Drug Development.

Background: Genetic variants in GRN, the gene encoding progranulin, are causal for or are associated with the risk of multiple neurodegenerative diseases. Modulating progranulin has been considered as a therapeutic strategy for neurodegenerative diseases including Frontotemporal Dementia (FTD) and Alzheimer's Disease (AD). Here, we integrated genetics with proteomic data to determine the causal human evidence for the therapeutic benefit of modulating progranulin in AD.

The stereoselective bioactivity and mechanism of indoxacarb against Spodoptera frugiperda.

Background: Indoxacarb, a type of chiral pesticide, is used to control Lepidoptera insects. Most studies had focused on the environmental behavior and selective toxicity of indoxacarb enantiomers, and the mechanism behind its selective biological activity against target organisms is not well understood.

Results: Spodoptera frugiperda was selected as the target insect.

Intraoperative right ventricular end-systolic pressure-volume loop analysis in patients undergoing cardiac surgery: A proof-of-concept methodology.

Background: Perioperative right ventricular (RV) dysfunction is associated with increased morbidity and mortality in cardiac surgery patients. This study aimed to demonstrate proof of concept in generating intraoperative RV pressure-volume (PV) loops and conducting an end-systolic PV relationship (ESPVR) analysis using data obtained from routinely used intraoperative monitors.

Methods: Adult patients undergoing cardiac surgery with the placement of a pulmonary artery catheter (PAC) between May 2023 and March 2024 were included prospectively.

La Doped Nickel-Manganese Oxide as High-Capacity Cathode for Sodium-Ion Batteries Guided by Bayesian Optimization.

In sodium-ion batteries, the layered transition metal oxides used as cathode often experience interlayer sliding of interlayer spacing and lattice variations during charge/discharge, leading to structural damage and capacity degradation. To address this challenge, a La doping strategy guided by Bayesian optimization has been employed to prepare the high-performance O3-NaNiMnCuLaO (NMCL) cathode material. Density functional theory calculations reveal that the O 2p orbital overlaps with the t orbital of transition metals in NMCL, facilitating the formation of Na-O-La bonds and promoting the oxygen redox reaction kinetics.

Arachidonic acid synergizes with aspirin preventing myocardial ischemia-reperfusion injury and mitigates bleeding risk.

Aims: The therapeutic efficacy of coronary revascularization is compromised by myocardial ischemia-reperfusion (MI/R) injury. Higher levels of circulating arachidonic acid (AA) are reportedly associated with lower risk of cardiovascular disease. The cyclooxygenase (COX) pathway metabolizes AA into prostaglandins (PGs) and the platelet-activating thromboxane A2 (TXA2), which is inhibited by aspirin.