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Common pathogenic bacteria contaminate the environment through various modes of transmission. It is thus crucial to develop simple preparation methods of residue-free environmental disinfectants. β-Lactam antibiotics are frequently prescribed in clinical practice to treat bacterial infections. In this study, we used electrochemical exfoliation to synthesize graphene oxide (GO) with abundant ketene functional groups. A residue-free GO-β-lactam (GOβL) was subsequently obtained by mixing ketene and azomethine-H via a [2 + 2] cycloaddition reaction in the aqueous phase. GOβL has shown broad-spectrum bacterial inhibition against four bacteria (

In recent years, graphene oxide quantum dots (GOQDs) have emerged as novel nanomaterials for optical sensing, bioimaging, clinical testing, and environmental testing. However, GOQDs demonstrate unique photoluminescence properties, with GOQDs having quantum limitations and edge effects that often affect the accuracy of the test results in the sensory field. Herein, GOQDs with a large content of hydroxyl groups and low fluorescence intensity were first prepared via an improved Fenton reaction in this study, which introduces a large amount of epoxy groups to break the C–C bonds. The synthesized GOQDs show no significant variation in the fluorescence intensity upon ultraviolet and visible light excitations. We further utilized the GOQDs as fluorescence quenchers for different fluorescent dyes in real-time fluorescence quantitative polymerase chain reaction (qRT-PCR), and verified that the addition of GOQDs (5.3 μg ml−1) into a qRT-PCR system could reduce the background fluorescence intensity of the reaction by fluorescence resonance energy transfer (FRET) during its initial stage and its non-specific amplification, and improve its specificity. In addition, the qRT-PCR method could detect two different lengths of DNA sequences with a high specificity in the 104 to 1010 copies per μl range. It is of paramount importance to carry out further investigations to establish an efficient, sensitive, and specific RT-PCR method based on the use of GOQD nanomaterials as fluorescence quenchers.

Methylparaben (MeP) is one of the most frequently used preservatives in our daily products. However, it is becoming an aquatic pollutant of emerging concern. To reveal the endocrine disruption mechanism and reproductive impairment of MeP, the present study exposed adult zebrafish to 0, 1, 3, and 10 μg/L (0, 6.6, 19.7, and 65.7 nM) of MeP for 28 days. The results showed that subchronic exposure to 10 μg/L of MeP significantly increased the gonadosomatic index in zebrafish. Spermatogenesis and oogenesis were blocked by MeP at concentrations as low as 1 μg/L. Furthermore, parental exposure to MeP induced developmental deficits in offspring larvae, by increasing mortality, stimulating precocious hatching, and elevating heart rate. Blood concentrations of estradiol, testosterone, and 11-keto-testosterone were consistently lowered in MeP exposure groups. Transcriptional results evidenced that the disturbance in steroidogenesis and feedback regulation mechanisms along the hypothalamic-pituitary-gonadal axis underlay the imbalance of sex hormones. In line with the low estradiol level, hepatic production of vitellogenin (VTG) was significantly down-regulated, subsequently leading to a deficiency of VTG supply during oogenesis. To our knowledge, this is the first study to provide systemic insight about the antiestrogenic activity and reproductive toxicity of MeP.

The aging process leads to the gradual impairment of physiological functions in the elderly, making them more susceptible to the toxicity of environmental pollutants. In this study, aged zebrafish were first transplanted with the feces from young donors and subsequently exposed to perfluorobutanesulfonate (PFBS), an emerging persistent toxic pollutant. The interaction between young fecal transplant and PFBS inherent toxicity was investigated, focusing on reproductive performance and the underlying endocrine mechanism. The results showed that PFBS single exposure increased the percentage of primary oocytes in aged ovaries, implying a blockage of oogenesis. However, transplantation of young feces completely abolished the effects of PFBS and promoted oocyte growth, as inferred by the obviously lower percentage of primary oocytes, accompanied by a higher percentage of cortical-alveolar oocytes. Measurement of sex hormones found that PFBS significantly increased the blood concentration of estradiol and disrupted the balance of sex hormones in the elderly, which were, however, efficiently ameliorated by young fecal transplantation. Based on gene transcription along the hypothalamic-pituitary-gonadal axis, hierarchical clustering analysis showed similar profiles of the reproductive endocrine system between young zebrafish and their aged counterparts transplanted with young feces, implying that young fecal transplantation might refresh the endocrine system of aged recipients, regardless of PFBS exposure. The increased transcription levels of mRNAs encoding vitellogenin, activinBA, and membrane bound progestin receptors would cooperatively enhance the growth and maturation of oocytes in the ovaries of aged zebrafish receiving young fecal transplantation. Overall, the findings highlighted the potent efficacy of young fecal transplantation to improve the reproductive function of the elderly and to mitigate the endocrine disruption of an environmental pollutant. These findings are expected to broaden our understanding of the efficacy, mechanisms, and application of fecal transplantation.

Paraben preservatives have been listed as emerging pollutants due to their ubiquity in various environmental matrices, especially the water bodies. How to efficiently and practically eliminate these paraben pollutants is therefore of great importance. Herein, a designed S-scheme heterojunction photocatalyst, consisting of graphitic carbon nitride (g-C

Probiotic supplements are able to attenuate the developmental toxicity of perfluorobutanesulfonate (PFBS) pollutant. However, the underlying mechanisms remain unexplored. To this end, the present study acutely exposed zebrafish larvae for 4 days to 0 and 10 mg/L of PFBS, with or without the addition of probiotic Lactobacillus rhamnosus in the rearing water. The metabolomics approach was used to reveal the combined effects of PFBS and probiotics on metabolic dynamics, based on which gene transcriptions, enzymatic activities, and behavioral endpoints were further examined. The results showed that probiotic supplements were the major driver of the metabolomic fingerprints in coexposed zebrafish larvae. The addition of probiotic bacteria significantly decreased the methylation potential whilst up-regulating the demethylation process of genomic DNA, which may globally stimulate the gene expression to improve somatic growth. Acute exposure to PFBS significantly increased the cortisol concentration in zebrafish larvae, subsequently inducing stress response and hyperactive behavior. In contrast, probiotic supplementation promoted the degradation of cortisol, thus alleviating the stressful state. Antagonistic action of probiotics against PFBS developmental toxicity was also noted regarding the locomotor behavior. In addition, gut microbiota-mediated production of secondary bile acids was remarkably enhanced by probiotic supplements regardless of PFBS exposure. Overall, the present study underlines the efficacy of probiotic bacteria to protect zebrafish larvae from the metabolic disturbances of PFBS, thereby providing more evidence to support the application of probiotics in aquaculture and fishery as an environmentally-friendly choice.

Perfluorobutanesulfonate (PFBS) is an emerging pollutant of potent toxicity to impair visual system. Previous studies highlighted the applicability of gut microbiota manipulation to mitigate the toxicities of PFBS. However, it remains unknown whether transplantation of whole fecal microbiota to PFBS-disturbed gut can restore the health of the recipient animals, especially for aged fish that are of high susceptibility. In the present study, aged zebrafish of 3 years old were first transplanted with feces from young counterparts and then exposed to environmentally relevant concentrations of PFBS. After exposure, toxic effects of PFBS on visual system of aged zebrafish were elucidated based on transcriptional, proteomic, biochemical, histological, and behavioral evidences. In addition, interaction between young fecal transplant and innate visual toxicity of PFBS was further explored in the aged. The results showed that PFBS singular exposure induced lipid peroxidation (by 1.9-fold) in aged male eyes, which were alleviated by young fecal transplantation. PFBS also disturbed the retinal structure of the aged, which was characterized by increases in plexiform layers, but decreases in ganglion neuron number (by 26.8% and 26.0% in males and females, respectively) and optic nerve width (by 14.1% and 12.7% in males and females, respectively). It was unexpected that young fecal transplant was very potent in re-organizing the histological assembly of aged eyes regardless of PFBS coexposure, underlining the intimate interplay between gut and retina. Proteomic profiling provided more clues about the visual toxicology mechanism of PFBS, which was found to typically interfere with synaptic neurotransmission occurring in plexiform layers. However, proteome perturbation of aged eyes by PFBS exposure was effectively shifted by the transplantation of young feces towards the control phenotype, suggesting the high ameliorative potential of young fecal transplantation along the gut-retina axis. Overall, the present study pinpoints the potent visual toxicity of PFBS in aged animals and highlights the efficacy of young fecal transplant to regulate the inherent toxicity of PFBS. Future studies are necessitated to sequence the gut microbiota and unveil the underlying interactive routes between gut microbes and visual system.

Parabens are a class of aquatic pollutants of emerging concern, among which methylparaben (MeP) causes severe pollution worldwide. However, aquatic toxicology of MeP remains largely unknown, which hinders ecological risk evaluation. In the present study, adult zebrafish were exposed to environmentally realistic concentrations (0, 1, 3, and 10 μg/L) of MeP for 28 days, with objectives to reveal the hepatotoxicity based on transcriptional, biochemical, metabolomics, and histopathological evidences. The results showed that MeP subchronic exposure induced the occurrence of hepatocellular vacuolization in zebrafish. The most severe symptom was noted in 10 μg/L MeP-exposed female liver, which was characterized by rupture of cell membrane and small nuclei. In addition, MeP exposure disturbed the balance between oxidative stress and antioxidant capacity. Lipid metabolism dynamics across gut, blood, and liver system were significantly dysregulated after MeP exposure by altering the transcriptions of lipid nuclear receptors and concentrations of key metabolites. Metabolomic profiling of MeP-exposed liver identified differential metabolites mainly belonging to fatty acyls, steroids, and retinoids. In particular, hepatic concentration of cortisol was increased in male liver by MeP pollutant, implying the activation of stress response. Exposure to MeP also inhibited the synthesis and conjugation of primary bile acid (e.g., 7-ketolithocholic acid and taurochenodeoxycholic acid) in female liver. Furthermore, degradation of biologically active molecules, including retinoic acid and estradiol, was enhanced in the liver by MeP. Overall, the present study highlights the hepatotoxicity caused by MeP pollutant even at environmentally realistic concentrations, which necessitates an urgent and accurate risk assessment.

Perfluorobutanesulfonate (PFBS) is an emerging pollutant in aquatic environments and potently disrupts the early developmental trajectory of teleosts. Considering the persistent and toxic nature of PFBS, it is necessary to develop in situ protective measures to ameliorate the toxic damage of PFBS. Probiotic supplements are able to mitigate the growth retardation defects of PFBS. However, the interactive mechanisms remain elusive. To this end, this study acutely exposed zebrafish larvae to a concentration gradient of PFBS (0, 1, 3.3 and 10 mg/L) for 4 days, during which probiotic bacteria Lactobacillus rhamnosus were added in the rearing water. After exposure, alterations in gene transcriptions and key hormones along the hypothalamus–pituitary–interrenal (HPI), growth hormone/insulin–like growth factor (GH/IGF) and hypothalamus–pituitary–thyroid (HPT) axes were examined. The results showed that PFBS single exposure significantly increased the cortisol concentrations, suggesting the induction of stress response, while probiotic supplementation effectively decreased the cortisol levels in coexposed larvae in an attempt to relieve the stress of PFBS toxicant. It was unexpected that probiotic additive significantly decreased the larval GH concentrations independent of PFBS, thereby eliminating the contribution of GH/IGF axis to the growth improvement of probiotics. In contrast, probiotic bacteria remarkably increased the concentration of thyroid hormones, particularly the thyroxine (T4), in zebrafish larvae. The pronounced down-regulation of uridinediphosphate glucoronosyltransferases (UDPGT) gene pointed to the blocked elimination process of T4 by probiotics. Furthermore, proteomic fingerprinting found that probiotics were potent to shape the protein expression pattern in PFBS-exposed zebrafish larvae and modulated multiple biological processes that are essential for the growth. In summary, the present findings suggest that HPI and HPT axes may cooperate to enhance the growth of fish larvae under PFBS and probiotic coexposures.

Dysbiosis of fish skin microbiome and immunity by environmental pollutants are rarely studied in toxicological research in spite of their importance for fish health. In the present study, adult zebrafish were exposed to 0 and 10 μg/L of perfluorobutanesulfonate (PFBS) for 40 days, with or without the supplementation of probiotic Lactobacillus rhamnosus, with objectives to explore the interaction between PFBS pollutant and probiotic bacteria on skin mucosal microbiota and immune response. Amplicon sequencing analysis found that PFBS alone significantly disturbed the microbial community composition and abundance on the skin, favoring the growth of stress-tolerant bacteria (e.g., Deinococcus and Enhydrobacter genera). However, the administration of probiotic inhibited the dysbiosis of PFBS and shaped the skin microbiome in the combined exposure group. PFBS single exposure also promoted the production of mucus on the skin of male zebrafish, which may be related to the growth of Limnobacter bacteria. In contrast, probiotic supplements remarkably improved the immune functions in male skin mucus from the combined group, as evidenced by the consistent increases in lysozyme activity, immunoglobulin concentrations and peroxidase activity. Overall, the present study provides the first clue about the singular and combined effects of PFBS and probiotic on skin microbiota and immunity, highlighting the beneficial action of probiotic L. rhamnosus against PFBS stress.

Environmental microbiota play essential roles in the maintenance of many biogeochemical processes, including nutrient cycling and pollutant degradation. They are also highly susceptible to changes in environmental stressors, with environmental pollutants being key disruptors of microbial dynamics. In the present study, a scientific cruise was launched on July 2017 around Pearl River Delta, a suitable studying site for perfluoroalkyl substances (PFASs) in the wake of the severe PFAS pollution. Surface sediment samples were collected from 18 representative stations to assess PFAS accumulation and profile microbial community. PFAS concentrations ranged from 24.2 to 181.4 pg/g dry weight in sediment, and perfluorooctanesulfonic acid (PFOS) was the dominant homologue. The concentrations of PFAS homologues in the current study were much lower than those reported in previous studies, implying effective management and control of pollution from PFAS-related industries. 16S rRNA gene amplicon sequencing revealed that Proteobacteria was the dominant phylum, while nitrogen-metabolizing Nitrosopumilus and sulfate-reducing Desulfococcus genera were the most abundant. Variations in microbial communities among sampling stations were mainly due to the differences in abundances of Escherichia, Nitrosopumilus, and Desulfococcus. The outbreak of Escherichia bacteria at specific coastal stations potentially indicated the discharge of fecal matter into the marine environment. Dissolved oxygen (DO) in bottom seawater significantly influenced the structure of microbial communities in the sediment, while current study failed to observe significant effects from PFAS pollutants. Positive correlations were found between DO and sulfate-reducing bacteria in Desulfococcus and GOUTA19 genera. Overall, this study explored relationships between environmental variables (e.g., PFAS pollutants) and sediment bacteria. Biogeochemical parameters significantly influenced the structure and composition of microbial communities in sediment.

Titanium dioxide (TiO2) nanoparticles and bisphenol A (BPA) in aquatic environments interact reciprocally to enhance the maternal transfer of pollutants to offspring, thus varying the innate toxicities during early embryonic development. However, it remains unexplored regarding the molecular mechanisms of developmental toxicity in offspring after parental coexposure. In the present study, adult zebrafish were exposed to TiO2 nanoparticles (100 mu g/L), BPA (20 mu g/L) or their binary mixture for four months. Then, eggs of F1 generation were collected and reared in clean water until 5 days post-fertilization. In characteristic of larval survival and growth, parental coexposure to TiO2 particles and BPA caused a severer inhibition of F1 offspring larvae compared with single exposure. Mechanistic investigation by shotgun proteomics found that development of larval offspring from coexposed parents was impaired through a distinct mode of toxicity, that is, specifically altering the activity of phagosome and lysosome. Single exposure of adult zebrafish to TiO2 mainly affected insulin-responsive compartment; and BPA parental exposure mainly affected carbohydrate metabolism and calcium signaling of larval offspring. Furthermore, considering the tight regulation of sex hormones in the expression of vitellogenin (VTG), addition of nanoparticles during parental exposure led to inconsistencies between VTG induction and endogenous levels of sex hormones (estradiol and testosterone) in F1 offspring fish. This implied that transfer of nanoparticles to offspring larvae may change the availability of hormonal molecules and BPA at target tissues. Overall, current results provided mechanistic clues into the multigenerational developmental toxicity by parental coexposure to TiO2 particles and BPA. (C) 2018 Elsevier Ltd. All rights reserved.

Perfluorobutanesulfonate (PFBS) pollutant and probiotic bacteria can interact to affect the reproductive outcomes of zebrafish. However, it is still unexplored how the growth and health of offspring are modulated by the combination of PFBS and probiotic. In the present study, adult zebrafish were exposed to 0 and 10 μg/L PFBS for 40 days, with or without dietary supplementation of probiotic Lactobacillus rhamnosus. After parental exposure, the development, growth and viability of offspring larvae were examined, with the integration of molecular clues across proteome fingerprint, growth hormone/insulin-like growth factor (GH/IGF) axis, calcium homeostasis, hypothalamic-pituitary-adrenal (HPA) axis and nutrient metabolism. Parental probiotic supplementation significantly increased the body weight and body length of offspring larvae. Despite the spiking of PFBS, larvae from the combined exposure group still had longer body length. RNA processing and ribosomal assembly pathways may underlie the enhancement of offspring growth by probiotic bacteria. However, the presence of PFBS remarkably increased the concentrations of cortisol hormone in offspring larvae as means to cope with the xenobiotic stress, which required more energy production. As evidenced by the proteomic analysis, the addition of probiotic bacteria likely alleviated the energy metabolism disorders of PFBS, thus allocating more energy for the larval offspring growth from the combined group. It was noteworthy that multiple molecular disturbances caused by PFBS were antagonized by probiotic additive. Overall, the present study elucidated the intergenerational interaction between PFBS and probiotic on offspring growth and health after parental exposure.

Background Ovarian cancer (OC) is a leading cause of death in gynecological malignancies worldwide. Multitudinous studies have suggested the potential of circulating tumor DNA (ctDNA), circulating microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) as novel diagnostic molecular biomarkers for OC. Here, we include three updated meta-analysis methods using different molecular biomarkers to evaluate their discriminative value in OC diagnosis. Methods We conducted three meta-analyses after searching different databases, and 23 eligible articles, including 8 concerning ctDNA, 11 concerning miRNAs, and 4 concerning lncRNAs, were found. Further, we pooled data concerning the sensitivity, specificity, and other indicators of accuracy for ctDNA/miRNAs/lncRNAs in the diagnosis of OC. The heterogeneity was further explored by meta-regressions and subgroup analyses, and Deeks’ funnel plots were used to measure the publication bias of these three meta-analyses. Results In all, this meta-analysis included 1732 OC patients and 3958 controls. The sensitivity of ctDNA for OC diagnosis was superior to that of lncRNA and miRNA (84% vs. 81% vs. 78%). Moreover, the specificity and area under the receiver-operating characteristic (ROC) curve (AUC) of ctDNA were 91% and 94%, which were significantly higher than those of miRNA and lncRNAs (78% and 85%; 78% and 86%, respectively). No significant difference was observed among the two meta-analyses of ctDNA and lncRNA (P > 0.05) with regard to publication bias, while the meta-analysis of miRNA observed a significantly small publication bias (P < 0.05). Conclusion ctDNA/miRNAs/lncRNAs may be promising molecular biomarkers for OC diagnosis. Further large-scale studies are needed to verify the potential applicability of ctDNA/miRNAs/lncRNAs molecular signatures alone or in combination as diagnostic molecular biomarkers for OC.

Parental exposure to perfluorobutane sulfonate (PFBS), an aquatic pollutant of emerging concern, is previously found to impair the embryonic development of offspring. However, the impairing mechanisms remain to clarify. In the present study, adult zebrafish were exposed to 0, 10 and 100 μg/L PFBS for 28 d, after which disturbances in maternal transcript transfer and offspring embryogenesis were investigated. Prior to zygotic genome activation, high-throughput transcriptomic sequencing revealed that parental PFBS exposure significantly altered the transcript profile of maternal origin in offspring eggs, while toxic actions varied as a function of PFBS concentrations. In offspring eggs derived from 10 μg/L exposure group, differential transcripts were mainly associated with the histone-DNA interaction of nucleosome, which would modify the compacted chromatin configuration and accessibility of transcriptional factors to DNA sequences. In this regard, the timing of zygotic genome activation was presumably disrupted. Parental exposure to 100 μg/L PFBS primarily interrupted the maternal transfer of adherens junction transcripts, which was supposed to dysregulate the cell-cell adhesion during early embryo formation. Development and growth of offspring embryos were significantly compromised by parental PFBS exposure, as exemplified by higher mortality, delayed hatching, slower heart rate, reduced body weight and neurobehavioral disorders. Overall, the present study presented the first toxicological evidence about the disturbances of PFBS in maternal transcript transfer, although the inherent linkage between maternal transcript modifications and offspring development defects still needs future works to construct.

Perfluorobutane sulfonate (PFBS), an environmental pollutant of emerging concern, is previously shown to dynamically interact with hypoxia on aquatic developmental toxicities. However, the molecular mechanisms underlying the interaction remain unknown. In this follow-up study, marine medaka embryos were exposed to 0 and 3.3 mg/L of PFBS under normoxia (6.9 mg/L) or hypoxia (1.7 mg/L) condition till 15 days post-fertilization. High-throughput transcriptomic sequencing was employed to filter differentially expressed genes and provide mechanistic insight into interactive action between hypoxia and PFBS. The results showed that hypoxia alone and the coexposure paradigm were similarly potent to modify transcriptional profiles, with the majority of genes significantly down-regulated. In contrast, transcriptional toxicity of PFBS was relatively milder. Functional annotation analyses found that hypoxia and coexposure groups mainly impacted phototransduction signaling by decreasing the transcriptions of cyclic nucleotide-gated (CNG) cation channels and retinol transport genes. However, this study demonstrated the first toxicological evidence that toxic effects of PFBS targeted the perception of chemical stimulus through olfactory and gustatory receptors. The addition of PFBS moderately exacerbated the toxic actions of hypoxia, which largely shaped the transcriptional pattern of coexposure group. In addition, gene interactive networks were constructed for hypoxia and coexposure groups, underlining the increased chromatin deacetylation and methylation to epigenetically repress genome-wide transcriptional initiation. Overall, PFBS and hypoxia interact to interrupt the embryonic development of sensory systems, which may compromise the individual fitness and survival, especially during early life stages when precocious perception of food and escape from predators are essential.

The co-occurrence of hypoxia and xenobiotics is extremely common in natural environments, highlighting the necessity to elicit their interaction on aquatic toxicities. In the present study, marine medaka embryos were exposed to various concentrations (nominal 0, 1, 3.3 and 10 mg/L) of perfluorobutane sulfonate (PFBS), an environmental pollutant of emerging concern, under either normoxia (6.9 mg/L) or hypoxia (1.7 mg/L) condition. After acute exposure till 15 days post-fertilization, single or combined toxicities of PFBS and hypoxia on embryonic development (e.g., mortality, hatching and heartbeat) and endocrine systems were investigated. Sex and thyroid hormones were measured by enzyme-linked immunosorbent assay. Transcriptional changes of endocrine genes were determined by quantitative real-time PCR assays. Co-exposure to 10 mg/L PFBS and hypoxia caused a further reduction in survival rate and heart beat compared to single exposure. PFBS induced a precocious hatching, while no larvae hatched under hypoxia condition. By disturbing the balance of sex hormones, either PFBS or hypoxia single exposure produced an anti-estrogenic activity in medaka larvae. However, PFBS and hypoxia combinations reversed to estrogenic activity in co-exposed larvae. Variation in disrupting pattern may be attributed to the interactive effects on steroidogenic pathway involving diverse cytochrome P450 enzymes. Regarding thyroid system, PFBS exposure caused detriments of multiple processes along thyroidal axis (e.g., feedback regulation, synthesis and transport of thyroid hormones, receptor-mediated signaling and thyroid gland development), while hypoxia potently impaired the development and function of thyroid gland. Combinations of PFBS and hypoxia interacted to dysregulate the function of thyroid endocrine system. In summary, the present study revealed the dynamic interaction of PFBS pollutant and hypoxia on aquatic developmental toxicities and endocrine disruption. Considering the frequent co-occurrence of xenobiotics and hypoxia, current results would be beneficial to improve our understanding about their interactive mechanisms and provide baseline evidences for accurate ecological risk evaluation.

Contamination from lower brominated PBDEs is ubiquitous in the environments. However, their effects on gut microbiota and intestinal health have not yet been investigated. This study exposed adult zebrafish to an environmentally realistic concentration of pentaBDE mixture (DE-71) at 5.0 ng/L for 7 days, after which metagenomic sequencing of the intestinal microbiome was conducted and host physiological activities in the intestine and liver were also examined. The results showed that acute exposure to DE-71 significantly shifted the gut microbial community in a sex-specific manner. Certain genera (e.g., Mycoplasma, Ruminiclostridium, unclassified Firmicutes sensu stricto, and Fusobacterium) disappeared from the DE-71-exposed intestines, resulting in decreased bacterial diversity. Bacterial metabolic functions in guts were also affected by DE-71, namely those covering energy metabolism, virulence, respiration, cell division, cell signaling, and stress response. In addition, measurement of diverse sensitive biomarkers showed that the health of male intestines was remarkably compromised by the DE-71 exposure, as indicated by the disruption to its neural signaling (serotonin), epithelial barrier integrity (tight junction protein 2), inflammatory response (interleukin 1β), oxidative stress and antioxidant capacity, as well as detoxifying potential (ethoxyresorufin-O-deethylase activity). However, female intestines maintained intact physiological activities. Compared to the direct impact on intestines, a latent effect of DE-71 was observed in livers. Co-occurrence network analysis demonstrated that the gut bacteria vigorously interacted to establish the fittest community under DE-71 stress by promoting the reproduction of favorable genera, while diminishing the survival of unfavorable ones. Significant correlations between the zebrafish gut microbiota and physiological activities (e.g., oxidative stress, detoxification, neurotransmission, and epithelial integrity) were also observed. Overall, this study has demonstrated, for the first time, the high susceptibility of gut microbiota and intestinal health of zebrafish to DE-71, thus warranting more work to reveal its mode of toxicity.

As an alternative to perfluorooctane sulfonate (PFOS), increasing usage of perfluorobutane sulfonate (PFBS) has led to ubiquitous presence in the environment. PFBS is also shown to potently disrupt the thyroid endocrine system. Considering the regulation of thyroid hormones in visual development, PFBS is likely to adversely affect the development and function of visual systems, which is a sensitive target of environmental pollutants. Therefore, the present study exposed marine medaka embryos to environmentally realistic concentrations of PFBS (0, 1.0, 2.9 and 9.5 μg/L) for an entire life-cycle. After exposure until sexual maturity, eyes of adult medaka were dissected to directly investigate the ocular accumulation and toxicity of PFBS. For the first time, substantial accumulation of an environmental pollutant (i.e., PFBS) was observed in the eye tissue. PFBS exposure was also found to impair the visual development and function in a sex-dependent manner. In female medaka, weight of eyes was significantly decreased, while content of water was increased, probably resulting in higher intraocular pressure. Multiple neural signaling processes were also disturbed by PFBS life-cycle exposure, including cholinergic, glutamatergic, GABAergic and monoaminergic systems. Increased levels of norepinephrine and epinephrine neurotransmitters may adaptively decrease the intraocular hypertension in female eyes. In addition, proteomic profiling identified the visual proteins of differential expressions (e.g., beta and gamma crystallins, arrestin and lumican), which were significantly associated with visual perception and motor activity of eyes. Overall, this study found that PFBS was able to accumulate in the eyes and induce ocular toxicities. The susceptibility and sex-specific responses of visual systems to environmental pollutants warrants more works for a comprehensive risk assessment.

Gut microbiota is of critical relevance to host health. However, toxicological understanding of environmental pollutants on gut microbiota is limited, not to mention their combined effects. In the present study, adult zebrafish (Danio rerio) were exposed to titanium dioxide nanoparticles (nano-TiO2; 100 μg/L), bisphenol A (BPA; 0, 2, and 20 μg/L) or their binary mixtures for three months. Sequencing of 16S rRNA amplicons found that nano-TiO2 and BPA coexposure shifted the intestinal microbial community, interacting in an antagonistic manner when the BPA concentration was low but in a synergistic manner at a higher BPA concentration. Sex- and concentration-dependent responses to the coexposure regime were also observed for zebrafish growth and intestinal health (e.g. neurotransmission, epithelial barrier permeability, inflammation, and oxidative stress). Correlation analysis showed that oxidative stress after nano-TiO2 and BPA coexposure was tightly associated with the imbalanced ratio of pathogenic Lawsonia and normal metabolic Hyphomicrobium, where higher abundance of Lawsonia but lower abundance of Hyphomicrobium were induced concurrently. A positive relationship was observed between zebrafish body weight and the abundance of Bacteroides in the gut, which was also closely associated with the genera of Anaerococcus, Finegoldia, and Peptoniphilus. This study revealed, for the first time, the combined effects of nano-TiO2 and BPA coexposure on the dynamics of the gut microbiome, which proved to have toxicological implications for zebrafish host health.

Probiotic supplementation is effective to modulate the metabolic disorders caused by perfluorobutanesulfonate (PFBS). However, the underlying mechanisms remain unclear. To this end, the present study exposed adult zebrafish to PFBS (0 and 10 μg/L), probiotics, or their binary combinations for 40 days. After the exposure, the nutritional stores, intestinal organization, and metabolic activities along the gut-liver axis were investigated. The results showed that PFBS exposure decreased the nutrient reserves significantly, especially the lipid content, which was alleviated by the probiotic administration. Intestinal mucus secretion was promoted remarkably in the presence of the probiotic, which enhanced epithelial protection against PFBS damage. Metagenomic analysis showed that PFBS alone induced gut microbial dysbiosis, which was efficiently antagonized by the probiotic bacteria. Intestinal metabolomic profiling revealed that ferroptosis occurred because of the unrestricted lipid peroxidation following PFBS exposure. However, probiotic administration prevented the ferroptotic symptoms induced by PFBS, further highlighting the beneficial effects of the probiotic on the host. In PFBS-exposed livers, high levels of bile acid metabolites (e.g., taurochenodeoxycholic acid) accumulated, implying the induction of cholestasis. Notably, probiotic addition recovered the metabolomic homeostasis under PFBS stress, probably resulting from the activation of detoxification pathways based on the pentose and glucuronate interconversion. Overall, the present study provides systematic evidence of the antagonistic interaction between PFBS and the probiotic regarding the metabolic activities along the microbe, gut and liver axis, highlighting the application values of probiotic recipe in aquaculture industry and ecological reservation.

Perfluorobutanesulfonate (PFBS) and probiotic bacteria can interact to induce hepatic hypertrophy. However, the molecular events occurring in the hypertrophic liver are still unknown. Therefore, we performed this follow-up study using adult zebrafish that were exposed for 40 days to 0 and 10 μg/L PFBS, with or without dietary supplementation of probiotic Lactobacillus rhamnosus. After PFBS or/and probiotic exposures, proteome perturbation, histological pathogenesis and glucose metabolism were investigated in the livers. Proteomic analysis showed potent intervention of PFBS or/and probiotic with hepatic functions. PFBS single exposure caused marked disturbances in lipid metabolisms, which may underlie the severe vacuolization in male liver. The addition of probiotic alleviated the lipid metabolic disorders of PFBS. Furthermore, probiotic supplementation enhanced ATP energy production using glucose in mitochondrial respiratory chain of male fish. However, PFBS alone caused remarkable increase in blood glucose level (by 2.5-fold relative to the control), underlining the onset of hyperglycemia symptom. In contrast, the liver of male fish from the coexposure group functioned appropriately, which immediately increased insulin levels by 2.2-fold to reduce the glucose accumulation in blood. In female liver, PFBS alone significantly decreased the blood glucagon concentration by 2.9-fold. The deficiency of glucagon hormone consequently contributed to the accumulation of glycogen (3.2-fold) therein. Vigorous antagonistic interaction between PFBS and probiotic was noted with respect to glucose metabolism, which restored ATP, glucose, glycogen and glucagon to the control levels. Overall, the present study finds that probiotic L. rhamnosus is efficient to mitigate the metabolic disorders of PFBS on lipid and glucose, highlighting the potential values of probiotic bacteria to protect the aquatic ecosystem.

Organic ultraviolet (UV) filters are common ingredients of personal care products and occur ubiquitously in the aquatic environment; however, little is known about their distribution in and potential effects to the marine environment. This study reports the occurrence, toxicological effects and risk assessment of eleven commonly consumed UV filters in marine surface water collected from the South China Sea (SCS) coastal region. The concentrations of UV filters ranged fromMDL to 145 ng/L in the SCS, in which benzophenone-3, octocrylene and butyl methoxydibenzoylmethane were the most dominant compounds with their detection frequencies over 97%. Relatively higher levels of total UV filters were found near the highly industrialized and urbanized Pearl River Estuary (PRE) and the concentrations gradually decreased towards the SCS. In general, the environmental levels of UV filters were higher at the western marine waters in Hong Kong than the eastern marine waters. Significant negative correlations were observed between benzophenone-4 and water temperature, as well as ethylhexyl methoxycinnamate and salinity (P 0.001; r -0.5). Immobilization test of barnacle nauplius larvae (Balanus amphitrite) was conducted to assess the acute toxicity of organic UV filters to marine organisms. Benzophenone-8 and 4-methylbenzylidene camphor showed relatively higher toxicity with the 50% effect concentrations (EC

Triphenyl phosphate (TPhP) is an organophosphate flame retardant that is frequently detected in the environments. TPhP exposure is known to cause developmental toxicity. However, the underlying molecular mechanisms remain underestimated. In the present study, zebrafish embryos were acutely exposed to 0, 4 and 100 μg/L TPhP until 144 h post-fertilization. Profiles of differentially expressed proteins were constructed using a shotgun proteomic. With the input of differential proteins, principal component analysis suggested different protein expression profiles for 4 and 100 μg/L TPhP. Gene ontology and KEGG pathway analyses further found that effects of TPhP at 4 μg/L targeted phagosome and lysosome activity, while 100 μg/L TPhP mainly affected carbohydrate metabolism, muscular contraction and phagosome. Based on proteomic data, diverse bioassays were employed to ascertain the effects of TPhP on specific proteins and pathways. At gene and protein levels, expressions of critical visual proteins were significantly changed by TPhP exposure, including retinoschisin 1a, opsins and crystallins, implying the impairment of ocular development and function. TPhP exposure at 100 μg/L also altered the abundances of diverse muscular proteins and disordered the assembly of muscle fibers. Effects of TPhP on visual development and motor activity may be combined to disturb larval swimming behavior. In summary, current results provided mechanistic clues to the developmental toxicities of TPhP. Future works are inspired to broaden the toxicological knowledge of TPhP based on current proteomic results.

Perfluorobutanesulfonate (PFBS), an aquatic pollutant of emerging concern, is found to disturb gut microbiota, retinoid metabolism and visual signaling in teleosts, while probiotic supplementation can shape gut microbial community to improve retinoid absorption. However, it remains unknown whether probiotic bacteria can modulate the toxicities of PFBS on retinoid metabolism and visual physiology. In the present study, adult zebrafish were exposed for 28 days to 0, 10 and 100 μg/L PFBS, with or without dietary administration of probiotic Lactobacillus rhamnosus. Interaction between PFBS and probiotic was examined regarding retinoid dynamics (intestine, liver and eye) and visual stimuli transmission. PFBS single exposures remarkably inhibited the absorption of retinyl ester in female intestines, which were, however, restored by probiotic to normal status. Although coexposure scenarios markedly increased the hepatic storage of retinyl ester in females, mobilization of retinol was reduced in livers by single or combined exposures regardless of sex. In the eyes, transport and catalytic conversion of retinol to retinal and retinoic acid were interrupted by PFBS alone, which were efficiently antagonized by probiotic presumably through an indirect action. In response to the availability of retinal chromophore, transcriptions of opsins and arrestin genes were altered adaptively to control visual perception and termination. Neurotransmission across retina circuitry was changed accordingly, centering on epinephrine and norepinephrine. In summary, the present study found the efficient modulation of probiotic on retinoid metabolic disorders of PFBS pollution, which subsequently impacted visual signaling. A future work is warranted to provide mechanistic clues in retinoid interaction.

Perfluorobutanesulfonate (PFBS), an aquatic pollutant of emerging concern, is found to disturb the neural signaling along gut-brain axis, whereas probiotic additives have been applied to improve neuroendocrine function of teleosts. Both PFBS and probiotics can commonly target nervous system. However, whether and how probiotic bacteria can modulate the neurotoxicities of PFBS remain not explored. It is thus necessary to elucidate the probiotic modulation of PFBS neurotoxicity, which can provide implications to the application of probiotic bacteria in aquaculture industry. In the present study, adult zebrafish were exposed to 0, 10 and 100 μg/L PFBS with or without dietary administration of probiotic Lactobacillus rhamnosus. Interaction between PFBS and probiotic along gut-brain axis was examined, covering three dominant pathways (i.e., neurotransmission, immune response and hypothalamic-pituitary-adrenal (HPA) axis). The results showed that, compared to the single effects, PFBS and probiotic coexposure significantly altered the acetylcholinesterase activity and neurotransmitter profiles in gut and brain of zebrafish, with mild effects on neuronal integrity. Neurotransmitters closely correlated reciprocally in intestines, which, however, was distinct from the correlation profile in brains. In addition, PFBS and probiotic were combined to impact brain health through absorption of bacterial lipopolysaccharides and production of inflammatory cytokines. Relative to neurotransmission and immune signaling, HPA axis was not involved in the neurotoxicological interaction between PFBS and probiotic. Furthermore, it needs to point out that interactive modes between PFBS and probiotic varied a lot, depending on exposure concentrations, sex and toxic indices. Overall, the present study provided the first evidence that probiotic supplement could dynamically modulate the neurotoxicities of PFBS in teleost.

Titanium dioxide (TiO

Gut microbiota is of critical importance to host health. Aryl hydrocarbon receptor (AhR) is found to be closely involved in the regulation of gut microbial dynamics. However, it is still not clear how AhR signaling shapes the gut microbiota. In the present study, adult zebrafish were acutely exposed to an AhR antagonist (CH223191), an AhR agonist (polychlorinated biphenyl 126; PCB126) or their combination for 7 d. Overall intestinal health and gut microbial community were temporally monitored (1 d, 3 d and 7 d) and inter-compared among different groups. The results showed that single exposure to PCB126 significantly disrupted the overall health of intestines (i.e., neural signaling, inflammation, epithelial barrier integrity, oxidative stress). However, CH223191 failed to inhibit but enhanced the physiological toxicities of PCB126, implying the involvement of extra mechanisms rather than AhR in the regulation of intestinal physiological activities. Dysbiosis of gut microbiota was also caused by PCB126 over time as a function of sex. It is intriguing that CH223191 successfully abolished the holistic effects of dioxin on gut microbiota, which inferred that growth of gut microbes was directly controlled by AhR activation without the involvement of host feedback modulation. When coming to detailed alterations at certain taxon, both antagonistic and synergistic interactions existed between CH223191 and dioxin, depending on fish sex, exposure duration and bacterial species. Correlation analysis found that gut inflammation was positively associated with pathogenic Legionella bacteria, but was negatively associated with epithelial barrier integrity, suggesting that integral intestinal epithelial barrier can prevent the influx of pathogenic bacteria to induce inflammatory response. Overall, this study has deciphered, for the first time, the direct regulative effects of AhR activity on gut microbiota. Future research is warranted to elucidate the specific mechanisms of AhR action on certain bacterial population.

3,3'-Diindolylmethane (DIM) has been promoted as an effective chemopreventive and antifouling additive. However, the concurrent risks or side effects of DIM are not fully understood, especially on tissues responsive to estrogen. Therefore, this study employed marine medaka (Oryzias melastigma) as a test model to evaluate relative safety and explore mechanisms of toxic action of DIM on development and function of gonad after chronic (28days) aqueous exposure to relatively low doses (0μg/L or 8.5μg/L). Integration of comprehensive toxicogenomic analysis at the transcriptome and proteome levels with apical endpoints, such as production of eggs and swimming performance of larvae, elucidated the molecular linkage in gonad from bottom up along the reproductive adverse outcome pathway. A series of sequential changes at the transcript and protein levels were linked to lesser fecundity and viability of larvae exposed to DIM. Anomalous production of vitellogenin (VTG) and eggshell proteins in testis confirmed the estrogenic potency of DIM. In the ovary, although storage of VTG was greater, lesser expressions of cathepsin enzymes blocked cleavage and incorporation of VTG into oocytes as yolk, which acted together with lower eggshell proteins to inhibit maturation of primary oocyte and thus contributed to impairment of fecundity. Overall, this study demonstrated that exposure to DIM impaired reproductive fitness. Diverse molecular initiating changes in gonads were linked to apical endpoints that could be used in assessment of risks posed by DIM on gametogenesis. In combination with chemical stability and potent endocrine disruption, the results of this study can inform decisions about the use of DIM either as chemopreventive or antifouling agent.

The objectives of the present study were to investigate the effects of acute exposure to PBDEs on retinoid signaling in fish. Zebrafish embryos (2 h post-fertilization, hpf) were exposed to DE-71 (0, 31.0, 68.7, and 227.6 mu g/L) until 120 hpf. Retinoid profiles showed the content of retinal and retinoic acid was reduced significantly. While a significant up-regulation was observed in the transcription of retinal dehydrogenase (raldh2), the transcription of retinol binding protein (rbp1a), retinol dehydrogenase (rdh1), cellular retinoic acid binding protein.(crabp1a and crabp2a) and retinoic acid receptor subunit (raraa) were down-regulated significantly, indicating disruption of retinoid signaling. However, the transcriptions of five opsin genes (zfrho, zfuv, zfred, zfblue, and zfgr1) were up-regulated. Furthermore, whole mount immunostaining and western blotting demonstrated increased rhodopsin protein expression in the exposure groups. Overall, the results indicated that acute exposure to PBDEs could disturb retinoid signaling and may impact on eye development of zebrafish larvae. (C) 2012 Elsevier B.V. All rights reserved.

This paper introduces a new allocation method on discharge loading of each function zone in a total emission control region. The wind frequency, the position of each district, and the pollutant's influence area were taken into account in this new method. The concept of "average downwind distance" was brought forward in this paper. The method here is more reasonable than the original method of area distribution, which was proposed by the "A-value" method in regulation of total emissions in China, by means of the simulation of annual average concentration in the total emission control region.

This study examined the disruptive effect of exposure to polybrominated diphenyl ethers (PBDEs) on retinoid content in zebrafish (Danio rerio). Adult zebrafish were exposed to an environmentally relevant concentration (0.45 μg/L) and a higher concentration (9.6 μg/L) of DE-71 for 60 days. Retinoid content and gene transcription levels were examined in female zebrafish. PBDE exposure caused a significant decrease of retinyl ester content in the intestine and a downregulation of intestinal cellular retinol binding protein gene transcription (CRBP1a). In the liver, retinyl ester content was significantly decreased, while retinol content was increased. An upregulation of liver CRBP2a and retinol binding protein (RBP) gene transcription and an increased level of RBP protein were observed. In the eyes, both the retinal and retinyl ester content were increased and CRBP1a gene transcription was upregulated. However, the gene encoding for retinal dehydrogenase (RALDH2), responsible for retinoic acid synthesis, was downregulated in the eyes. CYP26a, the gene responsible for retinoic acid degradation, was upregulated, which indicated an increased level of retinoic acid. In the ovaries, the increased deposition of retinoids was also observed, while gene transcription levels of both CRBPs (CRBP1a and CRBP1b) were upregulated. An increased deposition of retinal was measured in the eggs. Overall, this study demonstrated that long-term exposure of zebrafish to environmentally relevant concentrations of DE-71 disrupted the transport, storage and metabolism of retinoid in various tissues. This study also indicated that retinoid levels in zebrafish are sensitive to PBDE exposure and highlighted the importance of liver storage, which appears to support important functions in reproduction and vision.