Use of PD-1 inhibitors in patients with end-stage renal disease: safety and clinical outcomes from real-world data

Use of PD-1 inhibitors in patients with end-stage renal disease: safety and clinical outcomes from real-world dat

General Method to Synthesize Highly Stable Nanoclusters via Pickering-Stabilized Microemulsions

The ability to not only control but also maintain the well-defined size of nanoclusters is key to a scientific understanding as well as their practical application. Here, we report a synthetic protocol to prepare and stabilize nanoclusters of different metals and even metal salts. The approach builds on a Pickering stabilization effect inside a microemulsion system. We prove that the emulsion interface plays a critical role in the formation of nanoclusters, which are encapsulated in situ into a silica matrix. The resulting nanocapsule is characterized by a central cavity and a porous shell composed of a matrix of both silica and nanoclusters. This structure endows the nanoclusters simultaneously with high thermal stability, good biocompatibility, and excellent photostability, making them well suited for fundamental studies and practical applications ranging from materials chemistry, catalysis, and optics to bioimaging

Table1_Integrated virtual screening and in vitro studies for exploring the mechanism of triterpenoids in Chebulae Fructus alleviating mesaconitine-induced cardiotoxicity via TRPV1 channel.DOCX

Background: In traditional Mongolian or Tibetan medicine in China, Chebulae Fructus (CF) is widely used to process or combine with aconitums to decrease the severe toxicity of aconitums. Researches in this area have predominantly focused on tannins, with few research on other major CF components for cardiotoxicity mitigation. The present study aimed to clarify whether triterpenoids can attenuate the cardiotoxicity caused by mesaconitine (MA) and investigate the mechanism of cardiotoxicity attenuation.Methods: Firstly, the pharmacophore model, molecular docking, and 3D-QSAR model were used to explore the mechanism of CF components in reducing the toxicity of MA mediated by the TRPV1 channel. Then three triterpenoids were selected to verify whether the triterpenoids had the effect of lowering the cardiotoxicity of MA using H9c2 cells combined with MTT, Hoechst 33258, and JC-1. Finally, Western blot, Fluo-3AM, and MTT assays combined with capsazepine were used to verify whether the triterpenoids reduced H9c2 cardiomyocyte toxicity induced by MA was related to the TRPV1 channel.Results: Seven triterpenoids in CF have the potential to activate the TRPV1 channel. And they exhibited greater affinity for TRPV1 compared to other compounds and MA. However, their activity was relatively lower than that of MA. Cell experiments revealed that MA significantly reduced H9c2 cell viability, resulting in diminished mitochondrial membrane potential and nuclear pyknosis and damage. In contrast, the triterpenoids could improve the survival rate significantly and counteract the damage of MA to the cells. We found that MA, arjungenin (AR), and maslinic acid (MSA) except corosolic acid (CRA) upregulated the expression of TRPV1 protein. MA induced a significant influx of calcium, whereas all three triterpenoids alleviated this trend. Blocking the TRPV1 channel with capsazepine only increased the cell viability that had been simultaneously treated with MA, and AR, or MSA. However, there was no significant difference in the CRA groups treated with or without capsazepine.Conclusion: The triterpenoids in CF can reduce the cardiotoxicity caused by MA. The MSA and AR function as TRPV1 agonists with comparatively reduced activity but a greater capacity to bind to TRPV1 receptors, thus antagonizing the excessive activation of TRPV1 by MA.</p

Detection of Thrombin with an Aptamer-Based Macromolecule Biosensor Using Bacterial Ghost System

A rapid on-site detection of exogenous proteins without the need for equipped laboratories or skilled personnel would benefit many areas. We built a rapid protein detection platform based on aptamer-induced inner-membrane scaffolds dimerization by virtue of bacterial ghost system. When the detection platform was coincubated with two kinds of aptamers targeting two different sites of thrombin, green fluorescence or β-lactamase activity were yielded with two different designs. The latter was detected by commercially available testing strips