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.

[Analysis of microbial diversity of supra-gingival plaque in dental caries].

OBJECTIVE: To investigate the microbial composition and differences in dental plaque of caries and caries-free adults. METHODS: Caries-active (n = 16) was defined as an individual who had at least three untreated decayed tooth and decayed-missing-filled-tooth (DMFT) score greater than 6. Caries-free (n = 16) was defined as an individual who had a DMFT score equal to zero. The patients were 18-35 years old. Samples from supra-gingival plaque were obtained and PCR-denaturing gel electrophoresis cloning and sequencing of caries pathogens were used to catch the core microbial of dental caries. RESULTS: Six phylum, 28 genus and 88 species were detected. In caries group, Prevotella, Capnocytophaga, Actinomyces, Veillonella and Corynebacterium were predominant, accounting for 56.2% (334/594) of the total cloning number of caries group. Caries-free group contained more predonminant genus than caries group. Prevotella, Veillonella, Capnocytophaga, Corynebacterium, Streptococcus, Actinomyces, Aggregatibacter and Neisseria were predominant, accounting for 65.2% (354/543) of the total cloning number of caries-free group. Caries group had less diversity than the caries-free group. The difference was statistically significant (P < 0.05). CONCLUSIONS: Caries might be caused by potentially pathogenic microbial communities rather than a single pathogen. In the progress of dental caries, the microbial diversity decreased.

Experiment of low resistance joints for the ITER correction coil.

A test method was designed and performed to measure joint resistance of the ITER correction coil (CC) in liquid helium (LHe) temperature. A 10 kA superconducting transformer was manufactured to provide the joints current. The transformer consisted of two concentric layer-wound superconducting solenoids. NbTi superconducting wire was wound in the primary coil and the ITER CC conductor was wound in the secondary coil. The primary and the secondary coils were both immersed in liquid helium of a 300 mm useful bore diameter cryostat. Two ITER CC joints were assembled in the secondary loop and tested. The current of the secondary loop was ramped to 9 kA in several steps. The two joint resistances were measured to be 1.2 nΩ and 1.65 nΩ, respectively.