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Abstract Graphene quantum dots (GQDs) possess great potential in various applications due to their superior physicochemical properties and wide array of available surface modifications. However, the toxicity of GQDs has not been systematically assessed, thus hindered their further development; especially, the risk of surface modifications of GQDs is largely unknown. In this study, we employed a lung carcinoma A549 cells as the model to investigate the cytotoxicity and autophagy induction of three types GQDs, including cGQDs (COOH-GQDs), hGQDs (OH-GQDs), and aGQDs (NH 2 -GQDs). The results showed hGQDs was the most toxic, as significant cell death was induced at the concentration of 100 μg/mL, determining by WST-1 assay as well as Annexin-V-FITC/PI apoptosis analysis, whereas cGQDs and aGQDs were non-cytotoxic within the measured concentration. Autophagy detection was performed by TEM examination, LC3 fluorescence tracking, and Western-blot. Both aGQDs and hGQDs induced cellular autophagy to various degrees except for cGQDs. Further analysis on autophagy pathways indicated all GQDs significantly activated p-p38MAPK; p-ERK1/2 was inhibited by aGQDs and hGQDs but activated by cGQDs. p-JNK was inhibited by aGQDs and cGQDs, while activated by hGQDs. Simultaneously, Akt was activated by hGQDs but inhibited by aGQDs. Inhibition of autophagy by 3-MA significantly increased the cytotoxicity of GQDs, suggesting that autophagy played a protective role against the toxicity of GQDs. In conclusion, cGQDs showed excellent biocompatibility and may be considered for biological applications. Autophagy induction may be included in the health risk assessment of GQDs as it reflects the stress status which may eventually lead to diseases. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

• TCBPA caused developmental neurotoxicity in zebrafish. • TCBPA caused developmental cardiovascular toxicity in zebrafish. • Focal adhesion, ECM-receptor interaction pathways were involved in the developmental toxicity of TCBPA. • TCBPA led to alterations in the arginine-related metabolic pathway. Tetrachlorobisphenol A (TCBPA), a widely used halogenated flame retardant, is frequently detected in environmental compartments and human samples. However, unknown developmental toxicity and mechanisms limit the entire understanding of its effects. In this study, zebrafish (Danio rerio) embryos were exposed to various concentrations of TCBPA while a combination of transcriptomics, behavioral and biochemical analyzes as well as metabolomics were applied to decipher its toxic effects and the potential mechanisms. We found that TCBPA could interfere with nervous and cardiovascular development through focal adhesion and extracellular matrix-receptor (ECM-receptor) interaction pathways through transcriptomic analysis. Behavioral and biochemical analysis results indicated abnormal swimming behavior of zebrafish larvae. Morphological observations revealed that TCBPA could cause the loss of head blood vessels. Metabolomic analysis showed that arginine-related metabolic pathways were one of the main pathways leading to TCBPA developmental toxicity. Our study demonstrated that by using omics, TCBPA was shown to have neurological and cardiovascular developmental toxicity and the underlying mechanisms were uncovered and major pathways identified. [Display omitted] [ABSTRACT FROM AUTHOR]

Previous animal experiments have implied that organophosphate esters (OPEs) have a disruption effect on the thyroid endocrine system. However, knowledge of the toxicological mechanism remains limited. In this study, the activities of four OPEs have been characterized against the thyroid hormone (TH) nuclear receptor (TR) using two in vitro models, with the aim of evaluating their toxicity mechanisms towards the TR. The results of a TH-dependent cell proliferation assay showed that tris(2-chloro-1-(chloromethyl)ethyl)phosphate (TDCPP) could induce cell growth, while the other three OPEs had no effect. The results of a luciferase reporter gene assay revealed that all four of the OPEs tested in the current study showed agonistic activity towards TRβ, with TDCPP being the most potent one. Moreover, molecular docking revealed that all the tested OPEs could fit into the ligand binding pocket of TRβ, with TDCPP binding more effectively than the other three OPEs. Taken together, these data suggest that OPEs might disrupt the thyroid endocrine system via a mechanism involving the activation of TR. [ABSTRACT FROM AUTHOR]