In vivo toxic and lethal cardiorespiratory effects of a synthetic quaternary ammonium salt derivative of haloperidol in mice.

Background: To investigate the toxicity of N-n-butyl haloperidol iodide (F2), a quaternary ammonium salt derivative of haloperidol, in mice for potential therapeutic purposes.

Methods: The acute median lethal dose (LD) of F2 was determined using the Bliss method following intravenous administration in mice. Routine surface electrocardiograms (ECGs) and arterial blood pressures (aBPs) were recorded under general anesthesia in untreated and pharmacologically vagotomized mice injected with F2.

Role of copper homeostasis and cuproptosis in heart failure pathogenesis: implications for therapeutic strategies.

Copper is an essential micronutrient involved in various physiological processes in various cell types. Consequently, dysregulation of copper homeostasis-either excessive or deficient-can lead to pathological changes, such as heart failure (HF). Recently, a new type of copper-dependent cell death known as cuproptosis has drawn increasing attention to the impact of copper dyshomeostasis on HF.

Development and validation of a prediction model for coronary heart disease risk in depressed patients aged 20 years and older using machine learning algorithms.

Background: Depression is being increasingly acknowledged as an important risk factor contributing to coronary heart disease (CHD). Currently, there is no predictive model specifically designed to evaluate the risk of coronary heart disease among individuals with depression. We aim to develop a machine learning (ML) model that will analyze risk factors and forecast the probability of coronary heart disease in individuals suffering from depression.

Flexible Tail of Antimicrobial Peptide PGLa Facilitates Water Pore Formation in Membranes.

PGLa, an antimicrobial peptide (AMP), primarily exerts its antibacterial effects by disrupting bacterial cell membrane integrity. Previous theoretical studies mainly focused on the binding mechanism of PGLa with membranes, while the mechanism of water pore formation induced by PGLa peptides, especially the role of structural flexibility in the process, remains unclear. In this study, using all-atom simulations, we investigated the entire process of membrane deformation caused by the interaction of PGLa with an anionic cell membrane composed of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG).