Perfluorooctane sulfonate (PFOS) is one of the most widely used and distributed perfluorinated compounds proven to cause adverse health outcomes. Datasets of ecotoxico-genomics and proteomics have given greater insights for PFOS toxicological effect. However, the molecular mechanisms of hepatotoxicity of PFOS on post-translational modifications (PTMs) regulation, which is most relevant for regulating the activity of proteins, are not well elucidated. Protein glycosylation is one of the most ubiquitous PTMs associated with diverse cellular functions, which are critical towards the understanding of the multiple biological processes and toxic mechanisms exposed to PFOS. Here, we exploit the multilayered glycoproteomics to quantify the global protein expression levels, glycosylation sites, and glycoproteins in PFOS exposure and wild-type mouse livers. The identified 2439 proteins, 1292 glycosites, and 799 glycoproteins were displayed complex heterogeneity in PFOS exposure mouse livers. Quantification results reveal that 241 dysregulated proteins (fold change ≥ 2, p < 0.05) in PFOS exposure mouse livers were involved in the lipid and xenobiotic metabolism. While, 16 overexpressed glycoproteins were exclusively related to neutrophil degranulation, cellular responses to stress, protein processing in endoplasmic reticulum (ER). Moreover, the interactome and functional network analysis identified HP and HSP90AA1 as the potential glycoprotein biomarkers. These results provide unique insights into a deep understanding of the mechanisms of PFOS induced hepatotoxicity and liver disease. Our platform of multilayered glycoproteomics can be adapted to diverse ecotoxicological research.

Perfluoroalkyl acids (PFAAs) are persistent in the environment, highly bio-accumulative in the body, and likely hepatotoxic in humans. There is evidence of sex-specific physiological responses to PFAA exposure. However, epidemiological studies seldom stratify the analyses by sex. Given the high prevalence of liver disease in general population adolescents, this study was designed to determine whether or not there is association between exposure to PFAAs and biomarkers of liver function in adolescent participants of the 2013–2016 National Health and Nutrition Examination Survey, and whether or not such association is sex-specific. Multivariate linear regressions were performed to examine the association between single PFAAs [perfluorooctane sulfonic acid (PFOS); linear form of perfluorooctanoic acid (PFOA); perfluorohexane sulfonic acid (PFHxS); perfluorononanoic acid (PFNA)], and biomarkers of liver function — gamma glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin. Multivariate logistic regressions were performed to estimate adjusted odd ratios (aOR) of elevated ALT, AST and GGT. The study results show that, in females, there was a positive association of the highest PFOA quartile with increased ALT, AST and GGT, and the highest PFNA quartile with increased ALT and AST. Conversely, in male adolescents there was an association of the highest linear PFOA quartile with decreased ALT, and the highest PFNA quartile with ALT and AST. Females had higher odds of clinically-defined elevated ALT with increased PFOA (aOR = 1.79; 95% CI: 1.05, 3.04) or PFNA (aOR = 2.28; 95% CI: 1.08, 2.28), whereas males had decreased odds of clinically-defined elevated ALT with increased n-PFOA (aOR = 0.43; 95% CI: 0.20, 0.93) or PFNA (aOR = 0.5; 95% CI: 0.28, 0.89). In conclusion, there were sex differences in the association between serum PFAA levels and biomarkers of liver function. These results may provide support for analyzing sex-based adverse effects of PFAAs.

Bisphenols (BPs) are common environmental pollutants that are ubiquitous in the natural environment and can affect human health. In this study, we explored the effects of perinatal exposure to BPA, BPF and BPAF on liver function involving in oxidative damage and metabolic disorders in male mouse offspring. We found that BPA exposure impairs the antioxidant defense system, increases lipid peroxidation, and causes oxidative damage in the liver. Furthermore, the levels of 13 metabolites were significantly altered following BPA exposure. We found that BPF exposure significantly increased the expression and activity of CAT, suggesting disturbances in the antioxidant defense system. Moreover, BPF exposure led to metabolic disorders in the liver due to changes in the levels of 8 key metabolites. Exposure to BPAF caused no negative effects on oxidative damage, but altered the levels of β-glucose and glycogen. In summary, perinatal exposure to BPA, BPF and BPAF differentially influence oxidative damage and metabolic disorders in the livers of male mouse offspring. The impact of early life exposure to BPs now warrants future investigations.

Occupational and experimental studies have revealed the organs most affected by dimethylformamide (DMF) are liver and gastrointestinal tract. However, few studies have focused on the potential effect of outdoor pollution of DMF. This study examined the health risk of hospitalization due to digestive system disease by time series studies in a case city Longwan, China. The urine metabolite of DMF was correlated well with DMF exposure concentration (EC). A 101.0-μg/m3 (interquartile range) increase in the two-day moving average of DMF EC was associated with a 1.10 (1.01 ˜ 1.20), 1.22 (1.10 ˜ 1.35), and 1.05 (0.90 ˜ 1.22) increase in hospitalization for total digestive system diseases, liver disease, and gastrointestinal tract disease, respectively. The exposure-dose response between DMF and the relative risk of liver disease was linear only below 350 μg/m3. These findings highlight a previously unrecognized health problem related to VOCs released into the outdoor environment.

Public health is threatened by air pollution and high temperature, especially in urban areas and areas impacted by climate change. Well-designed urban forms have co-benefits on promoting human health and mediating atmospheric environment-related threats (e.g., high temperature and air pollution). Previous studies overlooked these mediating effects of urban form on suicide mortality. This study used partial least squares modeling and countywide data in Taiwan to identify the crucial influences and pathways of urban environment, socioeconomic status, and diseases on suicide mortality. The model considered the impact of the characteristics of urban form (i.e., urban development intensity, land mix, and urban sprawl), urban industrial status (i.e., industrial level), urban greening (i.e., green coverage), disease (i.e., important diseases morbidity of human immunodeficiency virus [HIV], cerebrovascular disease [CVD], chronic liver disease and cirrhosis [CLDC], nephritis, nephrotic syndrome and nephrosis [NNSN], malignant tumor [MT]), socioeconomic status (i.e., income level and aging population rate), and the atmospheric environment (i.e., air pollution and high temperature) on suicide mortality. Optimizing land mix and minimizing urban development intensity and urban sprawl have been found to reduce suicide mortality. The mediating effect of urban form on suicide mortality originated from air pollution and high temperature, and mediating air pollution was greater than high temperature. Furthermore, industrial level, important diseases (HIV, CVD, CLDC, NNSN, and MT) morbidity, an aging population rate, air pollution, and high temperature were associated with an increase in suicide mortality, whereas green coverage and income level were associated with a reduction in suicide rates. The findings demonstrate that appropriate urban policy and urban planning may lower suicide mortality, be useful strategies for suicide prevention, and be a foundation for building a healthy city. Moreover, this study provides clarity on the complex relationship of suicide and the urban environment while identifying crucial factors.

Liver disease has become a growing health burden, and little is known about the impairment of liver function caused by exposure to organophosphate esters (OPEs) in adolescents aged 12–19 years in the United States. To investigate the relationship between urinary metabolites of OPEs including diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(1-chloroethyl) phosphate (BCPP), bis(2-chloroethyl) phosphate (BCEP), and dibutyl phosphate (DBUP) and liver function in US adolescents aged 12–19 years. Liver function tests (LFTs) include aspartate aminotransferase (AST), albumin (ALB), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin (TBIL), total protein (TP), and AST/ALT. Meanwhile, potential confounding and interaction effects were assessed. The study sample included 592 adolescents aged 12–19 from two consecutive NHANES cycles (2011–2012, 2013–2014). A composite statistical strategy combining traditional linear regression with advanced multi-pollutant models quantile based g-computation (QGC) and eXtreme Gradient Boosting (XGBoost) regression was used to analyze the joint effects of multiple OPEs on liver function indicators, and to describe the interaction between different OPEs in detail. 592 adolescent participants were 15 (14–17) years old, with similar numbers of males and females (304 vs. 288). The analysis results showed that (1) in the linear regression model, individual DPHP, BCEP exposure and ALP changes, BCEP and AST/ALT changes were positively associated. DPHP, BDCPP were negatively associated with TP changes. (2) The combined effects of various OPEs on ALB, ALT, ALP, GGT, TBIL, TP, and AST/ALT were statistically significant. (3) There is no potential interaction between different OPEs. Several OPEs and their combinations are closely related to the 8 LFT indicators. In addition, data suggest that exposure to OPEs in adolescents may be associated with liver damage. Due to limited evidence in the literature and potential limitations of the current study, our findings require more studies to confirm.

Exposure to lead can cause adverse health problems incorporating hypophosphatemia, heart and liver disease, cancers, neurological and cardiovascular diseases, central nervous disorders, and sensory disorders. This study investigated the blood lead level in the general Iranian population with environmental exposure to lead. In the presented systematic review and meta-analysis, the authors searched Iranian dataset, including Magiran, SID, Iranmedex, and Nopa, and the main dataset, comprising PubMed, Scopus, Embase, and Web of Science, all available articles until 12 January 2019, and extracting 55 studies (with 63 data for analysis) to a meta-analysis. A comprehensive meta-analysis software, pooled standard deviation, mean, sample size, and the utterly random effects model was analyzed in this study. The results showed that the overall mean BLL (95% CI) in total inquiries was 6.41 μg/dL (5.96 to 6.87). Besides, the results for gender and age subgroups were as follows: mean BLL, 6.47 μg/dL, 95% CI, 5.79, to 7.15, mean BLL, 6.44 μg/dL, 95% CI, 5.96, to 6.91, respectively. Conclusively the mean BLL in the Iranian population was higher than the recommended level by the US Centers for Disease Control and Prevention (CDC). Results indicated that the mean BLL in men and adults was more elevated than in women and children, respectively. Therefore, BLL monitoring and screening of the general Iranian population are is necessary to determine a reference value.

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants formed from the incomplete combustion of carbon-containing products. Exposure can occur through ingestion or inhalation and has been linked to depression, stroke, liver disease, asthma, diabetes, heart failure, and cancer. Few studies have investigated the association between exposure to PAHs and chronic kidney disease (CKD) in humans. This study aims to investigate the association between seven urinary PAH concentrations (1-hydroxynaphthalene, 2-hydroxynaphthalene, 3-hydroxyfluorene 2-hydroxyfluorene, 1-hydroxyphenanthrene, 1-hydroxypyrene, and 2 & 3-hydroxyphenanthrene) and CKD in the US adult population. A cross-sectional analysis using the 2015–2016 National Health and Nutrition Examination Survey (NHANES) dataset was conducted. CKD was defined with estimated glomerular filtration rate (eGFR) and albumin to creatinine ratio (ACR). Participants with an eGFR < 60 ml/min/1.73m² or ACR > 30 mg/gm were considered to have CKD. A specialized complex survey design analysis package using R version 4.0.3 was used in the data analysis. Multivariate logistic regression was used to study the correlation between seven forms of urinary PAH concentrations and CKD associated with abnormal eGFR or ACR. The models were adjusted for lifestyle and demographic factors. The study included a total of 4117 adults aged ≥ 20 years, with 49.6% males and 50.4% females. Urinary 2-hydroxynaphthalene (OR: 1.600, 95% CI: 1.141, 2.243) was significantly associated with an increased odds of CKD; the other six forms of urinary PAHs were not associated with CKD. Non-Hispanic Black (OR: 1.569, 95% CI: 1.168, 2.108), age of 60 years and older (OR: 2.546, 95% CI: 1.865, 3.476), and BMIs of underweight (OR: 2.386, 95% CI: 1.259, 4.524) and obese (OR: 1.407, 95% CI: 1.113, 1.778) all had significantly increased odds for CKD. Our study concluded that urinary 2-hydroxynaphthalene, a form of PAH, is significantly associated with CKD.

Polycyclic aromatic hydrocarbons (PAHs) are a group of chemicals produced from incomplete combustion of carbon-containing products. PAH exposure is associated with pulmonary disease, cardiovascular disease, liver disease, and cancer. However, studies on the exposure to PAHs and depression are limited. The aim of this study is to investigate the relationship between seven types of urinary PAH exposure and depression in the adult population using the National Health and Nutrition Examination Survey (NHANES)2015–2016 dataset. The nine-item Patient Health Questionnaire (PHQ-9) was used to assess for depression; a PHQ-9 score ≥ 10 was considered depressed. Multivariate logistic regression analysis for complex survey procedures was used to assess the relationship between seven types of PAH exposure and depression. A total of 4,123 adults aged ≥20 years were included in the study sample. All forms of urinary PAHs studied, including 1-hydroxynaphthalene, 2-hydroxynaphthalene, 3-hydroxyfluorene, 2-hydroxyfluorene, 1-hydroxyphenanthrene, 1-hydroxypyrene, and 2 and 3-hydroxyphenanthrene, were positively associated with depression.

In the study, 305 patients of both genders were enrolled and divided into three groups: obese (BMI > 30 kg/m²), patients who were diagnosed type 2 diabetes mellitus (T2DM), and control, normal weight healthy volunteers. At least one of ten different phthalate metabolites was determined in the urine samples of 49.84% all enrolled participants. In the obese subgroup, the sum of all urinary phthalate metabolites was positively associated with TG levels (p = 0.031) together with derived TC/HDL and TG/HDL ratios (p = 0.023 and 0.015), respectively. Urinary MEP concentration was positively correlated with the HOMA-IR in T2DM subgroup (p = 0.016) while in the control subgroup, log₁₀MEP levels were negatively correlated with total cholesterol (p = 0.0051), and LDL serum levels (p = 0.0015), respectively. Also, in the control subgroup, positive linear correlations between urinary log₁₀MEP levels and TyG and TYG-BMI values (p = 0.028 and p = 0.027), respectively, were determined. Urinary MEHP levels were associated with glucose serum levels (p = 0.02) in T2DM subgroup, while in the control HDL values were negatively associated with log₁₀MEHP (p = 0.0035). Healthy volunteers exposed to phthalates had elevated AST levels in comparison to non-exposed ones (p = 0.023). In control subgroup, ALT and AST values were increased (p = 0.02 and p = 0.01, respectively) in MEP exposed while GGT levels were enhanced (p = 0.017) in MEHP exposed in comparison with non-exposed. Combined phthalates influence on glucose and lipid metabolism may increase the possibility for NAFLD and insulin resistance development among exposed individuals.