GALNT4-induced O-GalNAc glycosylation of MUC1 accelerates the invasive phenotype of PDAC.

Background: Pancreatic ductal adenocarcinoma (PDAC), the predominant form of pancreatic cancer, remains a therapeutic challenge. While GALNT4 (a member of the N-acetylgalactosaminyltransferases family) shows significant upregulation in PDAC cells, its precise oncogenic mechanisms remain poorly understood.

Methods: Bioinformatics analysis was performed to examine the expression of GALNT4 and MUC1 in pancreatic adenocarcinoma (PAAD) and to predict the glycosylation sites of MUC1.

Transcriptomic analysis of the mechanism of male reproductive injuries caused by the mixture of three phthalates in rats.

Phthalates (PEs) are widespread in environment, and human beings are unavoidably exposing to the mixture of PEs, which may induce male reproductive health risks. In order to investigate the mechanism of male reproductive injuries caused by the mixture of di-2-ethylhexyl phthalate, dibutyl phthalate and butyl benzyl phthalate (MPEs), male rats were orally exposed to 16 mg/kg/d MPEs (L-MPEs) and 450 mg/kg/d MPEs (H-MPEs) for 90 days, and the results showed that MPEs decreased the weights of testes, epididymis and periepididymis fat, decreased serum levels of male hormones, increased abnormal sperm rate, and caused testicular histopathological damages, such as atrophy and cavitation of seminiferous tubules, spermatids exfoliation, Leydig cells hyperplasia and accumulation of lipid droplets in the testicular interstitium. Testicular transcriptomic analysis identified 100 differently expressed genes (DEGs) in L-MPEs group and 10,880 DEGs in H-MPEs group, and these DEGs mainly involved in signaling pathways of focal adhesion, PI3K-Akt, AGE-RAGE, axon guidance, PPAR, MAPK and etc.

Beaver behavior optimizer: A novel metaheuristic algorithm for solar PV parameter identification and engineering problems.

Introduction: Numerical optimization plays a key role in improving the efficiency of solar photovoltaic (PV) systems and solving complex engineering problems. Traditional optimization methods often struggle with finding optimal solutions within a reasonable timeframe due to high-dimensional and non-linear problem landscapes.

Objectives: This study aims to introduce a novel swarm intelligence algorithm, the Beaver Behavior Optimizer (BBO), inspired by the cooperative behaviors of beavers during dam construction.

Substrate and inhibitor binding of human GABA transporter 3.

GABA (g-aminobutyric acid) transporter 3 (GAT3) is primarily found in glial cells and is essential for regulating GABA homeostasis in the central nervous system by mediating GABA uptake. Consequently, GAT3 has emerged as a significant therapeutic target for the treatment of epilepsy. In this study, we present the cryoelectron microscopy (cryo-EM) structures of GAT3 bound to its substrate GABA, the selective inhibitor SNAP-5114, and in the substrate-free state.

Lipid-conjugated nucleoside prodrugs for antiviral therapy.

Nucleoside analogs have served as the cornerstone of antiviral therapy by acting as antimetabolites that disrupt viral DNA or RNA synthesis, thereby effectively inhibiting viral replication. Despite their clinical success, many nucleoside-based antivirals suffer from intrinsic limitations such as poor lipophilicity, low membrane permeability, and rapid metabolic degradation, all of which compromise oral bioavailability and therapeutic efficacy. To address these challenges, lipid conjugation has emerged as a promising prodrug strategy that enhances pharmacokinetic properties, improves cellular uptake, and enables targeted delivery.