Machine-Learning-Aided Engineering Hemoglobin as Carbene Transferase for Catalyzing Enantioselective Olefin Cyclopropanation.

In this study, we developed a machine-learning-aided protein design strategy for engineering hemoglobin (VHb) as carbene transferase. A Natural Language Processing (NLP) model was used for the first time to construct an algorithm (EESP, enzyme enantioselectivity score predictor) and predict the enantioselectivity of VHb. We identified critical amino acid residue sites by molecular docking and established a simplified mutation library by site-saturated mutagenesis.

Preliminary study of the role of inner ear proteins in vestibular neuritis.

Objective: To evaluate the plasma levels of the otoconial proteins, otoconin-90 and otolin-1, in individuals diagnosed with vestibular neuritis (VN) and determine the feasibility of using these proteins as biomarkers for VN.

Methods: In this preliminary study, 30 patients diagnosed with VN and 70 healthy individuals were recruited and followed to confirm whether they had benign paroxysmal positional vertigo (BPPV) during the following time. The recorded data included measurements of height, weight, and history of diabetes mellitus or hypertension.

Prognostic Value and Immunological Role of POP7 in Clear Cell Renal Cell Carcinoma.

Background: Studies have found that RNA-binding proteins (RBPs) are participated in the occurrence or development of tumours. However, the role of processing of precursor family (POP family) in clear cell renal cell carcinoma (ccRCC) has not been studied yet. Here, we analyzed the expression and prognostic value of POP family in ccRCC analyzed and subsequently revealed the relationship between POP7 and immune infiltration in ccRCC patients.

Database, prediction, and antibacterial research of astringency based on large language models.

Astringency, a sensory experience causing mouth dryness, significantly impacts the taste of foods such as wine and tea, and astringent molecules may exhibit antibacterial properties. Traditional methods for predicting astringency are costly, and the connection between astringency and antibacterial activity remains largely unexplored. In this study, we present a pioneering computational approach that includes: (1) the creation of the first comprehensive astringency database comprising 238 molecules; (2) the development of a Ligand-Based Prediction (LBP) framework that combines large language models, deep learning, and traditional machine learning for enhanced molecular and peptide prediction; (3) an astringency predictor achieving 0.

Mechanistic study of Nidus Vespae inhibiting gastric cancer in vitro through the JAK2/STAT3 signaling pathway.

Ethnopharmacological Relevance: Nidus Vespae, an animal-derived traditional Chinese medicine, has a long-standing history in treating inflammatory conditions and tumor-related diseases. Notably, Nidus Vespae decoction (NVD) has been shown to inhibit the proliferation of gastric cancer cells, although the underlying mechanisms remain unclear.

Objective: This study aimed to elucidate the efficacy and mechanisms by which NVD exerts its therapeutic effects on gastric cancer.

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.

Molecular Dynamics Simulation Combined with Neural Relationship Inference and Markov Model to Reveal the Relationship between Conformational Regulation and Bioluminescence Properties of Luciferase.

luciferase (Gluc) is currently known as the smallest naturally secreted luciferase. Due to its small molecular size, high sensitivity, short half-life, and high secretion efficiency, it has become an ideal reporter gene and is widely used in monitoring promoter activity, studying protein-protein interactions, protein localization, high-throughput drug screening, and real-time monitoring of tumor occurrence and development. Although studies have shown that different Gluc mutations exhibit different bioluminescent properties, their mechanisms have not been further investigated.

Regulating Strain and Electronic Structure of Indium Tin Oxide Supported IrO Electrocatalysts for Highly Efficient Oxygen Evolution Reaction in Acid.

The development of proton exchange membrane water electrolysis is a promising technology for hydrogen production, which has always been restricted by the slow kinetics of the oxygen evolution reaction (OER). Although IrO is one of the benchmark acidic OER electrocatalysts, there are still challenges in designing highly active and stable Ir-based electrocatalysts for commercial application. Herein, a Ru-doped IrO electrocatalyst with abundant twin boundaries (TB-RuIrO@ITO) is reported, employing indium tin oxide with high conductivity as the support material.

Switching engineered Vitreoscilla hemoglobin into carbene transferase for enantioselective SH insertion.

An attractive strategy for efficiently forming CS bonds is through the use of diazo compounds SH insertion. However, achieving good enantioselective control in this reaction within a biocatalytic system has proven to be challenging. This study aimed to enhance the activity and enantioselectivity of to enable asymmetric SH insertion.

NRIMD, a Web Server for Analyzing Protein Allosteric Interactions Based on Molecular Dynamics Simulation.

Long-range allosteric communication between distant sites and active sites in proteins is central to biological regulation but still poorly characterized, limiting the development of protein engineering and drug design. Addressing this gap, NRIMD is an open-access web server for analyzing long-range interactions in proteins from molecular dynamics (MD) simulations, such as the effect of mutations at distal sites or allosteric ligand binding at allosteric sites on the active center. Based on our recent works on neural relational inference using graph neural networks, this cloud-based web server accepts MD simulation data on any length of residues in the alpha-carbon skeleton format from mainstream MD software.

[The effect of narrow band imaging in CO2 laser therapy in early-stage glottic cancer].

To explore efficacy of narrow band imaging（NBI） technique in CO2laser therapy in Early-Stage Glottic cancer. The clinical data of patients with Early-Stage Glottic cancer who underwent CO2laser vocal cord resection from June 2011 to August 2022 were retrospectively analyzed. Among these, 27 patients who underwent surgery assisted by NBI were assigned to the observation group, while 25 patients who underwent conventional CO2 laser microsurgery with a suspension laryngoscope were assigned to the control group.

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.

PredCoffee: A binary classification approach specifically for coffee odor.

Compared to traditional methods, using machine learning to assess or predict the odor of molecules can save costs in various aspects. Our research aims to collect molecules with coffee odor and summarize the regularity of these molecules, ultimately creating a binary classifier that can determine whether a molecule has a coffee odor. In this study, a total of 371 coffee-odor molecules and 9,700 non-coffee-odor molecules were collected.

Integrating Computational and Experimental Methods to Identify Novel Sweet Peptides from Egg and Soy Proteins.

Sweetness in food delivers a delightful sensory experience, underscoring the crucial role of sweeteners in the food industry. However, the widespread use of sweeteners has sparked health concerns. This underscores the importance of developing and screening natural, health-conscious sweeteners.

Directed evolution of surface-displayed hemoglobin as an artificial metalloenzyme for the synthesis of 5-imino-1,2,4-thiadiazoles.

Artificial metalloenzymes (ArMs) are constructed by anchoring organometallic catalysts to an evolvable protein scaffold. They present the advantages of both components and exhibit considerable potential for the catalysis of new-to-nature reactions. Herein, surface-displayed hemoglobin (VHb) that anchored the cobalt porphyrin cofactor instead of the original heme cofactor was used as an artificial thiourea oxidase (ATOase) to synthesize 5-imino-1,2,4-thiadiazoles.

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.

Synthesis of Indolyl Phenyl Diketones through Visible-Light-Promoted Ni-Catalyzed Intramolecular Cyclization/Oxidation Sequence of Ynones.

The combination of visible light catalysis and Ni catalysis has enabled the synthesis of indolyl phenyl diketones through the cyclization/oxidation process of ynones. This reaction proceeded under mild and base-free conditions and showed a broad scope and feasibility for gram-scale synthesis. Several natural products and biologically interesting molecules could be readily postfunctionalized by this method.

Dual-polarization RF channelizer based on microcombs.

We report a dual-polarization radio frequency (RF) channelizer based on microcombs. Two high-Q micro-ring resonators (MRRs) with slightly different free spectral ranges (FSRs) are used: one MRR is pumped to yield soliton crystal microcombs ("active"), and the other MRR is used as a "passive" periodic optical filter supporting dual-polarization operation to slice the RF spectrum. With the tailored mismatch between the FSRs of the active and passive MRRs, wideband RF spectra can be channelized into multiple segments featuring digital-compatible bandwidths via the Vernier effect.