Selective Degradation of TEADs by a PROTAC Molecule Exhibited Robust Anticancer Efficacy In Vitro and In Vivo.

Genetic mutations in components of the Hippo pathway frequently lead to the aberrant activation of TEADs, which is often associated with cancer. Consequently, TEADs have been actively pursued as therapeutic targets for diseases driven by TEAD overactivation. In this study, we report two series of TEAD PROTACs based on CRBN binders and VHL binders.

Dysregulated Signaling Pathways in Canine Mammary Tumor and Human Triple Negative Breast Cancer: Advances and Potential Therapeutic Targets.

In 2022, human breast cancer (HBC) and canine mammary tumors (CMTs) remained the most prevalent malignant tumors worldwide, with high recurrence and lethality rates, posing a significant threat to human and dog health. The development of breast cancer involves multiple signaling pathways, highlighting the need for effective inhibitory drugs that target key proteins in these pathways. This article reviews the dysregulation of the EGFR, PI3K/AKT/mTOR, Hippo, pyroptosis, and PD-1/PD-L1 signaling pathways in HBC and CMT, as well as the corresponding drugs used to inhibit tumor growth, with the aim of providing theoretical support for the development of more efficient drugs.

Phycospheric Bacteria Alleviate the Stress of Erythromycin on by Regulating Nitrogen Metabolism.

Macrolide pollution has attracted a great deal of attention because of its ecotoxic effects on microalgae, but the role of phycospheric bacteria under antibiotic stress remains unclear. This study explored the toxic effects of erythromycin (ERY) on the growth and nitrogen metabolism of ; then, it analyzed and predicted the effects of the composition and ecological function of phycospheric bacteria on microalgae under ERY stress. We found that 0.

Intrinsic Anti-Freezing, Tough, and Transparent Hydrogels for Smart Optical and Multi-Modal Sensing Applications.

Hydrogels have received great attention due to their molecular designability and wide application range. However, they are prone to freeze at low temperatures due to the existence of mass water molecules, which can damage their flexibility and transparency, greatly limiting their use in cold environments. Although adding cryoprotectants can reduce the freezing point of hydrogels, it may also deteriorate the mechanical properties and face the risk of cryoprotectant leakage.

SAHA inhibits lung fibroblast activation by increasing p66Shc expression epigenetically.

Objectives: To investigate the effects of suberoylanilide hydroxamic acid (SAHA) on lung fibroblast activation and to examine the role of p66Shc in this process.

Methods: An in vitro pulmonary fibrosis model was established using transforming growth factor-β (TGF-β)-induced MRC-5 lung fibroblasts. The proliferation and migration capacities of MRC-5 cells, along with the expression of fibrosis-related genes, were assessed following treatment with SAHA and/or silence of p66Shc.