The air pollution related health hazards have been a major public health issue for a long time. As an important source of air pollution, diesel exhaust (DE) exposure associates with serious adverse health outcomes. Apart from the exposure in general population, extensive occupational DE exposure populations are reported in many industries, such as transportation, mining, shipping, and construction. Therefore, the studies for internal exposure levels, biomarkers, and toxic mechanisms of DE in occupational population are critical for protecting human from DE-posed health hazards. This special column published some novel findings involving DE exposure (internal & external exposure level), multiple biological effects, toxicity mechanisms, key molecular events, and crucial biomarkers. These studies will provide scientific data for controlling DE associated occupational health hazards, formulating effective DE pollution control strategies, and provide a new scientific perspective and evidence for health risk assessment and prevention.

Background The exposure to diesel particulate matter (DPM) and its polycyclic aromatic hydrocarbons (PAH) is closely related to the morbidity and mortality of ischemic heart disease (IHD). However, it is unclear what key components and targets of DPM exposure involve in myocardial ischemia-hypoxia injury and associated mechanisms. Objective To identify key PAH components of DPM that act on myocardial hypoxic injury, andclarify the role of oxygen sensors-regulated anaerobic metabolism in DPM and key components-induced hypoxic injury and the targets of the key PAH components. Methods Human cardiomyocyte cell line AC16 cells were exposed to 0, 1, 5, and 10 μg·mL⁻¹ DPM in a high glucose DMEM medium with 10% fetal bovine serum (FBS) (HGM) or low FBS (0.5%) in high glucose DMEM medium (LFM), for 12 h under 2% O₂, and expression of hypoxia-inducible factor-1α (HIF-1α), Bax, and Cleaved-caspase3 was determined by Western blotting. Under normal condition, the cell viability was detected after PAH exposure for 12 h. Under the condition of ischemia-hypoxia model, cells were exposed to 0, 0.005, 0.5, and 5 µg·mL⁻¹ PAH for 12 h, and the protein expression of HIF-1α, Bax, and Cleaved-caspase3 was determined. After exposure to DPM or PAH for 12 h, the contents of pyruvate and lactate in cells were detected. Pretreatment with glycolysis inhibitor GSK2837808A was used to explore the role of glycolysis in DPM and benzo[a]pyrene (BaP)-induced hypoxia injury. A molecular docking technique was used to analyze the binding affinity between PAH and oxygen sensors (prolyl hydroxylase domain-containing protein 2, PHD2, and factor-inhibiting hypoxia-inducible factor 1, FIH1), and the protein levels of PHD2, FIH1, and hydroxyl-HIF-1-alpha (OH-HIF-1α) after the DPM or BaP treatment were further determined. Results Under hypoxia, DPM exposure in the LFM induced the expression of HIF-1α, Bax, and Cleaved-caspase3 (P<0.01). Therefore, hypoxia and LFM were selected as the basic ischemia and hypoxia condition. Except for anthracene (Ant) (P>0.05), other PAH decreased cell viability when the concentration was above 1 μg·mL⁻¹ (P<0.05). All concentrations of BaP induced the expression of HIF-1α protein (P<0.05), and the protein levels of Bax and Cleaved-caspase3 were up-regulated after the 0.5 and 5 µg·mL⁻¹ BaP exposure (P<0.01). After exposure to DPM (1, 5 and 10 μg·mL⁻¹) or BaP (0.5 and 5 μg·mL⁻¹), the intracellular pyruvate and lactate contents increased (P<0.05). The glycolysis inhibitor co-treatment decreased the levels of HIF-1α, Bax, and Cleaved-caspase3 proteins compared with the DPM or BaP exposure group for 12 h (P＜0.05). The binding abilities of the five PAHs to the oxygen sensors PHD2 and FIH1 were strong, and BaP was the strongest. Although the DPM or BaP exposure had no effects on the protein levels of PHD2 and FIH1 in AC16 cells (P＜0.05), the protein level of OH-HIF-1α was decreased (P＜0.01). Conclusion BaP exposure can promote hypoxia and injury of myocardial cells and is the key PAH component of DPM that induces myocardial ischemia and hypoxia injury. BaP exposure inhibits the hydroxylation function of PHD2 on HIF-1α by combining with PHD2, decreases the level of OH-HIF-1α and induces HIF-1α accumulation. And then HIF-1α promotes anaerobic metabolism and accelerates ischemia and hypoxia injury of myocardial cells.

Background Due to the limited availability of established research models, very few studies addressed the health effects and underlying mechanisms following exposure to diesel exhaust during the initiation of pulmonary respiration. It is highly demanded to elucidate such health effects and underlying mechanisms, so as to exert protective measures during the early stages of life. Objective To evaluate the health effects of diesel exhaust very-early-in-life inhalation in hatchling chicken with a novel chicken embryo air cell inhalation exposure model, and to explore the potential roles of aryl hydrocarbon receptor signaling pathways in the observed effects with a specific aryl hydrocarbon receptor inhibitor. Methods Fertilized chicken eggs were assigned into five groups randomly (15 eggs per group): control group, air control group, aryl hydrocarbon receptor inhibitor (PDM2) group, diesel exhaust group, and diesel exhaust + aryl hydrocarbon receptor inhibitor (PDM2) group. Fertilized eggs were incubated with standard procedure. At embryonic day 17 (ED17), aryl hydrocarbon receptor inhibitor was administered to the corresponding animals. During embryonic day 18-19 (ED18-19), chicken embryos were exposed to diesel exhaust via air cell inhalation, then placed back to incubator until hatch. The air control group received clean air infusion during ED18-19, while the control group did not receive any treatment. Within 24 h post-hatch, 26 hatchling chickens were anesthetized with sodium pentobarbital, subjected to electrocardiography, and sacrificed to harvest tissue samples of heart and lung. Cardiopulmonary toxicities were evaluated by histopathology, and potential changes in the protein expression levels of aryl hydrocarbon receptor pathway molecule cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) and fibrosis-related pathway molecule phosphorylated SMAD family member 2 (pSMAD2) were assessed by Western blotting. The remaining 29 hatchling chickens were reared until two weeks old, and then subjected to identical treatments. Results The inhalation exposure to diesel exhaust at initiation of pulmonary respiration resulted in thickened right ventricular wall (by 220.3% relative to the control group, same hereafter) and elevated heart rate (17.4%) in one-day-old hatchling chickens. Although no remarkable fibrotic lesions were observed at this point, the expression levels of CYP1A1 and phosphorylation levels of SMAD2 in the lung tissues significantly increased (by 81.3% and 71.6%, respectively). Such changes were effectively abolished by the aryl hydrocarbon receptor inhibitor PDM2 pretreatment. In the two-week-old animals, the thickened right ventricular wall (by 339.3%) and elevated heart rate (by 18.9%) persisted, and significant fibrotic lesions were observed in the lung tissue samples under Masson staining. Again, the aryl hydrocarbon receptor inhibitor PDM2 pretreatment effectively abolished such changes. In addition, no statistically significant changes in CYP1A1 expression levels were observed in the two-week-old chicken lung samples, and a remarkable down-regulation of SMAD2 phosphorylation was observed. The aryl hydrocarbon receptor inhibitor PDM2 pretreatment independently decreased the phosphorylation levels of SMAD2 in the two-week-old chicken lung samples. Conclusion Inhalation exposure to diesel exhaust at initiation of pulmonary respiration could result in persistent cardiopulmonary injury in hatchling chickens, and the underlying mechanism might be associated with the regulation of pSMAD2 by the aryl hydrocarbon receptor signaling pathway.

Background Air pollution is related to the occurrence and development of mental diseases. Olfactory bulb damage might be the potential prodromal symptom and sign of these diseases. The toxicity of diesel exhaust (DE), one of the main sources of air pollution, on olfactory bulb and the underlying mechanisms remain to be elucidated. Objective To explore the toxicity of DE on mouse olfactory bulb and underlying mechanisms. Methods A total of 40 C57BL/6 mice were randomly divided into four groups for exposure to DE by systemic inhalation: control group (filtered air), low exposure group (750 μg·m⁻³ DE), medium exposure group (1500 μg·m⁻³ DE), and high exposure group (3000 μg·m⁻³ DE). The mouse inhalation exposure to DE was performed 1 h per day for 28 d. HE staining was performed to observe pathological changes in mouse olfactory bulb tissue. TUNEL assay was used to observe apop-tosis in olfactory bulb. Kyoto Encyclopedia of Genes and Genomes (KEGG) was exhibited to explore potential mechanisms of olfactory bulb damage associated with DE. Quantitative real-time PCR (qPCR) was used to determine mRNA expression levels of inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Immunofluorescence staining was conducted to observed the microglia and astrocyte activation in olfactory bulb. Results The HE staining results showed that the number of periglomerular cells in the glomerular layer of olfactory bulb decreased in a dose-dependent manner, and the cells in the granule cell layer of olfactory bulb became disordered after DE exposure. The TUNEL staining showed that TUNEL positive cells in olfactory bulb tissue and neuronal apoptosis increased in the exposed groups compared with the control group (P＜0.05). The KEGG pathway analysis showed that DE associated with significant enrichment of TNF signaling pathway in olfactory bulb tissue. The qPCR results showed that the TNF-α relative expression level significantly increased by 67% and the IL-6 relative expression level by 340% in the DE high exposure dose group compared with the control group (P＜0.05). According to the immunofluorescence staining results, the numbers of activated microglia and astrocytes in olfactory bulb tissue significantly increased in the DE high exposure group, the relative fluorescence intensity of ionized calcium binding adaptor molecule 1 (IBA-1) increased by 120%, the granule cell layer relative fluorescence intensity of glial fibrillary acidic protein (GFAP) increased by 400%, and the glomerular layer relative fluorescence intensity of GFAP increased by 240% than those in the control group (P＜0.05). Conclusion Inhalation exposure to DE can lead to glial cell activation including microglia and astrocytes in olfactory bulb tissue by activating inflammatory pathways and releasing inflammatory factors TNF-α and IL-6, leading to neuronal apoptosis in olfactory bulb tissue.

Diesel exhaust (DE) is an important pollution source widely existing in the living and production environment, which is closely related to the health of the public and occupational groups. The International Agency for Research on Cancer has classified DE as a Group 1 carcinogen. Considering the negative health impacts on the respiratory system due to DE exposure in vitro, it is crucial to apply reliable test systems allowing accurate assessment of the biological effects of DE. The exposure technology of respiratory system in vitro is considered as one of the feasible measures to implement the 3R (reduce, refine, and replace) principle in animal experiments. Compared with the traditional submerged culture in vitro models, the air-liquid interface (ALI) exposure technology has the advantages including fewer influencing factors, easier exposure condition control, and shorter exposure cycle. ALI has become an important tool to study molecular events associated with physiology and pathology of respiratory system, and action modes and interactions of different cell types. Also, ALI has been increasingly widely used because it can simulate the actual processes of human respiratory system cells and/or tissues to DE exposure. This review was intended to introduce the development and advantages of ALI exposure technology, and further summarized the application progress of ALI exposure technology in studying the respiratory toxicity induced by DE exposure in vitro, so as to provide new ideas and pathways for the use of ALI exposure technology in the study of biomarkers and mechanisms of respiratory toxicity associated with DE exposure, and provide basic data to screen and promote biomarkers for exposed populations.

Diesel exhaust (DE) can enter the organism body and cause multiple organ damage. DE contains particles that can be suspended in the air for a long time. Epigenetic regulation is a post transcriptional regulation change that does not involve DNA sequence changes. Many evidences showed that DE can affect the normal physiological functions of multiple organs and systems through epigenetic changes, thus regulating the occurrence and development of multiple diseases. This paper reviewed the research progress of DNA methylation and non-coding RNA in the biological harmful effects of DE. This will provide a basis for the safety evaluation, health risk assessment, and management of DE.

As a source of traffic-related air pollution, diesel particulate matter (DPM) associate with a variety of lung-related diseases, but there is no systematic review of the relationship between DPM and the development and progression of asthma. This article reviewed the relationship between DPM and asthma, the effect and mechanism of DPM on airway inflammation and remodeling in asthma, and illustrated that DPM exposure may participate in airway inflammation and remodeling through oxidative stress, immune regulation and regulation of lung and intestinal microecology, so as to promote the development and progression of asthma.

Diesel exhaust (DE), Group 1 carcinogen, is an important source of air pollutants. Studies show that DE exposure associates with elevated incidences of respiratory and cardiovascular diseases. The toxic effects of DE are closely related to its components. Polycyclic aromatic hydrocarbons (PAHs) are one of the main toxic components in DE and are often used as human exposure biomarkers to DE. However, the exposure assessment of DE using PAHs as biomarkers could be interfered due to the other sources of PAHs. Therefore, identification of highly specific and reliable PAHs sourced biomarkers of DE exposure has become a hotspot of current research. New biomarkers of DE may play an important role in determining human exposure to DE and establishing dose-response relationship of DE exposure and health outcomes of interest. This paper focused on current progress in terms of PAHs sourced biomarkers of human exposure to DE with the following aims: (1) to clarify the types of PAHs sourced biomarkers to DE; (2) to explore the applicability and limitations of PAHs sourced biomarkers for DE exposure assessment in occupational exposure and environmental exposure analysis; and (3) to summarize the analysis methods for PAHs sourced exposure biomarkers in human urine samples and compare the advantages and disadvantages of different analytical methods.

Background Long working hours are a common occupational health risk factor. The problem of long working hours and its impact on health of medical staff cannot be ignored. Objective To investigate long working hours in medical staff of tertiary grade A hospitals in Shanghai, and evaluate the relationships of long working hours with occupational stress and fatigue accumulation. Methods A total of 1531 medical staff in departments of emergency, internal medicine, surgery, intensive care unit (ICU), anesthesiology, and obstetrics and gynecology from 6 hospitals in 6 districts of Shanghai were selected using stratified random sampling. A structured questionnaire was used to collect information on social demographics, occupational characteristics, andbehavior and lifestyle. The Core Occupational Stress Scale (COSS) and the Self-diagnostic Questionnaire on the Accumulation of Fatigue of Laborers were used to assess occupational stress and fatigue accumulation condition. Chi-square test and Kruskal-Wallis H test were used to analyze the distributions of long working hours, occupational stress, and fatigue accumulation, log-binomial models were used to analyze the relationships of long working hours with occupational stress and fatigue accumulation, and job title stratified models were also constructed. Results The average weekly working hours of the study subjects was (47.84±11.40) h, 65.90% of the medical staff worked more than 40 h every week. The percentages of the weekly working hours categories of 41-48 h, 49-54 h, and ≥55 h were 31.42%, 13.46%, and 21.03%, respectively. The positive rates of occupational stress and fatigue accumulation were 25.87% and 65.64% respectively, and the differences among different age, gender, job title, education, length of service, and shift system groups were statistically significant (P<0.05). The results of log-binomial regression showed that after adjusting for gender, age, monthly income, marital status, education, physical exercise, smoking, job position, length of service, and shift system, weekly working hours were an influencing factor of occupational stress and fatigue accumulation (P<0.05). Compared with weekly working hours≤40 h, the risk, PR(95%CI), of reporting occupational stress and fatigue accumulation increased to 2.595 (1.989, 3.385) and 1.578 (1.349, 1.845) times respectively for weekly working hours≥55 h (P<0.001). The results of job title stratification analysis showed that the risk of occupational stress among physicians, nurses, and medical technicians increased when weekly working hours≥55 h versus ≤40 h, and the PR (95%CI) values were 2.003 (1.383, 2.902), 1.971 (1.068, 3.636), and 2.770 (1.220, 6.288), respectively (P<0.05). The risk of fatigue accumulation was increased in physicians when weekly working hour≥55 h versus ≤40 h, with a PR (95%CI) value of 1.594 (1.208, 2.103) (P<0.001). Conclusion Long working hours are common among medical personnel and related to the occurrence of occupational stress and fatigue accumulation.

Background Previous studies show that aluminum exposure could increase the expression of miRNA-134-3p, which is involved in the mechanism of aluminum induced learning and memory impairment. However, it has not been investigated whether the expression level of miRNA-134-3p in the peripheral blood of occupational aluminum exposed workers is related to the blood aluminum concentration yet. Objective To evaluate a potential correlation between aluminum concentration in peripheral blood and miR-134-3p expression in occupational aluminum exposed workers. Methods A total of 184 male aluminum workers in the electrolytic aluminum workshop, aluminum oxide workshop, and thermal power workshop of an aluminum plant in Shanxi were selected by cluster sampling. They were divided into four groups (Q₁-Q₄) according to the quartiles of blood aluminum concentration, with 46 workers in each group. The basic information of workers was collected by questionnaire survey, and the cognitive function of workers was evaluated by Montreal Cognitive Assessment (MoCA). The plasma of workers was collected, and the relative expression level of miR-134-3p in plasma was detected by real-time quantitative polymerase chain reaction (RT-PCR). The plasma aluminum concentration was detected by inductively coupled plasma mass spectrometry (ICP-MS). The associations among workers' peripheral blood aluminum concentration, plasma miR-134-3p expression level, and total MoCA score were evaluated by generalized linear models. Results The workers' medians (P₂₅, P₇₅) of blood aluminum concentration, plasma relative expression level of miR-134-3p, and MoCA score were 39.31 (25.30, 57.41) μg·L^-1, 2.93 (2.29, 3.74), and 22.0 (20.0, 26.0), respectively. The results of the generalized linear model showed that after adjusting for age, body mass index, smoking, and alcohol consumption, compared with the Q₁ group, blood aluminum in the Q₂, Q₃, or Q₄ group had an impact on related plasma miR-134-3p expression level and total MoCA score (P<0.05). With increasing blood aluminum concentration, the expression level of miR-134-3p in workers' plasma gradually increased, showing a positive correlation (b>0, P_trend<0.001), while the total score of MoCA gradually decreased, showing a negative correlation (b<0, P_trend<0.001). As the expression level of miR-134-3p in plasma increased, the total score of MoCA gradually decreased, showing a negative correlation (b<0, P_trend<0.001). There was a linear relationship between peripheral blood aluminum concentration and plasma relative expression level of miR-134-3p of the workers in the middle school and below group and the high school group (P_trend<0.05), b (95%CI)=1.796 (1.248, 2.344) and 1.192 (0.874, 1.510), and no correlation was found in the workers in the college and above group (P_trend>0.05). Conclusion Occupational aluminum exposure can lead to an increase in the expression level of miR-134-3p in plasma of workers, which may be related to a decrease in cognitive function of workers.