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Background While androgen-deprivation-therapy with the recently developed anti-androgen enzalutamide (Enz) shows promising therapeutic benefits in men with metastatic castration-resistant prostate cancer (PCa), many patients develop resistance to Enz, which may involve the induction of the androgen receptor (AR) splicing variant 7 (AR-v7). Objective Our aim is to identify the mechanisms responsible for AR-v7 production and to develop novel preclinical approaches to suppress the Enz-resistant (EnzR) PCa. Design, setting, and participants We established EnzR-PCa cell lines and examined the long noncoding RNA Malat1 (Malat1) function in conferring Enz resistance. We also examined the in vivo effects of Malat1 short interfering RNA and the AR-v7 degradation enhancer, ASC-J9®. Outcome measurements and statistical analysis Enz resistance and expression of Malat1 and AR-v7. All statistical comparisons were analyzed with a t-test or one way analysis of variance followed by t-test. Results and limitations We demonstrated that Malat1 is indispensable for Enz-induced AR-v7 production in VCaP and EnzR-C4-2 cells. We observed increased AR-v7 and Malat1 expression in our established EnzR-PCa cell lines and in some PCa patients who received Enz treatment. Targeting the Malat1/AR-v7 axis resulted in altering the PCa resistance to androgen deprivation therapy with Enz. The limitation of this study includes the small sample size from the same human patients before and after receiving Enz treatment. Conclusions Targeting the Malat1/AR-v7 axis via Malat1-short interfering RNA or AR-v7 degradation enhancer ASC-J9® in EnzR-PCa cell lines and mouse models suppressed EnzR-PCa progression. Patient summary Androgen deprivation therapy-enzalutamide treatment may not be the best choice for prostate cancer patients who have higher expression of the Malat1/ androgen receptor splicing variant 7 axis, and new therapies using Malat1-short interfering RNA or ASC-J9® may be developed in the future to better suppress enzalutamide-resistant prostate cancer.

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The practical application of Na–S batteries is largely hindered by their low mass loading, inferior rate capability, and poor cycling performance. Herein, we report a design strategy for encapsulation of sodium polysulfides using Ti3C2T x MXene. Porous nitrogen-doped Ti3C2T x MXene microspheres have been synthesized by a facile synthesis method. Porous nitrogen-doped Ti3C2T x MXene microspheres contain abundant pore structures and heteroatom functional groups for structural and chemical synergistic encapsulation of sodium polysulfides. Sodium–sulfur batteries, based on the as-proposed cathode, demonstrated outstanding electrochemical performances, including a high reversible capacity (980 mAh g–1 at 0.5 C rate) and extended cycling stability (450.1 mAh g–1 at 2 C after 1000 cycles at a high areal sulfur loading of 5.5 mg cm–2). This MXene-based hybrid material is a promising cathode host material for polysulfide-retention, enabling high-performance Na–S batteries.

Background: PCa stem/progenitor cells develop higher chemoresistance. Results: High TR4 levels in PCa stem/progenitor cells were shown to be critical in conferring chemoresistance to these cells. Conclusion: TR4-Oct4-IL1Ra signaling is important in conferring chemoresistance to PCa stem/progenitor cells. Significance: This finding suggests that targeting TR4 and its downstream molecules may be a better therapeutic approach to battle PCa stem/progenitor cell-originated chemoresistance.