Macrocyclic peptides as a new class of targeted protein degraders.

Targeted protein degraders, in the form of proteolysis targeting chimaeras (PROTACs) and molecular glues, leverage the ubiquitin-proteasome system to catalytically degrade specific target proteins of interest. Because such molecules can be extremely potent, they have attracted considerable attention as a therapeutic modality in recent years. However, while targeted degraders have great potential, they are likely to face many of the same challenges as more traditional small molecules when it comes to their development as therapeutics.

Feasibility of home blood pressure screening in the paediatric outpatient clinic setting.

Objective: The aim of this study was to evaluate the acceptability and feasibility of home-based blood pressure (BP) screening in a group of paediatric patients with known elevated risk of developing hypertension.

Design: Cross-sectional study.

Setting: Specialist outpatient clinic and patient homes.

Effectiveness of interventions to prevent drowning among children under age 20 years: a global scoping review.

Background: Drowning is a leading cause of death among young children. The United Nations Resolution on global drowning prevention (2021) and World Health Assembly Resolution in 2023 have drawn attention to the issue. This scoping review synthesizes the current evidence on the effectiveness of child drowning prevention interventions since the 2008 World Report on Child Injury Prevention and implications for their implementation.

De novo transcriptome assembly and discovery of drought-responsive genes in white spruce (Picea glauca).

Forests face an escalating threat from the increasing frequency of extreme drought events driven by climate change. To address this challenge, it is crucial to understand how widely distributed species of economic or ecological importance may respond to drought stress. In this study, we examined the transcriptome of white spruce (Picea glauca (Moench) Voss) to identify key genes and metabolic pathways involved in the species' response to water stress.

Synaptic modulation of glutamate in striatum of the YAC128 mouse model of Huntington disease.

Background: Altered balance between striatal direct and indirect pathways contributes to early motor, cognitive and psychiatric symptoms in Huntington disease (HD). While degeneration of striatal D2-type dopamine receptor (D2)-expressing indirect pathway medium spiny neurons (iMSNs) occurs prior to that of D1-type dopamine receptor (D1)-expressing direct pathway neurons, altered corticostriatal synaptic function precedes degeneration. D2-mediated signaling on iMSNs reduces their excitability and promotes endocannabinoid (eCB) synthesis, suppressing glutamate release from cortical afferents.