Alterations of gut microbiota and its metabolomics in children with 6PPDQ, PBDE, PCB, and metal(loid) exposure.

The composition and metabolites of the gut microbiota can be altered by environmental pollutants. However, the effect of co-exposure to multiple pollutants on the human gut microbiota has not been sufficiently studied. In this study, gut microorganisms and their metabolites were compared between 33 children from Guiyu, an e-waste dismantling and recycling area, and 34 children from Haojiang, a healthy environment. The exposure level was assessed by estimating the daily intake (EDI) of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), 6PPD-quinone (6PPDQ), and metal(loid)s in kindergarten dust. Significant correlations were found between the EDIs of 6PPDQ, BDE28, PCB52, Ni, Cu, and the composition of gut microbiota and specific metabolites. The Bayesian kernel machine regression model showed negative correlations between the EDIs of five pollutants (6PPDQ, BDE28, PCB52, Ni, and Cu) and the composition of gut microbiota. The EDIs of these five pollutants were positively correlated with the levels of the metabolite 2,4-diaminobutyric acid, while negatively correlated with the levels of d-erythro-sphingosine and d-threitol. Our study suggests that exposure to 6PPDQ, BDE28, PCB52, Ni, and Cu in kindergarten dust is associated with alterations in the composition and metabolites of the gut microbiota. These alterations may be associated with children's health.

Associations of co-exposure to polycyclic aromatic hydrocarbons and lead (Pb) with IGF1 methylation in peripheral blood of preschool children from an e-waste recycling area.

BACKGROUND: Childhood exposure to polycyclic aromatic hydrocarbons (PAHs) or lead (Pb) is associated with epigenetic modifications. However, the effects of their co-exposures on IGF1 (Insulin-like growth factor 1) methylation and the potential role in child physical growth are unclear. METHODS: From our previous children study (N = 238, ages of 3-6), 75 children with higher total concentrations of urinary ten hydroxyl PAH metabolites (∑10OH-PAHs) from an e-waste recycling area, Guiyu, and 75 with lower ∑10OH-PAHs from Haojiang (reference area) were included. Pb and IGF1 P2 promoter methylation in peripheral blood were also measured. Multivariable linear regression analyses were performed to estimate individual associations, overall effects and interactions of co-exposure to OH-PAHs and Pb on IGF1 methylation were further explored using Bayesian kernel machine regression. RESULTS: Methylation of IGF1 (CG-232) was lower (38.00 vs. 39.74 %, P < 0.001), but of CG-207 and CG-137 were higher (59.94 vs. 58.41 %; 57.60 vs. 56.28 %, both P < 0.05) in exposed children than the reference. The elevated urinary 2-OHPhe was associated with reduced methylation of CG-232 (B = -0.051, 95 % CI: -0.096, -0.005, P < 0.05), whereas blood Pb was positively associated with methylation of CG-108 (B = 0.106, 95 %CI: 0.013, 0.199, P < 0.05), even after full adjustment. Methylations of CG-224 and 218 significantly decreased when all OH-PAHs and Pb mixtures were set at 35th - 40th and 45th - 55th percentile compared to when all fixed at 50th percentile. There were bivariate interactions of co-exposure to the mixtures on methylations of CG-232, 224, 218, and 108. Methylations correlated with height, weight, were observed in the exposed children. CONCLUSIONS: Childhood co-exposure to high PAHs and Pb from the e-waste may be associated with IGF1 promoter methylation alterations in peripheral blood. This, in turn, may interrupt the physical growth of preschool children.

Elevated plasma solMER concentrations link ambient PM2.5 and PAHs to myocardial injury and reduced left ventricular systolic function in children.

Exposure to fine particulate matter (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) is known to be associated with the polarization of pro-inflammatory macrophages and the development of various cardiovascular diseases. The pro-inflammatory polarization of resident cardiac macrophages (cMacs) enhances the cleavage of membrane-bound myeloid-epithelial-reproductive receptor tyrosine kinase (MerTK) and promotes the formation of soluble MerTK (solMER). This process influences the involvement of cMacs in cardiac repair, thus leading to an imbalance in cardiac homeostasis, myocardial injury, and reduced cardiac function. However, the relative impacts of PM2.5 and PAHs on human cMacs have yet to be elucidated. In this study, we aimed to investigate the effects of PM2.5 and PAH exposure on solMER in terms of myocardial injury and left ventricular (LV) systolic function in healthy children. A total of 258 children (aged three to six years) were recruited from Guiyu (an area exposed to e-waste) and Haojiang (a reference area). Mean daily PM2.5 concentration data were collected to calculate the individual chronic daily intake (CDI) of PM2.5. We determined concentrations of solMER and creatine kinase MB (CKMB) in plasma, and hydroxylated PAHs (OH-PAHs) in urine. LV systolic function was evaluated by stroke volume (SV). Higher CDI values and OH-PAH concentrations were detected in the exposed group. Plasma solMER and CKMB were higher in the exposed group and were associated with a reduced SV. Elevated CDI and 1-hydroxynaphthalene (1-OHNa) were associated with a higher solMER. Furthermore, increased solMER concentrations were associated with a lower SV and higher CKMB. CDI and 1-OHNa were positively associated with CKMB and mediated by solMER. In conclusion, exposure to PM2.5 and PAHs may lead to the pro-inflammatory polarization of cMacs and increase the risk of myocardial injury and systolic function impairment in children. Furthermore, the pro-inflammatory polarization of cMacs may mediate cardiotoxicity caused by PM2.5 and PAHs.

Cell type-dependent response to benzo(a)pyrene exposure of human placental cell lines under normoxic, hypoxic, and pro-inflammatory conditions.

Benzo(a)pyrene (BaP) can be detected in the human placenta. However, little is known about the effects of BaP exposure on different placental cells under various conditions. In this study, we aimed to investigate the effects of BaP on mitochondrial function, pyrin domain-containing protein 3 (NLRP3) inflammasome, and apoptosis in three human trophoblast cell lines under normoxia, hypoxia, and inflammatory conditions. JEG-3, BeWo, and HTR-8/SVneo cell lines were exposed to BaP under normoxia, hypoxia, or inflammatory conditions for 24 h. After treatment, we evaluated cell viability, apoptosis, aryl hydrocarbon receptor (AhR) protein and cytochrome P450 (CYP) gene expression, mitochondrial function, including mitochondrial DNA copy number (mtDNAcn), mitochondrial membrane potential (ΔΨm), intracellular adenosine triphosphate (iATP), and extracellular ATP (eATP), nitric oxide (NO), NLPR3 inflammasome proteins, and interleukin (IL)-1ß. We found that BaP upregulated the expression of AhR or CYP genes to varying degrees in all three cell lines. Exposure to BaP alone increased ΔΨm in all cell lines but decreased NO in BeWo and HTR-8/SVneo, iATP in HTR-8/SVneo, and cell viability in JEG-3, without affecting apoptosis. Under hypoxic conditions, BaP did not increase the expression of AhR and CYP genes in JEG-3 cells but increased CYP gene expression in two others. Pro-inflammatory conditions did not affect the response of the 3 cell lines to BaP with respect to the expression of CYP genes and changes in the mitochondrial function and NLRP3 inflammasome proteins. In addition, in HTR-8/SVneo cells, BaP increased IL-1ß secretion in the presence of hypoxia and poly(I:C). In conclusion, our results showed that BaP affected mitochondrial function in trophoblast cell lines by increasing ΔΨm. This increased ΔΨm may have rescued the trophoblast cells from activation of the NLRP3 inflammasome and apoptosis after BaP treatment. We also observed that different human trophoblast cell lines had cell type-dependent responses to BaP exposure under normoxia, hypoxia, or pro-inflammatory conditions.

Spatiotemporal variation of 6PPD and 6PPDQ in dust and soil from e-waste recycling areas.

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its derivative 6PPDQ have been detected in various environmental media, with harmful consequences for both ecosystems and biological health. However, the distribution of 6PPD and 6PPDQ in areas around e-waste recycling areas is currently unknown. We collected soil and dust samples from areas around a traditional e-waste recycling zone, an emerging recycling park, and a reference area. Higher levels of 6PPD were found in dust from residential areas around the traditional e-waste recycling zone compared to the reference area (median: 108.99 versus 33.57 ng/g, P < 0.01). Lower levels of 6PPDQ were detected in dust samples from around the emerging e-waste recycling parks compared to traditional e-waste recycling zones (median: 15.40 versus 46.37 ng/g, P < 0.05). The median concentrations of 6PPD and 6PPDQ were higher in the dust samples than in the soil samples (P < 0.001). The concentrations of 6PPD and 6PPDQ in the dust and soil varied seasonally, with the highest total concentrations occurring in the winter. Results from a multiple linear regression analysis indicate that 6PPDQ is negatively correlated with temperature and positively correlated with 6PPD, O3, and radiation. This study confirms that e-waste is a potential contributor to 6PPD and 6PPDQ. In residential areas, 6PPD and 6PPDQ are more likely to accumulate in dust than in soil. The emerging e-waste recycling parks have greatly improved the local 6PPDQ pollution situation. Further studies are necessary to understand the distribution of newly found substances in various settings.

Effects of endocrine disrupting chemicals and their interactions with genetic risk scores on cardiometabolic traits.

Ubiquitous non-persistent endocrine disrupting chemicals (EDCs) have inconsistent associations with cardiometabolic traits. Additionally, large-scale genome-wide association studies (GWASs) have yielded many genetic risk variants for cardiometabolic traits and diseases. This study aimed to investigate the associations between a wide range of EDC exposures (parabens, bisphenols, and phthalates) and 14 cardiometabolic traits and whether these are moderated by their respective genetic risk scores (GRSs). Data were from 1074 participants aged 18 years or older of the Lifelines Cohort Study, a large population-based biobank. GRSs for 14 cardiometabolic traits were calculated based on genome-wide significant common variants from recent GWASs. The concentrations of 15 EDCs in 24-hour urine were measured by isotope dilution liquid chromatography tandem mass spectrometry technology. The main effects of trait-specific GRSs and each of the EDC exposures and their interaction effects on the 14 cardiometabolic traits were examined in multiple linear regression. The present study confirmed significant main effects for all GRSs on their corresponding cardiometabolic trait. Regarding the main effects of EDC exposures, 26 out of 280 EDC-trait tests were significant with explained variances ranging from 0.43 % (MMP- estimated glomerular filtration rate (eGFR)) to 2.37 % (PrP-waist-hip ratio adjusted body mass index (WHRadjBMI)). We confirmed the association of MiBP and MBzP with WHRadjBMI and body mass index (BMI), and showed that parabens, bisphenol F, and many other phthalate metabolites significantly contributed to the variance of WHRadjBMI, BMI, high-density lipoprotein (HDL), eGFR, fasting glucose (FG), and diastolic blood pressure (DBP). Only one association between BMI and bisphenol F was nominally significantly moderated by the GRS explaining 0.36 % of the variance. However, it did not survive multiple testing correction. We showed that non-persistent EDC exposures exerted effects on BMI, WHRadjBMI, HDL, eGFR, FG, and DBP. However no evidence for a modulating role of GRSs was found.

Association between 6PPD-quinone exposure and BMI, influenza, and diarrhea in children.

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-quinone) has received extensive attention due to its ubiquitous distribution and potential toxicity. However, the distribution characteristics of 6PPD-quinone in dust from e-waste recycling areas and the consequential health risks to children are unclear. A total of 183 dust samples were collected from roads (n = 40), homes (n = 91), and kindergartens (n = 52) in Guiyu (the e-waste-exposed group) and Haojiang (the reference group) from 2019 to 2021. The results show that the concentrations of 6PPD-quinone in kindergarten and house dust from the exposed group were significantly higher than those from the reference group (P < 0.001). These findings show that e-waste may be another potential source of 6PPD-quinone, in addition to rubber tires. The exposure risk of 6PPD-quinone in children was assessed using their daily intake. The daily intake of 925 kindergarten children was calculated using the concentration of 6PPD-quinone in kindergarten dust. The daily intake of 6PPD-quinone via ingestion was approximately five orders of magnitude higher than via inhalation. Children in the exposed group had a higher exposure risk to 6PPD-quinone than the reference group. A higher daily intake of 6PPD-quinone from kindergarten dust was associated with a lower BMI and a higher frequency of influenza and diarrhea in children. This study reports the distribution of 6PPD-quinone in an e-waste recycling town and explores the associated health risks to children.

A genome-wide association study of 24-hour urinary excretion of endocrine disrupting chemicals.

Ubiquitous exposure to environmental endocrine disrupting chemicals (EDCs) instigates a major public health problem, but much remains unknown on the inter-individual differences in metabolism and excretion of EDCs. To examine this we performed a two-stage genome-wide association study (GWAS) for 24-hour urinary excretions of four parabens, two bisphenols, and nine phthalate metabolites. Results showed five genome-wide significant (p-value < 5x10-8) and replicated single nucleotide polymorphisms (SNPs) representing four independent signals that associated with mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). Three of the four signals were located on chromosome 10 in a locus harboring the cytochrome P450 (CYP) genes CYP2C9, CYP2C58P, and CYP2C19 (rs117529685, pMECPP = 5.38x10-25; rs117033379, pMECPP = 1.96x10-19; rs4918798, pMECPP = 4.01x10-71; rs7895726, pMEHHP = 1.37x10-15, r2 with rs4918798 = 0.93). The other signal was on chromosome 6 close to the solute carrier (SLC) genes SLC17A1, SLC17A3, SLC17A4, and SCGN (rs1359232, pMECPP = 7.6x10-16). These four SNPs explained a substantial part (8.3 % - 9.2 %) of the variance in MECPP in the replication cohort. Bioinformatics analyses supported a likely causal role of CYP2C9 and SLC17A1 in metabolism and excretion of MECPP and MEHHP. Our results provide biological insights into mechanisms of phthalate metabolism and excretion with a likely causal role for CYP2C9 and SLC17A1.

Kindergarten dust heavy metal(loid) exposure associates with growth retardation in children.

Heavy metal contamination from electronic waste recycling sites is present in dust found in indoor kindergartens located in e-waste recycling areas, and its potential impact on child health is a significant concern. The association between heavy metal(loid)s and the child developmental indicators is still unclear. In 2019 and 2020, we enrolled 325 and 319 children in an e-waste recycling town, respectively. Corresponding 61 and 121 dust samples were collected from roads, houses, and kindergartens in the two years. The median concentrations of metals, including Cr, Ni, Cu, Zn, and Pb exceeded the allowable limits. The highest amount of cumulative enrichment (cEF) was observed in indoor kindergarten dust (cEF = 112.3400), followed by house dust (cEF = 76.6950) and road dust (cEF = 39.7700). Children residing in the e-waste town had below-average height and weight compared to their Chinese peers. Based on linear regression analysis, the daily intake of Cd, V, Mn, and Pb in indoor kindergarten dust was found to be negatively associated with head circumference (HeC) (P < 0.05). Similarly, the daily intake of As, Cd, and Ba in indoor kindergarten dust was found to be negatively associated with chest circumference (ChC) (P < 0.05). In addition, the daily intake of As, Cd, and Ba in indoor kindergarten dust was negatively correlated with body mass index (BMI), as per the results of the study (P < 0.05). Cross-product term analysis revealed a negative correlation between daily intake of heavy metal(loid)s and HeC, ChC, and BMI, with age and sex serving as influencing factors. In conclusion, exposure to heavy metal(loid)s in indoor kindergarten dust increases the risk of growth retardation and developmental delay in children.

Risk assessment and partitioning behavior of PFASs in environmental matrices from an e-waste recycling area.

OBJECTIVE: Perfluoroalkyl and polyfluoroalkyl substance (PFAS) contamination and their human exposure risks are a major concern. However, knowledge of PFAS contamination in environments near e-waste recycling sites and their health risk assessment are scarce. METHODS: We measured the concentrations of PFASs in soil (n = 12), water (n = 12) and atmospheric samples (n = 26) by LCP-MS/MS, analyzed the source apportionment of PFASs by PCA, and investigated the child health risk assessment from an e-waste recycling area (Guiyu) and a reference area (Haojiang). RESULTS: We found high concentrations of PFASs in the atmosphere and low concentrations of PFASs in soil. The average concentration of perfluoro-n-heptanoic acid (PFHpA) (9.43 ng/L) was highest among PFASs in water. The concentrations PFASs in the atmosphere and water were higher in the e-waste recycling area than in the reference area (p < 0.05). According to Multi-Linear regression model, we found that daily intake doses for PFASs in air of PFODA [ß (95 % CI): -0.217 (-0.332, -0.048), p < 0.05] and PFBS [ß (95 % CI): -0.064 (-0.106, -0.006), p < 0.05] were negatively associated with child BMI. PFBA [ß (95 % CI: -1.039 (-2.454, -0.010), p < 0.05] was negatively correlated with child head circumference. CONCLUSION: The concentrations of PFASs in the water and atmosphere are higher in the e-waste recycling site than in the reference area. We found that their intake affected growth and development in children. We need to reduce pollution from PFASs in the e-waste recycling area while maintaining a focus on their impact on child health.

Effects of polycyclic aromatic hydrocarbons (PAHs) on pregnancy, placenta, and placental trophoblasts.

Polycyclic aromatic hydrocarbons (PAHs) are a group of persistent organic pollutants that are carcinogenic, mutagenic, endocrine-toxic, and immunotoxic. PAHs can be found in maternal and fetal blood and in the placenta during pregnancy. They may thus affect placental and fetal development. Therefore, the exposure levels and toxic effects of PAHs in the placenta deserve further study and discussion. This review aims to summarize current knowledge on the effects of PAHs and their metabolites on pregnancy and birth outcomes and on placental trophoblast cells. A growing number of epidemiological studies detected PAH-DNA adducts as well as the 16 high-priority PAHs in the human placenta and showed that placental PAH exposure is associated with adverse fetal outcomes. Trophoblasts are important cells in the placenta and are involved in placental development and function. In vitro studies have shown that exposure to either PAH mixtures, benzo(a)pyrene (BaP) or BaP metabolite benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) affected trophoblast cell viability, differentiation, migration, and invasion through various signaling pathways. Furthermore, similar effects of BPDE on trophoblast cells could also be observed in BaP-treated mouse models and were related to miscarriage. Although the current data show that PAHs may affect placental trophoblast cells and pregnancy outcomes, further studies (population studies, in vitro studies, and animal studies) are necessary to show the specific effects of different PAHs on placental trophoblasts and pregnancy outcomes.

Blood lead levels of children exposed to e-waste: a systematic review and meta-analysis.

Blood lead levels (BLLs) have been decreasing worldwide for decades. However, systematic reviews and quantitative syntheses of BLLs in electronic waste (e-waste)-exposed children are lacking. To summarize temporal trend of BLLs among children in e-waste-recycling areas. Fifty-one studies met the inclusion criteria and included participants from six countries. Meta-analysis was performed using the random-effects model. Results showed that among e-waste-exposed children, the total geometric mean (GM) BLL was 7.54 µg/dL (95% CI: 6.77, 8.31). Children's BLLs displayed a decreasing temporal trend, from 11.77 µg/dL in phase I (2004-2006) to 4.63 µg/dL in phase V (2016-2018). Almost 95% of eligible studies found that children exposed to e-waste had significantly higher BLLs than reference groups. The difference of children's BLLs between the exposure group and the reference group was from 6.60 µg/dL (95% CI: 6.14, 7.05) in 2004 to 1.99 µg/dL (95% CI: 1.61, 2.36) in 2018. For subgroup analyses, except for Dhaka and Montevideo, the BLLs of children from Guiyu in the same survey year were higher than those of children from other regions. Our findings indicate that the gap between BLLs of children exposed to e-waste and those of reference group children is closing, and we appeal that the critical value for blood lead poisoning in children should be lowered in key e-waste-dismantling areas of developing countries, such as Guiyu.

Epidemiological evidence for the effect of environmental heavy metal exposure on the immune system in children.

Heavy metals exist widely in daily life, and exposure to heavy metals caused by environmental pollution has become a serious public health problem worldwide. Due to children's age-specific behavioral characteristics and imperfect physical function, the adverse health effects of heavy metals on children are much higher than in adults. Studies have found that heavy metal exposure is associated with low immune function in children. Although there are reviews describing the evidence for the adverse effects of heavy metal exposure on the immune system in children, the summary of evidence from epidemiological studies involving the level of immune molecules is not comprehensive. Therefore, this review summarizes the current epidemiological study on the effect of heavy metal exposure on childhood immune function from multiple perspectives, emphasizing its risks to the health of children's immune systems. It focuses on the effects of six heavy metals (lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), nickel (Ni), and manganese (Mn)) on children's innate immune cells, lymphocytes and their subpopulations, cytokines, total and specific immunoglobulins, and explores the immunotoxicological effects of heavy metals. The review finds that exposure to heavy metals, particularly Pb, Cd, As, and Hg, not only reduced lymphocyte numbers and suppressed adaptive immune responses in children, but also altered the innate immune response to impair the body's ability to fight pathogens. Epidemiological evidence suggests that heavy metal exposure alters cytokine levels and is associated with the development of inflammatory responses in children. Pb, As, and Hg exposure was associated with vaccination failure and decreased antibody titers, and increased risk of immune-related diseases in children by altering specific immunoglobulin levels. Cd, Ni and Mn showed activation effects on the immune response to childhood vaccination. Exposure age, sex, nutritional status, and co-exposure may influence the effects of heavy metals on immune function in children.

Current status of indoor dust PBDE pollution and its physical burden and health effects on children.

Polybrominated diphenyl ethers (PBDEs) are widely detected in indoor dust, which has been identified as a more important route of PBDE exposure for children than food intake. The physical burden and health hazards to children of PBDE exposure in house dust have not been adequately summarized; therefore, this article reviews the current status of PBDE pollution in indoor dust associated with children, highlighting the epidemiological evidence for physical burden and health risks in children. We find that PBDEs remain at high levels in indoor dust, including in homes, schools, and cars, especially in cars showing a significant upward trend. There is a trend towards an increase in the proportion of BDE-209 in household dust, which is indicative of recent PBDE contamination. Conversely, PBDE congeners in car and school indoor dust tended to shift from highly brominated to low brominated, suggesting a shift in current pollution patterns. Indoor dust exposure causes significantly higher PBDE burdens in children, especially infants in early life, than in adults. Exposure to dust also affects breast milk, putting infants at high risk of exposure. Although evidence is limited, available epidemiological studies suggest that exposure to indoor dust PBDEs promotes neurobehavioral problems and cancer development in children.

Pyroptosis in NLRP3 inflammasome-related atherosclerosis.

Pyroptosis is a proinflammatory form of programmed cell death in response to inflammation. It involves in the pathogenesis and outcomes of atherosclerosis characterized by NLRP3 inflammasome assembly, membrane pore formation, cell swelling, pro-inflammatory mediator and cytokine release. There are known pyroptosis molecular pathways including the caspase-1 depended canonical signaling pathway and the caspase-4/5/11 determined non-canonical signaling pathway. It is essential to explore the connection among NLRP3 inflammasome, pyroptosis and atherosclerosis, which may shed light on the potential therapeutic strategies that target pyroptosis in atherosclerotic treatment.

Kindergarten indoor dust metal(loid) exposure associates with elevated risk of anemia in children.

Exposure to metals and metalloids in indoor dust is associated with adverse health effects in young children, but there is limited evidence for an association with anemia, which is at high risk in children. The aim of this study was to investigate the association between exposure to multiple metal(loid)s in indoor dust in kindergartens and the risk of anemia in children. In 2021, 2165 children from 25 kindergartens in eastern China were included in the study and had their hemoglobin (Hb) measured. Indoor dust samples were collected from the children's kindergartens, and the concentrations of 11 metals and metalloids in the samples were measured using inductively coupled plasma mass spectrometry (ICP-MS). The daily exposure dose (DED) of dust was used to assess the risk of metal(loid) exposure in the children. The results showed that of the 2165 children with available data, 351 (16.2 %) met the WHO definition of anemia. In multiple linear regression and logistic regression analyses, we found that for each quartile of DED increase in Cd inhalation, child Hb levels decreased by 2.703 g/L (95 % CI: -4.055, -1.351), and the risk of anemia increased 1.602-fold (95 % CI: 1.087, 2.360). Mn ingestion was associated with increased odds of anemia [odds ratio (OR) = 1.760 (95 % CI: 1.217, 2.544)]. Interaction analysis indicated that metal(loid)s exposure effects were modified by child sex, age, and body mass index (BMI). Cluster analysis found that children at high risk of metal(loid) exposure in the school environment tended to have lower Hb levels and higher prevalence of anemia compared with those at low risk, although this was not statistically significant. These findings suggest that child school exposure to metal(loid)s in indoor dust is associated with an increased risk of developing anemia in children, modified by child sex, age, and BMI.

[Dual-specificity Phosphatase 1 Suppresses Vascular Smooth Muscle Cell Calcification by Optical Atrophy 1-related Pathway].

Objective To investigate the effect of dual-specificity phosphatase 1/optical atrophy 1 (DUSP1/OPA1) signaling pathway on vascular smooth muscle cell (VSMC) calcification.Methods An in vitro model of VSMC calcification was induced by exposure to ß-glycerophosphate and calcium chloride.VSMC calcification was assessed by Alizarin Red S staining and calcium content by ELISA.Apoptosis was detected by TUNEL.Western blotting was employed to determine the protein levels of DUSP1,OPA1,Runt-related transcription factor 2 (Runx-2),bone morphogenetic protein 2 (BMP-2),and cysteinyl aspartate-specific proteinase-3 (Caspase-3).The effects of DUSP1 overexpression and OPA1 knockdown on cell calcification were investigated.Results Calcium chloride and ß-glycerolphosphate induced VSMC calcification and down-regulated the expression levels of DUSP1 (t=11.951,P<0.001) and OPA1 (t=8.487,P<0.001).DUSP1 overexpression promoted OPA1 expression (t=-8.921,P<0.001),attenuated VSMC calcification,reduced calcium content and apoptosis rate,and down-regulated the expression of Runx-2,BMP-2,and active Caspase-3 (all P<0.001).OPA1 knockdown increased calcium content and apoptosis rate,up-regulated the expression of Runx-2,BMP-2,and active Caspase-3,and promoted VSMC calcification (all P<0.001).Conclusion DUSP1 may inhibit the VSMC calcification through the OPA1 signaling pathway.

Maternal exposure to atmospheric PM2.5 and fetal brain development: Associations with BAI1 methylation and thyroid hormones.

Maternal exposure to atmospheric fine particulate matter (PM2.5) during pregnancy is associated with adverse fetal development, including abnormal brain development. However, the underlying mechanisms and influencing factors remain uncertain. This study investigated the roles of DNA methylation in genes involving neurodevelopment and thyroid hormones (THs) in fetal brain development after maternal exposure to PM2.5 from e-waste. Among 939 healthy pregnant women recruited from June 2011 to September 2012, 101 e-waste-exposed and 103 reference mother-infant pairs (204 pairs totally) were included. Annual ground-level PM2.5 concentrations over e-waste-exposed area (116.38°E, 23.29°N) and reference area (116.67°E, 23.34°N) in 2011, 2012 were obtained by estimates and maternal exposure was evaluated by calculating individual chronic daily intakes (CDIs) of PM2.5. Methylation and THs including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) level were measured in umbilical cord blood collected shortly after delivery. We found higher ground-level PM2.5 concentrations led to greater individual CDI of PM2.5 in e-waste-exposed pregnant women. After adjustment for gender and birth BMI, significant mediation effects on the adverse associations of maternal PM2.5 exposure with birth head circumference were observed for methylations at positions +13 and + 32 (respectively mediated proportion of 9.8% and 5.3%, P < 0.05 and P < 0.01) in the brain-specific angiogenesis inhibitor 1 (BAI1) gene, but not for methylations in the catenin cadherin-associated protein, alpha 2 (CTNNA2) gene. BAI1 (position +13) methylation was also significantly correlated with FT3 levels (rs = -0.156, P = 0.032), although maternal CDI of PM2.5 was positively associated with higher odds of abnormal TSH levels (OR = 5.03, 95% CI: 1.00, 25.20, P = 0.05) rather than FT3 levels. Our findings suggest that methylation (likely linked to THs) in neonates may play mediation roles associated with abnormal brain development risk due to maternal exposure to atmospheric PM2.5 from e-waste.

Metabolomics insights into the prenatal exposure effects of polybrominated diphenyl ethers on neonatal birth outcomes.

BACKGROUND: Effects of polybrominated diphenyl ethers (PBDEs) on neonatal birth outcomes vary across previous studies, and the related mechanism investigation remains poorly understood, especially at the metabolic level. OBJECTIVES: To evaluate the associations between prenatal PBDEs exposure and neonatal birth outcomes including gestational age, neonatal weight, birth length, head circumference (HC), Apgar score at 1 min (Apgar1) and 5 min, and further reveal the underlying metabolic disorders in a population-based birth cohort study. METHODS: Gas chromatography-triple quadrupole tandem mass spectrometry (GC-MS/MS) based targeted method and GC-MS based untargeted method were respectively conducted to obtain PBDE levels and metabolic profiles of 200 placental tissue samples from a typical e-waste recycling area (Guiyu) and reference area (Haojiang) in China. Spearman correlation and regression analyses were applied to assess the associations between the placental PBDE levels and birth outcomes. Metabolome-wide association studies and the meet-in-the-middle approach were employed to explore disruptions linking PBDE exposures and the corresponding adverse birth outcomes. RESULTS: Eight out of 27 PBDE congeners were detected in placenta with more than 50% frequency in at least one district and significantly higher in Guiyu than those in Haojiang. The lower HC and Apgar1 had significant associations with PBDE exposures after adjustment for potential confounders. A total of 66, 16 and 14 metabolites were significantly correlated with PBDE exposures, HC and Apgar1, respectively. 4 and 12 PBDE-related metabolites were significantly associated with the risks of decreasing neonatal HC and Apgar1. The disrupted metabolites were mainly involved in the pentose phosphate pathway, ascorbate metabolism, threonine metabolism, butanoate metabolism, lipid metabolism, and arginine biosynthesis. CONCLUSIONS: In this birth cohort, higher placental PBDE levels were significantly associated with the lower HC and Apgar1. The associations might be modified by multiple metabolic disturbances through increasing oxidative stress, mediating neurotoxicity, maternal gut microbiota dysbiosis and vasodilatation regulation.