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The therapeutic efficacy of metformin in prostate cancer (PCa) appears uncertain based on various clinical trials. Metformin treatment failure may be attributed to the high frequency of transcriptional dysregulation, which leads to drug resistance. However, the underlying mechanism is still unclear. In this study, we found evidences that metformin resistance in PCa cells may be linked to cell cycle reactivation. Super-enhancers (SEs), crucial regulatory elements, have been shown to be associated with drug resistance in various cancers. Our analysis of SEs in metformin-resistant (MetR) PCa cells revealed a correlation with Prostaglandin Reductase 1 (PTGR1) expression, which was identified as significantly increased in a cluster of cells with metformin resistance through single-cell transcriptome sequencing. Our functional experiments showed that PTGR1 overexpression accelerated cell cycle progression by promoting progression from the G0/G1 to the S and G2/M phases, resulting in reduced sensitivity to metformin. Additionally, we identified key transcription factors that significantly increase PTGR1 expression, such as SRF and RUNX3, providing potential new targets to address metformin resistance in PCa. In conclusion, our study sheds new light on the cellular mechanism underlying metformin resistance and the regulation of the SE-TFs-PTGR1 axis, offering potential avenues to enhance metformins therapeutic efficacy in PCa.

Abstract To improve the reliability of Two-level three phase voltage source inverters, a uniform fault tolerant strategy based on space vector pulse width modulation is proposed for different leg faults. The reconstructed topologies of inverters with different bridge arm faults are different, which makes the basic voltage vector phase of each reconstructed topology inconsistent, resulting in different calculations. Therefore, the coordinate transformation is applied to place the basic voltage vectors of each reconstructed topology on the synchronous stationary αβ coordinate system so that the calculations of the reconstructed topology under different bridge arm faults are unified, thus reducing the complexity of fault-tolerant control. Aiming at the three-phase current asymmetry caused by the neutral point voltage oscillation in inverter topology reconstruction, a transient compensation method of neutral point voltage offset for the α-axis component of the reference voltage vector is introduced to suppress the adverse effects. The compensation method directly offers a neutral point voltage offset value after Clarke transformation and corrects the α-axis component of the reference voltage vector, avoiding the integral calculation in the conventional voltage compensation algorithm. The correctness and effectiveness of the proposed fault-tolerant control strategy are verified experimentally.

Power li-ion batteries are often used in fields such as electric vehicles due to their high energy density, long cycle life, and low self-discharge. To ensure safe, stable, and reliable operation of power li-ion batteries, accurate and effective detection of battery performance is crucial. Conventional detection methods of battery capacity, remaining life, and other battery performance parameters usually require complete charge-discharge cycle data, resulting in long detection times and low efficiency. Therefore, how to achieve rapid detection of battery performance has become a hot research topic with engineering demands. There have been certain research achievements in the rapid detection technology of power li-ion battery performance. This article elaborates on the significance of rapid detection of li-ion power battery performance, summarizes key technologies and technical characteristics related to rapid detection based on current research achievements, and provides reference to the rapid detection of li-ion power battery performance.

Introduction: Percutaneous nephrolithotomy (PCNL) is the recommended treatment for 2–4-cm renal stones. Minimally invasive PCNL (MPCNL) with ≤22F sheath was frequently used instead of standard PCNL. MPCNL uses pressurized irrigation to flush out stone fragments through a conventional nephrostomy sheath (cNS), which may result in higher intrarenal pressure (IRP) and longer operating time. The novel vacuum-assisted nephrostomy sheath (vaNS) was developed to mitigate higher IRP and to facilitate stone removal. It might improve the performance of MPCNL. This prospective and randomized trial compares these two sheaths. Materials and Methods: In total, 120 patients with 2–4-cm renal stones were accrued in six tertiary medical centers with equal numbers in 2021. In total, 120 patients underwent mPCNL, 60 using 18F cNS and 60 using 18F vaNS, in a prospective and randomized assignment. The primary outcome measurement is decrease in IRP. The secondary outcome is efficacy in stone retrieval. Results: The IRP was lower with vaNS than with cNS: mean IRP during lithotripsy was 12.0 ± 2.7 mm Hg with vaNS vs 20.4 ± 6.0 mm Hg with cNS, p = 0.000. IRP duration ≥30 mm Hg was shorter with vaNS than with cNS (6.7 ± 7.4 seconds vs 113.4 ± 222.7 seconds, p = 0.001). vaNS has shorter stone removal time (26.9 ± 14.3 minutes vs 35.7 ± 11.8 minutes, p = 0.000). Stone extraction rate was higher (166.4 ± 88.1 mm3/min vs 90.4 ± 31.7 mm3/min, p = 0.000). Stone grasper usage was less (1.4 ± 2.6 vs 11.9 ± 9.7, p = 0.000). vaNS maintained the safety profile. Blood loss, creatinine changes, perioperative complications, and hospital stays were the same in both groups, all p > 0.05. Conclusion: MPCNL for stones 2–4 cm using vaNS has shorter stone removal time, higher stone extraction rate, and less use of stone extractor. vaNS is superior to cNS at reducing IRP and is associated with improved stone free rates at 3 days but not at 30 days postoperatively. The trial was registered with Chinese Clinical Trial Registry (ClinicalTrials.gov, NCT ChiCTR2000039681). [ABSTRACT FROM AUTHOR]