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.

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.

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.

Combined toxicity of air pollutants related to e-waste on inflammatory cytokines linked with neurotransmitters and pediatric behavioral problems.

E-waste usually refers to the discarded electrical or electronic equipment that is no longer used. Informal e-waste recycling methods, such as burning, roasting, acid leaching, and shredding, had resulted in serious air pollution, which is a prominent risk factor for children's health. However, the combined toxicity of air pollutants on children's behavioral health remains unclear. This study collected data on air pollution exposure, calculated the average daily dose (ADD) based on these air pollutants for children in Guiyu (e-waste group, n = 112) and Haojiang (reference group, n = 101), then assessed children's behavioral health using the Strengths and Difficulties Questionnaire (SDQ), and further estimated the associations of ADD, inflammatory cytokines, neurotransmitters, and children's behavioral problems. Compared with Haojiang, Guiyu has poorer air quality and higher levels of ADD, inflammatory cytokines (such as IL-1ß, IL-6, and TNF-α), neurotransmitters (such as DA and SP), and SDQ scores, but lower levels of serum neuropeptide Y (NPY) levels. Spearman correlation analyses indicated that there were significant relationships among inflammatory cytokines, neurotransmitters, and behavioral scores. Multiple linear regression analyses showed that each unit increase in ADD was associated with serum levels of DA and SP, the serum NPY subsequently changed by B (95% CI): 0.99 (0.14, 1.84) nmol/L, 0.25 (0.08, 0.42) ng/mL, and - 0.16 (-0.26, -0.05) ng/mL, respectively. After adjustment for confounders, logistic regression analyses suggested that with each one-fold increase in ADD was associated with the risk of emotional symptoms [OR (95% CI): 18.15 (2.72, 121.06)], hyperactivity-inattention [13.64 (2.28, 81.65)] and total difficulties [8.90 (1.60, 49.35)] and prosocial behavior [- 7.32 (-44.37, -1.21)]. Taken together, this study demonstrates that combined exposure to air pollutants may alter the levels of inflammatory cytokines and serum neurotransmitter to subsequently impact behavioral health in children.

[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.

Prenatal smoke effect on mouse offspring Igf1 promoter methylation from fetal stage to adulthood is organ and sex specific.

Prenatal smoke exposure (PSE) is associated with reduced birth weight, impaired fetal development, and increased risk for diseases later in life. Changes in DNA methylation may be involved, as multiple large-scale epigenome-wide association studies showed that PSE is robustly associated with DNA methylation changes in blood among offspring in early life. Insulin-like growth factor-1 (IGF1) is important in growth, differentiation, and repair processes after injury. However, no studies investigated the organ-specific persistence of PSE-induced methylation change of Igf1 into adulthood. Based on our previous studies on the PSE effect on Igf1 promoter methylation in fetal and neonatal mouse offspring, we now have extended our studies to adulthood. Our data show that basal Igf1 promoter methylation generally increased in the lung but decreased in the liver (except for 2 persistent CpG sites in both organs) across three different developmental stages. PSE changed Igf1 promoter methylation in all three developmental stages, which was organ and sex specific. The PSE effect was less pronounced in adult offspring compared with the fetal and neonatal stages. In addition, the PSE effect in the adult stage was more pronounced in the lung compared with the liver. For most CpG sites, an inverse correlation was found for promoter methylation and mRNA expression when the data of all three stages were combined. This was more prominent in the liver. Our findings provide additional evidence for sex- and organ-dependent prenatal programming, which supports the developmental origins of health and disease (DOHaD) hypothesis.

Differential DNA methylation in newborns with maternal exposure to heavy metals from an e-waste recycling area.

This study explored the effects of maternal exposure to e-waste environmental heavy metals on neonatal DNA methylation patterns. Neonatal umbilical cord blood (UCB) samples were collected from participants that resided in an e-waste recycling area, Guiyu and a nearby non-e-waste area, Haojiang in China. The concentrations of UCB lead (Pb), cadmium (Cd), manganese (Mn) and chromium (Cr) were measured by graphite furnace atomic absorption spectrometry. Epigenome-wide DNA methylation at 473, 844 CpG sites (CpGs) were assessed by Illumina 450 K BeadChip. The differential methylation of CpG sites from the microarray were further validated by bisulfite pyrosequencing. Bioinformatics analysis showed that 125 CpGs mapped to 79 genes were differential methylation in the e-waste exposed group with higher concentrations of heavy metals in neonatal UCB. These genes mainly involve in multiple biological processes including calcium ion binding, cell adhesion, embryonic morphogenesis, as well as in signaling pathways related to NFkB activation, adherens junction, TGF beta and apoptosis. Among them, BAI1 and CTNNA2 (involving in neuron differentiation and development) were further verified to be hyper- and hypo-methylated, respectively, which were associated with maternal Pb exposure. These results suggest that maternal exposure to e-waste environmental heavy metals (particularly lead) during pregnancy are associated with peripheral blood differential DNA methylation in newborns, specifically the genes involving in brain neuron development.

MicroRNAs and their role in environmental chemical carcinogenesis.

MicroRNAs (miRNAs) are a class of small, noncoding RNA species that play crucial roles across many biological processes and in the pathogenesis of major diseases, including cancer. Recent studies suggest that the expression of miRNA is altered by certain environmental chemicals, including metals, organic pollutants, cigarette smoke, pesticides and carcinogenic drugs. In addition, extensive studies have indicated the existence and importance of miRNA in different cancers, suggesting that cancer-related miRNAs could serve as potential markers for chemically induced cancers. The altered expression of miRNA was considered to be a vital pathogenic role in xenobiotic-induced cancer development. However, the significance of miRNA in the etiology of cancer and the exact mechanisms by which environmental factors alter miRNA expression remain relatively unexplored. Hence, understanding the interaction of miRNAs with environmental chemicals will provide important information on mechanisms underlying the pathogenesis of chemically induced cancers, and effectively diagnose and treat human cancers resulting from chronic or acute carcinogen exposure. This study presents the current evidence that the miRNA deregulation induced by various chemical carcinogens, different cancers caused by environmental carcinogens and the potentially related genes in the onset or progression of cancer. For each carcinogen, the specifically expressed miRNA may be considered as the early biomarkers of the cancer process. In this review, we also summarize various target genes of the altered miRNA, oncogenes or anti-oncogenes, and the existing evidence regarding the gene regulation mechanisms of cancer caused by environmentally induced miRNA alteration. The future perspective of miRNA may become attractive targets for the diagnosis and treatment of carcinogen-induced cancer.

Heavy metal exposure has adverse effects on the growth and development of preschool children.

The purpose of this study was to investigate the associations between levels of lead (Pb), cadmium (Cd), chromium (Cr), and manganese (Mn) in the PM2.5 and blood and physical growth, and development parameters including birth length and weight, height, weight, body mass index (BMI), head circumference, and chest circumference in preschool children from Guiyu (e-waste exposure area) and Haojiang (the reference area). A total of 470 preschool children from Guiyu and Haojiang located in southeast coast of China were recruited and required to undergo physical examination and blood tests during the study period. Birth length and weight were obtained by birth records and questionnaire. Pb and Cd in both PM2.5 and blood were significantly higher in Guiyu than Haojiang. Remarkably, the children of Guiyu had significantly lower birth weight and length, BMI, and chest circumference when compare to their peers from the reference area (all p value < 0.05). Spearman correlation analyses showed that blood Pb was negatively correlated with height (r = -0.130, p < 0.001), weight (r = -0.169, p < 0.001), BMI (r = -0.100, p < 0.05), head circumference (r = -0.095, p < 0.05), and chest circumference (r = -0.112, p < 0.05). After adjustment for the potential confounders in further linear regression analyses, blood Pb was negatively associated with height (ß = -0.066, p < 0.05), weight (ß = -0.119, p < 0.001), head circumference (ß = -0.123, p < 0.01), and chest circumference (ß = -0.104, p < 0.05), respectively. No significant association between blood Cd, Cr, or Mn was found with any of our developmental outcomes. Taken together, lead exposure limits or delays the growth and development of preschool children.

Interactions between polycyclic aromatic hydrocarbons and epoxide hydrolase 1 play roles in asthma.

Asthma, as one of the most common chronic diseases in children and adults, is a consequence of complex gene-environment interactions. Polycyclic aromatic hydrocarbons (PAHs), as a group of widespread environmental organic pollutants, are involved in the development, triggering and pathologic changes of asthma. Various previous studies reported the critical roles of PAHs in immune changes, oxidative stress and environment-gene interactions of asthma. EPHX1 (the gene of epoxide hydrolase 1, an enzyme mediating human PAH metabolism) had a possible association with asthma by influencing PAH metabolism. This review summarized that (1) the roles of PAHs in asthma-work as risk factors; (2) the possible mechanisms involved in PAH-related asthma-through immunologic and oxidative stress changes; (3) the interactions between PAHs and EPHX1 involved in asthma-enzymatic activity of epoxide hydrolase 1, which affected by EPHX1 genotypes/SNPs/diplotypes, could influence human PAH metabolism and people's vulnerability to PAH exposure. This review provided a better understanding of the above interactions and underlying mechanisms for asthma which help to raise public's concern on PAH control and develop strategies for individual asthma primary prevention.

Air pollution and body burden of persistent organic pollutants at an electronic waste recycling area of China.

This paper reviews the concentrations of persistent organic pollutants (POPs) in atmosphere of an electronic waste (e-waste) recycling town, Guiyu, in Southeast China, focusing on polybrominated diphenyl ethers (PBDEs), polychlorinated dibenzo-p-dioxin and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). We assess the evidence for the association between air pollution and human body burden, to provide an indication of the severity of respiratory exposure. Compared with standards and available existing data for other areas, it clearly shows that four typical POPs, derived from recycling processes, lead to serious atmospheric pollution and heavy body burden. From published data, the estimated respiratory exposure doses of Guiyu adults and children, varied between 2.48-10.37 and 3.25-13.6 ng kg-1 body weight (bw) day-1 for PBDEs, 2.31-7.6 and 4.09-13.58 pg World Health Organization-Toxic Equivalent Quantity (WHO-TEQ) kg-1 bw day-1 for PCDD/Fs, 5.57 and 20.52 ng kg-1 bw day-1 for PCBs, and 8.59-50.01 and 31.64-184.14 ng kg-1 bw day-1 for PAHs, respectively. These results show that air pollution is more harmful to children. Furthermore, except for PBDEs, the hazard quotient (HQ) of the other three pollutants was rated more than 1 by respiratory exposure only, and all of them are at risk of carcinogenesis. So we speculate these pollutants enter the body mainly through air inhalation, making respiratory exposure may be more important than dietary exposure in the Guiyu e-waste recycling area. Effective management policies and remediation techniques are urgently needed to prevent the deterioration of ambient air quality in the e-waste recycling area.

Blood concentrations of lead, cadmium, mercury and their association with biomarkers of DNA oxidative damage in preschool children living in an e-waste recycling area.

Reactive oxygen species (ROS)-induced DNA damage occurs in heavy metal exposure, but the simultaneous effect on DNA repair is unknown. We investigated the influence of co-exposure of lead (Pb), cadmium (Cd), and mercury (Hg) on 8-hydroxydeoxyguanosine (8-OHdG) and human repair enzyme 8-oxoguanine DNA glycosylase (hOGG1) mRNA levels in exposed children to evaluate the imbalance of DNA damage and repair. Children within the age range of 3-6 years from a primitive electronic waste (e-waste) recycling town were chosen as participants to represent a heavy metal-exposed population. 8-OHdG in the children's urine was assessed for heavy metal-induced oxidative effects, and the hOGG1 mRNA level in their blood represented the DNA repair ability of the children. Among the children surveyed, 88.14% (104/118) had a blood Pb level >5 µg/dL, 22.03% (26/118) had a blood Cd level >1 µg/dL, and 62.11% (59/95) had a blood Hg level >10 µg/dL. Having an e-waste workshop near the house was a risk factor contributing to high blood Pb (r s  = 0.273, p < 0.01), while Cd and Hg exposure could have come from other contaminant sources. Preschool children of fathers who had a college or university education had significantly lower 8-OHdG levels (median 242.76 ng/g creatinine, range 154.62-407.79 ng/g creatinine) than did children of fathers who had less education (p = 0.035). However, we did not observe a significant difference in the mRNA expression levels of hOGG1 between the different variables. Compared with children having low lead exposure (quartile 1), the children with high Pb exposure (quartiles 2, 3, and 4) had significantly higher 8-OHdG levels (ß Q2 = 0.362, 95% CI 0.111-0.542; ß Q3 = 0.347, 95% CI 0.103-0.531; ß Q4 = 0.314, 95% CI 0.087-0.557). Associations between blood Hg levels and 8-OHdG were less apparent. Compared with low levels of blood Hg (quartile 1), elevated blood Hg levels (quartile 2) were associated with higher 8-OHdG levels (ß Q2 = 0.236, 95% CI 0.039-0.406). Compared with children having low lead exposure (quartile 1), the children with high Pb exposure (quartiles 2, 3, and 4) had significantly higher 8-OHdG levels.

No convincing association between genetic markers and respiratory symptoms: results of a GWA study.

BACKGROUND: Respiratory symptoms are associated with accelerated lung function decline, and increased hospitalization and mortality rates in the general population. Although several environmental risk factors for respiratory symptoms are known, knowledge on genetic risk factors is lacking. We aim to identify genetic variants associated with respiratory symptoms by genome-wide association (GWA) analyses. METHODS: We conducted the first GWA study on cough, dyspnea and phlegm among 7,976 participants in the LifeLines I cohort and used the LifeLines II cohort (n = 5,260) and the Vlagtwedde-Vlaardingen cohort (n = 1,529) for replication. RESULTS: We identified 50 SNPs that were assessed for replication. Rs16918212, located in the alpha-2-macroglobulin pseudogene 1 (A2MP1), was associated with cough in both the identification (odds ratio (OR) = 0.72, p = 5.41 × 10-5) and the meta-analyzed replication cohorts (OR = 0.83, p = 0.033). No other significant replicated associations were found. CONCLUSIONS: Given that only 1 out of 50 SNPs showed significant replication (i.e. 2%) we conclude that we did not find a convincing association between genetic markers and respiratory symptoms. Since, environmental exposures are important risk factors for respiratory symptoms, the next step is to perform a genome-wide interaction (GWI) study to identify genetic susceptibility loci for respiratory symptoms in interaction with known harmful environmental exposures.

Alteration of the number and percentage of innate immune cells in preschool children from an e-waste recycling area.

Heavy metal lead (Pb) and cadmium (Cd) are widespread environmental contaminants and exert detrimental effects on the immune system. We evaluated the association between Pb/Cd exposures and innate immune cells in children from an electronic waste (e-waste) recycling area. A total number of 294 preschool children were recruited, including 153 children from Guiyu (e-waste exposed group), and 141 from Haojiang (reference group). Pb and Cd levels in peripheral blood were measured by graphite furnace atomic absorption spectrophotometer, NK cell percentages were detected by flow cytometer, and other innate immune cells including monocytes, eosinophils, neutrophils and basophils were immediately measured by automated hematology analyzer. Results showed children in Guiyu had significantly higher Pb and Cd levels than in reference group. Absolute counts of monocytes, eosinophils, neutrophils and basophils, as well as percentages of eosinophils and neutrophils were significantly higher in the Guiyu group. In contrast, NK cell percentages were significantly lower in Guiyu group. Pb elicited significant escalation in counts of monocytes, eosinophils and basophils, as well as percentages of monocytes, but decline in percentages of neutrophils in different quintiles with respect to the first quintile of Pb concentrations. Cd induced significant increase in counts and percentages of neutrophils in the highest quintile compared with the first quintile of Cd concentrations. We concluded alteration of the number and percentage of innate immune cells are linked to higher levels of Pb and Cd, which indicates Pb and Cd exposures might affect the innate and adaptive immune response in Guiyu children.

Associations between maternal phenolic exposure and cord sex hormones in male newborns.

STUDY QUESTION: Are maternal urinary phenol concentrations associated with cord steroid hormone levels and anogenital distance (AGD) in male newborns? SUMMARY ANSWER: High maternal urinary Bisphenol A (BPA) levels are associated with decreases in cord testosterone levels and the ratio of testosterone to estradiol in male newborns, but there was no significant association with AGD. WHAT IS KNOWN ALREADY: Early life exposure to phenolic endocrine disrupting compounds (EDCs) is known to disrupt hormonal activities and affect reproductive development in males. However, studies on the health effects of prenatal human exposure are scarce. STUDY DESIGN, SIZE, DURATION: This was a cross-sectional study to investigate the association between maternal phenolic exposure and cord sex steroid hormones and AGD in male newborns. We recruited 100 mother-infant pairs from each of two hospitals, one in a polluted town (Guiyu) and the other in a cleaner town (Haojiang), from September 2010 to September 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: One hundred and seventy eight maternal urine samples and 137 cord blood samples were available for quantification, thus 137 complete records entered into the final analysis. Of them, 77 pairs were from Guiyu, and 60 were from Haojiang. The chemical concentrations were determined by solid phase extraction and gas chromatography-mass spectrometry (SPE-GC-MS), and cord sex hormones were detected by radioimmunoassay (RIA). Neonatal anthropometric parameters including AGD were measured. MAIN RESULTS AND THE ROLE OF CHANCE: Log2-transformed maternal urinary BPA concentration was negatively correlated with testosterone level and the ratio of testosterone to estradiol (T/E2) in male fetal cord blood after adjustment for potential confounders in linear regression models (ßadjusted = -31.09 (95% CI, -53.07 to -9.11) and ßadjusted = -0.08 (95% CI, -0.13 to -0.01), respectively). Moreover, compared with the lowest quartile group of BPA level, the highest group showed a significant decrease in testosterone level and T/E2 (ßadjusted = -179.84 (95% CI, -333.45 to -26.24) and ßadjusted = -0.37 (95% CI, -0.81 to 0.07), respectively). No significant associations between AGD or anogenital index (AGI, [AGI = AGD/birthweight (mm/kg)]) and phenolic EDCs or cord hormone levels were found. LIMITATIONS, REASONS FOR CAUTION: Results in the present study should be interpreted with caution because of its cross-sectional nature, small sample size and sampling time. WIDER IMPLICATIONS OF THE FINDINGS: Testosterone plays an important role in sex differentiation and normal development of the fetus and newborn, and the balance between testosterone and estradiol is thought an important mediator of prostate disease. Therefore, our findings may have important implications for human reproductive health. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Natural Science Foundation of China (21377077) and Guangdong University Project for International Cooperation and Innovation Platform (2013gjhz0007). The authors declare they have no actual or potential competing financial interests.

Attention-deficit/hyperactivity symptoms in preschool children from an e-waste recycling town: assessment by the parent report derived from DSM-IV.

BACKGROUND: To investigate the attention-deficit/hyperactivity disorder (ADHD) status among preschool-aged children in Guiyu, an electronic waste (e-waste) recycling town in Guangdong, China. METHODS: Two hundred and forty-three parents were surveyed regarding ADHD behaviors in their children (aged 3-7 years) based solely on the DSM-IV criteria. The peripheral blood samples were taken from these children to measure blood lead levels (BLLs) and blood cadmium levels (BCLs). RESULTS: 12.8% of children met the criteria for ADHD, of which the inattentive, hyperactive/impulsive and combined subtypes were 4.5%, 5.3% and 2.9% respectively. Of all children, 28.0% had BLLs ≥ 10 ug/dL and only 1.2% had BCLs ≥ 2 ug/L, levels conventionally considered high. Either modeled by univariate or multivariable analysis, the three ADHD scores (inattentive, hyperactive/impulsive and total scores) calculated from the Parent Rating Scale showed strong positive correlations with BLLs but not with BCLs. Furthermore, children with high BLLs had 2.4 times higher risk of ADHD than those with low BLLs (OR: 2.4 [95% CI: 1.1-5.2]). When each of the 18 categories on the Parent Rating Scale was separately analyzed, children with high BLLs had significant higher risks for positive ADHD symptoms than those with low BLLs in 12 of the 18 categories (ORs ranged from 2.1 [95% CI: 1.1-3.9] to 3.6 [95% CI: 1.7-7.5]). CONCLUSIONS: This study suggests that environmental lead contamination due to e-waste recycling has an impact on neurobehavioral development of preschool children in Guiyu.

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.

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.