Monitoring minuscule mechanical signals,both in magnitude and direction,is imperative in many application scenarios,e.g.,structural health monitoring and robotic sensing systems.However,the piezoelectric sensor strugg...Monitoring minuscule mechanical signals,both in magnitude and direction,is imperative in many application scenarios,e.g.,structural health monitoring and robotic sensing systems.However,the piezoelectric sensor struggles to satisfy the requirements for directional recognition due to the limited piezoelectric coefficient matrix,and achieving sensitivity for detecting micrometer-scale deformations is also challenging.Herein,we develop a vector sensor composed of lead zirconate titanate-electronic grade glass fiber composite filaments with oriented arrangement,capable of detecting minute anisotropic deformations.The as-prepared vector sensor can identify the deformation directions even when subjected to an unprecedented nominal strain of 0.06%,thereby enabling its utility in accurately discerning the 5μm-height wrinkles in thin films and in monitoring human pulse waves.The ultra-high sensitivity is attributed to the formation of porous ferroelectret and the efficient load transfer efficiency of continuous lead zirconate titanate phase.Additionally,when integrated with machine learning techniques,the sensor’s capability to recognize multi-signals enables it to differentiate between 10 types of fine textures with 100%accuracy.The structural design in piezoelectric devices enables a more comprehensive perception of mechanical stimuli,offering a novel perspective for enhancing recognition accuracy.展开更多
BACKGROUND Skeletal muscle handles about 80% of insulin-stimulated glucose uptake and become the major organ occurring insulin resistance(IR).Many studies have confirmed the interactions between macrophages and skelet...BACKGROUND Skeletal muscle handles about 80% of insulin-stimulated glucose uptake and become the major organ occurring insulin resistance(IR).Many studies have confirmed the interactions between macrophages and skeletal muscle regulated the inflammation and regeneration of skeletal muscle.However,despite of the decades of research,whether macrophages infiltration and polarization in skeletal muscle under high glucose(HG)milieus results in the development of IR is yet to be elucidated.C2C12 myoblasts are well-established and excellent model to study myogenic regulation and its responses to stimulation.Further exploration of macrophages'role in myoblasts IR and the dynamics of their infiltration and polarization is warranted.AIM To evaluate interactions between myoblasts and macrophages under HG,and its effects on inflammation and IR in skeletal muscle.METHODS We detected the polarization status of macrophages infiltrated to skeletal muscles of IR mice by hematoxylin and eosin and immunohistochemical staining.Then,we developed an in vitro co-culture system to study the interactions between myoblasts and macrophages under HG milieus.The effects of myoblasts on macrophages were explored through morphological observation,CCK-8 assay,Flow Cytometry,and enzyme-linked immunosorbent assay.The mediation of macrophages to myogenesis and insulin sensitivity were detected by morphological observation,CCK-8 assay,Immunofluorescence,and 2-NBDG assay.RESULTS The F4/80 and co-localization of F4/80 and CD86 increased,and the myofiber size decreased in IR group(P<0.01,g=6.26).Compared to Mc group,F4/80+CD86+CD206-cells,tumor necrosis factor-α(TNFα),inerleukin-1β(IL-1β)and IL-6 decreased,and IL-10 increased in McM group(P<0.01,g>0.8).In McM+HG group,F4/80+CD86+CD206-cells,monocyte chemoattractant protein 1,TNFα,IL-1βand IL-6 were increased,and F4/80+CD206+CD86-cells and IL-10 were decreased compared with Mc+HG group and McM group(P<0.01,g>0.8).Compered to M group,myotube area,myotube number and E-MHC were increased in MMc group(P<0.01,g>0.8).In MMc+HG group,myotube area,myotube number,E-MHC,GLUT4 and glucose uptake were decreased compared with M+HG group and MMc group(P<0.01,g>0.8).CONCLUSION Interactions between myoblasts and macrophages under HG milieus results in inflammation and IR,which support that the macrophage may serve as a promising therapeutic target for skeletal muscle atrophy and IR.展开更多
Background: The role of vitamin D and parathyroid hormone in the metabolic profile of type 2 diabetes mellitus in sub-Saharan Africa has not been adequately assessed. The aim of this study was to determine the prevale...Background: The role of vitamin D and parathyroid hormone in the metabolic profile of type 2 diabetes mellitus in sub-Saharan Africa has not been adequately assessed. The aim of this study was to determine the prevalence of low vitamin D level and secondary hyperparathyroidism and their association with insulin sensitivity and β-cell secretory function among Congolese type 2 diabetics. Methodology: Fasting glycaemia, fasting insulin, 25OH D3 and human parathyroid hormone (hPTH) were measured in one hundred and eighty-four type 2 diabetic patients followed as outpatients in South Kivu. Levels of 25OH D3 65 pg/ml defined low vitamin D and elevated parathyroid hormone levels, respectively. The HOMA model was used to measure insulin sensitivity and β-cell secretory function. Results: Medians (IQR) were 25.3 (20.4 - 32.4) ng/ml for 25OH D3 and 53.7 (38.4 - 115.7) pg/ml for hPTH. 58.7% of diabetics had insulin resistance, 126 (68.5%) had low vitamin D and 80 (43.5%) had hyperparathyroidism. In multivariate analysis, hPTH (partial r = −0.28;p = 0.0002) and 25OH D3 (partial r = 0.16;p = 0.03) showed an independent association with insulin sensitivity after adjustment for body mass index and waist circumference. Finally, hPTH (partial r = 0.27;p = 0.0002) was the sole determinant of β-cell secretory function. Conclusions: This study confirms the high prevalence of low vitamin D level and secondary hyperparathyroidism and their association with insulin resistance and impaired islet β-cell secretory function among Congolese with type 2 diabetes mellitus. Vitamin D and calcium supplementation should be envisaged for cases of deficiency in this region.展开更多
Aim To reveal the main active components and the action mechanisms of Radix astragali on insulin sensitivity improvement, we have investigated the effects of polysaccharide portion and saponin portion of Radix astraga...Aim To reveal the main active components and the action mechanisms of Radix astragali on insulin sensitivity improvement, we have investigated the effects of polysaccharide portion and saponin portion of Radix astragali extracts on blood biochemical indices and related gene expression of dexamethasone-induced SD rats. Methods SD rats (6 per group) received 2 μg/day subcutaneous dexamethasone for 4 weeks plus same dose (10 g material/kg) of polysaccharide or saponin extracts of Radix astragali. Blood samples, kidney tissues and epididymal fat pads were taken at the end of the experiment. Serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), glucose (GLU) and insulin (INS) levels were measured, respectively, mRNA levels of angiotensinogen in kidney, adiponectin and leptin as well as TNF-α in epididymal fats were determined by RT-PCR assay using GAPDH gene as an internal control. Results Both of polysaccharide and saponin extracts of Radix astragali exhibited positive effects in reducing serum triglycerides, glucose, and insulin levels of dexamethasone-induced SD rats. The saponin group showed more improvements on quantitive insulin sensitivity check index (QUICKI) than the polysaccharide group did. Both of the extracts down-regulated kidney angiotensinogen and fat TNF-α mRNA levels while they were simultaneously up-regulating fat adiponectin and leptin mRNA levels. No significant difference was found between actions of the two extracts. Conclusion Both of polysaccharide and saponin extracts of Radix astragali can improve insulin sensitivity. This action might be closely related to down-regulation of angiotensinogen, TNF-α and up-regulation of adiponectin and leptin expression. The results partly explained the improvement of type Ⅱ diabetes and diabetic nephropathy by Radix astragali. The similar actions of the two crude extracts suggest that unknown key active compounds might exist in both and remain to be discovered.展开更多
Objective: To examine the effect of Pandanus amaryllifolius(P. amaryllifolius) leaf extract on the insulin resistance state in obese ICR mice.Methods: Obesity was induced in mice fed with high-fat diet(45% fat) for 12...Objective: To examine the effect of Pandanus amaryllifolius(P. amaryllifolius) leaf extract on the insulin resistance state in obese ICR mice.Methods: Obesity was induced in mice fed with high-fat diet(45% fat) for 12 weeks. After the first six weeks on the diet, the obese mice were administered with the water extract of P. amaryllifolius leaf at 125 and 250 mg/kg/day, respectively for another six weeks. At the5 th week of treatment, oral glucose tolerance test was conducted. After six weeks of treatment, the levels of blood glucose, serum insulin, leptin, adiponectin, and lipid profiles were determined. The liver, muscle and epididymal fat tissues were removed for measuring the biochemical parameters and protein expression, as well as histological examination.Results: Six weeks of treatment with P. amaryllifolius led to a significant reduction in the blood glucose level as well as improvement in the insulin resistance. P. amaryllifolius also increased the liver glycogen storage and serum adiponectin and decreased the serum leptin levels. A reduction in the serum and hepatic triglyceride, and non-esterified fatty acid levels was also observed. The histological examination showed that the obese mice treated with P. amaryllifolius reduced the lipid droplet in liver tissue and adipocyte size in epididymal fat tissue. The treatment also increased the protein expression of glucose transporter 4 in the muscle and fat tissues.Conclusions: The treatment with P. amaryllifolius could decrease several parameters of impaired glucose and lipid metabolism. To the best of our knowledge, this is the first report on the role of P. amaryllifolius leaf extract in alleviating the insulin dysfunction in obesity state.展开更多
Maize(Zea mays L.) is an economically vital grain crop that is cultivated worldwide. In 2011, a maize foliar disease was detected in Lingtai and Lintao counties in Gansu Province, China. The characteristic signs and s...Maize(Zea mays L.) is an economically vital grain crop that is cultivated worldwide. In 2011, a maize foliar disease was detected in Lingtai and Lintao counties in Gansu Province, China. The characteristic signs and symptoms of this disease include irregular chlorotic lesions on the tips and edges of infected leaves and black punctate fruiting bodies in dead leaf tissues. Given favourable environmental conditions, this disease spread to areas surrounding Gansu. In this study, infected leaves were collected from Gansu and Ningxia Hui Autonomous Region between 2018and 2020 to identify the disease-causing pathogen. Based on morphological features, pathogenicity tests, and multilocus phylogenetic analysis involving internal transcribed spacer(ITS), 18S small subunit rDNA(SSU), 28S large subunit rDNA(LSU), translation elongation factor 1-alpha(TEF), and β-tubulin(TUB) sequences, Eutiarosporella dactylidis was identified as the causative pathogen of this newly discovered leaf blight. Furthermore, an in vitro bioassay was conducted on representative strains using six fungicides, and both fludioxonil and carbendazim were found to significantly inhibit the mycelial growth of E. dactylidis. The results of this study provide a reference for the detection and management of Eutiarosporella leaf blight.展开更多
Diacylglycerol(DAG)-based edible oils have attracted increasing research interest owing to their healthpromoting properties.Recent animal and human studies showed that an increased 1,2-DAG content in the liver and ske...Diacylglycerol(DAG)-based edible oils have attracted increasing research interest owing to their healthpromoting properties.Recent animal and human studies showed that an increased 1,2-DAG content in the liver and skeletal muscle may cause insulin resistance.However,earlier studies using animal models or humans reported that dietary DAGs with a 1,2-DAGs to 1,3-D AGs ratio of approximately 3:7 could improve insulin sensitivity in type 2 diabetic patients.This conflict raises the question of whether there is a link between the ingested DAGs and endogenous DAGs during their metabolism.To make a contribution to this field,this review provides an overview of the metabolic pathways of ingested DAGs and biological roles of DAGs(ingested and endogenous)in the change of insulin sensitivity.Accordingly,strategies for further investigations on the metabolism of DAGs are proposed.展开更多
Precipitation projections over the Tibetan Plateau(TP)show diversity among existing studies,partly due to model uncertainty.How to develop a reliable projection remains inconclusive.Here,based on the IPCC AR6–assesse...Precipitation projections over the Tibetan Plateau(TP)show diversity among existing studies,partly due to model uncertainty.How to develop a reliable projection remains inconclusive.Here,based on the IPCC AR6–assessed likely range of equilibrium climate sensitivity(ECS)and the climatological precipitation performance,the authors constrain the CMIP6(phase 6 of the Coupled Model Intercomparison Project)model projection of summer precipitation and water availability over the TP.The best estimates of precipitation changes are 0.24,0.25,and 0.45 mm d^(−1)(5.9%,6.1%,and 11.2%)under the Shared Socioeconomic Pathway(SSP)scenarios of SSP1–2.6,SSP2–4.5,and SSP5–8.5 from 2050–2099 relative to 1965–2014,respectively.The corresponding constrained projections of water availability measured by precipitation minus evaporation(P–E)are 0.10,0.09,and 0.22 mm d^(−1)(5.7%,4.9%,and 13.2%),respectively.The increase of precipitation and P–E projected by the high-ECS models,whose ECS values are higher than the upper limit of the likely range,are about 1.7 times larger than those estimated by constrained projections.Spatially,there is a larger increase in precipitation and P–E over the eastern TP,while the western part shows a relatively weak difference in precipitation and a drier trend in P–E.The wetter TP projected by the high-ECS models resulted from both an approximately 1.2–1.4 times stronger hydrological sensitivity and additional warming of 0.6℃–1.2℃ under all three scenarios during 2050–2099.This study emphasizes that selecting climate models with climate sensitivity within the likely range is crucial to reducing the uncertainty in the projection of TP precipitation and water availability changes.展开更多
AIM:To test the efficacy of a proprietary nutraceutical combination in reducing insulin resistance associated with the metabolic syndrome(MetS).METHODS:Sixty-four patients with MetS followed at a tertiary outpatient c...AIM:To test the efficacy of a proprietary nutraceutical combination in reducing insulin resistance associated with the metabolic syndrome(MetS).METHODS:Sixty-four patients with MetS followed at a tertiary outpatient clinic were randomly assigned to receive either placebo or a proprietary nutraceutical combination(AP)consisting of berberine,policosanol and red yeast rice,in a prospective,double-blind,placebo-controlled study.Evaluations were performed at baseline and after 18 wk of treatment.The homeostasis model assessment of insulin resistance(HOMAIR)index was the primary outcome measure.Secondary endpoints included lipid panel,blood glucose and insulin fasting,after a standard mixed meal and after an oral glucose tolerance test(OGTT),ow-mediated dilation(FMD),and waist circumference.RESULTS:Fifty nine patients completed the study,2 withdrew because of adverse effects.After 18 wk there was a signif icant reduction in the HOMA-IR index in the AP group compared with placebo(ΔHOMA respectively-0.6 ± 1.2 vs 0.4 ± 1.9;P < 0.05).Total and low density lipoprotein cholesterol also significantly decreased in the treatment arm compared with placebo(Δlow density lipoprotein cholesterol-0.82 ± 0.68 vs-0.13 ± 0.55 mmol/L;P < 0.001),while triglycerides,high density lipoprotein cholesterol,and the OGTT were not affected.In addition,there were significant reductions in blood glucose and insulin after the standard mixed meal,as well as an increase in FMD(ΔFMD 1.9 ± 4.2 vs 0 ± 1.9 %;P < 0.05)and a significant reduction in arterial systolic blood pressure in the AP arm.CONCLUSION:This short-term study shows that AP has relevant beneficial effects on insulin resistance and many other components of MetS.展开更多
This paper introduces a novel approach for parameter sensitivity evaluation and efficient slope reliability analysis based on quantile-based first-order second-moment method(QFOSM).The core principles of the QFOSM are...This paper introduces a novel approach for parameter sensitivity evaluation and efficient slope reliability analysis based on quantile-based first-order second-moment method(QFOSM).The core principles of the QFOSM are elucidated geometrically from the perspective of expanding ellipsoids.Based on this geometric interpretation,the QFOSM is further extended to estimate sensitivity indices and assess the significance of various uncertain parameters involved in the slope system.The proposed method has the advantage of computational simplicity,akin to the conventional first-order second-moment method(FOSM),while providing estimation accuracy close to that of the first-order reliability method(FORM).Its performance is demonstrated with a numerical example and three slope examples.The results show that the proposed method can efficiently estimate the slope reliability and simultaneously evaluate the sensitivity of the uncertain parameters.The proposed method does not involve complex optimization or iteration required by the FORM.It can provide a valuable complement to the existing approximate reliability analysis methods,offering rapid sensitivity evaluation and slope reliability analysis.展开更多
AIM: To assess the regulatory effect of microRNA-185 (miR-185) on lipid metabolism and the insulin signalling pathway in human HepG2 hepatocytes and a high-fat diet mouse model.
Background: We aimed to evaluate the short-term metabolic effects of a GLP-1a, (liraglutide) versus a DPP-4i, (vildagliptin) in a group of sub-Saharan type 2 diabetes patients. Methods: We conducted a randomized contr...Background: We aimed to evaluate the short-term metabolic effects of a GLP-1a, (liraglutide) versus a DPP-4i, (vildagliptin) in a group of sub-Saharan type 2 diabetes patients. Methods: We conducted a randomized controlled single blinded clinical trial in 14 uncontrolled type 2 diabetes patients (HbA1c ≥ 53 mmol/mol) with mean duration of diabetes of 8 [1 - 12] years and median age of 57 [49 - 61] years. Baseline treatment consisted of metformin in monotherapy or metformin plus sulfonylureas. Participants were randomly allocated to 2 groups of add-on 1.2 mg/day subcutaneous liraglutide in group 1 or 100 mg/day of oral vildagliptin in group 2 for 2 weeks. In all participants, insulin secretion in response to mixed meal tolerance test, insulin sensitivity by 80 mU/m<sup>2</sup>/min hyperinsulinemic-euglycemic clamp, body composition, and lipid profile were measured before and after intervention. Results: At the end of intervention, insulin sensitivity remained unchanged both with liraglutide from 6.6 [4.2 - 7.9] to 6.9 [4.3 - 10.8] mg/kg/min;p = 0.61 and vildagliptin from 7.1 [5.3 - 9.0] to 6.5 [5.6 - 9.4] mg/kg/min (p = 0.86). The area under the C-peptide curve varied from 5.5 [1.0 - 10.9] to 14.9 [10.8 - 17.2] nmol/L/120min, p = 0.09 in group 1 and from 1.1 [0.5 - 14.1] to 13.0 [9.6 - 16.9] nmol/L/120min (p = 0.17) in group 2. LDL Cholesterol levels decreased significantly with liraglutide from 0.85 g/L [0.51 - 1.02] to 0.54 g/L [0.50 - 0.73] (p = 0.04) but not with Vildagliptin. Body weight tended to decrease in group 1 (−0.6 kg) versus modest increase in group 2 (+1.1 kg). Conclusion: Short-term metabolic effects of Liraglutide and Vildagliptin add-on therapy are comparable in sub-Saharan type 2 diabetes patients with a more favorable trend for Liraglutide on body weight, lipid profile, and insulin secretion.展开更多
Let(X,T)be a linear dynamical system,where X is a Banach space and T:X→X is a bounded linear operator.This paper obtains that(X,T)is sensitive(Li-Yorke sensitive,mean sensitive,syndetically mean sensitive,respectivel...Let(X,T)be a linear dynamical system,where X is a Banach space and T:X→X is a bounded linear operator.This paper obtains that(X,T)is sensitive(Li-Yorke sensitive,mean sensitive,syndetically mean sensitive,respectively)if and only if(X,T)is Banach mean sensitive(Banach mean Li-Yorke sensitive,thickly multi-mean sensitive,thickly syndetically mean sensitive,respectively).Several examples are provided to distinguish between different notions of mean sensitivity,syndetic mean sensitivi`ty and mean Li-Yorke sensitivity.展开更多
Objective To study the effect of β3 adrenergic receptor (β3AR) Trp64Arg and peroxisome proliferator activated receptor gamma 2 (PPAR72) Prol2Ala polymorphisms on insulin resistance. Methods One hundred and eight...Objective To study the effect of β3 adrenergic receptor (β3AR) Trp64Arg and peroxisome proliferator activated receptor gamma 2 (PPAR72) Prol2Ala polymorphisms on insulin resistance. Methods One hundred and eight dizygotic twin pairs were enrolled in this study. Microsatellite polymorphism was used to diagnose zygosity of twins. Insulin sensitivity was estimated with logarithm transformed homeostasis model assessment (HOMA). PCR-RFLP analysis was performed to detect the variants. As a supplement to the sib-pair method, identity by state (IBS) was used to analyze the association of polymorphisms with insulin sensitivity. Results The genotype frequencies of Trp64Trg, Trp64Arg, and Arg64Arg were 72.3%, 23.8%, and 3.9%, respectively, while the genotype frequencies of Pro12Pro, Pro12Ala, and Ala12Ala were 89.9%, 9.6%, and 0.5%, respectively. For β3AR Trp64Arg the interclass co-twin correlations of Waist-to-hip ratio (WHR), blood glucose (GLU), and insulin (INS), homeostasis model assessment insulin resistance index (HOMA-IR) of the twin pairs sharing 2 alleles of IBS were greater than those sharing 0-1 allele of IBS, and HOMA4R had statistic significance. For PPAR3t2 Prol2Ala most traits of twin pairs sharing 2 alleles of IBS had greater correlations and statistic significance in body mass index (BMI), WHR, percent of body fat (PBF) and GLU, but there were low correlations of either insulin or HOMA-IR of twin pairs sharing 1 or 2 alleles of IBS. The combined effects of the two variations showed less squared significant twin-pair differences of INS and HOMA-IR among twins sharing 4 alleles of IBS. Condusions β3AR Trp64Arg and PPAR),2 Pro 12Ala polymorphisms might be associated with insulin resistance and obesity, and there might be slight synergistic effects between this two gene loci, and further studies are necessary to confirm this finding.展开更多
Phosphatidylcholine(PC) and phosphatidylethanolamine(PE), which make up the bulk of mammalian cell membrane phospholipids, are recognized for their importance in metabolic health. Perturbations in the ratio of PC:PE c...Phosphatidylcholine(PC) and phosphatidylethanolamine(PE), which make up the bulk of mammalian cell membrane phospholipids, are recognized for their importance in metabolic health. Perturbations in the ratio of PC:PE can affect membrane integrity and function, which thus have serious health consequences. Imbalance in the hepatic PC and PE membrane content can be linked to metabolic disturbances such as ER stress, fatty liver and insulin resistance. Given that impaired insulin sensitivity underlies the pathology of many metabolic disorders and skeletal muscle is a significant regulator of energy metabolism, it is likely that aberrant phospholipid metabolism in skeletal muscle affects whole-body insulin sensitivity. Sarco/endoplasmic reticulum Ca^(2+) ATPase(SERCA) activity and mitochondrial function respond to alterations in PC:PE ratio and are associated with glucose homeostasis. Moreover, PC and PE content within the mitochondrial membrane influence mitochondrial respiration and biogenesis and thus, metabolic function. As skeletal muscle phospholipids respond to stimuli such as diet and exercise, understanding the implications of imbalances in PC:PE ratio is of great importance in the face of the rising epidemic of obesity related diseases. This review will summarize the current state of knowledge signifying the links between skeletal muscle PC:PE ratio and insulin sensitivity with respects to PC and PE metabolism, SERCA activity, mitochondrial function and exercise.展开更多
Clarifying the relationship between stress sensitivities of permeability and porosity is of great significance in guiding underground resource mining.More and more studies focus on how to construct stress sensitivity ...Clarifying the relationship between stress sensitivities of permeability and porosity is of great significance in guiding underground resource mining.More and more studies focus on how to construct stress sensitivity models to describe the relationship and obtain a comprehensive stress sensitivity of porous rock.However,the limitations of elastic deformation calculation and incompleteness of considered tortuosity sensitivity lead to the fact that the existing stress sensitivity models are still unsatisfactory in terms of accuracy and generalization.Therefore,a more accurate and generic stress sensitivity model considering elastic-structural deformation of capillary cross-section and tortuosity sensitivity is proposed in this paper.The elastic deformation is derived from the fractal scaling model and Hooke's law.Considering the effects of elastic-structural deformation on tortuosity sensitivity,an empirical formula is proposed,and the conditions for its applicability are clarified.The predictive performance of the proposed model for the permeability-porosity relationships is validated in several sets of publicly available experimental data.These experimental data are from different rocks under different pressure cycles.The mean and standard deviation of relative errors of predicted stress sensitivity with respect to experimental data are 2.63%and 1.91%.Compared with other models,the proposed model has higher accuracy and better predictive generalization performance.It is also found that the porosity sensitivity exponent a,which can describe permeability-porosity relationships,is 2 when only elastic deformation is considered.a decreases from 2 when structural deformation is also considered.In addition,a may be greater than 3 due to the increase in tortuosity sensitivity when tortuosity sensitivity is considered even if the rock is not fractured.展开更多
Insulin resistance is an essential characteristic of type 2 diabetes mellitus(T2DM),which can be induced by glucotoxicity and adipose chronic inflammation.Mesenchymal stem cells(MSCs)and their exosomes were reported t...Insulin resistance is an essential characteristic of type 2 diabetes mellitus(T2DM),which can be induced by glucotoxicity and adipose chronic inflammation.Mesenchymal stem cells(MSCs)and their exosomes were reported to ameliorate T2DM and its complications by their immunoregulatory and healing abilities.Exosomes derived from MSCs contain abundant molecules to mediate crosstalk between cells and mimic biological function of MSCs.But the role of exosomes derived from human umbilical cord mesenchymal stem cells(hUC-MSCs)in insulin resistance of human adipocytes is unclear.In this study,exosomes were harvested from the conditioned medium of hUC-MSCs and added to insulin-resistant adipocytes.Insulin-stimulated glucose uptake was measured by glucose oxidase/peroxidase assay.The signal pathway involved in exosome-treated adipocytes was detected by RT-PCR and Western blotting.The biological characteristics and function were compared between hUC-MSCs and human adipose-derived mesenchymal stem cells(hAMSCs).The results showed that hAMSCs had better adipogenic ability than hUC-MSCs.After induction of mature adipocytes by adipogenesis of hAMSC,the model of insulin-resistant adipocytes was successfully established by TNF-αand high glucose intervention.After exosome treatment,the insulin-stimulated glucose uptake was significantly increased.In addition,the effect of exosomes could be stabilized for at least 48 h.Furthermore,the level of leptin was significantly decreased,and the mRNA expression of sirtuin-1 and insulin receptor substrate-1 was significantly upregulated after exosome treatment.In conclusion,exosomes significantly improve insulin sensitivity in insulin-resistant human adipocytes,and the mechanism involves the regulation of adipokines.展开更多
Background: Lack of first phase insulin secretion during oral glucose tolerance test [OGTT] in Type 2 Diabetes Mellitus (DM) is attributed to glucose toxicity. Alternatively, the role of insulin resistance in impaired...Background: Lack of first phase insulin secretion during oral glucose tolerance test [OGTT] in Type 2 Diabetes Mellitus (DM) is attributed to glucose toxicity. Alternatively, the role of insulin resistance in impaired insulin release secondary to lack of glucose entry into β cells may be responsible, but is not examined. Aim: The role of insulin sensitivity in 1st phase insulin secretion was assessed. Material and Methods: Plasma glucose (G) and insulin (I) concentrations were determined after an overnight fast (F) and upto 60 minutes during OGTT with glucose 75g in 12 normal (N), 14 with impaired glucose tolerance (IGT) and 41 subjects with Type 2 DM. First phase insulin secretion (Δ Insulin) was determined as a percentage rise from baseline 100x (Peak-Basal)/Basal. Insulin sensitivity was determined as FI x FG (mUxmM/L). Results: FG were normal (7.0 mM/L in Type 2 DM. FI x FG and ? insulin were 35 ± 4 and 389 ± 89% in N;77 ± 5 and 254 ± 65% in IGT;and 235 ± 19 and 95 ± 15% in Type 2 DM. Significant negative correlations were noted between ? insulin one hand and FI x FG on the other amongst all subjects [p < 0.0001 for all correlations]. Conclusion: Decline of 1st phase insulin secretion in IGT and Type 2 DM may be attributed to inhibited release of depleted insulin stores in the β Cells induced by impaired glucose entry due to insulin resistance, and is unlikely to be caused by glucose toxicity in IGT in presence of fasting euglycemia.展开更多
Fluopyram is an succinate dehydrogenase inhibitors(SDHI)fungicide that has been registered in China to control gummy stem blight(GSB)in watermelons for many years.However,whether the field pathogens of GSB are still s...Fluopyram is an succinate dehydrogenase inhibitors(SDHI)fungicide that has been registered in China to control gummy stem blight(GSB)in watermelons for many years.However,whether the field pathogens of GSB are still sensitive to fluopyram or not is unknown.Therefore,we collected 69 Didymella bryoniae isolates from the fields that usually use fluopyram to control GSB to determine the sensitivity change.The EC_(50)(50%inhibition effect)values of fluopyram against D.bryoniae ranged from 0.0691 to 0.3503μg mL^(–1) and the variation factor was 5.07.The mean EC_(50) value was(0.1579±0.0669)μg mL^(–1) and the curve of sensitivity was unimodal.No resistant strains were found in the isolates,which means that the pathogens were still sensitive to fluopyram.The minimal inhibition concentration(MIC)of fluopyram against D.bryoniae was 3μg mL^(–1).Four low-resistant mutants and two medium-resistant mutants were obtained using fungicide taming and the resistance of mutants could be inherited stably.The growth rate of mutants decreased significantly compared with that of wild-type strains while the biomass of most mutants was similar to that of wild-type strains.The sensitivity of most resistant mutants to various stresses was increased compared with that of wild-type strains.The virulence of mutants receded except for low-resistant mutant XN51FR-1,which had the same lesion area as XN51 on the watermelon leaves.The results indicated that the fitness of resistant mutants was decreased compared with that of wild-type strains.The cross-resistance assay indicated that fluopyram-resistant mutants were positive cross-resistant to all six SDHI fungicides in this test but were still sensitive to fluazinam and tebuconazole.So the resistance risk of D.bryoniae to fluopyram was moderate.In addition,we found that the SdhB gene of low-resistant mutant XN30FR-1 had three new point mutations at positions K258N,A259P,and H277N.Medium-resistant mutant XN52FR-1 showed a mutation at position H277N and other mutants did not have any point mutation.展开更多
基金financially supported by the National Key Research and Development Program of China(No.2022YFA1205300 and No.2022YFA1205304)the Oceanic Interdisciplinary Program of Shanghai Jiao Tong University(SL2022ZD103).
文摘Monitoring minuscule mechanical signals,both in magnitude and direction,is imperative in many application scenarios,e.g.,structural health monitoring and robotic sensing systems.However,the piezoelectric sensor struggles to satisfy the requirements for directional recognition due to the limited piezoelectric coefficient matrix,and achieving sensitivity for detecting micrometer-scale deformations is also challenging.Herein,we develop a vector sensor composed of lead zirconate titanate-electronic grade glass fiber composite filaments with oriented arrangement,capable of detecting minute anisotropic deformations.The as-prepared vector sensor can identify the deformation directions even when subjected to an unprecedented nominal strain of 0.06%,thereby enabling its utility in accurately discerning the 5μm-height wrinkles in thin films and in monitoring human pulse waves.The ultra-high sensitivity is attributed to the formation of porous ferroelectret and the efficient load transfer efficiency of continuous lead zirconate titanate phase.Additionally,when integrated with machine learning techniques,the sensor’s capability to recognize multi-signals enables it to differentiate between 10 types of fine textures with 100%accuracy.The structural design in piezoelectric devices enables a more comprehensive perception of mechanical stimuli,offering a novel perspective for enhancing recognition accuracy.
基金Supported by National Natural Science Foundation of China,No.32200944“Qing Lan”Project of Jiangsu Provincethe Jiangsu Research Institute of Sports Science Foundation,No.BM-2023-03.
文摘BACKGROUND Skeletal muscle handles about 80% of insulin-stimulated glucose uptake and become the major organ occurring insulin resistance(IR).Many studies have confirmed the interactions between macrophages and skeletal muscle regulated the inflammation and regeneration of skeletal muscle.However,despite of the decades of research,whether macrophages infiltration and polarization in skeletal muscle under high glucose(HG)milieus results in the development of IR is yet to be elucidated.C2C12 myoblasts are well-established and excellent model to study myogenic regulation and its responses to stimulation.Further exploration of macrophages'role in myoblasts IR and the dynamics of their infiltration and polarization is warranted.AIM To evaluate interactions between myoblasts and macrophages under HG,and its effects on inflammation and IR in skeletal muscle.METHODS We detected the polarization status of macrophages infiltrated to skeletal muscles of IR mice by hematoxylin and eosin and immunohistochemical staining.Then,we developed an in vitro co-culture system to study the interactions between myoblasts and macrophages under HG milieus.The effects of myoblasts on macrophages were explored through morphological observation,CCK-8 assay,Flow Cytometry,and enzyme-linked immunosorbent assay.The mediation of macrophages to myogenesis and insulin sensitivity were detected by morphological observation,CCK-8 assay,Immunofluorescence,and 2-NBDG assay.RESULTS The F4/80 and co-localization of F4/80 and CD86 increased,and the myofiber size decreased in IR group(P<0.01,g=6.26).Compared to Mc group,F4/80+CD86+CD206-cells,tumor necrosis factor-α(TNFα),inerleukin-1β(IL-1β)and IL-6 decreased,and IL-10 increased in McM group(P<0.01,g>0.8).In McM+HG group,F4/80+CD86+CD206-cells,monocyte chemoattractant protein 1,TNFα,IL-1βand IL-6 were increased,and F4/80+CD206+CD86-cells and IL-10 were decreased compared with Mc+HG group and McM group(P<0.01,g>0.8).Compered to M group,myotube area,myotube number and E-MHC were increased in MMc group(P<0.01,g>0.8).In MMc+HG group,myotube area,myotube number,E-MHC,GLUT4 and glucose uptake were decreased compared with M+HG group and MMc group(P<0.01,g>0.8).CONCLUSION Interactions between myoblasts and macrophages under HG milieus results in inflammation and IR,which support that the macrophage may serve as a promising therapeutic target for skeletal muscle atrophy and IR.
文摘Background: The role of vitamin D and parathyroid hormone in the metabolic profile of type 2 diabetes mellitus in sub-Saharan Africa has not been adequately assessed. The aim of this study was to determine the prevalence of low vitamin D level and secondary hyperparathyroidism and their association with insulin sensitivity and β-cell secretory function among Congolese type 2 diabetics. Methodology: Fasting glycaemia, fasting insulin, 25OH D3 and human parathyroid hormone (hPTH) were measured in one hundred and eighty-four type 2 diabetic patients followed as outpatients in South Kivu. Levels of 25OH D3 65 pg/ml defined low vitamin D and elevated parathyroid hormone levels, respectively. The HOMA model was used to measure insulin sensitivity and β-cell secretory function. Results: Medians (IQR) were 25.3 (20.4 - 32.4) ng/ml for 25OH D3 and 53.7 (38.4 - 115.7) pg/ml for hPTH. 58.7% of diabetics had insulin resistance, 126 (68.5%) had low vitamin D and 80 (43.5%) had hyperparathyroidism. In multivariate analysis, hPTH (partial r = −0.28;p = 0.0002) and 25OH D3 (partial r = 0.16;p = 0.03) showed an independent association with insulin sensitivity after adjustment for body mass index and waist circumference. Finally, hPTH (partial r = 0.27;p = 0.0002) was the sole determinant of β-cell secretory function. Conclusions: This study confirms the high prevalence of low vitamin D level and secondary hyperparathyroidism and their association with insulin resistance and impaired islet β-cell secretory function among Congolese with type 2 diabetes mellitus. Vitamin D and calcium supplementation should be envisaged for cases of deficiency in this region.
文摘Aim To reveal the main active components and the action mechanisms of Radix astragali on insulin sensitivity improvement, we have investigated the effects of polysaccharide portion and saponin portion of Radix astragali extracts on blood biochemical indices and related gene expression of dexamethasone-induced SD rats. Methods SD rats (6 per group) received 2 μg/day subcutaneous dexamethasone for 4 weeks plus same dose (10 g material/kg) of polysaccharide or saponin extracts of Radix astragali. Blood samples, kidney tissues and epididymal fat pads were taken at the end of the experiment. Serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), glucose (GLU) and insulin (INS) levels were measured, respectively, mRNA levels of angiotensinogen in kidney, adiponectin and leptin as well as TNF-α in epididymal fats were determined by RT-PCR assay using GAPDH gene as an internal control. Results Both of polysaccharide and saponin extracts of Radix astragali exhibited positive effects in reducing serum triglycerides, glucose, and insulin levels of dexamethasone-induced SD rats. The saponin group showed more improvements on quantitive insulin sensitivity check index (QUICKI) than the polysaccharide group did. Both of the extracts down-regulated kidney angiotensinogen and fat TNF-α mRNA levels while they were simultaneously up-regulating fat adiponectin and leptin mRNA levels. No significant difference was found between actions of the two extracts. Conclusion Both of polysaccharide and saponin extracts of Radix astragali can improve insulin sensitivity. This action might be closely related to down-regulation of angiotensinogen, TNF-α and up-regulation of adiponectin and leptin expression. The results partly explained the improvement of type Ⅱ diabetes and diabetic nephropathy by Radix astragali. The similar actions of the two crude extracts suggest that unknown key active compounds might exist in both and remain to be discovered.
基金Supported by the research grant from the Faculty of Medicine,Thammasat University(Contract number:GEN2-22/2015)
文摘Objective: To examine the effect of Pandanus amaryllifolius(P. amaryllifolius) leaf extract on the insulin resistance state in obese ICR mice.Methods: Obesity was induced in mice fed with high-fat diet(45% fat) for 12 weeks. After the first six weeks on the diet, the obese mice were administered with the water extract of P. amaryllifolius leaf at 125 and 250 mg/kg/day, respectively for another six weeks. At the5 th week of treatment, oral glucose tolerance test was conducted. After six weeks of treatment, the levels of blood glucose, serum insulin, leptin, adiponectin, and lipid profiles were determined. The liver, muscle and epididymal fat tissues were removed for measuring the biochemical parameters and protein expression, as well as histological examination.Results: Six weeks of treatment with P. amaryllifolius led to a significant reduction in the blood glucose level as well as improvement in the insulin resistance. P. amaryllifolius also increased the liver glycogen storage and serum adiponectin and decreased the serum leptin levels. A reduction in the serum and hepatic triglyceride, and non-esterified fatty acid levels was also observed. The histological examination showed that the obese mice treated with P. amaryllifolius reduced the lipid droplet in liver tissue and adipocyte size in epididymal fat tissue. The treatment also increased the protein expression of glucose transporter 4 in the muscle and fat tissues.Conclusions: The treatment with P. amaryllifolius could decrease several parameters of impaired glucose and lipid metabolism. To the best of our knowledge, this is the first report on the role of P. amaryllifolius leaf extract in alleviating the insulin dysfunction in obesity state.
基金supported by the Doctor Foundation of Gansu Academy of Agricultural Sciences,China(2020GAAS33)the Young Science and Technology Lifting Engineering Talents in Gansu Province,China(2020-18)the Agricultural Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences(CAAS-ASTIP-2017-ICS)。
文摘Maize(Zea mays L.) is an economically vital grain crop that is cultivated worldwide. In 2011, a maize foliar disease was detected in Lingtai and Lintao counties in Gansu Province, China. The characteristic signs and symptoms of this disease include irregular chlorotic lesions on the tips and edges of infected leaves and black punctate fruiting bodies in dead leaf tissues. Given favourable environmental conditions, this disease spread to areas surrounding Gansu. In this study, infected leaves were collected from Gansu and Ningxia Hui Autonomous Region between 2018and 2020 to identify the disease-causing pathogen. Based on morphological features, pathogenicity tests, and multilocus phylogenetic analysis involving internal transcribed spacer(ITS), 18S small subunit rDNA(SSU), 28S large subunit rDNA(LSU), translation elongation factor 1-alpha(TEF), and β-tubulin(TUB) sequences, Eutiarosporella dactylidis was identified as the causative pathogen of this newly discovered leaf blight. Furthermore, an in vitro bioassay was conducted on representative strains using six fungicides, and both fludioxonil and carbendazim were found to significantly inhibit the mycelial growth of E. dactylidis. The results of this study provide a reference for the detection and management of Eutiarosporella leaf blight.
基金supported by Chinese National Natural Foundation for Distinguished Young Scholars(31725022)Beijing Advanced Innovation Center for Food Nutrition and Human Health+1 种基金Beijing Technology and Business University(BTBU)(20171049)the Science&Technology Department of Shaanxi Province(2019JM-333)。
文摘Diacylglycerol(DAG)-based edible oils have attracted increasing research interest owing to their healthpromoting properties.Recent animal and human studies showed that an increased 1,2-DAG content in the liver and skeletal muscle may cause insulin resistance.However,earlier studies using animal models or humans reported that dietary DAGs with a 1,2-DAGs to 1,3-D AGs ratio of approximately 3:7 could improve insulin sensitivity in type 2 diabetic patients.This conflict raises the question of whether there is a link between the ingested DAGs and endogenous DAGs during their metabolism.To make a contribution to this field,this review provides an overview of the metabolic pathways of ingested DAGs and biological roles of DAGs(ingested and endogenous)in the change of insulin sensitivity.Accordingly,strategies for further investigations on the metabolism of DAGs are proposed.
基金supported by the Second Tibetan Plateau Scientific Expedition and Research(STEP)program[grant number 2019QZKK0102]the Chinese Academy of Sciences[grant number 060GJHZ2023079GC].
文摘Precipitation projections over the Tibetan Plateau(TP)show diversity among existing studies,partly due to model uncertainty.How to develop a reliable projection remains inconclusive.Here,based on the IPCC AR6–assessed likely range of equilibrium climate sensitivity(ECS)and the climatological precipitation performance,the authors constrain the CMIP6(phase 6 of the Coupled Model Intercomparison Project)model projection of summer precipitation and water availability over the TP.The best estimates of precipitation changes are 0.24,0.25,and 0.45 mm d^(−1)(5.9%,6.1%,and 11.2%)under the Shared Socioeconomic Pathway(SSP)scenarios of SSP1–2.6,SSP2–4.5,and SSP5–8.5 from 2050–2099 relative to 1965–2014,respectively.The corresponding constrained projections of water availability measured by precipitation minus evaporation(P–E)are 0.10,0.09,and 0.22 mm d^(−1)(5.7%,4.9%,and 13.2%),respectively.The increase of precipitation and P–E projected by the high-ECS models,whose ECS values are higher than the upper limit of the likely range,are about 1.7 times larger than those estimated by constrained projections.Spatially,there is a larger increase in precipitation and P–E over the eastern TP,while the western part shows a relatively weak difference in precipitation and a drier trend in P–E.The wetter TP projected by the high-ECS models resulted from both an approximately 1.2–1.4 times stronger hydrological sensitivity and additional warming of 0.6℃–1.2℃ under all three scenarios during 2050–2099.This study emphasizes that selecting climate models with climate sensitivity within the likely range is crucial to reducing the uncertainty in the projection of TP precipitation and water availability changes.
文摘AIM:To test the efficacy of a proprietary nutraceutical combination in reducing insulin resistance associated with the metabolic syndrome(MetS).METHODS:Sixty-four patients with MetS followed at a tertiary outpatient clinic were randomly assigned to receive either placebo or a proprietary nutraceutical combination(AP)consisting of berberine,policosanol and red yeast rice,in a prospective,double-blind,placebo-controlled study.Evaluations were performed at baseline and after 18 wk of treatment.The homeostasis model assessment of insulin resistance(HOMAIR)index was the primary outcome measure.Secondary endpoints included lipid panel,blood glucose and insulin fasting,after a standard mixed meal and after an oral glucose tolerance test(OGTT),ow-mediated dilation(FMD),and waist circumference.RESULTS:Fifty nine patients completed the study,2 withdrew because of adverse effects.After 18 wk there was a signif icant reduction in the HOMA-IR index in the AP group compared with placebo(ΔHOMA respectively-0.6 ± 1.2 vs 0.4 ± 1.9;P < 0.05).Total and low density lipoprotein cholesterol also significantly decreased in the treatment arm compared with placebo(Δlow density lipoprotein cholesterol-0.82 ± 0.68 vs-0.13 ± 0.55 mmol/L;P < 0.001),while triglycerides,high density lipoprotein cholesterol,and the OGTT were not affected.In addition,there were significant reductions in blood glucose and insulin after the standard mixed meal,as well as an increase in FMD(ΔFMD 1.9 ± 4.2 vs 0 ± 1.9 %;P < 0.05)and a significant reduction in arterial systolic blood pressure in the AP arm.CONCLUSION:This short-term study shows that AP has relevant beneficial effects on insulin resistance and many other components of MetS.
基金supported by the National Natural Science Foundation of China(Grant Nos.52109144,52025094 and 52222905).
文摘This paper introduces a novel approach for parameter sensitivity evaluation and efficient slope reliability analysis based on quantile-based first-order second-moment method(QFOSM).The core principles of the QFOSM are elucidated geometrically from the perspective of expanding ellipsoids.Based on this geometric interpretation,the QFOSM is further extended to estimate sensitivity indices and assess the significance of various uncertain parameters involved in the slope system.The proposed method has the advantage of computational simplicity,akin to the conventional first-order second-moment method(FOSM),while providing estimation accuracy close to that of the first-order reliability method(FORM).Its performance is demonstrated with a numerical example and three slope examples.The results show that the proposed method can efficiently estimate the slope reliability and simultaneously evaluate the sensitivity of the uncertain parameters.The proposed method does not involve complex optimization or iteration required by the FORM.It can provide a valuable complement to the existing approximate reliability analysis methods,offering rapid sensitivity evaluation and slope reliability analysis.
基金Supported by National Natural Science Foundation of China,No.30950005the Department of Education of Heilongjiang Province,No.12511233
文摘AIM: To assess the regulatory effect of microRNA-185 (miR-185) on lipid metabolism and the insulin signalling pathway in human HepG2 hepatocytes and a high-fat diet mouse model.
文摘Background: We aimed to evaluate the short-term metabolic effects of a GLP-1a, (liraglutide) versus a DPP-4i, (vildagliptin) in a group of sub-Saharan type 2 diabetes patients. Methods: We conducted a randomized controlled single blinded clinical trial in 14 uncontrolled type 2 diabetes patients (HbA1c ≥ 53 mmol/mol) with mean duration of diabetes of 8 [1 - 12] years and median age of 57 [49 - 61] years. Baseline treatment consisted of metformin in monotherapy or metformin plus sulfonylureas. Participants were randomly allocated to 2 groups of add-on 1.2 mg/day subcutaneous liraglutide in group 1 or 100 mg/day of oral vildagliptin in group 2 for 2 weeks. In all participants, insulin secretion in response to mixed meal tolerance test, insulin sensitivity by 80 mU/m<sup>2</sup>/min hyperinsulinemic-euglycemic clamp, body composition, and lipid profile were measured before and after intervention. Results: At the end of intervention, insulin sensitivity remained unchanged both with liraglutide from 6.6 [4.2 - 7.9] to 6.9 [4.3 - 10.8] mg/kg/min;p = 0.61 and vildagliptin from 7.1 [5.3 - 9.0] to 6.5 [5.6 - 9.4] mg/kg/min (p = 0.86). The area under the C-peptide curve varied from 5.5 [1.0 - 10.9] to 14.9 [10.8 - 17.2] nmol/L/120min, p = 0.09 in group 1 and from 1.1 [0.5 - 14.1] to 13.0 [9.6 - 16.9] nmol/L/120min (p = 0.17) in group 2. LDL Cholesterol levels decreased significantly with liraglutide from 0.85 g/L [0.51 - 1.02] to 0.54 g/L [0.50 - 0.73] (p = 0.04) but not with Vildagliptin. Body weight tended to decrease in group 1 (−0.6 kg) versus modest increase in group 2 (+1.1 kg). Conclusion: Short-term metabolic effects of Liraglutide and Vildagliptin add-on therapy are comparable in sub-Saharan type 2 diabetes patients with a more favorable trend for Liraglutide on body weight, lipid profile, and insulin secretion.
文摘Let(X,T)be a linear dynamical system,where X is a Banach space and T:X→X is a bounded linear operator.This paper obtains that(X,T)is sensitive(Li-Yorke sensitive,mean sensitive,syndetically mean sensitive,respectively)if and only if(X,T)is Banach mean sensitive(Banach mean Li-Yorke sensitive,thickly multi-mean sensitive,thickly syndetically mean sensitive,respectively).Several examples are provided to distinguish between different notions of mean sensitivity,syndetic mean sensitivi`ty and mean Li-Yorke sensitivity.
基金This study was supported by the National Natural Science Foundation of China (30371223)the Major State Basic Research Development Program of China (2001CB510310).
文摘Objective To study the effect of β3 adrenergic receptor (β3AR) Trp64Arg and peroxisome proliferator activated receptor gamma 2 (PPAR72) Prol2Ala polymorphisms on insulin resistance. Methods One hundred and eight dizygotic twin pairs were enrolled in this study. Microsatellite polymorphism was used to diagnose zygosity of twins. Insulin sensitivity was estimated with logarithm transformed homeostasis model assessment (HOMA). PCR-RFLP analysis was performed to detect the variants. As a supplement to the sib-pair method, identity by state (IBS) was used to analyze the association of polymorphisms with insulin sensitivity. Results The genotype frequencies of Trp64Trg, Trp64Arg, and Arg64Arg were 72.3%, 23.8%, and 3.9%, respectively, while the genotype frequencies of Pro12Pro, Pro12Ala, and Ala12Ala were 89.9%, 9.6%, and 0.5%, respectively. For β3AR Trp64Arg the interclass co-twin correlations of Waist-to-hip ratio (WHR), blood glucose (GLU), and insulin (INS), homeostasis model assessment insulin resistance index (HOMA-IR) of the twin pairs sharing 2 alleles of IBS were greater than those sharing 0-1 allele of IBS, and HOMA4R had statistic significance. For PPAR3t2 Prol2Ala most traits of twin pairs sharing 2 alleles of IBS had greater correlations and statistic significance in body mass index (BMI), WHR, percent of body fat (PBF) and GLU, but there were low correlations of either insulin or HOMA-IR of twin pairs sharing 1 or 2 alleles of IBS. The combined effects of the two variations showed less squared significant twin-pair differences of INS and HOMA-IR among twins sharing 4 alleles of IBS. Condusions β3AR Trp64Arg and PPAR),2 Pro 12Ala polymorphisms might be associated with insulin resistance and obesity, and there might be slight synergistic effects between this two gene loci, and further studies are necessary to confirm this finding.
基金supported by the Canadian Institutes of Health Research grant(CIHR-ECD-144626 Ref#46309)。
文摘Phosphatidylcholine(PC) and phosphatidylethanolamine(PE), which make up the bulk of mammalian cell membrane phospholipids, are recognized for their importance in metabolic health. Perturbations in the ratio of PC:PE can affect membrane integrity and function, which thus have serious health consequences. Imbalance in the hepatic PC and PE membrane content can be linked to metabolic disturbances such as ER stress, fatty liver and insulin resistance. Given that impaired insulin sensitivity underlies the pathology of many metabolic disorders and skeletal muscle is a significant regulator of energy metabolism, it is likely that aberrant phospholipid metabolism in skeletal muscle affects whole-body insulin sensitivity. Sarco/endoplasmic reticulum Ca^(2+) ATPase(SERCA) activity and mitochondrial function respond to alterations in PC:PE ratio and are associated with glucose homeostasis. Moreover, PC and PE content within the mitochondrial membrane influence mitochondrial respiration and biogenesis and thus, metabolic function. As skeletal muscle phospholipids respond to stimuli such as diet and exercise, understanding the implications of imbalances in PC:PE ratio is of great importance in the face of the rising epidemic of obesity related diseases. This review will summarize the current state of knowledge signifying the links between skeletal muscle PC:PE ratio and insulin sensitivity with respects to PC and PE metabolism, SERCA activity, mitochondrial function and exercise.
基金funding support from the State Key Program of National Natural Science Foundation of China(Grant No.U1637206)Shanghai Sailing Program(Grant No.20YF1417200).
文摘Clarifying the relationship between stress sensitivities of permeability and porosity is of great significance in guiding underground resource mining.More and more studies focus on how to construct stress sensitivity models to describe the relationship and obtain a comprehensive stress sensitivity of porous rock.However,the limitations of elastic deformation calculation and incompleteness of considered tortuosity sensitivity lead to the fact that the existing stress sensitivity models are still unsatisfactory in terms of accuracy and generalization.Therefore,a more accurate and generic stress sensitivity model considering elastic-structural deformation of capillary cross-section and tortuosity sensitivity is proposed in this paper.The elastic deformation is derived from the fractal scaling model and Hooke's law.Considering the effects of elastic-structural deformation on tortuosity sensitivity,an empirical formula is proposed,and the conditions for its applicability are clarified.The predictive performance of the proposed model for the permeability-porosity relationships is validated in several sets of publicly available experimental data.These experimental data are from different rocks under different pressure cycles.The mean and standard deviation of relative errors of predicted stress sensitivity with respect to experimental data are 2.63%and 1.91%.Compared with other models,the proposed model has higher accuracy and better predictive generalization performance.It is also found that the porosity sensitivity exponent a,which can describe permeability-porosity relationships,is 2 when only elastic deformation is considered.a decreases from 2 when structural deformation is also considered.In addition,a may be greater than 3 due to the increase in tortuosity sensitivity when tortuosity sensitivity is considered even if the rock is not fractured.
基金the grants from National Key Research and Development Program of China(2016YFA0101002)National Key R&D Program of China(2017YFC1309603)National Natural Science Foundation of China(Nos.81170736,81570715,81870579).
文摘Insulin resistance is an essential characteristic of type 2 diabetes mellitus(T2DM),which can be induced by glucotoxicity and adipose chronic inflammation.Mesenchymal stem cells(MSCs)and their exosomes were reported to ameliorate T2DM and its complications by their immunoregulatory and healing abilities.Exosomes derived from MSCs contain abundant molecules to mediate crosstalk between cells and mimic biological function of MSCs.But the role of exosomes derived from human umbilical cord mesenchymal stem cells(hUC-MSCs)in insulin resistance of human adipocytes is unclear.In this study,exosomes were harvested from the conditioned medium of hUC-MSCs and added to insulin-resistant adipocytes.Insulin-stimulated glucose uptake was measured by glucose oxidase/peroxidase assay.The signal pathway involved in exosome-treated adipocytes was detected by RT-PCR and Western blotting.The biological characteristics and function were compared between hUC-MSCs and human adipose-derived mesenchymal stem cells(hAMSCs).The results showed that hAMSCs had better adipogenic ability than hUC-MSCs.After induction of mature adipocytes by adipogenesis of hAMSC,the model of insulin-resistant adipocytes was successfully established by TNF-αand high glucose intervention.After exosome treatment,the insulin-stimulated glucose uptake was significantly increased.In addition,the effect of exosomes could be stabilized for at least 48 h.Furthermore,the level of leptin was significantly decreased,and the mRNA expression of sirtuin-1 and insulin receptor substrate-1 was significantly upregulated after exosome treatment.In conclusion,exosomes significantly improve insulin sensitivity in insulin-resistant human adipocytes,and the mechanism involves the regulation of adipokines.
文摘Background: Lack of first phase insulin secretion during oral glucose tolerance test [OGTT] in Type 2 Diabetes Mellitus (DM) is attributed to glucose toxicity. Alternatively, the role of insulin resistance in impaired insulin release secondary to lack of glucose entry into β cells may be responsible, but is not examined. Aim: The role of insulin sensitivity in 1st phase insulin secretion was assessed. Material and Methods: Plasma glucose (G) and insulin (I) concentrations were determined after an overnight fast (F) and upto 60 minutes during OGTT with glucose 75g in 12 normal (N), 14 with impaired glucose tolerance (IGT) and 41 subjects with Type 2 DM. First phase insulin secretion (Δ Insulin) was determined as a percentage rise from baseline 100x (Peak-Basal)/Basal. Insulin sensitivity was determined as FI x FG (mUxmM/L). Results: FG were normal (7.0 mM/L in Type 2 DM. FI x FG and ? insulin were 35 ± 4 and 389 ± 89% in N;77 ± 5 and 254 ± 65% in IGT;and 235 ± 19 and 95 ± 15% in Type 2 DM. Significant negative correlations were noted between ? insulin one hand and FI x FG on the other amongst all subjects [p < 0.0001 for all correlations]. Conclusion: Decline of 1st phase insulin secretion in IGT and Type 2 DM may be attributed to inhibited release of depleted insulin stores in the β Cells induced by impaired glucose entry due to insulin resistance, and is unlikely to be caused by glucose toxicity in IGT in presence of fasting euglycemia.
基金sponsored by the National Key R&D Program of China(2022YFD1400900)the National Natural Science Foundation of China(32272585)the Fundamental Research Funds for the Central Universities,China(KYCXJC2023003)。
文摘Fluopyram is an succinate dehydrogenase inhibitors(SDHI)fungicide that has been registered in China to control gummy stem blight(GSB)in watermelons for many years.However,whether the field pathogens of GSB are still sensitive to fluopyram or not is unknown.Therefore,we collected 69 Didymella bryoniae isolates from the fields that usually use fluopyram to control GSB to determine the sensitivity change.The EC_(50)(50%inhibition effect)values of fluopyram against D.bryoniae ranged from 0.0691 to 0.3503μg mL^(–1) and the variation factor was 5.07.The mean EC_(50) value was(0.1579±0.0669)μg mL^(–1) and the curve of sensitivity was unimodal.No resistant strains were found in the isolates,which means that the pathogens were still sensitive to fluopyram.The minimal inhibition concentration(MIC)of fluopyram against D.bryoniae was 3μg mL^(–1).Four low-resistant mutants and two medium-resistant mutants were obtained using fungicide taming and the resistance of mutants could be inherited stably.The growth rate of mutants decreased significantly compared with that of wild-type strains while the biomass of most mutants was similar to that of wild-type strains.The sensitivity of most resistant mutants to various stresses was increased compared with that of wild-type strains.The virulence of mutants receded except for low-resistant mutant XN51FR-1,which had the same lesion area as XN51 on the watermelon leaves.The results indicated that the fitness of resistant mutants was decreased compared with that of wild-type strains.The cross-resistance assay indicated that fluopyram-resistant mutants were positive cross-resistant to all six SDHI fungicides in this test but were still sensitive to fluazinam and tebuconazole.So the resistance risk of D.bryoniae to fluopyram was moderate.In addition,we found that the SdhB gene of low-resistant mutant XN30FR-1 had three new point mutations at positions K258N,A259P,and H277N.Medium-resistant mutant XN52FR-1 showed a mutation at position H277N and other mutants did not have any point mutation.