MicroRNA-34a Attenuates Paclitaxel Resistance in Prostate Cancer Cells via Direct Suppression of JAG1/Notch1 Axis

Background/Aims: Treatment options for metastatic castrate-resistant prostate cancer (mCRPC) are limited and typically centered on paclitaxel-based chemotherapy. In this study, we aimed to evaluate whether miR-34a attenuates chemoresistance to paclitaxel by regulating target genes associated with drug resistance. Methods: We used data from The Cancer Genome Atlas to compare miR-34a expression levels in prostate cancer (PC) tissues with normal prostate tissues. The effects of miR-34a inhibition and overexpression on PC proliferation were evaluated in vitro via Cell Counting Kit-8 (CCK-8) proliferation, colony formation, apoptosis, and cell-cycle assays. A luciferase reporter assay was employed to identify the interactions between miR-34a and specific target genes. To determine the effects of up-regulation of miR-34a on tumor growth and chemo-resistance in vivo, we injected PC cells overexpressing miR-34a into nude mice subcutaneously and evaluated the rate of tumor growth during paclitaxel treatment. We examined changes in the expression levels of miR-34a target genes JAG1 and Notch1 and their downstream genes via miR-34a transfection by quantitative reverse transcription PCR (qRT-PCR) and western blot assay. Results: miR-34a served as an independent predictor of reduced patient survival. MiR-34a was down-regulated in PC-3PR cells compared with PC-3 cells. The CCK-8 assay showed that miR-34a overexpression resulted in increased sensitivity to paclitaxel while miR-34a down-regulation resulted in chemoresistance to paclitaxel in vitro. A study of gain and loss in a series of functional assays revealed that PC cells expressing miR-34a were chemosensitive. Furthermore, the overexpression of miR-34a increased the sensitivity of PC-3PR cells to chemotherapy in vivo. The luciferase reporter assay confirmed that JAG1 and Notch1 were directly targeted by miR-34a. Interestingly, western blot analysis and qRT-PCR confirmed that miR-34a inhibited the Notch1 signaling pathway. We found that miR-34a increased the chemosensitivity of PC-3PR cells by directly repressing the TCF1/ LEF1 axis. Conclusion: Our results showed that miR-34a is involved in the development of chemosensitivity to paclitaxel. By regulating the JAG1/Notch1 axis, miR-34a or its target genes JAG1 or Notch1 might serve as potential predictive biomarkers of response to paclitaxel-based chemotherapy and/or therapeutic targets that will help to overcome chemoresistance at the mCRPC stage

The corona of a surface bubble promotes electrochemical reactions

The evolution of gaseous products is a feature common to several electrochemical processes, often resulting in bubbles adhering to the electrode’s surface. Adherent bubbles reduce the electrode active area, and are therefore generally treated as electrochemically inert entities. Here, we show that this general assumption does not hold for gas bubbles masking anodes operating in water. By means of imaging electrochemiluminescent systems, and by studying the anisotropy of polymer growth around bubbles, we demonstrate that gas cavities adhering to an electrode surface initiate the oxidation of water-soluble species more effectively than electrode areas free of bubbles. The corona of a bubble accumulates hydroxide anions, unbalanced by cations, a phenomenon which causes the oxidation of hydroxide ions to hydroxyl radicals to occur at potentials at least 0.7 V below redox tabled values. The downhill shift of the hydroxide oxidation at the corona of the bubble is likely to be a general mechanism involved in the initiation of heterogeneous electrochemical reactions in water, and could be harnessed in chemical synthesis.S.C., N.D., and M.L.C. were supported by the Australian Research Council (grant nos. DP190100735, FT190100148, FL170100041, and CE140100012). M.L.C. acknowledges generous supercomputing time from the National Computational Infrastructure. C.W.E. and K.S.I. acknowledge the facilities and technical assistance of Microscopy Australia at the Centre for Microscopy, Characterisation & Analysis, The University of Western Australia, a facility funded by the University, State and Commonwealth Government

PDE1A polymorphism contributes to the susceptibility of nephrolithiasis

We here provide evidence for a monogenic cause of nephrolithiasis, or kidney stones, based on an association of a polymorphism in the <i>PDE1A</i> gene. This variant was detected through whole-exome analysis of ten members of an affected family, as well as a case–control study of a validation cohort including over 2000 patients at our hospital

A monolithic gallium nitride‐based two‐phase synchronous buck converter with high operating frequency

Abstract The need for a high‐frequency and high‐efficiency gallium nitride (GaN)‐based buck converter that can be controlled directly by a low swing pulse width‐modulated (PWM) signal, without the need for additional buffers or preamplifiers, poses a significant challenge in the field of power conversion and dynamically power supply applications. To solve this problem, this letter presents a monolithic two‐phase synchronous buck converter, fabricated using a 0.25‐um GaN‐on‐Si process, integrated both the drivers and power stage transistors, without requiring additional buffers or preamplifiers. So, the proposed converter can be directly controlled by a PWM signal with a swing of only 1 V (−0.5 to 0.5 V). At a 100‐MHz switching frequency, the converter achieves a maximum output power of 12 W with a power stage efficiency of 82%. The converter includes two identical half‐bridge Monolithic Microwave Integrated Circuit (MMICs), and with the frequency multiplication property of multi‐phase topology, the equivalent switching frequency can reach 200 MHz in the open‐loop operating mode. The experimental results show that the converter can track a 40‐MHz bandwidth envelope signal (256 QAM, 6 dB PAPR) with 80.1% efficiency

Controlling the Morphologies of Silver Aggregates by Laser-Induced Synthesis for Optimal SERS Detection

Controlling the synthesis of metallic nanostructures for high quality surface-enhanced Raman scattering (SERS) materials has long been a central task of nanoscience and nanotechnology. In this work, silver aggregates with different surface morphologies were controllably synthesized on a glass&ndash;solution interface via a facile laser-induced reduction method. By correlating the surface morphologies with their SERS abilities, optimal parameters (laser power and irradiation time) for SERS aggregates synthesis were obtained. Importantly, the characteristics for largest near-field enhancement were identified, which are closely packed nanorice and flake structures with abundant surface roughness. These can generate numerous hot spots with huge enhancement in nanogaps and rough surface. These results provide an understanding of the correlation between morphologies and SERS performance, and could be helpful for developing optimal and applicable SERS materials

A Prospective Comparison of Three Strategies for Evaluating Blood Loss in Transurethral Resection of the Prostate

Objective. The aim of the current investigation is to develop a new strategy for evaluating blood loss in the process of transurethral resection of the prostate (TURP). Methods. 318 patients diagnosed with benign prostatic hyperplasia (BPH) that need TURP were enrolled in this study. Hospitalization information including age, height, weight, surgery time, prostate volume, hemoglobin (Hb) concentration, hematocrit (HCT) percentage, and red blood cell count (RBC) was evaluated for each patient. All statistical analysis drawing were conducted using R software. Results. Three methods were employed for calculating blood loss in TURP. Results from a new method display 0 missing value and got higher confidence (0 of 318, Poisson distribution, P<0.001) compared with blood loss calculated with hemoglobin concentration (20.44%) and hematocrit percentage (19.18%). Also, the new method demonstrated narrow range (0.03~270.03 ml) and approximate normal distribution compared with blood loss calculated with hemoglobin concentration and hematocrit percentage. More importantly, the new method explained positive correlation with prostate volume (R2=0.138, P<0.001) and also surgery lasting time (R2=0.193, P<0.001). Conclusion. Methods developed for calculating blood loss in TURP in the current study displayed more accurate and reasonable evaluation of bleeding, which can guide the transfusion blood for patients