hERGAT: predicting hERG blockers using graph attention mechanism through atom- and molecule-level interaction analyses.

The human ether-a-go-go-related gene (hERG) channel plays a critical role in the electrical activity of the heart, and its blockers can cause serious cardiotoxic effects. Thus, screening for hERG channel blockers is a crucial step in the drug development process. Many in silico models have been developed to predict hERG blockers, which can efficiently save time and resources.

A pediatric emergency prediction model using natural language process in the pediatric emergency department.

This study developed a predictive model using deep learning (DL) and natural language processing (NLP) to identify emergency cases in pediatric emergency departments. It analyzed 87,759 pediatric cases from a South Korean tertiary hospital (2012-2021) using electronic medical records. Various NLP models, including four machine learning (ML) models with Term Frequency-Inverse Document Frequency (TF-IDF) and two DL models based on the KM-BERT framework, were trained to differentiate emergency cases using clinician transcripts.

Activation of lysophagy by a TBK1-SCF-TMEM192-TAX1BP1 axis in response to lysosomal damage.

Lysophagy eliminates damaged lysosomes and is crucial to cellular homeostasis; however, its underlying mechanisms are not entirely understood. We screen a ubiquitination-related compound library and determine that the substrate recognition component of the SCF-type E3 ubiquitin ligase complex, SCF(FBXO3), which is a critical lysophagy regulator. Inhibition of FBXO3 reduces lysophagy and lysophagic flux in response to L-leucyl-L-leucine methyl ester (LLOMe).

Structural insights into the role of reduced cysteine residues in SOD1 amyloid filament formation.

The formation of superoxide dismutase 1 (SOD1) filaments has been implicated in amyotrophic lateral sclerosis (ALS). Although the disulfide bond formed between Cys57 and Cys146 in the active state has been well studied, the role of the reduced cysteine residues, Cys6 and Cys111, in SOD1 filament formation remains unclear. In this study, we investigated the role of reduced cysteine residues by determining and comparing cryoelectron microscopy (cryo-EM) structures of wild-type (WT) and C6A/C111A SOD1 filaments under thiol-based reducing and metal-depriving conditions, starting with protein samples possessing enzymatic activity.

A Natural Autophagy Activator Castanea crenata Flower Alleviates Skeletal Muscle Ageing.

Background: Sarcopenia, characterized by a gradual decline in skeletal muscle mass and function with age, significantly impacts both quality of life and mortality. Autophagy plays a crucial role in maintaining muscle health. There is growing interest in leveraging autophagy to mitigate muscle ageing effects.