Quercetin regulates dendritic cell activation by targeting STAT4 in the treatment of experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a class of autoimmune diseases mainly caused by the immune system attacking the myelin sheath of the axons in the nervous system. Although the pathogenesis of MS is complex, studies have shown that dendritic cells (DCs) play a vital role in the pathogenesis of MS. Quercetin (QU) has a unique advantage in clinical application, especially for treating autoimmune diseases. However, the mechanism of QU in the treatment of experimental autoimmune encephalomyelitis (EAE) remains unclear. In this study, we explore the potential role of QU in EAE. Finally, we find that QU has anti-inflammatory activities and neural protective effects in EAE. The experimental results suggest that the cellular basis for QU's function is to inhibit the activation of DCs while modulating the Th17 cell differentiation in the co-culture system. Further, QU may target STAT4 to inhibit its activation in DCs. This work will be of great significance for the future development and utilization of QU.

Study on the mechanisms by which pumpkin polysaccharides regulate abnormal glucose and lipid metabolism in diabetic mice under oxidative stress.

Pumpkin polysaccharide (PPe-H) can perform physiological functions through its antioxidative and hypoglycemic effects; however, the mechanisms through which PPe-H regulates abnormal glucose and lipid metabolism caused by oxidative stress injury remain unclear. In the present study, streptozotocin was used to generate an acute diabetic mouse model, and the effects of PPe-H on glucose and lipid metabolism impaired by oxidative stress in diabetic mice were studied. PPe-H significantly reduced blood glucose levels and enhanced the oral glucose tolerance of diabetic mice under stress injury (p < 0.05). The analysis of liver antioxidant enzymes showed that PPe-H significantly enhanced the activities of SOD and CAT (p < 0.05), increased the GSH level, and decreased the level of MDA (p < 0.05). Transcriptomic and metabolomic analyses of the liver tissues of mice revealed characteristic differences in the genetic and metabolic levels of the samples, which showed that PPe-H treatment may play a positive role in regulating the metabolism of methionine, cysteine, glycerol phospholipid, and linoleic acid. These results indicated that PPe-H alleviated the symptoms of hyperglycemia by regulating metabolites related to oxidative stress and glycolipid metabolism in diabetic mice.

Effects of Auricularia auricula-judae (Bull.) Quél. polysaccharide acid hydrolysate on glucose metabolism in diabetic mice under oxidative stress.

BACKGROUND: Oxidative stress can lead to uncontrolled glucose metabolism and, thus, diabetes. Auricularia auricula-judae (Bull.) Quél. polysaccharides possess biological activities, such as antioxidant and hypoglycemic effects, but their mechanism of their acid hydrolysates on oxidative stress-injured glucose metabolism disorders is unclear. PURPOSE: Using diabetic mice, we investigated the effect of the acid hydrolysate of polysaccharides from Auricularia auricula-judae (Bull.) Quél. on improving diabetes. STUDY DESIGN AND METHODS: The structural information of sample polysaccharides was measured by high performance gel permeation chromatography, nuclear magnetic resolution, and high performance liquid chromatography. The diabetic model was established by intraperitoneal injection of streptozotocin. For eight consecutive weeks, the mice were orally administered sample polysaccharides (100, 200, and 300 mg/kg b.w. per day) for intervention. The improvement effect of the samples on diabetes was explored by detecting the changes in biochemical indicators in mice, and the underlying mechanism was studied by transcriptomic and metabolomic analysis. RESULTS: The results showed that acid hydrolysate of Auricularia auricula-judae (Bull.) Quél. polysaccharides consisted mainly of mannose, xylose, glucuronic acid, and glucose; its weight-averaged molecular weight was 6.3842 × 104 Dalton, its number average molecular weight was 2.9594 × 104 Dalton; and the molecule contained α-Glc(1→4)-, ß-Glc(1→3)-, and ß-Man(1→4)-linked glycosidic bonds. A total of 100 mg/kg b.w. per day sample was the best intervention concentration. After eight weeks of intervention, the sample polysaccharides significantly reduced dynamic blood glucose and serum lipids, enhanced antioxidant enzyme activities, promoted glucagon like peptide-1 and insulin secretion, improved insulin sensitivity and alleviated insulin resistance in diabetic mice. Transcriptomic and metabolomic analyses showed that sample polysaccharides was able to ameliorate disorders of glucose metabolism by modulating gene expression such as glucokinase; and modulate the state of oxidative stress in mice in vivo by regulating the glutathione metabolism pathway. CONCLUSION: Acid hydrolysate of Auricularia auricula-judae (Bull.) Quél. polysaccharides improved glucose metabolism disorders by slowing down the oxidative stress injury in mice, thereby alleviating diabetes. This study provided a basis for determining the underlying mechanism of the antidiabetic effect of Auricularia auricula-judae (Bull.) Quél. polysaccharides, which would significantly improve the deep development and application of these materials in diabetes control.

Learning Stiffness Tensors in Self-Activated Solids via a Local Rule.

Mechanical metamaterials are often designed with particular properties for specific load-bearing functions. Alternatively, this study aims to create a class of active lattice metamaterials, dubbed self-activated solids, that can learn desired stiffness tensors from the elastic deformations they experienced, a crucial feature to improve the performance, efficiency, and functionality of materials. Artificial adaptive matters that combine sensory, control, and actuation elements can offer appealing solutions. However, challenges still remain: The designs will rely on accurate off-line and global computations, as well as intricate coordination among individual elements. Here, a simple online and local learning strategy is initiated based on contrastive Hebbian learning to gradually guide self-activated solids to possess sought-after stiffness tensors autonomously and reversibly. During learning, the bond stiffness of the active lattice varies depending only on its local strain. The numerical tests show that the self-activated solid can not only achieve the desired bulk, shear, and coupling moduli but also manifest uni-mode and bi-mode extremal materials by itself after experiencing the corresponding elastic deformations. Further, the self-activated solid can also achieve the desired time-varying moduli when exposed to temporally different loads. The design is applicable to any lattice geometries and is resistant to damage and instabilities. The material design approach and the physical learning strategy suggested can benefit the design of autonomous materials, physical learning machines, and adaptive robots.