Astaxanthin activates the Nrf2/Keap1/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity.

Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the mechanism remains unclear. In this study, we involved zebrafish to explore the new mechanism of TPhP inducing oxidative stress and ferroptosis to promote neurodevelopmental toxicity. The results suggested that TPhP affected the embryonic development, reduced the number of new neurons, and led to abnormal neural behavior in zebrafish larvae. TPhP also induced ROS accumulation, activated the antioxidant defense signal Nrf2 and Keap1, and significantly changed the activities of Acetylcholinesterase (AChE), Adenosine triphosphatase (ATPase) and glutathione S-transferase (GST). In addition, TPhP induced ferroptosis in zebrafish, which was reflected in the increase of Fe2+ content, the abnormal expression of GPX4 protein and genes related to iron metabolism (gpx4a, slc7a11, acsl4b, tfa, slc40a1, fth1b, tfr2, tfr1a, tfr1b and ncoa4). Astaxanthin intervention specifically inhibited ROS levels, and reversed SLC7A11 and GPX4 expression levels and Fe2+ metabolism thus alleviating ferroptosis induced by TPhP. Astaxanthin also partially reversed the activity of AChE, GST and the expression of neurodevelopmental-related genes (gap43, gfap, neurog1 and syn2a), so as to partially rescue the embryonic developmental abnormalities and motor behavior disorders induced by TPhP. More interestingly, the expression of mitochondrial apoptosis-related protein BAX, anti-apoptotic protein BCL-2, Caspase3 and Caspase9 was significantly altered in the TPhP exposed group, which could be also reversed by Astaxanthin intervention. In summary, our results suggested that TPhP exposure can induce oxidative stress and ferroptosis, thereby causing neurodevelopment toxicity to zebrafish, while Astaxanthin can partially reverse oxidative stress and reduce the neurodevelopmental toxicity of zebrafish larvae by activating Nrf2/Keap1/HO-1 signaling pathway.

Association between heavy metals exposure and risk of attention deficit hyperactivity disorder (ADHD) in children: a systematic review and meta-analysis.

Heavy metals can negatively affect children's neurodevelopment, yet the relationship between heavy metals exposure and attention deficit hyperactivity disorder (ADHD) in children remains unclear. We aimed to examine associations between exposure to five common heavy metals (lead, arsenic, mercury, cadmium, and manganese) with neurodevelopmental toxicity and the risk of ADHD in children. Online databases of PubMed, Web of Science, and Embase were searched before February 29, 2024. A total of 31 studies involving 25,258 children were included in the final analysis. Our findings revealed that lead exposure was positively associated with ADHD risk in children (OR = 1.95, 95% CI: 1.57-2.41) overall, while the associations varied among different WHO regions, with the strongest in the Americas. Sensitivity analyses revealed significant associations between arsenic (OR = 1.53, 95% CI: 1.01-2.32) and manganese (OR = 1.79, 95% CI: 1.28-2.49) exposure and ADHD risk after omitting one study. Arsenic exposure was positively associated with ADHD risk in studies conducted in the Americas and adjusted for environmental smoke exposure. Positive associations between manganese exposure and ADHD risk were also found in several subgroup analyses. No significant associations were found for mercury and cadmium exposure. Dose-response meta-analysis suggested that children with higher blood lead levels exhibited a higher probability of ADHD diagnosis. Lead exposure consistently increases the risk of ADHD in children, while arsenic and manganese exposure may be associated with ADHD under different occasions. More research is required to understand heavy metals' impact on ADHD across varying exposure levels, particularly in less contaminated regions.

Adipose tissue levels of polybrominated diphenyl ethers in relation to prognostic biomarkers and progression-free survival time of breast cancer patients in eastern area of southern China: A hospital-based study.

Evidence indicates that individual or groups of polybrominated diphenyl ethers (PBDEs) are associated with risk of breast cancer (BC). Epidemiological studies of PBDEs and BC progression are scarce. This study aimed to investigate the relationships between PBDE burdens in adipose tissues and prognostic biomarkers of BC as well as progression-free survival (PFS) of patients for the first time. The concentrations of 14 PBDE congeners in breast adipose tissues of 183 cases from the eastern area of southern China were analyzed by gas chromatography-mass spectrometry (GC-MS). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression models for the associations between PBDE levels and prognostic biomarkers. Kaplan-Meier and Cox regression analyses were conducted to identify the correlations between PBDEs and PFS. The results showed that BDE-99 and 190 levels were positively associated with clinical stage and N stage respectively (OR = 2.61 [1.26-5.40], OR = 2.78 [1.04-7.46]). Concentrations of BDE-28 and BDE-183 were negatively associated with the expression of estrogen receptor (ER) (OR = 0.30 [0.11-0.81]; 0.39 [0.15-0.99]) and progesterone receptor (PR) (OR = 0.36 [0.14-0.92]; 0.37 [0.15-0.91]), and increased BDE-47 was associated with lower human epidermal growth factor receptor 2 (HER2) expression (OR = 0.44 [0.23-0.86]). Adipose levels of BDE-71, 99, 138, 153, 154 and total PBDEs were positively associated with p53 expression (all P < 0.05). Finally, BDE-47, 99 and 183 were considered as independent prognostic factors for shorter PFS in the Cox models (adjusted hazard ratios = 3.14 [1.26-7.82]; 2.25 [1.03-4.94]; 2.60 [1.08-6.25], respectively). The recurrence risk and prognosis of BC may be closely bound to the body burdens of certain PBDE congeners. Further epidemiological and experimental studies are needed for confirmation.

Developmental hazards of 2,2',4,4'-tetrabromodiphenyl ether induced endoplasmic reticulum stress on early life stages of zebrafish (Danio rerio).

Polybrominated diphenyl ether flame retardants are known to have adverse effects on the development of organisms. We investigated the molecular mechanisms associated with the developmental hazards of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) in zebrafish, as well as the behavioral and morphological alterations involved, focusing on endoplasmic reticulum stress (ERS), oxidative stress, and apoptosis. Our study revealed behavioral alterations in zebrafish exposed to BDE-47, including impaired motor activity, reduced exploration, and abnormal swimming patterns. In addition, we observed malformations in craniofacial regions and other developmental abnormalities that may be associated with ERS-induced cellular dysfunction. BDE-47 exposure showed apparent changes in ERS, oxidative stress, and apoptosis biomarkers at different developmental stages in zebrafish through gene expression analysis and enzyme activity assays. The study indicated that exposure to BDE-47 results in ERS, as supported by the upregulation of ERS-related genes and increased activity of ERS markers. In addition, oxidative stress-related genes showed different expression patterns, suggesting that oxidative stress is involved in the BDE-47 toxic effects. Moreover, an assessment of apoptotic biomarkers revealed an imbalance in the expression levels of pro- and anti-apoptotic genes, suggesting that BDE-47 exposure activated the apoptotic pathway. These results highlight the complex interactions between ERS, oxidative stress, apoptosis, behavioral alterations, and morphological malformations following BDE-47 exposure in zebrafish. Understanding the mechanisms of toxicity of developmental hazards is essential to elucidate the toxicological effects of environmental contaminants. The knowledge can help develop strategies to mitigate their adverse effects on the health of ecosystems and humans.

Associations between polybrominated diphenyl ethers (PBDEs) levels in adipose tissues and blood lipids in women of Shantou, China.

Animal studies have indicated that exposure to polybrominated diphenyl ethers (PBDEs) during development can permanently affect blood/liver lipid balance. However, no epidemiological study has assessed the relationship between PBDEs in adipose tissues and blood lipid metabolism. In this study, we explored the associations between PBDEs levels in female adipose tissues and lipid profiles. We recruited 150 female patients undergoing plastic surgery from hospital in Shantou, China, collected their characteristics, clinical information, and adipose tissue samples. Fourteen PBDE congeners in adipose tissues were analyzed by gas chromatography-mass spectrometry (GC-MS). Multiple linear and logistic regression models were used to explore the relationships between PBDEs and lipid profiles, while restricted cubic spline (RCS) regression and Bayesian kernel machine regression (BKMR) models were used to evaluate the nonlinearity of mixtures. Median levels of ΣPBDEs and dominant congeners BDE-153, -209, and -183 in adipose tissues were 73.91, 26.12, 14.10 and 9.01 ng/g lipid, respectively. In the multiple linear model, BDE-153 and BDE-209 were negatively associated with triglycerides (TG), similarly for BDE-190 and total cholesterol (TC). While in the adjusted logistic models, BDE-138 was negatively associated with TC (OR = 0.76, 95%CI: 0.58, 0.99) and total lipids (TL) (OR = 0.76, 95%CI: 0.58, 0.99). Diastolic blood pressure was positively correlated with BDE-28 and BDE-71 (P < 0.05). Furthermore, a non-linear relationship was observed in BDE-138 and blood lipid levels using a RCS model (Pnonlinearity<0.05). BKMR analysis indicated that with the cumulative levels across PBDEs increased, the health risks of hypertriglyceridemia gradually rebounded, and the health risks of hypercholesterolemia and high total lipid gradually rebounded and then declined, but without statistical significance. PBDEs pollution was still prevalent in Shantou city, and several PBDE congeners were significant risk factors for dyslipidemia and blood pressure alteration. There exist deleterious effects of PBDEs and blood lipids.

Behavioral changes and transcriptomic effects at embryonic and post-embryonic stages reveal the toxic effects of 2,2',4,4'-tetrabromodiphenyl ether on neurodevelopment in zebrafish (Danio rerio).

Polybrominated biphenyl ethers (PBDEs) are new persistent pollutants that are widely exist in the environment and have many toxic effects. However, their toxicity mechanisms on neurodevelopment are still unclear. In this study, zebrafish embryos were exposed to 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) (control, 10, 50 and 100 µg/L) at 2 h postfertilization (hpf) - 7 dpf. Locomotion analysis indicated that BDE-47 increased spontaneous coiling activity in zebrafish embryos under high-intensity light stimuli and decreased locomotor in zebrafish larvae. RNA-Seq analysis revealed that most of the up-regulated pathways were related to the metabolism of cells and tissues, while the down-regulated pathways were related to neurodevelopment. Consistent with the locomotion and KEGG results, BDE-47 affected the expression of genes for central nervous system (gfap, mbpa, bdnf & pomcb), early neurogenesis (neurog1 & elavl3), and axonal development (tuba1a, tuba1b, tuba1c, syn2a, gap43 & shha). Furthermore, BDE-47 interfered with gene expression of the Wnt signaling pathway, especially during embryonic stages, suggesting that the mechanisms of BDE-47 toxicity to zebrafish at various stages of neurodevelopment may be different. In summary, early neurodevelopment effects and metabolic disturbances may have contributed to the abnormal neurobehavioral changes induced by BDE-47 in zebrafish embryos/larvae, suggesting the neurodevelopmental toxicity of BDE-47.

Effects of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on reproductive and endocrine function in female zebrafish (Danio rerio).

BACKGROUND: Polybrominated diphenyl ethers (PBDEs), a group of brominated flame retardants (BFRs), were reported exist extensively in various ecological environmental. Studies have indicated that PBDEs induce reproductive toxic effects on human health, but the mechanisms remain poorly understood. In this study, the adult female zebrafish were used to investigate the effects of 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) on the reproductive endocrine system and its mechanism. METHODS: Female zebrafish (AB strains) were continuously exposed to BDE-47 at the concentrations of 0, 10, 50, 100 and 500 µg/L till 21 days. The morphology of ovary were stained and evaluated with hematoxylin-eosin (H&E), and levels of sex hormones including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and 17ß-estradiol (E2) and the biomarkers of oxidative stress such as superoxide dismutase (SOD) and malondialdehyde (MDA), were measured via ELISA. Subsequently, the expression of genes along the hypothalamic pituitary-gonad (HPG) and oxidative stress were determined using quantitative real-time PCR (qRT-PCR). RESULT: The results showed that exposure to high level of BDE-47 reduced the index of condition factor (CF) and gonadosomatic index (GSI). Treatment with BDE-47 impaired the normal development and structure of oocytes in zebrafish ovary. Moreover, the steroid hormone of FSH, LH, T and E2 were significantly decreased in BDE-47 exposure group. A dose-dependent elevation in SOD activity and MDA levels were recorded. Meanwhile, the transcription level of cyp19a, cyp19b, fshß, lhß were up-regulated while the transcription of fshr, lhr, cyp17a, 17ßhsd were down-regulated in the gonad of female adult zebrafish. CONCLUSION: Exposure to BDE-47 have detrimental impact on the development of ovary, decreasing sex hormone levels, inducing oxidative damage as well as altering HPG axis-related genes.

Bioinformatic analyses of hydroxylated polybrominated diphenyl ethers toxicities on impairment of adrenocortical secretory function.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) and their metabolites have severe impact on human health, but few studies focus on their nephrotoxicity. This study was conceived to explore hub genes that may be involved in two hydroxylated polybrominated diphenyl ethers toxicities on impairment of adrenocortical secretory function. METHODS: Gene dataset was obtained from Gene Expression Omnibus (GEO). Principal component analysis and correlation analysis were used to classify the samples. Differentially expressed genes (DEGs) were screened using the limma package in RStudio (version 4.1.0). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome enrichment analyses of DEGs were conducted. Protein-protein interaction (PPI) network was established using STRING network, and genes were filtered by Cytoscape (version 3.8.2). Finally, the hub genes were integrated by plug-in CytoHubba and RobustRankAggreg, and were preliminarily verified by the Comparative Toxicogenomics Database (CTD). RESULTS: GSE8588 dataset was selected in this study. About 190 upregulated and 224 downregulated DEGs in 2-OH-BDE47 group, and 244 upregulated and 276 downregulated DEGs in 2-OH-BDE85 group. Functional enrichment analyses in the GO, KEGG and Reactome indicated the potential involvement of DEGs in endocrine metabolism, oxidative stress mechanisms, regulation of abnormal cell proliferation, apoptosis, DNA damage and repair. 2-OH-BDE85 is more cytotoxic in a dose-dependent manner than 2-OH-BDE47. A total of 98 hub genes were filtered, and 91 nodes and 359 edges composed the PPI network. Besides, 9 direct-acting genes were filtered for the intersection of hub genes by CTD. CONCLUSIONS: OH-PBDEs may induce H295R adrenocortical cancer cells in the disorder of endocrine metabolism, regulation of abnormal cell proliferation, DNA damage and repair. The screened hub genes may play an important role in this dysfunction.

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.

Effect of bisphenol A on craniofacial cartilage development in zebrafish (Danio rerio) embryos: A morphological study.

Bisphenol A (BPA), an endocrine-disrupting chemical, is present in everyday-used consumables and common household products. Although the side effects of BPA have been sufficiently explored, little is known the effects of environmentally relevant low levels of BPA on chondrogenesis in skeletal development. Here we used a morphological approach to investigate whether exposure to BPA (0, 0.0038, 0.05, 0.1, 1.0 µM) could affect craniofacial cartilage development of zebrafish embryo. Furthermore, we sought to determine receptor-mediated BPA induced chondrogenesis toxicity by co-exposing developing embryos to BPA and various inhibitors. Low-dose BPA affected heart rate and induced body and head elongation of larvae. Quantitative morphometric and histopathological analysis revealed that BPA exposure changed the angle and length of craniofacial cartilage elements and disrupted chondrocytes. BPA induced pharyngeal cartilage defects via multiple cellular pathways, including estrogen receptor, androgen receptor, and estrogen-related receptors. Our findings demonstrate that BPA alters the normal development of cartilage and craniofacial structures in zebrafish embryos. Furthermore, in this study we find multiple cellular pathways mediating the effects of BPA-induced craniofacial chondrogenesis toxicity. Further experiments will allow for establishing a connection between BPA and increased risk of congenital malformation of the facial cranium in BPA-exposed populations.

Morphology and epidemiological study of idiopathic scoliosis among primary school students in Chaozhou, China.

BACKGROUND: Idiopathic scoliosis (IS) affects patients' quality of life, yet there have been few reports of its morphology and epidemiological study in the southeast region of China. The aim of this study is to access the curve characteristics, prevalence, and factors associated with IS in Chaozhou city. METHODS: A cross-sectional study was performed in 2018, in which scoliosis screening was conducted among 5497 primary school students in Chaozhou city. Then, a case-control study based on the screening involving 2547 children was followed for the exploration of the associated factors. The questionnaires covering demographic characteristics, postural habits, cognition and self-sensation of scoliosis, and physical conditions were addressed for the investigation. ORs with 95%CIs were calculated based on logistic regression analysis to evaluate the factors associated with scoliosis. RESULTS: The prevalence of IS among primary school students was 6.15% in Chaozhou city, with 4.04% for males and 8.71% for females. The average Cobb angle was 15° (range 8 to 37°). Multiple logistic regression analysis suggested that female (OR=2.45), BMI (OR=0.67), having myopia (OR=1.49), self-sensation of scoliosis with symptoms (OR=5.52), insufficient sleep time (OR=2.65, 3.33), and less exercise time (OR=7.09, 7.29) were significantly associated with IS. CONCLUSIONS: The prevalence of IS among primary school students in Chaozhou was at an average level, and it was significantly higher in females than in males. Lower body mass, having myopia, insufficient sleep time, and lower physical activity were associated with IS.

Associations between functional polychlorinated biphenyls in adipose tissues and prognostic biomarkers of breast cancer patients.

BACKGROUND: Exposure to polychlorinated biphenyls (PCBs) has been shown to influence expression of some biomarkers that are predictive/prognostic for breast cancer. Therefore, our study was conducted to further investigating associations of different functional PCBs in adipose tissue with breast cancer prognostic biomarkers. METHODS: Two hundred and five breast cancer patients were recruited in Shantou, China. Breast adipose tissues were collected during their resection surgery and levels of 7 PCB congeners were analyzed by gas chromatography-mass spectrometry (GC-MS). The PCB congeners were divided into 4 groups according to structure-activity. Socio-demographic, clinical and pathological information were obtained from questionnaire and digital medical records. Odds ratios (ORs) for associations between prognostic biomarkers and PCB levels (tertile 3 [T3], tertile 2 [T2] vs. tertile 1) were estimated from logistic regression models. RESULTS: Most PCB congeners were detectable, with a highest level (22.06 ng/g lipid) of PCB153. As for estrogenic PCBs, increased PCB52 exposure was positively associated with PR expression (ORT2 = 2.36, Ptrend = 0.054), but higher PCB101 level was negatively associated with HER-2 (ORT3 = 0.24, Ptrend = 0.029) and tumor size (OR = 0.43). Limited dioxin-like PCB138 exposure was positively associated with ER (ORT2 = 3.23, ORT3 = 3.77, Ptrend = 0.047) but negatively with Top-IIα expression (ORT2 = 0.35, ORT3 = 0.28, Ptrend = 0.080). Higher PCB153 (CYP inducer) level was negatively associated with ER (ORT2 = 0.32, ORT3 = 0.19, Ptrend = 0.038) but positively with Ki-67 expression (ORT2 = 1.43, ORT3 = 3.60, Ptrend = 0.055). Higher neurotoxic PCB28 was positively associated with HER-2 (ORT3 = 5.43, Ptrend = 0.006) and tumor size (OR = 2.37). Moreover, total PCBs exposure was positively associated with VEGF-C (ORT2 = 76.91, ORT3 = 97.96, Ptrend = 0.041) and tumor metastasis (OR = 2.25). CONCLUSIONS: Different functional PCB congeners have different associations (both positive and negative) with breast cancer prognostic biomarkers, as well as tumor classification stage. Therefore, the development and aggressiveness of breast cancer may depend upon exposure to specific structure-activity of PCBs.

A transcriptomics-based analysis of toxicity mechanisms of zebrafish embryos and larvae following parental Bisphenol A exposure.

BACKGROUND: Bisphenol A (BPA) is a well-known xenobiotic endocrine disrupting chemical, with estrogenic activity and many other potential biological effects. Although multiple toxicities have been reported for BPA, molecular mechanisms underlying the transgenerational toxic effects of BPA are still underestimated. METHODS: Parental F0 fish were exposed to 1.0 µM BPA or control (0.1% DMSO, v/v) for 7 days. Eggs (F1) were collected and kept in control medium until 4.5 or 120 h post fertilization (hpf). RNA sequencing (RNA-seq) was conducted on embryos and larvae, to discover differentially expressed genes (DEGs), and then KEGG pathway, GO enrichment and GSEA were performed to interpret functional ontology. Histopathology was performed to explore the morphological and structural alterations in liver tissues of zebrafish larvae (120 hpf) after parental BPA exposure. RESULTS: Parental BPA exposure induced global transcriptomic changes in zebrafish embryos and larvae. For embryos, epigenetic regulation genes were decidedly affected, highlighted epigenotoxicity might involve in the transgenerational effects during embryogenesis and early development. By further investigation on its delayed effects, our RNA-Seq data of larvae suggested ROS metabolic process, apoptosis, p53 and MAPK signaling pathway were concentrated, indicating defensive cellular processes still involved in protecting against BPA toxicity. Furthermore, parental BPA-treated larvae manifested hepatic injury by histopathological analysis. CONCLUSIONS: Parental BPA exposure led to global transcriptomic changes involved in epigenetic regulation, oxidative stress, apoptosis and DNA damage of offspring. These findings advanced the field of the parental-mediated subsequent generational toxic effects of BPA.

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.

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.

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.

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.

Association of total testosterone, free testosterone, bioavailable testosterone and sex hormone-binding globulin with hepatic steatosis and the ratio of aspartate aminotransferase to alanine aminotransferase.

Several articles have shown the inverse association between total testosterone (TT) or sex hormone-binding globulin (SHBG) and hepatic steatosis. No articles report associations of TT, SHBG, free testosterone (FT), and bioavailable testosterone (BioT) with aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratios. Therefore, we investigated the associations of TT, FT, BioT and SHBG with hepatic steatosis and AST/ALT ratios. A total of 218 men were enrolled. We diagnosed hepatic steatosis by ultrasound. TT and SHBG showed a reduced risk for hepatic steatosis when analyzed with or without adjusting for age, smoking, alcohol consumption and physical activity. Compared with the lowest quartile, the ORs for hepatic steatosis in the third and fourth quartiles (0.32 [95% CI: 0.14-0.75] and 0.27 [95% CI: 0.10-0.73], respectively) of SHBG were significantly lower after adjustments. The OR for hepatic steatosis in the fourth quartile of TT (0.41 [95% CI: 0.17-0.95]) was significantly lower than in the lowest quartile after adjustments. The mean AST/ALT ratios in men with hepatic steatosis were lower than those without hepatic steatosis (0.83 and 1.04, respectively), due to the elevated ALT levels in hepatic steatosis groups. Furthermore, TT and SHBG were positively associated with AST/ALT ratios with and without adjustments. In conclusion, higher TT and SHBG levels in men are associated with the reduced risk of hepatic steatosis and elevated AST/ALT ratios, independent of age, smoking, alcohol consumption and physical activity.

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.

Predictable weathering of puparial hydrocarbons of necrophagous flies for determining the postmortem interval: a field experiment using Chrysomya rufifacies.

Preadult development of necrophagous flies is commonly recognized as an accurate method for estimating the minimum postmortem interval (PMImin). However, once the PMImin exceeds the duration of preadult development, the method is less accurate. Recently, fly puparial hydrocarbons were found to significantly change with weathering time in the field, indicating their potential use for PMImin estimates. However, additional studies are required to demonstrate how the weathering varies among species. In this study, the puparia of Chrysomya rufifacies were placed in the field to experience natural weathering to characterize hydrocarbon composition change over time. We found that weathering of the puparial hydrocarbons was regular and highly predictable in the field. For most of the hydrocarbons, the abundance decreased significantly and could be modeled using a modified exponent function. In addition, the weathering rate was significantly correlated with the hydrocarbon classes. The weathering rate of 2-methyl alkanes was significantly lower than that of alkenes and internal methyl alkanes, and alkenes were higher than the other two classes. For mono-methyl alkanes, the rate was significantly and positively associated with carbon chain length and branch position. These results indicate that puparial hydrocarbon weathering is highly predictable and can be used for estimating long-term PMImin.