Molecular simulation for food protein-ligand interactions: A comprehensive review on principles, current applications, and emerging trends.

In recent years, investigations on molecular interaction mechanisms between food proteins and ligands have attracted much interest. The interaction mechanisms can supply much useful information for many fields in the food industry, including nutrient delivery, food processing, auxiliary detection, and others. Molecular simulation has offered extraordinary insights into the interaction mechanisms. It can reflect binding conformation, interaction forces, binding affinity, key residues, and other information that physicochemical experiments cannot reveal in a fast and detailed manner. The simulation results have proven to be consistent with the results of physicochemical experiments. Molecular simulation holds great potential for future applications in the field of food protein-ligand interactions. This review elaborates on the principles of molecular docking and molecular dynamics simulation. Besides, their applications in food protein-ligand interactions are summarized. Furthermore, challenges, perspectives, and trends in molecular simulation of food protein-ligand interactions are proposed. Based on the results of molecular simulation, the mechanisms of interfacial behavior, enzyme-substrate binding, and structural changes during food processing can be reflected, and strategies for hazardous substance detection and food flavor adjustment can be generated. Moreover, molecular simulation can accelerate food development and reduce animal experiments. However, there are still several challenges to applying molecular simulation to food protein-ligand interaction research. The future trends will be a combination of international cooperation and data sharing, quantum mechanics/molecular mechanics, advanced computational techniques, and machine learning, which contribute to promoting food protein-ligand interaction simulation. Overall, the use of molecular simulation to study food protein-ligand interactions has a promising prospect.

Study on the Correlation between 7-joint Ultrasound Score and Disease Activity in Patients with Rheumatoid Arthritis.

Background: The objective of this study was to investigate the correlation between the 7-joint ultrasound score (US7) and disease activity in patients with rheumatoid arthritis (RA). Methods: Forty-four patients with active RA were assessed, and the correlation between US7 and disease activity indicators such as the disease activity score (DAS28), rheumatoid factor (RF), the erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) was analyzed. In addition, the proportions of US7 points accounted for by different joint regions and joint surfaces were analyzed. Results: RF, CRP, and ESR were significantly increased in the RA group compared with the control group (P < 0.05). In the RA group, DAS28 (r = 0.0.561, P < 0.01), RF (r = 0.635, P < 0.01), ESR (r = 0.585, P < 0.01), and CRP (r = 0.492, P < 0.01) were positively correlated with US7. In terms of contributions to US7, the most susceptible joint surface is the dorsal surface, and the most susceptible joint area is the dorsal wrist. Conclusion: US7 is positively correlated with disease activity indicators of RA, which can objectively reflect disease activity in RA patients and provide a reference for clinical diagnosis and efficacy evaluation.

Association between triglyceride-glucose index and acute kidney injury in patients with acute myocardial infarction based on medical information mart for intensive care database: A cross-sectional study.

Background: The relationship between triglyceride glucose (TyG) index and the incidence of acute kidney injury (AKI) in patients with acute myocardial infarction (AMI) is unclear. This study aims to explore the relationship between the two. Methods: Participants were enrolled from Medical Information Mart for Intensive Care IV (MIMICIV) and grouping of subjects based on the quartile interval of the TyG index. With the presence of AKI as the main outcome, a logistic regression model was constructed. The correlation of the TyG index with the results obtained was examined by using a restricted cubic spline (RCS) model.

Research progress on Sirtuins (SIRTs) family modulators.

Sirtuins (SIRTs) represent a class of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases that exert a crucial role in cellular signal transduction and various biological processes. The mammalian sirtuins family encompasses SIRT1 to SIRT7, exhibiting therapeutic potential in counteracting cellular aging, modulating metabolism, responding to oxidative stress, inhibiting tumors, and improving cellular microenvironment. These enzymes are intricately linked to the occurrence and treatment of diverse pathological conditions, including cancer, autoimmune diseases, and cardiovascular disorders. Given the significance of histone modification in gene expression and chromatin structure, maintaining the equilibrium of the sirtuins family is imperative for disease prevention and health restoration. Mounting evidence suggests that modulators of SIRTs play a crucial role in treating various diseases and maintaining physiological balance. This review delves into the molecular structure and regulatory functions of the sirtuins family, reviews the classification and historical evolution of SIRTs modulators, offers a systematic overview of existing SIRTs modulation strategies, and elucidates the regulatory mechanisms of SIRTs modulators (agonists and inhibitors) and their clinical applications. The article concludes by summarizing the challenges encountered in SIRTs modulator research and offering insights into future research directions.

SIRT6 Reduces Rheumatoid Arthritis Injury by Inhibiting MyD88-ERK Signaling Pathway.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease characterized by destruction of synovial joints, abnormal immune responses and chronic inflammatory manifestations, which seriously affects patients' well-being. We explored this study to ascertain the effect and mechanism of silent information regulator 6 (SIRT6) on RA. METHODS: Genes of RA patients and normal volunteers were analyzed using Gene Expression Omnibus (GEO), Kyoto-Encyclopedia of Genes and Genomes (KEGG) and Disconet databases. Serum samples of RA patients and normal subjects were collected before detection of myeloid differentiation factor-88 (MyD88)-extracellular signal-regulated kinase (ERK) pathway proteins expression with Western blot. In vitro RA fibroblast-like synoviocytes (FLS) cell model (RA-FLS) was established by treating RSC-364 with recombinant rat IL-1ß (10 ng/mL) after which SIRT6 and MyD88 adenoviruses treatment was carried out. The enzyme linked immunoassay (ELISA), real time polymerase chain reaction (RT-PCR) and Western blot were respectively used to measure inflammatory factors, related messenger ribonucleic acid (mRNA) and protein expressions. Also, we constructed RA rat model with bovine type II collagen (BIIC) and complete Freund's adjuvant, before treatment with SIRT6 and MyD88 adenoviruses. RESULTS: Low expression of SIRT6 gene were detected in RA patients. Also, levels of MyD88, ERK and phosphorylated extracellular signal-regulated protein kinase (p-ERK) protein expressions in RA patients were increased, whilst that of SIRT6 protein decreased. Compared to FLS cells in Control group, inflammatory factors levels of rats in Model batch increased significantly. SIRT6 adenovirus treatment potentially and significantly inhibited inflammation including suppression of increased inflammatory factors induced by MyD88. In comparison with FLS cells in Control group, Model batch cells' MyD88, interleukin (IL)-1ß, IL-21, IL-22, IL-6, IL-17, tumor necrosis factor-alpha (TNF-α) and monocyte chemo-attractant protein-1 (MCP-1) mRNA expressions increased but SIRT6 gene treatment could reduce mRNA expression of the aforesaid factors, even after MyD88 adenovirus treatment. Besides, overpressed SIRT6 negatively regulated levels of MyD88, ERK and p-ERK proteins expressions. SIRT6 demonstrated anti-RA effect by regulating MyD88-ERK pathway and inhibiting inflammatory response in RA rats. CONCLUSIONS: SIRT6 could potentially inhibit the inflammatory response of RA via a regulatory mechanism mainly relating to MyD88-ERK signal pathway. Thus, SIRT6 and its agonists may serve as new targets for developing drugs that can potentially treat RA.

Multiple Self-Powered Sensor-Integrated Mobile Manipulator for Intelligent Environment Detection.

A multiple self-powered sensor-integrated mobile manipulator (MSIMM) system was proposed to address challenges in existing exploration devices, such as the need for a constant energy supply, limited variety of sensed information, and difficult human-computer interfaces. The MSIMM system integrates triboelectric nanogenerator (TENG)-based self-powered sensors, a bionic manipulator, and wireless gesture control, enhancing sensor data usability through machine learning. Specifically, the system includes a tracked vehicle platform carrying the manipulator and electronics, including a storage battery and a microcontroller unit (MCU). An integrated sensor glove and terminal application (APP) enable intuitive manipulator control, improving human-computer interaction. The system responds to and analyzes various environmental stimuli, including the droplet and fall height, temperature, pressure, material type, angles, angular velocity direction, and acceleration amplitude and direction. The manipulator, fabricated using 3D printing technology, integrates multiple sensors that generate electrical signals through the triboelectric effect of mechanical motion. These signals are classified using convolutional neural networks for accurate environmental monitoring. Our database shows signal recognition and classification accuracy exceeding 94%, with specific accuracies of 100% for pressure sensors, 99.55% for angle sensors, and 98.66, 95.91, 96.27, and 94.13% for material, droplet, temperature, and acceleration sensors, respectively.

Angiostrongylus cantonensis induces energy imbalance and dyskinesia in mice by reducing the expression of melanin-concentrating hormone.

BACKGROUND: Infection with Angiostrongylus cantonensis (AC) in humans or mice can lead to severe eosinophilic meningitis or encephalitis, resulting in various neurological impairments. Developing effective neuroprotective drugs to improve the quality of life in affected individuals is critical. METHODS: We conducted a Gene Ontology enrichment analysis on microarray gene expression (GSE159486) in the brains of AC-infected mice. The expression levels of melanin-concentrating hormone (MCH) were confirmed through real-time quantitative PCR (RT-qPCR) and immunofluorescence. Metabolic parameters were assessed using indirect calorimetry, and mice's energy metabolism was evaluated via pathological hematoxylin and eosin (H&E) staining, serum biochemical assays, and immunohistochemistry. Behavioral tests assessed cognitive and motor functions. Western blotting was used to measure the expression of synapse-related proteins. Mice were supplemented with MCH via nasal administration. RESULTS: Postinfection, a marked decrease in Pmch expression and the encoded MCH was observed. Infected mice exhibited significant weight loss, extensive consumption of sugar and white fat tissue, reduced movement distance, and decreased speed, compared with the control group. Notably, nasal administration of MCH countered the energy imbalance and dyskinesia caused by AC infection, enhancing survival rates. MCH treatment also increased the expression level of postsynaptic density protein 95 (PSD95) and microtubule-associated protein-2 (MAP2), as well as upregulated transcription level of B cell leukemia/lymphoma 2 (Bcl2) in the cortex. CONCLUSIONS: Our findings suggest that MCH improves dyskinesia by reducing loss of synaptic proteins, indicating its potential as a therapeutic agent for AC infection.