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1.
A series of β-acetamido carbonyl compounds (S1S7) were prepared using Dakin-West reaction from different substituted aldehyde and acetophenone in the presence of lanthanum triflate as a solid catalyst. All the compounds were tested for their α-glucosidase inhibitory potential against rat intestinal α-glucosidase. The most potent rat intestinal α-glucosidase inhibitors S5 and S7 were tested for their antihyperglycemic activity following carbohydrate tolerance test. Both the compounds displayed antihyperglycemic activity equivalent to the standard drug acarbose.  相似文献   

2.
Insulin production afforded by hepatic gene therapy (HGT) retains promise as a potential treatment for type 1 diabetes, but successful approaches have been limited. We employed a novel and previously untested promoter for this purpose, glucose transporter-2 (GLUT2) to drive insulin production via delivery by recombinant adeno-associated virus (rAAV). In vitro, the GLUT2 promoter was capable of robust glucose-responsive expression in transduced HepG2 human hepatoma cells. Therefore, rAAV constructs were designed to express the furin-cleavable human preproinsulin B10 gene, under the control of the murine GLUT2 promoter and packaged for delivery with rAAV expressing the type 5 capsid. Streptozotocin-induced diabetic mice were subjected to hepatic portal vein injection immediately followed by implantation of a sustained-release insulin pellet to allow time for transgenic expression. All mice injected with the rAAV5-GLUT2-fHPIB10 virus remained euglycemic for up to 35 days post-injection, with 50% euglycemic after 77 days post-injection. In contrast, mock-injected mice became hyperglycemic within 15 days post-injection following dissolution of the insulin pellet. Serum levels of both human insulin and C-peptide further confirmed successful transgenic delivery by the rAAV5-GLUT2-fHPIB10 virus. These findings indicate that the GLUT2 promoter may be a potential candidate for regulating transgenic insulin production for hepatic insulin gene therapy in the treatment of type I diabetes.  相似文献   

3.
Type 2 diabetes is characterized by cellular and extracellular Mg depletion. Epidemiologic studies showed a high prevalence of hypomagnesaemia and lower intracellular Mg concentrations in diabetic subjects. Insulin and glucose are important regulators of Mg metabolism. Intracellular Mg plays a key role in regulating insulin action, insulin-mediated-glucose uptake and vascular tone. Reduced intracellular Mg concentrations result in a defective tyrosine-kinase activity, post-receptorial impairment in insulin action, and worsening of insulin resistance in diabetic patients. Mg deficit has been proposed as a possible underlying common mechanism of the "insulin resistance" of different metabolic conditions. Low dietary Mg intake is also related to the development of type 2 diabetes. Benefits of Mg supplementation on metabolic profile in diabetic subjects have been found in most, but not all clinical studies, and larger prospective studies are needed to support the potential role of dietary Mg supplementation as a possible public health strategy in diabetes risk.  相似文献   

4.
AimsThis study investigates the relationships between matrix metalloproteinases, inflammations mediators and type 2 diabetes mellitus in Tunisians metabolic syndrome (Mets) patients.MethodsThe study has included 239 MetS patients and 247 controls. Mets was defined according to the NCEP–ATPIII report. Mets patients were also divided into two categories: 29 MetS non-diabetics and 210 MetS diabetics. Dysglycemia markers, matrix metalloproteinase-9 (MMP-9), Tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), tumor necrosis factor α (TNF-α), C-reactive protein (CRP) levels and White Blood Cells (WBC) counts were determined in patients and controls.ResultsIn our study, the level of inflammatory markers WBC, TNF-α and matrix metalloproteinases (MMP-8 and MMP-9) were significantly higher in diabetic patients with MetS, as compared with non-diabetic MetS patients. Inflammation mediators and MMP-9 were significantly associated with many clinical characteristics of MetS. The use of ROC “Receiver Operating Characteristic” analysis revealed the impact of TNF alpha on diabetes patients with MetS. In fact TNF alpha was found as a sensitive parameter in these patients with a sensitivity of 85%.ConclusionInflammation, matrix metalloproteinases and dysglycemia markers are not expressed in isolation but rather concurrently and are continuously interacting with each other, in MetS and diabetics patients. These markers fit with an early stage of cardiovascular disease (CVD); and measuring them could improve the risk evaluation, an early diagnosis, and the prognosis of CVD.  相似文献   

5.
目的

探讨低碳水化合物饮食对2型糖尿病(T2DM)患者肠道微生物和空腹高血糖的影响。

方法

选择2019年5月至2019年8月我院内分泌科招募的100例T2DM患者为研究对象,患者随机分配到干预饮食组(LCD组,低碳水化合物饮食)或控制饮食组(LFD组)。LFD组患者的饮食为500 g蔬菜/d,100 g主食/餐(300 g/d),3汤匙油/d,两餐之间提供稳定血糖、低血糖指数水果,5种蛋白质(220 mL牛奶、1个鸡蛋、100 g鱼虾、50 g大豆、50 g肉)/d,6 g盐/ d。LCD组每天摄入杏仁56 g以取代150 g/d富含碳水化合物的主食,其余饮食方案与LFD组相同。收集所有参与者的粪便标本,取豌豆大小的粪便置入1.5 mL的试管中,立即于−80 ℃保存。使用QIAAMP® DNA粪便抽提试剂盒进行粪便样本的总DNA提取,随后进行16S rRNA基因测序,对其菌群进行分析。

结果

LCD组患者肠道微生物群Shannon指数,Chao指数和Simpson指数显著高于LFD组(均P<0.05)。两组患者按照规定饮食3个月后肠道微生物组检测显示,总共有9个门,其中排名前5位的细菌门约占所有细菌的96.00%。LCD组患者以拟杆菌门为主(72.32%),其次为假单胞菌门(13.81%)、变形菌门(8.22%)、梭杆菌门(0.03%)、放线菌门(0.63%)。LFD组患者肠道菌群门水平的细菌组成与LCD组相近。其中,LFD组梭杆菌门丰度(0.35%)高于LCD组(0.03%)。同时,LCD组产单链脂肪酸细菌(Roseburis)和瘤胃球菌的相对丰度升高。两组之间3种主要营养素的总能量和热量比例差异无统计学意义(均P>0.05)。干预3个月时,两组患者的总能量差异无统计学意义(P>0.05)。与LFD组相比,LCD组患者来自碳水化合物的热量减少,而来自脂肪的热量显著增加(均P<0.05)。此外,干预后,LCD组患者中有40%来自碳水化合物的热量达到LCD标准,而LFD组患者中有25%来自脂肪的热量达到LFD标准。治疗3个月时,LCD组患者HbA1c下降幅度大于LFD组(P<0.05)。干预期间,LCD组有3例、LFD组有5例患者降糖药物使用量减少,其余受试者无显著变化。

结论

低碳水化合物饮食可能通过改善T2DM患者肠道菌群区系进一步改善患者的糖代谢。

  相似文献   

6.
7.
目的

探讨红茶对2型糖尿病(T2DM)小鼠肠道菌群分布的影响,为研究红茶在代谢性疾病的辅助治疗机制提供参考。

方法

构建 T2DM小鼠模型,将其随机分为模型组(T2DM组)和茶水饲喂组(T2DM_T组),取健康小鼠作为对照组(Control组),每组各15只。实验终点收集3组小鼠粪便进行宏基因组测序,分析组间菌群差异;同时进行肝脏组织形态学检查,观察组织病理学改变。

结果

与Control组和T2DM组相比,T2DM_T组拟杆菌门(F = 21.056,P<0.001)、邓肯氏菌属(F = 13.330,P = 0.001)、乳杆菌属(F = 36.546,P<0.001)和粘液乳杆菌属(F = 43.813,P<0.001)的相对丰度增加,担子菌门(F = 8.676,P = 0.005)、MuribaculumF = 8.151,P = 0.006)和肠球菌属(F = 4.271,P = 0.040)的相对丰度降低。与T2DM组小鼠相比,T2DM_T组小鼠肝细胞排列较为紧密,细胞空泡变性程度有所减弱。

结论

红茶在一定范围内能调节T2DM模型小鼠肠道菌群结构和相对丰度,红茶水喂饲可减缓造模所致的T2DM小鼠肝脏细胞的损伤,其具体作用机制值得深入研究和探讨。

  相似文献   

8.
Type 2 diabetes mellitus (DM) is associated often with underlying zinc deficiency and nutritional supplements such as zinc may be of therapeutic benefit in the disease. In a randomized, double-blind, placebo-controlled, 12-week trial in postmenopausal women (n = 48) with Type 2 DM we investigated the effects of supplementation with zinc (40 mg/d) and flaxseed oil (FSO; 2 g/d) on the gene expression of zinc transporters (ZnT1, ZnT5, ZnT6, ZnT7, ZnT8, Zip1, Zip3, Zip7, and Zip10) and metallothionein (MT-1A, and MT-2A), and markers of glycemic control (glucose, insulin, glycosylated hemoglobin [HbA1c]). The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. No significant effects of zinc or FSO supplementation were observed on glycemic marker concentrations, HOMA-IR or fold change over 12 weeks in zinc transporter and metallothionein gene expression. In multivariate analysis, the change over 12 weeks in serum glucose concentrations (P = 0.001) and HOMA-IR (P = 0.001) predicted the fold change in Zip10. In secondary analysis, marginal statistical significance was observed with the change in both serum glucose concentrations (P = 0.003) and HOMA-IR (P = 0.007) being predictive of the fold change in ZnT6. ZnT8 mRNA expression was variable; HbA1c levels were higher (P = 0.006) in participants who exhibited ZnT8 expression compared to those who did not. The significant predictive relationships between Zip10, ZnT6, serum glucose and HOMA-IR are preliminary, as is the relationship between HbA1c and ZnT8; nevertheless the observations support an association between Type 2 DM and zinc homeostasis that requires further exploration.  相似文献   

9.
目的:探讨2型糖尿病(T2DM)患者微量白蛋白尿与代谢综合征(MS)的相关性。方法:282例T2DM患者根据是否合并MS分为MS组(163例)和非MS组(119例),测定24h尿白蛋白(UAlb)及相关生化指标,比较两组UAlb水平及糖尿病肾病(DN)患病率,采用多元Logistic回归方法分析T2DM患者微量白蛋白尿的危险因素。结果:MS组的UAlb及DN患病率明显高于非MS组,且随着MS组分增加,UAlb水平显著升高。多元Logistic回归分析表明甘油三酯、糖化血红蛋白、收缩压为影响UAlb的独立危险因素。结论:T2DM患者微量白蛋白尿与MS密切相关,需采取综合干预措施避免或延缓DN的发生发展。  相似文献   

10.
Diabetes is a metabolic disorder prevalent across the globe and is known to cause brain dysfunction, especially memory and cognitive decline. The current study investigates the effect of aqueous Ajwa seeds extract (AASE) on type-2 diabetes mellitus (T2DM)-induced memory deficits using a rat model. T2DM was induced by an administration of nicotinamide (120 mg/kg, i.p.) and streptozotocin (STZ) (60 mg/kg, i.p.). AASE (200 and 400 mg/kg, p.o.) were treated to T2DM rats for 30 days and the results were compared with the metformin (200 mg/kg). Elevated plus maze (EPM), Y-maze, and novel object recognition (NOR) tests were performed to assess the memory functions. The blood glucose and plasma insulin levels were estimated to assess the anti-diabetic effects of AASE. Acetylcholine (ACh) and acetylcholinesterase (AChE) levels were estimated from brain homogenates to assess cholinergic transmission. Treatment with AASE resulted in the reversal of behavioral deficits. EPM showed, a significant reduction in transfer latency (TL) among T2DM rats. High exploration time with a novel object and improvement in discrimination index were observed among treated groups during the NOR test. The Y-Maze test improved the entries and also time spent in the novel arm. Moreover, treatment of AASE reversed hyperglycemic and enhanced plasma insulin levels (200 mg/kg: 3.81 ± 0.08 ng/ml and 400 mg/kg: 4.09 ± 0.10 ng/ml) among T2DM rats (2.81 ± 0.15 ng/ml). Improved ACh levels (200 mg/kg: 186.6 ± 9.51 pg/mg protein and 400 mg/kg: 165.5 ± 9.25 pg/mg protein) and reduced AChE levels (200 mg/kg: 0.29 ± 0.02 ng/mg protein and 400 mg/kg: 0.32 ± 0.03 ng/mg protein) were also noted in the brain of AASE treated groups as referred to diabetic group (ACh: 107.1 ± 7.16 pg/mg protein and AChE: 0.51 ± 0.03 ng/mg protein). The above results were found to be comparable with the metformin-treated groups. From the results, it can be concluded that AASE has the potential to improve T2DM associated cognitive deficits.  相似文献   

11.
目的研究2型糖尿病患者行胃转流术前后肠道菌群是否发生变化。方法收集30例2型糖尿病患者术前和术后粪便,测肠道菌群,以25例健康志愿者的粪便为对照组。结果 2型糖尿病患者的肠杆菌较健康人增多,双歧杆菌较正常人减少,胃转流术后双歧杆菌增加,肠杆菌减少。结论 2型糖尿病患者出现肠道菌群失调,胃转流术后控制了血糖,双歧杆菌数量增加。  相似文献   

12.
The aim of the present study was to investigate whether altered serum total sialic acid (TSA), lipid-associated sialic acid (LSA), copper (Cu), manganese (Mn), zinc (Zn), chromium (Cr), iron (Fe), and magnesium (Mg) levels had an interactive connection with diabetes and also whether they were correlated with each other in diabetic patients. Two study groups (control and type 2 diabetic subjects) were included. Two hundred patients (108 female and 92 male), diagnosed and treated for type 2 diabetes in the Yuzuncu Yil University Hospital (Van, Turkey), were selected consecutively to represent type 2 diabetic patients. Fifty healthy individuals (29 female and 21 male) served as the control group matched for age, sex, body mass index, and smoking status were selected from hospital staff and other outpatient clinics. All participants had not taken vitamin or mineral supplements for at least 2 wk before sampling. Blood samples were drawn after an overnight fasting in both groups for the determination of serum glucose, TSA, LSA, Cu, Zn, Mn, Cr, Fe, and Mg. It was found that diabetics had higher TSA, LSA, Fe, Mn, Fe/Zn, and Cu/Zn levels, and lower Zn and Mg levels than those of controls. Although, Cu levels were higher, and Cr levels were lower in total and male diabetic patients, they were not different in female diabetic patients than in controls. The Cu/Fe ratio was lower in total and female diabetic patients, but not different in male diabetic patients than controls. The Zn/Cr ratio, on the other hand, was not different in diabetics than in controls. There was only a positive correlation between Fe-Mn levels in male diabetic patients. There was a negative correlation in LSA-Mn, Fe-Cu, Cu-Fe/Zn, and Mn-Cu/Zn levels in total diabetic patients. There was a positive correlation in TSA-Cr, TSA-Mg, LSA-Cu/Fe, LSA-Zn/Cr levels, and a negative correlation in TSA-Cu/Zn, LSA-Mn, Fe-Cu, Mn-Cu, Cu-Fe/Zn, Fe-cholesterol, and Cr-cholesterol in female diabetic patients. Our results showed that TSA, LSA, and selected minerals have interactive connections with diabetes mellitus (DM). There are also many sex-related positive or negative correlations between the altered parameters in diabetic patients. These parameters might be used as diagnostic index in patients with DM.  相似文献   

13.
目的:探讨辛伐他汀治疗对Ⅱ型糖尿病(T2DM)合并肾病患者糖代谢水平的影响.方法:选取新乡医学院第一附属医院60名T2DM合并肾病患者行辛伐他汀治疗3个月.比较治疗前后空腹血糖(FBG)、游离脂肪酸(FFA)、脂联素(ANP)、C肽、HOMA-IR、胰岛素/葡萄糖比率(IGR)、胰岛素敏感指数(ISI)、空腹胰岛素水平(FINS)、C反应蛋白(CRP)、糖基化血红蛋白(HbA1c)水平等变化,以评价辛伐他汀对T2DM病合并肾病患者的治疗效果.结果:在辛伐他汀治疗3个月后的葡萄糖耐量试验(OGTT)中,对比治疗前,各时点血糖水平均显著下降(P<0.05),而C肽与胰岛素在0 min和30 min时显著下降(P<0.05).在辛伐他汀治疗后,HO-MA-IR、游离脂肪酸(FFA)、ISI、FINS、胰岛素AUC、血糖曲线下面积(AUC)、CRP、HbA1c、FBG与治疗前相比均显著下降(P<0.05),尿白蛋白排泄率(UAER)也明显下降(P<0.01),但是APN(P<0.01)以及C肽AUC(P <0.05)均显著上升,而校正胰岛素反应(CIR)及IGR无显著变化(P>0.05).结论:辛伐他汀治疗可以改善胰岛素抵抗,提高患者对胰岛素的敏感性,并显著降低血糖,从而改善T2DM合并肾病患者的糖代谢.  相似文献   

14.
目的 探讨益生菌制剂对2型糖尿病患者的疗效及其对肠道菌群的影响。 方法 选取医院收治的92例2型糖尿病患者随机分为对照组和研究组,各46例。对照组给予基础治疗,研究组给予基础治疗联合益生菌制剂。对比治疗前后两组患者临床症状评分和糖代谢指标水平变化,肠道菌群的组成及多样性变化,治疗效果和药物不良反应。 结果 治疗后两组患者Chao1指数和Shannon指数均升高(均P0.05)。 结论 益生菌制剂能够控制2型糖尿病患者的临床症状,改善糖代谢,增加肠道菌群的多样性,调节肠道菌群属水平相对丰度,还可增强疗效且安全。  相似文献   

15.
Interleukin-12 (IL-12) has been identified as a pro-inflammatory cytokine which is thought to contribute to the development of atherosclerosis. However, to date, the various associations between factors related to the course of type 2 diabetes, like metabolic compensation, beta cell secretory dysfunction, insulin resistance and IL-12 serum levels, remain unclear. Our study involved 41 patients with type 2 diabetes, 19 patients with coronary artery disease (CAD), and 19 healthy controls. We measured serum levels of fasting glucose, HbA1c, 1,5-anhydro-d-glucitol, and lipids. In addition, serum levels of C-peptide, insulin, proinsulin and IL-12 were assayed. HOMAIR score was calculated. The serum concentrations of IL-12 were higher in diabetics than in either patients with CAD or healthy controls, and were correlated with BMI, C-peptide, insulin, HOMAIR, proinsulin and HDL serum levels. Multiple regression analysis revealed that the IL-12 serum level in type 2 diabetics primarily is dependent upon fasting proinsulin concentration. Our results demonstrate that elevated IL-12 serum levels in type 2 diabetics treated with sulphonylureas are induced especially by peripheral insulin resistance and beta cells dysfunction, as expressed by fasting serum proinsulin levels. This finding gives us hope that treatment to decrease peripheral insulin resistance and to avoid excessive proinsulin secretion might be successful in the prevention of IL-12-induced atherosclerosis.  相似文献   

16.
目的目的对老年糖尿病患者的空腹血浆成纤维细胞生长因子(Fibroblast growth factor21,FGF21)的水平与其临床参数进行相关性分析。方法对辽宁省沈阳市部分社区进行糖尿病普查,对78名65岁以上老年糖尿病患者的空腹血浆FGF21的水平与其临床参数进行相关性分析。其中包括腰围、体重指数(BMI)、血生化学指标、应用针对糖尿病,高血压和血脂异常治疗药物的情况等。结果在单变量分析中,2型糖尿病患者的FGF21水平与是否使用贝特类药物、甘油三酯水平、肌酐水平、腰围和BMI有独立相关性。经过校正年龄,性别和BMI之后进行多元线性回归分析发现,血清FGF21水平与贝特类药物的使用、TG水平、肌酐水平、LDL-C水平、胰高血糖素水平等独立相关。结论在老年2型糖尿病患者中,空腹血清FGF21水平与使用贝特类降脂药物,血脂水平,肾功等密切相关,说明FGF21水平在此类患者的糖脂代谢中占有重要地位。  相似文献   

17.
The lead optimization studies of a series of GPR119 agonists incorporating a nortropanol scaffold are described. Extensive structure-activity relationship (SAR) studies of the lead compound 20f led to the identification of compound 36j as a potent, single digit nanomolar GPR119 agonist with high agonist activity. Compound 36j was orally active in lowering blood glucose levels in a mouse oral glucose tolerance test and increased plasma insulin levels in a rat hyperglycemic model. It showed good to excellent pharmacokinetic properties in rats and monkeys and no untoward activities in counter-screen assays. Compound 36j demonstrated an attractive in vitro and in vivo profile for further development.  相似文献   

18.
目的 探讨老年2型糖尿病患者肠道双歧杆菌生长与血糖的相关性,从肠道菌群角度为2型糖尿病的防治与研究提供新的途径。方法 根据纳入和排除标准,抽取2015年4月‒10月福建某三甲医院糖尿病健康教育俱乐部的2型糖尿病患者90例,收集其粪便和血液标本,检测患者肠道双歧杆菌以及血糖状况,采用Spearman等级相关法分析两者之间的相关性。结果 老年2型糖尿病患者肠道长双歧杆菌、短双歧杆菌、青春双歧杆菌、婴儿双歧杆菌和双歧杆菌总菌的定量结果分别是(0.0001±0.0006)、(4.405±8.475)、(4.752±2.779)、(0.003±0.005)和(8.069±8.206)logN/g。空腹血糖和早餐餐后血糖分别为(8.638±1.913)、(9.763±1.910)mmol/L。相关分析显示:青春双歧杆菌和婴儿双歧杆菌与早餐后2 h血糖呈现负相关(r=-0.213、-0.217,P<0.05),但相关性不显著;双歧杆菌总菌与空腹血糖和早餐后2 h血糖有负相关关系(r=-0.302、-0.559,P<0.01)。结论 老年2型糖尿病患者肠道内双歧杆菌数量减少,血糖与肠道双歧杆菌的数量呈负相关,尤其是早餐后2 h血糖,其相关机制有待进一步研究。  相似文献   

19.
目的探讨益生菌对老年2型糖尿病患者肠道菌群、肠道屏障功能及糖脂代谢水平的影响。方法选取2017年10月至2019年10月我院收治的200例2型糖尿病患者为研究对象。入选患者随机分为观察组和对照组,各100例。比较两组患者治疗前后肠道菌群变化情况,血清二胺氧化酶(DAO)、内毒素(ET)、D 乳酸(D lac)、糖化血红蛋白(HbA1c)、空腹血糖(FPG)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL C)、高密度脂蛋白胆固醇(HDL C)水平。记录两组患者治疗过程中不良反应发生情况。结果治疗前,两组患者肠道双歧杆菌、乳杆菌、拟杆菌、肠球菌、肠杆菌及酵母菌数量比较差异无统计学意义(均P>0.05);治疗后,两组患者肠道双歧杆菌、乳杆菌、拟杆菌数量均显著增加,而肠球菌、肠杆菌及酵母菌数量显著降低,同时观察组患者变化幅度大于对照组(均P<0.05)。治疗前,两组患者血清DAO、ET、D lac、HbA1c、FPG、TC、TG、LDL C、HDL C水平比较差异无统计学意义(均P>0.05)。治疗后,两组患者血清DAO、ET、D lac、HbA1c、FPG、TC、TG、LDL C、HDL C水平均显著降低(P<0.05),同时观察组上述指标水平低于对照组(P<0.05)。观察组患者治疗过程中不良反应总发生率为9.0%,对照组为7.0%,两组比较差异无统计学意义(χ2=0.272,P=0.602)。结论益生菌可有效调节老年2型糖尿病患者肠道菌群,提高肠道屏障功能,控制糖脂代谢水平,安全性较高,具有较好的辅助治疗作用。  相似文献   

20.
The pathophysiological changes of erythrocytes are detected at the molecular scale, which is important to reveal the onset of diseases. Type 2 diabetes is an age-related metabolic disorder with high prevalence in elderly (or old) people. Up to now, there are no treatments to cure diabetes. Therefore, early detection and the ability to monitor the progression of type 2 diabetes are very important for developing effective therapies. Type 2 diabetes is associated with high blood glucose in the context of insulin resistance and relative insulin deficiency. These abnormalities may disturb the architecture and functions of erythrocytes at molecular scale. In this study, the aging- and diabetes-induced changes in morphological and biomechanical properties of erythrocytes are clearly characterized at nanometer scale using atomic force microscope (AFM). The structural information and mechanical properties of the cell surface membranes of erythrocytes are very important indicators for determining the healthy, diseased or aging status. So, AFM may potentially be developed into a powerful tool in diagnosing diseases.  相似文献   

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