Discovery of an Efficacious RET PROTAC Degrader with Enhanced Antiproliferative Activity against Resistant Cancer Cells Harboring RET Solvent-Front Mutations.

Rearranged during transfection (RET) kinase is a validated therapeutic target for various cancers characterized by RET alterations. Although two selective RET inhibitors, selpercatinib and pralsetinib, have been approved by the FDA, acquired resistance through solvent-front mutations has been identified rapidly. Developing proteolysis targeting chimera (PROTAC) targeting RET mutations offers a promising strategy to combat drug resistance.

Acoustic Exaggeration Enhances Speech Discrimination in Young Autistic Children.

Child-directed speech (CDS), which amplifies acoustic and social features of speech during interactions with young children, promotes typical phonetic and language development. In autism, both behavioral and brain data indicate reduced sensitivity to human speech, which predicts absent, decreased, or atypical benefits of exaggerated speech signals such as CDS. This study investigates the impact of exaggerated fundamental frequency (F0) and voice-onset time on the neural processing of speech sounds in 22 Chinese-speaking autistic children aged 2-7 years old with a history of speech delays, compared with 25 typically developing (TD) peers.

Self-monitoring of blood pressure following a stroke or transient ischaemic attack (TASMIN5S): a randomised controlled trial.

Background: Blood pressure (BP) control following stroke is important but currently sub-optimal. This trial aimed to determine whether self-monitoring of hypertension with telemonitoring and a treatment escalation protocol, results in lower BP than usual care in people with previous stroke or transient ischaemic attack (TIA).

Methods: Unblinded randomised controlled trial, comparing a BP telemonitoring-based intervention with control (usual care) for hypertension management in 12 primary care practices in England.

Dissolved oxygen depletion in Chinese coastal waters.

Estuarine and coastal environments have experienced dissolved oxygen (DO hereafter) depression and hypoxia due to increasingly intensified anthropogenic eutrophication and climate warming. This review compared diverse systems in Chinese coastal waters that experience DO depletion or hypoxia, aiming to identify essential aspects in advancing the abilities in comprehensively understanding DO dynamics across systems that span wide ranges of physical and biogeochemical environments. The coastal DO depression and relevant ecological consequences around the world are generally overviewed.

The effects of a psychoeducational intervention on caregivers of colorectal cancer patients: A meta-analysis of randomized controlled trials.

Purpose: To investigate the impacts of psychoeducational interventions in adjusting the physical and psychological statuses of caregivers of CRC patients.

Methods: Nine electronic databases, including Medline, Web of Science, Embase, Cochrane Library, CINAHL Complete, CNKI, Wan Fang Database, VIP Database, and CBM, were searched to identify eligible randomized controlled trials from January 2000 to July 2023. From 1498 articles, 9 articles that met the inclusion criteria were identified and systematically analyzed.