TBBPA and Its Alternatives Disturb the Early Stages of Neural Development by Interfering with the NOTCH and WNT Pathways

Tetrabromobisphenol A (TBBPA), as well as its alternatives Tetrabromobisphenol S (TBBPS) and Tetrachlorobisphenol A (TCBPA), are widely used halogenated flame retardants. Their high detection rates in human breast milk and umbilical cord serum have raised wide concerns about their adverse effects on human fetal development. In this study, we evaluated the cytotoxicity and neural developmental toxicity of TBBPA, TBBPS, and TCBPA with a mouse embryonic stem cell (mESC) system, at human body fluid and environmental relevant doses. All the three compounds showed similar trends in their cytotoxic effects. However, while TBBPA and TBBPS stimulated ESC neural differentiation, TCBPA significantly inhibited neurogenesis. Mechanistically, we demonstrated that, as far as the NOTCH (positive regulator) and WNT (negative regulator) pathways were concerned, TBBPA only partially and slightly disturbed them, whereas TBBPS significantly inhibited the WNT pathway, and TCBPA down-regulated the expression of NOTCH effectors but increased the WNT signaling, actions which both inhibited neural specification. In conclusion, our findings suggest that TBBPS and TCBPA may not be safe alternatives to TBBPA, and their toxicity need to be comprehensively evaluated

Carbon Dots with Continuously Tunable Full-Color Emission and Their Application in Ratiometric pH Sensing

Two types of carbon dots (C dots) exhibiting respective excitation-independent blue emission and excitation-dependent full-color emissions have been synthesized via a mild one-pot process from chloroform and diethylamine. This new bottom-up synthetic strategy leads to highly stable crystalline C dots with tunable surface functionalities in high reproducibility. By detailed characterization and comparison of the two types of C dots, it is proved concretely that the surface functional groups, such as CO and CN, can efficiently introduce new energy levels for electron transitions and result in the continuously adjustable full-color emissions. A simplified energy level and electron transition diagram has been proposed to help understand how surface functional groups affect the emission properties. By taking advantage of the unique excitation-dependent full-color emissions, various new applications can be anticipated. Here, as an example, a ratiometric pH sensor using two emission wavelengths of the C dots as independent references has been constructed to improve the reliability and accuracy, and the pH sensor is applied to the measurement of intracellular pH values and cancer diagnosis