Search

Proton exchange membrane water electrolyzer (PEMWE) technology is of interest in the context of electrocatalytic hydrogen generation from renewable energies. It has the benefits of immediate response, higher proton conductivity, lower ohmic losses, and gas crossover rate. One key step toward to large‐scale application, is the development of highly efficient, durable, and compatible anodic oxygen evolution electrocatalysts in acidic media to decrease the usage of expensive and scarce precious metals. Within this scenario, an in‐depth understanding of oxygen evolution reaction mechanisms including the adsorption evolution mechanism and lattice oxygen evolution mechanism is first provided to aid development of innovative materials and elucidate the origin of catalyst degradation. Second, recent progress in the development of oxygen evolution electrocatalysts in acid media is reviewed with an emphasis on the underlying structure–performance relationships. Third, the current application status and research progress in PEMWEs along with representative examples are discussed. Last, the remaining challenges and promising insights are proposed to inspire future studies on the development of hydrogen production technology from renewable energy. [ABSTRACT FROM AUTHOR]

This study aimed to establish a prognosis-prediction model based on serological indicators in patients with epithelial ovarian cancer (EOC). Patients initially diagnosed as ovarian cancer and surgically treated in Fudan University Shanghai Cancer Center from 2014 to 2018 were consecutively enrolled. Serological indicators preoperatively were collected. A risk model score (RMS) was constructed based on the levels of serological indicators determined by receiver operating characteristic curves. We correlated this RMS with EOC patients' overall survival (OS). Finally, 635 patients were identified. Pearson's χ2 results showed that RMS was significantly related to clinical parameters. Kaplan–Meier analysis demonstrated that an RMS less than 3 correlated with a longer OS (p < 0.0001). Specifically, significant differences were perceived in the survival curves of different subgroups. Multivariate Cox analysis revealed that age (p = 0.015), FIGO stage (p = 0.006), ascites (p = 0.015) and RMS (p = 0.005) were independent risk factors for OS. Moreover, RMS combined with age, FIGO and ascites could better evaluate for patients' prognosis in DCA analyses. Our novel RMS-guided classification preoperatively identified the prognostic subgroups of patients with EOC and showed higher accuracy than the conventional method, meaning that it could be a useful and economical tool for tailored monitoring and/or therapy. [ABSTRACT FROM AUTHOR]

Background: Remimazolam has shown similar or even superior properties to propofol in procedural sedation in adults, but few studies have been conducted in pediatric populations. Thus, we aimed to compare the effect and safety of remimazolam and propofol combined with low dose esketamine for pediatric same-day bidirectional endoscopy (BDE). Methods: Pediatrics <18 years scheduled for elective BDE under sedation were included and randomly assigned to remimazolam group (R group) or propofol group (P group). The primary outcome was the success rate of sedation. Secondary outcomes include sedation-related information and adverse events. Mean arterial pressure (MAP), heart rate (HR), and perfusion index (PI) were recorded during sedation. Results: A total of 106 patients were enrolled and analyzed. The success rate of sedation was 100% in both groups. Compared with the P group, the induction time of the R group was significantly prolonged ( p < 0.001), and the incidence of injection pain, intraoperative respiratory depression, hypotension and bradycardia was significantly lower ( p < 0.001). The changes in MAP, HR and PI were relatively stable in the R group compared with the P group. Additionally, awake time significantly decreased with age by approximately 1.12 index points for each increase in age in the P group ( p = 0.002) but not in the R group ( p > 0.05). Furthermore, the decline in PI and PI ratio during BDE was related to body movement in the P group. Conclusion: Remimazolam combined with low dose esketamine has a non-inferior sedative effect than propofol for pediatric BDE, with no injection pain, less respiratory depression, more stable hemodynamics. Moreover, early detection of the decline in PI may avoid harmful stimulation under light anesthesia. Clinical trial registration: https://www.clinicaltrials.gov/study/NCT05686863?id=NCT05686863&rank=1, NCT05686863., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chu, Zhou, Wan, Liu, Xin, Tian, Yan and Xu.)

Background: High levels of COP9 signalosome subunit 5 (CSN5) in epithelial ovarian cancer (EOC) are associated with poor prognosis and are implicated in mediating platinum resistance in EOC cells. The underlying mechanisms, however, remained undefined. This study aimed to elucidate the molecular process and identify potential therapeutic targets. Methods: RNA-sequencing was used to investigate differentially expressed genes between platinum-resistant EOC cells with CSN5 knockdown and controls. O-GlcNAc proteomics were employed to identify critical modulators downstream of CSN5. The omics findings were confirmed through qRT-PCR and immunoblotting. In vitro and in vivo experiments assessed the sensitivity of resistant EOCs to platinum. Results: We demonstrated an involvement of aberrant O-GlcNAc and endoplasmic reticulum (ER) stress disequilibrium in CSN5-mediated platinum resistance of EOC. Genetic or pharmacologic inhibition of CSN5 led to tumor regression and surmounted the intrinsic EOC resistance to platinum both in vitro and in vivo. Integration of RNA-sequencing and O-GlcNAc proteomics pinpointed calreticulin (CRT) as a potential target of aberrant O-GlcNAc modification. CSN5 upregulated O-GlcNAc-CRT at T346 to inhibit ER stress-induced cell death. Blocking T346 O-GlcNAc-CRT through CSN5 deficiency or T346A mutation resulted in Ca 2+ disturbances, followed by ER stress overactivation, mitochondrial dysfunction, and ultimately cell apoptosis. Conclusion: This study reveals that CSN5-mediated aberrant O-GlcNAc-CRT acts as a crucial ER stress checkpoint, governing cell fate response to stress, and emphasizes an unrecognized role for the CSN5/CRT O-GlcNAc/ER stress axis in platinum resistance of EOC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The endoplasmic reticulum (ER), an organelle present in various eukaryotic cells, is responsible for intracellular protein synthesis, post-translational modification, and folding and transport, as well as the regulation of lipid and steroid metabolism and Ca 2+ homeostasis. Hypoxia, nutrient deficiency, and a low pH tumor microenvironment lead to the accumulation of misfolded or unfolded proteins in the ER, thus activating ER stress (ERS) and the unfolded protein response, and resulting in either restoration of cellular homeostasis or cell death. ERS plays a crucial role in cancer oncogenesis, progression, and response to therapies. This article reviews current studies relating ERS to ovarian cancer, the most lethal gynecologic malignancy among women globally, and discusses pharmacological agents and possible targets for therapeutic intervention., Competing Interests: No potential conflicts of interest are disclosed., (Copyright © 2023 Cancer Biology & Medicine.)

The oxygen evolution reaction (OER) severely limits the efficiency of proton exchange membrane (PEM) electrolyzers due to slow reaction kinetics. IrO 2 is currently a commonly used anode catalyst, but its large-scale application is limited due to its high price and scarce reserves. Herein, we reported a practical strategy to construct an acid OER catalyst where Iridium oxide loading and iridium element bulk doping are realized on the surface and inside of W 18 O 49 nanowires by immersion adsorption, respectively. Specifically, W 0.7 Ir 0.3 O y has an overpotential of 278 mV at 10 mA·cm -2 in 0.1 M HClO 4 . The mass activity of 714.10 A·g Ir -1 at 1.53 V vs. the reversible hydrogen electrode (RHE) is 80 times that of IrO 2 , and it can run stably for 55 h. In the PEM water electrolyzer device, its mass activity reaches 3563.63 A·g Ir -1 at the cell voltage of 2.0 V. This improved catalytic performance is attributed to the following aspects: (1) The electron transport between iridium and tungsten effectively improves the electronic structure of the catalyst; (2) the introduction of iridium into W 18 O 49 by means of elemental bulk doping and nanoparticles supporting for the enhanced conductivity and electrochemically active surface area of the catalyst, resulting in extensive exposure of active sites and increased intrinsic activity; and (3) during the OER process, partial iridium elements in the bulk phase are precipitated, and iridium oxide is formed on the surface to maintain stable activity. This work provides a new idea for designing oxygen evolution catalysts with low iridium content for practical application in PEM electrolyzers.

Development of platinum resistance is one of the major causes of epithelial ovarian cancer (EOC) treatment failure. COP9 signalosome subunit 5 (COPS5) was found to take part in the progression of EOC in our previous study. Herein, we aim to uncover the potential utility of COPS5 in EOC chemoresistance. COPS5 levels were analyzed to define clinic pathologic correlates using a matched tissue microarray and online datasets. The effect of COPS5 inhibition by the lentivirus-mediated short hairpin RNA on cell viability, proliferation and migration was accessed in vitro and in vivo. Results showed that COPS5 was upregulated in patients after platinum resistance. Kaplan-Meier survival curves revealed that COPS5 overexpression was correlated with shorter PFS and OS. COPS5 downregulation inhibited the cell proliferation, migration, and reduced the sensitivity of EOC to platinum. Overall, our data indicated that COPS5 inhibition might represent a new therapeutic strategy for overcoming platinum resistance in patients with EOC.

KRAB domain-associated protein 1 (KAP1) is highly expressed in atherosclerotic plaques. Here, we studied the role of KAP1 in atherosclerosis development using a cell model of endothelial dysfunction induced by oxidative low-density lipoprotein (OxLDL). The phosphorylation and protein levels of KAP1 were similar between OxLDL-treated and non-treated endothelial cells (ECs). KAP1 depletion significantly inhibited the production of OxLDL-enhanced reactive oxygen species and the expression of adhesion molecules in ECs. Treatment with OxLDL promoted the proliferation and migration of ECs, which was also confirmed by the elevated levels of the proliferative markers c-Myc and PCNA, as well as the migratory marker MMP-9. However, these effects were also abrogated by KAP1 depletion. Moreover, the depletion of KAP1 in OxLDL-treated ECs resulted in decreases in the LOX-1 level and increases in eNOS expression. Generally, the data suggest that strategies targeting KAP1 depletion might be particularly useful for the prevention or treatment of atherosclerosis., (© 2020 The Author(s).)