Recent Advances of Electrocatalysts and Electrodes for Direct Formic Acid Fuel Cells:from Nano to Meter Scale Challenges

Direct formic acid fuel cells are promising energy devices with advantages of low working temperature and high safety in fuel storage and transport. They have been expected to be a future power source for portable electronic devices. The technology has been developed rapidly to overcome the high cost and low power performance that hinder its practical application, which mainly originated from the slow reaction kinetics of the formic acid oxidation and complex mass transfer within the fuel cell electrodes. Here, we provide a comprehensive review of the progress around this technology, in particular for addressing multiscale challenges from catalytic mechanism understanding at the atomic scale, to catalyst design at the nanoscale, electrode structure at the micro scale and design at the millimeter scale, and finally to device fabrication at the meter scale. The gap between the highly active electrocatalysts and the poor electrode performance in practical devices is highlighted. Finally, perspectives and opportunities are proposed to potentially bridge this gap for further development of this technology

Adjuvant chemotherapy of megestrol acetate in advanced breast cancer: A meta-analysis

To evaluate the effectiveness and safety of adjuvant chemotherapy of megestrol acetate (MA) in advanced breast cancer, we searched CBM, CNKI, VIP, Wangfang Data and PubMed, and collected randomized controlled trials (RCT) of adjuvant chemotherapy of MA in advanced breast cancer. MA significantly increased treatment efficiency (p=0.0010); improve weight (p<0.0001), appetite (p=0.001) and KPS (p=0.06); ameliorate leucopenia (p=0.02), thrombocytopenia (p=0.02) and hemoglobin (p=0.01); reduce gastrointestinal reaction (p=0.0005) of the patients of adjuvant chemotherapy in advanced breast cancer. MA significantly increased treatment efficiency, improve the nutritional situation, reduce bone marrow suppression, and gastrointestinal reaction of the patients of adjuvant chemotherapy in advanced breast cancer. High-quality RCTs are needed to guidance for preliminary studies of the effective treatment of adjuvant chemotherapy of MA in advanced breast cancer.

Targeting the MYC Ubiquitination-Proteasome Degradation Pathway for Cancer Therapy

Deregulated MYC overexpression and activation contributes to tumor growth and progression. Given the short half-life and unstable nature of the MYC protein, it is not surprising that the oncoprotein is highly regulated via diverse posttranslational mechanisms. Among them, ubiquitination dynamically controls the levels and activity of MYC during normal cell growth and homeostasis, whereas the disturbance of the ubiquitination/deubiquitination balance enables unwanted MYC stabilization and activation. In addition, MYC is also regulated by SUMOylation which crosstalks with the ubiquitination pathway and controls MYC protein stability and activity. In this mini-review, we will summarize current updates regarding MYC ubiquitination and provide perspectives about these MYC regulators as potential therapeutic targets in cancer

Targeting the MYC Ubiquitination-Proteasome Degradation Pathway for Cancer Therapy

Deregulated MYC overexpression and activation contributes to tumor growth and progression. Given the short half-life and unstable nature of the MYC protein, it is not surprising that the oncoprotein is highly regulated via diverse posttranslational mechanisms. Among them, ubiquitination dynamically controls the levels and activity of MYC during normal cell growth and homeostasis, whereas the disturbance of the ubiquitination/deubiquitination balance enables unwanted MYC stabilization and activation. In addition, MYC is also regulated by SUMOylation which crosstalks with the ubiquitination pathway and controls MYC protein stability and activity. In this mini-review, we will summarize current updates regarding MYC ubiquitination and provide perspectives about these MYC regulators as potential therapeutic targets in cancer.</jats:p

The Ubiquitin-specific Protease USP36 Associates with the Microprocessor Complex and Regulates miRNA Biogenesis by SUMOylating DGCR8

miRNA biogenesis is a cellular process that produces mature miRNAs from their primary transcripts, pri-miRNAs, via two RNAse III enzyme complexes: the Drosha-DGCR8 microprocessor complex in the nucleus and the Dicer-TRBP complex in the cytoplasm. Emerging evidence suggests that miRNA biogenesis is tightly regulated by posttranscriptional and posttranslational modifications and aberrant miRNA biogenesis is associated with various human diseases including cancer. DGCR8 has been shown to be modified by SUMOylation. Yet, the SUMO ligase mediating DGCR8 SUMOylation is currently unknown. Here, we report that USP36, a nucleolar ubiquitin-specific protease essential for ribosome biogenesis, is a novel regulator of DGCR8. USP36 interacts with the microprocessor complex and promotes DGCR8 SUMOylation, specifically modified by SUMO2. USP36-mediated SUMOylation does not affect the levels of DGCR8 and the formation of the Drosha-DGCR8 complex, but promotes the binding of DGCR8 to pri-miRNAs. Consistently, abolishing DGCR8 SUMOylation significantly attenuates its binding to pri-miRNAs and knockdown of USP36 attenuates pri-miRNA processing, resulting in marked reduction of tested mature miRNAs. Induced expression of a SUMOylation-defective mutant of DGCR8 inhibits cell proliferation. Together, these results suggest that USP36 plays an important role in regulating miRNA biogenesis by SUMOylating DGCR8.Significance:This study identifies that USP36 mediates DGCR8 SUMOylation by SUMO2 and is critical for miRNA biogenesis. As USP36 is frequently overexpressed in various human cancers, our study suggests that deregulated USP36-miRNA biogenesis pathway may contribute to tumorigenesis.</jats:sec

Regulation of the MDM2-p53 pathway by ribosomal protein L11 involves a post-ubiquitination mechanism

Inhibition of the MDM2-p53 feedback loop is critical for p53 activation in response to cellular stresses. The ribosomal proteins L5, L11, and L23 can block this loop by inhibiting MDM2-mediated p53 ubiquitination and degradation in response to ribosomal stress. Here, we show that L11, but not L5 and L23, leads to a drastic accumulation of ubiquitinated and native MDM2. This effect is dependent on the ubiquitin ligase activity of MDM2, but not p53, and requires the central MDM2 binding domain (residues 51-108) of L11. We further show that L11 inhibited 26 S proteasome-mediated degradation of ubiquitinated MDM2 in vitro and consistently prolonged the half-life of MDM2 in cells. These results suggest that L11, unlike L5 and L23, differentially regulates the levels of ubiquitinated p53 and MDM2 and inhibits the turnover and activity of MDM2 through a post-ubiquitination mechanism