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Abundant repressor binding sites in human enhancers are associated with the fine-tuning of gene regulation.
iScience
January 2025
Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
The regulation of gene expression relies on the coordinated action of transcription factors (TFs) at enhancers, including both activator and repressor TFs. We employed deep learning (DL) to dissect HepG2 enhancers into positive (PAR), negative (NAR), and neutral activity regions. Sharpr-MPRA and STARR-seq highlight the dichotomy impact of NARs and PARs on modulating and catalyzing the activity of enhancers, respectively.
View Article and Find Full Text PDFMassive endocytosis mechanisms are involved in uptake of HIV-1 particles by monocyte-derived dendritic cells.
Front Immunol
January 2025
IrsiCaixa, Badalona, Spain.
Introduction: HIV-1 exploits dendritic cells (DCs) to spread throughout the body via specific recognition of gangliosides present on the viral envelope by the CD169/Siglec-1 membrane receptor. This interaction triggers the internalization of HIV-1 within a structure known as the sac-like compartment. While the mechanism underlying sac-like compartment formation remains elusive, prior research indicates that the process is clathrin-independent and cell membrane cholesterol-dependent and involves transient disruption of cortical actin.
View Article and Find Full Text PDFActive Ingredients and Potential Mechanism of Additive Sishen Decoction in Treating Rheumatoid Arthritis with Network Pharmacology and Molecular Dynamics Simulation and Experimental Verification.
Drug Des Devel Ther
January 2025
Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation, College of Traditional Chinese Medicine and Food Engineering, Shanxi University of Chinese Medicine, Jinzhong, People's Republic of China.
Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease in which macrophages produce cytokines that enhance inflammation and contribute to the destruction of cartilage and bone. Additive Sishen decoction (ASSD) is a widely used traditional Chinese medicine for the treatment of RA; however, its active ingredients and the mechanism of its therapeutic effects remain unclear.
Methods: To predict the ingredients and key targets of ASSD, we constructed "drug-ingredient-target-disease" and protein-protein interaction networks.
Molecular Epidemiology of Type F Among Diarrheal Patients and Virulence-Resistance Dynamics - 11 Provinces, China, 2024.
China CDC Wkly
January 2025
Department of Clinical Laboratory, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, China.
Introduction: Type F () represents a significant pathogen in human gastrointestinal diseases, primarily through its gene encoding enterotoxin (CPE). This investigation examined the prevalence, antimicrobial resistance patterns, and genetic characteristics of Type F within the Chinese population.
Methods: The study analyzed 2,068 stool samples collected from 11 provincial hospitals in 2024.
Computational identification of novel natural inhibitors against triple mutant DNA gyrase A in fluoroquinolone-resistant Typhimurium.
Biochem Biophys Rep
March 2025
Department of Integrative Biology, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, 632014, Tamil Nadu, India.
The rising resistance to fluoroquinolones in Typhimurium poses a significant global health challenge. This computational research addresses the pressing need for new therapeutic drugs by utilizing various computational tools to identify potential natural compounds that can inhibit the triple mutant DNA gyrase subunit A enzyme, which is crucial in fluoroquinolone resistance. Initially, the three-dimensional structure of the wild-type DNA gyrase A protein was modeled using homology modeling, and followed by mutagenesis to create the clinically relevant triple mutant (SER83PHE, ASP87GLY, ALA119SER) DNA gyrase A protein structure.
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