Tropifexor for nonalcoholic steatohepatitis: an adaptive, randomized, placebo-controlled phase 2a/b trial.

The multimodal activities of farnesoid X receptor (FXR) agonists make this class an attractive option to treat nonalcoholic steatohepatitis. The safety and efficacy of tropifexor, an FXR agonist, in a randomized, multicenter, double-blind, three-part adaptive design, phase 2 study, in patients with nonalcoholic steatohepatitis were therefore assessed. In Parts A + B, 198 patients were randomized to receive tropifexor (10-90 μg) or placebo for 12 weeks.

Digital pathology with artificial intelligence analyses provides greater insights into treatment-induced fibrosis regression in NASH.

Background & Aims: Liver fibrosis is a key prognostic determinant for clinical outcomes in non-alcoholic steatohepatitis (NASH). Current scoring systems have limitations, especially in assessing fibrosis regression. Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence analyses provides standardized evaluation of NASH features, especially liver fibrosis and collagen fiber quantitation on a continuous scale.

The mechanism of activation of a [NiFe]-hydrogenase by electrons, hydrogen, and carbon monoxide.

Activation of the oxidized inactive state (termed Unready or Ni(u)) of the [NiFe]-hydrogenase from Allochromatium vinosum requires removal of an unidentified oxidizing entity [O], produced by partial reduction of O(2). Dynamic electrochemical kinetic studies, subjecting enzyme molecules on an electrode to sequences of potential steps and gas injections, establish the order of events in an otherwise complex sequence of reactions that involves more than one intermediate retaining [O] or its redox equivalent; fast and reversible electron transfer precedes the rate-determining step which is followed by a reaction with H(2), or the inhibitor CO, that renders the reductive activation process irreversible.

Electrochemical potential-step investigations of the aerobic interconversions of [NiFe]-hydrogenase from Allochromatium vinosum: insights into the puzzling difference between unready and ready oxidized inactive states.

Dynamic electrochemical studies, incorporating catalytic voltammetry and detailed potential-step manipulations, provide compelling evidence that the oxidized inactive state of [NiFe]-hydrogenases termed Unready (or Ni-A) contains a product of partial reduction of O(2) that is trapped in the active site.

Enzyme electrokinetics: electrochemical studies of the anaerobic interconversions between active and inactive states of Allochromatium vinosum [NiFe]-hydrogenase.

The cycling between active and inactive states of the catalytic center of [NiFe]-hydrogenase from Allochromatium vinosum has been investigated by dynamic electrochemical techniques. Adsorbed on a rotating disk pyrolytic graphite "edge" electrode, the enzyme is highly electroactive: this allows precise manipulations of the complex redox chemistry and facilitates quantitative measurements of the interconversions between active catalytic states and the inactive oxidized form Ni(r) (also called Ni-B or "ready") as functions of pH, H(2) partial pressure, temperature, and electrode potential. Cyclic voltammograms for catalytic H(2) oxidation (current is directly related to turnover rate) are highly asymmetric (except at pH > 8 and high temperature) due to inactivation being much slower than activation.