Electrophysiological characterization of human KCNT1 channel modulators and the therapeutic potential of hydroquinine and tipepidine in KCNT1 mutation-associated epilepsy mouse model.

Patients suffering epilepsy caused by the gain-of-function mutants of the hKCNT1 potassium channels are drug refractory. In this study, we cloned a novel human KCNT1B channel isoform using the brain cDNA library and conducted patch-clamp and molecular docking analyses to characterize the pharmacological properties of the hKCNT1B channel using thirteen drugs. Among cinchona alkaloids, we found that hydroquinine exerted the strongest blocking effect on the hKCNT1B channel, especially the F313L mutant.

CHMP4C promotes pancreatic cancer progression by inhibiting necroptosis via the RIPK1/RIPK3/MLKL pathway.

Introduction: Pancreatic cancer (PC) cannot currently be completely cured and has a poor prognosis. Necroptosis is a distinct form of regulated cell death that differs from both necrosis and apoptosis. Understanding the role of necroptosis during PC progression would open new avenues for targeted therapy.

Targeted FTO knockout in endothelial cells Boosts adhesion and lowers inflammatory infiltration to alleviate pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a syndrome characterized by increased pulmonary vascular resistance and elevated pulmonary artery pressure, ultimately leading to right heart failure and even death. Increasing evidence implicates the fat mass and obesity-associated protein (FTO) in various metabolic and inflammatory pathways; however, its role in pulmonary endothelial function and PAH remains largely unexplored. In this study, we examined the effects of endothelial cell-specific FTO knockout on PAH development.

Biomimetic Air-Lifted Organ Culture System with a Protective Coverage Membrane for Full-Thickness Corneal Preservation.

Effective storage and utilization of limited donor corneal resources are in high demand to alleviate the shortage of donor corneal tissue. Here, we designed a static air-lifted organ culture system equipped with a protective coverage membrane, namely, an air-lifted OC-P system, to provide a biomimetic physiological environment for full-thickness corneal preservation. The air-lifted OC-P system features a unique collagen-based protective coverage membrane that can offer a moist, oxygen-rich environment for corneal epithelium, produce an appropriate intraocular pressure onto the cornea by gravity, and facilitate the maintenance of the organ culture medium level for nutrient supply during corneal preservation.

Patients With Chronic Lateral Ankle Instability and Small Osteochondral Lesions of the Talus Obtain Good Postoperative Results: A Minimum 10-Year Follow-up With Radiographic Evidence.

Background: Few studies reported the long-term clinical outcomes and joint degeneration of patients with chronic lateral ankle instability (CLAI) and small osteochondral lesions of the talus (OLTs) following simultaneous open modified Broström-Gould (MBG) surgery and arthroscopic bone marrow stimulation (BMS). The purpose of this study was to study the long-term results of patients after BMS and BMG surgery, and to further evaluate the potential effect of OLT size on postoperative results.

Methods: In this retrospective study, 110 CLAI patients were divided into 57 patients with OLTs (including 24 patients having combined small osteochondral lesions of the tibial plafond) receiving simultaneous BMS and MBG surgeries (BMS+MBG group), and 53 patients without OLTs receiving isolated open MBG surgery (MBG group).