Melatonin mitigates manganese-induced neural damage via modulation of gut microbiota-metabolism in mice.

Manganese (Mn), a common environmental and occupational risk factor for Parkinson's disease (PD), can cause central nervous system damage and gastrointestinal dysfunction. The melatonin has been shown to effectively improve neural damage and intestinal microbiota disturbances in animal models. This research investigated the mechanism by which exogenous melatonin prevented Mn-induced neurogenesis impairment and neural damage. Here, we established subchronic Mn-exposed mice model and melatonin supplement tests to evaluate the role of melatonin in alleviating Mn-induced neurogenesis impairment. Mn induced neurogenesis impairment and microglia overactivation, behavioral dysfunction, gut microbiota dysbiosis and serum metabolic disorder in mice. All these events were reversed with the melatonin supplement. The behavioral tests revealed that melatonin group showed approximately 30 % restoration of motor activity. According to quantitative real time polymerase chain reaction (qPCR) results, melatonin group showed remarkable restoration of the expression of dopamine neurons and neurogenesis markers, approximately 46.4 % (TH), 68.4 % (DCX in hippocampus) and 48 % (DCX in striatum), respectively. Interestingly, melatonin increased neurogenesis probably via the gut microbiota and metabolism modulation. The correlation analysis of differentially expressed genes associated with hippocampal neurogenesis indicated that Firmicutes-lipid metabolism might mediate the critical repair role of melatonin in neurogenesis in Mn-exposed mice. In conclusion, exogenous melatonin supplementation can promote neurogenesis, and restore neuron loss and neural function in Mn-exposed mice, and the multi-omics results provide new research ideas for future mechanistic studies.

The Associations between Exposure to Multiple Heavy Metals and Total Immunoglobulin E in U.S. Adults.

Immunoglobulin E (IgE) is a type of immunoglobulin, and elevated serum total IgE is often present in allergic diseases. Exposure to environmental heavy metals has been markedly linked to allergic diseases, leading to elevated total IgE levels. However, studies concerning the effects of multiple metal exposures on total IgE levels are limited. Therefore, the current study seeks to explore the correlation between heavy-metal co-exposure and total IgE levels based on the National Health and Nutrition Examination Survey (NHANES, 2005-2006). Participants possessed complete data on total IgE levels, 11 urinary metal concentrations and other covariates. The correlations between 11 metals and total IgE levels were analyzed using multiple linear regression, and total IgE levels were a continuous variable. Total IgE levels exceeding 150 kU/L were considered sensitized. Binary logistic regression analyses were employed to assess the correlation between metal exposure and the occurrence of an allergic state. Then, the association between co-exposure to the 11 metals and total IgE levels or the occurrence of sensitization status was further analyzed by Bayesian kernel machine regression (BKMR), a multi-contaminant model. There were 1429 adults with complete data included. Based on the median concentration, molybdenum (Mo) had the highest concentration (46.60 µg/L), followed by cesium (Cs), barium (Ba), lead (Pb), and mercury (Hg). And the median (interquartile range) for total IgE levels was 43.7 (17.3, 126.0) kU/L. Multiple linear regression results showed that Pb was significantly and positively associated with total IgE levels (ß = 0.165; 95% CI: 0.046, 0.284). Binary logistic regression showed a significant positive correlation between urinary Pb (OR: 1.258; 95% CI: 1.052, 1.510) and tungsten (W) (OR: 1.251; 95% CI: 1.082, 1.447). Importantly, the BKMR model found a positive correlation between combined-metal exposure and total IgE levels and the occurrence of sensitization status. The mixed heavy-metal exposure was associated with increased total IgE levels, and this association may be driven primarily by the exposure of Pb and W. This study provides new insights into the relationship between heavy-metal exposure and allergic diseases. More research is needed to confirm these findings.

Mediation effect of serum zinc on insulin secretion inhibited by methyl tert-butyl ether in gas station workers.

Methyl tert-butyl ether (MTBE), a type of gasoline additive, has been found to affect insulin function and glucose homeostasis in animal experiments, but there is still no epidemiological evidence. Zinc (Zn) is a key regulatory element of insulin secretion and function, and Zn homeostasis can be disrupted by MTBE exposure through inducing oxidative stress. Therefore, we suspected that Zn might be involved and play an important role in the process of insulin secretion inhibited by MTBE exposure. In this study, we recruited 201 male subjects including occupational and non-occupational MTBE exposure from Anhui Province, China in 2019. Serum insulin and functional analog fibroblast growth factor 1 (FGF1) and blood MTBE were detected by Elisa and headspace solid-phase microextraction and gas chromatography-high-resolution mass spectrometry. According to MTBE internal exposure level, the workers were divided into low- and high-exposed groups and found that the serum insulin level in the high-exposed group was significantly lower than that in the low-exposed group (p = 0.003) while fasting plasma glucose (FPG) level increased obviously in the high-exposed group compared to the low-exposed group (p = 0.001). Further analysis showed that MTBE exposure level was positively correlated with FPG level, but negatively correlated with serum insulin level, which suggested that the FPG level increase might be related to the decrease of serum insulin level induced by MTBE exposure. The results of further mediation effect analysis showed that changes in serum zinc levels played a major intermediary role in the process of insulin secretion inhibition and blood glucose elevation caused by MTBE exposure. In addition, a significant negative correlation was found between MTBE exposure and serum Zn level, which might play a strong mediating effect on the inhibition of insulin secretion induced by MTBE exposure. In conclusion, our study provided evidence that MTBE could inhibit insulin secretion and interfere with Zn metabolism in gas station workers for the first time, and found that Zn might play an important mediation effect during the process of inhibiting insulin secretion and interfering with glucose metabolism induced by MTBE exposure.

MTBE exposure may increase the risk of insulin resistance in male gas station workers.

Insulin resistance is closely related to many metabolic diseases and has become a serious public health problem worldwide. So, it is crucial to find its environmental pathogenic factors. Methyl tert-butyl ether (MTBE), a widely used unleaded gasoline additive, has been proven to affect glycolipid metabolism. However, results from population studies are lacking. For this purpose, the potential relationships between MTBE exposure and the triglyceride glucose (TyG) index, a useful surrogate marker of insulin resistance, were evaluated using a small-scale occupational population. In this study, 201 participants including occupational and non-occupational MTBE exposure workers were recruited from the Occupational Disease Prevention and Control Hospital of Huaibei, and their health examination information and blood samples with informed consent were collected. The internal exposure levels were assessed by detecting blood MTBE using solid-phase-micro-extraction gas chromatography-mass spectrometry. Then the adjusted linear regression model was used to assess the relationship between MTBE exposure and fasting plasma glucose (FPG), or TyG index. Then, receiver-operating-characteristic (ROC) curves were performed to calculate the optimal cut-off points. Multivariable and hierarchical logistic regression models were used to analyze the impact of MTBE exposure on the risk of insulin resistance. Obvious correlations were observed between blood MTBE levels with TyG index (p = 0.016) and FPG (p = 0.001). Further analysis showed that using the mean of the TyG index (8.77) as a cutoff value had a good effect on reflecting the risk of insulin resistance. Multivariable logistic regression analysis also indicated that MTBE exposure was an independent risk factor for a high TyG index (OR = 1.088, p = 0.038), which indicated that MTBE exposure might be a new environmental pathogenic factor leading to insulin resistance, and MTBE exposure might increase the risk of insulin resistance by independently elevating the TyG index in male gas station workers.

Single-cell transcriptomics analysis of zebrafish brain reveals adverse effects of manganese on neurogenesis.

Manganese (Mn) is considered as an important environmental risk factor for Parkinson's disease. Excessive exposure to Mn can damage various neural cells and affect the neurogenesis, resulting in neurological dysfunction. However, the specific mechanisms of Mn exposure affecting neurogenesis have not been well understood, including compositional changes and heterogeneity of various neural cells. Zebrafish have been successfully used as a neurotoxicity model due to its homology with mammals in several key regions of the brain, as well as its advantages such as small size. We performed single-cell RNA sequencing of zebrafish brains from normal and Mn-exposed groups. Our results suggested that low levels of Mn exposure activated neurogenesis in the zebrafish brain, including promoting the proliferation of neural progenitor cells and differentiation to newborn neurons and oligodendrocytes, while high levels of Mn exposure inhibited neurogenesis and neural function. Mn could affect neurogenesis through specific molecular pathways. In addition, Mn regulated intercellular communication and affected cellular communication in neural cells through specific signaling pathways. Taken together, our study elucidates the cellular composition of the zebrafish brain and adds to the understanding of the mechanisms involved in Mn-induced neurogenesis damage.

The association of serum neurofilament light chains with early symptoms related to Parkinson's disease: A cross-sectional study.

Neurofilament light chains (NfL), released with neural axon injury, is considered as a potential biomarker for Parkinson's disease (PD). The relationship between NfL and PD has been studied mainly in diagnosed patients. Few large-scale studies analyze the association between NfL levels and multiple non-motor symptoms linked to early PD in the general population. Therefore, this study aims to determine the association of NfL with early symptoms of PD, and effectively respond to the development of early symptoms of PD. We examined the relationship between serum NfL and early non-motor symptoms of PD (smell dysfunction, sleep problems, cognitive function) and serum Klotho levels in the general population using data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES). The relationship between serum NfL and early symptoms of PD in 1125 participants was analyzed by multiple linear regression and logistic regression models. The results showed a significant association between serum NfL and early symptoms of PD. There was a significant positive correlation between NfL and smell dysfunction, short sleep and long sleep. There was a significant negative correlation between NfL and Klotho levels and cognitive function test results. Further, we observed gender and age differences in the association of NfL with early symptoms of PD. Our study demonstrate that elevated serum NfL levels are positively associated with an increased risk of early PD-related symptoms, suggesting that serum NfL can be a promising biomarker for early PD.

The association between nasal mucosa bacteria and serum metals in children with nasal diseases.

Allergic rhinitis (AR) and adenoid hypertrophy (AH) are common nasal diseases in children. Studies have shown that heavy metals are environmental risk factors for nasal diseases, and the pathogenic mechanisms may be related to dysregulation of nasal mucosal microbiota. However, it is unclear how heavy metal exposure relates to the nasal mucosal microbiota in nasal diseases. Therefore, we explored serum metal exposure levels and nasal mucosal microbiota composition in children with different nasal disease, and further studied the potential correlation between metal exposure and disease-related taxa. There were 64 children recruited for this study. The 23 metals concentrations in serum were measured by inductively coupled plasma mass spectrometry, and nasal mucosal bacteria was identified by 16S rRNA sequencing. Nasal diseases (AR and AH) in children were associated with alterations in the abundance and diversity of the nasal mucosal microbiota. The nasal microbiota of children with AR showed lower diversity, while the microbiota of children with AH showed higher diversity. Linear discriminant analysis Effect Size showed 108 differentially abundant taxa between AR and control groups, 35 differentially abundant taxa among large adenoid, moderate adenoid and small adenoid groups. The serum zinc concentration was negatively correlated with Pielou's eveness index and Simpson's Index in children classified by adenoid size. The spearman correlation analysis showed that multiple disease-related taxa were closely associated with metal concentrations in serum. Our findings may support a link between metal exposure and the diversity and composition of nasal bacteria in children with nasal disease, which present new evidence for the effects of metals on children health.

Glutamine supplementation reverses manganese neurotoxicity by eliciting the mitochondrial unfolded protein response.

Excessive exposure to manganese (Mn) can cause neurological abnormalities, but the mechanism of Mn neurotoxicity remains unclear. Previous studies have shown that abnormal mitochondrial metabolism is a crucial mechanism underlying Mn neurotoxicity. Therefore, improving neurometabolic in neuronal mitochondria may be a potential therapy for Mn neurotoxicity. Here, single-cell sequencing revealed that Mn affected mitochondrial neurometabolic pathways and unfolded protein response in zebrafish dopaminergic neurons. Metabolomic analysis indicated that Mn inhibited the glutathione metabolic pathway in human neuroblastoma (SH-SY5Y) cells. Mechanistically, Mn exposure inhibited glutathione (GSH) and mitochondrial unfolded protein response (UPRmt). Furthermore, supplementation with glutamine (Gln) can effectively increase the concentration of GSH and triggered UPRmt which can alleviate mitochondrial dysfunction and counteract the neurotoxicity of Mn. Our findings highlight that UPRmt is involved in Mn-induced neurotoxicity and glutathione metabolic pathway affects UPRmt to reverse Mn neurotoxicity. In addition, Gln supplementation may have potential therapeutic benefits for Mn-related neurological disorders.

Exposure to volatile organic compounds is a risk factor for diabetes: A cross-sectional study.

Currently, more studies showed that environmental chemicals were associated with the development of diabetes. However, the effect of volatile organic compounds (VOCs) on diabetes remained uncertain and needed to be studied. This cross-sectional study examined whether exposure to low levels of VOCs was associated with diabetes, insulin resistance (TyG index) and glucose-related indicators (FPG,HbA1c, insulin) in the general population by using the NHANES dataset (2013-2014 and 2015-2016). We analyzed the association between urinary VOC metabolism (mVOCs) and these indicators in 1409 adults by multiple linear regression models or logistic regression models, further Bayesian kernel machine regression (BKMR) models were performed for mixture exposure analysis. The results showed positive associations between multiple mVOCs and diabetes, TyG index, FPG, HbA1c and insulin, respectively. Among them, HPMMA concentration in urine was significantly positively correlated with diabetes and related indicators (TyG index, FPG and HbA1c), and the concentration of CEMA was significantly positively correlated with insulin. The positive association of mVOCs with diabetes and its related indicators was more significant in the female group and in the 40-59 years group. Thus, our study suggested that exposure to VOCs affected insulin resistance and glucose homeostasis, further affecting diabetes levels, which had important public health implications.

Glutaminase 1 isoform up-regulation associated with lipid metabolism disorder induced by methyl tertiary-butyl ether in male rats.

Methyl tertiary-butyl ether (MTBE) is a new unleaded gasoline additive, which is considered to be associated with abnormal lipid metabolism in many studies, but the metabolic characteristics and mechanism are still unclear. To observe the characteristics of lipid metabolism induced by MTBE and possible pathways, 21 male Wistar rats got intragastric administration for 24 weeks. The serum lipid metabolism indexes and metabolites were analyzed separately by a biochemical analyzer and untargeted metabolomics. And found that serum high-density lipoprotein cholesterol (HDL-C) levels in the exposure group were significantly reduced, and serum very low-density lipoprotein (VLDL) levels were significantly increased. In untargeted metabolomics, 190 differential metabolites were obtained. Among them, 23 metabolites were found to show the same trend in MTBE exposure groups, which might play a key role in systemic energy metabolism. Further metabolic pathways analysis showed that D-Glutamine, D-glutamate metabolism, and the other three pathways were affected by MTBE significantly. Therefore, we evaluated serum glutamine and glutamate levels and found that MTBE exposure significantly reduced glutamine levels and increased glutamate levels in rat serum and L-02 cells. Further, the key regulatory gene of glutamine metabolism, glutaminase 1 isoform (GLS1), was significantly up-regulated in rat liver and L-02 cells exposed to MTBE. While the effect of glutamine and glutamate metabolism induced by MTBE could be weakened by BPTES, an antagonist of GLS1. In conclusion, our results indicated that MTBE exposure could change the level of glutamine metabolism by promoting GLS1 expression and ultimately lead to abnormal lipid metabolism.

Multi-omics analysis reveals Mn exposure affects ferroptosis pathway in zebrafish brain.

Manganese (Mn) accumulates in the central nervous system and can cause neurotoxicity, but the mechanisms of Mn-induced neurotoxicity remain unclear. We performed single-cell RNA sequencing (scRNA-seq) of zebrafish brain after Mn exposure and identified 10 cell types by marker genes: cholinergic neurons, dopaminergic (DA) neurons, glutaminergic neurons, GABAergic neurons, neuronal precursors, other neurons, microglia, oligodendrocyte, radial glia, and undefined cells. Each cell type has its distinct transcriptome profile. Pseudotime analysis revealed that DA neurons had a critical role in Mn-induced neurological damage. Combined with metabolomic data, chronic Mn exposure significantly impaired amino acid and lipid metabolic processes in the brain. Furthermore, we found that Mn exposure disrupted the ferroptosis signaling pathway in the DA neurons in zebrafish. Overall, our study employed joint analysis of multi-omics and revealed ferroptosis signaling pathway is a novel potential mechanism of Mn neurotoxicity.

Associations between multiple heavy metals exposure and neural damage biomarkers in welders: A cross-sectional study.

BACKGROUND: Both occupational and environmental exposure to heavy metals are associated with various neurodegenerative diseases. However, limited evidence is available on the potential effects of exposure to metallic mixtures and neural damage. OBJECTIVES: This study aimed to evaluate the association between metal mixtures in urine and neural damage biomarkers in welders. METHODS: In this cross-sectional study, a total of 186 workers were recruited from steel mills. Twenty-three metals in urine were measured by inductively coupled plasma mass spectrometry. Serum neural damage biomarkers, including neurofilament light chain (NfL), sphingosine-1-phosphate (S1P), prolactin (PRL), and dopamine (DA) were detected using enzyme-linked immunosorbent assay kits. Multivariable linear regression, Bayesian kernel machine regression (BKMR), and Quantile g-computation (QG-C) were employed to estimate the association between metals exposure and neural damage biomarkers. RESULTS: Inverted u-shaped associations of nickel with NfL, S1P, and DA were observed in the BKMR model. A non-linear relationship was also found between Fe and PRL. Urinary cobalt was positively associated with serum PRL and had the strongest positive weights in the QG-C model. Urinary lead was associated with higher serum S1P levels. We also found the interaction among nickel, zinc, arsenic, strontium, iron, and lead with the neural damage biomarkers. CONCLUSION: This study provides new evidence of a direct association between metal mixture exposure and the serum biomarkers of neural damage. Several metals Ni, Co, Pb, Sr, As and Fe, may have adverse effects on the nervous system, while Zn may have neuroprotective effects.

Transcriptome Evidence Reveals Mitochondrial Unfolded Protein Response Participate in SH-SY5Y Cells Exposed to Manganese.

BACKGROUND: Overexposure to manganese (Mn) can lead to neurodegenerative damage, resulting in manganism with similar syndromes to Parkinson's disease (PD). However, little is known about changes in transcriptomics induced by the toxicological level of Mn. In this study, we conducted RNA-seq to explore the candidate genes and signaling pathways included by Mn in human SH-SY5Y neuroblastoma cells. METHODS: The differentially expressed genes (DEGs) between the Mn-treated group and the control group were screened, and weighted gene co-expression network analysis (WGCNA) was employed to identify hub genes. Then, pathway enrichment analyses for those candidate genes were performed in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We further validated the concentration- and time-response effects of Mn exposure (0-500 µM, 3-12 h) on mitochondrial unfolded protein response (UPRMT) by real-time quantitative reverse transcription PCR (qRT-PCR). RESULTS: The results showed 179 up-regulated differentially expressed genes (DEGs) and 681 down-regulated DEGs after Mn exposure. Based on the intersection of DEGs genes and hub genes, 73 DEGs were related to neurotoxicity. The comprehensive pathway analysis showed Mn had widespread effects on the mitogen-activated protein kinase (MAPK) signaling pathway, unfolded protein response, longevity regulating pathway, inflammatory bowel disease, and mitophagy signaling pathway. After Mn exposure, the expressions of activating transcription factor 3 (ATF3) and C-C motif chemokine ligand 2 (CCL2) increased, while the expressions of C/EBP homologous protein (CHOP), caseinolytic protease P (CLPP), and Lon protease 1 (LONP1) decreased in a concentration- and time-dependent manner. CONCLUSIONS: Overall, our study suggests that UPRMT is a new sight in understanding the mechanism of Mn-induced neurotoxicity.

The burden of pneumoconiosis in China: an analysis from the Global Burden of Disease Study 2019.

BACKGROUND: Pneumoconiosis refers to a class of serious diseases threatening the health of workers exposed to coal or silicosis dust. However, the burden of pneumoconiosis is unavailable in China. METHODS: Incident cases, deaths, and disability-adjusted life years (DALYs) from pneumoconiosis and its subtypes in China were estimated from the Global Burden of Disease Study 2019 using a Bayesian meta-regression method. The trend of the burden from pneumoconiosis was analyzed using percentage change and annualized rate of change (ARC) during the period 1990-2019. The relationship between subnational socio-demographic index (SDI) and the ARC of age-standardised death rate was measured using Spearman's Rank-Order Correlation. RESULTS: In 2019, there were 136.8 (95% uncertainty interval [UI] 113.7-162.5) thousand new cases, 10.2 (8.1-13.6) thousand deaths, and 608.7 (473.6-779.4) thousand DALYs from pneumoconiosis in China. Of the global burdens from pneumoconiosis, more than 60% were in China. Both the total number of new cases and DALYs from pneumoconiosis was keeping increasing from 1990 to 2019. In contrast, the age-standardised incidence, death, and DALY rates from pneumoconiosis and its subtypes, except for the age-standardised incidence rate of silicosis, and age-standardised death rate of asbestosis, experienced a significant decline during the same period. The subnational age-standardised death rates were higher in western China than in eastern China. Meanwhile, the subnational ARC of age-standardised death rates due to pneumoconiosis and its subtypes were significantly negatively correlated with SDI in 2019. CONCLUSION: China suffers the largest health loss from pneumoconiosis in the world. Reducing the burden of pneumoconiosis is still an urgent task in China.

Associations of multiple metals with lung function in welders by four statistical models.

BACKGROUND: Exposure to heavy metals has been related to decreased lung function in workers. However, due to limitations in statistical methods for mixtures, previous studies mainly focused on single or several toxic metals, with few studies involving metal exposome and lung function. OBJECTIVES: The study aimed to evaluate the effects of co-exposure to the metal mixtures on multiple parameters of pulmonary function tests and to identify the elements that play an essential role in elastic-net regression (ENET), multivariate linear regression, bayesian kernel machine regression (BKMR), and quantile g-computation (QG-C) models. METHODS: We have recruited 186 welders from Anhui (China) in 2019. And their end-of-shift urine and lung function measure data were collected with informed consent. The urinary concentrations of 23 metals were measured by inductively coupled urinary mass spectrometry. The lung function measures including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and peak expiratory flow (PEF) were also detected as outcome indicators. Four statistical methods, ENET, multivariate linear regression, BKMR, and QG-C models were used to evaluate the associations of element mixtures on lung function comprehensively. RESULTS: Lead and cadmium were negatively associated with FVC and FEV1, nickel and chromium were inversely associated with PEF, and strontium showed significant positive effects in linear regression models, which were consistent with the results in BKMR and QG-C models. Both BKMR and QG-C models showed a significantly negative overall effect of metal mixtures on lung function parameters (FVC, FEV1, and PEF). Meanwhile, BKMR showed the non-linear relationships of cadmium with FVC. CONCLUSION: Multi-pollutant mixtures of metals were negatively associated with lung function. Lead, cadmium, nickel, and strontium might be crucial elements. Our findings highlight a need to prioritize workers' environmental health, and guide future research into the toxic mechanisms of metal-mediated lung function injury.

Reduced mitochondrial DNA copy number in occupational workers from brominated flame retardants manufacturing plants.

Decabrominated diphenyl ether (BDE-209) and its substitute decabromodiphenyl ethane (DBDPE) are two flame retardants that have similar structure and are widely used in various industrial products. The accumulation and potential toxicity of them to human health have already aroused attention, and some research showed that they may affect mitochondrial function. Therefore, this study focused on the population with high exposure to brominated flame retardants (BFRs) and the related changes in mtDNA copy number (mtDNAcn) in whole blood. 334 blood samples were collected from three groups of people in Shandong Province, including 42 BDE-209 occupational exposure workers from the BDE-209 manufacturing plant, 131 DBDPE occupational exposure workers from the DBDPE manufacturing plant, and 161 non-BFRs occupational exposure residents from the BFRs contaminated area. We measured the levels of BDE-209, DBDPE in serum sample, and the mtDNAcn in whole blood sample and analyzed these data by multiple linear regression. The average concentrations of BDE-209, DBDPE and ∑(BDE-209 + DBDPE) in BDE-209 occupational workers were 3510, 639 and 4600 ng/g lw, respectively; the average concentrations of BDE-209, DBDPE and ∑(BDE-209 + DBDPE) in DBDPE occupational workers were 229, 4040 and 4470 ng/g lw, respectively; the average concentrations of BDE-209, DBDPE and ∑(BDE-209 + DBDPE) in non-BFRs occupational exposure residents were 66.3, 45.7 and 137 ng/g lw, respectively. The relative mtDNAcn was 0.823 in BDE-209 occupational workers, 0.845 in DBDPE occupational workers and 0.989 in non-BFRs occupational exposure residents. A 10-fold increase in BDE-209, DBDPE concentrations was separately associated with a 0.068 and 0.063 decrease in mtDNAcn. Therefore, our study implied that BFRs may affect mitochondrial function. As increasing BFRs exposure has emerged in recent years, the relationship between BFRs exposure and mitochondrial function needs further study.

Exposure to the real ambient air pollutants alters the composition of nasal mucosa bacteria in the rat model.

Studies have indicated that ambient pollutant exposure correlates with nasal disease, in which nasal mucosa microbiota play a crucial role. However, the association between exposure to real-ambient air pollutants and the composition of nasal mucosa microbiota has not been well studied. This study aimed to explore the composition of nasal mucosa microbiota after exposure to real-ambient air pollutants with a special system. We monitored PM2.5, O3, etc. in the system and confirmed PM2.5 and O3 were the main pollutants. SD rats were exposed to the system for 16 weeks in summer or 22 weeks in autumn-winter. The concentrations of PM2.5 were 24.00 µg/m3 in the Summer stage and 22.21 µg/m3 in the autumn-winter stage. The O3 concentrations were 25.46 and 13.55 µg/m3, respectively. Exposure altered bacterial beta diversity in the summer stage. There were 4 and 3 different bacteria at the king, order, family and genus levels between the two groups at the two stages, respectively. The abundance of opportunistic pathogens changed, Pseudomonas decreased in summer stage, and Bifidobacterium increased in the autumn-winter stage. The influence of the season on the nasal mucosa microbiota was analyzed. The alpha diversity of the autumn-winter stage was higher than that of the summer stage. LEfSe analysis revealed 34 differential bacterial taxa at the king, order, family and genus level in the two control groups and 31 of the two exposure groups, which were not the same as the bacteria between the control groups and exposure groups. We found that PM2.5 combined with O3 exposure was associated with the composition of the nasal mucosa microbiota and the abundance of opportunistic pathogens, in which season likely impacted the microbiota.

Associations of low level of fluoride exposure with dental fluorosis among U.S. children and adolescents, NHANES 2015-2016.

Drinking water fluoridation was a mid-twentieth century innovation based on the medical hypothesis that consuming low doses of fluoride at the teeth forming years provided protection against dental decays. Numerous studies showed that high level exposure to fluoride could cause dental and skeleton fluorosis. However, there was limited study focusing on the fluorosis effect of low levels of exposure to fluoride. Therefore, our study aimed to examine whether the low level of fluoride exposure (measured in blood plasma and household tap water) was associated with the risk of dental fluorosis based on data of the National Health and Nutrition Examination Survey (NHANES) 2015-2016. We analyzed data in 2098 children and adolescents who had Dean's Index scores, and water and plasma fluoride measures. The Dean's Index score was measured by calibrated dental examiners using the modified Dean's fluorosis classification system. Fluoride was measured in plasma and household tap water. In this study, we found that the rate of fluoride concentration in water above the recommended level of 0.7 mg/L was 25%, but the prevalence of dental fluorosis was 70%. Binary logistic regression adjusted for covariates showed that higher water fluoride concentrations (0.31-0.50, 0.51-0.70, > 0.70 compared 0.00-0.30) were associated with higher odds of dental fluorosis (OR = 1.48, 95% CI: 1.13-1.96, p = 0.005; OR = 1.92, 95% CI: 1.44-2.58, p < 0.001, and OR = 2.30, 95% CI: 1.75-3.07, p < 0.001, respectively). The pattern of regression between plasma fluoride and dental fluorosis was similar. Inclusion, our study showed that even low level of water or plasma fluoride exposure was associated with increased the risk of dental fluorosis. The safety of public health approach of drinking water fluoridation for global dental caries reduction are urgently needed further research.

Amorphous silica nanoparticles accelerated atherosclerotic lesion progression in ApoE-/- mice through endoplasmic reticulum stress-mediated CD36 up-regulation in macrophage.

BACKGROUND: The biosafety concern of silica nanoparticles (SiNPs) is rapidly expanding alongside with its mass production and extensive applications. The cardiovascular effects of SiNPs exposure have been gradually confirmed, however, the interaction between SiNPs exposure and atherosclerosis, and the underlying mechanisms still remain unknown. Thereby, this study aimed to explore the effects of SiNPs on the progression of atherosclerosis, and to investigate related mechanisms. RESULTS: We firstly investigated the in vivo effects of SiNPs exposure on atherosclerosis via intratracheal instillation of ApoE-/- mice fed a Western diet. Ultrasound microscopy showed a significant increase of pulse wave velocity (PWV) compared to the control group, and the histopathological investigation reflected a greater plaque burden in the aortic root of SiNPs-exposed ApoE-/- mice. Compared to the control group, the serum levels of total triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) were elevated after SiNPs exposure. Moreover, intensified macrophage infiltration and endoplasmic reticulum (ER) stress was occurred in plaques after SiNPs exposure, as evidenced by the upregulated CD68 and CHOP expressions. Further in vitro, SiNPs was confirmed to activate ER stress and induce lipid accumulation in mouse macrophage, RAW264.7. Mechanistic analyses showed that 4-PBA (a classic ER stress inhibitor) pretreatment greatly alleviated SiNPs-induced macrophage lipid accumulation, and reversed the elevated CD36 expression induced by SiNPs. CONCLUSIONS: Our results firstly revealed the acceleratory effect of SiNPs on the progression of atherosclerosis in ApoE-/- mice, which was related to lipid accumulation caused by ER stress-mediated upregulation of CD36 expression in macrophage.