Objective:To observe the relationship between the different stages of type 2 diabetes mellitus(T2DM)and the intestinal flora and verify its underlying mechanism.Methods:T2DM rats were generated by high-fat diet(HFD)combined with intraperitoneal streptozo-tocin(STZ)injection.The rats were divided into four groups:the control group(fed with normal feed for 1 month),the HFD group(fed with HFD for 1 month),the T2DM group(HFD combined with STZ and blood glucose＞11.1 mM),and the unformed T2DM model(Un-mod)group(HFD combined with STZ and blood glucose＜11.1 mM).Feces were collected,and bacterial communities in the fecal samples were analyzed by 16S rRNA gene sequencing.The content of short-chain fatty acids(SCFAs)in feces was measured by gas chromatography.Western blot and quantitative real-time polymerase chain reaction were used to detect the expression of G protein-coupled receptor 41(GPR41)and GPR43.Results:At different stages of T2DM,the intestinal flora and SCFAs content of rats were significantly decreased(all P＜.05).Our results indicated that g_Prevotella had a significant negative correlation,and g_Ruminococcus_torques_group and g_lachnoclastic had a significant positive correlation with blood glucose.The content of SCFAs,in particular acetate and butyrate,in rat feces of different stages of T2DM were significantly reduced,as well as GPR41 and GPR43 expression.The results in the Un-mod group were similar to the T2DM group,and the expression of GPR41 and GPR43 proteins were significantly higher than those in the T2DM group(both P＜.001).Conclusion:The intestinal flora-SCFAs-GPR41/GPR43 network may be important in the development of T2DM.Decreasing blood glucose levels by regulating the intestinal flora may become a new therapeutic strategy for T2DM,which has very important clinical and social values.

Objective:This study aimed to develop a promising transistor assay for 2019 novel coronavirus (2019-nCoV) antigen detection with easiness, high sensitivity and rapid response.Methods:A graphene field effect transistor (GFET) sensor with the channel material modified with antibody probes was fabricated. Transfer curves were measured at different 2019-nCoV spike protein concentrations to evaluate the validity and sensitivity of the method.Results:The antibody probes were successfully anchored on the graphene through linker molecules to ensure specificity and precision of this technique. Electrical measurements of the device showed a detectable concentration down to 3.6×10 -17 g/ml within a response time as short as 3 minutes. Conclusions:A sensitive, efficient and simple method for 2019-nCoV antigen detection through GFET was preliminarily established.

ObjectiveTo explore the mechanism of aerobic capacity on depression in school-age children, and the multiple mediators of the five dimensions of psychosocial functioning (emotional symptoms, conduct problems, peer problems, prosocial behavior and hyperactivity) between aerobic capacity and depression. MethodsFrom October to December, 2021, pupils of Grade two to Grade five from two primary schools were chester-sampled and investigated using 20-meter multistage shuttle run test, Depression Self-Rating Scale for Children, Self-reported Strengths and Difficulties Questionnaire. ResultsA total of 391 pupils underwent 20-meter multistage shuttle run test, and 312 out of them answering the questionnaires, and 294 questionnaires were valid. Aerobic capacity, depression, emotional symptoms, peer problems, prosocial behavior and hyperactivity were significantly correlated with each other (|r| > 0.127, P < 0.05) (except aerobic capacity and peer problems, and emotional symptoms and prosocial behavior). The results of the multiple mediation effect model showed that aerobic capacity could directly and negatively predict depression, and the mediating effects of emotional symptoms, peer problems, prosocial behavior and hyperactivity were significant, accounting for 34.37%, 12.54%, 34.06% and 17.80% of the total mediating effect, respectively. ConclusionThe aerobic capacity could not only directly affect depression of school-age children, but also improve their psychosocial functioning by reducing emotional symptoms, peer problems and hyperactivity, and increasing prosocial behavior, to indirectly affect their depression.

ObjectiveTo systematically review the effect of neurofeedback training on cognitive function in the elderly within the framework of the International Classification of Diseases 11th Revision (ICD-11), and International Classification of Functioning, Disability and Health (ICF). MethodsA PICO framework was constructed. Randomized controlled trials on neurofeedback training for cognitive function in the elderly from PubMed, Web of Science, ProQuest, and CNKI up to July, 2023 were systematically reviewed. Methodological quality assessment of the included literature was performed using Physiotherapy Evidence Database scale. ResultsA total of 15 researches were included, from ten countries, involving 520 participants, who were healthy elderly individuals or those with mild cognitive impairment. Various neurofeedback waveforms were utilized, such as alpha, beta, theta, beta/alpha, and sensorimotor rhythm (SMR) waves. Intervention duration ranged from 20 to 90 minutes, with intervention frequencies spanning from a long-term intervention of 30 sessions over 12 weeks to a high-frequency short-term intervention of eight sessions over one week. The primary health outcomes focused on cognitive function, including memory, attention, inhibitory control and executive function. ConclusionNeurofeedback training can improve the cognitive function of the eldery, and alleviate cognitive aging.

ObjectiveTo investigate the effect of rutin on the browning of 3T3-L1 preadipocytes and the mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the effect of different concentration of rutin （3.125， 6.25， 12.5， 25， 50， 100， 200 μmol·L^-1） on 3T3-L1 cell activity， and Western blot to examine the effect of rutin （12.5， 25， 50 μmol·L^-1） on the expression of thermogenesis-associated proteins uncoupling protein 1 （UCP1）， PR domain containing 16 （PRDM16） and peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） in adipocytes. After the optimal concentration of rutin was determined， the effect of rutin on lipid droplet formation in adipocytes was observed based on oil red O staining， and the expression of nuclear respiratory factor 1 （NRF1）， nuclear respiratory factor 2 （NRF2） and mitochondrial transcription factor A （TFAM）， which were the landmark proteins of mitochondrial biosynthesis， was detected by Western blot. ResultCompared with the blank group， 200 μmol·L^-1 rutin inhibited 3T3-L1 cell activity （P<0.01）. Compared with the blank group， at the concentration of 12.5， 25， 50 μmol·L^-1 rutin significantly promoted the expression of thermogenesis-associated proteins （UCP1， PRDM16， and PGC-1α） （P<0.01）， which was determined as the optimal concentration. Compared with the blank group， 50 μmol·L^-1 rutin significantly increased the immunofluorescence intensity of mitochondrial UCP1 protein in 3T3-L1 cells （P<0.01） and the expression of the markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM） （P<0.01）. In addition， 50 μmol·L^-1 rutin significantly inhibited lipid droplet formation of 3T3-L1 adipocytes （P<0.01）. ConclusionRutin inhibited lipid droplet deposition in 3T3-L1 adipocytes and increased the expression of thermogenesis-related proteins （UCP1， PRDM16， and PGC-1α） and markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM）， thereby inducing the browning of 3T3-L1 adipocytes. This lays a basis for the development of drugs that safely regulate the browning of white cells.

Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.
Mice ; Animals ; Adipose Tissue, Brown ; Sirtuin 1/pharmacology* ; Diabetes Mellitus, Type 2/metabolism* ; AMP-Activated Protein Kinases/metabolism* ; Morus/metabolism* ; Flavonoids/metabolism* ; Prospective Studies ; Signal Transduction ; Adipose Tissue, White ; Plant Leaves ; Uncoupling Protein 1/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism*

The incidence of diabetes has been on the rise as the result of lifestyle changes， especially the high-fat diet and reduced exercise. Thus， it has become a global public health problem and it is an urgent task to explore effective therapy. There has been an explosion of research on the relationship of transforming growth factor-β （TGF-β） signaling pathways with diabetes complications and tumors， but the role of the pathways in the occurrence and progression of diabetes remains unclear. TGF-β signaling pathways can be activated by many factors， directly or indirectly leading to the apoptosis of islet β cells and insulin resistance （IR）， and thus they are expected to become new targets for the treatment of diabetes. TGF-β-related signaling pathways involve AMP-activated proteinkinase （AMPK）， protooncogene （c-Myc）， Ski-relatednovel protein N （SnoN）， Smad ubiquitination regulatory factor 1 （Smurf1）， miR-335-5p， and other signaling molecules. They participate in the occurrence and development of IR， apoptosis of islet β cells， insulin secretion disorder， fibrosis of adipocytes， and metabolic disorder of adipocytes， and inhibit the browning of white adipose tissue， playing an important part in the pathological process of human diabetes. According to traditional Chinese medicine （TCM）， the pathogenesis of diabetes is the deficiency of Qi and Yin， and the late stage is characterized by the syndrome of Qi deficiency， and Yang deficiency and blood stasis， which should be treated according to the principle of replenishing Qi and nourishing Yin， warming Yang and activating blood. It has been found that the efficacy of some Chinese medicinals and compound prescriptions on diabetes is closely related to the TGF-β signaling pathways. This paper reviews TGF-β-associated signaling pathways， elucidating the roles of them in pathogenesis of diabetes， and analyzes the relationship of TGF-β-associated signaling pathways with the effect of compound Chinese medicine prescriptions against diabetes. This study is expected to lay a theoretical basis for the research on the treatment diabetes.

ObjectiveTo investigate the medicinal effect of total flavonoids of mulberry leaves on regulating liver lipid metabolism disorder in diabetes mellitus type 2 （T2DM） rats， and the mechanism based on liver peroxidase proliferators activate receptors-α （PPAR-α） and carnitine palmityl transferase-1 （CPT-1） proteins. MethodTotal flavonoids of mulberry leaves were extracted and purified by ethanol extraction + macroporous resin purification and then identified. T2DM rat model was induced by high fat diet （HFD） + streptozocin（STZ）method. Rats with blood glucose ≥ 11.1 mmol·L^-1 were divided into three administration groups with the high dose （300 mg·kg^-1）， medium dose （150 mg·kg^-1）， and low dose （75 mg·kg^-1） of total flavonoids of mulberry leaves for 8 weeks， respectively， to observe the weight and blood glucose of the rats. The pathological changes of rat livers were observed by hematoxylin-eosin （HE） staining. Biochemical method was used to detect the levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein-cholesterol （LDL-C）， and high density lipoprotein-cholesterol （HDL-C） of blood lipid metabolism in rats. The messenger ribonucleic acid （mRNA） and protein expressions of PPAR-α and CPT-1 were determined by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultAfter 8 weeks of intervention of total flavonoids of mulberry leaves， compared with the control group， the food intake， liver index， and fasting blood glucose of rats in the model group increased significantly （P<0.01）. Compared with the model group， the food intake， fasting blood glucose， and liver index of rats in the administration groups decreased significantly （P<0.01）. The results of HE staining showed that the liver tissue structure of rats in the control group was complete and there was no obvious abnormality. The model group showed vacuolar degeneration and inflammatory infiltration of hepatocytes of rats. There was no obvious abnormality in the liver structure of rats in the administration groups. The results of blood lipid showed that compared with the control group， the levels of TC， TG， and LDL-C increased significantly （P<0.01）， but the level of HDL-C decreased significantly （P<0.01） in the model group. Compared with the model group， the levels of TC， TG， and LDL-C decreased significantly （P<0.05， P<0.01）， whereas the level of HDL-C increased significantly （P<0.01） in the administration groups. The results of Real-time PCR showed that compared with the control group， the mRNA expression of PPAR-α and CPT-1 of rats in the model group decreased significantly （P<0.01）. Compared with the model group， the mRNA expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly （P<0.01）. The results of Western blot showed that compared with the control group， the protein expressions of PPAR-α and CPT-1 of rats in the model group decreased significantly （P<0.01）. Compared with the model group， the protein expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly （P<0.05， P<0.01）. ConclusionTotal flavonoids of mulberry leaves can effectively reduce blood glucose and improve liver lipid metabolism disorder in T2DM rats. The total flavonoids of mulberry leaves could regulate lipid metabolism and play a hypoglycemic role by activating and regulating PPAR-α and CPT-1 proteins and promoting oxidative decomposition of fatty acids.