Spatial and Temporal Distribution Characteristics and Cytotoxicity of Atmospheric PM2.5 in the Main Urban Area of Lanzhou City.

PM2.5, as one of the most harmful pollutant in the atmospheric environment and population health, has received much attention. We monitored PM2.5 levels at five sampling sites in the Lanzhou City and collected PM2.5 particles from two representative sites for cytotoxicity experiment. The cytotoxicity of PM2.5 samples on A549 cells and migration ability of the cells were respectively detected by Cell Counting kit-8 (CCK-8) assay and scratch assay. We detected the levels of cellular inflammatory factors and oxidative damage-related biochemical indexes. RT-qPCR was used to detect the mRNA levels of NF-κB and epithelial-mesenchymal transition (EMT)-related genes. We found that the Lanlian Hotel station had the highest PM2.5 annual average concentration. The annual average concentration change curve of PM2.5 showed a roughly "U"-shaped distribution during the whole sampling period. The cytotoxicity experiment showed the viability of A549 cells decreased and the scratch healing rate increased in the 200 and 400 µg/mL PM2.5-treated groups. We also found 400 µg/mL PM2.5 induced changes in the mRNA levels of NF-κB and EMT-related genes, the mRNA levels of IKK-α, NIK, and NF-κB in the 400 µg/mL PM2.5 group were higher than those in the control group. The mRNA levels of E-cadherin decreased and α-SMA increased in the 400 µg/mL PM2.5 groups, and the mRNA levels of Fibronectin increased in the 400 µg/mL PM2.5 groups. Moreover, we found hydroxyl radical scavenging ability and T-AOC levels were lower, and LPO levels were higher in the 200 and 400 µg/mL PM2.5 groups, and the SOD activity of cells in the 400 µg/mL PM2.5 group decreased. And compared with the control group, the levels of TNF-α were higher in the 200 and 400 µg/mL PM2.5 groups and the levels of IL-1 were higher in the 400 µg/mL PM2.5 group. The results indicated that the cytotoxicity of atmospheric PM2.5 was related to oxidative damage, inflammatory response, NF-κB activity and EMT.

The impact of settleable atmospheric particulate on the energy metabolism, biochemical processes, and behavior of a sentinel mangrove crab.

We use the sentinel mangrove crab, Minuca rapax, as a model to investigate the effects of metallic settleable particulate matter (SePM) on wetland. Multiple levels of energetic responses, including (i) metabolic rate and energy budget, (ii) oxidative stress, and (iii) behavioral response by righting time, were assessed as well as the metal and metalloid content in crabs exposed to 0, 0.1 and 1 g.L-1 of SePM, under emerged and submerged conditions over five days, simulating the rigors of the intertidal habitat. Al, Fe, Mn, Cr, and Y exhibited a concentration-dependent increase. Metal concentrations were higher in submerged crabs due to the continuous ingestion of SePM and direct exposure through gills. Exposure concentration up to 1 g.L-1 decreased metabolic rate and enzymatic activities, reduced assimilation efficiency and energy for maintenance, and induces a slower response to righting time, probably by metal effects on nervous system and energy deficits. In conclusion, SePM exposure affects the redox status and physiology of M. rapax depending on he submersion regime and SePM concentration. The disruption to the energy budget and the lethargic behavior in M. rapax exposed to SePM implies potential ecological alterations in the mangrove ecosystem with unknown consequences for the local population.

Exposure to volatile organic compounds and growth indicators in adolescents: Unveiling the association and potential intervention strategies.

Environmental pollutant is considered to be one of the important factors affecting adolescent growth. However, the effects of volatile organic compounds (VOCs) exposure on adolescent growth have not been assessed. Data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 was used to examine the associations between VOCs exposure and adolescent growth indicators through three statistical models. The mediating effect of bone mineral density (BMD) on these associations was examined. The potential pathways and key targets were identified by the network pharmacology analysis methods. This study included 746 adolescents. Three statistical methods consistently showed a negative correlation between VOCs exposure and adolescent growth indicators. Furthermore, BMD mediated the relationship between VOCs exposure and adolescent growth indicators, with mediated proportion ranging from 4.3 % to 53.4 %. Network pharmacology analysis found a significant enrichment in IL-17 signaling pathway. Moreover, the adverse effects of VOCs exposure on adolescent growth were observed to significantly attenuate in adolescents with high serum vitamin D levels. Our results suggested that VOCs exposure was an adverse factor affecting adolescent growth, with BMD playing a significant regulatory role, and IL-17 signaling pathway was the underlying mechanism. Vitamin D supplementation may be a viable strategy to prevent VOCs exposure from affecting adolescent growth.

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.

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.

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.

Joint Effect of Short-Term Exposure to Fine Particulate Matter and Ozone on Mortality: A Time Series Study in 272 Chinese Cities.

Short-term exposure to PM2.5 or O3 can increase mortality risk; however, limited studies have evaluated their interaction. A multicity time series study was conducted to investigate the synergistic effect of PM2.5 and O3 on mortality in China, using mortality data and high-resolution pollutant predictions from 272 cities in 2013-2015. Generalized additive models were applied to estimate associations of PM2.5 and O3 with mortality. Modification and interaction effects were explored by stratified analyses and synergistic indexes. Deaths attributable to PM2.5 and O3 were evaluated with or without modification of the other pollutant. The risk of total nonaccidental mortality increased by 0.70% for each 10 µg/m3 increase in PM2.5 when O3 levels were high, compared to 0.12% at low O3 levels. The effect of O3 on total nonaccidental mortality at high PM2.5 levels (1.26%) was also significantly higher than that at low PM2.5 levels (0.59%). Similar patterns were observed for cardiovascular or respiratory diseases. The relative excess risk of interaction and synergy index of PM2.5 and O3 on nonaccidental mortality were 0.69% and 1.31 with statistical significance, respectively. Nonaccidental deaths attributable to short-term exposure of PM2.5 or O3 when considering modification of the other pollutant were 28% and 31% higher than those without considering modification, respectively. Our results found synergistic effects of short-term coexposure to PM2.5 and O3 on mortality and suggested underestimations of attributable risks without considering their synergistic effects.

Microbial Buffer? The Human Lung Microbiome and Immune Responses to Diesel Exhaust.

Having a more diverse lung microbiome was associated better lung capacity and lower measures of airway inflammation among a small group of volunteers exposed to diesel exhaust-even in those with COPD.

Prenatal exposure to PM2.5 and childhood body mass index growth trajectories from birth to 6 years old.

This study aimed to determine the relationships between prenatal PM2.5 exposure and childhood growth trajectories during the first 6 years of life. A total of 47,625 pairs of mothers and children were recruited from a prospective birth cohort conducted between 2011 and 2013 in Wuhan, China, and followed for 6 years. We used the group-based trajectory models to classify the population into three trajectory groups: slow growth (n = 13,671, 28.7%), normal growth (n = 29,736, 62.4%), and rapid growth (n = 4218, 8.9%). Multinomial logistic regression models were used to determine the associations of prenatal PM2.5 exposure and childhood growth trajectories. Compared to normal growth trajectory, increased PM2.5 exposure in trimester 1, trimester 2 and the entire pregnancy showed significant associations with an increased risk of the slow growth trajectory but reduced the risk for the rapid growth trajectory, significant association of prenatal PM2.5 exposure with rapid growth trajectory was only observed in the trimester 3. Stratified analyses displayed relatively stronger associations among those mothers with maternal age over 35 years, pre-pregnancy BMI ≥ 25 kg/m2, and previous delivery experience. Prenatal exposure to PM2.5, particularly during the midpoint period of pregnancy, was more likely to have a slow growth trajectory and a lower risk of rapid growth trajectory. Maternal age, pre-pregnancy BMI, and previous delivery experience might modify these associations.

Year-long and seasonal differences of PM2.5 chemical characteristics and their role in the viability of human lung epithelial cells (A549).

Fine particulate matters-PM2.5 in the air can have considerable negative effects on human health and the environment. Various human cell-based studies examined the effect of PM2.5 on human health in different cities of the world using various chemical parameters. Unfortunately, limited information is available regarding the relationship between toxicity and chemical characteristics of PM2.5 collected in Istanbul, Türkiye, located in one of the most populated cities in the world. To investigate the chemical characteristics and cytotoxicity of PM2.5 in Istanbul, samples were collected for 12 months, then potentially toxic metals, oxidative potential, and particle indicators (e.g., functional groups and elements) were determined, and the cytotoxicity of PM2.5 on human A549 lung alveolar epithelial cells was examined. The mean PM2.5 mass concentration was 24.0 ± 17.4 µg m-3 and higher in cold months compared to other seasons. Moreover, the results of the metals, elemental, and functional groups indicated that seasonal and monthly characteristics were influenced by the regional anthropogenic sources and photochemistry input. The cytotoxicity results also showed that the viability of A549 cells was reduced with the exposure of PM2.5 (30-53%) and higher cytotoxicity was obtained in summer compared to the other seasons due to the impact of the metals, elements, and oxidative characteristics of PM2.5.

Both Short-term and Long-term Ozone Pollution Alters the Chemical Composition of rice Grain.

The increasing ground-level ozone (O3) is threatening food security, especially in Asian areas, where rice is one of the most important staple crops. O3 impacts on rice could be exacerbated by its spatiotemporal heterogeneity. To improve evaluation accuracy and develop effective adaptations, direct data is urgently needed. Studies on the short-term effects of O3 on rice grain, however, are lacking. Which may lead to an underestimation of the O3 impacts. Through a field experiment, we studied the responses of grain nitrogen, grain carbon, and grain protein in rice cultivars to elevated concentrations of O3 (40 ppb plus that in background air, eO3), especially examining the effects of short-term eO3 during different plant growth stages. We found that long-term eO3 increased grain nitrogen by 29.29% in a sensitive rice cultivar, and short-term eO3 at the tillering and jointing stages increased grain nitrogen by 19.31%, and the grain carbon to nitrogen ratio was decreased by 14.70%, and 21.14% by short-term and long-term eO3. Here we demonstrate that short-term eO3 may significantly affect the chemical composition of rice grains. Previous evaluations of the effects of eO3 may be underestimated. Moreover, changes in the grain nitrogen and grain protein were greater when the short-term eO3 was added to rice plants during the tillering and jointing stage, compared to heading and ripening stage. These results suggest that to improve the tolerance of rice to eO3 to achieve food security, studies on cultivar screening, as well as developing growth-stage-specific adaptations are needed in future.

Inflammatory Status in Trained and Untrained Mice at Different Pollution Levels.

Atmospheric pollution can be defined as a set of changes that occur in the composition of the air, making it unsuitable and/or harmful and thereby generating adverse effects on human health. The regular practice of physical exercise (PE) is associated with the preservation and/or improvement of health; however, it can be influenced by neuroimmunoendocrine mechanisms and external factors such as air pollution, highlighting the need for studies involving the practice of PE in polluted environments. Herein, 24 male C57BL/6 mice were evaluated, distributed into four groups (exposed to a high concentration of pollutants/sedentary, exposed to a high concentration of pollutants/exercised, exposed to ambient air/sedentary, and exposed to ambient air/exercised). The exposure to pollutants occurred in the environmental particle concentrator (CPA) and the physical training was performed on a treadmill specially designed for use within the CPA. Pro- and anti-inflammatory markers in blood and bronchoalveolar lavage (BALF), BALF cellularity, and lung tissue were evaluated. Although the active group exposed to a high concentration of pollution showed a greater inflammatory response, both the correlation analysis and the ratio between pro- and anti-inflammatory cytokines demonstrated that the exercised group presented greater anti-inflammatory activity, suggesting a protective/adaptative effect of exercise when carried out in a polluted environment.

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.

Neurotoxicity of fine and ultrafine particulate matter: A comprehensive review using a toxicity pathway-oriented adverse outcome pathway framework.

Fine particulate matter (PM2.5) can cause brain damage and diseases. Of note, ultrafine particles (UFPs) with an aerodynamic diameter less than or equal to 100 nm are a growing concern. Evidence has suggested toxic effects of PM2.5 and UFPs on the brain and links to neurological diseases. However, the underlying mechanism has not yet been fully illustrated due to the variety of the study models, different endpoints, etc. The adverse outcome pathway (AOP) framework is a pathway-based approach that could systematize mechanistic knowledge to assist health risk assessment of pollutants. Here, we constructed AOPs by collecting molecular mechanisms in PM-induced neurotoxicity assessments. We chose particulate matter (PM) as a stressor in the Comparative Toxicogenomics Database (CTD) and identified the critical toxicity pathways based on Ingenuity Pathway Analysis (IPA). We found 65 studies investigating the potential mechanisms linking PM2.5 and UFPs to neurotoxicity, which contained 2, 675 genes in all. IPA analysis showed that neuroinflammation signaling and glucocorticoid receptor signaling were the common toxicity pathways. The upstream regulator analysis (URA) of PM2.5 and UFPs demonstrated that the neuroinflammation signaling was the most initially triggered upstream event. Therefore, neuroinflammation was recognized as the MIE. Strikingly, there is a clear sequence of activation of downstream signaling pathways with UFPs, but not with PM2.5. Moreover, we found that inflammation response and homeostasis imbalance were key cellular events in PM2.5 and emphasized lipid metabolism and mitochondrial dysfunction, and blood-brain barrier (BBB) impairment in UFPs. Previous AOPs, which only focused on phenotypic changes in neurotoxicity upon PM exposure, we for the first time propose AOP framework in which PM2.5 and UFPs may activate pathway cascade reactions, resulting in adverse outcomes associated with neurotoxicity. Our toxicity pathway-based approach not only advances risk assessment for PM-induced neurotoxicity but shines a spotlight on constructing AOP frameworks for new chemicals.

Mechanism underlying the role of integrin α3ß1 in adhesive dysfunction between thyroid cells induced by diesel engine exhaust particles.

The role and mechanisms of DEP exposure on thyroid injury are not yet clear. This study explores thyroid damage induced by in vivo DEP exposure using a mouse model. This study has observed alterations in thyroid follicular architecture, including rupture, colloid overflow, and the formation of voids. Additionally, there was a significant decrease in the expression levels of proteins involved in thyroid hormone synthesis, such as thyroid peroxidase and thyroglobulin, their trend of change is consistent with the damage to the thyroid structure. Serum levels of triiodothyronine and tetraiodothyronine were raise. However, the decrease in TSH expression suggests that the function of the HPT axis is unaffected. To delve deeper into the intrinsic mechanisms of thyroid injury, we performed KEGG pathway enrichment analysis, which revealed notable alterations in the cell adhesion signaling pathway. Our immunofluorescence results show that DEP exposure impairs thyroid adhesion, and integrin α3ß1 plays an important role. CD151 binds to α3ß1, promoting multimolecular complex formation and activating adhesion-dependent small GTPases. Our in vitro model has confirmed the pivotal role of integrin α3ß1 in thyroid cell adhesion, which may be mediated by the CD151/α3ß1/Rac1 pathway. In summary, exposure to DEP disrupts the structure and function of the thyroid, a process that likely involves the regulation of cell adhesion through the CD151/α3ß1/Rac1 pathway, leading to glandular damage.

A review of disrupted biological response associated with volatile organic compound exposure: Insight into identification of biomarkers.

Volatile organic compounds (VOCs) are widespread harmful atmospheric pollutants, which have long been concerned and elucidated to be one of the risks of acute and chronic diseases for human, such as leukemia and cancer. Although numerous scientific studies have documented the potential adverse outcomes caused by VOC exposure, the mechanisms which biological response pathways of these VOC disruption remain poorly understood. Therefore, the identification of biochemical markers associated with metabolism, health effects and diseases orientation can be an effective means of screening biological targets for VOC exposure, which provide evidences to the toxicity assessment of compounds. The current review aims to understand the mechanisms underlying VOCs-elicited adverse outcomes by charactering various types of biomarkers. VOCs-related biomarkers from three aspects were summarized through in vitro, animal and epidemiological studies. i) Unmetabolized and metabolized VOC biomarkers in human samples for assessing exposure characteristics in different communities; ii) Adverse endpoint effects related biomarkers, mainly including (anti)oxidative stress, inflammation response and DNA damage; iii) Omics-based molecular biomarkers alteration in gene, protein, lipid and metabolite aspects associated with biological signaling pathway disorders response to VOC exposure. Further research, advanced machine learning and bioinformation approaches combined with experimental results are urgently needed to ascertain the selection of biomarkers and further illuminate toxic mechanisms of VOC exposure. Finally, VOCs-induced disease causes can be predicted with proven results.