The Effects of Compressive Residual Stress on Properties of Kyanite-Coated Zirconia Toughened Alumina Ceramics.

In this study, the prestressed coating reinforcement method was employed to create kyanite-coated zirconia toughened alumina (ZTA) prestressed ceramics. Due to the mismatch of the coefficient of thermal expansion (CTE) between the coating and substrate, compressive residual stress was introduced in the coating. The effects of compressive residual stress on the mechanical properties of ZTA have been demonstrated. Results show that the flexural strength of the kyanite-coated ZTA ceramics improved by 40% at room temperature compared to ZTA ceramics. In addition, the temperature dependence of mechanical properties has also been discussed. And the results show that the reinforcement gradually diminished with increasing temperature and eventually disappeared at 1000 °C. The modulus of elasticity of the material also exhibits a decreasing trend. Furthermore, the introduction of the prestressing coating enhanced the thermal shock resistance, but the strengthening effect diminished as the temperature increased and completely disappeared at 800 °C.

Targeting NRF2 uncovered an intrinsic susceptibility of acute myeloid leukemia cells to ferroptosis.

Drug resistance and poor treatment response are major obstacles to the effective treatment of acute myeloid leukemia (AML). A deeper understanding of the mechanisms regulating drug resistance and response genes in AML is therefore urgently needed. Our previous research has highlighted the important role of nuclear factor E2-related factor 2 (NRF2) in AML, where it plays a critical role in detoxifying reactive oxygen species and influencing sensitivity to chemotherapy. In this study, we identify a core set of direct NRF2 targets that are involved in ferroptosis, a novel form of cell death. Of particular interest, we find that glutathione peroxidase 4 (GPX4) is a key ferroptosis gene that is consistently upregulated in AML, and high expression of GPX4 is associated with poor prognosis for AML patients. Importantly, simultaneous inhibition of NRF2 with ML385 and GPX4 with FIN56 or RSL3 synergistically targets AML cells, triggering ferroptosis. Treatment with ML385 + FIN56/RSL3 resulted in a marked reduction in NRF2 and GPX4 expression. Furthermore, NRF2 knockdown enhanced the sensitivity of AML cells to the ferroptosis inducers. Taken together, our results suggest that combination therapy targeting both NRF2 and GPX4 may represent a promising approach for the treatment of AML.