Elucidating the Mechanism of VVTT Infection Through Machine Learning and Transcriptome Analysis.

The vaccinia virus (VV) is extensively utilized as a vaccine vector in the treatment of various infectious diseases, cardiovascular diseases, immunodeficiencies, and cancers. The vaccinia virus Tiantan strain (VVTT) has been instrumental as an irreplaceable vaccine strain in the eradication of smallpox in China; however, it still presents significant adverse toxic effects. After the WHO recommended that routine smallpox vaccination be discontinued, the Chinese government stopped the national smallpox vaccination program in 1981.

Clone-Resolved Chemical Depletion of T cells via Cellular Proximity Chemistry.

T cells play a pivotal role in the development of autoimmune diseases. To mitigate autoimmune inflammation without inducing global immunosuppression, it is crucial to selectively eliminate autoreactive T cell clones while preserving the normal T cell repertoire. In this study, we applied cellular proximity chemistry to develop a T-cell depletion method with clonal precision.

Unveiling the Anti-Obesity Potential of Thunder God Vine: Network Pharmacology and Computational Insights into Celastrol-like Molecules.

Obesity, characterized by abnormal or excessive fat accumulation, has become a chronic degenerative health condition that poses significant threats to overall well-being. Pharmacological intervention stands at the forefront of strategies to combat this issue. Recent studies, notably by Umut Ozcan's team, have uncovered the remarkable potential of Celastrol, a small-molecule compound derived from the traditional Chinese herb thunder god vine (Tripterygium wilfordii) as an anti-obesity agent.

Specific Substrate Activity of Lotus Root Polyphenol Oxidase: Insights from Gaussian-Accelerated Molecular Dynamics and Markov State Models.

Polyphenol oxidase (PPO) plays a key role in the enzymatic browning process, and this study employed Gaussian-accelerated molecular dynamics (GaMD) simulations to investigate the catalytic efficiency mechanisms of lotus root PPO with different substrates, including catechin, epicatechin, and chlorogenic acid, as well as the inhibitor oxalic acid. Key findings reveal significant conformational changes in PPO that correlate with its enzymatic activity. Upon substrate binding, the alpha-helix in the Q53-D63 region near the copper ion extends, likely stabilizing the active site and enhancing catalysis.

Interactions between Inhibitors and 5-Lipoxygenase: Insights from Gaussian Accelerated Molecular Dynamics and Markov State Models.

Inflammation is a protective stress response triggered by external stimuli, with 5-lipoxygenase (5LOX) playing a pivotal role as a potent mediator of the leukotriene (Lts) inflammatory pathway. Nordihydroguaiaretic acid (NDGA) functions as a natural orthosteric inhibitor of 5LOX, while 3-acetyl-11-keto-β-boswellic acid (AKBA) acts as a natural allosteric inhibitor targeting 5LOX. However, the precise mechanisms of inhibition have remained unclear.

VmmScore: An umami peptide prediction and receptor matching program based on a deep learning approach.

Peptides, with recognized physiological and medical implications, such as the ability to lower blood pressure and lipid levels, are central to our research on umami taste perception. This study introduces a computational strategy to tackle the challenge of identifying optimal umami receptors for these peptides. Our VmmScore algorithm includes two integral components: Mlp4Umami, a predictive module that evaluates the umami taste potential of peptides, and mm-Score, which enhances the receptor matching process through a machine learning-optimized molecular docking and scoring system.

Molecular insights into chronic atrophic gastritis treatment: Coptis chinensis Franch studied via network pharmacology, molecular dynamics simulation and experimental analysis.

Chronic atrophic gastritis (CAG), characterized by inflammation and erosion of the gastric lining, is a prevalent digestive disorder and considered a precursor to gastric cancer (GC). Coptis chinensis France (CCF) is renowned for its potent heat-clearing, detoxification, and anti-inflammatory properties. Zuojin Pill (ZJP), a classic Chinese medicine primarily composed of CCF, has demonstrated effectiveness in CAG treatment.

Using Gaussian accelerated molecular dynamics combined with Markov state models to explore the mechanism of action of new oral inhibitors on Complex I.

In this study, our focus was on investigating H-1,2,3-triazole derivative HP661 as a novel and highly efficient oral OXPHOS inhibitor, with its molecular-level inhibitory mechanism not yet fully understood. We selected the ND1, NDUFS2, and NDUFS7 subunits of Mitochondrial Complex I as the receptor proteins and established three systems for comparative analysis: protein-IACS-010759, protein-lead compound 10, and protein-HP661. Through extensive analysis involving 500 ns Gaussian molecular dynamics simulations, we gained insights into these systems.

Elucidating the structural basis of vitamin B derivatives as novel potent inhibitors of PTP1B: Insights from inhibitory mechanisms using Gaussian accelerated molecular dynamics (GaMD) and in vitro study.

Vitamin B is a group of biologically active cobalamin compounds. In this study, we investigated the inhibitory effects of methylcobalamin (MeCbl) and hydroxocobalamin acetate (OHCbl Acetate) on protein tyrosine phosphatase 1B (PTP1B). MeCbl and OHCbl Acetate exhibited an IC of approximately 58.

Mulberry Leaf Compounds and Gut Microbiota in Alzheimer's Disease and Diabetes: A Study Using Network Pharmacology, Molecular Dynamics Simulation, and Cellular Assays.

Recently, studies have reported a correlation that individuals with diabetes show an increased risk of developing Alzheimer's disease (AD). Mulberry leaves, serving as both a traditional medicinal herb and a food source, exhibit significant hypoglycemic and antioxidative properties. The flavonoid compounds in mulberry leaf offer therapeutic effects for relieving diabetic symptoms and providing neuroprotection.

Mlp4green: A Binary Classification Approach Specifically for Green Odor.

Fresh green leaves give off a smell known as "green odor." It has antibacterial qualities and can be used to attract or repel insects. However, a common method for evaluating green odor molecules has never existed.

Exploring the anti-gout potential of sunflower receptacles alkaloids: A computational and pharmacological analysis.

Gout, a painful condition marked by elevated uric acid levels often linked to the diet's high purine and alcohol content, finds a potential treatment target in xanthine oxidase (XO), a crucial enzyme for uric acid production. This study explores the therapeutic properties of alkaloids extracted from sunflower (Helianthus annuus L.) receptacles against gout.

Study on the Mechanism of Interaction between Dipeptidyl Peptidase 4 and Inhibitory Peptides Based on Gaussian Accelerated Molecular Dynamic Simulation.

Dipeptidyl peptidase 4 (DPP4) inhibitors can effectively inhibit the activity of DPP4, increasing the concentrations of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which allows for them to effectively contribute to the reduction of blood sugar levels. Leu-Pro-Ala-Val-Thr-Ile-Arg (LPAVTIR) and Leu-Pro-Pro-Glu-His-Asp-Trp-Arg (LPPEHDWR) were the two peptides with the strongest inhibitory activity against DPP4 selected from silkworm pupa proteins. In this study, four systems were established: Apo (ligand-free DPP4), IPI (IPI-bound DPP4), LPAVTIR (LPAVTIR-bound DPP4), LPPEHDWR (LPPEHDWR-bound DPP4), and Gaussian accelerated molecular dynamic (GaMD) simulation was conducted to investigate the mechanism of action of two inhibitory peptides binding to DPP4.

Using deep learning and molecular dynamics simulations to unravel the regulation mechanism of peptides as noncompetitive inhibitor of xanthine oxidase.

Xanthine oxidase (XO) is a crucial enzyme in the development of hyperuricemia and gout. This study focuses on LWM and ALPM, two food-derived inhibitors of XO. We used molecular docking to obtain three systems and then conducted 200 ns molecular dynamics simulations for the Apo, LWM, and ALPM systems.

Deciphering single-cell protein secretion and gene expressions by constructing cell-antibody conjugates.

Secreted proteins play critical roles in regulating immune responses, exerting cytotoxic effects on tumor cells, promoting inflammatory processes, and influencing cellular metabolism. Deciphering the intricate relationship between the heterogeneity of secreted proteins and their transcriptional states is pivotal in the study of cellular heterogeneity. Here we proposed a cell-antibody conjugate-based sequencing methodology (Cellab-seq) for joint characterization of secreted proteins and transcriptome.

Network Pharmacology Combined with Machine Learning to Reveal the Action Mechanism of Licochalcone Intervention in Liver Cancer.

There are reports indicating that licochalcones can inhibit the proliferation, migration, and invasion of cancer cells by promoting the expression of autophagy-related proteins, inhibiting the expression of cell cycle proteins and angiogenic factors, and regulating autophagy and apoptosis. This study aims to reveal the potential mechanisms of licochalcone A (LCA), licochalcone B (LCB), licochalcone C (LCC), licochalcone D (LCD), licochalcone E (LCE), licochalcone F (LCF), and licochalcone G (LCG) inhibition in liver cancer through computer-aided screening strategies. By using machine learning clustering analysis to search for other structurally similar components in licorice, quantitative calculations were conducted to collect the structural commonalities of these components related to liver cancer and to identify key residues involved in the interactions between small molecules and key target proteins.

Probing the mechanisms of hydrazide-based HDAC inhibitors binding to HDAC3 using Gaussian accelerated molecular dynamics (GaMD) simulations.

Histone deacetylases (HDACs) have emerged as promising targets for anticancer drug development. They regulate gene expression by removing acetyl groups from lysine residues on histone tails, leading to chromatin condensation. A hydrazide-based HDAC inhibitor, N-(4-(2-Propylhydrazine-1-carbonyl)benzyl)-1H-indole-2-carboxamide (11h), has been reported to exhibit significant antitumor activity.

Functionalized Fullerene Potentially Inhibits SARS-CoV-2 Infection by Modulating Spike Protein Conformational Changes.

The disease of SARS-CoV-2 has caused considerable morbidity and mortality globally. Spike proteins on the surface of SARS-CoV-2 allow it to bind with human cells, leading to infection. Fullerenes and their derivatives are promising SARS-CoV-2 inhibitors and drug-delivery vehicles.

Investigating the Vital Role of the Identified Abietic Acid from L. Calathide Extract against Hyperuricemia via Human Embryonic Kidney 293T Cell Model.

To explore the anti-hyperuricemia components in sunflower ( L.) calathide extract (SCE), we identified abietic acid (AA) via liquid chromatography-mass spectrometry and found an excellent inhibitor of xanthine oxidase (IC = 10.60 µM, Ki = 193.

Ru(bpy) -Enabled Cell-Surface Photocatalytic Proximity Labeling toward More Efficient Capture of Physically Interacting Cells.

Intercellular proximity labeling has emerged as a promising approach to enable the study of cell-cell interactions (CCIs), but the efficiency of current platforms is limited. Here, we use Ru(bpy) to construct an efficient photocatalytic proximity labeling (PPL) system on the cell surface that allows the highly discriminative CCI detection with spatiotemporal resolution. Through the mechanism study and quantitative characterization on living cells, we demonstrate that the singlet-oxygen ( O ) mechanism is more efficient and specific than the single electron transfer (SET) mechanism in Ru-mediated PPL.

Use of intercellular proximity labeling to quantify and decipher cell-cell interactions directed by diversified molecular pairs.

FucoID is an intercellular proximity labeling technique for studying cell-cell interactions (CCIs) via fucosyltransferase (FT)-meditated fucosyl-biotinylation, which has been applied to probe antigen-specific dendritic cell (DC)-T cell interactions. In this system, bait cells of interest with cell surface-anchored FT are used to capture the interacting prey cells by transferring a biotin-modified substrate to prey cells. Here, we leveraged FucoID to study CCIs directed by different molecular pairs, e.

In Silico Discovery of Anticancer Peptides from Sanghuang.

Anticancer peptide (ACP) is a short peptide with less than 50 amino acids that has been discovered in a variety of foods. It has been demonstrated that traditional Chinese medicine or food can help treat cancer in some cases, which suggests that ACP may be one of the therapeutic ingredients. Studies on the anti-cancer properties of have concentrated on polysaccharides, flavonoids, triterpenoids, etc.