Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase.

Hepatocellular carcinoma (HCC) is a frequently diagnosed malignancy with a high mortality rate. Cisplatin (CDDP) is a widely applied anti-cancer drug. However, a large population of liver cancer patients developed CDDP resistance. The polypyrimidine tract binding protein (PTBP1) is an RNA-binding protein involving in progressions of diverse cancers. Here we report PTBP1 was significantly upregulated in liver tumors and cell lines. Silencing PTBP1 effectively sensitized HCC cells to CDDP. From the established CDDP-resistant HCC cell line (HepG2 CDDP Res), we observed that CDDP-resistant cells were more sensitive to CDDP under low glutamine supply compared with that in HCC parental cells. CDDP-resistant HCC cells displayed elevated glutamine metabolism rate. Consistently, PTBP1 promotes glutamine uptake and the glutamine metabolism key enzyme, glutaminase (GLS) expression. Bioinformatics analysis predicted that the 3'-UTR of GLS mRNA contained PTBP1 binding motifs which were further validated by RNA immunoprecipitation and RNA pull-down assays. PTBP1 associated with GLS 3'-UTR to stabilize GLS mRNA in HCC cells. Finally, we demonstrated that the PTBP1-promoted CDDP resistance of HCC cells was through modulating the GLS-glutamine metabolism axis. Summarily, our findings uncovered a PTBP1-mediated CDDP resistance pathway in HCC, suggesting that PTBP1 is a promisingly therapeutic target to overcome chemoresistance of HCC.

All-MXene-Based Integrated Membrane Electrode Constructed using Ti3C2Tx as an Intercalating Agent for High-Performance Desalination.

2D-Ti3C2Tx MXene flake restacking and the small interlayer spacing of these MXenes limit their application in capacitive deionization. Here, we designed an all-MXene-based (L-S-Ti3C2Tx) flexible film electrode, enabled by large-size Ti3C2Tx (lateral dimensions of ⩾1 µm) MXene (L-Ti3C2Tx) nanosheets, which provided conductive pathways and were active substances, and by small-size Ti3C2Tx (500 nm) MXene (S-Ti3C2Tx) nanosheets, which were used as intercalation materials and active substances, for high-performance desalination in capacitive deionization applications. The as-synthesized L-S-Ti3C2Tx electrode achieved an excellent capacitance (169 F/g at 5 mV/s) and long-term cycling stability (maintained 91.7% of the initial capacitance after 5000 cycles). Additionally, these electrodes exhibited a high electroadsorption capacity (72 mg NaCl/g L-S-Ti3C2Tx, 10 mM NaCl solution). The improved electrochemical and desalination performance and outstanding long-term cycling stability can be attributed to the small Ti3C2Tx sheets that were introduced, which could be beneficial in exposing more active sites, facilitating electron transport, and shortening the diffusion path of Na ions. Our work opens up a new design space for the development of high-performance anode materials.

Study on Properties of 45 Carbon Steel Ni-P Electroless Plating Reinforced by Si3N4-Al2O3 Particle Based on Response Surface Method.

The effects of the different content of Si³N4 particles and Al²O³ particles in the plating solution and the different ratios on the wear resistance, microhardness, corrosion resistance and other properties of the coating were analyzed by using the centre composite surface design of response surface method (RSM). Meanwhile the phase composition, appearance, microhardness, friction coefficient and corrosion resistance of the electroless coating were tested. The results show that the addition of Al²O³ and Si³N4 particles in the bath can increase the microhardness of the electroless composite coating. In a certain range, the increase of Al²O³ or Si³N4 particles in the bath causes the microhardness of the coating to increase, but the excessive addition of particles makes microhardness decrease; the electroless coating with two particles added will have a low coefficient of friction; and with respect to corrosion resistance, the addition of Al²O³ or Si³N4 particles will increase the corrosion resistance of the coating. Overall, the electroless coating with the Al²O³ content of 16 g/L and the Si³N4 content of 12.63 g/L has the better comprehensive performance.

Loss of PTEN promotes podocyte cytoskeletal rearrangement, aggravating diabetic nephropathy.

In diabetic nephropathy (DN), podocyte cytoskeletal rearrangement occurs followed by podocyte effacement and the development of proteinuria. PTEN (phosphatase and tensin homologue) is a ubiquitously expressed phosphatase that plays a critical role in cell proliferation, cytoskeletal rearrangement, and motility. In mouse models of diabetes mellitus, PTEN expression is reportedly decreased in mesangial cells, contributing to expansion of the mesangial matrix, but how PTEN in the podocyte influences the development of DN is unknown. We observed that PTEN expression is down-regulated in the podocytes of diabetic db/db mice and patients with DN. In cultured podocytes, PTEN inhibition caused actin cytoskeletal rearrangement and this response was associated with unbalanced activation of the small GTPases Rac1/Cdc42 and RhoA. In mice treated with PTEN inhibitor, actin cytoskeletal rearrangement occurred in podocytes and was accompanied by increased albumin excretion. We also created mice with an inducible deletion of PTEN selectively in podocytes. These mice exhibited increased albumin excretion and moderate foot process effacement. When the mice were challenged with a high fat diet, podocyte-specific knockout of PTEN resulted in substantially increased proteinuria and glomeruloclerosis compared to control mice fed a high fat diet or mice with PTEN deletion fed a normal diet. These results indicate that PTEN is involved in the regulation of cytoskeletal rearrangement in podocytes and that loss of PTEN predisposes to the development of proteinuria and DN.