outcome measurements from the MarketScan dataset. We augment the EHR with publicly available environmental data, including levels of particulate matter 2.5 (PM2.5), nitrogen dioxide (NO2), climate, and sociodemographic data. We refine the estimates of genetic heritability and quantify community-level environmental contributions. We also use wind speed and direction as instrumental variables to assess the causal effects of air pollution. In total, we find PM2.5 or NO2 have statistically significant causal effects on 135 diseases, including respiratory, musculoskeletal, digestive, metabolic, and sleep disorders, where PM2.5 and NO2 tend to affect biologically distinct disease categories. These analyses showcase several robust strategies for jointly modeling genetic and environmental effects on disease risk using large EHR datasets and will benefit upcoming biobank studies in the era of precision medicine.

Air-liquid interface exposure of A549 human lung cells to characterize the hazard potential of a gaseous bio-hybrid fuel blend.

Gaseous and semi-volatile organic compounds emitted by the transport sector contribute to air pollution and have adverse effects on human health. To reduce harmful effects to the environment as well as to humans, renewable and sustainable bio-hybrid fuels are explored and investigated in the cluster of excellence "The Fuel Science Center" at RWTH Aachen University. However, data on the effects of bio-hybrid fuels on human health is scarce, leaving a data gap regarding their hazard potential. To help close this data gap, this study investigates potential toxic effects of a Ketone-Ester-Alcohol-Alkane (KEAA) fuel blend on A549 human lung cells. Experiments were performed using a commercially available air-liquid interface exposure system which was optimized beforehand. Then, cells were exposed at the air-liquid interface to 50-2000 ppm C3.7 of gaseous KEAA for 1 h. After a 24 h recovery period in the incubator, cells treated with 500 ppm C3.7 KEAA showed significant lower metabolic activity and cells treated with 50, 250, 500 and 1000 ppm C3.7 KEAA showed significant higher cytotoxicity compared to controls. Our data support the international occupational exposure limits of the single KEAA constituents. This finding applies only to the exposure scenario tested in this study and is difficult to extrapolate to the complex in vivo situation.

Impact of Airborne Exposure to PM10 Increases Susceptibility to P. aeruginosa Infection.

The effects of exposure to airborne particulate matter with a size of 10 µm or less (PM10) on C57BL/6 mouse corneas, their response to Pseudomonas aeruginosa (PA) infection, and the protective effects of SKQ1 were determined. C57BL/6 mouse corneas receiving PBS or SKQ1 were exposed to control (air) or PM10 for 2 weeks, infected, and the disease was documented by clinical score, PMN quantitation, bacterial plate count, RT-PCR and Western blot. PBS-treated, PM10-exposed corneas did not differ at 1 day postinfection (dpi), but exhibited earlier (3 dpi) corneal thinning compared to controls. By 3 dpi, PM10 significantly increased corneal mRNA levels of several pro-inflammatory cytokines, but decreased IL-10, NQO1, GR1, GPX4, and Nrf2 over control. SKQ1 reversed these effects and Western blot selectively confirmed the RT-PCR results. PM10 resulted in higher viable bacterial plate counts at 1 and 3 dpi, but SKQ1 reduced them at 3 dpi. PM10 significantly increased MPO in the cornea at 3 dpi and was reduced by SKQ1. SKQ1, used as an adjunctive treatment to moxifloxacin, was not significantly different from moxifloxacin alone. Exposure to PM10 increased the susceptibility of C57BL/6 to PA infection; SKQ1 significantly reversed these effects, but was not effective as an adjunctive treatment.

An Assessment of the Ocular Toxicity of Two Major Sources of Environmental Exposure.

The effect of airborne exposure on the eye surface is an area in need of exploration, particularly in light of the increasing number of incidents occurring in both civilian and military settings. In this study, in silico methods based on a platform comprising a portfolio of software applications and a technology ecosystem are used to test potential surface ocular toxicity in data presented from Iraqi burn pits and the East Palestine, Ohio, train derailment. The purpose of this analysis is to gain a better understanding of the long-term impact of such an exposure to the ocular surface and the manifestation of surface irritation, including dry eye disease. In silico methods were used to determine ocular irritation to chemical compounds. A list of such chemicals was introduced from a number of publicly available sources for burn pits and train derailment. The results demonstrated high ocular irritation scores for some chemicals present in these exposure events. Such an analysis is designed to provide guidance related to the needed ophthalmologic care and follow-up in individuals who have been in proximity to burn pits or the train derailment and those who will experience future toxic exposure.

Air quality and kidney health: Assessing the effects of PM10, PM2.5, CO, and NO2 on renal function in primary glomerulonephritis.

BACKGROUND: While extensive studies have elucidated the relationships between exposure to air pollution and chronic diseases, such as cardiovascular disorders and diabetes, the intricate effects on specific kidney diseases, notably primary glomerulonephritis (GN)-an immune-mediated kidney ailment-are less well understood. Considering the escalating incidence of GN and conspicuous lack of investigative focus on its association with air quality, investigation is dedicated to examining the long-term effects of air pollutants on renal function in individuals diagnosed with primary GN. METHODS: This retrospective cohort analysis was conducted on 1394 primary GN patients who were diagnosed at Seoul National University Bundang Hospital and Seoul National University Hospital. Utilizing time-varying Cox regression and linear mixed models (LMM), we examined the effect of yearly average air pollution levels on renal function deterioration (RFD) and change in estimated glomerular filtration rate (eGFR). In this context, RFD is defined as sustained eGFR of less than 60 mL/min per 1.73 m2. RESULTS: During a mean observation period of 5.1 years, 350 participants developed RFD. Significantly, elevated interquartile range (IQR) levels of air pollutants-including PM10 (particles ≤10 micrometers, HR 1.389, 95 % CI 1.2-1.606), PM2.5 (particles ≤2.5 micrometers, HR 1.353, 95 % CI 1.162-1.575), CO (carbon monoxide, HR 1.264, 95 % CI 1.102-1.451), and NO2 (nitrogen dioxide, HR 1.179, 95 % CI 1.021-1.361)-were significantly associated with an increased risk of RFD, after factoring in demographic and health variables. Moreover, exposure to PM10 and PM2.5 was associated with decreased eGFR. CONCLUSIONS: This study demonstrates a substantial link between air pollution exposure and renal function impairment in primary GN, accentuating the significance of environmental determinants in the pathology of immune-mediated kidney diseases.

The influence of pre- and postnatal exposure to air pollution and green spaces on infant's gut microbiota: Results from the MAMI birth cohort study.

BACKGROUND: Animal and human studies indicate that exposure to air pollution and natural environments might modulate the gut microbiota, but epidemiological evidence is very scarce. OBJECTIVES: To assess the potential impact of pre- and postnatal exposure to air pollution and green spaces on infant gut microbiota assembly and trajectories during the first year of life. METHODS: MAMI ("MAternal MIcrobes") birth cohort (Valencia, Spain, N = 162) was used to study the impact of environmental exposure (acute and chronic) on infant gut microbiota during the first year of life (amplicon-based 16S rRNA sequencing). At 7 days and at 1, 6 and 12 months, residential pre- and postnatal exposure to air pollutants (NO2, black carbon -BC-, PM2.5 and O3) and green spaces indicators (NDVI and area of green spaces at 300, 500 and 1000 m buffers) were obtained. For the association between exposures and alpha diversity indicators linear regression models (cross-sectional analyses) and mixed models, including individual as a random effect (longitudinal analyses), were applied. For the differential taxon analysis, the ANCOM-BC package with a log count transformation and multiple-testing corrections were used. RESULTS: Acute exposure in the first week of life and chronic postnatal exposure to NO2 were associated with a reduction in microbial alpha diversity, while the effects of green space exposure were not evident. Acute and chronic (prenatal or postnatal) exposure to NO2 resulted in increased abundance of Haemophilus, Akkermansia, Alistipes, Eggerthella, and Tyzerella populations, while increasing green space exposure associated with increased Negativicoccus, Senegalimassilia and Anaerococcus and decreased Tyzzerella and Lachnoclostridium populations. DISCUSSION: We observed a decrease in the diversity of the gut microbiota and signs of alteration in its composition among infants exposed to higher levels of NO2. Increasing green space exposure was also associated with changes in gut microbial composition. Further research is needed to confirm these findings.

Neurodegenerative pathways and metabolic changes in the hippocampus and cortex of mice exposed to urban particulate matter: Insights from an integrated interactome analysis.

Recently, urban particulate matter (UPM) exposure has been associated with the development of brain disorders. This study uses bioinformatic analyses to elucidate the molecular unexplored mechanisms underlying the effects of UPM exposure on the brain. Mice are exposed to UPM (from 3 days to 20 weeks), and their behavioral patterns measured. We measure pathology and gene expression in the hippocampus and cortical regions of the brain. An integrated interactome of genes is established, which enriches information on metabolic processes. Using this network, we isolate the core genes that are differentially expressed in the samples. We observe cognitive loss and pathological changes in the brains of mice at 16 or 20 weeks of exposure. Through network analysis of core-differential genes and measurement of pathway activity, we identify differences in the response to UPM exposure between the hippocampus and cortex. However, neurodegenerative disease pathways are implicated in both tissues following short-term exposure to UPM. There were also significant changes in metabolic function in both tissues depending on UPM exposure time. Additionally, the cortex of UPM-exposed mice shows more similarities with psychiatric disorders than with neurodegenerative diseases. The connectivity map database is used to isolate genes contributing to changes in expression due to UPM exposure. New approaches for inhibiting or preventing the brain damage caused by UPM exposure can be developed by targeting the functions and selected genes identified in this study.