1,7-diphenyl-4-hepten-3-one mitigates Alzheimer's-like pathology by inhibiting pyroptosis via activating the Nrf2 pathway.

Pyroptosis-mediated neuron death plays a crucial role in neurodegenerative diseases, such as Alzheimer's disease (AD). However, the effect of 1,7-diphenyl-4-hepten-3-one (C1), a natural diarylheptanoid, on AD is unclear. Herein, we investigated the therapeutic effect of C1 on APP/PS1 mice and ß-amyloid (Aß)-induced HT22 cells. Our findings showed that C1 attenuated cognitive impairment and mitigated pathological damage in APP/PS1 mice. Furthermore, we found that C1 prevented oxidative stress damage and decreased the levels of pyroptosis-related proteins. In vitro experiments showed that C1 can improve the proliferation of Aß-induced HT22 cells and decrease the levels of pyroptosis-related proteins in them. When Nrf2 was silenced, the positive effects of C1 in inhibiting pyroptosis were inhibited. Particularly, the production of pyroptosis-associated proteins, including NLRP3, GSDMD, and caspase-1, and the secretion of pro-inflammatory molecules, including IL-1 and IL-18, were increased. Altogether, these findings indicate that C1 can mitigate AD-like pathology via the inhibition of pyroptosis by activating the Nrf2 pathway. We believe that this study can provide alternative strategies for the prevention and treatment of AD.

The Use of Spray-Dried Mn3O4/C Composites as Electrocatalysts for Li-O2 Batteries.

The electrocatalytic activities of Mn3O4/C composites are studied in lithium-oxygen (Li-O2) batteries as cathode catalysts. The Mn3O4/C composites are fabricated using ultrasonic spray pyrolysis (USP) with organic surfactants as the carbon sources. The physical and electrochemical performance of the composites is characterized by X-ray diffraction, scanning electron microscopy, particle size analysis, Brunauer-Emmett-Teller (BET) measurements, elemental analysis, galvanostatic charge-discharge methods and rotating ring-disk electrode (RRDE) measurements. The electrochemical tests demonstrate that the Mn3O4/C composite that is prepared using Trition X-114 (TX114) surfactant has higher activity as a bi-functional catalyst and delivers better oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalytic performance in Li-O2 batteries because there is a larger surface area and particles are homogeneous with a meso/macro porous structure. The rate constant (kf) for the production of superoxide radical (O2•-) and the propylene carbonate (PC)-electrolyte decomposition rate constant (k) for M3O4/C and Super P electrodes are measured using RRDE experiments and analysis in the 0.1 M tetrabutylammonium hexafluorophosphate (TBAPF6)/PC electrolyte. The results show that TX114 has higher electrocatalytic activity for the first step of ORR to generate O2•- and produces a faster PC-electrolyte decomposition rate.

Investigation of MnO2 and Ordered Mesoporous Carbon Composites as Electrocatalysts for Li-O2 Battery Applications.

The electrocatalytic activities of the MnO2/C composites are examined in Li-O2 cells as the cathode catalysts. Hierarchically mesoporous carbon-supported manganese oxide (MnO2/C) composites are prepared using a combination of soft template and hydrothermal methods. The composites are characterized by X-ray powder diffraction, scanning electron microscopy, transmission electron microscopy, small angle X-ray scattering, The Brunauer-Emmett-Teller (BET) measurements, galvanostatic charge-discharge methods, and rotating ring-disk electrode (RRDE) measurements. The electrochemical tests indicate that the MnO2/C composites have excellent catalytic activity towards oxygen reduction reactions (ORRs) due to the larger surface area of ordered mesoporous carbon and higher catalytic activity of MnO2. The O2 solubility, diffusion rates of O2 and O2•- coefficients (DO2 and DO-2), the rate constant (kf) for producing O2•-, and the propylene carbonate (PC)-electrolyte decomposition rate constant (k) of the MnO2/C material were measured by RRDE experiments in the 0.1 M TBAPF6/PC electrolyte. The values of kf and k for MnO2/C are 4.29 × 10-2 cm·s-1 and 2.6 s-1, respectively. The results indicate that the MnO2/C cathode catalyst has higher electrocatalytic activity for the first step of ORR to produce O2•- and achieves a faster PC-electrolyte decomposition rate.

Combination of low-dose gemcitabine in 6-hour infusion and carboplatin is a favorable option for patients in poor performance status with advanced non-small cell lung cancer.

This study sought to investigate the efficacy and tolerability of the regimen of low-dose gemcitabine combined with carboplatin in chemo-naïve patients with non-small cell lung cancer (NSCLC). The study involved 37 chemo-naive patients with unresectable stage IIIB or stage IV NSCLC. The predominant histological type was squamous carcinoma (22/37), and the performance status (PS) was 2 in 23 patients (62%). All received gemcitabine, 250 mg/m(2) in 6-hour infusion on days 1 and 8 plus carboplatin area under the curve (AUC)  =  5 on day 1, every 28 days. The overall response rate (ORR) was 62·2% and disease stabilization was achieved in 21·6% of the patients. After a median follow-up duration of 13 months, the median overall survival (OS) time was 14·0 months (95% CI 13·3-16·6 months), and the median progression-free survival (PFS) time was 7·0 months (95% CI 6·1-8·9 months). Hematological toxicities were well-tolerated with the development of grade 3/4 neutropenia and thrombocytopenia in 10·3 and 10·3% of patients respectively, and the gastrointestinal toxicities were mild.