Search

Background: Calcium dobesilate (CaD) is a microvascular protective agent that can significantly improve kidney function by reducing urinary protein, serum creatinine, and urea nitrogen levels. The effects of CaD on ischemia-reperfusion-induced acute kidney injury (AKI) were investigated in this study. Method: In this study, The Balb/c mice were randomly divided into (1) sham group, (2) I/R group, (3) I/R group + CaD (50 mg/kg) and (4) I/R group + CaD (500 mg/kg). After treatment, serum creatinine and urea nitrogen were detected. The levels of superoxide dismutase (SOD) and malonaldehyde (MDA) were examined. Then, the effects of CaD H2O2-damaged HK-2 cells were investigated, as reflected by the results of cell viability, reactive oxygen species (ROS) level, apoptosis and markers of kidney injury. Results: The results showed that CaD treatment effectively attenuated the renal functions, pathological changes, and oxidative stress in I/R-induced AKI mice. It effectively reduced ROS production and improved MMP and apoptosis in H2O2-damaged HK-2 cells. The increased expression of apoptosis-related proteins and kidney injury biomarkers were significantly ameliorated after CaD treatment. Conclusion: Overall, CaD effectively ameliorated renal injury by eliminating ROS and demonstrated in vivo and in vitro for I/R-induced AKI. CaD has been shown to be a promising therapeutic agent for the treatment of I/R-induced AKI.

Spermatogonial stem cells (SSCs) are adult stem cells in the testis of male animals and have the ability in self-renewal and differentiation. SSCs are derived from primordial germ cells (PGCs) that are mitotically arrested in the embryo before birth. Following the birth of the animal, PGCs resume mitosis and migrate from the centre of the seminiferous tubules to the basement membrane. The descendent of PGCs (also called gonocytes) establish stable SSC colonies in about a week postnatally in order to support the life-long spermatogenesis. Whether SSCs at different developmental stages differ in their molecular and cellular characteristics is currently unclear. In the presented study, we conducted bioinformatics analyses using transcriptomics data established previously in the laboratory on OCT4 (encoded by the pluripotent gene Pou5f1) expressing SSCs from the neonatal (3 days-post-partum, 3-dpp), juvenile (7-dpp) and adult (2~3-month) mice, including screen of differentially expressed genes (DEGs), protein-protein interaction (PPI) network analysis of DEGs and clustering of sub-networks from PPI. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses were also performed on clustered sub-networks of the PPI. In addition, all genes were analyzed using GSEA (gene set enrichment analysis) based on GO, KEGG and HALLMARK gene sets. The results showed that SSCs have a large number of DEGs among OCT4-positive SSCs from neonatal, juvenile and adult mice. The distinguishable biological functions encoded by these DEGs include biosynthesis and energy metabolism, immune response, cell junction and expression of migration and cell differentiation-related genes. Significant changes in the cell membrane composition of OCT4-positive SSCs may not only cause hypersensitive immune reactions but also affect the cell-cell contact and responses to secreted cytokines in the extracellular environment. The results also suggest that OCT4-positive SSCs may shift metabolic state from oxidative phosphorylation to glycolysis and significantly reduce the transcription of genes related to ribosome formation during aging. These results provide new clues for future research on the regulatory mechanisms of male germline stem cell development, growth and aging.精原干细胞(spermatogonial stem cells, SSCs)是成年动物睾丸中的成体干细胞,具有自我更新与分化的能力。小鼠(Mus musculus)精原干细胞来源于胚胎期的原始生殖细胞(primodial germ cells, PGCs),小鼠出生前原始生殖细胞处于有丝分裂静止状态,出生后恢复增殖并由曲细精管中央迁移至管壁基质,建立稳定的精原干细胞克隆。成熟小鼠的精原干细胞周期性地启动精子发生以维持雄性动物长期稳定的生殖能力。精原干细胞在其建立和成熟后是否具有特征上的差异目前尚不清楚。本研究在前期建立的不同年龄小鼠精原干细胞(表达多能性基因Pou5f1编码的OCT4)转录组数据基础上,对小鼠新生期(出生后3天)、幼年期(出生后7天)和成熟期(2~3月龄)精原干细胞的基因表达差异进行了生物信息学分析,包括差异表达基因(differentially expression genes, DEGs)的筛选、DEGs编码的蛋白相互作用网络(protein-protein interaction, PPI)的建立、功能聚类富集(Gene Ontology, GO)和通路分析(Kyoto Encyclopedia of Genes and Genomes, KEGG),以及使用基于GO、KEGG和HALLMARK的基因集富集分析(gene set enrichment analysis, GSEA)。结果显示,OCT4阳性精原干细胞在小鼠新生期、幼年期和成熟期存在大量差异表达基因,所编码的蛋白主要生物学功能集中在生物合成和能量代谢、免疫反应、细胞连接和迁移以及细胞分化等方面。精原干细胞细胞膜成分的显著变化可能影响精原干细胞的超敏反应、细胞间相互作用以及对细胞外环境因子的应答反应。在能量代谢方式上,随着年龄的增加,OCT4阳性精原干细胞逐渐从线粒体氧化磷酸化作用转变为糖酵解作用,同时也显著减少了细胞内核糖体形成相关基因的转录。这些结果为进一步研究雄性生殖干细胞形成和成熟的调控机制提供了新的思路。.

The nonvolatility and resistance variability of memristor make it a candidate for emulating complex dynamic behaviors in the neural system. In this paper, the memristive neuron with homeostatic plasticity is implemented. The memristor is applied to the neuron circuit, and its memristance represents the membrane sensibility of neurons. Composed of a trigger module, a pulse generation module and a feedback module, the memristor-based neuron can adaptively adjust the firing rate of neuron and maintain it in the inherent firing rate range, which shows similarities to its biological counterpart. The proposed design can mimic firing rate behaviors of the electrophysiological experiment performed in rodent, where the homeostatic plasticity of neuron is inhibited by sleep signal and promoted by wake signal. Furthermore, all the simulations are conducted in Cadence PSPICE, and the functionality of the design is proved with the simulation.

Ginsenosides regulate glucose homeostasis. This study investigated the effect of ginsenoside Rg5 (Rg5) on the hepatic glucagon response, focusing on the regulation of metabolism. Mice fed a high-fat diet (HFD) showed increased hepatic glucose production (HGP). We observed the effects of Rg5 on hepatic fatty acid oxidation and glucagon response. The regulation of phosphodiesterase (PDE) 4B by succinate was also investigated in hepatocytes. Rg5 inhibited endogenous glucose production in HFD-fed mice. Rg5 reduced cyclic AMP (cAMP) accumulation and inhibited transcriptional regulation of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) by dephosphorylation of the cAMP response element-binding transcription factor in the liver, demonstrating the inhibitory effect on hepatic glucagon response. HFD feeding increased succinate accumulation in the liver due to the reversal of succinate dehydrogenase activation and triggered hypoxia-inducible factor-1α (HIF-1α) induction. Succinate prevented cAMP degradation by inactivating PDE4B, thereby increasing cAMP accumulation in response to glucagon. Knockdown of HIF-1α with small interfering RNA diminished the effect of succinate, indicating that HIF-1α was essential for succinate to inactivate PDE4B. Rg5 inhibited succinate accumulation in hepatocytes by combating fatty acid oxidation, and thus reduced cAMP accumulation by blocking succinate/HIF-1α induction. Rg5 reduced HGP as a consequence of the inhibition of the glucagon response. Succinate acted as a metabolic signal to enhance the hepatic glucagon response. Rg5 reduced hepatic succinate accumulation by combating fatty acid oxidation and attenuated the hepatic glucagon response by suppressing succinate/HIF-1α induction, suggesting that succinate-associated HIF-1α induction in hepatocytes might be a therapeutic target in the treatment of diabetes.

Baicalin and scutellarin, two flavonoid glucuronic acids isolated from Scutellaria baicalensis, exhibit beneficial effects on glucose homeostasis. Baicalin and scutellarin are similar in structure except scutellarin has an additional hydroxyl at composition C-4'. In this work, we observed that baicalin and scutellarin promoted glucose disposal in mice and in adipocytes. Baicalin selectively increased phosphorylation of AMP-activated kinase (AMPK), while scutellarin selectively enhanced Akt phosphorylation. Both of them increased AS160 phosphorylation and glucose uptake in basal condition. AMPK inhibitor or knockdown of AMPK by siRNA blocked baicalin-induced AS160 phosphorylation and glucose uptake, but showed no effects on scutellarin. In contrast, Akt inhibitor and knockdown of Akt with siRNA decreased scutellarin-stimulated glucose uptake but had no effects on baicalin. The molecular dynamic simulations analysis showed that the binding energy of baicalin to AMPK (-34.30kcal/mol) was more favorable than scutellarin (-21.27kcal/mol), while the binding energy of scutellarin (-29.81kcal/mol) to Akt was much more favorable than baicalin (4.04kcal/mol). Interestingly, a combined treatment with baicalin and scutellarin acted synergistically to enhance glucose uptake in adipocytes (combination index: 0.94-0.046). In conclusion, baicalin and scutellarin, though structurally similar, promoted glucose disposal in adipocytes by differential regulation on AMPK and Akt activity. Our data provide insight that multicomponent herbal medicines may act synergistically on multiple targets.

Two chemosensors with large hexaazatriphenylene-pyrene chromophores were designed and synthesized. Both of them exhibit a selective fluorescence quenching response to Hg2+ in aqueous acetonitrile solution, and their detection limits are lower than the toxic level of Hg2+. Additionally, these compounds were successfully used for test paper detection.

Endoplasmic reticulum (ER) stress, inflammation, and lipolysis occur simultaneously in adipose dysfunction and contribute to insulin resistance. This study was designed to investigate whether ginsenoside Rg5 could ameliorate adipose dysfunction and prevent muscle insulin resistance. Short-term high-fat diet (HFD) feeding induced hypoxia with ER stress in adipose tissue, leading to succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activity. Rg5 treatment reduced cellular energy charge, suppressed ER stress and then prevented succinate accumulation in adipose tissue. Succinate promoted IL-1β production through NLRP3 inflammasome activation and then increased cAMP accumulation by impairing PDE3B expression, leading to increased lipolysis. Ginsenoside Rg5 treatment suppressed NLRP3 inflammasome activation, preserved PDE3B expression and then reduced cAMP accumulation, contributing to inhibition of lipolysis. Adipose lipolysis increased FFAs trafficking from adipose tissue to muscle. Rg5 reduced diacylglycerol (DAG) and ceramides accumulation, inhibited protein kinase Cθ translocation, and prevented insulin resistance in muscle. In conclusion, succinate accumulation in hypoxic adipose tissue acts as a metabolic signaling to link ER stress, inflammation and cAMP/PKA activation, contributing to lipolysis and insulin resistance. These findings establish a previously unrecognized role of ginsenosides in the regulation of lipid and glucose homeostasis and suggest that adipose succinate-associated NLRP3 inflammasome activation might be targeted therapeutically to prevent lipolysis and insulin resistance.

By retaining the quadrapyridyl receptor of polypyridylhexaazatriphenylene (a Cd(2+) sensor reported by us) and extending its chromophoric group with pyrene, a chemical sensor (1) was designed and synthesized in this work. This sensor exhibit selective off-on fluorescence response to Cd(2+) over other metal ions, and the detection limit is as low as 0.02 μM. The Cd(2+) sensing of 1 has high water toleration and can be carried out in the media with the water content up to 70%. Additionally, 1 was successfully applied to the in vivo imaging of intracellular Cd(2+) in living HaLa cells, and showed low cytotoxicity and cell membrane permeability in these experiments. These results suggest that 1 has potential application in the Cd(2+) analysis of environmental and biological samples.

Quercetin is a natural flavonoid widely distributed in human diet and functional foods. Quercetin 3-O-β-glucuronide (Q3G) is present in wine and some medicinal plants. Quercetin and Q3G may be metabolized from each other in vivo. While quercetin has been the subject of many studies, the pharmacokinetic profiles of quercetin and Q3G (in animals) have not yet been compared. Herein, we prepared a column-based method for rapid isolation of Q3G from Nelumbo nucifera. Then, we developed an UHPLC-MS/MS method to compare the pharmacokinetics of quercetin and Q3G. Our results showed that the plasma concentration-time curves of quercetin and Q3G show two maxima (Tmax1 ≈ 0.75 h, Tmax2 ≈ 5 h). After oral administration of 100 mg/kg quercetin or 100 mg/kg Q3G in rats, predominantly Q3G was detected in plasma with AUC at 39529.2 ± 6108.2 mg·h·L−1 or 24625.1 ± 1563.8 mg·h·L−1, 18-fold higher than quercetin with AUC at 1583.9 ± 583.3 mg·h·L−1 or 1394.6 ± 868.1 mg·h·L−1, respectively. After intravenous injection of 10 mg/kg in rats, Q3G showed extensive tissue uptake in kidney (409.2 ± 118.4 ng/g), liver (166.1 ± 52.9 ng/g), heart (97.7 ± 22.6 ng/g), and brain (5.8 ± 1.2 ng/g). In conclusion, we have shown that Q3G is a major active component in plasma and tissue for oral administration of quercetin or Q3G.

This paper combines virtual technology with visualization visual simulation theory, construct the framework of visual simulation platform, apply open source software FlightGear simulator combined with GoogleEarth design a small UAV flight visual simulation platform. Using software AC3D to build 3D models of aircraft and complete the model loading based on XML configuration, the design and simulation of visualization modeling visual platform is presented. By using model-driven and data transforming in FlightGear , the design of data transmission module is realized based on Visual Studio 2010 development platform. Finally combined with GoogleEarth it can achieve the tracking and display.

The article focuses on the research of moving target detection and tracking algorithm in Aerial monitoring. Study includes moving target detection, moving target behavioral analysis and Target Auto tracking. In moving target detection, the paper considering the characteristics of background subtraction and frame difference method, using background reconstruction method to accurately locate moving targets; in the analysis of the behavior of the moving object, using matlab technique shown in the binary image detection area, analyzing whether the moving objects invasion and invasion direction; In Auto Tracking moving target, A video tracking algorithm that used the prediction of object centroids based on Kalman filtering was proposed.

cope Quercetin is a dietary flavonoid whose role in the regulation of the activity of insulin remains controversial. Our study aimed to investigate how quercetin and its major metabolite quercetin-3-glucuronide (Q-3-G) regulate insulin-mediated glucose disposal in skeletal muscle under normal and inflammatory conditions. Methods and results Under normal conditions, quercetin impaired glucose and insulin tolerance and attenuated insulin-mediated phosphorylation of Akt substrate of 160 kDa (AS160) and TBC1D1 without affecting Akt activity in male Institute of Cancer Research (ICR) mice. However, under inflammatory conditions, quercetin exhibited an opposite effect in these animals. In C2C12 cells, quercetin also decreased insulin-stimulated AS160 and TBC1D1 phosphorylation and glucose uptake in the absence of an inflammatory insult, whereas it improved the action of insulin under inflammatory conditions. Knockdown of adenosine 5′-monophosphate-activated protein kinase α (AMPKα) blocked the differential effects of quercetin under both conditions. Unlike quercetin, Q-3-G had no influence on insulin-induced phosphorylation of AS160 and TBC1D1 and glucose uptake in C2C12 myotubes under normal conditions. Q-3-G displayed a similar regulation with quercetin in glucose disposal under inflammatory conditions. Conclusion Quercetin suppressed insulin-mediated glucose disposal in skeletal muscle tissue/cells under normal conditions while it ameliorated impaired glucose uptake under inflammatory conditions with activation of AMPK. In contrast, Q-3-G ameliorated insulin resistance in skeletal cells under inflammatory conditions without affecting glucose disposal under normal conditions.

To investigate the role of transforming growth factor-β1 (TGF-β1) in periodontal tissue reconstruction during rapid teeth movement through reducing resistance and distraction.Twenty Beagle dogs were randomly divided into five groups according to time points: distraction for 5 days, 10 days, 15 days, retaining 10 days after distraction for 15 days, and retaining 90 days after distraction for 15 days. The mandibular first premolar was moved by using reducing resistance and distraction (experimental group) or conventional distraction (control group) randomly. For each group, tooth movement distance was measured and first premolar periodontal tissue pieces were obtained in scheduled time. Hematoxylin-eosin stain, Picric acid-Sirius red, and immunohistochemistry were performed. The data was analyzed by using SPSS 18.0 software package.The speed of tooth movement and periodontal reconstruction of the experimental group were significantly faster than the control group. TGF-β1 positive expression in two groups had similar distribution area, and reached peak at most active stage of osteogenesis in both groups. But in different stages of distraction, the positive expression in the experimental group was significantly higher than the control group(P0.05).Compared with conventional orthodontic method, reducing resistance and distraction can obviously increase the expression of TGF-β1 of tension side of the distracted tooth, and accelerate periodontal tissue reconstruction.

By retaining the quadrapyridyl receptor of polypyridylhexaazatriphenylene (a Cd(2+) sensor reported by us) and extending its chromophoric group with pyrene, a chemical sensor (1) was designed and synthesized in this work. This sensor exhibit selective off-on fluorescence response to Cd(2+) over other metal ions, and the detection limit is as low as 0.02 μM. The Cd(2+) sensing of 1 has high water toleration and can be carried out in the media with the water content up to 70%. Additionally, 1 was successfully applied to the in vivo imaging of intracellular Cd(2+) in living HaLa cells, and showed low cytotoxicity and cell membrane permeability in these experiments. These results suggest that 1 has potential application in the Cd(2+) analysis of environmental and biological samples.

By a one-pot method, monodisperse micro/nanoscale Zn-based coordination polymers (CPs) were synthesized. The morphologies of products could be feasibly modulated with the change of the synthesis medium. These CPs were used as precursors to prepare ZnO architectures, which are mesoporous, inherit the morphology of CP precursors and exhibit high photoactivity.

A luminescent two-dimensional (2D) coordination polymer is demonstrated to be a selective sensing material for the straightforward detection of nitrobenzene via a redox fluorescence quenching mechanism.