Liver-targeted degradation of BRD4 reverses hepatic fibrosis and enhances metabolism in murine models.

Liver fibrosis, characterized by excessive extracellular matrix deposition, is a precursor to cirrhosis and hepatocellular carcinoma, and current treatments are often limited by off-target toxicities. We repurposed the liver-targeting chimera (LIVTAC) XZ1606, a novel proteolysis-targeting chimera (PROTAC) conjugated with a triantennary -acetylgalactosamine (tri-GalNAc) moiety, to degrade BRD4 in hepatic stellate cells. , XZ1606 induced potent, dose- and time-dependent BRD4 degradation in LX-2 cells via the ubiquitin-proteasomal pathway after ASGPR-mediated endocytosis, with minimal cytotoxicity in normal hepatocytes.

Regional and aging-specific cellular architecture of non-human primate brains.

Background: Deciphering the functionality and dynamics of brain networks across different regions and age groups in non-human primates (NHPs) is crucial for understanding the evolution of human cognition as well as the processes underlying brain pathogenesis. However, systemic delineation of the cellular composition and molecular connections among multiple brain regions and their alterations induced by aging in NHPs remain largely unresolved.

Methods: In this study, we performed single-nucleus RNA sequencing on 39 samples collected from 10 brain regions of two young and two aged rhesus macaques using the DNBelab C4 system.

The Role of Hypoxia in Longevity.

Aging is marked by a progressive decrease in physiological function and reserve capacity, which results in increased susceptibility to diseases. Understanding the mechanisms of driving aging is crucial for extending health span and promoting human longevity. Hypoxia, marked by reduced oxygen availability, has emerged as a promising area of study within aging research.

Therapeutic potential of nicotinamide and ABT263 in alcohol-associated liver disease through targeting cellular senescence.

Alcohol-associated liver disease (ALD) is a major cause of liver-related morbidity and mortality, yet clinically effective therapies for ALD remain lacking. Here, we demonstrate that alcohol intake and its metabolite, acetaldehyde (ACH), induce senescence in the liver and liver cells, respectively. To assess the therapeutic potential of targeting liver senescence in ALD, we treated ALD-affected mice with the senolytic compound ABT263 and the senomorphic NAD precursor, nicotinamide (NAM).

Abundance and characteristics of microplastics in municipal wastewater treatment plant effluent: a case study of Guangzhou, China.

Wastewater treatment plants (WWTPs) have been proposed as significant sources of microplastics (MPs) in freshwater and estuarine environments. WWTPs, even those with high removal efficiencies, release millions of MPs per plant daily. China is the largest plastic producer worldwide, but only a few studies of MP pollution from WWTPs have been carried out in China.

[Removal of Urea by Heterotrophic Nitrification-Aerobic Denitrification Mixed Strains and Effects of Heavy Metals and Salinity].

To explore the effect of heterotrophic nitrification-aerobic denitrification mixed strains on urea removal, the removal characteristics of urea and effects of heavy metals and salinity on urea removal by mixed strains (DM01+YH01+YH02) were investigated. The results showed that urea could be efficiently degraded by mixed strains at 24 h in 200.0 mg·L urea wastewater when the carbon source was sodium citrate, C/N was 10, temperature was 30℃, pH was 7, and rotation speed was 130 r·min.

OPA1-Exon4b Binds to mtDNA D-Loop for Transcriptional and Metabolic Modulation, Independent of Mitochondrial Fusion.

Optic Atrophy 1 (OPA1) has well-established roles in both mitochondrial fusion and apoptotic crista remodeling and is required for the maintenance and distribution of mitochondrial DNA (mtDNA), which are essential for energy metabolism. However, the relationship between OPA1 and mitochondrial metabolism and the underlying mechanisms remain unclear. Here, we show that OPA1-Exon4b modulates mitochondrial respiration and rescues inner mitochondrial membrane potential (Δψm), independent of mitochondrial fusion.