Mutations are an important origin of antibiotic resistance in bacteria. While there is increasing evidence showing promoted resistance mutations by environmental stresses, no retrospective research has yet been conducted on this phenomenon and its mechanisms. Herein, we summarized the phenomena of stress-elevated resistance mutations in bacteria, generalized the regulatory mechanisms and discussed the environmental and human health implications. It is shown that both chemical pollutants, such as antibiotics and other pharmaceuticals, biocides, metals, nanoparticles and disinfection byproducts, and non-chemical stressors, such as ultraviolet radiation, electrical stimulation and starvation, are capable of elevating resistance mutations in bacteria. Notably, resistance mutations are more likely to occur under sublethal or subinhibitory levels of these stresses, suggesting a considerable environmental concern. Further, mechanisms for stress-induced mutations are summarized in several points, namely oxidative stress, SOS response, DNA replication and repair systems, RpoS regulon and biofilm formation, all of which are readily provoked by common environmental stresses. Given bacteria in the environment are confronted with a variety of unfavorable conditions, we propose that the stress-elevated resistance mutations are a universal phenomenon in the environment and represent a nonnegligible risk factor for ecosystems and human health. The present review identifies a need for taking into account the pollutants’ ability to elevate resistance mutations when assessing their environmental and human health risks and highlights the necessity of including resistance mutations as a target to prevent antibiotic resistance evolution.

Environmental heavy metal exposure has been considered to be the risk factor for neurodevelopmental disorders in children. However, the available data on the associations between multiple metals exposure and the risk of dyslexia in China are limited. The purpose of our study was to examine the associations between urinary metal concentrations and Chinese dyslexia risk. A total of 56 Chinese dyslexics and 60 typically developing children were recruited. The urinary concentration of 13 metals were measured by inductively coupled plasma-mass spectrometer (ICP-MS). Binary logistic regression and the Probit extension of Bayesian kernel machine regression (BKMR-P) were used to explore the associations between multiple metal exposure and the risk of Chinese dyslexia. Our results indicated that Co, Zn and Pb were significantly associated with Chinese dyslexia in the multiple-metal exposure model. After adjusting the covariates, a positive association was observed between Pb and the risk of Chinese dyslexia, with the odds ratio (OR) in the highest quartiles of 6.81 (95%CI: 1.07–43.19; p–trend = 0.024). Co and Zn were negatively associated with the risk of Chinese dyslexia. Compared to the lowest quartile, the ORs of Co and Zn in the highest quartile are 0.13 (95%CI: 0.02–0.72; p–trend = 0.026) and 0.18 (95%CI: 0.04–0.88; p–trend = 0.038), respectively. In addition, BKMR-P analysis indicated that with the cumulative level across Co, Zn and Pb increased, the risk of Chinese dyslexia gradually declined and then rebounded, albeit non-significantly, and Pb was the major contributor in this association. In general, the urinary concentrations of Co, Zn and Pb were significantly associated with Chinese dyslexia. More prospective studies are needed to confirm the health effects of multiple metals exposure in children with Chinese dyslexia.

Air pollution has been an important risk factor for female reproductive health. However, epidemiological evidence of ambient air pollution on the predictor for ovarian reserve (antral follicle count, AFC) is deficient. We aim to comprehensively evaluate the association of long-term exposure to ambient air pollution with AFC among women of reproductive age in Shanxi of north China. 600 women with spontaneous menstrual cycle, not using controlled ovarian stimulation, were enrolled in the retrospective study. Two distinct periods of antral follicle development were designed as exposure windows. Generalized linear model was employed to estimate the change of AFC associated with exposure of atmospheric pollutants (SO₂, NO₂, PM₁₀, PM₂.₅, CO and O₃). Stratification analysis based on age (<30, ≥30 years), university degree (yes, no), years of exposure (2013–2016, 2017–2019) and duration of infertility (<2, 2–5, >5 years) along with two pollutants model were employed to further illustrate the association. We found every 10 μg/m³ increase in SO₂ concentration level during the entire development stage of antral follicle was associated with a −0.01 change in AFC (95% confidence interval: −0.016, −0.002) adjusting for the confounders including age, BMI, parity and infertility diagnosis factors. The significant association of increased SO₂ level with decreased AFC was particularly observed during the early transition from primary follicle to preantral follicle stage by 10 μg/m³ increase in SO₂ exposure level with a −0.01 change (95% CI: -0.015, −0.002) in AFC. The negative association was pronounced among women aged ≥30 years old, and also significant in two pollutants model after adjusting the confounders. No significant associations between other air pollutants and AFC were observed. Our finding suggests that long-term exposure to air pollutant SO₂ is associated with lower AFC, raising our concern that atmospheric SO₂ exposure may have potential adverse impact on women ovarian reserve.

Goiter is one of common endocrine diseases, and its etiology has not been fully elucidated. The changes in trace elements' levels have an important impact on the thyroid. We designed a case-control study, which involved 383 goiter cases and 383 matched controls. We measured these elements in the urine of participants by inductively coupled plasma optical emission spectrometry (ICP-OES), graphite furnace atomic absorption spectrometry (GFAAS) and As³⁺-Ce⁴⁺ catalytic spectrophotometry. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to select the elements into multi-element models, conditional logistic regression models were applied to analyze the association between elements and goiter risk. Bayesian kernel machine regression (BKMR) model was used to depict elements’ mixtures and evaluate their joint effects. Finally, 7 elements were included in the multi-element model. We found that the concentrations of lithium (Li), strontium (Sr) and barium (Ba) had a negative effect with goiter risk, and lead (Pb) and iodine (I) showed an extreme positive effect. Additionally, compared with the lowest levels, patients with highest quartiles of I and Pb were 6.49 and 1.94 times more likely to have goiter, respectively. On the contrary, in its second and third quartiles, arsenic (As) showed a negative effect (both OR<1). BKMR model showed a certain interaction among Pb, As, Sr and Li on goiter risk. Further large sample studies are needed to confirm these findings in the future.

Air pollution is an important risk factor for autoimmune diseases, but its association with the recurrence of rheumatoid arthritis (RA) remains unclear so far. This study aimed to investigate the short-term association between traffic-related air pollutants and hospital readmissions for RA in Hefei, China. Data on daily hospital readmissions for RA and traffic-related air pollutants, including particulate matter (PM₂.₅ and PM₁₀), nitrogen dioxide (NO₂), and carbon monoxide (CO), from 2014 to 2018 were retrieved. A time-series approach using generalized linear regression model was employed. The analysis was further stratified by sex, age and season. A total of 1153 readmissions for RA were reported during the study period. A significant association between high-concentration PM₂.₅ (90th percentile) and RA readmissions was observed on lag1 (relative risk (RR) = 1.09, 95% confidence interval (CI): 1.01–1.19) and lasted until lag3 (RR = 1.06, 95%CI: 1.01–1.12). From lag2 to lag5, high-concentration NO₂ (90th percentile) was associated with increased risk of RA readmissions, with the highest RR observed at lag 4 (1.11, 95%CI: 1.05–1.17). Stratified analyses indicated that females and the elderly appeared to be more vulnerable to high-concentration PM₂.₅ and NO₂ exposure. High-concentration PM₂.₅ and NO₂ in cold seasons were consistently significantly associated with increased risk of RA readmissions. Exposure to high-concentration PM₂.₅ and NO₂ was associated with increased risk of RA readmissions. Protective measures against the exposure to high-concentration PM₂.₅ and NO₂ should be taken to reduce the recurrence risk in RA patients, especially in females, the elderly and during cold seasons.

Heart development requires a precise temporal regulation of gene expression in cardiomyoblasts. Therefore, the transcriptional changes in differentiating cells can lead to congenital heart diseases. Although the genetic mutations underlie most of these alterations, exposure to environmental contaminants, such as bisphenol A (BPA), has been recently considered as a risk factor as well. In this study we investigated the genotoxic and epigenotoxic effects of BPA throughout cardiomyocyte differentiation. H9c2 cells (rat myoblasts) were exposed to 10 and 30 μM BPA before and during the last two days of cardiac-driven differentiation. Then, we have analysed the phenotypic and molecular modifications (at transcriptional, genetic and epigenetic level). The results showed that treated myoblasts developed a skeletal muscle cell-like phenotype. The transcriptional changes induced by BPA in genes codifying proteins involved in heart differentiation and function depend on the window of exposure to BPA. The exposure before differentiation repressed the expression of heart transcription factors (Hand2 and Gata4), whereas exposure during differentiation reduced the expression of cardiac-specific genes (Tnnt2, Myom2, Sln, and Atp2a1). Additionally, significant effects were observed regarding DNA damage and histone acetylation levels after the two periods of BPA exposure: in cells exposed to the toxicant the percentage of DNA repair foci (formed by the co-localization of γH2AX and 53BP1) increased in a dose-dependent manner, whereas the treatment with the toxicant triggered a decrease in the epigenetic marks H3K9ac and H3K27ac. Our in vitro results reveal that BPA seriously interferes with the process of cardiomyocyte differentiation, which could be related to the reported in vivo effects of this toxicant on cardiogenesis.

Cardiovascular diseases (CVD) are leading global health issue. More studies have linked indoor air pollution from solid fuel usage to hypertension risk, a leading risk factor for CVD. We conducted a systematic review and meta-analysis of observational studies assessing the relationship of indoor air pollution from solid fuel with hypertension risk. Using a protocol standardized a priori, two independent reviewers searched PubMed, the Cochrane Library, Ovid MEDLINE, Web of Science and EMBASE for available studies published before Dec.1, 2019. A random effects model was used to analyse the pooled results. Out of 3740 articles, 47 were reviewed in depth and 11 contributing to this meta-analysis. The use of household solid fuel was significantly associated with an increased risk of hypertension (OR = 1.52, 95% CI = 1.26 to 1.85). The smoking-controlled group (OR = 2.38, 95% CI = 1.58 to 3.60) had greater effect size of hypertension than the uncontrolled group (OR = 1.11, 95% CI = 1.10 to 1.11). These findings implicate that indoor air pollution from solid fuel may be an important risk factor for hypertension.

Polycyclic Aromatic Hydrocarbons are strongly associated with agricultural, residential, transportation, and industrial activities. This study determined by GC-MS the concentration of 15 PAHs in soil and sediments at different sites from the Awotan-Asunle dumpsite area in the Southwestern region of Nigeria, which is one of the largest dumpsites in Africa. The sources of contamination, toxicity and associated risks for human health were also evaluated. Total PAHs concentrations were from 489 to 5616 μg kg⁻¹, and 642–2159 μg kg⁻¹, for soil and sediment, respectively. For soils, the highest values were observed for indeno[1,2,3-c,d]pyrene, coronene, and phenanthrene, while for sediments, the most abundant species were pyrene, fluoranthene and phenanthrene. Diagnostic ratios were used to determine the sources of PAHs and suggested that the compounds were mainly emitted from non-traffic sources. The total BaP-TEQ and BaP-MEQ for soils did not exceed the value recommended by the Canadian guideline since the country does not present guidelines. The analysis of incremental lifetime cancer risk was high mostly for dermal and ingestion exposures in the population. This study might provide valuable information regarding exposure to PAHs in soils of a Nigerian community.

Neonicotinoids (Neonics) have become the most widely used insecticides around the world in recent years. Due to the hydrophilic character, neonics are emerging contaminants in drinking water. In this study, we aimed to characterize and quantify the fate and transport of neonics in the drinking water treatment system and their contributions to the overall dietary risks. Seven neonics in 97 surface and drinking water samples in the city of Hangzhou, China were analyzed. The relative potency factor method was adopted in order to calculate the total neonics concentrations. We then used the Monte Carlo simulation to calculate the chronic daily intake (CDI) of total neonics from water consumption. All 16 surface water samples collected from two rivers contained at least two neonics, and more than 93% of those contained 3 or more neonics. Imidacloprid was detected in all 16 surface water samples, followed by clothianidin and acetamiprid with average concentrations of 11.9, 7.6, 17.6 ng L-1, respectively. The drinking water treatment plants removed approximately 50% of neonics from surface water. However, 68 out of 71 tap water samples that we collected from the household faucets contained at least one neonic, with the highest average concentrations of 5.8 ng L-1 for acetamiprid. The maximum of CDIs of total neonics from water consumption for adult and children were 10.2 and 12.4 ng kg-1 d-1, respectively, which are significantly lower than the acceptable daily intake (ADI). The results presented here shown drinking water consumption only represented an insignificant portion of dietary risks of total neonics, mainly due to the modern drinking water treatment technologies that are capable of removing significant amount of neonics from drinking water. However, the ubiquity of neonics in the drinking water sources to kitchen faucets, should be a concern for public health.

Fluoride has been considered as a risk factor of cardiovascular disease due to its endothelial toxicology. However, the mechanism underlying the endothelial toxicity of fluoride has not been clearly illustrated. MiR-200c-3p was strongly linked with endothelial function and its level is increased in serum of fluorosis patients, but it is unclear the role of miR-200c-3p in the fluoride induced endothelial dysfunction. In this study, we confirmed that fluoride exposure induced the apoptosis of endothelial cells both in established rats model and cultured human umbilical vein endothelial cells (HUVECs). And miR-200c-3p was found to be upregulated in NaF treated HUVECs. Fluoride stimulation increased caspase-dependent apoptosis through miR-200c-3p upregulation, with repressing expression of its target gene Fas-associated phosphatase 1 (Fap-1), which functioned as Fas inhibitor. This resulted in activation of Fas-associated extrinsic apoptosis via interaction with increased Fas, Fadd, Cleaved Caspase-8 and Cleaved Caspase-3. The activation of Fas-associated extrinsic apoptosis was abrogated by miR-200c-3p inhibitor. Furthermore, the antiapoptotic effect of downregulated miR-200c-3p was restored by Fap-1 siRNA. These results suggested a determinant role of the miR-200c-3p/Fap-1 axis in fluoride induced endothelial apoptosis.