The binding and mechanism of a positive allosteric modulator of Kv3 channels.

Small-molecule modulators of diverse voltage-gated K (Kv) channels may help treat a wide range of neurological disorders. However, developing effective modulators requires understanding of their mechanism of action. We apply an orthogonal approach to elucidate the mechanism of action of an imidazolidinedione derivative (AUT5), a highly selective positive allosteric modulator of Kv3.

Lactic Acid from CO: A Carbon Capture and Utilization Strategy Based on a Biocatalytic Approach.

The EU low-carbon economy aims to reduce the level of CO emission in the EU to 80% by 2050. High efforts are required to achieve this goal, where successful CCU (Carbon Capture and Utilization) technologies will have a high impact. Biocatalysts offer a greener alternative to chemical catalysts for the development of CCU strategies since biocatalysis conforms 10 of the 12 principles of green chemistry.

Pharmacological modulation of Kv3 voltage-gated potassium channels regulates fear discrimination and expression in a response-dependent manner.

Various psychiatric diseases are characterized by aberrant cognition and emotional regulation. This includes inappropriately attributing affective salience to innocuous cues, which can be investigated using translationally relevant preclinical models of fear discrimination. Activity in the underpinning corticolimbic circuitry is governed by parvalbumin-expressing GABAergic interneurons, which also regulate fear discrimination.

Efficacy and Safety of Pirfenidone in Advanced Versus Non-Advanced Idiopathic Pulmonary Fibrosis: Post-Hoc Analysis of Six Clinical Studies.

Introduction: In the European Union (EU), the indication for the antifibrotic pirfenidone prior to April 2023 did not include patients with advanced idiopathic pulmonary fibrosis (IPF). This analysis compared the efficacy and safety of pirfenidone in advanced IPF versus non-advanced IPF.

Methods: Data were included from the following studies of pirfenidone: ASCEND (NCT01366209); CAPACITY (004 [NCT00287716] and 006 [NCT00287729]); RECAP (NCT00662038; advanced IPF defined as percent predicted forced vital capacity [%FVC] < 50% and/or percent predicted carbon monoxide diffusing capacity [%DLco] < 35% at baseline); PASSPORT (NCT02699879; advanced IPF defined as baseline %FVC < 50%); and SP-IPF (NCT02951429; patients with advanced IPF [defined as %DLco ≤ 40% at screening] at risk of group 3 pulmonary hypertension).

Wall Thickness Ratio-A New Magnetic Resonance Parameter-Is Associated With the Outcome of Biological Therapy in Patients With Ileal and Ileocolonic Crohn's Disease.

Goals: The present study was aimed at identifying a new magnetic resonance enterography (MRE) parameter assessing the clinical outcome of biological therapy in patients with active ileal/ileocolonic Crohn's disease (CD).

Background: Transmural healing (TH) has been associated with improved outcomes in CD. However, some patients with clinical remission and inactive disease at endoscopy do not achieve TH.