Maternal methylosome protein 50 is essential for embryonic development in medaka Oryzias latipes.

Methylosome protein 50 (Mep50) is a protein that is rich in WD40 domains, which mediate and regulate a variety of physiological processes in organisms. Previous studies indicated the necessity of Mep50 in embryogenesis in mice Mus musculus and fish. This study aimed to further understand the roles of maternal Mep50 in early embryogenesis using medaka Oryzias latipes as a model. Without maternal Mep50, medaka zygotes developed to the pre-early gastrula stage but died later. The transcriptome of the embryos at the pre-early gastrula stage was analyzed by RNA sequencing. The results indicated that 1572 genes were significantly upregulated and 741 genes were significantly downregulated in the embryos without maternal Mep50. In the differentially expressed genes (DEGs), the DNA-binding proteins, such as histones and members of the small chromosome maintenance complex, were enriched. The major interfered regulatory networks in the embryos losing maternal Mep50 included DNA replication and cell cycle regulation, AP-1 transcription factors such as Jun and Fos, the Wnt pathway, RNA processing, and the extracellular matrix. Quantitative RT-PCR verified 16 DEGs, including prmt5, H2A, cpsf, jun, mcm4, myc, p21, ccne2, cdk6, and col1, among others. It was speculated that the absence of maternal Mep50 could potentially lead to errors in DNA replication and cell cycle arrest, ultimately resulting in cell apoptosis. This eventually resulted in the failure of gastrulation and embryonic death. The results indicate the importance of maternal Mep50 in early embryonic development, particularly in medaka fish.

Methylosome protein 50 is necessary for oogenesis in medaka.

Methylosome protein 50 (Mep50) functions as a partner to protein arginine methyltransferase 5. MEP50 serves as a coactivator for both the androgen receptor and estrogen receptor in humans. Mep50 plays a crucial role in the development of germ cells in Drosophila. The precise role of Mep50 in oogenesis remains unclear in vertebrates. The objective of this study was to investigate the role of Mep50 in oogenesis in medaka fish. Disruption of Mep50 resulted in impaired oogenesis and the formation of multiple oocyte follicles in medaka. RNA-seq analysis revealed significant differential gene expression in the mutant ovary, with 4542 genes up-regulated and 1264 genes down-regulated. The regulated genes were found to be enriched in cellular matrices and ECM-receptor interaction, the Notch signaling pathway, the PI3K-Akt signaling pathway, the MAPK signaling pathway, the Hippo signaling pathway, and the Jak-Stat pathway, among others. In addition, the genes related to the hypothalamus-pituitary-gonad axis, steroid metabolism, and IGF system were impacted. Furthermore, the mutation of mep50 caused significant alterations in alternative splicing of pre-mRNA in ovarian cells. Quantitative RT-PCR results validated the findings from RNA-seq analysis in the specific genes, including akt2, map3k5, yap1, fshr, cyp17a, igf1, ythdc2, cdk6, and col1, among others. The findings of this study demonstrate that Mep50 plays a crucial role in oogenesis, participating in a diverse range of biological processes such as steroid metabolism, cell matrix regulation, and signal pathways. This may be achieved through the regulation of gene expression via mRNA splicing in medaka ovarian cells.

In situ growth of BiOBr on copper foam conductive substrate with enhanced photocatalytic performance.

Photocatalysis technology based on solar-powered semiconductors is widely recognized as a promising approach for achieving eco-friendly, secure, and sustainable degradation of organic contaminants. Nevertheless, conventional photocatalysts exhibit drawbacks such as a wide bandgap, and rapid recombination of photoinduced electron/hole pairs, in addition to complicated separation and recovery procedures. In this research, we cultivated BiOBr in situ on the surface of copper foam to fabricate a functional photocatalyst (denoted as BiOBr/Cu foam), which was subsequently employed for the photodegradation of Methylene Blue. Based on photodegradation experiments, the 0.3 BiOBr/Cu foam demonstrates superior photocatalytic efficacy compared to other photocatalysts under solar light irradiation. Furthermore, its ease of separation from the solution enhances its potential for reuse. The analysis of charge transfer revealed that the copper foam functions as an effective electron scavenger within the BiOBr/Cu foam, thereby facilitating charge separation and the generation of photo-induced holes. This phenomenon contributes to a significantly enhanced production of hydroxyl radicals. This study provides a valuable perspective on the design and synthesis of photocatalysts with heightened practicality, employing a conductive substrate.

Foraging behavior and sea ice-dependent factors affecting the bioaccumulation of mercury in Antarctic coastal waters.

To elucidate the potential risks of the toxic pollutant mercury (Hg) in polar waters, the study of accumulated Hg in fish is compelling for understanding the cycling and fate of Hg on a regional scale in Antarctica. Herein, the Hg isotopic compositions of Antarctic cod Notothenia coriiceps were assessed in skeletal muscle, liver, and heart tissues to distinguish the differences in Hg accumulation in isolated coastal environments of the eastern (Chinese Zhongshan Station, ZSS) and the antipode western Antarctica (Chinese Great Wall Station, GWS), which are separated by over 4000 km. Differences in odd mass-independent isotope fractionation (odd-MIF) and mass-dependent fractionation (MDF) across fish tissues were reflection of the specific accumulation of methylmercury (MeHg) and inorganic Hg (iHg) with different isotopic fingerprints. Internal metabolism including hepatic detoxification and processes related to heart may also contribute to MDF. Regional heterogeneity in iHg end-members further provided evidence that bioaccumulated Hg origins can be largely influenced by polar water circumstances and foraging behavior. Sea ice was hypothesized to play critical roles in both the release of Hg with negative odd-MIF derived from photoreduction of Hg2+ on its surface and the impediment of photochemical transformation of Hg in water layers. Overall, the multitissue isotopic compositions in local fish species and prime drivers of the heterogeneous Hg cycling and bioaccumulation patterns presented here enable a comprehensive understanding of Hg biogeochemical cycling in polar coastal waters.

Tetrahydroxystilbene Glucoside Attenuates Oxidative Stress-Induced Aging by Regulating Oxidation Resistance and Inflammation in Larval Zebrafish.

Population aging is a global problem worldwide, and the discovery of antiaging drugs and knowledge of their potential molecular mechanisms are research hotspots in biomedical field. Tetrahydroxystilbene glucoside (TSG) is a natural component isolated from Heshouwu (Polygonum multiflorum Thunb.). It has been widely used to treat various chronic diseases for its remarkable biological activities. In this study, we successfully established aging larval zebrafish by exposing larvae to 2 mM hydrogen peroxide (H2O2). Using this aging model, we assessed the antiaging effect of TSG with different concentrations (25-100 µg/mL). After being treated with H2O2, zebrafish showed the obvious aging-associated phenotypes characterized by higher senescence-associated ß-galactosidase activity, significantly downregulated expression of sirtuin 1 (sirt1) and telomerase reverse transcriptase (tert), and upregulated serpine1 mRNA level compared to the control group. TSG pretreatment delayed the aging process of oxidative stress-induced zebrafish, indicative of the reduced positive rate of senescence-associated ß-galactosidase, improved swimming velocity, and stimulus-response capacity. Further studies proved that TSG could suppress reactive oxygen species production and enhance the activity of antioxidant enzymes superoxide dismutase and catalase. TSG also inhibited the H2O2-induced expressions of inflammation-related genes il-1ß, il-6, cxcl-c1c, and il-8 in aging zebrafish, but it did not affect apoptosis-related genes (bcl-2, bax, and caspase-3) of aging zebrafish. In conclusion, TSG can protect against aging by regulating the antioxidative genes and enzyme activity, as well as inflammation in larval zebrafish, providing insight into the application of TSG for clinical treatment of aging or aging-related diseases.

Mep50 is essential for embryonic development in medaka fish.

Mep50 as a partner promotes the activity and substrate affinity of Prmt5. Prmt5 and Mep50 function together in multiple bioprocesses of the cells. Both Prmt5 and Mep50 are necessary for maintenance of the stem cells and are indispensable in the embryogenesis in the mammals. However, the role of Mep50 is rarely studied in fish. This study was to investigate the role of Mep50 in embryonic development of medaka. Medaka mep50 was mutated by genomic editing with CRISPR-Cas9 technology. Two mutants with a deletion of 22 and 46 bp separately in mep50 caused premature stopping of translation. The homozygotes of these mutant fish were obtained by self-crossing of the heterozygotes. These homozygotic mutants could reproduce embryos but the offspring were not viable. The apoptotic cells were significantly more in the mutant embryos than that in the wild type indicated by TUNEL assay. Quantitative RT-PCR showed that the expression of oct4 and sox2 were significantly decreased, but p53 was increased in the mutant embryos. These results suggest that disruption of mep50 severely interferes with embryogenesis and mep50 is necessary for embryonic development by maintaining stem cells and repression of apoptosis in medaka.

Pollution status and risk assessment of heavy metals in the sediment of a historically contaminated lake treated by oxidation pond in China.

Sediment plays an important role in controlling biogeochemical cycling of heavy metals in aquatic environment. The Ya-Er Lake is a typical lake which was historically contaminated by heavy metals in Hubei province, China. After industries surrounding the Ya-Er Lake being shut down, oxidation pond treatment and dredging program were conducted for pollution management since 1970s. To date, the Ya-Er Lake has been used for aquaculture for several decades. However, the status of heavy metal levels and ecological risks in this lake remains unclear. Herein, concentrations, chemical fractions, and risk assessment of heavy metals were investigated in the Ya-Er Lake sediment. Results showed that concentrations of heavy metals in the Ya-Er Lake sediment were higher than other reported lake systems, suggesting that heavy metal pollution in the Ya-Er Lake is still serious. Relatively higher proportions of carbonates bound form of Cd and Ni indicated high-risk potential of these two heavy metals, and Cd and Ni should be listed as the primary heavy metal pollutants in the Ya-Er Lake according to the results of potential ecological risk index (PERI) and sediment quality guidelines (SQGs). The risk assessment code (RAC) analysis showed that Ni and Cd poses higher bioavailability and mitigation potential, and may affect the Ya-Er Lake ecosystem and downstream aquatic environment. These findings reflected that oxidation pond treatment and dredging sediment to near place are not effective to control heavy metal pollution, and a long-term ecological risk is still posed to surrounding aquatic environment. Our study provides scientific basis on pollution control and management in aquatic system contaminated by heavy metals.

Antagonistic mechanisms of bisphenol analogues on the estrogen receptor α in zebrafish embryos: Experimental and computational studies.

Bisphenol A (BPA) can disturb the estrogen receptor α (ERα)-mediated signaling pathway, which results in endocrine-disrupting effects and reproductive toxicity. Most BPA analogues as alternatives were evidenced to generate estrogenic activity as agonists or partial agonists of ERα. Recent studies indicated that certain BPA analogues, such as bisphenol M (BPM), bisphenol P (BPP), and bisphenol FL (BPFL), exhibited strong anti-estrogenic effects comparable with the typical antagonist 4-hydroxytamoxifen. However, conflicting findings were also observed for the compounds in different in vitro assays, and whether these BPA analogues can elicit an in vivo effect on ERα at environmentally relevant concentrations remains unknown. The underlying structural basis of estrogenic/anti-estrogenic activity should be further elucidated at the atomic level. To address these issues, we combined zebrafish-based in vivo and in silico methods to assess the effects of the compounds on ERα. The results show that the expressions of ERα-mediated downstream related genes in zebrafish embryos decreased after exposed to the compounds. Further molecular dynamics simulations were used to probe the antagonistic mechanisms of the compounds on ERα. The key H-bonding interactions were identified as important ligand recognition by ERα in the analysis of binding modes and binding free energy calculations. In summary, the current study provides preliminary in vivo evidence of fish species for the anti-estrogenic activity of certain BPA analogues.

PFAS-induced lipidomic dysregulations and their associations with developmental toxicity in zebrafish embryos.

Per- and polyfluoroalkyl substances (PFASs) are persistent environmental contaminants, posing developmental toxicity to fish and human. PFAS-induced lipid metabolism disorders were demonstrated using the zebrafish (Danio rerio) embryo model, but the detailed changes of lipid compositions and the influence of these changes on the biological development are still unclear. Herein, lipidomics analysis was performed to reveal the dysregulations of lipid metabolism in zebrafish embryos exposed to perfluorooctanoic acid (PFOA) or perfluorooctane sulfonate (PFOS) through microinjection. Various abnormal phenotypes were observed, including heart bleeding, pericardium edema, spinal curvature and increased heart rate at 72 h after fertilization, especially in the PFOS exposure groups. Lipidomic profiling found downregulated phosphatidylethanolamines in the PFAS-exposed embryos, especially those containing a docosahexaenoyl (DHA) chain, indicating an excessive oxidative damage to the embryos. Glycerolipids were mainly upregulated in the PFOA groups but downregulated in the PFOS groups. These aberrations may reflect oxidative stress, energy metabolism malfunction and proinflammatory signals induced by PFASs. However, supplement of DHA may not be effective in recovering the lipidomic dysregulations and protecting from the developmental toxicity induced by PFASs, showing the complexity of the toxicological mechanisms. This work has revealed the associations between the abnormal phenotypes and dysregulations of lipid metabolism in zebrafish embryos induced by PFASs from the aspect of lipidomics, and discovered the underlying molecular mechanisms of the developmental toxicity of PFASs.

Polychlorinated dibenzo-p-dioxins/dibenzofurans and mercury in vegetable of the contaminated Ya-Er Lake area: Concentrations, sources, and health risk.

The Ya-Er Lake is a seriously polychlorinated dibenzo-p-dioxins/dibenzo-furans (PCDD/Fs) and mercury (Hg)-contaminated lake by pesticide and chlor-alkali plants in China. The oxidation pond method has been conducted to control pollution, moreover, the contaminated sediment was dredged and stacked, becoming a sediment stack yard for vegetable cultivation. To assess effects of oxidation pond method and dredging programme on pollution management and long-term risks of PCDD/Fs and Hg, the concentrations of PCDD/Fs, total Hg (THg), and methylmercury (MeHg) in soil and vegetable sampled from the sediment stack yard were measured and analyzed. Significantly positive relationships between concentrations of PCDD/Fs (p < 0.01), THg, and MeHg (p < 0.05) in edible parts of vegetable and soil were found, suggesting that bioaccumulation from contaminated soil derived from sediment dredging is important sources of PCDD/Fs and Hg in vegetable. Much higher PCDD/Fs (12 ± 9 pg/g dw) and Hg (THg, 0.14 ± 0.23 µg/g dw; MeHg,12.63 ± 13.31 ng/g dw) levels in vegetable were found compared with those from other contaminated regions, indicative of serious PCDD/Fs and Hg pollution in vegetable harvested from contaminated soil. Finally, the calculated provisional tolerable daily intake (PTDI) values showed higher health risk of PCDD/Fs and Hg exposure to local residents through consumption of purple and white flowering stalk, and oilseed rape. Our study established a good model to evaluate the long-term risks of PCDD/Fs and Hg. Moreover, the results indicate that the oxidation pond method and dredging programme were not effective to remove PCDD/Fs and Hg in sediment, which shed new light on management strategy of PCDD/Fs and Hg pollution in contaminated regions.

Tetrabromobisphenol A perturbs cell fate decisions via BMP signaling in the early embryonic development of zebrafish.

Tetrabromobisphenol A (TBBPA) readily accumulates in the egg yolk of aquatic oviparous animals and is transferred to their embryos. Early embryogenesis is vital for organ formation and subsequent development. The developmental toxicity of TBBPA in aquatic animals has been extensively reported. However, few studies have assessed the toxic effects of TBBPA in the early embryonic development. In this work, we found that TBBPA perturbed cell fate decisions along the dorsal-ventral (DV) axis during gastrulation, further disrupting early organogenesis in the entire embryo. TBBPA exposure increased the number of embryonic cells that acquired a ventral cell fate, which formed epidermis, blood and heart tissues. In return, the number of embryonic cells that acquired a dorsal cell fate was greatly decreased, causing the TBBPA-exposed embryos to develop a small brain and small eyes. We revealed that TBBPA elevated the activity gradient of bone morphogenetic protein (BMP) signaling which is responsible for cell fate specification along the DV axis, with up-regulation of BMP ligands (bmp4, bmp7a) and target genes (szl) and promotion signal transduction through phosphorylation of Smad1/5. As the function of BMP signaling in embryogenesis is highly conserved among many vertebrates, these findings highlight the ecological and health risks of TBBPA.

Long-term investigation of heavy metal variations in mollusks along the Chinese Bohai Sea.

Biomonitoring is an effective way to assess the effects of pollutants on marine ecosystems. As an important fishing region in China, the Chinese Bohai Sea has been contaminated with heavy metals, posing great risks to seafood safety and human health. Herein, the spatiotemporal variations in the concentrations of seven heavy metals (As, Cd, Cr, Cu, Ni, Pb, and Zn) in 11 species of mollusks (658 samples) collected from the Chinese Bohai Sea were studied during 2006-2016. The concentrations of Cr, As, Cd, and Pb in approximately 41%, 100%, 71%, and 18% of the sampled mollusks exceeded the maximum permissible levels in aquatic products set by China, indicating that the mollusks were contaminated with varied concentrations of heavy metals. Except for slight fluctuations, no significant temporal variations were observed during the sampling period, suggesting a relatively stable status of these metals. Cluster analysis showed that oyster had higher bioaccumulation potential for Zn and Cu, whereas Mactra veneriformis, Rapana venosa, Meretrix meretrix, Chlamys farreri, and Mya arenaria had higher bioaccumulation potentials for Cr, As, Ni, Cd, and Pb, respectively. These findings are useful for biomonitoring and developing guidelines for seafood consumption in coastal regions. Significant relationships were observed between heavy metal concentrations in mollusks and socioeconomic indices (gross domestic product, per capita gross domestic product, and population amount), suggesting the effects of anthropogenic activities on heavy metal contamination. Our study established a good model to evaluate the risks of heavy metals and provided a sound scientific basis for controlling seafood safety in coastal regions.

Molecular composition and biotoxicity effects of dissolved organic matters in sludge-based carbon: Effects of pyrolysis temperature.

Sludge pyrolysis carbonization has shown potential to convert sludge biomass into multifunctional carbon materials. However, ecological risks of dissolved organic matters (DOMs) with obscure molecular characteristics retaining in sludge-based carbons (SBCs) have received little attention. This study investigated the impact of pyrolysis temperatures on the molecular conversion and biotoxicity effects of DOMs in SBCs. The results revealed that DOMs in SBCs300-400 were mainly derived from depolymerization of biopolymers and the polycondensation and cyclization of small intermediate molecules, which mainly consisted of aromatic CHON compounds with 1-3 N atoms, featuring high unsaturation and molecular weights. High-temperature pyrolysis (500-800 °C) promoted the decomposition and ring-opening of aromatic CHON compounds into saturated aliphatic CHO compounds with 2-4 O atoms in SBCs500-800. Noteworthily, SBCs300-400-derived DOMs showed relatively strong biotoxicity on the growth and development of wild-type zebrafish embryos, pakchoi seeds, and Vibrio qinghaiensis Q67, which was significantly related to aromatic amines, phenols, and heterocyclic-N compounds in DOMs of SBCs300-400. SBCs500-800-derived DOMs were mainly straight-chain fatty acids and showed no observable acute biotoxicity. This study highlights the negative impact of DOMs in SBCs on the ecological environment, and provides the theoretical basis for controlling toxic byproducts in sludge pyrolysis process.

Alternative splicing of medaka bcl6aa and its repression by Prdm1a and Prdm1b.

Bcl6 and Prdm1 (Blimp1) are a pair of transcriptional factors that repressing each other in mammals. Prdm1 represses the expression of bcl6 by binding a cis-element of the bcl6 gene in mammals. The homologs of Bcl6 and Prdm1 have been identified in teleost fish. However, whether these two factors regulate each other in the same way in fish like that in mammals is not clear. In this study, the regulation of bcl6aa by Prdm1 was investigated in medaka. The mRNA of bcl6aa has three variants (bcl6aaX1-X3) at the 5'-end by alternative splicing detected by RT-PCR. The three variants can be detected in adult tissues and developing embryos of medaka. Prdm1a and prdm1b are expressed in the tissues and embryos where and when bcl6aa is expressed. The expression of prdm1a was high while the expression of bcl6aa was low, and vice versa, detected in the spleen after stimulation with LPS or polyI:C. In vitro reporter assay indicated that bcl6aa could be directly repressed by both Prdm1a and Prdm1b in a dosage-dependent manner. After mutation of the key base, G, of all predicted binding sites in the core promoter region of bcl6aa, the repression by Prdm1a and/or Prdm1b disappeared. The binding site of Prdm1 in the bcl6aa gene is GAAAA(T/G). These results indicate that both Prdm1a and Prdm1b directly repress the expression of bcl6aa by binding their binding sites where the 5'-G is critical in medaka fish.

Release of legacy mercury and effect of aquaculture on mercury biogeochemical cycling in highly polluted Ya-Er Lake, China.

Although global mercury (Hg) emission from chlor-alkali industry is decreasing, the legacy Hg may still have potential risks due to its environmental persistence. The objective of this work is to study the biogeochemical cycling and potential risk of Hg in the Ya-Er Lake, which was heavily contaminated by historical chlor-alkali production. Higher concentrations of total Hg (THg) in Ya-Er Lake water (16.8 ± 8.4 ng L-1) and sediment (547 ± 489 ng g-1) than other lake systems were observed, reflecting serious Hg pollution in this system. Diffusion rates of Hg at sediment-water interface and budget of Hg showed that release of legacy Hg in sediment (accounting for ∼80%) dominated THg in water, and about 80% methylmercury (MeHg) of total was diffused from sediment. Significant correlations between total organic carbon (TOC) derived from aquaculture and THg diffusion and MeHg concentrations in sediment suggest that TOC plays important roles in controlling legacy Hg release and MeHg production. The actual weekly intakes of Hg via consumption of cultured catfish and wild topmouth culter were higher than the established provisional tolerable weekly intake (PTWI) of MeHg. These results indicated that although the nearby chlor-alkali plant has been shut down for three decades, the release of legacy Hg stored in the sediment still adversely affects this ecosystem. Moreover, aquaculture could enhance MeHg production and control MeHg distribution in the polluted aquatic ecosystem, potentially posing a health risk to surrounding inhabitants through consumption of fish.

Synthesis and Toxicity of Halogenated Bisphenol Monosubstituted-Ethers: Establishing a Library for Potential Environmental Transformation Products of Emerging Contaminant.

As an important branch of halogenated bisphenol compounds, the halogenated bisphenol monosubstituted-ether compounds have received a lot of attention in environmental health science because of their toxicity and variability. In this study, a synthetic method for bisphenol monosubstituted-ether byproduct libraries was developed. By using the versatile and efficient method, tetrachlorobisphenol A, tetrabromobisphenol A, and tetrabromobisphenol S monosubstituted alkyl-ether compounds were accessed in 39-82 % yield. Subsequently, the cytotoxicity of 27 compounds were screened using three different cell lines (HepG2, mouse primary astrocytes and Chang liver cells). Compound 2,6-dibromo-4-[3,5-dibromo-4-(2-hydroxyethoxy)benzene-1-sulfonyl]phenol was more toxic than other compounds in various cells, and the sensitivity of this compound to the normal hepatocytes and cancer cells was inconsistent. The compounds 2,6-dichloro-4-(2-{3,5-dichloro-4-[(prop-2-en-1-yl)oxy]phenyl}propan-2-yl)phenol and 2,6-dibromo-4-(2-{3,5-dibromo-4-[(prop-2-en-1-yl)oxy]phenyl}propan-2-yl)phenol were the most toxic to HepG2 cells, and most of the other compounds inhibited cell proliferation. Moreover, typical compounds were also reproductive and developmental toxic to zebrafish embryos at different concentrations. The synthetic byproduct libraries could be used as pure standard compounds and applied in research on environmental behavior and the transformation of halogenated flame retardants.

Toxicity of silver nanoparticles on wound healing: A case study of zebrafish fin regeneration model.

Dressings coated with silver nanoparticle (AgNP) are widely used in the management of acute and chronic wounds. However, whether AgNP exerts toxicity on wound healing remains ambiguous. To demonstrate the effects of AgNP on wound healing, we precisely quantified the recovery speed of wound by taking advantage of the fin regeneration of zebrafish. This method also enabled assessment of the adverse effect of AgNP on various steps of wound healing in vivo. We revealed that AgNP treatment at the concentration of 2 µg/ml impaired fin regeneration when exposure was performed at the phases of epithelialization and the beginning of blastema formation. Cell proliferation of regenerative blastema was significantly decreased after AgNP exposure. But the canonical signals including Wingless/Integrated (Wnt), Notch and Fibroblast growth factor (Fgf) which play important roles in cell proliferation during fin regeneration were not modulated at 36 hours post amputation (hpa). Further study showed that AgNP impaired fin regeneration through declining amputation-induced ROS as early as epithelialized phase at 18 hpa, rather than inducing ROS generation. AgNP exposure also promoted recruitment of neutrophils in the early phase of wound healing, which suggests that this event dampened amputation-induced ROS. Overall, this study suggested that application of AgNP-coated dressings should be carefully considered at the beginning stage of wound healing.

Computational insights on agonist and antagonist mechanisms of estrogen receptor α induced by bisphenol A analogues.

Structural analogues of bisphenol A (BPA) have become widely used as alternatives in BPA-free products. Most toxicological investigations have focused on the estrogenic activities of these analogues, which have been considered as potential environmental estrogens. However, recent studies revealed that certain BPA analogues could dramatically inhibit the proliferation of breast cancer cells, and exhibited strong anti-estrogenic effects compared with the antagonist 4-hydroxytamoxifen (OHT). Thus, we adopted computational models combining molecular dynamics simulations and binding free energy calculations to explore the underlying molecular basis of BPA analogues binding to estrogen receptor α (ERα). We also evaluated ligand-induced structural rearrangements of ERα at the atomic level. Conformational analyses showed that induced-fit H-bonding recognition by Thr347 was an important factor distinguishing antagonist from agonist BPA analogues. Moreover, antagonists of BPA analogues could indirectly induce the structural reposition of key helix 12 and produce an antagonistic conformation of ERα. Compared with OHT, the binding affinity of BPA analogues is stronger for antagonists than agonists. Taken together, we therefore propose computational indicators for screening of anti-estrogenic activities of BPA analogues, which may be beneficial for predicting the estrogenic or anti-estrogenic effects of BPA alternatives.

Identification of Potential Long Noncoding RNA Biomarker of Mercury Compounds in Zebrafish Embryos.

Heavy metal pollution elicits severe environmental concern and health problem worldwide. Mercury is considered as a ubiquitous pollutant due to its versatile application in medicine, industry, and cosmetics. Long noncoding RNAs (lncRNAs) are transcripts greater than 200 nt without protein-encoding function. However, little is known about the mechanism of heavy metals-induced noncoding RNA changes in aquatic organisms. To reveal the epigenetic mechanism of mercury toxicity in zebrafish embryos and explore novel specific mercury-toxicological biomarkers, several well-studied lncRNAs were screened by real-time PCR, and the spatial-temporal expression of lncRNAs biomarker was evaluated by in situ hybridization. The nerve systems of zebrafish embryos were evaluated by detecting locomotor behavior and the expression of neuro-genes. We identified a mercury responsive lncRNA, metastasis-associated lung adenocarcinoma transcript 1 (malat1), among five candidate lncRNAs. HgCl2, MeHg, PbCl2, CdCl2, and K2CrO4 exposure assay showed that malat-1 was a mercury specific induced lncRNAs. Malat1 was highly expressed in the brain region, eyes, and notochord of developing zebrafish embryos after exposure to mercury compounds. HgCl2 showed neurobehavior disturbance and changed neuro-genes expression pattern in zebrafish larvae. This study provides a biological method to detect inorganic or organic mercury using malat1 as a novel biomarker of mercury contamination and also clues for the exploration of neurotoxicity mechanism of mercury compounds.

Growth Hormone Overexpression Disrupts Reproductive Status Through Actions on Leptin.

Growth and reproduction are closely related. Growth hormone (GH)-transgenic common carp exhibit accelerated growth and delayed reproductive development, which provides an amenable model to study hormone cross talk between the growth and reproductive axes. We analyzed the energy status and reproductive development in GH-transgenic common carp by using multi-tissue RNA sequencing, real-time-PCR, Western blotting, ELISA, immunofluorescence, and in vitro incubation. The expression of gys (glycogen synthase) and igfbp1 (insulin-like growth factor binding protein) as well as blood glucose concentrations are lower in GH-transgenic carp. Agrp1 (agouti-related protein 1) and sla (somatolactin a), which are related to appetite and lipid catabolism, are significantly higher in GH-transgenic carp. Low glucose content and increased appetite indicate disrupted metabolic and energy deprivation status in GH-transgenic carp. Meanwhile, the expression of genes, such as gnrhr2 (gonadotropin-releasing hormone receptor 2), gthα (gonadotropin hormone, alpha polypeptide), fshß (follicle stimulating hormone, beta polypeptide), lhß [luteinizing hormone, beta polypeptide] in the pituitary, cyp19a1a (aromatase A) in the gonad, and cyp19a1b (aromatase B) in the hypothalamus, are decreased in GH-transgenic carp. In contrast, pituitary gnih (gonadotropin inhibitory hormone), drd1 (dopamine receptor D1), drd3 (dopamine receptor D3), and drd4 (dopamine receptor D4) exhibit increased expression, which were associated with the retarded reproductive development. Leptin receptor mRNA was detected by fluorescence in situ hybridization in the pituitary including the pars intermedia and proximal pars distalis, suggesting a direct effect of leptin on LH. Recombinant carp Leptin protein was shown to stimulate pituitary gthα, fshß, lhß expression, and ovarian germinal vesicle breakdown in vitro. In addition to neuroendocrine factors, we suggest that reduced hepatic leptin signaling to the pituitary might be part of the response to overexpression of GH and the resulting delay in puberty onset.