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The arrival of 5G has facilitated further development of the Internet of Things (IoT) which is vulnerable to hacking because of its widespread use. Large networks oriented toward endpoints risk privacy leakage if attacked. Therefore, studying intrusion detection in the IoT is crucial. Current models are trained on large samples, whereas IoT devices can only intercept a limited attack samples in some scenarios, resulting in poor detection performance. A domain adaptation algorithm based on transfer learning can effectively transfer the source domain samples to the target domain, as a solution to the above problem. However, inconsistencies in categories and domains are not adequately addressed. In view of this, we propose a multi-source refined adversarial domain adaptation model with transfer complementarity infusion (MRADDA-TC) for IoT intrusion detection under limited samples. First, a lightweight scale-aware bilateral feature pyramid network is built for intrusion feature extraction, with three additional parallel modules for the MRADDA-TC model. In the multi-source refined adversarial domain adaptation component, knowledge transfer between the multi-source and target domains is achieved by optimizing the difference in category distribution between each pair of domains. Finally, the additive margin Softmax and multi-classifier complementarity infusion modules are designed to determine the similarity of the adaptation modules. The results are fed back into the multi-source refined adversarial adaptation module to guide the adaptation process. Extensive results on four IoT datasets validate the feasibility and superiority of the proposed model for detecting IoT intrusions with limited samples. Specifically, it has an average detection accuracy of more than 95 % under different limited sample tasks for the four datasets and has good robustness in the presence of noise. [ABSTRACT FROM AUTHOR]

Duan, H.-W.; Ma, C.-S., and Ding, X.-D., 2019. Profit calculation and allocation for rail-sea intermodal transportation alliance in port. In: Gong, D.; Zhu, H., and Liu, R. (eds.), Selected Topics in Coastal Research: Engineering, Industry, Economy, and Sustainable Development. Journal of Coastal Research, Special Issue No. 94, pp. 385–391. Coconut Creek (Florida), ISSN 0749-0208. In order to promote the alliance of railway and marine transport enterprises in port and ensure the alliance stability, the alliance profit calculation model and allocation scheme is studied. Firstly, the essence of the alliance is analyzed. Secondly, the pricing game models of different alliance structures are established and solved to get the alliance profit. Thirdly, the alliance profit is allocated by Myerson value method. Then the allocation scheme is adjusted considering the difference of the resources invested by the alliance members. Finally, numerical example is contructed to verify the validity of the profit calculation model and allocation scheme. Following conclusions are drawn. The more enterprises to participate in the alliance, the more favorable to the customer and the port. Alliance profit is related to the number of enterprises participating in the alliance, but is not related to the nature of the participation. The smaller transportation cost, the greater the alliance profit. It is feasible to allocate the alliance profit in an effective and fair manner based on Myerson value method, but adjustments are necessary to express the influence exerted by resource inputs. [ABSTRACT FROM AUTHOR]

The behavior of changing lanes has a great impact on road traffic with heavy traffic. Traffic flow density is one of the important parameters that characterize the characteristics of traffic flow, and it will also be affected by the behavior of changing lanes, especially in the case of each lane. The penetration of autonomous vehicles can effectively reduce lane-changing behavior. Studying the relationship between traffic flow density and lane-changing behavior under different autonomous vehicle penetration rates is of great significance for describing the operation mechanism of mixed traffic flow and the control of mixed traffic. In this article, we use empirical, simulation, and data-driven methods to analyze the urban expressway of autonomous vehicles with penetration rates of 10%, 20%, 30%, 40%, 50%, 60%, 70%, and 80%, respectively. A simulation experiment was carried out on the road, and data related to density, the rate of changing into the lanes, and the rate of changing out lanes were collected. The analysis of the experimental results found the following: (1) The increase in penetration of autonomous vehicles leads to a certain degree of downward trend in density, the rate of changing into the lanes, and the rate of changing out lanes. (2) Different lanes have different effects on the penetration of autonomous vehicles. In a 4-lane road, the two lanes farther from the entrance and exit are closer in appearance, while the two lanes closer to the entrance and exit are similar. (3) The relationship between density and the rate of changing into the lanes and the rate of changing out lanes shows a linear relationship with the penetration of autonomous vehicles. Although the performance of each lane is slightly different, in general, it can be carried out by a multiple regression model. The given parameter value range is relatively close under different permeability. In summary, autonomous vehicles effectively reduce the traffic density and lane-changing behavior of each lane. There is a linear relationship between traffic flow density and lane-changing behavior with the penetration of autonomous vehicles. The density-lane-changing behavior model proposed in this paper can better describe the relationship between the density of the circular multilane urban expressway and the lane-changing behavior in the case of a large traffic flow in mixed traffic. [ABSTRACT FROM AUTHOR]

Trichloroethylene-induced hypersensitivity dermatitis (TIHD) is a delayed hypersensitivity response that is affected by genetic and environmental factors. Occupational exposure to trichloroethylene (TCE) enhances antigen presentation, leading to hypersensitivity in workers with the HLA-B* 13:01 allele. Several studies have observed the activation of herpesviruses, such as Epstein Barr virus (EBV), in TIHD patients. However, the underlying mechanisms remain unclear. Toll-like receptors (TLRs) play a pivotal role in the pathogenesis of herpesvirus infection. This study aimed to explore whether TLRs serve as a shared mechanism for both herpesvirus and allergenic chemicals. In this study, HLA-B* 13:01-transfected Hmy2. A C1R cell model was constructed, and cells were treated with TCOH and EBV to explore the possible mechanisms. We established a mouse model of dermatitis and used a TLR4 agonist to verify the effect of herpesvirus on TIHD. The results showed that EBV and TCOH synergistically enhance antigen processing and presentation via the TLR2/NF-κB axis. Furthermore, TLR4 agonist further aggravated skin lesions and liver damage in TCE-sensitized mice through TLR4/NF-κB axis-mediated antigen processing and presentation. Together, this study indicates that viral infection further aggravates the inflammatory response in TIHD based on environment-gene interactions. • Trichloroethanol and EBV synergistically activated TLR2/NF-κB pathway. • Trichloroethanol and EBV promoted antigen processing and presentation. • TLR4 agonist aggravated trichloroethylene-induced antigen-presenting function. • TLR4 agonist potentiated the skin lesions of trichloroethylene-sensitized mice. [ABSTRACT FROM AUTHOR]

Oxidative stress is usually considered to be a common mechanism by which particulate matter (PM) exposure induces adverse effects. However, the further biological events such as organelle dysfunction following oxidative stress remain to be explored. In this study, we applied high-content screening (HCS) technique to investigate the toxicological effects of carbon black (CB), diesel exhaust particle (DEP) and PM2.5 on oxidative stress and organelle function in human bronchial epithelial cell (16HBE), human embryo lung fibroblast cell (HELF) and human umbilical vein endothelial cell (HUVEC) which were used to represent distinct regions of the lung, and compared the toxicity impacts of different PMs and the sensitiveness of cell lines. We found three types of PMs induced mitochondrial dysfunction in three cell lines and lysosomal alkalinization in HUVEC while only CB triggered endoplasmic reticulum (ER) stress in 16HBE and HUVEC, and oxidative stress might mediate these processes. Moreover, CB basically exhibited more potent toxicity compared with DEP and PM2.5, which might be attributed to its less oxygen content. Finally, the finding that PMs-induced toxicity impacts exhibited a cell-type dependent manner might provide some information to help to understand the sensitivity of different tissue in the lung. Unlabelled Image • PMs induced oxidative stress and organelle dysfunction. • Oxidative stress might mediate PMs-induced organelle dysfunction. • CB basically exhibited more potent toxicity compared with DEP and PM2.5. • Oxygen content might determine the toxicity difference among the three PMs. • PMs-induced toxicity impacts exhibited a cell-type dependent manner. [ABSTRACT FROM AUTHOR]

With the soaring use of rare earth elements (REEs) worldwidely in high-technology and clean energy industries, there were growing concerns for adverse health effect from the REEs exposure. However, there is a lack of biomonitoring research concerning both urine and blood in population with definite exposure. We performed a biomonitoring study that involved 103 REEs exposed males and 110 males as non-REEs exposed controls. We measured the levels of REEs in environment and urine and blood samples from participants, and explored the exposure-response relationship between REEs in environment and body fluids. The effects of exposure duration and smoking status on the internal exposure level of REEs were also investigated. The results showed environmental REEs level of exposure group was significantly higher than that of control group (range of geometric mean of exposure vs. control: 1.08-4.07 × 104 ng/m3 vs.

Particulate matter (PM) and its harmful components are significant contributors to respiratory diseases and impaired lung function, especially in children. Club cell secretory protein (CC16) is a maker of lung epithelium or club cell injuries. To date, the relationship between metals related with PM and CC16 and lung function impairment has been overlooked in children. We enrolled 603 schoolchildren exposed to different levels of PM in China. We found per doubling increase, urinary thallium, and iron was associated with a 3.42 % (95 % CI: 0.01, 6.72) and 3.09 % (95 % CI: 0.55, 5.56) decrease of serum CC16, respectively, whereas urinary cadmium was associated with a 4.74 % (95 % CI: 1.29, 8.31) increase of serum CC16. The Bayesian kernel machine regression (BKMR) model confirmed these associations and showed a potential synergistic interaction between thallium and cadmium. Urinary metal mixtures were associated with lower CC16 when they were below the 35th percentile compared with their median. Serum CC16 mediated 11.47 % (95 % CI: 0.06, 45.00) of the association between urinary thallium and FEV 1 /FVC decline. The inverted U-shaped association with CC16 and the mediation role of CC16 on associations with lung function provide insight into the mechanisms underlying lung injury induced by metals related with PM. [Display omitted] • Urinary thallium and cadmium were independently and interactively associated with serum CC16 in schoolchildren. • Inverted U-shaped association was observed between urinary metal mixtures with serum CC16. • Serum CC16 mediated the association between urinary thallium and lung function decline. [ABSTRACT FROM AUTHOR]

Systematic studies on the associations between co-exposure to multiple metals and chronic kidney disease (CKD), as well as the underlying mechanisms, remain insufficient. This study aimed to provide a comprehensive perspective on the risk of CKD induced by multiple metal co-exposures through the integration of occupational epidemiology and adverse outcome pathway (AOP). The study participants included 401 male mine workers whose blood metal, β2-microglobulin (β2-MG), and cystatin C (Cys-C) levels were measured. Generalized linear models (GLMs), quantile g-computation models (qgcomp), least absolute shrinkage and selection operator (LASSO), and bayesian kernel machine regression (BKMR) were utilized to identify critical nephrotoxic metals. The mean concentrations of lead, cadmium, mercury, arsenic, and manganese were 191.93, 3.92, 4.66, 3.11, 11.35, and 16.33 µg/L, respectively. GLM, LASSO, qgcomp, and BKMR models consistently identified lead, cadmium, mercury, and arsenic as the primary contributors to kidney toxicity. Based on our epidemiological analysis, we used a computational toxicology method to construct a chemical-genetic-phenotype-disease network (CGPDN) from the Comparative Toxicogenomics Database (CTD), DisGeNET, and GeneCard databases, and further linked key events (KEs) related to kidney toxicity from the AOP-Wiki and PubMed databases. Finally, an AOP framework of multiple metals was constructed by integrating the common molecular initiating events (reactive oxygen species) and KEs (MAPK signaling pathway, oxidative stress, mitochondrial dysfunction, DNA damage, inflammation, hypertension, cell death, and kidney toxicity). This is the first AOP network to elucidate the internal association between multiple metal co-exposures and CKD, providing a crucial basis for the risk assessment of multiple metal co-exposures. [Display omitted] • Occupational exposure to multi-metals was associated with decreased kidney function. • Lead, cadmium, arsenic, and mercury were critical metals for kidney toxicity. • Integrated expert knowledge & data mining to develop an Adverse Outcome Pathway (AOP). • The AOP framework reveals the link between these metals and chronic kidney disease. • A promising method assesses the renal risk of multiple metal co-exposures. [ABSTRACT FROM AUTHOR]

Benzo(a)pyrene (B[a]P) is the most widely concerned polycyclic aromatic hydrocarbons (PAHs), which metabolizes benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) in vivo to produce carcinogenic effect on the body. Currently, there is limited research on the role of the variation of metabolic enzymes in this process. We carried out a study including 752 participants, measured the concentrations of 16 kinds PAHs in both particle and gaseous phases, urinary PAHs metabolites, leukocyte BPDE-DNA adduct and serum BPDE- Albumin (BPDE-Alb) adduct, and calculated daily intake dose (DID) to assess the cumulative exposure of PAHs. We conducted single nucleotide polymorphism sites (SNPs) of metabolic enzymes, explored the exposure–response relationship between the levels of exposure and BPDE adducts using multiple linear regression models. Our results indicated that an interquartile range (IQR) increase in B[a]P, PAHs, BaPeq, 1-hydroxypyrene (1-OHP), 1-hydroxynaphthalene (1-OHNap) and 2-hydroxynaphthalene (2-OHNap) were associated with 26.53 %, 24.24 %, 28.15 %, 39.15 %, 12.85 % and 14.09 % increase in leukocyte BPDE-DNA adduct (all P < 0.05). However, there was no significant correlation between exposure with serum BPDE-Alb adduct (P > 0.05). Besides, we also found the polymorphism of CYP1A1(Gly45Asp), CYP2C9 (Ile359Leu), and UGT1A1(downstream) may affect BPDE adducts level. Our results indicated that leukocyte BPDE-DNA adduct could better reflect the exposure to PAHs. Furthermore, the polymorphism of CYP1A1, CYP2C9 and UGT1A1affected the content of BPDE adducts. [ABSTRACT FROM AUTHOR]

Trichloroethylene (TCE), extensively used as an organic solvent in various industrial applications, has been identified as a causative factor in inducing hypersensitivity syndrome (THS). Currently, there is no specific treatment for THS, and most patients experience serious adverse outcomes due to extensive skin damage leading to severe infection. However, the pathogenesis of THS-associated skin damage remains unclear. This study aims to elucidate the mechanism underlying skin damage from the perspective of intercellular communication and gap junctions in THS. Our results verified that hyperactivation of connexin43 gap junctions, caused by the aberrantly elevated expression of connexin43, triggers a bystander effect that promotes apoptosis and inflammation in THS via the TNF-TNFRSF1B and mitochondria-associated pathways. Additionally, we identified the gap junction inhibitor Carbenoxolone disodium (CBX) as a promising agent for the treatment of skin damage in THS. CBX protects against inflammatory cell infiltration in the skin and decreases immune cell imbalance in the peripheral blood of THS mice. Furthermore, CBX reduces connexin43 expression, apoptosis and inflammation in THS mice. The study reveals new insights into the mechanisms underlying TCE-induced skin damage, offering a potential treatment strategy for the development of effective therapies targeting severe dermatitis induced by chemical exposure. • Cx43 gap junction-mediated bystander effects to exacerbate skin damage in THS. • TNF-TNFRSF1B pathway contributes to bystander effects in THS. • The mitochondrial apoptotic pathway is involved in bystander effects in THS. • Carbenoxolone disodium inhibits Cx43 gap junction activity, mitigating skin damage in THS. [ABSTRACT FROM AUTHOR]

Carbon black (CB) particulates as virtually pure elemental carbon can deposit deep in the lungs of humans. International Agency for Research on Cancer classified CB as a Group 2B carcinogen due to inconclusive human evidence. A molecular epidemiological study was conducted in an established cohort of CB packers (CBP) to assess associations between CB exposure and genomic instability in peripheral lymphocytes using cytokinesis-block micronucleus assay (CBMN). Carbon content in airway macrophages (CCAM) was quantified as a bio-effective dosimeter for chronic CB exposure. Dose–response observed in CBPs was compared to that seen in workers exposed to diesel exhaust. The association between CB exposure status and CBMN endpoints was identified in 85 CBPs and 106 non-CBPs from a 2012 visit and replicated in 127 CBPs and 105 non-CBPs from a 2018 visit. The proportion of cytoplasm area occupied by carbon particles in airway macrophages was over fivefold higher in current CBPs compared to non-CBPs and was associated with CBMN endpoints in a dose-dependent manner. CB aerosol and diesel exhaust shared the same potency of inducing genomic instability in workers. Circulatory pro-inflammatory factors especially TNF-α was found to mediate associations between CB exposure and CBMN endpoints. In vitro functional validation supported the role of TNF-α in inducing genomic instability. An estimated range of lower limits of benchmark dose of 4.19–7.28% of CCAM was recommended for risk assessment. Chronic CB exposure increased genomic instability in human circulation and this provided novel evidence supporting its reclassification as a human carcinogen. [ABSTRACT FROM AUTHOR]

Abstract Exposure to air pollution is associated with an increased risk of respiratory infection, to which children are more susceptible than adults. However, epidemiological evidence regarding the association of chronic exposure to air pollution with the immune and systemic inflammatory function of children is scarce, especially in the context of higher exposure levels. In this study, we included 163 chronically exposed schoolchildren from a polluted area and 110 schoolchildren from a control area in Licheng district, Jinan, China. Immune biomarkers, including the absolute counts of lymphocyte subsets and the levels of immunoglobulins G, A, and M, C3, and C4 were determined. To explore the related biological process of altered immune biomarkers, 2 systemic inflammatory biomarkers, including C-reactive protein and the neutrophil-to-lymphocyte ratio, were also determined. After adjusting for confounders, the decreased B lymphocyte count (p = 0.021) and C3 and C4 levels (both p < 0.001) and the increased monocyte count (p = 0.009) and CD8+ T lymphocyte proportion (p = 0.054) were associated with living in the polluted area. Significant differences in the C4 and C3 levels between the areas were only seen in male schoolchildren and in schoolchildren without passive smoking exposure (P interaction = 0.036 and 0.042, respectively). The alterations in immune biomarkers suggested that air pollution-induced immunotoxic effects and relevant adaptive responses were simultaneously present in schoolchildren exposed to a higher level of air pollution. Future studies investigating the temporal patterns of these biomarkers among children are warranted. Graphical abstract Unlabelled Image Highlights • Exposure to air pollution may affect immune and inflammatory function of children. • We enrolled schoolchildren living in polluted or control areas from China. • Decreased B lymphocyte, C3 and C4 levels were found in children from polluted area. • Increased monocyte and CD8+ T proportion were found in children from polluted area. • Immunotoxic effects and adaptive responses were simultaneously present. [ABSTRACT FROM AUTHOR]

Abstract Mechanisms responsible for diesel exhaust particle (DEP)-induced toxicity in respiratory disorders are poorly understood, recent experimental and controlled exposure studies suggested that oxidative stress might be involved. To investigate the time-course effects DEP on nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator in cellular adaptive antioxidant response, mice were intratracheal instilled with 100 μg DEP/mouse and sacrificed after 30 min, 6 h, 12 h, 24 h, 48 h, and 72 h. We measured reactive oxygen species (ROS) as well as Nrf2 and antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and phase II enzymes including heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase-1 (NQO1), glutamate–cysteine ligase catalytic subunit (GCLC), glutamate–cysteine ligase modifier subunit (GCLM) in the lungs. Additionally, histopathological changes were examined. At 6 h, ROS peaked, most of the enzymes were activated, and the histology showed the lungs were damaged. At 12 h, ROS returned to normal level and CAT activity decreased, while protein expression of Nrf2, HO-1, NQO1, GCLC, and GCLM increased, and the lungs were recovering from damage. After 24 h, ROS started to decrease and Nrf2 showed a decreasing trend at both gene and protein levels, while the lung damage had been entirely restored. These results suggested that a single exposure to DEP induce transient oxidative stress in the lungs, with time-dependent effects on Nrf2 and antioxidant enzymes and phase II enzymes. Graphical abstract Unlabelled Image Highlights • Single exposure to DEP induced a transient oxidative stress in lung. • Nrf2 were activated in response of oxidative stress caused by DEP. • Antioxidant enzymes and phase II enzymes revealed time course effects after DEP exposure. [ABSTRACT FROM AUTHOR]

The ribosomal DNA (rDNA) plays a crucial role in maintaining genome stability. So far, alterations of rDNA from airborne pollutants exposure remain unclear. Nasal epithelial cells are the earliest respiratory barrier, which has an accessible surrogate for evaluating respiratory impairment. We developed a mixture-centered biomarkers study integrated epidemiological and biological evidence among 768 subjects, a mixture of polycyclic aromatic hydrocarbons (PAHs) and metals. We identified the mixed exposure of PAHs and metals by environmental and biological monitoring, selected urinary 8-hydroxy-2′-deoxyguanosine as DNA oxidative stress marker, and measured their rDNA copy number (rDNA CN) in nasal epithelial cells. We performed linear regression, adaptive elastic net regression, BKMR, and mediation analyses to assess the direct and indirect effects. We found a 10% elevation in urinary 1-hydroxypyrene was correlated with a separate 0.31% and 0.82% amplification of nasal 5S and 45S rDNA CN, respectively (all P < 0.05). A 10% increment of urine nickel was associated with a separate 0.37% and 1.18% elevation of nasal 5S and 45S rDNA CN, respectively (all P < 0.05). BKMR results also confirmed our findings of PAHs and nickel. Our findings suggested that DNA oxidative stress might trigger rDNA instability induced by inhaled PAHs and metals. [Display omitted] • The nasal rDNA CN amplification presented in PAHs and metals exposed population. • PAHs and Ni in the mixture played a substantial role in expanding nasal rDNA. • DNA oxidative stress might trigger rDNA instability induced by inhaled PAHs and Ni. • Nasal rDNA alteration may serve as the predictive biomarker of respiratory impairment. [ABSTRACT FROM AUTHOR]

Diesel exhaust has long been of health concern due to established toxicity including carcinogenicity in humans. However, the precise components of diesel engine emissions that drive carcinogenesis are still unclear. Limited work has suggested that nitrated polycyclic aromatic hydrocarbons (NPAHs) such as 1-nitropyrene and 2-nitrofluorene may be more abundant in diesel exhaust. The present study aimed to examine whether urinary amino metabolites of these NPAHs were associated with high levels of diesel engine emissions and urinary mutagenicity in a group of highly exposed workers including both smokers and nonsmokers. Spot urine samples were collected immediately following a standard work shift from each of the 54 diesel engine testers and 55 non-tester controls for the analysis of five amino metabolites of NPAHs, and cotinine (a biomarker of tobacco smoke exposure) using liquid chromatography–mass spectrometry. An overnight urine sample was collected in a subgroup of non-smoking participants for mutagenicity analysis using strain YG1041 in the Salmonella (Ames) mutagenicity assay. Personal exposure to fine particles (PM 2.5) and more-diesel-specific constituents (elemental carbon and soot) was assessed for the engine testers by measuring breathing-zone concentrations repeatedly over several full work shifts. Results showed that it was 12.8 times more likely to detect 1-aminopyrene and 2.9 times more likely to detect 2-aminofluorene in the engine testers than in unexposed controls. Urinary concentrations of 1-aminopyrene were significantly higher in engine testers (p < 0.001), and strongly correlated with soot and elemental carbon exposure as well as mutagenicity tested in strain YG1041 with metabolic activation (p < 0.001). Smoking did not affect 1-aminopyrene concentrations and 1-aminopyrene relationships with diesel exposure. In contrast, both engine emissions and smoking affected 2-aminofluorene concentrations. The results confirm that urinary 1-aminopyrene may serve as an exposure biomarker for diesel engine emissions and associated mutagenicity. [ABSTRACT FROM AUTHOR]

PIG-A gene mutations can be detected in humans, and PIG-A assays can potentially predict the risk of exposure to carcinogens. However, extensive, population-based studies to validate this are lacking. We studied a cohort of occupational coke oven workers with chronic high exposure to carcinogenic polycyclic aromatic hydrocarbons, which are well-studied genotoxins classified by the IARC as carcinogenic to humans. Peripheral blood erythrocytes of workers were assessed for gene mutations using a PIG-A assay, and chromosome damage using the cytokinesis-block micronucleus test with lymphocytes. Two sample populations from a non-industrialized city and new employees in industrial plants were selected as controls. We observed a significantly elevated PIG-A mutation frequency (MF) and increased frequencies of micronuclei (MN) and nuclear buds (NBUDs) in coke oven workers, compared with levels in the control groups. We found that the coke oven workers with different lengths of service had a relatively high mutation frequency. Overall, the study findings showed that occupational exposure of coke oven workers increases the genetic damage and the PIG-A MF could be a potential biomarker for risk assessment of carcinogen exposure. • Occupational coke oven workers assessed for gene mutations using PIG-A assays. • Non-industrialized city population and new plant employees used as controls. • PIG-A mutation frequency (MF) significantly elevated in coke oven workers. • Frequencies of micronuclei and nuclear buds also increased in coke oven workers. [ABSTRACT FROM AUTHOR]

Early life is a susceptible period of air pollution-related adverse health effects. Hypertension in children might be life-threatening without prevention or treatment. Nevertheless, the causative association between environmental factors and childhood hypertension was limited. In the light of particulate matter (PM) as an environmental risk factor for cardiovascular diseases, this study investigated the association of pre- and postnatal PM exposure with blood pressure (BP) and hypertension among children and adolescents. Four electronic databases were searched for related epidemiological studies published up to September 13, 2022. Stata 14.0 was applied to examine the heterogeneity among the studies and evaluate the combined effect sizes per 10 μg/m3 increase of PM by selecting the corresponding models. Besides, subgroup analysis, sensitivity analysis, and publication bias test were also conducted. Prenatal PM 2.5 exposure was correlated with increased diastolic blood pressure (DBP) in offspring [1.14 mmHg (95% CI: 0.12, 2.17)]. For short-term postnatal exposure effects, PM 2.5 (7-day average) was significantly associated with systolic blood pressure (SBP) [0.20 mmHg (95% CI: 0.16, 0.23)] and DBP [0.49 mmHg (95% CI: 0.45, 0.53)]; and also, PM 10 (7-day average) was significantly associated with SBP [0.14 mmHg (95% CI: 0.12, 0.16)]. For long-term postnatal exposure effects, positive associations were manifested in SBP with PM 2.5 [β = 0.44, 95% CI: 0.40, 0.48] and PM 10 [β = 0.35, 95% CI: 0.19, 0.51]; DBP with PM 1 [β = 0.45, 95% CI: 0.42, 0.49], PM 2.5 [β = 0.31, 95% CI: 0.27, 0.35] and PM 10 [β = 0.32, 95% CI: 0.19, 0.45]; and hypertension with PM 1 [OR = 1.43, 95% CI: 1.40, 1.46], PM 2.5 [OR = 1.65, 95% CI: 1.29, 2.11] and PM 10 [OR = 1.26, 95% CI: 1.09, 1.45]. Both prenatal and postnatal exposure to PM can increase BP, contributing to a higher prevalence of hypertension in children and adolescents. [Display omitted] • Effects of pre- and postnatal PM exposure on childhood blood pressure were analyzed. • 23 studies involving ∼ 0.9 million participants from 13 countries were reviewed. • Maternal PM2.5 exposure could raise blood pressure in offspring. • Postnatal PM exposure increased the risk of hypertension in children and adolescents. • Effective intervention against PM pollution was needed, specially at early life. [ABSTRACT FROM AUTHOR]

Recently, Trichloroethylene (TCE) induced TCE hypersensitivity syndrome (THS) has attracted the attention of many researchers in the field of environmental and occupational health. Studies have revealed that Human leukocyte antigen (HLA) polymorphisms were the important genetic determinants of the diseases, but the potential molecular mechanism remains unclear. This study aimed to investigate the association between THS and HLA at the molecular level. We chose the human B-lymphoblastoid cell line Hmy2.C1R transfected with cDNA of HLA-B*13:01 and HLA-B*13:02 to analyze the characteristics of HLA-B-binding peptides and investigate the effect of TCE on the binding affinity of peptides to the HLA-B molecules. Further, the mathematical model was used to identify the possible interaction between TCE and HLA-B*13:01 or HLA-B*13:02 molecule. 54 HLA-B*13:01-binding peptides and 85 HLA-B*13:02-binding peptides were identified. Comparing the protein sequences of HLA-B*13:01 and HLA-B*13:02, amino acids were different at positions 94, 95 and 97. The results of the binding affinity of self-peptides to HLA molecules in the presence of TCE showed that TCE significantly decreased the binding affinity of peptides to HLA-B*13:01 only, but did not affect that of HLA-B*13:02. Molecular docking model showed that there was a unique high-affinity binding mode between TCE and HLA-B*13:01 (but not HLA-B*13:02), and the binding site located in the region of F pocket, suggesting that the unique structure of the F pocket of HLA-B*13:01 might provide the possibility of binding TCE. The pathogenesis of interaction between HLA-B*13:01 and TCE might belong to the model of the alteration of the HLA-presented self-peptide repertoire. This study explored the molecular mechanism of the association between THS and HLA-B*13:01 , and had important implications for understanding the role of gene-environment interaction in the development of complex environment-related diseases. Trichloroethylene significantly decreases the binding affinity of peptides to HLA-B*13:01. Trichloroethylene could bind with F pocket of HLA-B*13:01. Trichloroethylene hypersensitivity syndrome might cause by alteration of the HLA-presented self-peptide repertoire. [ABSTRACT FROM AUTHOR]

Air pollution exposure has been found to be associated with epigenetic modification of the mitochondrial genome, which could subsequently induce adverse health outcomes. However, very limited studies exist regarding the association between fine particulate matter (PM 2.5) exposure and pulmonary function at the molecular level of mitochondrial epigenetic changes. This study aimed to investigate the association of platelet mitochondrial DNA (mtDNA) methylation with occupational PM 2.5 exposure and pulmonary function. First, 768 participants were occupationally exposed to polycyclic aromatic hydrocarbon (PAH)-enriched PM 2.5 in a coke-oven plant in East China. The levels of PM 2.5 , PAH components bound to PM 2.5 , and urinary PAH metabolites in the workplace environment were measured as an internal dose, respectively. mtDNA methylation was measured by bisulfite pyrosequencing of two genes of ATP synthase (MT-ATP6 and MT-ATP8). Mediation analysis was conducted to evaluate the role of mtDNA methylation in pulmonary alteration induced by PAH. A decreasing trend of platelet mtDNA methylation was observed with increase in PM 2.5 exposure across all participants. As an important PAH metabolite in urine, 1-hydroxypyrene (1-OHP) was significantly negatively associated with FEV1/FVC (Forced Expiratory Volume in 1s/Forced Vital Capacity) ratio. The participants with high serum folate levels (≥10 nmol/L) showed positive association between MT-ATP6 methylation and FEV1/FVC ratio. Mediation analysis suggested that MT-ATP6 methylation mediated the significant association of urinary 1-OHP with FEV1/FVC. Our findings suggested the methylation of platelet mitochondrial gene MT-ATP6 and FEV1/FVC to be negatively associated with PM exposure. Platelet mtDNA methylation acted as an intermediary between PAH exposure and lung function decline. The mitochondrial epigenetic regulation in platelets, in response to PM exposure, might be involved in subsequent progress of abnormal pulmonary function. • Particulate matter and its PAH exposure are associated with mtDNA hypomethylation. • MT-ATP6 methylation positively correlates with FEV 1 /FVC among normal folate participants. • MT-ATP6 methylation acted as an intermediary between PAH composition and FEV 1 /FVC declining. [ABSTRACT FROM AUTHOR]

We investigated whether exposure to carcinogenic diesel engine exhaust (DEE) was associated with altered adduct levels in human serum albumin (HSA) residues. Nano-liquid chromatography-high resolution mass spectrometry (nLC-HRMS) was used to measure adducts of Cys34 and Lys525 residues in plasma samples from 54 diesel engine factory workers and 55 unexposed controls. An untargeted adductomics and bioinformatics pipeline was used to find signatures of Cys34/Lys525 adductome modifications. To identify adducts that were altered between DEE-exposed and unexposed participants, we used an ensemble feature selection approach that ranks and combines findings from linear regression and penalized logistic regression, then aggregates the important findings with those determined by random forest. We detected 40 Cys34 and 9 Lys525 adducts. Among these findings, we found evidence that 6 Cys34 adducts were altered between DEE-exposed and unexposed participants (i.e., 841.75, 851.76, 856.10, 860.77, 870.43, and 913.45). These adducts were biologically related to antioxidant activity. • Cys34/Lys525 adducts reflect long-lasting effects of reactive oxygen/electrophilic species. • Investigated Cys34/Lys525 adductome alterations among diesel engine exhaust exposed workers. • Six Cys34 adducts were altered between exposed and unexposed participants. • Reactive oxygen/electrophilic species are involved in carcinogenicity of diesel exhaust. [ABSTRACT FROM AUTHOR]

Environmental insults can lead to alteration in DNA methylation of specific genes. To address the role of altered DNA methylation in prediction of polycyclic aromatic hydrocarbons (PAHs) exposure-induced genetic damage, we recruited two populations, including diesel engine exhausts (low-level) and coke oven emissions (high-level) exposed subjects. The positive correlation was observed between the internal exposure marker (1-hydroxypyrene) and the extents of DNA damage (P < 0.05). The methylation of representative genes, including TRIM36 , RASSF1a , and MGMT in peripheral blood lymphocytes was quantitatively examined by bisulfite-pyrosequencing assay. The DNA methylation of these three genes in response to PAHs exposure were changed in a CpG-site-specific manner. The identified hot CpG site-specific methylation of three genes exhibited higher predictive power for DNA damage than the respective single genes in both populations. Furthermore, the dose-response relationship analysis revealed a nonlinear U-shape curve of TRIM36 or RASSF1a methylation in combined population, which led to determination of the threshold of health risk. Furthermore, we established a prediction model for genetic damage based on the unidirectional-alteration MGMT methylation levels. In conclusion, this study provides new insight into the application of multiple epi-biomarkers for health risk assessment upon PAHs exposure. [Display omitted] [ABSTRACT FROM AUTHOR]

Air particulate matter (PM) pollution is associated with the alterations in circulating pulmonary damage proteins. But there are not consistent results among the epidemiological studies. The aim of this study is to investigate the alteration of surfactant protein (SP) from PM exposure. We conducted a comprehensive meta-analysis by searching the databases of PubMed, Medline, EMBASE, Web of Science and CNKI before October 2020 which reported PM pollutants and surfactant protein in the population. The sources of heterogeneity were assessed by subgroup (smoking, particulate matter with different aerodynamic diameter, exposure duration) analysis. We also used the publication bias tests for the comprehensive assessment. This meta-analysis consisted of 10 studies with 1985 subjects. The results showed that the combined standardized mean difference (SMD) value was 0.05, 95% confidence interval (CI) was −0.07 to 0.17 for serum SP-A and −0.81 (95% CI: -1.41 to −0.21) for circulating SP-D. Among smokers, the combined SMD value of SP-A were 0.29 (95% CI: 0.05 to 0.52). We did not find the correlation between publication year of SP-A and SP-D and study heterogeneity. Circulating SP-D was significantly decreased by air particulate matter. Serum SP-A was significantly increased by PM exposure among smokers. Circulating surfactant protein may be considered as a biomarker for respiratory injury caused by air particulate matter. • Comprehensive analysis on circulating surfactant proteins and air particulate matter in population. • PM exposure was associated with a reduction of circulating SP-D. • Circulating surfactant protein can be a biomarker for respiratory injury caused by particulate matter. [ABSTRACT FROM AUTHOR]

• Comprehensive exposure–response analysis on oxidative stress and PM exposure in population. • Increased oxidative stress on DNA and lipid correlated with elevated PM mixture. • Compositions of PAHs and heavy metals need more attention. Oxidative stress has been suggested to be one of the key drivers of health impact of particulate matter (PM). More studies on the oxidative potential of PM alone, but fewer studies have comprehensively evaluated the effects of external and internal exposure to PM compositions on oxidative stress in population. To comprehensively investigate the exposure–response relationship between PM and its main compositions with oxidative stress indicators. We conducted a cross-sectional study including 768 participants exposed to particulates. Environmental levels of fine particulate matter (PM 2.5), polycyclic aromatic hydrocarbons (PAHs) and metals in PM were measured, and urinary levels of PAHs metabolites and metals were measured as internal dose, respectively. Multivariable linear regression models were used to analyze the correlations of PM exposure and urinary levels of 8-hydroxy-2́′-deoxyguanosine (8-OHdG), and 8- iso -prostaglandin-F2α (8- iso -PGF2α) and malondialdehyde (MDA). The concentration of both PM 2.5 and total PAHs was significantly correlated with increased urinary 8-OHdG, 8- iso -PGF2α and MDA levels (all p < 0.05). The levels of 4 essential metals all showed significant exposure–response increase in urinary 8-OHdG in both current and non-current smokers (all p < 0.05); ambient selenium, cobalt and zinc were found to be significantly correlated with urinary 8- iso -PGF2α (p = 0.002, 0.003, 0.01, respectively); only selenium and cobalt were significantly correlated with urinary MDA (p < 0.001, 0.01, respectively). Furthermore, we found each one-unit increase in urinary total OH-PAHs generated a 0.32 increase in urinary 8-OHdG, a 0.22 increase in urinary 8- iso -PGF2α and a 0.19 increase in urinary MDA (all p < 0.001). Furthermore, it was found that the level of 12 urinary metals all showed significant and positive correlations with three oxidative stress biomarkers in all subjects (all p < 0.001). Our systematic molecular epidemiological study showed that particulate matter components could induce increased oxidative stress on DNA and lipid. It may be more important to monitor and control the harmful compositions in PM rather than overall particulate mass. [ABSTRACT FROM AUTHOR]

Airborne particulate matter (PM) is a complex mixture containing various kinds of harmful components. Exposure to air PM is associated with childhood respiratory disease, but epidemiological data are limited concerning the circulating respiratory injury protein on the etiology of childhood respiratory disease. Specifically, the role of PM toxic components or its biological effective dose (adduct) in respiratory injury remains unclear. To demonstrate the dose-response relationship and the main mechanism on circulating club cell secretory protein (CC16) from PM compositions among children, we enrolled 273 boarding schoolchildren in China, including 110 and 163 children of whom were in the low- and high-PM exposed areas, respectively. In this study, we measured the internal exposure levels, including serum polycyclic aromatic hydrocarbons (PAH) adduct, urinary metals, and AhR expression, and detected the serum CC16 level as a lung injury marker. Environmental tobacco exposure in children was assessed by urinary cotinine. We found that significantly higher levels of serum CC16, benzo[a]pyridin-7,8-dihydroglycol-9,10-epoxide (BPDE)-albumin adduct, urinary molybdenum, selenium, arsenic, cadmium and barium, and lower level of AhR expression in high-PM exposed group. There was a good association between serum BPDE-albumin adduct and CC16 (β = 0.222, P = 0.006). There was no association on urinary metals and serum CC16. BPDE-albumin adduct was directly associated with serum CC16 alternation [direct effect = 0.2044, 95% confidence interval (CI) = (0.0426, 0.36)]. PM could cause serum CC16 increased in children. PAH and its adduct might play a key role in lung injury during PM exposure. • PM was associated with significantly increased serum club cell secretory protein in children. • PAH adduct was directly associated with the serum CC16 increment. • PAH and its adduct might play a key role in lung injury during PM exposure. [ABSTRACT FROM AUTHOR]

• PM 2.5 impaired mitochondrial morphology and function, ensuing apoptosis. • PM 2.5 disturbed mito-dynamic, leading to mitochondrial fragmentation via DRP1. • PM 2.5 induced apoptosis via ROS-DRP1-mitochondrial fission axis. Epidemiological studies revealed a sharp increase in respiratory diseases attributed to PM 2.5. However, the underlying mechanisms remain unclear. Evidence suggested mitochondrion as a sensitive target upon the stimulus of PM 2.5 , and the centrality in the pathological processes and clinical characterization of lung diseases. To investigate cell fate and related mechanisms caused by PM 2.5 , we exposed human lung epithelial cells (BEAS-2B) to PM 2.5 (0-100 μg/mL). Consequently, PM 2.5 components were found in cytoplasm, and morphological and functional alterations in mitochondria occurred, as evidenced by loss of cristae, vacuolization and even the outer mitochondrial membrane rupture, mitochondrial membrane potential collapse, enhanced reactive oxygen species (ROS)/mtROS level, calcium overload, suppressed cellular respiration and ATP production in PM 2.5 -treated cells. Further, disturbed dynamics toward fission was clearly observed in PM 2.5 -treated mitochondria, associated with DRP1 mitochondrial translocation and phosphorylation. Besides, PM 2.5 induced mitochondria-mediated apoptosis. More importantly, mechanistic results revealed ROS- and DRP1-mediated mitochondrial fission in a reciprocal way, and DRP1 inhibitor (Mdivi-1) significantly alleviated the pro-apoptotic effect of PM 2.5 through reversing the activated mitochondrial apoptotic pathway. In summary, our results firstly revealed PM 2.5 induced apoptosis in lung epithelial cells through a ROS-DRP1-mitochodrial fission axis-mediated mitochondrial apoptotic pathway, ultimately contributing to the onset and development of pulmonary diseases. [ABSTRACT FROM AUTHOR]

To date, only a limited number of toxicological studies have focused on the establishment and validation of in vitro genotoxicity screening systems using primary hepatocytes, and the results of these studies have been inconsistent. Therefore, the aim of this study was to develop an effective co-culture model of mouse-derived primary hepatocytes and splenocytes for screening chemicals for genotoxicity using the medium-throughput Comet assay. This cocultured model was constructed and verified using known genotoxic and non-genotoxic compounds as positive and negative controls, respectively. Cytotoxicity was measured using Cell Counting Kit-8 and lactate dehydrogenase methods. DNA damage was detected using both alkaline and formamidopyrimidine DNA glycosylase (FPG) Comet assays. Compared with the controls, DNA strand breaks and FPG-sensitive sites showed significant concentration-dependent increases in genotoxic-agent-treated groups. In contrast, DNA damage remained unchanged in non-genotoxic-agent-treated groups. In addition, different types of genotoxic agents resulted in different time-dependent DNA lesions. Our results indicated that the % tail DNA indicating both DNA strand breaks and FPG-sensitive sites might be effective markers for predicting chemical-induced DNA damage and oxidative DNA damage using the cocultured model of hepatocytes and splenocytes. Collectively, these findings provide reliable experimental data for the establishment of in vitro genotoxicity screening methods. Unlabelled Image • We developed an effective co-culture model of mouse-derived primary hepatocytes and splenocytes. • We determined chemical-induced DNA damage using the in vitro cocultured model combined with medium-throughput Comet assay. • The % tail DNA indicating both SSBs and FPG sites might be useful markers for predicting DNA damage and oxidative damage. [ABSTRACT FROM AUTHOR]

• Cell-based bioassays were applied to assess diverse toxic potencies of PM2.5. • BMD modeling was useful in interpretation of concentration-response effects. • Health risk was calculated by toxic potencies and lung deposited dose. The determination of PM 2.5 -induced biological response is essential for understanding the adverse health risk associated with PM 2.5 exposure. In this study, we conducted cell-based bioassays to measure the toxic effects of PM 2.5 exposure, including cytotoxicity, oxidative stress, genotoxicity and inflammatory response. The concentration-response relationship was analyzed by benchmark dose (BMD) modeling and the BMDL 10 was used to estimate the biological potency of PM 2.5 exposure. PM 2.5 samples were collected from three typical megacities of China (Beijing, BJ; Wuhan, WH; Guangzhou, GZ) in typical seasons (winter and summer). The total PM, water-soluble fractions (WSF), and organic extracts (OE) were prepared and subjected to examination of toxic effects. The biological potencies for cytotoxicity, oxidative stress and genotoxicity were generally higher in winter samples, while the inflammatory potency of PM 2.5 was higher in summer samples. The relative health risk (RHR) was determined by integration of the biological potencies and the cumulative exposure level, and the ranks of RHR were BJ-W > WH-W > BJ-S > WH-S > GZ-W > GZ-S. Notably, we note that different PM 2.5 compositions were associated with distinct biological effects, and the health effects distribution of PM 2.5 varied in regions and seasons. These findings demonstrate that the approach of integrated cell-based bioassays could be used for the evaluation of health effects of PM 2.5 exposure. [ABSTRACT FROM AUTHOR]

Pregnancy complications, such as gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP), have a great impact on public health. Exposure to ambient air pollution during pregnancy may cause pregnancy complications. The aim of our study is to explore the risk of trimester-specific maternal exposure to air pollutants on complications of pregnancy. PubMed, EMBASE, Web of Science, and Cochrane were systematically searched for cohort studies published before October 27, 2019 which reported the association between ambient air pollutants (PM 2.5 , PM 10 , CO, NO, NO 2 , NO x , O 3 , and SO 2) and pregnancy complications (GDM, HDP, preeclampsia, and gestational hypertension) during different exposure windows. A meta-analysis was applied to combine relative risks (RRs) and their confidence intervals (CIs) from eligible studies. Quality assessment was conducted and Egger test was used to evaluate the publication bias. All statistical analyses were performed by STATA software (Version 15, StataCorp, College Station, Texas, USA). This meta-analysis consisted of 33 cohort studies conducted on 22,253,277 pregnant women. Meta-analyses showed during the first trimester, there were significant associations of PM 10 with gestational hypertension (RR = 1.07, 95% CI: 1.02–1.12 per 10 μg/m3, I 2 = 0.0%), of SO 2 with GDM (RR = 1.04, 95% CI: 1.00–1.08 per 1 ppb increment, I 2 = 54.1%), of PM 2.5 with preeclampsia (RR = 0.97, 95% CI: 0.95–1.00 per 5 μg/m3, I 2 = 4.1%). During the entire pregnancy, PM 2.5 significantly increased the risk of hypertensive disorders of pregnancy (RR = 1.18, 95% CI: 1.02–1.34 per 5 μg/m3, I 2 = 85.1%). Egger test indicated that wide-scale publication bias was unlikely. Maternal exposure to ambient air pollutants is associated with pregnancy complications especially during the first trimester. Further large multicenter cohort studies considering different constituents of pollutants, levels of disease severity, sensitive populations, and various exposure windows are warranted in the future research. • This study summarized the evidence from a large number of cohort studies. • During the first trimester, exposure to PM 2.5 , PM 10 , and SO 2 was associated with pregnancy complications. • PM 2.5 significantly increased the risk of hypertensive disorders of pregnancy during the entire pregnancy. [ABSTRACT FROM AUTHOR]

• We examine PM exposure and inflammation-related miRNAs/mRNAs among children in China. • BPDE-Alb adducts were associated with higher miRNAs and lower mRNAs expression. • Associations were stronger in girls and children with smoking exposure/low folic acid. • Mediation analyses indicated miRNAs could partly mediate the associations with mRNAs. Exposure to particulate matter (PM) has been associated with increased risk of various diseases, possibly through its effect on inflammatory response. MicroRNAs (miRNAs), an epigenetic mechanism regulating gene expression, can affect the expression of pro-inflammatory genes. However, few epidemiological studies have examined the impact of PM on inflammation-related miRNAs and their target mRNAs, especially among vulnerable population. We recruited 160 and 113 children from areas with different PM level in Jinan, China. We measured benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts in serum and the expression of 5 candidate miRNAs involved in inflammation regulation and 7 pro-inflammatory genes predicted to be their targets in leukocytes. Generally, children in the polluted area had higher miRNAs and lower mRNAs expression than those in the control area. An interquartile increase of BPDE-Alb adducts was associated with 12.66 %, 14.13 %, and 12.76 % higher of let-7a, miR-146a-5p, and miR-155-5p, as well as 21.61 %, 20.16 %, and 12.49 % lower of IL-6, CXCL8, and TLR2 mRNAs at false discovery rate<0.05, respectively. Additionally, let-7a, miR-146a-5p, and miR-155-5p were found to mediate the associations of BPDE-Alb adducts with IL-6 and/or TLR2 expression. Our findings suggested that PM exposure might attenuate inflammatory response among children in China, which was partly mediated by miRNAs regulating pro-inflammatory genes. [ABSTRACT FROM AUTHOR]

• Decrement of global DNA methylation presented in PM exposed population. • Global DNA hypomethylation associated with elevated PAHs and Ni levels. • Down-regulation of DNMT3B associated with elevated PM levels and PAHs component. There is a paucity of mechanistic information on the DNA methylation and particulate matter (PM) exposure. This study aimed to investigate the association of PM and its component with DNA methylation, and the roles of DNA methyltransferase (DNMTs). There were 240 high-exposed, 318 low-exposed and 210 non-exposed participants in this study. Individual concentrations of PM, polycyclic aromatic hydrocarbons (PAHs) and metals were identified by the monitoring data in their workplaces. Urinary 1-OHP and metals were determined as exposure markers. The global DNA methylation (% 5mC) and the mRNA expression of DNMT1 , DNMT3A and DNMT3B were measured. We used mediation analysis to evaluate the role of DNMTs expression on DNA methylation alteration induced by PAHs and metals components. The decreasing trend of % 5mC was associated with increment of PM exposure in all subjects. We found that one IQR increase in total PAHs (3.82 μg/m3) and urinary 1-OHP (1.06 μmol/mol creatinine) were associated with a separate 6.08% and 7.26% decrease in % 5mC (P = 0.009, P < 0.001), and one IQR increase in urinary Ni (27.75 μmol/mol creatinine) was associated with a 3.29% decrease in % 5mC (P = 0.03). The interaction of urinary 1-OHP with Ni on global DNA methylation (%5mC) was not found (P interaction = 0.89). PM exposure was significantly associated with decreased mRNA level of DNMT3B , but the mediated effect of the PAHs and Ni levels on % 5mC through the DNMT3B pathway was not observed. We found the decrement of global DNA methylation and DNMT3B expression with elevated PM levels in population. The independent mode of action on DNA hypomethylation was found from PAHs and metal components. Global DNA hypomethylation might be a potential biomarker for evaluation of adverse health effects in response to PM exposure. [ABSTRACT FROM AUTHOR]

To assess the carcinogenic potential of PM2.5 exposure, we developed a cell-based experimental protocol to examine the cell transformation activity of PM2.5 samples from different regions in China. The seasonal ambient PM2.5 samples were collected from three megacities, Beijing (BJ), Wuhan (WH), and Guangzhou (GZ), from November 2016 to October 2017. The mean concentrations of PM2.5 were much higher in the winter season (BJ: 109.64 μg/m3, WH: 79.99 μg/m3, GZ: 49.99 μg/m3) than that in summer season (BJ: 42.40 μg/m3, WH: 25.82 μg/m3, GZ: 19.82 μg/m3). The organic extracts (OE) of PM2.5 samples from combined summer (S) (June, July, August) or winter (W) (November, December, January) seasons were subjected to characterization of chemical components. We treated human bronchial epithelial (HBE) cells expressing CYP1A1 (HBE-1A1) with PM2.5 samples at doses ranging from 0 to 100 μg/mL (0, 1.563, 3.125, 6.25, 12.5, 25, 50, 100 μg/mL) and determined the phenotype of malignant cell transformation. A dose-response relationship was analyzed by benchmark dose (BMD) modeling, and the potential were indicated by BMDL 10. The order of the carcinogenic risk of seasonal PM2.5 samples from high to low was BJ-W, WH-W, GZ-W, WH-S, BJ-S, and GZ-S. Notably, we found that the alteration in the lung cancer-related biomarkers, KRAS, PTEN, p53, c-Myc, PCNA, pAKT/AKT, and pERK/ERK was congruent with the activity of cell transformation and the content of specific components of polycyclic aromatic hydrocarbon (PAHs) bound to PM2.5. Taken together, we have successfully developed a cell-based alternative model for the evaluation of potent carcinogenicity upon long-term PM2.5 exposure. Unlabelled Image • Human cell-based model was developed to assess the carcinogenic potential of PM2.5. • BMD modeling was used for delineating cell transformation activity of PM2.5 OEs. • Cancer biomarkers altered in concert with the activity of malignant transformation. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental and occupational pollutants. To date, the effect and mechanism by which PAHs exposure impaired hematopoietic system remains unclear. We examined the capability of PAHs to disrupt hematopoiesis in a study of 639 male participants in China by measuring complete blood counts (CBC) in 2013 and 2014. Gas chromatography–mass spectrometry (GC/MS) method was used to measure airborne levels of PAHs and benzene. We measured 1-hydroxypyrene (1-OHP), S -phenylmercapturic acid (SPMA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in urinary by ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method. We found decreased dose−response of white blood cells, eosinophils, monocytes and lymphocytes with increased PAHs exposure in two consecutive years. We did not find association between benzene with CBC in our study. After stratification analysis by smoking status, the findings were highly consistent. White blood cells, monocytes and red blood cell counts were decreased in high urinary 8-OHdG group. Our study showed that PAHs could impair the hematopoietic system independently, and oxidative stress might play an important role in potential hematotoxicity. • The first follow-up study to evaluate hematotoxicity from chronic PAHs exposure. • Negative association between white blood cells and PAHs exposure in population. • Oxidative stress might be a key role in potential hematotoxicity induced by PAHs. [ABSTRACT FROM AUTHOR]

Due to the complexity of environmental exposure factors and the low levels of exposure in the general population, identifying the key environmental factors associated with diabetes and understanding their potential mechanisms present significant challenges. This study aimed to identify key polycyclic aromatic hydrocarbons (PAHs) contributing to increased fasting blood glucose (FBG) concentrations and to explore their potential metabolic mechanisms. We recruited a highly PAH-exposed diesel engine exhaust testing population and healthy controls. Our findings found a positive association between FBG concentrations and PAH metabolites, identifying 1-OHNa, 2-OHPh, and 9-OHPh as major contributors to the rise in FBG concentrations induced by PAH mixtures. Specifically, each 10 % increase in 1-OHNa, 2-OHPh, and 9-OHPh concentrations led to increases in FBG concentrations of 0.201 %, 0.261 %, and 0.268 %, respectively. Targeted metabolomics analysis revealed significant alterations in metabolic pathways among those exposed to high levels of PAHs, including sirtuin signaling, asparagine metabolism, and proline metabolism pathway. Toxic function analysis highlighted differential metabolites involved in various dysglycemia-related conditions, such as cardiac arrhythmia and renal damage. Mediation analysis revealed that 2-aminooctanoic acid mediated the FBG elevation induced by 2-OHPh, while 2-hydroxyphenylacetic acid and hypoxanthine acted as partial suppressors. Notably, 2-aminooctanoic acid was identified as a crucial intermediary metabolic biomarker, mediating significant portions of the associations between the multiple different structures of OH-PAHs and elevated FBG concentrations, accounting for 16.73 %, 10.84 %, 10.00 %, and 11.90 % of these effects for 1-OHPyr, 2-OHFlu, the sum concentrations of 2- and 9-OHPh, and the sum concentrations of total OH-PAHs, respectively. Overall, our study explored the potential metabolic mechanisms underlying the elevated FBG induced by PAHs and identified 2-aminooctanoic acid as a pivotal metabolic biomarker, presenting a potential target for intervention., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yufei Dai reports was provided by National Natural Science Foundation of China. Yuxin Zheng reports was provided by National Key Research and Development Program of China. Yuanyuan Chen reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Trichloroethylene (TCE)-induced hypersensitivity syndrome (THS) has been a concern for many researchers in the field of environmental and occupational health. Currently, there is no specific treatment for THS, leaving patients to contend with severe infections arising from extensive skin lesions, consequently leading to serious adverse effects. However, the pathogenesis of severe skin damage in THS remains unclear. This study aims to investigate the specific danger signals and mechanisms underlying skin damage in THS through in vivo and in vitro experiments. We identified that cell supernatant containing 15 kDa granulysin (GNLY), released from activated CD3 - CD56 + NK cells or CD3 + CD56 + NKT cells in PBMC induced by TCE or its metabolite, promoted apoptosis in HaCaT cells. The apoptosis level decreased upon neutralization of GNLY in the supernatant by a GNLY-neutralizing antibody in HaCaT cells. Subcutaneous injection of recombinant 15 kDa GNLY exacerbated skin damage in the THS mouse model and better mimicked patients' disease states. Recombinant 15 kDa GNLY could directly induce cellular communication disorders, inflammation, and apoptosis in HaCaT cells. In addition to its cytotoxic effects, GNLY released from TCE-activated NK cells and NKT cells or synthesized GNLY alone could induce aberrant expression of the E3 ubiquitin ligase PDZRN3, causing dysregulation of the ubiquitination of the cell itself. Consequently, this resulted in the persistent opening of gap junctions composed of connexin43, thereby intensifying cellular inflammation and apoptosis through the "bystander effect". This study provides experimental evidence elucidating the mechanisms of THS skin damage and offers a novel theoretical foundation for the development of effective therapies targeting severe dermatitis induced by chemicals or drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influencethe work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Antimony (Sb) poses a significant threat to human health due to sharp increases in its exploitation and application globally, but few studies have explored the pathophysiological mechanisms of acute hepatotoxicity induced by Sb exposure. We established an in vivo model to comprehensively explore the endogenous mechanisms underlying liver injury induced by short-term Sb exposure. Adult female and male Sprague-Dawley rats were orally administrated various concentrations of potassium antimony tartrate for 28 days. After exposure, the serum Sb concentration, liver-to-body weight ratio, and serum glucose levels significantly increased in a dose-dependent manner. Body weight gain and serum concentrations of biomarkers of hepatic injury (e.g., total cholesterol, total protein, alkaline phosphatase, and the aspartate aminotransferase/alanine aminotransferase ratio) decreased with increasing Sb exposure. Through integrative non-targeted metabolome and lipidome analyses, alanine, aspartate, and glutamate metabolism; phosphatidylcholines; sphingomyelins; and phosphatidylinositols were the most significantly affected pathways in female and male rats exposed to Sb. Additionally, correlation analysis showed that the concentrations of certain metabolites and lipids (e.g., deoxycholic acid, N-methylproline, palmitoylcarnitine, glycerophospholipids, sphingomyelins, and glycerol) were significantly associated with hepatic injury biomarkers, indicating that metabolic remodeling may be involved in apical hepatotoxicity. Our study demonstrated that short-term exposure to Sb induces hepatotoxicity, possibly through a glycolipid metabolism disorder, providing an important reference for the health risks of Sb pollution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Understanding the underlying interactions of nanoparticles (NPs) with cells is crucial to the nanotoxicological research. Evidences suggested lysosomes as a vital target upon the accumulation of internalized NPs, and lysosomal damage and autophagy dysfunction are emerging molecular mechanisms for NPs-elicited toxicity. Nevertheless, the interaction with lysosomes, ensuing adverse effects and the underlying mechanisms are still largely obscure, especially in NPs-induced vascular toxicity. In this study, silica nanoparticles (SiNPs) were utilized to explore the adverse effects on lysosome in vascular endothelial cells by using in vitro cultured human endothelial cells (HUVECs), and in-depth investigated the mechanisms involved. Consequently, the internalized SiNPs accumulated explicitly in the lysosomes, and caused lysosomal dysfunction, which were prominent on the increased lysosomal membrane permeability, decline in lysosomal quantity, destruction of acidic environment of lysosome, and also disruption of lysosomal enzymes activities, resulting in autophagy flux blockage and autophagy dysfunction. More importantly, mechanistic results revealed the SiNPs-caused lysosomal impairments and resultant autophagy dysfunction could promote oxidative stress, DNA damage and the eventual cell apoptosis activated by ROS/PARP1/AIF signaling pathway. These findings improved the understanding of SiNPs-induced vascular injury, and may provide novel information and warnings for SiNPs applications in the fields of nanomedicine., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

What Is Already Known About This Topic?: Lung cancer has a high mortality, resulting in a severe disease burden. Polycyclic aromatic hydrocarbons (PAHs) are definitive carcinogen to human, and occupational exposure to PAHs is associated with lung cancer., What Is Added by This Report?: We analyzed the cancer cases from cohort studies on various PAHs exposed workers in China and other countries, calculated the quantitative risk of lung cancer based on meta-analyses, and confirmed the increased risk from lung cancer in selected PAHs exposed occupations., What Are the Implications for Public Health Practices?: There is a clear need to prevent lung cancer on a wide range of PAHs-related occupations in China and around the world. It is crucial to establish guidelines for improving the monitoring on exposure and health promotion in related working environments., Competing Interests: No conflicts of interest reported., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2022.)

What Is Already Known About This Topic?: Coke oven emissions are a complex mixture of particulate matter and gases, some with carcinogenicity, released during coke production. Lung cancer caused by coke oven emissions has been listed as a statutory occupational cancer in China and many countries., What Is Added by This Report?: In this study, coke oven emissions-induced lung cancer was mainly found in the manufacturing industries. Coke oven workers exposed to higher levels of polycyclic aromatic hydrocarbons in different workplaces had a high risk of occupational lung cancer., What Are the Implications for Public Health Practice?: It is necessary to take efforts to greatly reduce emissions from coke production and effectively monitor the health of workers., Competing Interests: No conflicts of interest reported., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2022.)

Coke oven emissions (COEs) are common particle pollutants in occupational environment and the major constituents of COEs are polycyclic aromatic hydrocarbons (PAHs). Previously, we identified aberrant methylation of the fms related tyrosine kinase 1 (FLT1) gene over the course of benzo(a)pyrene (BaP)-induced cell transformation via genome-wide methylation array. To quantify FLT1 methylation, we established a bisulfite pyrosequencing assay and examined the FLT1 hypermethylation in several human cancers. The results revealed that 70.0% (21/30 pairs) of lung cancers harbored hypermethylated FLT1 and concomitant suppression of gene expression compared to the adjacent tissues. This implies that FLT1 hypermethylation might play a role in malignant cell transformation. In addition, FLT1 hypermethylation and gene suppression appeared in primary human lymphocytes in a dose-response manner following COEs treatment. To explore whether FLT1 methylation is correlated with COEs exposure and DNA damage, we recruited 144 male subjects who had been exposed to high levels of COEs and 84 male control subjects. Notably, the FLT1 methylation in peripheral blood lymphocytes (PBLCs) of the COEs-exposed group (19.8 ± 3.2%) was enhanced by 17.9% compared to that of the control group (16.8 ± 2.8%) (P < 0.001). The FLT1 methylation status was positively correlated with urinary 1-hydroxypyrene (1-OHP) levels, an internal exposure marker of PAHs (β = 0.029, 95% CI = 0.010-0.048, P = 0.003) and positively correlated with DNA damage (β OTM  = 0.024, 95% CI = 0.007-0.040, P = 0.005; β Tail DNA  = 0.035, 95% CI = 0.0017-0.054, P < 0.001) indicated by comet assay. Taken together, these findings indicate that FLT1 might be a tumor suppressor, and its hypermethylation might contribute to PAHs-induced carcinogenicity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Exposure to fine particulate matter (PM 2.5 ) pollution is associated with increased morbidity and mortality from respiratory diseases. However, few population-based studies have been conducted to assess the alterations in circulating pulmonary proteins due to long-term PM 2.5 exposure., Methods: We designed a two-stage study. In the first stage (training set), we assessed the associations between PM 2.5 exposure and levels of pulmonary damage markers (CC16, SP-A and SP-D) and lung function in a coke oven emission (COE) cohort with 558 coke plant workers and 210 controls. In the second stage (validation set), significant initial findings were validated by an independent diesel engine exhaust (DEE) cohort with 50 DEE exposed workers and 50 controls., Results: Serum CC16 levels decreased in a dose response manner in association with both external and internal PM 2.5 exposures in the two cohorts. In the training set, serum CC16 levels decreased with increasing duration of occupational PM 2.5 exposure history. An interquartile range (IQR) (122.0μg/m 3 ) increase in PM 2.5 was associated with a 5.76% decrease in serum CC16 levels, whereas an IQR (1.06μmol/mol creatinine) increase in urinary 1-hydroxypyrene (1-OHP) concentration was associated with a 5.36% decrease in serum CC16 levels in the COE cohort. In the validation set, the concentration of serum CC16 in the PM 2.5 exposed group was 22.42% lower than that of the controls and an IQR (1.24μmol/mol creatinine) increase in urinary 1-OHP concentration was associated with a 12.24% decrease in serum CC16 levels in the DEE cohort., Conclusions: Serum CC16 levels may be a sensitive marker for pulmonary damage in populations with high PM 2.5 exposure., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Benzene is widely employed in the field of production, and its toxicity on biological systems has received increasing attention. Cell proliferation is a major life characteristic of living organisms. KLF15 and NOTCH1 are mature and classical genes in cell proliferation studies, particularly in the area of tumor investigation. The aim of this study was to investigate the effect and mechanism of VNN3 on cell proliferation induced by 1,4-benzoquinone (1,4-BQ), an important metabolite of benzene, and obtain a sensitive biomarker for the hazard screening and health care of benzene exposure. Normally growing AHH-1 cells were cultured in vitro and were incubated with different concentrations of 1,4-BQ (0, 10, 20, and 40 μM) for 24 h. A CCK-8 assay was used to assess the cell viability, whereas EdU was used to detect the cell proliferation of AHH-1 cells. The expression of VNN3, KLF15 and NOTCH1 was detected by real-time PCR. Moreover, a lentiviral model was constructed in AHH-1 cells to interfere with VNN3 expression. The results showed that 1,4-BQ clearly increased the expression of VNN3. Moreover, 1,4-BQ dose-dependently inhibited cell proliferation and caused increased KLF15 expression; in contrast, the NOTCH1 expression decreased in AHH-1 cells. Furthermore, following interference with the VNN3 expression, the cell proliferation inhibition and the expression of KLF15 and NOTCH1 were rescued. To further investigate the action of VNN3 in benzene hematotoxicity, we assessed it in benzene-exposed workers. The results showed that there was a remarkable correlation between the VNN3 expression and hemogram, which included RBC, NEUT and HGB. In addition, analysis of the KLF15 and NOTCH1 expression showed that the VNN3 expression was related to cell proliferation, which was consistent with the in vitro results. In conclusion, VNN3 influences cell proliferation induced by 1,4-BQ by regulating the expression of KLF15 and NOTCH1. VNN3 may represent a potential biomarker of benzene toxicity., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Long term exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the increasing risk of lung cancer. To identify differentially hypermethylated genes associated with PAHs-induced carcinogenicity, we performed genome-wide DNA methylation analysis in 20 μM benzo(a)pyrene (BaP)-transformed human bronchial epithelial (HBE) cells at different stages of cell transformation. Several methylated genes (CNGA4, FLT1, GAREM1, SFMBT2, TRIM36) were differentially hypermethylated and their mRNA was suppressed in cells at both pre-transformed and transformed stages. Similar results were observed in HBE cells transformed by 20 μg/mL coke oven emissions (COEs) mixture collected from a coking manufacturing facility. In particular, hypermethylation of TRIM36 and suppression of TRIM36 expression were gradually enhanced over the time of COEs treatment. We developed bisulfite pyrosequencing assay and assessed TRIM36 methylation quantitatively. We found that hypermethylation of TRIM36 and reduced gene expression was prevalent in several types of human cancers. TRIM36 hypermethylation appeared in 90.0% (23/30) of Non-Small Cell Lung Cancer (NSCLCs) tissues compared to their paired adjacent tissues with an average increase of 1.32 fold. Furthermore, an increased methylation rate (5.90% v.s 7.38%) and reduced levels of TRIM36 mRNA were found in peripheral lymphocytes (PBLCs) of 151 COEs-exposed workers. In all subjects, TRIM36 hypermethylation was positively correlated with the level of urinary 1-hydroxypyrene (P < 0.001), an internal exposure marker of PAHs, and the DNA damage (P = 0.013). These findings suggest that aberrant hypermethylation of TRIM36 might be involved in the acquisition of malignant phenotype and could be served as a biomarker for risk assessment of PAHs exposure., (Copyright © 2017 Elsevier Ltd. All rights reserved.)