F qNMR based pharmacokinetics, metabolism and mass balance studies of SARS-CoV-2-3CL protease inhibitor simnotrelvir (SIM0417) in humans.

Simnotrelvir (SIM0417), an inhibitor of the 3CL protease of SARS-CoV-2, has been identified as a CYP3A sensitive substrate. This study investigated the pharmacokinetics, metabolism, and mass balance of simnotrelvir following a single oral dose of 750 mg in six healthy Chinese male subjects, co-administered with four doses of 100 mg ritonavir. Analysis using F qNMR combined with LC-MS/MS showed that the parent drug M0 constituted over 90% of the drug-related components in plasma.

Drug-drug interactions of simnotrelvir/ritonavir: an open-label, fixed-sequence, two-period clinical trial.

Objectives: Simnotrelvir is a small-molecule highly specific 3C-like protease inhibitor for anti-SARS-CoV-2 and was approved as a combination drug with ritonavir (simnotrelvir/ritonavir) in China. Simnotrelvir is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), and a weak inhibitor of CYP3A. Ritonavir is a substrate and inhibitor of CYP3A and an inhibitor of P-gp.

Causal relationship between gut microbiota and diabetic nephropathy: A bidirectional mendelian randomization study.

In this study, we summarized the key findings and potential implications of association studies investigating the relationship between gut microbiota composition and risks for Diabetic nephropathy (DN). We used Mendelian randomization (MR) analysis to explore the relationship between gut microbiota and DN using two different publicly available DN databases. The results were also summarized using five mainstream MR analysis methods.

The influence of dusts on radiation and temperature over the eastern Asia with a regional climate model.

In order to investigate the climate effects of dusts, a regional climate model (RegCM 4.6) with the dust scheme was used to simulate the direct radiative forcing and air temperature response at 2 m near surface of dusts over the eastern Asia. Two sets of experiments were conducted, one with and one without dust aerosols.

C-arm CT imaging with the extended line-ellipse-line trajectory: first implementation on a state-of-the-art robotic angiography system.

Three-dimensional cone-beam imaging has become valuable in interventional radiology. Currently, this tool, referred to as C-arm CT, employs a circular short-scan for data acquisition, which limits the axial volume coverage and yields unavoidable cone-beam artifacts. To improve flexibility in axial coverage and image quality, there is a critical need for novel data acquisition geometries and related image reconstruction algorithms.