Neonatal stress exposure and DNA methylation of stress-related and neurodevelopmentally relevant genes: An exploratory study.

BACKGROUND: Stress exposure during Neonatal Intensive Care Unit (NICU) stay may have long-lasting effects on neurodevelopmental outcomes in extremely preterm infants. Altered DNA methylation of stress-related and neurodevelopmentally relevant genes may be an underlying mechanism. AIMS: This exploratory study aimed to investigate the association between neonatal stress exposure and DNA methylation in these genes at two different time points: early during the NICU stay (7-14 days after birth) and later, at discharge from the NICU. SUBJECTS: We included 45 extremely preterm infants in this prospective cohort study, gestational age 24-30 weeks. OUTCOME MEASURES: We collected fecal samples at days 7-14 (n = 44) and discharge (n = 28) and determined DNA methylation status in predefined regions of NR3C1, SLC6A4, HSD11B2, OPRM1, SLC7A5, SLC1A2, IGF2, NNAT, BDNF and GABRA6 using pyrosequencing. Because of low DNA concentrations in some fecal samples, we could do so in 25-50 % of collected samples. We prospectively quantified daily neonatal stress exposure using the Neonatal Infant Stressor Scale (NISS) and explored associations between cumulative NISS scores and average DNA methylation status. RESULTS: Rates of methylation of most genes were not statistically different between day 7-14 and discharge, except for OPRM1. We found moderately high and mostly negative correlation coefficients upon discharge with the cumulative NISS for the NR3C1, SLC6A4, SLC1A2, IGF2, BDNF and OPRM1 genes, albeit not statistically significant. CONCLUSIONS: Findings suggest that expression of stress-related and neurodevelopmentally relevant genes may be differently regulated following higher neonatal stress exposure. Larger studies should challenge the findings of this study and ideally test the effects on gene expression.

Discovery of 35 novel classes of per- and polyfluoroalkyl substances in representative commercial fluorinated products in China.

Per- and polyfluoroalkyl substances (PFAS) have received increasing scientific and regulatory attention due to their global distribution and health hazards. However, little is known about the PFAS composition of fluorinated products commercially available in China. In this study, a sensitive and robust analytical method was proposed for the comprehensive characterization of PFAS in aqueous film-forming foam and fluorocarbon surfactants in the domestic market based on liquid chromatography-high resolution mass spectrometry in full scan acquisition mode followed by parallel reaction monitoring mode. Consequently, a total of 102 PFAS from 59 classes were elucidated, of which 35 classes are reported for the first time, including 27 classes of anionic, seven classes of zwitterionic, and one class of cationic PFAS. The anionic-type products are mainly C6 fluorotelomerization-based (FT-based) PFAS. Perfluorooctanoic acid and perfluorooctane sulfonate are negligible, while some known electrochemical fluorination-based long-chain precursors in zwitterionic products are worthy of concern because of their high abundance and potential degradation. New precursors detected in zwitterionic products are FT-based PFAS, for example, 6:2 FTSAPr-AHOE and 6:2 FTSAPr-diMeAmPrC. The structural elucidation of PFAS in commercial products facilitates a better assessment of human exposure and environmental release.

Gene expression in the intestine of newborn piglets after hypoxia-reoxygenation.

BACKGROUND: In preterm infants, intestinal hypoxia may partly contribute to the pathophysiology of necrotizing enterocolitis through changes in gene expression. Splanchnic hypoxia can be detected with monitoring of regional splanchnic oxygen saturation (rsSO2). Using a piglet model of asphyxia, we aimed to correlate changes in rsSO2 to gene expression. METHODS: Forty-two newborn piglets were randomized to control or intervention groups. Intervention groups were subjected to hypoxia until they were acidotic and hypotensive. Next, they were reoxygenated for 30 min according to randomization, i.e., 21% O2, 100% O2, or 100% O2 for 3 min followed by 21% O2, and observed for 9 h. We continuously measured rsSO2 and calculated mean rsSO2 and variability of rsSO2 (rsCoVar = SD/mean). Samples of terminal ileum were analyzed for mRNA expression of selected genes related to inflammation, erythropoiesis, fatty acid metabolism, and apoptosis. RESULTS: The expression of selected genes was not significantly different between control and intervention groups. No associations between mean rsSO2 and gene expression were observed. However, lower rsCoVar was associated with the upregulation of apoptotic genes and the downregulation of inflammatory genes (P < 0.05). CONCLUSION: Our study suggests that hypoxia and reoxygenation cause reduced vascular adaptability, which seems to be associated with the upregulation of apoptosis and downregulation of inflammation. IMPACT: Our results provide important insight into the (patho)physiological significance of changes in the variability of rsSO2. Our findings may advance future research and clinical practice regarding resuscitation strategies of preterm infants.

Growth-Restricted Fetuses and Offspring Reveal Adverse Sex-Specific Metabolic Responses in Preeclamptic Mice Expressing Human sFLT1.

Fetal adaptations to harmful intrauterine environments due to pregnancy disorders such as preeclampsia (PE) can negatively program the offspring's metabolism, resulting in long-term metabolic changes. PE is characterized by increased circulating levels of sFLT1, placental dysfunction and fetal growth restriction (FGR). Here we examine the consequences of systemic human sFLT1 overexpression in transgenic PE/FGR mice on the offspring's metabolic phenotype. Histological and molecular analyses of fetal and offspring livers as well as examinations of offspring serum hormones were performed. At 18.5 dpc, sFLT1 overexpression resulted in growth-restricted fetuses with a reduced liver weight, combined with reduced hepatic glycogen storage and histological signs of hemorrhages and hepatocyte apoptosis. This was further associated with altered gene expression of the molecules involved in fatty acid and glucose/glycogen metabolism. In most analyzed features males were more affected than females. The postnatal follow-up revealed an increased weight gain of male PE offspring, and increased serum levels of Insulin and Leptin. This was associated with changes in hepatic gene expression regulating fatty acid and glucose metabolism in male PE offspring. To conclude, our results indicate that sFLT1-related PE/FGR in mice leads to altered fetal liver development, which might result in an adverse metabolic pre-programming of the offspring, specifically targeting males. This could be linked to the known sex differences seen in PE pregnancies in human.

Determination of Perfluorooctane Sulfonyl Fluoride and Perfluorohexane Sulfonyl Fluoride in Soil by Chemical Derivatization and Liquid Chromatography-Tandem Mass Spectrometry.

Perfluorooctane sulfonyl fluoride (PFOSF) and perfluorohexane sulfonyl fluoride (PFHxSF) were listed as persistent organic pollutants by the Stockholm Convention in 2009 and 2022, respectively. To date, their concentrations in environmental samples have not been reported due to the lack of sensitive methods. Herein, a novel chemical derivatization was developed for quantitative analysis of trace PFOSF and PFHxSF in soil by derivatizing them to the corresponding perfluoroalkane sulfinic acids. The method showed good linearity in the range from 25 to 500 ng L-1 with correlation coefficients (R2) better than 0.99. The detection limit of PFOSF in soil was 0.066 ng g-1 with recoveries in the range of 96-111%. Meanwhile, the detection limit of PFHxSF was 0.072 ng g-1 with recoveries in the range of 72-89%. Simultaneously, perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS) were also detected accurately without being affected by the derivative reaction. By applying this method in an abandoned fluorochemical manufacturing facility, PFOSF and PFHxSF were successfully detected at concentrations ranging from 2.7 to 357 ng g-1 and 0.23 to 26 ng g-1 dry weight, respectively. It is very interesting that 2 years after factory relocation, there still exists high concentrations of PFOSF and PFHxSF, which is of concern.

LPS versus Poly I:C model: comparison of long-term effects of bacterial and viral maternal immune activation on the offspring.

A prominent health issue nowadays is the COVID-19 pandemic, which poses acute risks to human health. However, the long-term health consequences are largely unknown and cannot be neglected. An especially vulnerable period for infection is pregnancy, when infections could have long-term health effect on the child. Evidence suggests that maternal immune activation (MIA) induced by either bacteria or viruses presents various effects on the offspring, leading to adverse phenotypes in many organ systems. This review compares the mechanisms of bacterial and viral MIA and the possible long-term outcomes for the offspring by summarizing the outcome in animal LPS and Poly I:C models. Both models are activated immune responses mediated by Toll-like receptors. The outcomes for MIA offspring include neurodevelopment, immune response, circulation, metabolism, and reproduction. Some of these changes continue to exist until later life. Besides different doses and batches of LPS and Poly I:C, the injection day, administration route, and also different animal species influence the outcomes. Here, we specifically aim to support colleagues when choosing their animal models for future studies.

Distribution of APOE gene polymorphism in the Chinese Uyghur children & its association with urolithiasis.

Background & objectives: This study was to survey the apolipoprotein E (APOE) gene polymorphism distribution among Chinese Uyghur children and to explore the relationship between APOE gene polymorphism and the occurrence of urolithiasis. Methods: A total of 144 Uyghur children with urolithiasis and 274 without the history of urolithiasis were enrolled in this study. Venous blood samples were collected from all participants, and APOE genotyping, derived from rs429358 and rs7412, was performed using Sanger sequencing. Results: Among the 418 children, the most prevalent genotype was E3/3, accounting for 71.3 per cent in the urolithiasis group and 71.4 per cent in the control group, followed by E3/4 and E2/3. Higher frequencies of the ɛ2 and ɛ4 alleles and lower frequencies of the ɛ3 allele were observed in the test group, and the unusual allele ɛ1 was also found in them. However, there were no significant differences between cases and controls at both rs429358 and rs7412 genotype and allele frequencies [odds ratio (OR)=0.98, 95% confidence interval (CI): 0.57-1.67; 0.98 (0.59-1.63); 1.43 (0.75-2.74) and 1.40 (0.74-2.62), respectively]. Likewise, none of significant differences was found between cases and controls at both APOE genotype and allele frequencies [OR=0.88, 95% CI: 0.51-1.53; 0.74 (0.33-1.64); 1.10 (0.73-1.66); 1.13 (0.76-1.67) and 1.14 (0.76-1.70), respectively]. Interpretation & conclusions: The present study does not support any association between APOE genotyping and urolithiasis in Uyghur children.

Perfluorooctane sulfonate exposure alters sexual behaviors and transcriptions of genes in hypothalamic-pituitary-gonadal-liver axis of male zebrafish (Danio rerio).

BACKGROUND: Perfluorooctane sulfonate (PFOS) has been reported to be widely distributed in the environment and wildlife with persistence. PFOS has various biological toxicity, especially disturbing the endocrine system. However, few studies have systematically evaluated its effect on sexual behaviors alteration and reproduction-related genes. This study was performed to assess the effect of PFOS exposure on sexual behaviors and genes in hypothalamic-pituitary-gonadal-liver (HPGL) axis in adult zebrafish. METHODS: Male adult zebrafish were exposed to PFOS (0, 2, 20, and 200 µg/L) and 5 µg/L estradiol (E2) continuously for 21 days. Sexual behaviors were analyzed by zebrafish behavior tracking system and the mRNA levels of HPGL-related genes was detected by RT-qPCR. RESULTS: Body weight of the fish was increased in 2, 200 µg/L PFOS and E2 groups, and body length was increased with exposure to 2 µg/L PFOS and E2. The hepatic-somatic index was decreased significantly after 2 and 20 µg/L PFOS treatments. Highest PFOS (200 µg/L) and E2 exposure impaired standard zebrafish sexual behaviors significantly such as chasing, nose-tail and tail-touching. In brains, the genes gonadotropin-releasing hormone (GnRH), gonadotropin-releasing hormone receptor (GnRHr) were down-regulated with exposure to PFOS with linear trend and E2 exposure, and follicle-stimulating hormone and luteinizing hormone were also down-regulated with exposure to 20 and 200 µg/L PFOS. In livers, the genes vitellogenin 1 and 3 were upregulated with some concentrations of PFOS and E2, but estrogenic receptor α, ß2 were upregulated in any concentration of PFOS and E2. In testes, the expressions of follicle-stimulating hormone receptor, luteinizing hormone receptor, and androgen receptor genes were all significantly down-regulated with any exposure concentration of PFOS and E2. CONCLUSIONS: PFOS may alter the zebrafish reproductive system by disrupting endocrine activity and impairing sexual behaviors.

Association Between Alcohol Consumption and Risk of Nasopharyngeal Carcinoma: A Comprehensive Meta-Analysis of Epidemiological Studies.

BACKGROUND: Alcohol consumption is increasing all over the world, but whether it is an independent factor affecting the occurrence of nasopharyngeal carcinoma (NPC) is inconsistent in many studies. We aimed to explore the association between alcohol consumption and NPC risk by integrating existing evidence in a meta-analysis. METHODS: We searched for relevant articles published up to August 2018 in PubMed, Cochrane Library, Web of Science, and China National Knowledge infrastructure (CNKI). The Newcastle-Ottawa scale was used to assess the quality of the included studies. Odds ratios (ORs) or relative risks were pooled to estimate the associations between alcohol consumption and NPC risk. RESULTS: The meta-analysis of cohort studies showed no significant association between alcohol consumption and NPC, but pooled results from case-control studies indicated that ever drinking increased the probability of NPC versus nondrinking (OR = 1.10; 95% confidence interval [CI]: 1.01, 1.19). As compared with nondrinkers, high-frequency drinking (≥7 times/wk) increased the NPC probability (OR = 1.29; 95% CI: 1.05, 1.53) and low-frequency drinking (<7 times/wk) decreased the probability (OR = 0.77; 95% CI: 0.60, 0.94), as did shorter duration of drinking (<20 years) (OR = 0.64; 95% CI: 0.49, 0.79). On subgroup analyses, significant pooled results were observed for studies with high quality, with hospital-based controls and with adjustment for confounding factors, smoking, age, and sex. CONCLUSIONS: The risk of NPC may increase with alcohol consumption. Ever drinking increased the risk versus nondrinking. Additionally, high-frequency drinking increased the risk, but low-frequency drinking decreased it to some extent. Further intensive studies based on well-designed methods are needed to examine the association.

Exposure to perfluorooctane sulfonate based on circadian rhythm changes the fecundity and expression of certain genes on the hypothalamic-pituitary-gonadal-liver axis of female zebrafish.

Exposure of a variety of experimental animals to perfluorooctane sulfonate (PFOS) has shown that it is a potent endocrine-disrupting chemical. However, its interaction with the circadian rhythm on responses along the hypothalamic - pituitary - gonadal - liver (HPGL) axis should be of significant value but has not been adequately investigated. In present study, the effects of PFOS on fecundity, levels of estradiol (E2) and expression of certain genes on the HPGL axis at two time points (8:00 AM and 7:00 PM) were compared after female zebrafish were exposed to 0, 2, 20 and 200 µg/L PFOS for 21 days. In brain, expressions of gonadotropin-releasing hormone (GnRH), gonadotropin-releasing hormone receptor (GnRHr), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were significantly different after the exposure when sampled at 8:00 AM and at 7:00 PM (P < .05). In liver, significant down-regulation of vitellogenin1 (VTG1) and estrogenic receptor α (ERα) were observed at 7:00 PM compared with 8:00 AM (P < .05). In ovary, the level of CYP19 was significantly different at the two time points (P < .05). The increase of E2 after exposure to 20 µg/L PFOS at 8:00 AM caused compensatory down-regulation of GnRHr and up-regulation of VTG1 and ERα, but not at 7:00 PM. Profiles of concentrations of E2 and several gene expressions alongside the HPGL axis were different between two times points. The change of E2 and gene expressions were more perturbed by PFOS at 8:00 AM than at 7:00 PM with circadian rhythm.

Blood Cadmium Level Is Associated with Short Progression-Free Survival in Nasopharyngeal Carcinoma.

The prognosis of nasopharyngeal carcinoma (NPC) is poor with disease progression. Cadmium exposure is a risk factor for NPC. We aimed to investigate the effect of cadmium exposure, by measuring cadmium level, and clinicopathologic factors on NPC disease progression and prognosis. A total of 134 NPC cases were analyzed and venous blood samples were collected. Blood cadmium level was analyzed by graphite furnace atomic absorption spectrophotometry. Clinical data were collected at baseline for patients and tumor characteristics from medical records. Progression-free survival (PFS) was analyzed during follow-up. The effect of cadmium exposure and clinical factors on PFS was analyzed by the Kaplan-Meier method and Cox regression models. Blood cadmium level was associated with history of disease and smoking history and pack-years. On Kaplan-Meier analysis, a high blood cadmium level, male sex, smoking history and increasing pack-years, as well as advanced clinical stage were all associated with short PFS. On multivariate analysis, blood cadmium level was an independent risk factor and predictor of NPC prognosis and disease progression. Cadmium exposure and related clinical factors can affect the prognosis of NPC, which merits further study to clarify.

Effects of Exposure to Bisphenol A during Pregnancy on the Pup Testis Function.

Testosterone plays an important prenatal role in male testis development. Bisphenol A (BPA) exposure during pregnancy affects testosterone levels and germ cell apoptosis of male pups, but little information is available for the mechanism. The aim of the present study was to investigate the mechanism by which BPA alters testosterone levels and germ cell apoptosis. Pregnant female C57BL/6J mice, throughout gestation, had access to drinking water containing BPA at 5 and 50 µg/mL. Male pups were euthanized on postnatal days (PNDs) 1, 14, and 35. Relative to control, BPA exposure at 5 and 50 µg/ml decreased testosterone level, as measured by chemiluminescent immunoassay, on PND14. Real-time PCR indicated mRNA levels for steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (CYP11A1), and 3-ß-hydroxysteroid dehydrogenase/△-5-4 isomerase (3ß-HSD) were significantly lower in the BPA pups compared to control. Additionally, BPA increased the percentage of TUNEL-positive seminiferous tubules, decreased the mRNA level of Bcl-2, and increased Bax expression, indicative of increased apoptosis. These results suggest that BPA exposure in utero decreases the testosterone concentration by decreasing steroidogenic enzymes (StAR, CYP11A1, and 3ß-HSD). Furthermore, BPA exposure increases the apoptosis of germ cells, which is associated with proapoptotic changes in the levels of Bcl-2 and Bax.

Expression of the p24 silencing suppressor of Grapevine leafroll-associated virus 2 from Potato virus X or Barley stripe mosaic virus vector elicits hypersensitive responses in Nicotiana benthamiana.

The 24-kDa protein (p24) encoded by Grapevine leafroll-associated virus 2 (GLRaV-2) is an RNA-silencing suppressor (RSS), but its effect on active viral infection is unclear. Using a Potato virus X (PVX)-based expression system, we demonstrated that p24 elicits lethal systemic necrosis in Nicotiana benthamiana, sharing typical characteristics of the hypersensitive response (HR), and that NbRAR1 (a cytoplasmic Zn2+-binding protein) is involved in the PVX-p24-mediated systemic necrosis. Moreover, expression of p24 from Barley stripe mosaic virus (BSMV) vector triggered local necrosis in infiltrated patches of N. benthamiana, likely inhibiting viral systemic spread. By deletion analysis, we demonstrated that amino acids (aa) 1 to 180, which are located in the region (aa 1-188) previously shown to be necessary for p24's RSS activity, is sufficient for p24 to elicit systemic necrosis in the context of PVX infection. Using substitution mutants, we revealed that silencing-suppression-defective mutants R2A and W54A induce only a mild necrotic response; two mutants without self-interaction ability previously shown to lose or retain weak suppression function also displayed decreased pathogenicity: W149A without RSS activity elicited a mild necrotic response, whereas V162H/L169H/L170H which retains weak RSS activity was able to induce systemic necrosis, but with a 1- to 2-day delay. Taken together, p24 plays an important role in GLRaV-2 pathogenesis, triggering HR-like necrosis in N. benthamiana plants when expressed from PVX or BSMV vector; both the silencing suppression and self-interaction are crucial for p24's pathogenicity activity, and the region of p24 for determining systemic necrosis is mapped to aa 1-180.

Effects of PM2.5 on Cardio-Pulmonary Function Injury in Open Manganese Mine Workers.

Exposure to fine particulate matter 2.5 (PM2.5) is associated with adverse health effects, varying by its components. The health-related effects of PM2.5 exposure from ore mining may be different from those of environment pollution. The aim of this study was to investigate the effects of different concentrations of PM2.5 exposure on the cardio-pulmonary function of manganese mining workers. A total of 280 dust-exposed workers who were involved in different types of work in an open-pit manganese mine were randomly selected. According to the different concentrations of PM2.5 in the working environment, the workers were divided into an exposed group and a control group. The electrocardiogram, blood pressure, and multiple lung function parameters of the two groups were measured and analyzed. The PM2.5 exposed group had significantly lower values in the pulmonary function indexes of forced expiratory volume in one second (FEV1.0), maximum mid expiratory flow (MMEF), peak expiratory flow rate (PEFR), percentage of peak expiratory flow out of the overall expiratory flow volume (PEFR%), forced expiratory flow at 25% and 75% of forced vital capacity (FEF 25, FEF75), forced expiratory flow when 25%, 50%, and 75% of forced vital capacity has been exhaled (FEF25%,FEF50%, FEF75%), and FEV1.0/FVC% (the percentage of the predicted value of forced vital capacity) than the control group (all p < 0.05). Both groups had mild or moderate lung injury, most of which was restrictive ventilatory disorder, and there was significant difference in the prevalence rate of restrictive respiratory dysfunction between the two groups (41.4% vs. 23.6%, p = 0.016). Electrocardiogram (ECG) abnormalities, especially sinus bradycardia, were shown in both groups, but there was no statistical difference of the prevalence rate between the two groups (p > 0.05). Also, no significant difference of the prevalence rate of hypertension was observed between the PM2.5 exposure and control groups (p > 0.05). PM2.5 exposure was associated with pulmonary function damage of the workers in the open-pit manganese mine, and the major injury was restrictive ventilatory disorder. The early effect of PM2.5 exposure on the cardiovascular system was uncertain at current exposure levels and exposure time.

Psychological resilience of women after breast cancer surgery: a cross-sectional study of associated influencing factors.

The psychological resilience (PR) of postoperative patients is found relatively low in clinical work. We recruited 220 postoperative women with breast cancer to survey PR of them and the influencing factors. General demographic data and physical exercise status were collected by questionnaire, clinical characteristics data were obtained from medical records. Measures comprised the Chinese version of the Connor and Davidson Resilience Scale (CD-RISC), General Self-Efficacy Scale (GSES), Family Hardiness Index (FHI) and Social Support Rate Scale (SSRS). The mean (±SD) PR score in women after breast cancer surgery was 65.18 ± 13.16. Clinical stage of breast cancer, courses of adjuvant therapy and physical exercise status affected PR level significantly. PR level was positively correlated with total GSES, FHI, and SSRS scores (r = 0.291, 0.378, 0.418, all P < 0.001); dimensions of FHI; and dimensions of SSRS. On multiple regression analysis, clinical stage of breast cancer and courses of adjuvant therapy negatively, but postoperative physical exercise status, commitment, control and social subjective support positively contributed to PR significantly. Psychological resilience of women after breast cancer surgery is relatively low. Moderate physical exercise, self-efficacy, family hardiness, and social support affect PR positively, promoting disease rehabilitation and improving the quality of life.

Biochemical metabolic levels and vitamin D receptor Fokâ gene polymorphisms in Uyghur children with urolithiasis.

Because of lacking studies of urolithiasis in children, we detected the biochemical metabolic levels and FokⅠ polymorphisms in the vitamin D receptor (VDR) in Uyghur children with urolithiasis, and evaluated the associations of biochemical metabolic levels with FokⅠ genotypes. We included 142 Uyghur children (108 males) under age 14 years with a diagnosis of urolithiasis and 238 Uyghur children (154 males) under age 14 years without a history of urolithiasis as controls. Baseline information and data for serum and urine parameters were obtained from medical records. PCR-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the VDR FokⅠ polymorphisms. In univariate analyses adjusting for age and sex, carbon dioxide combining power (CO2CP) (odds ratio [OR] = 1.13, 95% confidence interval [CI]: 1.07-1.19), serum magnesium (Mg) (OR = 1.27, 95% CI: 1.03-1.56) and serum chlorine (Cl) (OR = 0.93, 95% CI: 0.88-0.97) were related to Uyghur children urolithiasis risk. A multiple logistic regression model showed CO2CP (OR = 1.17, 95% CI: 1.09-1.26), levels of uric acid (OR = 1.01, 95% CI: 1.00-1.01) and serum sodium (Na) (OR = 0.90, 95% CI: 0.82-0.99) were associated with pediatric urolithiasis. The risk of urolithiasis was increased with the F versus f allele overall (OR = 1.42; 95% CI: 1.01-2.00) and for males (OR = 1.52, 95% CI: 1.02-2.27). However, metabolic levels did not differ by FokⅠ genotypes. In our population, CO2CP and levels of uric acid and serum Na as well as polymorphism of the F allele of the VDR FokⅠ may provide important clues to evaluate the risk of urolithiasis in Uyghur children.

Adipose tissue levels of polybrominated diphenyl ethers and breast cancer risk in Chinese women: A case-control study.

Polybrominated diphenyl ethers (PBDEs) are suspected to be associated with breast cancer risk because of their estrogenic potencies. Epidemiological studies of PBDEs and breast cancer are scarce. Our study aimed to estimate the association between adipose-tissue PBDE concentrations and breast cancer risk. A total of 209 breast cancer cases and 165 controls were recruited from hospitals between January 2014 and May 2016 in Shantou, Chaoshan area, China. Concentrations of 14 PBDE congeners were measured in adipose tissues obtained from the breast for cases and the abdomen/breast for controls during surgery. Demographic and clinicopathologic characteristics were obtained from medical records. Breast cancer risk as well as clinicopathologic characteristics were evaluated by adipose-tissue PBDE level. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for breast cancer risk associated with levels of PBDE congeners were estimated from logistic regression models for all cases and stratified by estrogen receptor (ER) status. Level of total PBDEs (∑PBDE) and most individual PBDE congeners were higher in breast cancer cases than controls (median ∑PBDE, 94.99 vs 73.72 ng/g lipid). In the adjusted univariate model for all cases, breast cancer risk was increased with both 2nd and 3rd tertiles versus the 1st tertile of BDE-47 level (OR 2.05 [95% CI 1.08-3.92]; 5.47 [2.96-10.11]) and BDE-209 level (2.48 [1.30-4.73]; 4.72 [2.52-8.83]) with trend (both P < 0.001) and with the 3rd tertile of BDE-28 level (2.83 [1.63-4.92]), BDE-99 (3.22 [1.85-5.60]), BDE-100 (5.45 [2.90-10.23]), BDE-138 (2.40 [1.37-4.20]), BDE-153 (1.74 [1.02-2.97]), BDE-154 (1.84 [1.05-3.22]), and ∑PBDE levels (1.83 [1.07-3.14]) but decreased with the 3rd tertile of BDE-71 level (0.38 [0.22-0.65]) with trend (all P < 0.01). After stratifying by ER-positive or -negative status, the adjusted results were similar for ER-positive patients except for BDE-153 and BDE-154, with no statistical significance. In the multivariate model for all cases, age, menarche age, BDE-47, 71, 99, 100, 183 and 209 were independent factors associated with breast-cancer risk. ∑PBDE and most individual PBDE congeners investigated were positively associated with breast cancer risk in women from the Chaoshan area, China. PBDE may play a role in the occurrence and development of breast cancer.

Effects of 2,2',4,4'-tetrabromodiphenyl ether on neurobehavior and memory change and bcl-2, c-fos, grin1b and lingo1b gene expression in male zebrafish (Danio rerio).

Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants in various environmental matrices and organisms and pose a threat to neural systems of organisms. However, though quite a few studies have explored the effect of PBDEs on neural behaviors such as learning and memory abilities in animals, their mechanisms are less known. We used the zebrafish model to evaluate neurotoxicity of PBDEs and observe changes in behavior and related gene expression. In behavioral testing, 50 zebrafish were divided into five groups treated with different concentrations of BDE-47. T-maze exploration was used for learning and memory testing, which was recorded by camera every 7days. After 21days, all fish were killed, and the gene expression of c-fos, bcl-2, lingo1b and grin1b in brain tissue was analyzed by RT-qPCR. The behavioral changes (latency to leave the start zone, reach the reward zone, and stay in the reward zone; accuracy in choosing the right maze arm, accumulation of freezing bouts, etc.) were related to BDE-47 concentration and had a time-effect relation with increasing exposure days, especially with 500µg/L BDE-47. BDE-47 elevated brain bcl-2, grin1b and lingo1b expression. The expression of c-fos showed an increase with 50 and 100µg/L BDE-47 exposure. The PBDE BDE-47 had a negative impact on the neurobehaviors of zebrafish and affected the expression of c-fos, bcl-2, lingo1b and grin1b in zebrafish brain tissue.