Les voies de l’intégration régionale en Asie orientale

Devant le succès de l’intégration européenne, on pourrait penser qu’il existe en Asie une volonté équivalente pour la formation d’une telle communauté. Or la réalité est tout autre. Bien qu’on ait l’habitude d’affirmer que le xxie siècle sera celui de l’Asie, les peuples asiatiques ne semblent cependant pas prêts pour une union, tant la « conscience de l’identité asiatique » leur fait encore défaut. Dans ce vaste « continent », le plus grand du monde, constitué de nombreux États très différen..

Comparison of Arthroscopic Partial Meniscectomy to Physical Therapy following Degenerative Meniscus Tears: A Systematic Review and Meta-analysis

Objective. To compare the effectiveness of arthroscopic partial meniscectomy (APM) and physical therapy (PT) for degenerative meniscus tears. Method. We conducted a literature search through PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Randomized controlled trials in adults with degenerative meniscal tears without symptoms of locking were considered for inclusion. Two researchers independently performed the literature search, assessed the risk of bias, and selected eligible studies. The primary outcome was function at different follow-up time points and the secondary outcome was pain at different follow-up time points. Results. We included 6 randomized controlled trials, with a total of 1006 participants, among which 495 were in the APM group and 511 were in the PT group. We found a small benefit in functional outcomes in the APM group until the 12 months follow-up time point (SMD=0.20; 95%CI=0.0‐0.33; p=0.002; I2=34%), but no significant differences in function between groups at the 24-month follow-up time point (SMD=0.12; 95%CI=−0.04−0.28;p=0.14; I2=28%). There was also small benefit in the APM group until the 12 months follow-up time point for pain (SMD=0.14; 95%CI=0.01−027; p=0.03; I2=36%), but no significant difference in pain between groups at 24 months (SMD=0.11; 95%CI=−0.05−0.28; p=0.18; I2=0%). Conclusion. In the treatment of degenerative meniscus tears, APM yielded better functional and pain outcomes compared with physical therapy in the short term until 12 months, but there were comparable results for pain and functional outcomes between the groups at the 24 months follow-up time point

Identification of Scopoletin and Chlorogenic Acid as Potential Active Components in Sunflower Calathide Enzymatically Hydrolyzed Extract towards Hyperuricemia

It is known that sunflower (Helianthus annuus L.) calathide enzymatically hydrolyzed extract (SCHE) contributes to the regulation of serum uric acid (UA); however, evidence regarding its bioactive components and mechanism are lacking. We identified two water-soluble components (scopoletin and chlorogenic acid) that are abundant in sunflower calathide, especially evaluated for the inhibition of xanthine oxidase (XO) and the expression levels of urate transporters with SCHE. Molecular docking of a chlorogenic acid–XO complex was more stable than that of the Scopoletin–XO, and its binding pockets, which closed the Mo = S center, was similar to xanthine pockets. Moreover, chlorogenic acid exhibited stronger inhibition than that of the scopoletin below 260 μM, despite the IC50 of scopoletin (577.7 μM) being lower than that chlorogenic acid (844.7 μM) on the UA generation assessed by a spectrophotometer in vitro. It revealed that chlorogenic acid and scopoletin were competitive inhibitors of XO. In addition, the SCHE (300 μg/mL) and chlorogenic acid (0.75 mM) obviously inhibited urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) expression levels, while scopoletin significantly upregulated the expression of GLUT9. To summarize, chlorogenic acid served a crucial role in UA regulation consistent with the SCHE and functioned as an important ingredient of SCHE. The strategic analysis of SCHE combined with scopoletin and chlorogenic acid may contribute to the development of food supplemental alternatives on UA metabolism and the reduction of agricultural byproduct waste

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 Sanghuangporus sanghuang have concentrated on polysaccharides, flavonoids, triterpenoids, etc. The function of peptides has not received much attention. The purpose of this study is to use computer mining techniques to search for potential anticancer peptides from 62 proteins of Sanghuang. We used mACPpred to perform sequence scans after theoretical trypsin hydrolysis and discovered nine fragments with an anticancer probability of over 0.60. The study used AlphaFold 2 to perform structural modeling of the first three ACPs discovered, which had blast results from the Cancer PPD database. Using reverse docking technology, we found the target proteins and interacting residues of two ACPs with an unknown mechanism. Reverse docking results predicted the binding modes of the ACPs and their target protein. In addition, we determined the active part of ACPs by quantum chemical calculation. Our study provides a framework for the future discovery of functional peptides from foods. The ACPs discovered have the potential to be used as drugs in oncology clinical treatment after further research

Lagrange Optimization of Shock Waves for Two-Dimensional Hypersonic Inlet with Geometric Constraints

The present paper focuses on the Lagrange optimization of shock waves for a two-dimensional hypersonic inlet by limiting the cowl internal angle and inlet length. The results indicate the significant influences of geometric constraints on the configuration of shock waves and performances of an inlet. Specifically, the cowl internal angle mainly affects the internal compression section; the inlet length affects both the internal and external compression sections where the intensity of internal and external compression shock waves shows a deviation of equal. In addition, the performances of optimized inlets at off-design points are further numerically simulated. A prominent discovery is that a longer inlet favors a higher total pressure recovery at the positive AOA; conversely, a shorter inlet can increase the total pressure recovery at the negative AOA

Molecular Dynamics Simulations Study of the Interactions between Human Dipeptidyl-Peptidase III and Two Substrates

Human dipeptidyl-peptidase III (hDPP III) is capable of specifically cleaving dipeptides from the N-terminal of small peptides with biological activity such as angiotensin II (Ang II, DRVYIHPF), and participates in blood pressure regulation, pain modulation, and the development of cancers in human biological activities. In this study, 500 ns molecular dynamics simulations were performed on free-hDPP III (PDB code: 5E33), hDPP III-Ang II (PDB code: 5E2Q), and hDPP III-IVYPW (PDB code: 5E3C) to explore how these two peptides affect the catalytic efficiency of enzymes in terms of the binding mode and the conformational changes. Our results indicate that in the case of the hDPP III-Ang II complex, subsite S1 became small and hydrophobic, which might be propitious for the nucleophile to attack the substrate. The structures of the most stable conformations of the three systems revealed that Arg421-Lys423 could form an α-helix with the presence of Ang II, but only part of the α-helix was produced in hDPP III-IVYPW. As the hinge structure in hDPP III, the conformational changes that took place in the Arg421-Lys423 residue could lead to the changes in the shape and space of the catalytic subsites, which might allow water to function as a nucleophile to attack the substrate. Our results may provide new clues to enable the design of new inhibitors for hDPP III in the future

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. Machine learning techniques are widely used in research to forecast molecular attributes for binary classification. In this work, the green odor molecules were first trained and learned using machine learning methods, and then clustering analysis and molecular docking were performed to further explore their molecular characteristics and mechanisms of action. For comparison, four algorithmic models were employed, MLP performed the best in all metrics, including Accuracy, Precision, Average Precision, Matthews coefficient, and Area under curve. We determined by difference analysis that, in comparison to non-green odor molecules, green odor molecules have a lower molecular mass and fewer electrons. Based on the MLP algorithm, we constructed a binary classification prediction website for green odors. The first application of deep learning techniques to the study of green odor molecules can be seen as a signal of a new era in which green odor research has advanced into intelligence and standardization

Magnolia officinalis Extract Contains Potent Inhibitors against PTP1B and Attenuates Hyperglycemia in db/db Mice

Protein tyrosine phosphatase 1B (PTP1B) is an established therapeutic target for type 2 diabetes mellitus (T2DM) and obesity. The aim of this study was to investigate the inhibitory activity of Magnolia officinalis extract (ME) on PTP1B and its anti-T2DM effects. Inhibition assays and inhibition kinetics of ME were performed in vitro. 3T3-L1 adipocytes and C2C12 myotubes were stimulated with ME to explore its bioavailability in cell level. The in vivo studies were performed on db/db mice to probe its anti-T2DM effects. In the present study, ME inhibited PTP1B in a reversible competitive manner and displayed good selectivity against PTPs in vitro. Furthermore, ME enhanced tyrosine phosphorylation levels of cellular proteins, especially the insulin-induced tyrosine phosphorylations of insulin receptor β-subunit (IRβ) and ERK1/2 in a dose-dependent manner in stimulated 3T3-L1 adipocytes and C2C12 myotubes. Meanwhile, ME enhanced insulin-stimulated GLUT4 translocation. More importantly, there was a significant decrease in fasting plasma glucose level of db/db diabetic mice treated orally with 0.5 g/kg ME for 4 weeks. These findings indicated that improvement of insulin sensitivity and hypoglycemic effects of ME may be attributed to the inhibition of PTP1B. Thereby, we pioneered the inhibitory potential of ME targeted on PTP1B as anti-T2DM drug discovery

Identification of Styryl Sulfonyl Fluoride (SSF) as An Efficient, Robust and Irreversible Cysteine-specific Protein Bioconjugation Reagent

Cysteine (Cys)-specific bioconjugation has found wide application in the synthesis of protein conjugates, particularly for the functionalization of antibody. Here, through direct assessment on protein substrate, we report the discovery of trans-styryl sulfonyl fluoride (SSF) as a near perfect Michael acceptor (MA) for cysteine-specific protein bioconjugation. Com-pared to predominantly used maleimides, SSF exhibited better chemoselectivity, self-stability and conjugate-stability while kept comparable reactivity. Using SSF-derived probes, proteins can be readily modified on the Cys residue(s) to install functionalities, e.g., fluorescent dyes, toxins and oligonucleotides (oligos), without the influence of activity. Fur-ther applications of SSF derived serum stable antibody-drug conjugates and PD-L1 nanobody-oligo conjugates demon-strate the great translational value of SSF-based bioconjugation in the drug development and single-cell sequencing