ZHX2 mediates proteasome inhibitor resistance via regulating nuclear translocation of NF‐κB in multiple myeloma

Abstract Background Multiple myeloma (MM) is an incurable hematological malignancy. Although proteasome inhibitors and immunomodulators have significantly improved patient outcomes, some patients respond poorly to treatment and almost all patients will relapse. Mechanisms of proteasome inhibitor resistance in multiple myeloma have not been fully elucidated. ZHX2 is a transcription regulator degraded via proteasome and presents both oncogenic or tumor suppressive effect in different cancers, however, it is still unknown that the role of ZHX2 in myeloma. In this study, we aim to demonstrate the effect and mechanism of ZHX2 on proteasome inhibitor resistance in MM. Methods GSE24080 gene expression profile datasets from Gene Expression Omnibus (GEO) were analyzed to evaluate the relationship between ZHX2 expression level and survival in MM. Expression of ZHX2 in human MM cell lines at baseline and after bortezomib (BTZ) treatment was determined by Western blotting (WB). The proliferation and apoptosis rate of MM cells treated with BTZ after the knockdown of ZHX2 were analyzed by flow cytometry. Nuclear translocation of NF‐κB after the knockdown of ZHX2 was evaluated by WB and immunofluorescence, and the expression of NF‐κB target genes was measured by real‐time quantitative PCR. Co‐immunoprecipitation (Co‐IP) and WB were used to detect the interaction of ZHX2 with NF‐κB. Results We found that higher ZHX2 expression was correlated with poorer clinical outcomes of patients. In addition, ZHX2 expression was relatively higher in RPMI‐8226 and MM.1S cell lines and the level of ZHX2 protein was upregulated after BTZ treatment. Knockdown of ZHX2 significantly enhanced the sensitivity of MM cells to BTZ, inhibited nuclear translocation of NF‐κB, and reduced mRNA expression of NF‐κB target genes. It was also revealed that ZHX2 directly binds to NF‐κB. Conclusion Our study showed that ZHX2 can promote proteasome inhibitor resistance in MM cells by regulating the nuclear translocation of NF‐κB

Efficient Spatial-Temporal Information Fusion for LiDAR-Based 3D Moving Object Segmentation

Accurate moving object segmentation is an essential task for autonomous driving. It can provide effective information for many downstream tasks, such as collision avoidance, path planning, and static map construction. How to effectively exploit the spatial-temporal information is a critical question for 3D LiDAR moving object segmentation (LiDAR-MOS). In this work, we propose a novel deep neural network exploiting both spatial-temporal information and different representation modalities of LiDAR scans to improve LiDAR-MOS performance. Specifically, we first use a range image-based dual-branch structure to separately deal with spatial and temporal information that can be obtained from sequential LiDAR scans, and later combine them using motion-guided attention modules. We also use a point refinement module via 3D sparse convolution to fuse the information from both LiDAR range image and point cloud representations and reduce the artifacts on the borders of the objects. We verify the effectiveness of our proposed approach on the LiDAR-MOS benchmark of SemanticKITTI. Our method outperforms the state-of-the-art methods significantly in terms of LiDAR-MOS IoU. Benefiting from the devised coarse-to-fine architecture, our method operates online at sensor frame rate. The implementation of our method is available as open source at: https://github.com/haomo-ai/MotionSeg3D.Comment: Accepted by IROS2022. Code: https://github.com/haomo-ai/MotionSeg3

The enhanced x-ray timing and polarimetry mission – eXTP: an update on its scientific cases, mission profile and development status

The enhanced x-ray timing and polarimetry mission (eXTP) is a flagship observatory for x-ray timing, spectroscopy and polarimetry developed by an international consortium. Thanks to its very large collecting area, good spectral resolution and unprecedented polarimetry capabilities, eXTP will explore the properties of matter and the propagation of light in the most extreme conditions found in the universe. eXTP will, in addition, be a powerful x-ray observatory. The mission will continuously monitor the x-ray sky, and will enable multi-wavelength and multi-messenger studies. The mission is currently in phase B, which will be completed in the middle of 2022