Loss of the vitamin D receptor triggers senescence in chronic myeloid leukemia via DDIT4-mediated DNA damage

Chronic myeloid leukemia(CML)is a hematopoietic malignancy driven by the fusion gene BCR::ABL1.Drug resistance to tyrosine kinase inhibitors(TKIs),due to BCR::ABL1 mutations and residual leukemia stem cells(LSCs),remains a major challenge in CML treatment.Here,we revealed the requirement of the vitamin D receptor(VDR)in the progression of CML.VDR was upregulated by BCR::ABL1 and highly expressed in CML cells.Interestingly,VDR knockdown inhibited the proliferation of CML cells driven by both BCR::ABL1 and TKI-resistant BCR::ABL1 mutations.Mechanistically,VDR transcriptionally regulated DDIT4 expression;reduced DDIT4 levels upon VDR knockdown triggered DNA damage and senescence via p53 signaling activation in CML cells.Furthermore,VDR deficiency not only suppressed tumor burden and progression in primary CML mice but also reduced the self-renewal capacity of CML-LSCs.Together,our study demonstrated that targeting VDR is a promising strategy to overcome TKI resistance and eradicate LSCs in CML.

Application of BIB polishing technology in cross-section preparation of porous, layered and powder materials: A review

For the accuracy of experimental results, preparing a high quality polished surface and cross-section of the materials for further analysis using electron backscattered diffraction (EBSD), electron probe microanalysis (EPMA), and scanning probe microscopy (SPM) is extremely important. Broad ion beam (BIB) polishing, a method based on the principle of ion bombardment, has irreplaceable advantages. It makes up for the drawbacks and limitations of traditional polishing methods such as mechanical polishing, electrochemical polishing, and chemical polishing. The ions will not leave the bombardment area during polishing, which makes the BIB method suitable for porous materials. The energy of the ion beam can be adjusted according to the sample to reduce the deformation and strain of the polishing area, especially for fragile, soft, and hard materials. The conditions that need to be controlled during BIB polishing are simple. This paper demonstrated the unique advantages of BIB polishing technology in porous, layered and powder materials characterization through some typical application examples, and guided more researchers to understand and utilize BIB polishing technology in the development of new applications.