Exposure Patterns of Multiple Pesticides and Urinary Alterations of Trimethylamine (TMA) and Trimethylamine N-Oxide (TMAO) among Pregnant Women.

Environmental exposure to pesticides is widespread and commonly occurs in mixtures, and pregnant women are particularly concerned. Trimethylamine N-oxide (TMAO), a dietary-derived catabolite linked to cardiometabolic disease, may be influenced by pesticide exposure. However, limited knowledge exists regarding the associations, and studies have primarily been restricted to single pesticides. To address this gap, we examined the associations of pesticide exposure with urinary TMA, TMAO, and TMAO-to-TMA ratio among 1067 pregnant women residing in a rural area. Latent class analysis (LCA) was applied to identify distinct patterns of pesticide exposure based on urinary metabolite concentrations. Multiple linear regression (MLR) models and Bayesian kernel machine regression (BKMR) models were employed to estimate the effects of single pesticides, exposure patterns, and combined exposure. Four distinct pesticide exposure patterns were identified. Higher concentrations of pesticide metabolites were found to be associated with increased urinary TMAO levels (ß: 0.043 to 0.254, p < 0.05). In the MLR models for individual pesticides and exposure patterns, carbofuran phenol (CFP), pentachlorophenol (PCP), and 2-phenylphenol (OPP) exhibited positive associations with urinary TMA concentrations, while pyrethroid pesticide metabolites were correlated with the up-regulation of the TMAO-to-TMA ratio. Significant positive associations of pesticide mixtures with TMA, TMAO, and TMAO-to-TMA ratio were observed in the BKMR model, primarily driven by PCP and trans-DCCA. Our findings provided a perspective to reveal that the mechanisms and contributions to TMAO alterations may vary among different pesticides in mixture exposure.

Prenatal exposure to per- and polyfluoroalkyl substances, fetal thyroid function, and intelligence quotient at 7 years of age: Findings from the Sheyang Mini Birth Cohort Study.

BACKGROUND: Prenatal exposure to per- and polyfluoroalkyl substances (PFASs) influences neurodevelopment. Thyroid homeostasis disruption is thought to be a possible underlying mechanism. However, current epidemiological evidence remains inconclusive. OBJECTIVES: This study aimed to explore the effects of prenatal PFAS exposure on the intelligence quotient (IQ) of school-aged children and assess the potential mediating role of fetal thyroid function. METHODS: The study included 327 7-year-old children from the Sheyang Mini Birth Cohort Study (SMBCS). Cord serum samples were analyzed for 12 PFAS concentrations and 5 thyroid hormone (TH) levels. IQ was assessed using the Wechsler Intelligence Scale for Children-Chinese Revised (WISC-CR). Generalized linear models (GLM) and Bayesian Kernel Machine Regression (BKMR) were used to evaluate the individual and combined effects of prenatal PFAS exposure on IQ. Additionally, the impact on fetal thyroid function was examined using a GLM, and a mediation analysis was conducted to explore the potential mediating roles of this function. RESULTS: The molar sum concentration of perfluorinated carboxylic acids (ΣPFCA) in cord serum was significantly negatively associated with the performance IQ (PIQ) of 7-year-old children (ß = -6.21, 95 % confidence interval [CI]: -12.21, -0.21), with more pronounced associations observed among girls (ß = -9.57, 95 % CI: -18.33, -0.81) than in boys. Negative, albeit non-significant, cumulative effects were noted when considering PFAS mixture exposure. Prenatal exposure to perfluorooctanoic acid, perfluorononanoic acid, and perfluorooctanesulfonic acid was positively associated with the total thyroxine/triiodothyronine ratio. However, no evidence supported the mediating role of thyroid function in the link between PFAS exposure and IQ. CONCLUSIONS: Increased prenatal exposure to PFASs negatively affected the IQ of school-aged children, whereas fetal thyroid function did not serve as a mediator in this relationship.

Associations of cord serum polybrominated diphenyl ether (PBDE) mixture with birth outcomes and mediating role of thyroid function: Evidence from the Sheyang Mini Birth Cohort Study.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs), a series of worldwide applied flame retardants, may influence fetal growth and interfere with thyroid function. The study intended to explore the relationship between in-utero exposure to PBDE mixture and newborn anthropometric indexes and to further examine the potential mediating role of thyroid function. METHODS: Demographics and laboratory measures of 924 mother-infant pairs were obtained from the database of the Sheyang Mini Birth Cohort Study. We applied gas chromatography-mass spectrometry (GC-MS) and electrochemiluminescence immunoassay to measure nine PBDE congeners and seven thyroid function parameters in umbilical cord serum samples, respectively. We fitted generalized linear models and Bayesian kernel machine regression (BKMR) to evaluate associations of lipid-adjusted cord serum PBDEs, as individuals and as a mixture, with newborn anthropometric and cord serum thyroid function parameters. We applied causal mediation analysis to test our hypothesis that thyroid function parameters act as a mediator between PBDEs and birth outcomes. RESULTS: The molarity of cord serum ∑9PBDE had a median value of 31.23 nmol/g lipid (IQR 19.14 nmol/g lipid, 54.77 nmol/g lipid). BDE-209 was the most dominant congener. Birth length was positively associated with both single exposure to BDE-28 and cumulative exposure to PBDEs. Correspondingly, ponderal index (PI) was negatively associated with BDE-28 and the total effects of PBDE mixture. Free triiodothyronine had a negative trend with BDE-209 and PBDE mixture. In the sex-stratified analysis, BDE-153 concentrations were positively correlated with PI among males (ß = 0.03; 95%CI: 0.01, 0.05; P = 0.01) but not among females. Cord serum thyrotropin mediated 14.92% of the estimated effect of BDE-153 on PI. CONCLUSIONS: In-utero mixture exposure to PBDEs was associated with birth outcomes and thyroid function. Thyroid function might act as a mediator in the process in which PBDEs impact the growth of the fetus.

Multiple mediation effects on association between prenatal triclosan exposure and birth outcomes.

BACKGROUND: Triclosan is a broad-spectrum antimicrobial, and was thought to affect intrauterine development, but the mechanism remains unclear. OBJECTIVE: To explore the association between prenatal triclosan exposure and birth outcomes. METHODS: Based on 726 mother-child pairs from the Sheyang Mini Birth Cohort Study (SMBCS), we used the available (published) data of triclosan in maternal urines, the hormones including thyroid-related hormones, gonadal hormones in cord blood, and adipokines, trimethylamine-N-oxide (TMAO) and its precursors in cord blood to explore possible health effects of triclosan on birth outcomes through assessing different hormones and parameters, using Bayesian mediation analysis. RESULTS: Maternal triclosan exposure was associated with ponderal index (ß = 0.317) and head circumference (ß = -0.172) in generalized linear models. In Bayesian mediation analysis of PI model, estradiol (ß = 0.806) and trimethylamine (TMA, ß = 0.164) showed positive mediation effects, while total thyroxine (TT4, ß = -0.302), leptin (ß = -2.023) and TMAO (ß = -0.110) showed negative mediation effects. As for model of head circumference, positive mediation effects were observed in free thyroxine (FT4, ß = 0.493), TMA (ß = 0.178), and TMAO (ß = 0.683), negative mediation effects were observed in TT4 (ß = -0.231), testosterone (ß = -0.331), estradiol (ß = -1.153), leptin (ß = -2.361), choline (ß = -0.169), betaine (ß = -0.104), acetyl-L-carnitine (ß = -0.773). CONCLUSION: The results indicated triclosan can affect intrauterine growth by interfering thyroid-related hormones, gonadal hormones, adipokines, TMAO and its precursors.

Carbamate pesticides exposure and delayed physical development at the age of seven: Evidence from the SMBCS study.

BACKGROUND: Carbamate pesticides are widely used in agriculture and cause widespread human exposure. The health effect of carbamates on physical development remains unclear. The current study aimed to explore the carbamate's health effect on physical development. METHODS: Prenatal, 3-year-old, 7-year-old urinary carbofuranphenol concentration was measured by gas chromatography tandem mass spectrometry and adjusted by creatinine. Anthropometric indices were measured by standard method and z-score standardized. Generalized linear models (GLM) were using to assess associations between exposure measurements and anthropometric indices. The generalized estimate equation (GEE) was applied to analyze the association between multiperiod exposure and anthropometric indices, and time-interaction terms were used to exam health effect consistency of exposure in each period. Gender-stratified analysis were conducted according to results of gender-interaction terms to identify gender-specific effects. RESULTS: The gender-interaction term of prenatal exposure with height z-score was significant (ß = -0.057; 95% CI: -0.113, -0.001; p = 0.045). The 3-year-old carbofuranphenol level showed negative associations with weight z-score (ß = -0.019; 95% CI: -0.038, -0.000; p = 0.040), height z-score (ß = -0.015; 95% CI: -0.028, -0.001; p = 0.026), chest circumference (ß = -0.086; 95% CI: -0.171, -0.001; p = 0.046), and waist circumference (ß = -0.128; 95% CI: -0.230, -0.026; p = 0.014). No statistically significant trend was found for prenatal and 7-year-old carbofuranphenol levels. In GEEs, carbofuranphenol level was negatively associated with weight z-score (ß = -0.103; 95% CI: -0.195, -0.011; p = 0.027), height z-score (ß = -0.087; 95% CI: -0.152, -0.022; p = 0.008), and chest circumference (ß = -0.472; 95% CI: -0.918, -0.026; p = 0.037). Boy's height z-score was inversely associated with carbamate exposure (ß = -0.140; 95% CI: -0.227, -0.053; p = 0.001). CONCLUSIONS: Prenatal and postnatal carbamate exposure may affect physical developmental process.

Umbilical cord serum PBDE concentrations and child adiposity measures at 7 years.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) exist extensively in the environment. Toxicological studies suggested PBDEs may interfere with adipogenic pathways. However, few human evidence addressed PBDE exposures in utero related to childhood adiposity. OBJECTIVE: We assessed associations between PBDEs concentrations in cord serum and childhood adiposity measures at 7 years. METHODS: Among 318 mother-child pairs from Sheyang Mini Birth Cohort Study (SMBCS) in China, nine PBDE congener concentrations were quantified in umbilical cord serum using gas chromatography-negative chemical ionization mass spectrometry (GC-NCI-MS). Anthropometric indicators of children aged 7 years were measured, including weight, height and waist circumference. Age and sex-specific body mass index (BMI) z scores were calculated based on World Health Organization (WHO)'s child growth standards. Multivariate linear and logistic regression models adjusted for putative confounders were performed to examine associations between PBDE congeners and adiposity parameters. RESULTS: BDE-209 was the most abundant congener of PBDEs with a median value of 19.5 ng/g lipid. The geometric mean values of nine PBDE congeners ranged from below limit of detection (LOD) to 18.1 ng/g lipid, and the detection rates were 46.5%~96.5%. Cord serum BDE-153 and BDE-154 concentrations were associated with lower childhood BMI z score (regression coefficient, ß=-0.15, 95% confidence interval: -0.29, -0.02; p=0.02; ß=-0.23, 95%CI: -0.43, -0.03; p=0.03, respectively) and lower waist circumference (ß=-0.75 cm, 95%CI: -1.43, -0.06; p=0.03; ß=-1.22 cm, 95%CI: -2.23, -0.21; p=0.02, respectively), after controlling for potential confounders. Moreover, prenatal BDE-154 exposure was related to a decreased obesity risk of children aged 7 years (odds ratio, OR=0.46, 95%CI: 0.22, 0.94; p=0.03). These effects were only observed among boys in sex-straitified analyses. CONCLUSIONS: Cord serum BDE-153 and BDE-154 concentrations were related to reduced adiposity measures at 7 years of age. Further evidence regarding the impacts of prenatal PBDE exposures on childhood development is warranted.

Associations of melamine and cyanuric acid exposure with markers of kidney function in adults: Results from NHANES 2003-2004.

Higher melamine exposure may increase the risk of kidney stone formation and kidney injury in infants, but little is known about the potential nephrotoxic effects of environmental low-dose melamine and its derivative exposure on kidney function of adults in the general population. Our objective was to assess associations between urinary concentrations of melamine and its derivative, cyanuric acid, and kidney function through analyzing the data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004. Information on 298 participants aged ≥20 years was utilized. Urinary melamine and cyanuric acid levels were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) were calculated to reflect kidney function. Covariate-adjusted creatinine standardization concentrations accounting for sex, race, age, race/ethically, and body mass index, was employed to control potential confounding of kidney function. Multivariable linear regression models were conducted to estimate associations of covariate-adjusted creatinine standardization urinary melamine and cyanuric acid concentrations with eGFR and UACR. Log-binomial regression models were performed to estimate risks of impaired kidney function and hypertension associated with urinary melamine and cyanuric acid levels. The geometric mean values of urinary melamine and cyanuric acid concentrations were 1.51 µg/L [95% confidence interval (CI): 1.21 µg/L, 1.89 µg/L] and 5.86 µg/L (95% CI: 5.34 µg/L, 6.44 µg/L), respectively. The median value of estimated daily intake (EDI) for melamine was 0.06 (ranging from undetectable to 1.11) µg/kg body weight/day calculated by urinary concentration and creatinine excretion accounting for sex and body weight. Adults in the fourth quartile of melamine and cyanuric acid exposure had 0.142 mL/min/1.73 m2 (95% CI: -0.271, -0.014) and 0.106 mL/min/1.73 m2 (95% CI: -0.020, 0.006) lower eGFR for melamine and cyanuric acid, respectively, compared to participants in the first quartile of exposure with adjustment for potential confounders. To our best knowledge, this is the first study to report associations between melamine and its derivative and kidney function of the U.S. adults from NHANES 2003-2004. The suggestive evidence revealed that individuals with high melamine exposure had lower eGFR than those with low melamine exposure, although no significant association between melamine and cyanuric acid exposure and markers of kidney function was observed. These findings should be interpreted with caution regarding the possible reverse causality.

Prenatal exposure to mixture of heavy metals, pesticides and phenols and IQ in children at 7 years of age: The SMBCS study.

OBJECTIVE: Prenatal exposure to heavy metals, pesticides and phenols has been suggested to interfere with neurodevelopment, but the neurotoxicity of their mixtures is still unclear. We aimed to elucidate the associations of maternal urinary concentrations of selected chemical mixtures with intelligence quotient (IQ) in children. METHODS: Maternal urinary concentrations of selected heavy metals, pesticide metabolites, and phenols were quantified in pregnant women who participated in the Sheyang Mini Birth Cohort Study (SMBCS) from June 2009 to January 2010. At age 7 years, child's IQ score was assessed using the Chinese version of Wechsler Intelligence Scale for Children (C-WISC) by trained pediatricians. Generalized linear regression models (GLM), Bayesian kernel machine regression (BKMR) models and elastic net regression (ENR) models were used to assess the associations of urinary concentrations individual chemicals and their mixtures with IQ scores of the 7-year-old children. RESULTS: Of 326 mother-child pairs, single-chemical models indicated that prenatal urinary concentrations of lead (Pb) and bisphenol A (BPA) were significantly negatively associated with full intelligence quotient (FIQ) among children aged 7 years [ß = -2.31, 95% confidence interval (CI): -4.13, -0.48; p = 0.013, sex interaction p-value = 0.076; ß = -1.18, 95% CI: -2.21, -0.15; p = 0.025; sex interaction p-value = 0.296, for Pb and BPA, respectively]. Stratified analysis by sex indicated that the associations were only statistically significant in boys. In multi-chemical BKMR and ENR models, statistically significant inverse association was found between prenatal urinary Pb level and boy's FIQ scores at 7 years. Furthermore, BKMR analysis indicated that the overall mixture was associated with decreases in boy's IQ when all the chemicals' concentrations were at their 75th percentiles or higher, compared to at their 50th percentiles. ENR models revealed that maternal urinary Pb levels were statistically significantly associated with lower FIQ scores (ß = -2.20, 95% CI: -4.20, -0.20; p = 0.031). CONCLUSIONS: Prenatal exposure to selected chemical mixtures may affect intellectual performance at 7 years of age, particularly in boys. Pb and BPA were suspected as primary chemicals associated with child neurodevelopment.

Sex-Specific Differences in Cognitive Abilities Associated with Childhood Cadmium and Manganese Exposures in School-Age Children: a Prospective Cohort Study.

To examine sex-specific associations of neonatal and childhood exposure to eight trace elements with cognitive abilities of school-age children. The association between exposure and effects was assessed among 296 school-age children from a population-based birth cohort study, who had manganese (Mn), cadmium (Cd), and lead (Pb) exposure measured in cord blood and chromium (Cr), manganese, cobalt (Co), copper (Cu), arsenic (As), selenium (Se), cadmium, and lead exposure quantified in spot urine. Cognitive abilities were assessed using the Wechsler Intelligence Scale for Children-Chinese Revised (WISC-CR). Generalized linear models were performed to analyze associations of intelligence quotient (IQ) with trace element concentrations in cord blood and urinary trace element levels. General linear models were used to evaluate association between exposure fluctuation and children's IQ. Urinary Cd concentrations were negatively associated with full-scale IQ (ß = - 3.469, 95% confidence interval (CI) - 6.291, - 0.647; p = 0.016) and performance IQ (ß = - 4.012, 95% CI - 7.088, - 0.936; p = 0.011) in girls; however, neonatal Cd exposure expressed as Cd concentrations in cord blood was in inverse associations with verbal IQ (ß = - 2.590, 95% CI - 4.570, - 0.609; p = 0.010) only in boys. Positive association between urinary Mn concentrations and performance IQ (ß = 1.305, 95% CI 0.035, 2.575; p = 0.044) of children was observed, especially in girls. In addition, inverse association of urinary Cu concentrations with verbal IQ (ß = - 2.200, 95% CI - 4.360, - 0.039; p = 0.046) was only found in boys. Childhood Cd exposure may adversely affect cognitive abilities, while Mn exposure may beneficially modify cognitive abilities of school-age children, particularly in girls.

Chromosome-level reference genome of X12, a highly virulent race of the soybean cyst nematode Heterodera glycines.

Soybean cyst nematode (SCN, Heterodera glycines) is a major pest of soybean that is spreading across major soybean production regions worldwide. Increased SCN virulence has recently been observed in both the United States and China. However, no study has reported a genome assembly for H. glycines at the chromosome scale. Herein, the first chromosome-level reference genome of X12, an unusual SCN race with high infection ability, is presented. Using whole-genome shotgun (WGS) sequencing, Pacific Biosciences (PacBio) sequencing, Illumina paired-end sequencing, 10X Genomics linked reads and high-throughput chromatin conformation capture (Hi-C) genome scaffolding techniques, a 141.01-megabase (Mb) assembled genome was obtained with scaffold and contig N50 sizes of 16.27 Mb and 330.54 kilobases (kb), respectively. The assembly showed high integrity and quality, with over 90% of Illumina reads mapped to the genome. The assembly quality was evaluated using Core Eukaryotic Genes Mapping Approach and Benchmarking Universal Single-Copy Orthologs. A total of 11,882 genes were predicted using de novo, homolog and RNAseq data generated from eggs, second-stage juveniles (J2), third-stage juveniles (J3) and fourth-stage juveniles (J4) of X12, and 79.0% of homologous sequences were annotated in the genome. These high-quality X12 genome data will provide valuable resources for research in a broad range of areas, including fundamental nematode biology, SCN-plant interactions and co-evolution, and also contribute to the development of technology for overall SCN management.

A New Race (X12) of Soybean Cyst Nematode in China.

The soybean cyst nematode (SCN), Heterodera glycines, is a serious economic threat to soybean-producing regions worldwide. A new SCN population (called race X12) was detected in Shanxi province, China. Race X12 could reproduce on all the indicator lines of both race and Heterodera glycines (HG) type tests. The average number of females on Lee68 (susceptible control) was 171.40 with the lowest Female Index (FI) 61.31 on PI88788 and the highest FI 117.32 on Pickett in the race test. The average number of females on Lee68 was 323.17 with the lowest FI 44.18 on PI88788 and the highest FI 97.83 on PI548316 in the HG type test. ZDD2315 and ZDD24656 are elite resistant germplasms in China. ZDD2315 is highly resistant to race 4, the strongest infection race in the 16 races with FI 1.51 while being highly sensitive to race X12 with FI 64.32. ZDD24656, a variety derived from PI437654 and ZDD2315, is highly resistant to race 1 and race 2. ZDD24656 is highly sensitive to race X12 with FI 99.12. Morphological and molecular studies of J2 and cysts confirmed the population as the SCN H. glycines. This is a new SCN race with stronger virulence than that of race 4 and is a potential threat to soybean production in China.

Adverse associations between maternal and neonatal cadmium exposure and birth outcomes.

Effects of low-level cadmium (Cd) exposure during early life on fetal growth remain unclear. Our aim was to evaluate whether Cd exposure in maternal urine and umbilical cord blood was associated with birth size parameters. A birth cohort study including 1073 mother-newborn pairs was conducted from 2009 to 2010 in an agricultural population in China. Cd concentrations were analyzed in both cord blood and maternal urine. Generalized linear models were performed to determine associations between maternal and neonatal exposure to Cd and birth indicators, including birth weight, length, head circumference and ponderal index. The median (25th to 75th percentile) value of Cd concentration in maternal urine and umbilical cord blood was 0.19 (0.08, 1.00) µg/L and 0.40 (

[Effects of extremely low frequency electromagnetic radiation on cardiovascular system of workers].

OBJECTIVE: To observe the exposure levels of extremely low frequency electromagnetic fields in workplaces and to analyze the effects of extremely low frequency electromagnetic radiation on cardiovascular system of occupationally exposed people. METHOD: Intensity of electromagnetic fields in two workplaces (control and exposure groups) was detected with EFA-300 frequency electromagnetic field strength tester, and intensity of the noise was detected with AWA5610D integral sound level. The information of health physical indicators of 188 controls and 642 occupationally exposed workers was collected. Data were analyzed by SPSS17.0 statistic software. RESULTS: The intensity of electric fields and the magnetic fields in exposure groups was significantly higher than that in control group (P < 0.05), but there was no significant difference of noise between two workplaces (P > 0.05). The results of physical examination showed that the abnormal rates of HCY, ALT, AST, GGT, ECG in the exposure group were significantly higher than those in control group (P < 0.05). There were no differences of sex, age, height, weight between two groups (P > 0.05). CONCLUSION: Exposure to extremely low frequency electromagnetic radiation may have some effects on the cardiovascular system of workers.