Integrated mRNA- and miRNA-sequencing analyses unveil the underlying mechanism of tobacco pollutant-induced developmental toxicity in zebrafish embryos.

Tobacco pollutants are prevalent in the environment, leading to inadvertent exposure of pregnant females. Studies of these pollutants' toxic effects on embryonic development have not fully elucidated the potential underlying mechanisms. Therefore, in this study, we aimed to investigate the developmental toxicity induced by cigarette smoke extract (CSE) at concentrations of 0.25, 1, and 2.5% using a zebrafish embryo toxicity test and integrated transcriptomic analysis of microRNA (miRNA) and messenger RNA (mRNA). The findings revealed that CSE caused developmental toxicity, including increased mortality and decreased incubation rate, in a dose-dependent manner. Moreover, CSE induced malformations and apoptosis, specifically in the head and heart of zebrafish larvae. We used mRNA and miRNA sequencing analyses to compare changes in the expression of genes and miRNAs in zebrafish larvae. The bioinformatics analysis indicates that the mechanism underlying CSE-induced developmental toxicity was associated with compromised genetic material damage repair, deregulated apoptosis, and disturbed lipid metabolism. The enrichment analysis and RT-qPCR show that the ctsba gene plays a crucial function in embryo developmental apoptosis, and the fads2 gene mainly regulates lipid metabolic toxicity. The results of this study improve the understanding of CSE-induced developmental toxicity in zebrafish embryos and contribute insights into the formulation of novel preventive strategies against tobacco pollutants during early embryonic development.

Construction of a novel S-type γ-Bi2O3/CeO2 heterojunction for highly efficient photocatalytic degradation of antibiotics.

Cubic nanoparticles of CeO2 were partly covered on the tetrahedron surface of γ-Bi2O3 through a hydrothermal reaction and then a calcination process to construct a novel S-type γ-Bi2O3/CeO2 heterojunction. The optimized sample removed 96% of lomefloxacin and 81% of tetracycline. During the cycling test, the photocatalytic efficiency of lomefloxacin and tetracycline was maintained above 87% and 80%, respectively, for five consecutive cycles. According to XRD and Raman spectra characterization, the sample after cycling held a stable crystal structure. Holes, OH-˙, O2˙, and electrons participated in the degradation of lomefloxacin, while tetracycline was removed via the effect of the former three active substances. Based on theoretical calculation and experimental tests, the excellent photocatalytic activity of γ-Bi2O3/CeO2 came from the fast transfer of charge carriers along the S-type path. Moreover, the CB electrons of γ-Bi2O3 and VB holes of CeO2 were preserved to generate free radicals for antibiotic degradation. The colony numbers of Escherichia coli were 1.50 × 10-6 CFU mL-1 and 1.39 × 10-6 CFU mL-1 in solutions after the degradation of the two pollutants, which represents the non-toxicity of the final products. The γ-Bi2O3/CeO2 sample has a potential application for antibiotic removal from modern sewage.

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.

CBX3 promotes clear cell renal carcinoma through PI3K/AKT activation and aberrant immunity.

BACKGROUND: A chromobox homologue 3 (CBX3) is elevated in various cancers and significantly contributes to the promotion of malignant behavior; despite this, its exact involvement in clear cell renal cell carcinoma (ccRCC) is yet unknown. METHODS: The Cancer Genome Atlas database served to evaluate CBX3 production and its connection to survival in patients with ccRCC. Our team evaluated the effects of knockdown of CBX3 levels in ccRCC cell populations using in vitro together with in vivo models. CBX3, proteins related to death, and epithelial-to-mesenchymal transition (EMT)-related proteins were measured in ccRCC cells using western blotting and immunohistochemical assays. Through the analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) and GeneOntology (GO) and Gene Set Enrichment Analysis (GSEA), the biological processes and signal pathways related to CBX3 expression were identified. Immune-related activity reduced by CBX3 was assessed using various online tools. RESULTS: Both genomic and protein expression showed that CBX3 was upregulated in ccRCC. Further functional analyses revealed that CBX3 played a crucial role in enhancing cell growth, migration, and EMT in vitro along with in vivo. Moreover, the study results provided distinct mechanistic evidence that CBX3 exerts its pathological functions in ccRCC by activating the PI3K/AKT pathway. Finally, immunoassays revealed that CBX3, a possible biomarker of ccRCC, was significantly associated with immunity. CONCLUSIONS: Our results suggest that the overexpression of CBX3 promotes ccRCC advancement through PI3K/AKT activation and even immunological dysregulation, making it a potentially viable and beneficial therapeutic target.

Frequency-domain-resolved investigation of unitary h-shaped pulses.

We experimentally investigate the generation of h-shaped pulse in an all-polarization-maintaining (PM) and all-normal-dispersion (ANDi) mode-locked fiber laser. The generated pulse is demonstrated to be a unitary pulse, instead of a noise-like pulse (NLP). Furthermore, by employing an external filtering system, the obtained h-shaped pulse can be resolved into rectangular-shaped pulses, chair-like pulses, and Gaussian pulses. The authentic AC traces with a double-scale structure of unitary h-shaped pulses and chair-like pulses are observed on the autocorrelator. The chirp of h-shaped pulses is also proved similar to that of DSR pulses. To the best of our knowledge, this is the first time that the existence of unitary h-shaped pulse generation has been confirmed. Moreover, our experimental results reveal the close relationship of formation mechanisms of dissipative soliton resonance (DSR) pulses, h-shaped pulses, and chair-like pulses, which helps to unify the essences of such "DSR-like" pulses.

976†nm all-polarization-maintaining mode-locked fiber laser based on nonlinear polarization evolution.

An all-polarization-maintaining (PM) mode-locked fiber laser based upon nonlinear polarization evolution (NPE) that operates around 976 nm is presented. The NPE-based mode-locking is realized using a special section of the laser which comprises three pieces of PM fibers with specific deviation angles between the polarization axes and a polarization-dependent isolator. By optimizing the NPE section and adjusting the pump power, dissipative soliton (DS) pulses with a pulse duration of ∼6 ps, a spectral bandwidth of >10 nm and a maximum pulse energy of 0.54 nJ are generated. Self-starting, steady mode-locking operation is achievable within a pump power range of ∼2 W. Moreover, by incorporating a segment of passive fiber into the appropriate location in the laser resonator, an intermediate regime between stable single-pulse mode-locking and noise-like pulse (NLP) is realized in the laser. Our work expands the dimension of the research on the mode-locked Yb-doped fiber laser operating around 976 nm.

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.

Tunable mode-locked Tm-doped fiber laser based upon cross-phase modulation.

We demonstrate the generation of soliton and dissipative soliton in an ultrafast thulium (Tm) doped fiber laser based upon cross-phase modulation (XPM) induced mode-locking. The mode-locking is realized by periodically modulating the 2-µm signal through XPM that is activated by an injected 1.5-µm pulsed laser. Such a mechanism enables the laser to be mode-locked in various operation regimes without any real or artificial saturable absorbers. Thanks to the XPM pulling effect, the wavelength of the Tm-doped fiber laser can be tuned by adjusting the repetition frequency of the 1.5-µm pulsed laser. The maximum tuning ranges achieved in this work for the soliton and dissipative soliton regimes are respectively 11 nm and 15 nm. The outcomes of this work not only provide a continuously and controllably wavelength-tunable ultrafast laser but also offer a passively synchronized dual-color fiber laser system, which is promised for many important applications such as Raman spectroscopy, nonlinear frequency conversion systems, and multi-color pump-probe systems.

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.

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.

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.

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.