Targeting TRPC channels for control of arthritis-induced bone erosion.

Arthritis leads to bone erosion due to an imbalance between osteoclast and osteoblast function. Our prior investigations revealed that the Ca-selective ion channel, Orai1, is critical for osteoclast maturation. Here, we show that the small-molecule ELP-004 preferentially inhibits transient receptor potential canonical (TRPC) channels.

A Pan-RAS Inhibitor with a Unique Mechanism of Action Blocks Tumor Growth and Induces Antitumor Immunity in Gastrointestinal Cancer.

RAS is a common driver of cancer that was considered undruggable for decades. Recent advances have enabled the development of RAS inhibitors, but the efficacy of these inhibitors remains limited by resistance. Here, we developed a pan-RAS inhibitor, ADT-007, that binds nucleotide-free RAS to block GTP activation of effector interactions and MAPK/AKT signaling, resulting in mitotic arrest and apoptosis.

Validation and expansion of Baveno VII criteria for cACLD and CSPH based on liver stiffness and platelet count: Correlation with risk of hepatic decompensation and death.

Background And Aims: Recently proposed "Rule-of-Five" criteria define compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension (CSPH) using liver stiffness (LS) and platelet count. We aimed to validate these criteria by determining whether they are associated with risk of adverse outcomes.

Approach And Results: Patients without prior hepatic decompensation or HCC who underwent LS and platelet measurements (n = 17,076) were categorized as follows: no cACLD (LS: 2.

A qualitative study exploring the digital therapeutic alliance with fully automated smartphone apps.

Background: Digital mental health interventions are increasingly used to scale up access to mental health support, yet very few mental health apps are empirically supported, with high attrition rates. The therapeutic alliance between therapists and clients is a key factor in predicting psychological therapy retention and outcomes. Understanding how this concept translates to the digital context, the so-called digital therapeutic alliance (DTA), may help enhance retention and outcomes in digital mental health.