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1.
自噬是机体维持自身稳态的一种重要生理活动,当体内氨基酸或葡萄糖等营养缺乏时,细胞会启动自噬。自噬受到多种信号通路的调节,哺乳动物雷帕霉素靶蛋白复合体C1(m TORC1)信号通路是其中重要的一条,它可以使自噬相关基因13(Atg13)磷酸化,抑制自噬起始。本文将围绕近年来报道的氨基酸缺乏诱导细胞自噬的m TORC1信号通路,包括小G蛋白、腺苷酸活化蛋白激酶(AMPK)、微小RNA(miRNA)、氨基酰-tRNA合成酶在其中的作用等研究进展进行综述。  相似文献   

2.
TOR(target of rapamycin)是一种进化上十分保守的丝氨酸(Ser)/苏氨酸(Thr)蛋白激酶,可以感知营养状况、能量、生长因子等信号,进而调节细胞的生长、增殖和凋亡等生理进程.本文综述了TOR的上、下游信号传导通路及各种氨基酸对TOR信号传导通路的影响,为探讨氨基酸调控蛋白质合成的作用机制及建立精确...  相似文献   

3.
As major fuels for the small intestinal mucosa, dietary amino acids (AA) are catabolized in the mitochondria and serve as sources of energy production. The present study was conducted to investigate AA metabolism that supply cell energy and the underlying signaling pathways in porcine enterocytes. Intestinal porcine epithelial cells (IPEC-J2) were treated with different concentrations of AA, inhibitor, or agonist of mammalian target of rapamycin complex 1 (mTORC1) and adenosine monophosphate activated protein kinase (AMPK), and mitochondrial respiration was monitored. The results showed that AA treatments resulted in enhanced mitochondrial respiration, increased intracellular content of pyruvic acid and lactic acid, and increased hormone-sensitive lipase mRNA expression. Meanwhile, decreased citrate synthase, isocitrate dehydrogenase alpha, and carnitine palmitoyltransferase 1 mRNA expression were also observed. We found that AA treatments increased the protein levels of phosphorylated mammalian target of rapamycin (p-mTOR), phosphorylated-p70 ribosomal protein S6 kinase, and phosphorylated-4E-binding protein 1. What is more, the protein levels of phosphorylated AMPK α (p-AMPKα) and nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase sirtuin-1 (SIRT1) were decreased by AA treatments in a time depending manner. Mitochondrial bioenergetics and the production of tricarboxylic acid cycle intermediates were decreased upon inhibition of mTORC1 or AMPK. Moreover, AMPK activation could up-regulate the mRNA expressions of inhibitor of nuclear factor kappa-B kinase subunit beta (Ikbkβ), integrin-linked protein kinase (ILK), unconventional myosin-Ic (Myo1c), ribosomal protein S6 kinase beta-2 (RPS6Kβ2), and vascular endothelial growth factor (VEGF)-β, which are downstream effectors of mammalian target of rapamycin (mTOR). The mRNA expressions of phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (PIK3CD) and 5′-AMP-activated protein kinase subunit gamma-1 (PRKAG1), which are upstream regulators of mTOR, were also up-regulated by AMPK activation. On the other hand, AMPK activation also down-regulated FK506-binding protein 1A (FKBP1A), serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform, phosphatase and tensin homolog (PTEN), and unc-51 like autophagy activating kinase 1 (Ulk1), which are up-stream regulators of mTORC1. Taken together, these data indicated that AA regulated cellular energy metabolism through mTOR and AMPK pathway in porcine enterocytes. These results demonstrated interactions of AMPK and mTORC1 pathways in AA catabolism and energy metabolism in intestinal mucosa cells of piglets, and also provided reference for using AA to remedy human intestinal diseases.  相似文献   

4.
Neonatal growth is characterized by a high protein synthesis rate that is largely due to an enhanced sensitivity to the postprandial rise in insulin and amino acids, especially leucine. The mechanism of leucine’s action in vivo is not well understood. In this study, we investigated the effect of leucine infusion on protein synthesis in skeletal muscle and liver of neonatal pigs. To evaluate the mode of action of leucine, we used rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) complex-1 (mTORC1). Overnight-fasted 7-day-old piglets were treated with rapamycin for 1 hour and then infused with leucine (400 μmol·kg -1 ·h -1 ) for 1 hour. Leucine infusion increased the rate of protein synthesis, and ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E-BP1) phosphorylation in gastrocnemius and masseter muscles (P < 0.05), but not in the liver. The leucine-induced stimulation of protein synthesis and S6K1 and 4E-BP1 phosphorylation were completely blocked by rapamycin, suggesting that leucine action is by an mTORC1-dependent mechanism. Neither leucine nor rapamycin had any effect on the activation of the upstream mTORC1 regulators, AMP-activated protein kinase and protein kinase B, in skeletal muscle or liver. The activation of eIF2a and elongation factor 2 was not affected by leucine or rapamycin, indicating that these two pathways are not limiting steps of leucine-induced protein synthesis. These results suggest that leucine stimulates muscle protein synthesis in neonatal pigs by inducing the activation of mTORC1 and its downstream pathway leading to mRNA translation.  相似文献   

5.
乳蛋白是乳中重要的营养成分之一,超过90%的乳蛋白是乳腺利用从血液中摄取的氨基酸从头合成,因此在保证氨基酸充足供给的前提下,乳腺对氨基酸摄取率的高低是影响乳蛋白产量的关键因素.血液中的氨基酸不能自由扩散进出乳腺,需要由乳腺上皮细胞膜上特异的氨基酸转运载体(AAT)协助完成.而乳腺AAT活性受到营养物质和激素水平的调节,...  相似文献   

6.
氨基酸转运载体(AAT)是一类介导氨基酸从细胞外转运到细胞内的重要蛋白,也是一类能介导氨基酸相关的信号通路的重要营养物质感受分子,在机体的生长代谢、营养健康等方面具有重要作用。动物机体中存在多种类型的AAT,它们能感知机体内相关氨基酸水平的变化,介导细胞氨基酸感知信号通路——哺乳动物雷帕霉素靶蛋白复合体1(mTORC1)和一般性调控阻遏蛋白激酶2(GCN2)的激活,从而引起通路下游发挥作用。在不同组织细胞中,发挥主导作用的AAT存在差异,表明AAT具有组织特异性,同时,AAT也受多种因素的影响,比如动物机体本身、营养物质水平、激素水平等。作者主要从AAT的类型及转运机制、介导营养信号启动及对mTORC1通路和GCN通路的影响、在不同组织中的作用及AAT表达的调控4个方面进行综述,从宏观方面介绍了AAT,旨在为AAT的研究提供一些参考。  相似文献   

7.
Alpacas have evolved digestive and metabolic adaptations that enable them to survive in environments where the available feed varies in nutritional quality. Alpacas are thought to derive glucose from the deamination of amino acids in the liver, rather than via the conversion of propionate like true ruminants. Because fibre growth is dependent on the availability of absorbed amino acids, alpacas using amino acids as a source of energy should leave less amino acids available for fibre growth. If alpacas were to obtain glucose from a source of propionate, such as calcium propionate, the dependence on amino acids would be reduced leaving more available for fibre growth. Calcium propionate was added to the ration fed to 32 alpaca wethers, and fibre production was measured to monitor important fibre attributes in response to calcium propionate. Although the diets supplemented with calcium propionate should have provided more energy than the diets without calcium propionate, the metabolisable energy intake of all animals was similar (p = 0.278). It seems that rather than sparing amino acids, the alpacas regulated their energy intake and refused to consume the additional energy offered as calcium propionate. Consequently, they produced less fibre, and the diameter of their fibre was smaller than those alpacas that were not fed calcium propionate. It seems that alpacas rely on their digestive and metabolic adaptations to efficiently obtain and conserve energy for their survival.  相似文献   

8.
Sulphur‐containing amino acids (SAA) are essential and usually the first limiting amino acids for growth, milk and wool production. The keratin fibre that grows from epidermal tissue is rich in SAA. The rate of fibre growth and its S content are influenced by the availability of SAA. Betaine is a dietary source for a labile methyl group and actively participates in methionine metabolism by donating methyl groups for the remethylation of homocysteine to methionine. Ruminants are capable of synthesizing SAA from inorganic S sources, and most bacteria in the rumen can use inorganic S to meet their requirements for growth. The objective of this study was to examine whether betaine and an inorganic sulphur supplement could provide methyl groups and sulphur amino acids in a way that growth performance and wool production of ewes and lambs are improved. Treatments performed included betaine supplementation, sulphate supplementation and betaine plus sulphate supplementation with five replications for each treatment. The dry matter intake of the ewes was affected by betaine plus sulphate supplementation (p < 0.05). In the ewes, betaine plus sulphate supplementation increased (p < 0.05) the wool growth rate, wool yield, staple length and wool sulphur concentration, while decreasing wool wax and wool yellowness (p < 0.05). In the lambs, wool growth rate, wool yield, fibre diameter, staple length, staple strength, wool sulphur concentration, wool wax and fibre percentage did not differ (p > 0.05) between treatments. In the ewes, plasma methionine concentration increased (p < 0.05) with betaine plus sulphate treatment. No corresponding difference (p > 0.05) was observed in plasma methionine concentration in the lambs. It can be concluded that betaine plus sulphate supplementation has the potential to change wool characteristics in the ewes, while these compounds were without any effect on growth and wool production of the lambs. Combining the two supplements was advantageous.  相似文献   

9.
Using the MAC-T cell line as a model, the effects of insulin-like growth factor (IGF)-1 on the regulation of protein synthesis through the mammalian target of rapamycin complex 1 (mTORC1) signaling in bovine mammary epithelial cells were evaluated. Global rates of protein synthesis increased by 47% within 30 min of IGF-1 treatment. The effect of IGF-1 on protein synthesis was associated with enhanced association of the eukaryotic initiation factor (eIF) 4E with eIF4G and a concomitant reduction of eIF4E association with eIF4E-binding protein-1 (4E-BP1). There was a progressive increase in the phosphorylation state of ribosomal protein S6 kinase-1, a downstream target of mTORC1 in response to IGF-1. In addition, IGF-1 stimulated mTORC1 kinase activity toward 4E-BP1 in vitro. Phosphorylation on Ser473 of Akt was induced by IGF-1 within 5 min and remained elevated throughout a 30-min time course. The effect of IGF-1 on Akt phosphorylation was also concentration dependent. Activation of Akt by IGF-1 led to increased phosphorylation of tuberous sclerosis complex 2 on Thr1426, without any change in its association with tuberous sclerosis complex 1. Phosphorylation of proline-rich Akt substrate of 40-kDa (PRAS40) at Thr246 was stimulated by IGF-1. The amount of PRAS40 associated with mTORC1 decreased in response to IGF-1, and PRAS40 binding to mTORC1 was inversely related to its phosphorylation level. Overall, these results suggest that activation of the PI3K-Akt pathway by IGF-1 stimulated global protein synthesis in bovine mammary epithelial cells through changes in the phosphorylation and association state of components of the mTORC1 signaling pathway.  相似文献   

10.
Free amino acids are important components of tastants and flavor precursors in meat. To clarify the correlation between muscle fiber type and free amino acids, we determined the concentrations of various free amino acids and dipeptides in samples of different muscle tissues (n = 21), collected from 26‐month‐old Japanese Black steers (n = 3) at 2 days postmortem. The proportions of the myosin heavy chain (MyHC), slow (MyHC1) and fast (MyHC2) isoforms were determined by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE). The contents of free amino acids and dipeptides were measured by high performance liquid chromatography (HPLC). The MyHC isoform composition varied among the tissue samples. The MyHC1 proportion ranged from 6.9% ± 3.9% to 83.3% ± 16.7%. We confirmed that there was a strong positive correlation between MyHC1 composition and total free amino acid concentrations, including those for two dipeptides. Among the 31 measured free amino acids and dipeptides, 11 showed significant positive correlations and five showed significant negative correlations with MyHC1 composition. These results suggest that a high MyHC1 content induces high free amino acid contents in bovine muscles possibly because of greater oxidative metabolism. This high level of free amino acids could contribute to the intense flavor of meat that is rich in slow‐twitch fibers.  相似文献   

11.
营养介导的TOR信号传导研究进展   总被引:1,自引:0,他引:1  
TOR(target of rapamycin)是一种结构和功能高度保守的蛋白激酶,它能够通过整合营养、能量、生长因子等信号调节细胞的增殖、体积增大及细胞周期进程。作者综述了TOR激酶的上下游信号传导途径及氨基酸和能量等营养状况对这些信号传导通路和细胞生长的影响,为探讨营养调控体蛋白合成的机制及精准营养供给技术的建立提供宝贵的理论基础和开创性思路。  相似文献   

12.
This study was conducted to determine the influence of exogenous acid protease (EAP) on growth performance, blood profiles, excreta noxious gas emissions, ileum digesta viscosity and apparent ileal digestibility in broilers. A total of 600 1-d-old broilers with average initial body weight of 47.0 ± 0.2 g were used in a 5-week feeding trial. The broilers were randomly allotted to 1 of 4 treatments with 10 replicate pens per treatment and 15 birds per cage. Dietary treatments consisted of: CON, basal diets; EAP1, CON + 2,700 exogenous acid protease unite (APU)/kg; EAP2, CON + 5,400 APU/kg; EAP3, CON + 8,100 APU/kg. The body weight gain (BWG) had a linear improvement when chicks fed 8,100 AP/kg diets from d 18 to 35 and overall (p < .05). Lower feed conversion ratio (FCR) was obtained in broilers fed 5,400 APU/kg and 8,100 APU/kg as compared with the CON during overall (p < .05). Birds fed diets supplemented with EAP diet led to a linear increase in the ileal digestibility of crude protein, energy and amino acids (lysine, methionine, cystine, threonine, isoleucine, leucine, histidine and tryptophan) compared with CON group (p < .05). In conclusion, based on our results, we suggest that supplementation with EAP diet was effective in improving growth performance through increasing ileal digestibility of some nutrients (crude protein, energy and amino acids) in broilers.  相似文献   

13.
For dairy production systems, nitrogen is an expensive nutrient and potentially harmful waste product. With three quarters of fed nitrogen ending up in the manure, significant research efforts have focused on understanding and mitigating lactating dairy cows' nitrogen losses. Recent changes proposed to the Nutrient Requirement System for Dairy Cattle in the US include variable efficiencies of absorbed essential AA for milk protein production. This first separation from a purely substrate-based system, standing on the old limiting AA theory, recognizes the ability of the cow to alter the metabolism of AA. In this review we summarize a compelling amount of evidence suggesting that AA requirements for milk protein synthesis are based on a demand-driven system. Milk protein synthesis is governed at mammary level by a set of transduction pathways, including the mechanistic target of rapamycin complex 1(mTORC1), the integrated stress response(ISR), and the unfolded protein response(UPR). In tight coordination, these pathways not only control the rate of milk protein synthesis, setting the demand for AA, but also manipulate cellular AA transport and even blood flow to the mammary glands, securing the supply of those needed nutrients. These transduction pathways, specifically mTORC1, sense specific AA, as well as other physiological signals, including insulin, the canonical indicator of energy status. Insulin plays a key role on mTORC1 signaling, controlling its activation, once AA have determined mTORC1 localization to the lysosomal membrane.Based on this molecular model, AA and insulin signals need to be tightly coordinated to maximize milk protein synthesis rate. The evidence in lactating dairy cows supports this model, in which insulin and glucogenic energy potentiate the effect of AA on milk protein synthesis. Incorporating the effect of specific signaling AA and the differential role of energy sources on utilization of absorbed AA for milk protein synthesis seems like the evident following step in nutrient requirement systems to further improve N efficiency in lactating dairy cow rations.  相似文献   

14.
A three‐day assay was developed to evaluate the effect of autoclaving on protein quality of vetch as an alternative to classical growth methods. Male chickens (n = 10/diet) were given approximately isonitrogenous diets based on raw or autoclaved vetch for 3 days. Samples of plasma, muscle and liver were obtained for free amino acid analysis. Heating vetch depressed growth (11.9 vs. 23.2 g/d; p < 0.05). Plasma methionine and histidine increased (0.05 < p < 0.06), while gluconeogenic amino acids tended to decrease (p < 0.10) after heating. Muscle free amino acids did not change except for a trend to increased methionine (p = 0.06) in birds fed autoclaved vetch. In liver, most essential amino acids, glycine, proline and tyrosine increased markedly with heated vetch diet. Correlations between plasma and muscle free amino acids were poor compared with those between plasma and liver free amino acids. Liver free amino acid pool was more sensitive than muscle or plasma pool to amino acid inflow modifications after vetch heating.  相似文献   

15.
Background: Understanding the mechanisms of N utilization for lactation can lead to improved requirement estimates and increased efficiency, which modern dairy diets currently fail to maximize. The mechanistic target of rapamycin complex 1(m TORC1) is a central hub of translation regulation, processing extra-and intra-cellular signals of nutrient availability and physiological state, such as amino acids and energy. We hypothesized that dietary amino acids regulate lactation through m TORC1, such that inhibition of m TORC1 will lead to decreased lactation performance when amino acids are not limiting. Our objectives were to assess lactation performance in lactating mice undergoing dietary and pharmacologic interventions designed to alter m TORC1 activity.Methods: First lactation mice(N = 18; n = 6/treatment) were fed an adequate protein diet(18% crude protein), or an isocaloric protein-restricted diet(9% crude protein) from the day after parturition until lactation day 13. A third group of mice was fed an adequate protein diet and treated with the m TORC1 inhibitor rapamycin(4 mg/kg every other day) intraperitoneally, with the first two groups treated with vehicle as control. Dams and pups were weighed daily, and feed intake was recorded every other day. Milk production was measured every other day beginning on lactation day 4 by the weigh-suckle-weigh method. Tissues were collected after fasting and refeeding.Results: Milk production and pup weight were similarly decreased by both protein restriction and rapamycin treatment, with final production at 50% of control(P = 0.008) and final pup weight at 85% of control(P 0.001).Mammary phosphorylation of m TORC1's downstream targets were decreased by protein restriction and rapamycin treatment(P 0.05), while very little effect was observed in the liver of rapamycin treated mice, and none by protein restriction.Conclusions: Overall, sufficient supply of dietary amino acids was unable to maintain lactation performance status in mice with pharmacologically reduced mammary m TORC1 activity, as evidenced by diminished pup growth and milk production, supporting the concept that m TORC1 activation rather than substrate supply is the primary route by which amino acids regulate synthesis of milk components.  相似文献   

16.
This experiment was conducted to investigate the effect of star anise essential oil (SAO) supplementation in diets with different energy levels on growth performance, nutrient metabolic efficiency of broilers. One hundred and ninety-two Arbor Acres male broiler chicks at 28 days of age were divided into a 3 × 4 factorial arrangement design with three dietary energy levels (13.41, 12.82, 12.23 MJ/kg) and 4 levels of SAO supplementation (0, 200, 400, and 600 mg/kg of diet). Dietary supplementation with SAO increased (p < .05) apparent metabolic efficiency of CP, EE, GE, and all of the amino acids except Trp. Significant interactions were noted between energy level and SAO administration for metabolic efficiency of CP, all of the amino acids except Cys. Inclusion of SAO enhanced apparent nutrient metabolic efficiency of broilers in a dose-dependent manner, birds supplemented with 400 mg/kg of SAO in high-energy diets appeared to contain highest nutrient metabolic efficiency, moreover, the metabolic efficiency of nutrients in low-energy diets along with 200 or 400 mg/kg of SAO was similar with that in high-energy diets without SAO, which indicated that the SAO might ameliorate the negative effects of reduced dietary metabolic energy on nutrient utilization in broilers.  相似文献   

17.
Animal protein sources such as fishmeal and plasma powder are excellent and indispensable sources of energy, amino acids, and minerals in animal production. Amino acid imbalance, especially methionine-to-sulfur amino acid (Met:SAA) ratio, caused by an imbalance of animal protein meal leads to growth restriction. This study was conducted to evaluate the effects of imbalanced Met:SAA ratio supplementation of different animal protein source diets on growth performance, plasma amino acid profiles, antioxidant capacity and intestinal morphology in a piglet model. Twenty-four weaned piglets (castrated males; BW = 10.46 ± 0.34 kg), assigned randomly into 3 groups (8 piglets/group), were fed for 28 d. Three experimental diets of equal energy and crude protein levels were as follows: 1) a corn-soybean basal diet with a Met:SAA ratio at 0.51 (BD); 2) a plasma powder diet with a low Met:SAA ratio at 0.41 (L-MR); 3) a fishmeal diet with a high Met:SAA ratio at 0.61 (H-MR). Results revealed that compared to BD, L-MR significantly decreased (P < 0.05) the activities of plasma total antioxidant capacity and glutathione peroxidase, plasma amino acid profiles, and significantly reduced (P < 0.05) villus height and crypt depth in the duodenum and jejunum. Additionally, L-MR significantly reduced (P < 0.05) the mRNA expression level of solute carrier family 7 member 9 (SlC7A9) in the ileum, and significantly increased (P < 0.05) mRNA expression levels of zonula occludens-1 (ZO-1) in the duodenum, and Claudin-1, ZO-1, sodium-coupled neutral amino acid transporters 2 (SNAT2) and SlC7A7 in the jejunum. H-MR significantly increased (P < 0.05) plasma SAA levels, and significantly reduced (P < 0.05) average daily feed intake, villus height, and villus height-to-crypt depth (VH:CD) ratio in the ileum compared to BD. In conclusion, L-MR may result in oxidative stress and villous atrophy but proves beneficial in improving intestinal barrier function and the activity of amino acid transporters for compensatory growth. H-MR may impair intestinal growth and development for weaned piglets. The research provides a guidance on the adequate Met:SAA ratio (0.51) supplementation in diet structure for weaned piglets.  相似文献   

18.
Threonine (Thr) is one of the four main limiting amino acids of poultry, and it plays a very important role in poultry's maintenance of normal growth, development and immune function. Although there have been very comprehensive studies on the mechanism of broilers and laying hens over the past ten years, there are still relatively fewer studies on ducks. This paper summarizes recent studies on Thr nutrition-physiological function in broilers, laying hens and ducks, including the influence of Thr on dietary amino acids balance, production performance, carcass quality, immune function and intestine health maintenance. At the same time, this paper also briefly analyzes the factors related to Thr requirement, including growth stage, crude protein level, energy concentration, other amino acids level in diet and raising environment. In brief, the review is respected to guide poultry production practices.  相似文献   

19.
苏氨酸是家禽体内4种主要的必需氨基酸之一,对维持家禽正常的生长、发育及免疫具有十分重要的作用。尽管过去十多年来有关苏氨酸对肉鸡、蛋鸡的影响机理研究较为全面,但在肉鸭上的研究相对较少。作者总结了近年来苏氨酸在肉鸡、蛋鸡和肉鸭生物学和营养生理功能上的研究成果,主要包括苏氨酸在平衡日粮氨基酸、促进蛋白质合成、提高生产性能、提升胴体品质、增强免疫机能及维护肠道健康等方面的作用效果;同时也简要分析了家禽苏氨酸需要量的影响因素,包括家禽的生长阶段、日粮粗蛋白质水平、日粮能量浓度、日粮其他氨基酸含量及饲养环境等,以期为家禽的生产实践提供一定的指导。  相似文献   

20.
The fermented feed has been identified as a potential alternative to antibiotics in feeds that markedly affects gut health and growth performance of pigs. Two recent studies performed in our laboratory investigated that the fermented corn–soybean meal (fermented feed, FF) improved the gut health of pigs. This study was conducted to determine the effect of a FF on the carcass, meat quality, muscle fatty acids profile, muscle amino acid and antioxidant ability of grower-finisher pigs. In this study, a total of 48 crossbred barrows (Duroc × Landrace × Large White) were randomly divided into 2 treatments with unfermented corn–soybean diet (Ctrl) and FF diet. Compared with control pigs fed a standard diet, the results showed that FF significantly increased the muscle colour of redness and significantly reduced muscle moisture loss rate. Furthermore, FF significantly increased the content of aromatic amino acids such as aspartic acid, glutamic acid and alanine. More importantly, FF increased monounsaturated fatty acid and polyunsaturated fatty acid content. Collectively, FF could be a promising feed strategy in improving meat quality and nutritional value in grower-finisher pig.  相似文献   

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