USP7 inhibitors suppress tumour neoangiogenesis and promote synergy with immune checkpoint inhibitors by downregulating fibroblast VEGF.

Background: Understanding how to modulate the microenvironment of tumors that are resistant to immune checkpoint inhibitors represents a major challenge in oncology.Here we investigate the ability of USP7 inhibitors to reprogram the tumor microenvironment (TME) by inhibiting secretion of vascular endothelial growth factor (VEGF) from fibroblasts.

Methods: To understand the role played by USP7 in the TME, we systematically evaluated the effects of potent, selective USP7 inhibitors on co-cultures comprising components of the TME, using human primary cells.

Creating conservation strategies with value-focused thinking.

Biodiversity and human well-being strategies are only as good as the set of ideas people think about. We evaluated value-focused thinking (VFT), a framework that emphasizes creating objectives and strategies that are responsive to the objectives. We performed a proof-of-concept study of VFT with 6 conservation planning teams at a global conservation organization.

Identification and development of a subtype-selective allosteric AKT inhibitor suitable for clinical development.

The serine/threonine protein kinase AKT plays a pivotal role within the PI3K pathway in regulating cellular proliferation and apoptotic cellular functions, and AKT hyper-activation via gene amplification and/or mutation has been implicated in multiple human malignancies. There are 3 AKT isoenzymes (AKT1-3) which mediate critical, non-redundant functions. We present the discovery and development of ALM301, a novel, allosteric, sub-type selective inhibitor of AKT1/2.

Efficacy of Carbohydrate Ingestion on CrossFit Exercise Performance.

The efficacy of carbohydrate (CHO) ingestion during high-intensity strength and conditioning type exercise has yield mixed results. However, little is known about shorter duration high-intensity exercise such as CrossFit. The purpose of this study was to investigate the performance impact of CHO ingestion during high-intensity exercise sessions lasting approximately 30 min.

Ingestion of an Amino Acid Electrolyte Beverage during Resistance Exercise Does Not Impact Fluid Shifts into Muscle or Performance.

The purpose of this study was to investigate the impact of ingesting an amino acid-electrolyte (AAE) beverage during upper body resistance exercise on transient muscle hypertrophy, exercise performance, markers of muscle damage, and recovery. Participants ( = 15) performed three sets of six repetitions-bench press, lat pull down, incline press, and seated row-followed by three sets of eight repetitions at 75% of the estimated 1 repetition maximum-triceps kickback, hammer curl, triceps push down, and preacher curl-with 90 s of rest between sets. The final set of the push down/preacher curl was performed to failure.