N-Butyrylated Hyaluronic Acid Achieves Anti-Inflammatory Effects In Vitro and in Adjuvant-Induced Immune Activation in Rats

Previously synthesized N-butyrylated hyaluronic acid (BHA) provides anti-inflammatory effects in rat models of acute gouty arthritis and hyperuricemia. However, the mechanism of action remains to be elucidated. Herein, the anti-inflammatory and antioxidative activities of BHA and the targeted signaling pathways were explored with LPS-induced RAW264.7 and an adjuvant-induced inflammation in a rat model. Results indicated that BHA inhibited the generation of pro-inflammatory cytokines TNFα, IL-1β and IL-6, reduced ROS production and down-regulated JAK1-STAT1/3 signaling pathways in LPS-induced RAW264.7. In vivo, BHA alleviated paw and joint swelling, decreased inflammatory cell infiltration in paw tissues, suppressed gene expressions of p38 and p65, down-regulated the NF-κB and MAPK signaling pathways and reduced protein levels of TNFα, IL-1β and IL-6 in joint tissues of arthritis rats. This study demonstrated the pivotal role of BHA in anti-inflammation and anti-oxidation, suggesting the potential clinical value of BHA in the prevention of inflammatory arthritis and is worthy for development as a new pharmacological treatment.     

Multi-Classifier Fusion Based on MI–SFFS for Cross-Subject Emotion Recognition

With the widespread use of emotion recognition, cross-subject emotion recognition based on EEG signals has become a hot topic in affective computing. Electroencephalography (EEG) can be used to detect the brain’s electrical activity associated with different emotions. The aim of this research is to improve the accuracy by enhancing the generalization of features. A Multi-Classifier Fusion method based on mutual information with sequential forward floating selection (MI_SFFS) is proposed. The dataset used in this paper is DEAP, which is a multi-modal open dataset containing 32 EEG channels and multiple other physiological signals. First, high-dimensional features are extracted from 15 EEG channels of DEAP after using a 10 s time window for data slicing. Second, MI and SFFS are integrated as a novel feature-selection method. Then, support vector machine (SVM), k-nearest neighbor (KNN) and random forest (RF) are employed to classify positive and negative emotions to obtain the output probabilities of classifiers as weighted features for further classification. To evaluate the model performance, leave-one-out cross-validation is adopted. Finally, cross-subject classification accuracies of 0.7089, 0.7106 and 0.7361 are achieved by the SVM, KNN and RF classifiers, respectively. The results demonstrate the feasibility of the model by splicing different classifiers’ output probabilities as a portion of the weighted features.     

Structural Characteristics,Antioxidant and Hypoglycemic Activities of Polysaccharide from Siraitia grosvenorii

The structural characterization, the in vitro antioxidant activity, and the hypoglycemic activity of a polysaccharide (SGP-1-1) isolated from Siraitia grosvenorii (SG) were studied in this paper. SGP-1-1, whose molecular weight is 19.037 kDa, consisted of Gal:Man:Glc in the molar ratio of 1:2.56:4.90. According to the results of methylation analysis, GC–MS, and NMR, HSQC was interpreted as a glucomannan with a backbone composed of 4)-β-D-Glcp-(1→4)-, α-D-Glcp-(1→4)-, and 4)-Manp-(1 residues. α-1,6 linked an α-D-Galp branch, and α-1,6 linked an α-D-Glcp branch. The study indirectly showed that SGP-1-1 has good in vitro hypoglycemic and antioxidant activities and that these activities may be related to the fact that the SGP-1-1’s monosaccharide composition (a higher proportion of Gal and Man) is the glycosidic-bond type (α- and β-glycosidic bonds). SGP-1-1 could be used as a potential antioxidant and hypoglycemic candidate for functional and nutritional food applications.     

The Antibacterial Activity Mode of Action of Plantaricin YKX against Staphylococcus aureus

We aimed to evaluate the inhibitory effect and mechanism of plantaricin YKX on S. aureus. The mode of action of plantaricin YKX against the cells of S. aureus indicated that plantaricin YKX was able to cause the leakage of cellular content and damage the structure of the cell membranes. Additionally, plantaricin YKX was also able to inhibit the formation of S. aureus biofilms. As the concentration of plantaricin YKX reached 3/4 MIC, the percentage of biofilm formation inhibition was over 50%. Fluorescent dye labeling combined with fluorescence microscopy confirmed the results. Finally, the effect of plantaricin YKX on the AI-2/LuxS QS system was investigated. Molecular docking predicted that the binding energy of AI-2 and plantaricin YKX was −4.7 kcal/mol and the binding energy of bacteriocin and luxS protein was −183.701 kcal/mol. The expression of the luxS gene increased significantly after being cocultured with plantaricin YKX, suggesting that plantaricin YKX can affect the QS system of S. aureus.     

Intelligent Fault Diagnosis of Industrial Robot Based on Multiclass Mahalanobis-Taguchi System for Imbalanced Data

One of the biggest challenges for the fault diagnosis research of industrial robots is that the normal data is far more than the fault data; that is, the data is imbalanced. The traditional diagnosis approaches of industrial robots are more biased toward the majority categories, which makes the diagnosis accuracy of the minority categories decrease. To solve the imbalanced problem, the traditional algorithm is improved by using cost-sensitive learning, single-class learning and other approaches. However, these algorithms also have a series of problems. For instance, it is difficult to estimate the true misclassification cost, overfitting, and long computation time. Therefore, a fault diagnosis approach for industrial robots, based on the Multiclass Mahalanobis-Taguchi system (MMTS), is proposed in this article. It can be classified the categories by measuring the deviation degree from the sample to the reference space, which is more suitable for classifying imbalanced data. The accuracy, G-mean and F-measure are used to verify the effectiveness of the proposed approach on an industrial robot platform. The experimental results show that the proposed approach’s accuracy, F-measure and G-mean improves by an average of 20.74%, 12.85% and 21.68%, compared with the other five traditional approaches when the imbalance ratio is 9. With the increase in the imbalance ratio, the proposed approach has better stability than the traditional algorithms.     

Heterogeneous Catalysis of Ozone Using Iron–Manganese Silicate for Degradation of Acrylic Acid

Iron–manganese silicate (IMS) was synthesized by chemical coprecipitation and used as a catalyst for ozonating acrylic acid (AA) in semicontinuous flow mode. The Fe-O-Mn bond, Fe-Si, and Mn-Si binary oxide were formed in IMS on the basis of the results of XRD, FTIR, and XPS analysis. The removal efficiency of AA was highest in the IMS catalytic ozonation processes (98.9% in 15 min) compared with ozonation alone (62.7%), iron silicate (IS) catalytic ozonation (95.6%), and manganese silicate catalytic ozonation (94.8%). Meanwhile, the removal efficiencies of total organic carbon (TOC) were also improved in the IMS catalytic ozonation processes. The IMS showed high stability and ozone utilization. Additionally, H₂O₂ was formed in the process of IMS catalytic ozonation. Electron paramagnetic resonance (EPR) analysis and radical scavenger experiments confirmed that hydroxyl radicals (•OH) were the dominant oxidants. Cl⁻, HCO₃⁻, PO₄³⁻, Ca²⁺, and Mg²⁺ in aqueous solution could adversely affect AA degradation. In the IMS catalytic ozonation of AA, the surface hydroxyl groups and Lewis acid sites played an important role.     

Cardiac-specific overexpression of Ndufs1 ameliorates cardiac dysfunction after myocardial infarction by alleviating mitochondrial dysfunction and apoptosis

Myocardial infarction (MI) is the leading cause of premature death among adults. Cardiomyocyte death and dysfunction of the remaining viable cardiomyocytes are the main pathological factors of heart failure after MI. Mitochondrial complexes are emerging as critical mediators for the regulation of cardiomyocyte function. However, the precise roles of mitochondrial complex subunits in heart failure after MI remain unclear. Here, we show that NADH:ubiquinone oxidoreductase core subunit S1 (Ndufs1) expression is decreased in the hearts of heart failure patients and mice with myocardial infarction. Furthermore, we found that cardiac-specific Ndufs1 overexpression alleviates cardiac dysfunction and myocardial fibrosis in the healing phase of MI. Our results demonstrated that Ndufs1 overexpression alleviates MI/hypoxia-induced ROS production and ROS-related apoptosis. Moreover, upregulation of Ndufs1 expression improved the reduced activity of complex I and impaired mitochondrial respiratory function caused by MI/hypoxia. Given that mitochondrial function and cardiomyocyte apoptosis are closely related to heart failure after MI, the results of this study suggest that targeting Ndufs1 may be a potential therapeutic strategy to improve cardiac function in patients with heart failure.Subject terms: Heart failure, Myocardial infarction, Myocardial infarction     

Practical asymmetric amine nucleophilic approach for the modular construction of protected α-quaternary amino acids

We report the first amine nucleophilic approach for the modular construction of enantioenriched protected α-quaternary amino acids. The key to success is the use of an alcohol solvent, which makes a rationally designed COOMe-bonded Cu-allenylidene electrophilic intermediate stable enough to couple with amine nucleophiles before its decomposition. The reaction features wide functional group tolerance with high enantioselectivity, typically >90% ee, and is amenable to the modification of commercially available bioactive molecules. The resultant protected α-amino acids could be readily converted into a number of precious enantioenriched amines featuring α-hindered tertiary carbon centers, which are otherwise synthetically quite challenging, including those of α-amino aldehyde, peptides or α-vinyl amino ester with >92% ee in excellent yields. This protocol could be utilized for the synthesis of the protected bioactive α-ethylnorvaline in 3 steps, a significant advancement in comparison to an 11-step sequence reported previously.

We report the first amine nucleophilic approach for the modular construction of enantioenriched protected α-quaternary amino acids.     

Oxygen-supplied mesoporous carbon nanoparticles for enhanced photothermal/photodynamic synergetic therapy against antibiotic-resistant bacterial infections

Pandemic and epidemic spread of antibiotic-resistant bacterial infections would result in a huge number of fatalities globally. To combat antibiotic-resistant pathogens, new antimicrobial strategies should be explored and developed to confront bacteria without acquiring or increasing drug-resistance. Here, oxygen saturated perfluorohexane (PFH)-loaded mesoporous carbon nanoparticles (CIL@ICG/PFH@O₂) with photothermal therapy (PTT) and enhanced photodynamic therapy (PDT) utility are developed for antibacterial applications. Ionic liquid groups are grafted onto the surface of mesoporous carbon nanoparticles, followed by anion-exchange with the anionic photosensitizer indocyanine green (ICG) and loading oxygen saturated PFH to prepare CIL@ICG/PFH@O₂. These CIL@ICG/PFH@O₂ nanoparticles exhibit effective PTT and enhanced PDT properties simultaneously upon 808 nm light irradiation. In vitro assays demonstrate that CIL@ICG/PFH@O₂ shows a synergistic antibacterial action against antibiotic-resistant pathogens (methicillin-resistant Staphylococcus aureus and kanamycin-resistant Escherichia coli). Moreover, CIL@ICG/PFH@O₂ could effectively kill drug-resistant bacteria in vivo to relieve inflammation and eliminate methicillin-resistant Staphylococcus aureus-wound infection under NIR irradiation, and the released oxygen can increase collagen deposition, epithelial tissue formation and blood vessel formation to promote wound healing while enhancing the PDT effect. This study proposes a platform with enhanced PTT/PDT effects for effective, controlled, and precise treatment of topical drug-resistant bacterial infections.

We report oxygen saturated perfluorohexane (PFH)-loaded mesoporous carbon nanoparticles (CIL@ICG/PFH@O₂) with photothermal therapy (PTT) and enhanced photodynamic therapy (PDT) utility for antibacterial applications.     

Structural Investigation of the Interaction Mechanism between Chlorogenic Acid and AMPA Receptor via In Silico Approaches

Chlorogenic acid (CGA), an important metabolite in natural plant medicines such as honeysuckle and eucommia, has been shown to have potent antinociceptive effects. Nevertheless, the mechanism by which CGA relieves chronic pain remains unclear. α-amino-3-hydroxy-5-methyl-4-isooxazolpropionic acid receptor (AMPAR) is a major ionotropic glutamate receptor that mediates rapid excitatory synaptic transmission and its glutamate ionotropic receptor AMPA type subunit 1 (GluA1) plays a key role in nociceptive transmission. In this study, we used Western blot, surface plasmon resonance (SPR) assay, and the molecular simulation technologies to investigate the mechanism of interaction between CGA and AMPAR to relieve chronic pain. Our results indicate that the protein expression level of GluA1 showed a dependent decrease as the concentration of CGA increased (0, 50, 100, and 200 μM). The SPR assay demonstrates that CGA can directly bind to GluA1 (K_D = 496 μM). Furthermore, CGA forms a stable binding interaction with GluA1, which is validated by molecular dynamics (MD) simulation. The binding free energy between CGA and GluA1 is −39.803 ± 14.772 kJ/mol, where van der Waals interaction and electrostatic interaction are the major contributors to the GluA1–CGA binding, and the key residues are identified (Val-32, Glu-33, Ala-36, Glu-37, Leu-48), which play a crucial role in the binding interaction. This study first reveals the structural basis of the stable interaction between CGA and GluA1 to form a binding complex for the relief of chronic pain. The research provides the structural basis to understand the treatment of chronic pain and is valuable to the design of novel drug molecules in the future.