Coupling In silico and In vitro Mechanistic Models to Define Vitamin D3 Immunomodulation of IL-12 and Nitric Oxide in Mycobacterium tuberculosis Infection.

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a highly infectious disease mainly affecting the lungs. Macrophages are key phagocytic immune cells and the preferred hosts for intracellular bacteria growth. Macrophages are also important sites of vitamin D3 synthesis, with vitamin D3 deficiency associated with increased risk of developing active TB.

Evidence for Dark Energy Driven by Star Formation: Information Dark Energy?

Evidence is presented for dark energy resulting directly from star formation. A survey of stellar mass density measurements, SMD(), as a function of universe scale size , was found to be described by a simple CPL w - w parameterisation that was in good agreement with the dark energy results of 2018, Pantheon+ 2022, the Dark Energy Survey 2024, and the Dark Energy Spectroscopic Instrument 2024. The best-fit CPL values found were = -0.

Receptor CDCP1 is a potential target for personalized imaging and treatment of poor outcome HER2+, triple negative and metastatic ER+/HER2- breast cancers.

Purpose: Receptor CUB-domain containing- protein 1 (CDCP1) was evaluated as a target for detection and treatment of breast cancer.

Experimental Design: CDCP1 expression was assessed immunohistochemically in tumors from 423 patients (119 triple-negative breast cancer (TNBC); 75 HER2+; 229 ER+/HER2- including 228 primary tumors, 229 lymph node and 47 distant metastases). Cell cytotoxicity induced in vitro by a CDCP1-targeting antibody-drug conjugate (ADC), consisting of the human/mouse chimeric antibody ch10D7 and the microtubule disruptor monomethyl auristatin E (MMAE), was quantified, including in combination with HER2-targeting ADC T-DM1.

Identification of a selective pyruvate dehydrogenase kinase 1 (PDHK1) chemical probe by virtual screening.

PDHK1 is a non-canonical Ser/Thr kinase that negatively regulates the pyruvate dehydrogenase complex (PDC), restricting entry of acetyl-CoA into the tricarboxylic acid (TCA) cycle and downregulating oxidative phosphorylation. In many glycolytic tumors, PDHK1 is overexpressed to suppress activity of the PDC and cause a shift in metabolism toward an increased reliance on glycolysis (the Warburg effect). Genetic studies have shown that knockdown or knockout of PDHK1 reverts this phenotype and inhibits tumor growth in vitro and in vivo, but chemical tools to pharmacologically validate and build upon these data are lacking.

A novel small molecule Enpp1 inhibitor improves tumor control following radiation therapy by targeting stromal Enpp1 expression.

The uniqueness in each person's cancer cells and variation in immune infiltrates means that each tumor represents a unique problem, but therapeutic targets can be found among their shared features. Radiation therapy alters the interaction between the cancer cells and the stroma through release of innate adjuvants. The extranuclear DNA that can result from radiation damage of cells can result in production of the second messenger cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) by cyclic GMP-AMP synthase (cGAS).