Application of Se-Met to CdTe QDs significantly reduces toxicity by modulating redox balance and inhibiting apoptosis.

Cadmium tellurium quantum dots (CdTe QDs) as one of the most widely used QDs have been reported the toxicity and biosafety in recent years, little work has been done to reduce their toxicity however. Based on the mechanisms of toxicity of CdTe QDs on liver target organs such as oxidative stress and apoptosis previously reported by other researchers, we investigated the mechanism of action of trace element selenium (Se) to mitigate the hepatotoxicity of CdTe QDs. The experimental results showed that Se-Met at 40-140 µg L-1 could enhance the function of intracellular antioxidant defense system and the molecular structure of related antioxidant enzymes by reduce the production of ROS by 45%, protecting the activity of antioxidants and up-regulating the expression of selenoproteins with antioxidant functions, Gpx1 increase 225% and Gpx4 upregulated 47%. In addition, Se-Met could alleviate CdTe QDs-induced apoptosis by regulating two apoptosis-inducing factors, as intracellular caspase 3/9 expression levels were reduced by 70% and 87%, decreased Ca2+ concentration, and increased mitochondrial membrane potential measurements. Overall, this study indicates that Se-Met has a significant protective effect on the hepatotoxicity of CdTe QDs. Se-Met can be applied to the preparation of CdTe QDs to inhibit its toxicity and break the application limitation.

Widespread of Potential Pathogen-Derived Extracellular Vesicles Carrying Antibiotic Resistance Genes in Indoor Dust.

Extracellular vesicles (EVs) are newly recognized as important vectors for carrying and spreading antibiotic resistance genes (ARGs). However, the ARGs harbored by EVs in ambient environments and the transfer potential are still unclear. In this study, the prevalence of ARGs and mobile genetic elements (MGEs) in EVs and their microbial origins were studied in indoor dust from restaurants, kindergarten, dormitories, and vehicles. The amount of EVs ranged from 3.40 × 107 to 1.09 × 1011 particles/g dust. The length of EV-associated DNA fragments was between 21 bp and 9.7 kb. Metagenomic sequencing showed that a total of 241 antibiotic ARG subtypes encoding resistance to 16 common classes were detected in the EVs from all four fields. Multidrug, quinolone, and macrolide resistance genes were the dominant types. 15 ARG subtypes were exclusively carried and even enriched in EVs compared to the indoor microbiome. Moreover, several ARGs showed co-occurrence with MGEs. The EVs showed distinct taxonomic composition with their original dust microbiota. 30.23% of EV-associated DNA was predicted to originate from potential pathogens. Our results indicated the widespread of EVs carrying ARGs and virulence genes in daily life indoor dust, provided new insights into the status of extracellular DNA, and raised risk concerns on their gene transfer potential.

Perfluorinated compounds disrupted osmoregulation in Oryzias melastigma during acclimation to hypoosmotic environment.

Perfluorinated compounds (PFCs) are a type of ubiquitous contaminants spreading in the estuarine and coastal areas. Anadromous fish should deal with hypoosmotic challenge with PFCs stress during their migration from seawater to estuaries. However, few studies have been carried out to investigate the adverse impact of PFCs on fish osmoregulation and the underlying mechanism. In this study, Oryzias melastigma, an euryhaline fish model, were exposed to four representative PFC congeners including perfluorobutane sulfonate (PFBS), perfluorooctane sulfonates (PFOS), perfluorooctanoic acid (PFOA), and perfluorododecanoic acid (PFDoA) separately under both seawater and freshwater conditions. Histopathological changes in gills, ion homeostasis, Na+/K+-ATPase (NKA) activity, as well as the expression of related genes was detected upon exposure. Results showed that PFCs induced morphological changes in gills, disturbed the levels of major ions (Na+, Ca2+, Mg2+), and inhibited the NKA activity. Transcriptome analysis in fish gills during the acclimation to freshwater revealed that PFCs influenced the osmoregulation mainly by interfering with the endocrine system, signal transduction, as well as cellular community and motility. Validation with qRT-PCR confirmed that the mRNA expressions of osmoregulatory genes encoding hormones and receptors, as well as ion transmembrane transporters were disturbed by PFCs. Longer chain homolog (PFOS) showed a greater impact on osmoregulation than the shorter chain homolog (PFBS). Within the same carbon chain, sulfonic congener (PFOS) induced more serious injury to gills than carboxylic congener (PFOA). The interaction between PFCs and salinity varied in different adverse outcome. These results help to further understand the mechanism of how PFCs influence osmoregulation and elicit the need to assess the ecological risk of PFCs and other pollutants on anadromous migration.

A Multi-Level Feature Fusion Network for Remote Sensing Image Segmentation.

High-resolution remote sensing image segmentation is a mature application in many industrial-level image applications and it also has military and civil applications. The scene analysis needs to be automated as much as possible with high-resolution remote sensing images. This plays a significant role in environmental disaster monitoring, forestry industry, agricultural farming, urban planning, and road analysis. This study proposes a multi-level feature fusion network (MFNet) that can integrate the multi-level features in the backbone to obtain different types of image information. Finally, the experiments in this study demonstrate that the proposed network can achieve good segmentation results in the Vaihingen and Potsdam datasets. By aiming to achieve a large difference in the scale of the target objects in remote sensing images and achieving a poor recognition result for small objects, a multi-level feature fusion solution is proposed in this study. This investigation improves the recognition results of the remote sensing image segmentation to a certain extent.

Benzo[a]pyrene at human blood equivalent level induces human lung epithelial cell invasion and migration via aryl hydrocarbon receptor signaling.

Benzo[a]pyrene (B[a]P), a typical carcinogenic polycyclic aromatic hydrocarbon, exists worldwide in vehicle exhaust, cigarette smoke and other polluted environments. Recent studies have demonstrated a strong association between B[a]P and lung cancer. However, whether B[a]P at human blood equivalent level can promote epithelial-mesenchymal transition (EMT), a crucial molecular event during cell malignant transformation, remains unclear. Besides, whether B[a]P facilitates this progress via aryl hydrocarbon receptor (AhR) signaling pathway also lacks scientific evidence. In our study, the transwell assay showed that 5 µg/L of B[a]P promoted BEAS-2B cell invasion and migration. In addition, the mRNA and protein expression levels of AhR and its target genes involved in B[a]P metabolism, such as AhR nuclear translocator, heat shock protein 90 and CYP1A1, were significantly increased by B[a]P exposure. Moreover, the mRNA expression levels of downstream regulatory factors related to both AhR signaling pathway and EMT, such as NRF2, K-RAS and hypoxia-inducible factor 1-alpha, were significantly increased. Furthermore, the expression level of the epithelial marker E-cadherin was significantly downregulated, while the mRNA expression of mesenchymal phenotype markers, N-cadherin, fibronectin and vimentin, were significantly upregulated. Notably, the above changes induced by B[a]P were significantly attenuated or even stopped by resveratrol (RSV), a natural phenol, also an AhR inhibitor, when the AhR signaling pathway was inhibited by RSV, demonstrating the regulatory role of AhR signaling pathway in B[a]P-induced EMT. In conclusion, B[a]P at the human blood equivalent level induces BEAS-2B cell invasion and migration through the AhR signaling pathway.

Gut microbiota health closely associates with PCB153-derived risk of host diseases.

Although the production and use of PCB153 have been banned globally, PCB153 pollution remains because of its persistence and long half-life in the environment. There is ongoing evidence that exposure to PCB153 may influence gut microbiota health and increase the risk of host health. It is needed to illuminate whether there are associations between gut microbiota dysregulation and PCB153-induced host diseases. Importantly, it is urgently needed to find specific strains as biomarkers to monitor PCB153 pollution and associated disorders. The work aims to investigate the change of gut microbiota composition, structure and diversity and various host physiological indexes, to ravel the chain causality of PCB153, gut microbiota health and host health, and to find potential gut microbiota markers for PCB153 pollution. Here, adult female mice were administrated with PCB153. Obtained results indicated that PCB153 led to gut microbiota health deterioration. PCB153 exposure also induced obesity, hepatic lipid accumulation, abdominal adipose tissue depots and dyslipidemia in mice. Furthermore, specific gut microbiota significantly correlated with the host health indexes. This work provides support for the relationship between gut microbiota aberrance derived from PCB153 and risk of host health, and offers some indications of possible indicative functions of gut microbiota on PCB153 pollution.

Resveratrol inhibits lipid accumulation in the intestine of atherosclerotic mice and macrophages.

Disordered intestinal metabolism is highly correlated with atherosclerotic diseases. Resveratrol protects against atherosclerotic diseases. Accordingly, this study aims to discover novel intestinal proatherosclerotic metabolites and potential therapeutic targets related to the anti-atherosclerotic effects of resveratrol. An untargeted metabolomics approach was employed to discover novel intestinal metabolic disturbances during atherosclerosis and resveratrol intervention. We found that multiple intestinal metabolic pathways were significantly disturbed during atherosclerosis and responsive to resveratrol intervention. Notably, resveratrol abolished intestinal fatty acid and monoglyceride accumulation in atherosclerotic mice. Meanwhile, oleate accumulation was one of the most prominent alterations in intestinal metabolism. Moreover, resveratrol attenuated oleate-triggered accumulation of total cholesterol, esterified cholesterol and neutral lipids in mouse RAW 264.7 macrophages by activating ABC transporter A1/G1-mediated cholesterol efflux through PPAR (peroxisome proliferator-activated receptor) α/γ activation. Furthermore, we confirmed that PPARα and PPARγ activation by WY14643 and pioglitazone, respectively, alleviated oleate-induced accumulation of total cholesterol, esterified cholesterol and neutral lipids by accelerating ABC transporter A1/G1-mediated cholesterol efflux. This study provides the first evidence that resveratrol abolishes intestinal fatty acid and monoglyceride accumulation in atherosclerotic mice, and that resveratrol suppresses oleate-induced accumulation of total cholesterol, esterified cholesterol and neutral lipids in macrophages by activating PPARα/γ signalling.

Peroxisome proliferator-activated receptor A/G reprogrammes metabolism associated with lipid accumulation in macrophages.

INTRODUCTION: Macrophage metabolism contributes to the progression of metabolic diseases, and peroxisome proliferator-activated receptors (PPARs) play vital roles in macrophage metabolism and the treatment of metabolic diseases. However, the role of PPARs in metabolic reprogramming related to lipid accumulation in macrophages, a key pathological event in metabolic diseases, remains unclear. OBJECTIVES: We aimed to identify PPAR-mediated metabolic reprogramming and potential therapeutic targets associated with lipid accumulation in macrophages. METHODS: Following treatment with oleate, oleate + WY-14643 and oleate + pioglitazone to induce alterations in PPAR signaling, lipids and relevant metabolism, macrophage samples were analyzed employing an untargeted metabolomics based on gas chromatography-mass spectrometry. RESULTS: The metabolomics approach revealed that multiple metabolic pathways were altered during lipid accumulation in oleate-treated macrophages and responsive to WY-14643 and pioglitazone treatment. Notably, levels of most metabolites involved in amino acid metabolism and nucleotide metabolism were accumulated in oleate-treated macrophages, and these effects were alleviated or abolished by PPARA/G activation. Additionally, during oleate-induced lipid accumulation and lipid lowering with WY-14643 and pioglitazone in macrophages, levels of most amino acids were positively associated with neutral lipid, total cholesterol, cholesterol ester, total free fatty acid and triglyceride levels but negatively associated with expression of genes related to PPARA/G signaling. Furthermore, glycine was found to be a potential biomarker for assessing lipid accumulation and the lipid-lowering effects of PPARA/G in oleate-treated macrophages. CONCLUSION: The results of this study revealed a high correlation of amino acid metabolism with lipid accumulation and the lipid-lowering effects of PPARA/G in macrophages.

Sex hormones affect endothelial lipase-mediated lipid metabolism and atherosclerosis.

BACKGROUND: Endothelial lipase (EL) plays an important role in lipoprotein metabolism and atherosclerosis. To study the functional roles of EL, we recently generated transgenic (Tg) rabbits and reported that increased hepatic expression of EL in male Tg rabbits significantly reduced diet-induced hypercholesterolemia compared with non-Tg controls. This gender difference suggests that sex hormones may mediate EL functions thereby influencing lipoprotein metabolism. To examine this hypothesis, we compared the effects of orchiectomy and ovariectomy on plasma lipids and diet-induced atherosclerosis in both Tg and non-Tg rabbits. METHODS: Male rabbits were under orchiectomy whereas female rabbits were under ovariectomy. We compared plasma lipids, lipoproteins, and apolipoproteins of rabbits before and after surgery in each group fed either a chow diet or cholesterol-rich diet. RESULTS: On a chow diet, both male and female Tg rabbits showed lower plasma lipids than non-Tg counterparts and this lipid-lowering effect of EL was not affected by either orchiectomy in male or ovariectomy in female Tg rabbits. On a cholesterol diet; however, male Tg rabbits but not female Tg rabbits showed significant resistance to diet-induced hypercholesterolemia and atherosclerosis. The EL-mediated atheroprotective effect was eliminated after orchiectomy in male Tg rabbits. Female Tg rabbits showed similar levels of total cholesterol and lesion size of atherosclerosis compared with non-Tg rabbits and ovariectomy did not affect diet-induced hypercholesterolemia or atherosclerosis. CONCLUSION: These results suggest that increased EL protects against diet-induced hypercholesterolemia and atherosclerosis. The beneficial effect of EL was dependent upon the presence of androgenic hormones.

Metabolomics Reveals Protection of Resveratrol in Diet-Induced Metabolic Risk Factors in Abdominal Muscle.

BACKGROUND/AIMS: Abdominal obesity is recognized as the main reason of metabolic syndrome, which is closely related to disordered skeletal and/or abdominal muscle metabolic functions. Metabolomics is a comprehensive assessment system in biological metabolites. The aim of our present study is to investigate the diet-induced metabolic risk factors by metabolic in the abdominal muscles and clarify the relationship between atheroprotective effects of Resveratrol (Rev) and abdominal muscles metabolic components during the development of atherosclerosis. METHODS: The mice were randomly divided into three groups including normal group (N), high fat diet (HFD or H) group and high fat diet with Rev treated group (HR). GC-MS combined with pattern recognition approaches were employed to obtain comprehensive metabolic signatures and related differential metabolites after 24 week HFD feeding. Oil Red O staining and Electron microscopy technology (EMT) were employed to detect the size of fatty plaques and intracellular lipid accumulation, respectively. RESULTS: The result indicated that 22 types of metabolites in the abdominal muscles were obviously altered by HFD feeding group. Moreover, Rev treatment obviously increased 11 different kinds of metabolites, most of which were involved in the carbohydrate, amino acid and lipid metabolisms. Importantly, these elevated different metabolites were involved in pathways mainly related to galactose metabolism, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism in abdominal muscles. Oil Red O staining and Electron microscopy showed less lipid accumulation in the lesions and decreased intracellular lipid deposition in the foam cells in HR group. CONCLUSIONS: We concluded that Rev produced a beneficial effect partially by modulating multiple metabolism pathways and metabolites in the abdominal muscles, which may provide a new protective mechanism of Rev on the progression of atherosclerosis. These notably changed metabolites might be potential biomarkers or therapeutic targets during development of metabolic syndrome and atherosclerosis.

MiR-26a functions as a tumor suppressor in ambient particulate matter-bound metal-triggered lung cancer cell metastasis by targeting LIN28B-IL6-STAT3 axis.

Exposure to ambient particulate matter (PM) has been linked to the increasing incidence and mortality of lung cancer, but the principal toxic components and molecular mechanism remain to be further elucidated. In this study, human lung adenocarcinoma A549 cells were treated with serial concentrations of water-extracted PM10 (WE-PM10) collected from Beijing, China. Our results showed that exposure to 25 and 50 µg/ml of WE-PM10 for 48 h significantly suppressed miR-26a to upregulate lin-28 homolog B (LIN28B), and in turn activated interleukin 6 (IL6) and signal transducer and activator of transcription 3 (STAT3) in A549 cells, subsequently contributing to enhanced epithelial-mesenchymal transition and accelerated migration and invasion. In vivo pulmonary colonization assay further indicated that WE-PM10 enhanced the metastatic ability of A549 cells. In addition, luciferase reporter assay demonstrated that 3' untranslated region of LIN28B was a direct target of miR-26a. Last but not the least, the key toxic contribution of metals in WE-PM10 was confirmed by the finding that removal of metals through chelation significantly rescued WE-PM10-mediated inflammatory, carcinogenic and metastatic responses. Taken together, miR-26a could act as the tumor suppressor in PM10-related lung cancer, and PM10-bound metals promoted lung cancer cell metastasis through downregulation of miR-26a that directly mediated LIN28B expression.

Emerging roles of long non-coding RNAs in the toxicology of environmental chemicals.

Environmental chemicals (ECs) are drawing great attention to their effects on health and their toxicological mechanisms are being investigated. Long non-coding RNA (lncRNA) is a class of RNA with more than 200 nucleotides and does not have protein coding potential. Recently, it is emerging as a star molecule that participates in a wide range of physiological and pathological processes. It has been reported to be abnormally expressed in diseases. As an epigenetic factor, lncRNAs play an important role in the response of organisms to environmental stress. Their roles in the toxicity of ECs are being identified. Altered expression profiles of lncRNAs have been explored after exposure to ECs. Various kinds of ECs are reported to disturb the expression of lncRNAs in vitro and in vivo. Then, dysregulated lncRNAs can affect the expression of target genes directly or indirectly via regulating the level of microRNAs. The network among lncRNAs, microRNAs and mRNAs can initiate or impede specific signaling pathway and lead to adverse outcome upon exposure to ECs. Recovery of the lncRNAs level by overexpression or knockdown technology diminished the effect induced by ECs. In the review, biological roles of lncRNAs are depicted. The lncRNAs involved in the toxicology are summarized. Types of ECs that have been reported to affect the expression of lncRNAs are categorized. The interaction between various types of ECs and lncRNAs is discussed.

Environmental risk assessment of selected organic chemicals based on TOC test and QSAR estimation models.

Environmental risks of organic chemicals have been greatly determined by their persistence, bioaccumulation, and toxicity (PBT) and physicochemical properties. Major regulations in different countries and regions identify chemicals according to their bioconcentration factor (BCF) and octanol-water partition coefficient (Kow), which frequently displays a substantial correlation with the sediment sorption coefficient (Koc). Half-life or degradability is crucial for the persistence evaluation of chemicals. Quantitative structure activity relationship (QSAR) estimation models are indispensable for predicting environmental fate and health effects in the absence of field- or laboratory-based data. In this study, 39 chemicals of high concern were chosen for half-life testing based on total organic carbon (TOC) degradation, and two widely accepted and highly used QSAR estimation models (i.e., EPI Suite and PBT Profiler) were adopted for environmental risk evaluation. The experimental results and estimated data, as well as the two model-based results were compared, based on the water solubility, Kow, Koc, BCF and half-life. Environmental risk assessment of the selected compounds was achieved by combining experimental data and estimation models. It was concluded that both EPI Suite and PBT Profiler were fairly accurate in measuring the physicochemical properties and degradation half-lives for water, soil, and sediment. However, the half-lives between the experimental and the estimated results were still not absolutely consistent. This suggests deficiencies of the prediction models in some ways, and the necessity to combine the experimental data and predicted results for the evaluation of environmental fate and risks of pollutants.

Epithelial-mesenchymal transition effect of fine particulate matter from the Yangtze River Delta region in China on human bronchial epithelial cells.

Epidemiological studies have demonstrated that fine particulate matter (PM2.5) exposure causes airway inflammation, which may lead to lung cancer. The activation of epithelial-mesenchymal transition (EMT) is assumed to be a crucial step in lung tumor metastasis and development. We assessed the EMT effect of low concentrations (0, 0.1, 1.0, and 5.0µg/mL) of PM2.5 organic extract on a human bronchial epithelial cell line (BEAS-2B). PM2.5 samples were collected from three cities (Shanghai, Ningbo, and Nanjing) in the Yangtze River Delta (YRD) region in autumn 2014. BEAS-2B cells were exposed to the PM2.5 extract to assess cell viability, invasion ability as well as the relative mRNA and protein expressions of EMT markers. Our findings revealed that BEAS-2B cells changed from the epithelial to mesenchymal phenotype after exposure. In all groups, PM2.5 exposure dose-dependently decreased the expression of E-cadherin and increased the expression of Vimentin. The key transcription factors, including ZEB1 and Slug, were significantly up-regulated upon exposure. These results indicated that the PM2.5 organic extract induced different degrees of EMT progression in BEAS-2B cells. The cell invasion ability increased in a concentration-dependent manner after 48hr of treatment with the extract. This study offers a novel insight into the effects of PM2.5 on EMT and the potential health risks associated with PM2.5 in the YRD region.

Downregulation of miR-192 causes hepatic steatosis and lipid accumulation by inducing SREBF1: Novel mechanism for bisphenol A-triggered non-alcoholic fatty liver disease.

Exposure to Bisphenol A (BPA) has been associated with the development of nonalcoholic fatty liver disease (NAFLD) but the underlying mechanism remains unclear. Given that microRNA (miRNA) is recognized as a key regulator of lipid metabolism and a potential mediator of environmental cues, this study was designed to explore whether exposure to BPA-triggered abnormal steatosis and lipid accumulation in the liver could be modulated by miR-192. We showed that male post-weaning C57BL/6 mice exposed to 50µg/kg/day of BPA by oral gavage for 90days displayed a NAFLD-like phenotype. In addition, we found in mouse liver and human HepG2 cells that BPA-induced hepatic steatosis and lipid accumulation were associated with decreased expression of miR-192, upregulation of SREBF1 and a series of genes involved in de novo lipogenesis. Downregulation of miR-192 in BPA-exposed hepatocytes could be due to defective pre-miR-192 processing by DROSHA. Using HepG2 cells, we further confirmed that miR-192 directly acted on the 3'UTR of SREBF1, contributing to dysregulation of lipid homeostasis in hepatocytes. MiR-192 mimic and lentivirus-mediated overexpression of miR-192 improved BPA-induced hepatic steatosis by suppressing SREBF1. Lastly, we noted that lipid accumulation was not a strict requirement for developing insulin resistance in mice after BPA treatment. In conclusion, this study demonstrated a novel mechanism in which NAFLD associated with BPA exposure arose from alterations in the miR-192-SREBF1 axis.

Dioxin-like rather than non-dioxin-like PCBs promote the development of endometriosis through stimulation of endocrine-inflammation interactions.

Polychlorinated biphenyls (PCBs) contain 209 congeners with various structure-activities. Exposure to PCBs was related to disorders of female reproduction. Endometriosis (EM) is an estrogen- and inflammation-dependent disease with high prevalence and severe health outcomes. Epidemiological studies have shown the effects of PCBs exposure on EM in regard to various structures of PCBs. However, little evidence is available from the toxicology considering the structure of PCBs. In the study, environmentally relevant concentrations of PCBs were used to treat primary cultured endometrial cells and an EM mouse model. Dioxin-like CB126, but not non-dioxin-like CB153, significantly enhanced 17ß-estradiol (E2) biosynthesis in a dose-dependent manner. Among the genes related to estrogen metabolism, the level of 17ß-hydroxysteroid dehydrogenase 7 (HSD17B7) showed significant increase following CB126 exposure. We further found that CB126 exposure decreased the methylation of the HSD17B7 promoter. Elevated expression of HSD17B7 was observed in the eutopic endometrium of EM patients. CB126 rather than CB153 triggered the inflammatory response by directly stimulating the secretion of inflammatory factors and indirectly reducing the level of lipoxin A4 (LXA4). Furthermore, the inflammation enhanced the expression of HSD17B7. Antagonism of the aryl hydrocarbon receptor (AhR) diminished the effects induced by CB126. In vivo, the PCB-treated EM mouse model confirmed that CB126 rather than CB153 increased the levels of both E2 and inflammatory factors in peritoneal fluid and promoted the development of endometriotic lesions. In all, CB126, but not CB153, triggered EM development by stimulating estrogen biosynthesis, inflammation and their interactions and that these effects were mediated by the AhR receptor.

Enantiomeric resolution, stereochemical assignment and toxicity evaluation of TPA enantiomers.

Tetrahydro-α-(1-methylethyl)-2-oxo-1(2H)-pyrimidineacetic acid (TPA) is a critical intermediate in the synthesis of HIV protease inhibitors. A simple and efficient method for the separation and determination of TPA enantiomers was developed. The TPA was separated into its enantiomers with an enantiomeric purity of 99% using an HPLC system equipped with a Chiralpak OD-H column. Semi-preparative HPLC enantioseparations were carried out for further enrichment of the enantiomers. The validity of this method was evaluated on the basis of its precision, accuracy, linearity and recovery. The method was observed to be suitable for the rapid separation and semi-preparation of TPA isomers. The separated enantiomers were identified by optical rotation and high-resolution electrospray ionization mass spectrometry. Furthermore, the stereochemical structures of the TPA enantiomers were definitively confirmed using a combination of experimental and calculated electronic circular dichroism spectra. The toxicity of the separated pure enantiomers against Oryzias melastigma was evaluated using the median lethal concentration (LC50 ) values. The results indicated that (S)-(-)-TPA is ~2.5 times more toxic than its enantiomorphism.

Accumulation of di(2-ethylhexyl) phthalate causes endocrine-disruptive effects in marine medaka (Oryzias melastigma) embryos.

Di (2-ethylhexyl) phthalate (DEHP) is extensively distributed in marine environments. However, limited research on the toxicological and molecular effects of DEHP on marine organisms has been conducted. Our study investigated the accumulation, elimination, and endocrine-disruptive effects of DEHP on embryonic marine medaka (Oryzias melastigma). The medaka embryos were continuously exposed to DEHP (0.01, 0.1, and 1 mg/L) or 17ß-estradiol (E2, 0.01 mg/L) until hatching, and the newly hatched larvae were then transferred to clean sea water for 12 days of depuration. DEHP and E2 appeared to have no significant effects on the mortality and hatching rates of medaka embryos, but E2 exposure significantly delayed the hatching. Significantly higher DEHP embryonic burdens were detected in the group treated with higher DEHP (0.1 and 1 mg/L) at 10 dpf (days post fertilization). The recovered larvae showed an elimination tendency of DEHP during the recovery period. DEHP had no significant effects on the transcriptional responses of endocrine-disrupting biomarker genes in the 3-dpf embryos. Treatment with 0.1 and 1 mg/L DEHP elicited a significant induction of transcriptional responses of ER, PPAR, and the CYP19 genes in a concentration-dependent manner at 10 dpf, indicating endocrine disruption may be due to bioaccumulation of DEHP. With the elimination of DEHP during the depuration period, all of the effects on these genes showed no significant effects. However, 0.1 mg/L E2 significantly affected the expression of ER, PPAR, and the CYP19 genes in the exposed embryos at both 3 and 10 dpf and recovered larvae. Therefore, these results demonstrate that accumulation of DEHP caused endocrine disruption in medaka embryos and that recovery in clean sea water may weaken the endocrine-disrupting effects.

In situ combined chemical and biological assessment of estrogenic pollution in a water recycling system.

Estrogenic pollution and its control in aquatic systems have drawn substantial attention around the world. The chemical and biological assessment approaches currently utilized in the laboratory or field cannot give an integrated assessment of the pollution when used separately. In this study, in situ chemical and biological methods were combined to detect pollution in a water recycling system. Data for the water quality index (WQI) demonstrated that the water treatment resulted in the decline of pollution from upstream to downstream. Wild male Nile tilapia, Oreochromis niloticus, was sampled in June and September. The concentrations of four common endocrine disrupting chemicals (EDCs) were determined in the tilapia liver by chromatographic analysis methods. The level of 17ß-estradiol (E2) declined from upstream to downstream in both months. In contrast, the levels of bisphenol A (BPA), di-(2-ethylhcxyl) phthalate (DEHP), and perfluorooctane sulfonate (PFOS) did not display this declining tendency. The highest relative expression of vitellogenin 1 (VTG1) was observed in tilapia from upstream, then the level significantly decreased along the water system. The relative expression levels of CYP1A1 in the water system were also significantly higher than that of the control. However, no declining trend could be observed along the water system. The change of VTG1 expression corresponded well with that of E2 levels in the tilapia liver. Overall, our study assessed the pollution by endocrine disruptors using chemical and biological data with good correspondence. This study also demonstrated the effectiveness of the water recycling system in eliminating estrogen pollution in municipal sewage.

Di(2-ethylhexyl) phthalate-induced apoptosis in rat INS-1 cells is dependent on activation of endoplasmic reticulum stress and suppression of antioxidant protection.

Di(2-ethylhexyl) phthalate (DEHP) is used as plasticizer and is ubiquitously found in the environment. Exposure to DEHP has been linked to an increased incidence of type 2 diabetes. Pancreatic ß-cell dysfunction is a hallmark of type 2 diabetes; however, it is unknown whether DEHP exposure contributes to this risk. Here, we aimed to investigate the cytotoxic effects of DEHP on INS-1 cells and to further explore the related underlying mechanisms. INS-1 cells were exposed to 0, 5, 25, 125 or 625 µM DEHP for 24 hrs. Cell viability, glucose-stimulated insulin secretion, reactive oxygen species (ROS) generation, cellular antioxidant response, Ca(2+) homoeostasis and the levels of genes and proteins involved in endoplasmic reticulum (ER) stress were measured. The results showed that DEHP decreased insulin secretion and content and induced apoptosis in INS-1 cells in a dose-dependent manner. Furthermore, ROS generation was increased and Nrf2-dependent antioxidant defence protection was dysregulated in INS-1 cells after DEHP exposure. Most importantly, DEHP effectively depleted ER Ca(2+) and triggered the ER stress response as demonstrated by the elevated transcription and translation of the ER chaperone GRP78 and GRP94, the increased phosphorylation of protein kinase R-like endoplasmic reticulum kinase (PERK) and its downstream substrate eukaryotic translation initiation factor 2α (eIF2α), as well as the increased levels of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP). Taken together, DEHP exerted toxic effects on INS-1 cells by inducing apoptosis, which is dependent on the activation of the PERK-ATF4-CHOP ER stress signalling pathway and the suppression of Nrf2-dependent antioxidant protection.