Background: Gliomas are the most common primary tumors in central nervous system. Despite advances in diagnosis and therapy, the prognosis of glioma remains gloomy. Autophagy is a cellular catabolic process that degrades proteins and damaged organelles, which is implicated in tumorigenesis and tumor progression. Autophagy related 4C cysteine peptidase (ATG4C) is an autophagy regulator responsible for cleaving of pro-LC3 and delipidation of LC3 II. This study was designed to investigate the role of ATG4C in glioma progression and temozolomide (TMZ) chemosensitivity. Methods: The association between ATG4C mRNA expression and prognosis of gliomas patients was analyzed using the TCGA datasets. The role of ATG4C in proliferation, apoptosis, autophagy, and TMZ chemosensitivity were investigated by silencing ATG4C in vivo. Ectopic xenograft nude mice model was established to investigate the effects of ATG4C on glioma growth in vivo. Results: The median overall survival (OS) time of patients with higher ATG4C expression was significantly reduced (HR: 1.48, p = 9.91 × 10 − 7). ATG4C mRNA expression was evidently increased with the rising of glioma grade (p = 2.97 × 10 − 8). Knockdown ATG4C suppressed glioma cells proliferation by inducing cell cycle arrest at G1 phase. ATG4C depletion suppressed autophagy and triggered apoptosis through ROS accumulation. Depletion of ATG4C suppressed TMZ-activated autophagy and promoted sensitivity of glioma cells to TMZ. Additionally, ATG4C knockdown suppressed the growth of glioma remarkably in nude mice. Conclusion: ATG4C is a potential prognostic predictor for glioma patient. Targeting ATG4C may provide promising therapy strategies for gliomas treatment.
Conspectus The carbon balance has been disrupted by the widespread use of fossil fuels and subsequent excessive emissions of carbon dioxide (CO2), which has become an increasingly critical environmental challenge for human society. The production and use of renewable energy sources and/or chemicals have been proposed as important strategies to reduce emissions, of which the electrochemical CO2 (or CO) reduction reaction (CO2RR/CORR) in the aqueous systems represents a promising approach. Benefitted by the capacity of manufacturing high-value-added products (e.g., ethylene, ethanol, formic acid, etc.) with a net-zero carbon emission, copper-based CO2RR/CORR powered by sustainable electricity is regarded as a potential candidate for carbon neutrality. However, the diversity of selectivities in copper-based systems poses a great challenge to the research in this field and sets a great obstacle for future industrialization. To date, scientists have revealed that the electrocatalyst design and preparation play a significant role in achieving efficient and selective CO2-to-chemical (or CO-to-chemical) conversion. Although substantial efforts have been dedicated to the catalyst preparation and corresponding electrosynthesis of sustainable chemicals from CO2/CO so far, most of them are still derived from empirical or random searches, which are relatively inefficient and cost-intensive. Most of the mechanism studies have suggested that both intrinsic properties (such as electron states) and extrinsic environmental factors (such as surface energy) of a catalyst can significantly alter catalytic performance. Thus, these two topics are mainly discussed for copper-based catalyst developments in this Account. Here, we provided a concise and comprehensive introduction to the well-established strategies employed for the design of copper-based electrocatalysts for CO2RR/CORR. We used several examples from our research group, as well as representative studies of other research groups in this field during the recent five years, with the perspectives of tuning local electron states, regulating alloy phases, modifying interfacial coverages, and adjusting other interfacial microenvironments (e.g., molecule modification or surface energy). Finally, we employed the techno-economic assessment with a viewpoint on the future application of CO2/CO electroreduction in manufacturing sustainable chemicals. Our study indicates that when carbon price is taken into account, the electrocatalytic CO2-to-chemical conversion can be more market-competitive, and several potential value-added products including formate, methanol, ethylene, and ethanol can all make profits under optimal operating conditions. Moreover, a downstream module employing traditional chemical industrial processes (e.g., thermal polymerization, catalytic hydrolysis, or condensation process) will also make the whole electrolysis system profitable in the future. These design principles, combined with the recent advances in the development of efficient copper-based electrocatalysts,...
The development of catalysts and electrochemical systems for CO2 electroreduction has achieved substantial progress recently, while the long‐time operation of electrolyzing CO2 to formate with high activity and selectivity remains as a major challenge, due to the continuous carbonate precipitation at elevated pHs. Herein, hexagonal phase In2O3 (h‐In2O3) is demonstrated with a monodispersed porous nanosphere structure that can serve as an efficient electrocatalyst for converting CO2 to formate, with a peak Faradaic efficiency of 98%, high partial current densities for producing formate, and outstanding electrochemical stability, substantially exceeding cubic phase In2O3 and most of the previously reported electrocatalysts. Both experimental and theoretical studies reveal that the excellent activity and stability are attributed to the enhanced adsorption and activation of CO2 on the h‐In2O3 surface, and the rich surface hydroxyl groups further facilitate the inhibition of carbonate formation. This work suggests attractive features of the phase engineering to modulate surface hydroxyl groups for efficient and robust catalysts for CO2 electroreduction.
Electrochemical CO reduction reaction (CORR) represents a potential approach to generate value-added products. Nonetheless, it is generally challenging for conventional measurements to quantify the catalytic surface properties, due to the geometric blockage and synergistic effect from the support. Herein, the surface energy of copper-loaded nitrogen-doped carbon (Cu/NC) was investigated by adsorption with specific functional groups using inverse gas chromatography (IGC). The dispersive component (γS D) and the acid/base character of the surface energy were determined using non-polar and polar probe molecules. The specific free energy (ΔG AB), the enthalpy of adsorption (ΔH AB), and the acidic (K A) and basic (K D) parameters were obtained, which allowed to provide the affinity information of intermediates such as *CHO, *OCH2COH, and *H. The surface energy analysis suggested that the Cu/N0.17C catalyst with the highest basic parameter (K D = 7.350) and optimal acid interaction (K A/K D ∼ 0.046) exhibited high catalytic performance in the acetate production, with a Faradaic efficiency (FE) of 63% and a partial current density of −330 mA·cm–2. The exposed catalytic sites on Cu/NC were suggested to activate H2O and stabilize oxygenate intermediates favorably for the electrochemical CO-to-acetate conversion.
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