Selective degradation of multimeric proteins by TRIM21-based molecular glue and PROTAC degraders.

Targeted protein degradation (TPD) utilizes molecular glues or proteolysis-targeting chimeras (PROTACs) to eliminate disease-causing proteins by promoting their interaction with E3 ubiquitin ligases. Current TPD approaches are limited by reliance on a small number of constitutively active E3 ubiquitin ligases. Here, we report that (S)-ACE-OH, a metabolite of the antipsychotic drug acepromazine, acts as a molecular glue to induce an interaction between the E3 ubiquitin ligase TRIM21 and the nucleoporin NUP98, leading to the degradation of nuclear pore proteins and disruption of nucleocytoplasmic trafficking.

Impact of vitamins A, D, and homocysteine on cardiometabolic multimorbidity in Northwest China.

Objective: To investigate the impact of vitamin A (VA), vitamin D (VD), and homocysteine (Hcy) on cardiometabolic multimorbidity (CMM).

Methods: This study is a cross-sectional study conducted in Ningxia Province, China. A total of 5000 participants aged 25-74 were recruited and divided into two groups based on the definition of cardiometabolic multimorbidity: the CMM group and the Non CMM group.

Interaction of estradiol and vitamin D with low skeletal muscle mass among middle-aged and elderly women.

Background: Since the connection between muscle atrophy and vitamin D and estradiol status ambiguous, this study was thus conducted to determine whether low skeletal muscle mass (SMM) in middle-aged and elderly women was affected by estradiol and vitamin D levels together.

Methods: Baseline data from a sub-cohort of the China Northwest Natural Population Cohort: Ningxia Project (CNC-NX) were analyzed. Serum 25-hydroxyvitamin D (25(OH) D) and estradiol were measured by chemiluminescence immunoassay analyzer.

BTK kinase activity is dispensable for the survival of diffuse large B-cell lymphoma.

Inhibitors targeting Bruton's tyrosine kinase (BTK) have revolutionized the treatment for various B-cell malignancies but are limited by acquired resistance after prolonged treatment as a result of mutations in BTK. Here, by a combination of structural modeling, in vitro assays, and deep phospho-tyrosine proteomics, we demonstrated that four clinically observed BTK mutations-C481F, C481Y, C481R, and L528W-inactivated BTK kinase activity both in vitro and in diffused large B-cell lymphoma (DLBCL) cells. Paradoxically, we found that DLBCL cells harboring kinase-inactive BTK exhibited intact B cell receptor (BCR) signaling, unperturbed transcription, and optimal cellular growth.

Diversity synthesis of indole derivatives catalyst control cyclization reaction of 2-indolylmethanols and azonaphthalene.

A series of indole-fused scaffolds and derivatives was synthesized the cyclization reaction of 2-indolylmethanols with azonaphthalene. These reactions were realized under mild reaction conditions through catalyst control, providing structurally diverse indole derivatives with moderate to excellent yields. This protocol also shows good substrate adaptability, especially in six-membered ring products.

Discovery of AdipoRon analogues as novel AMPK activators without inhibiting mitochondrial complex I.

Activation of AMPK emerges as a potential therapeutic approach to metabolic diseases. AdipoRon is claimed to be an adiponectin receptor agonist that activates AMPK through adiponectin receptor 1 (AdipoR1). However, AdipoRon also exhibits moderate inhibition of mitochondrial complex I, leading to increased risk of lactic acidosis.

Genome-Wide Identification of Direct Targets of the TTG1-bHLH-MYB Complex in Regulating Trichome Formation and Flavonoid Accumulation in .

Extensive studies have shown that the MBW complex consisting of three kinds of regulatory proteins, MYB and basic helix-loop-helix (bHLH) transcription factors and a WD40 repeat protein, TRANSPARENT TESTA GLABRA1 (TTG1), acts in concert to promote trichome formation and flavonoid accumulation in . TTG1 functions as an essential activator in these two biological processes. However, direct downstream targets of the TTG1-dependent MBW complex have not yet been obtained in the two biological processes at the genome-wide level in .

Soil microbial biomass, basal respiration and enzyme activity of main forest types in the Qinling Mountains.

Different forest types exert essential impacts on soil physical-chemical characteristics by dominant tree species producing diverse litters and root exudates, thereby further regulating size and activity of soil microbial communities. However, the study accuracy is usually restricted by differences in climate, soil type and forest age. Our objective is to precisely quantify soil microbial biomass, basal respiration and enzyme activity of five natural secondary forest (NSF) types with the same stand age and soil type in a small climate region and to evaluate relationship between soil microbial and physical-chemical characters.