A multi-kinase inhibitor screen identifies inhibitors preserving stem-cell-like chimeric antigen receptor T cells.

Chimeric antigen receptor T cells (CAR T cells) with T stem (T) cell-like phenotypic characteristics promote sustained antitumor effects. We performed an unbiased and automated high-throughput screen of a kinase-focused compound set to identify kinase inhibitors (KIs) that preserve human T cell-like CAR T cells. We identified three KIs, UNC10225387B, UNC10225263A and UNC10112761A, that combined in vitro increased the frequency of CD45RACCR7TCF1 T cell-like CAR T cells from both healthy donors and patients with cancer.

Core-Shell Bottlebrush Polymers: Unmatched Delivery of Small Active Compounds Deep Into Tissues.

The chemical structure of a delivery nanovehicle plays a pivotal role in determining the efficiency of drug delivery within the body. Leveraging the unique architecture of bottlebrush (BB) polymers-characterized by variations in backbone length, grafting density, and self-assembly morphology-offers a novel approach to understanding the influence of structural properties on biological behavior. In this study, developed a drug delivery system based on core-shell BB polymers synthesized using a "grafting-from" strategy.

Clinical outcomes of untreated adults living with chronic hepatitis B in The Gambia: an analysis of data from the prospective PROLIFICA cohort study.

Background: Expanding antiviral therapy to people with chronic hepatitis B virus (HBV) infection who are ineligible to receive treatment under current international criteria has been increasingly debated. Evidence to support this approach is scarce, especially in Africa. We aimed to address this knowledge gap by analysing the clinical outcomes of people with chronic hepatitis B in The Gambia who were untreated and ineligible for antiviral therapy at diagnosis.

A novel small molecule screening assay using normal human chondrocytes toward osteoarthritis drug discovery.

Osteoarthritis (OA) is the most common form of arthritis and a leading cause of pain and disability in adults. A central feature is progressive cartilage degradation and matrix fragment formation driven by the excessive production of matrix metalloproteinases (MMPs), such as MMP-13, by articular chondrocytes. Inflammatory factors, including interleukin 6 (IL-6), are secreted into the joint by synovial fibroblasts, and can contribute to pain and inflammation.