More than half of the NIH's institutes and centers don’t have permanent directors, giving the Trump administration an unusual opportunity to reshape the agency. The latest departure came on Friday.

Synopsis. Social media has become widely used by the scientific community for a variety of professional uses, including networking and public outreach. For

The emergence of a chemical system capable of self-replication and evolution is a critical event in the origin of life. RNA polymerase ribozymes can replicate RNA, but their large size and structural ...

YouTube video by the bumbling biochemist

Catherine O'Hara's heart and organs were a mirror image of most people's. Though that is rare, congenital heart defects are fairly common.

A curious phenomenon seen by oncologists, that morning patients do better than those receiving afternoon infusions, gains credence in a clinical trial.

Inhibitor-induced kinase degradation is a common event that positions supercharging of endogenous degradation circuits as an alternative to classical proximity-inducing degraders.

Targeted protein degradation (TPD) has arisen as a therapeutic revolution for eliminating disease-relevant proteins, but its tissue-specific delivery remains a critical challenge. Here, we developed an asialoglycoprotein receptor (ASGPR)-based platform for the selective degradation of target proteins in hepatocytes. By conjugating the ASGPR ligand triantennary N-acetylgalactosamine (tri-GalNAc) with a BRD4-targeted proteolysis targeting chimera (PROTAC) via a cathepsin B (CTSB)-cleavable Val-Cit-PABC linker, we generated a prototype GalNAc-PROTAC conjugate, TMU454. TMU454 selectively degraded BRD4 in ASGPR-positive hepatocellular carcinoma cells while sparing ASGPR-negative cancer cells and normal cells. Mechanistic investigations confirmed that TMU454-mediated BRD4 degradation is dependent on the ASGPR-mediated endocytosis, CTSB-mediated linker cleavage, and ubiquitin-proteasome system (UPS). Furthermore, a fluorescein-labeled analogue, TMU670, revealed preferential liver accumulation. Importantly, TMU454 significantly inhibited tumor growth in a Huh7-derived liver cancer xenograft model without apparent systemic toxicity. Collectively, this study establishes a versatile approach for tissue-selective protein degradation and advances targeted therapies for liver cancer.

Population-scale WGS reveals genetic determinants of persistent EBV DNA, linking immune regulation—especially antigen processing and MHC class II variation—to EBV persistence and heterogeneous di...