Design, synthesis and preliminary bioactivity studies of 2-thioxo-4-thiazolidinone derivatives as Bcl-2 inhibitors.

The B-cell lymphoma-2 (Bcl-2) protein is a promising target for cancer therapy. In the present study, a series of 2-thioxo-4-thiazolidinone derivatives were designed and synthesized as Bcl-2 inhibitors. Most of them possessed decent inhibitory activity for anti-apoptotic Bcl-2 proteins. Among them, compound 31 has similar growth inhibition towards K562 compared to (R)-Gossypol. In addition, it inhibits the myeloid cell leukemia sequence 1 (Mcl-1) protein with a Ki value of 74 nM.

Electrical Resistance Performance of Cable Accessory Interface Considering Thermal Effects.

Power cables are widely used in various fields of power transmission, and cable accessories are the weakest link in power cable systems due to their complex structure and multi-layer insulation coordination issues. This paper investigates the changes in electrical properties of the silicone rubber/cross-linked polyethylene (SiR/XLPE) interface at high temperatures. The physicochemical properties of XLPE material under thermal effects with different times are characterized through FTIR, DSC, and SEM tests. Finally, the mechanism of the effects of the interface state on the electrical properties of the SiR/XLPE interface is analyzed. It is found that with the increase in temperature, the changes in electrical performance of the interface do not show a monotonic downward trend, while interestingly, they can be divided into three stages. Under the thermal effects for 40 d, the internal recrystallization of XLPE in the early stage improves the electrical properties of the interface. In the later stage of thermal effects, the amorphous region inside the material is severely damaged and the molecular chains are severely broken, resulting in a decrease in the electrical properties of the interface. The results above provide a theoretical basis for the interface design of cable accessories at high temperatures.

TSLP protects against sepsis-induced liver injury by inducing autophagy via activation of the PI3K/Akt/STAT3 pathway.

BACKGROUND: Liver injury is the main factor in multiple organ failure caused by sepsis. Thymic stromal lymphopoietin (TSLP) is derived from epithelial cells and plays an important role in inflammation, allergies and cancer. The role of TSLP in sepsis-induced liver injury (SILI) is unclear. The purpose of this study was to investigate the effect of TSLP on sepsis-induced liver injury and to clarify the mechanism. METHODS: Wild-type (WT) mice and TSLPR knockout (TSLPR-/-) mice were subjected to cecal ligation and puncture (CLP) to generate a SILI model. Liver injury was assessed by measuring the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), histologic liver injury scores, hepatocyte death, and liver inflammatory factors. Signal pathways were explored in vivo to identify possible mechanisms for TSLP in SILI. RESULTS: The expression of TSLP and TSLPR increased during SILI. Deletion of TSLPR exacerbated liver injury in terms of serum ALT, AST, histologic liver injury scores, and liver inflammatory factors. Compared with controls, administration of exogenous recombinant mouse TSLP reduced liver injury in WT mice during SILI, but failed to reduce liver injury in TSLPR-/- mice. TSLP induced autophagy in hepatocytes during SILI. Mechanistically, Akt and STAT3 were activated in WT mice during SILI. The opposite results were observed in TSLPR-/- mice. In addition, the protective effects of TSLP in WT mice were blocked by PI3K inhibitor, LY294002, during SILI. CONCLUSION: These results suggest that TSLP can improve liver injury caused by sepsis and its specific mechanism may be related to inducing autophagy through the PI3K/Akt/STAT3 signaling pathway.