Bisphenols induce cardiotoxicity in zebrafish embryos: Role of the thyroid hormone receptor pathway.

Bisphenols are frequently found in the environment and have been of emerging concern because of their adverse effects on aquatic animals and humans. In this study, we demonstrated that bisphenol A, S, and F (BPA, BPS, BPF) at environmental concentrations induced cardiotoxicity in zebrafish embryos. BPA decreased heart rate at 96 hpf (hours post fertilization) and increased the distance between the sinus venosus (SV) and bulbus arteriosus (BA), in zebrafish. BPF promoted heart pumping and stroke volume, shortened the SV-BAdistance, and increased body weight. Furthermore, we found that BPA increased the expression of the dio3b, thrß, and myh7 genes but decreased the transcription of dio2. In contrast, BPF downregulated the expression of myh7 but upregulated that of thrß. Molecular docking results showed that both BPA and BPF are predicted to bind tightly to the active pockets of zebrafish THRß with affinities of -4.7 and -4.77 kcal/mol, respectively. However, BPS did not significantly affect dio3b, thrß, and myh7 transcription and had a higher affinity for zebrafish THRß (-2.13 kcal/mol). These findings suggest that although BPA, BPS, and BPF have similar structures, they may induce cardiotoxicity through different molecular mechanisms involving thyroid hormone systems. This investigation provides novel insights into the potential mechanism of cardiotoxicity from the perspective of thyroid disruption and offer a cautionary role for the use of BPA substitution.

Transcriptomics unveiled metabolic perturbations in Desmodesmus quadricauda by sulfacetamide: Key functional genes involved in the tolerance and biodegradation process.

Antibiotic contamination in the environment has significant adverse effects on benthic microorganisms, which causes dysfunction of normal ecological processes. However, in-depth molecular mechanisms underlying the potential ecological impacts of these emerging pollutants are poorly understood. In this study, metabolic perturbations in a freshwater microalga, Desmodesmus quadricauda by sulfacetamide (SFM) were investigated using transcriptomics. The results found 28 genes in the tricarboxylic acid cycle and oxidative phosphorolysis pathways were significantly downregulated by 3.97 to 6.07, and 2.47 to 5.99 folds by 0.1 and 1 mg L-1 SFM, respectively. These results indicated that SFM disrupted the microalgal cellular activities through inhibition of energy metabolism. Whilst, the upregulated genes have been most enriched in porphyrin and chlorophyll metabolism (hemE, hemL, hemY, chlD, chlP, PAO, and CAO), and arachidonic acid metabolism (GGT1_5 and gpx). Expression of these genes was significantly upregulated by up to 3.36 times for tolerance against SFM. Moreover, the genes encoding decarboxylase, oxidoreductases, α-amylase, hydrolases, O-acetyltransferase, and lyase were upregulated by >2 folds, which can induce di/hydroxylation, decarboxylation, bond cleavage and deamination. These findings provide insights into the molecular mechanisms of the ecotoxicological effects of antibiotics on microalgae, and supply useful information for their environmental risk assessment and management.

Metabolic perturbations of Lolium perenne L. by enrofloxacin: Bioaccumulation and multistage defense system.

Plants are readily exposed to the antibiotics residues in reclaimed water indicating an urgent need to comprehensively analyze their ecotoxicological effects and fate of these emerging contaminants. Here, we unraveled the dissemination of enrofloxacin (ENR) in a pasture grass, Lolium perenne L., and identified multistage defense systems as its adaptation mechanism. Uptaken concentrations of ENR ranged from 1.28 to 246.60 µg g-1 with bioconcentration factors (BCF) upto 15.13, and translocation factors (TF) upto 0.332. The antioxidant enzymatic activities such as superoxide dismutase, peroxidase, and catalase were increased by upto 115%. Further transcriptomics demonstrated that differentially expressed genes (DEGs) involved in glycolysis, tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and glutathione metabolism were significantly up-regulated by 1.56-5.93, 3-7 and 1.04-6.42 times, respectively; whilst, the DEGs in nitrogen and sulfur metabolism pathways were significantly up-regulated by 1.06-5.64 and 2.64-3.54 folds. These processes can supply energy, signaling molecules, and antioxidants for detoxification of ENR in ryegrass. Such results provide understanding into fasting grass adaptability to antibiotics by enhancing the key protective pathways under organic pollutant stresses in environments.

Unraveling the mechanism of long-term bisphenol S exposure disrupted ovarian lipids metabolism, oocytes maturation, and offspring development of zebrafish.

Bisphenol S (BPS) acts as a xenoestrogen and disturbs the female reproductive system; however, the underlying mechanism has not been elucidated. In this study, the effect of chronic BPS exposure (1 µg/L and 100 µg/L) on ovarian lipid metabolism in zebrafish was investigated to determine its influence on adult reproductive capacity and offspring development. The results showed that long-term (240 days) exposure to BPS induced lipid accumulation in the ovaries by promoting the transport of more lipids from the circulation to the ovaries and by upregulating triacylglycerol synthesis-related genes. Significantly increased expression of cpt2, acadm, acadl, and pparα, which are involved in ß-oxidation in the ovarian mitochondria, indicated that more energy was provided for oocyte maturation in exposed zebrafish ovaries. Thus, the proportion of full-grown stage oocytes in ovaries and egg reproduction were elevated at an accelerated rate, which earlier than normal reproductive cycle (8-10 days posts pawning). Moreover, the maternally BPS-exposed F1 embryos (2 h post-spawning, hpf) showed higher neutral lipid levels, impaired hatching capacity, and increased occurrence of larval deformities. All these findings demonstrated that stimulated lipid synthesis and ß-oxidation in zebrafish ovaries significantly contribute to BPS-induced oocyte precociousness with subsequent effects on the development of unexposed offspring. This study provides new insight into the impact of xenoestrogens on oviparous reproduction in females and offspring development from the perspective of ovarian lipid metabolism.

A structural signature of the breakdown of the Stokes-Einstein relation in metallic liquids.

The breakdown of the Stokes-Einstein relation (SER) in three model metallic liquids is investigated via molecular dynamics simulations. It is found that the breakdown of SER is closely correlated with the clustering behavior of well-packed atoms. When the SER breaks down, many cluster properties have almost the same value in these metallic liquids. At the breakdown temperature of SER, the temperature dependence of the number of clusters begins to deviate from a linear increase and the average number of well-packed atoms in the clusters reaches about 2, which indicates an increase in structure heterogeneity. Moreover, the size of the largest cluster shows a direct correlation with the SER. Therefore, our study provides a possible structural origin for the breakdown of SER in metallic liquids.

Structural disorder in metallic glass-forming liquids.

We investigated structural disorder by a new structural parameter, quasi-nearest atom (QNA), in atomistic configurations of eight metallic glass-forming systems generated through molecular dynamics simulations at various temperatures. Structural analysis reveals that the scaled distribution of the number of QNA appears to be an universal property of metallic liquids and the spatial distribution of the number of QNA displays to be clearly heterogeneous. Furthermore, the new parameter can be directly correlated with potential energy and structural relaxation at the atomic level. Some straightforward relationships between QNA and other properties (per-atom potential energy and α-relaxation time) are introduced to reflect structure-property relationship in metallic liquids. We believe that the new structural parameter can well reflect structure disorder in metallic liquids and play an important role in understanding various properties in metallic liquids.

Crystallization pathways of liquid-bcc transition for a model iron by fast quenching.

We report simulations on the local structural evolution in the liquid-bcc transition of a model iron. Fourteen main Voronoi polyhedra are chosen as the representatives of short-range orders (SROs) and their transformations during crystallization are also investigated. Thus, the crystallization pathways for the main SROs are drawn. Our results also show that the transformations between two SROs in the crystallization pathways can be classified into two categories, first the enlargement of coordination number, second the transformation of local symmetry from five-fold to four-fold. The former reduces the potential energy while the latter increases it. It is found that the potential energy cannot decease monotonously whatever crystallization pathway is chosen to transform the icosahedral SRO to bcc SRO. Therefore, the latter transformation might provide the energy barrier of crystallization. We propose two transformation styles among SROs. All the transformations in the crystallization pathways can be achieved according to the styles. Moreover, the two transformation styles indicates that the bcc structure is more similar to liquid than other crystals. That might be the reason why the first phase nucleated during a rapid cooling process should be bcc crystal.