An Essential Role of cAMP Response Element Binding Protein in Ginsenoside Rg1-Mediated Inhibition of Na+/Glucose Cotransporter 1 Gene Expression.

The Na(+)/glucose cotransporter 1 (SGLT1) is responsible for glucose uptake in intestinal epithelial cells. It has been shown that the intestinal SGLT1 level is significantly increased in diabetic individuals and positively correlated with the pathogenesis of diabetes. The development of targeted therapeutics that can reduce the intestinal SGLT1 expression level is, therefore, important. In this study, we showed that ginsenoside Rg1 effectively decreased intestinal glucose uptake through inhibition of SGLT1 gene expression in vivo and in vitro. Transient transfection analysis of the SGLT1 promoter revealed an essential cAMP response element (CRE) that confers the Rg1-mediated inhibition of SGLT1 gene expression. Chromatin immunoprecipitation assay and targeted CRE-binding protein (CREB) silencing demonstrated that Rg1 reduced the promoter binding of CREB and CREB binding protein associated with an inactivated chromatin status. In addition, further studies showed that the epidermal growth factor receptor (EGFR) signaling pathway also plays an essential role in the inhibitory effect of Rg1; taken together, our study demonstrates the involvement of the EGFR-CREB signaling pathway in the Rg1-mediated downregulation of SGLT1 expression, which offers a potential strategy in the development of antihyperglycemic and antidiabetic treatments.

Real time observation of the formation of hollow nanostructures through solid state reactions.

We demonstrate the formation of hollow nickel germanide nanostructures of Ni-Ge core-shell nanoparticles by solid state reactions. The structural evolutions of nickel germanide hollow nanostructures have been investigated in real-time ultrahigh vacuum transmission electron microscopy (UHV-TEM). Annealed above 450 °C, the nonequilibrium interdiffusion of core and shell species occurred at the interface; thus, Ni germanide hollow nanostructures were formed by solid state reactions involving the Kirkendall effect. In addition, the different hollow nanostructures formed from different core diameters of Ni-Ge core-shell nanoparticles have been studied. Also, we propose the mechanism with effects of the size and annealing duration on the solid state reactions based on the Kirkendall effect.

Kinetic competition model and size-dependent phase selection in 1-D nanostructures.

The first phase selection and the phase formation sequence between metal and silicon (Si) couples are indispensably significant to microelectronics. With increasing scaling of device dimension to nano regime, established thermodynamic and kinetic models in bulk and thin film fail to apply in 1-D nanostructures. Herein, we present an unique size-dependent first phase formation sequence in 1-D nanostructures, with Ni-Si as the model system. Interfacial-limited phase which forms the last in thin film, NiSi(2), appears as the dominant first phase at 300-800 °C due to the elimination of continuous grain boundaries in 1-D silicides. On the other hand, θ-Ni(2)Si, the most competitive diffusion-limited phase takes over NiSi(2) and wins out as the first phase in small diameter nanowires at 800 °C. Kinetic parameters extracted from in situ transmission electron microscope studies and a modified kinetic growth competition model quantitatively explain this observation. An estimated critical diameter from the model agrees reasonably well with observations.

Improved performance of ZnO-based resistive memory by internal diffusion of Ag atoms.

An Ag/ZnO/Pt memory device, which has much better resistive switching behaviour than Pt/ZnO/Pt device was demonstrated. The detailed resistive mechanisms for the Pt/ZnO/Pt and the Ag/ZnO/Pt systems are proposed and investigated. Microstructures are observed by transmission electron microscope (TEM), indicating that the formation of conducting path for both systems is different. For the Pt/ZnO/Pt device, the conductive filament path is constructed by the oxygen vacancies from top to bottom electrodes under a larger enough bias at a forming process. For the Ag/ZnO/Pt device, the filament path was grown by oxygen vacancies combined with an internal diffusion of Ag atoms under a large bias and can provide the lowest energy barrier for electrons transported between two electrodes during set and reset processes, which reduces formation of other conducting paths after each switching. Accordingly, the stable switching performance of the Ag/ZnO/Pt device can be achieved over 100 cycles even the thickness of ZnO film <25 nm.

The influence of surface oxide on the growth of metal/semiconductor nanowires.

We report the critical effects of oxide on the growth of nanostructures through silicide formation. Under an in situ ultrahigh vacuum transmission electron microscope, it is observed from the conversion of Si nanowires into the metallic PtSi grains epitaxially through controlled reactions between lithographically defined Pt pads and Si nanowires. With oxide, instead of contact area, single crystal PtSi grains start forming either near the center between two adjacent pads or from the ends of Si nanowires, resulting in the heterostructure formation of Si/PtSi/Si. Without oxide, transformation from Si into PtSi begins at the contact area between them, resulting in the heterostructure formation of PtSi/Si/PtSi. The nanowire heterostructures have an atomically sharp interface with epitaxial relationships of Si(20-2)//PtSi(10-1) and Si[111]//PtSi[111]. Additionally, it has been observed that the existence of oxide significantly affects not only the growth position but also the growth behavior and the growth rate by two orders of magnitude. Molecular dynamics simulations have been performed to support our experimental results and the proposed growth mechanisms. In addition to fundamental science, the significance of the study matters for future processing techniques in nanotechnology and related applications as well.

Optimization of the nanotwin-induced zigzag surface of copper by electromigration.

By adding nanotwins to Cu, the surface electromigration (EM) slows down. The atomic mobility of the surface step-edges is retarded by the triple points where a twin meets a free surface to form a zigzag-type surface. We observed that EM can alter the zigzag surface structure to optimize the reduction of EM, according to Le Chatelier's principle. Statistically, the optimal alternation is to change an arbitrary (111)/(hkl) zigzag pair to a pair having a very low index (hkl) plane, especially the (200) plane. Using in situ ultrahigh vacuum and high-resolution transmission electron microscopy, we examined the effects of different zigzag surfaces on the rate of EM. The calculated rate of surface EM can be decreased by a factor of ten.

An essential role of cAMP response element-binding protein in epidermal growth factor-mediated induction of sodium/glucose cotransporter 1 gene expression and intestinal glucose uptake.

The sodium/glucose cotransporter 1 (SGLT1) is responsible for glucose uptake in intestinal epithelial cells. Its expression is decreased in individuals with intestinal inflammatory disorders and is correlated with the pathogenesis of disease. The aim of this study was to understand the regulatory mechanism of the SGLT1 gene. Using the trinitrobenzene sulfonic acid-induced mouse models of intestinal inflammation, we observed decreased SGLT1 expression in the inflamed intestine was positively correlated with the mucosal level of epidermal growth factor (EGF) and activated CREB. Overexpression of EGF demonstrated that the effect of EGF on intestinal glucose uptake was primarily due to the increased level of SGLT1. We identified an essential cAMP binding element (CRE) confers EGF inducibility in the human SGLT1 gene promoter. ChIP assay further demonstrated the increased binding of CREB and CBP to the SGLT1 gene promoter in EGF-treated cells. In addition, the EGFR- and PI3K-dependent CREB phosphorylations are involved in the EGF-mediated SGLT1 expression. This is the first report to demonstrate that CREB is involved in EGF-mediated transcription regulation of SGLT1 gene in the normal and inflamed intestine, which can provide potential therapeutic applications for intestinal inflammatory disorders.

A gut microbial metabolite of ginsenosides, compound K, induces intestinal glucose absorption and Na(+) /glucose cotransporter 1 gene expression through activation of cAMP response element binding protein.

SCOPE: The Na(+) /glucose cotransporter 1 (SGLT1) plays a crucial role in glucose uptake in intestinal epithelial cells (IECs), which has been shown essential in ameliorating intestinal inflammation. Ginseng has historically been used to treat inflammatory disorders. Understanding the regulatory mechanism of ginseng-mediated induction of SGLT1 gene expression in human intestinal cells is therefore important. METHODS AND RESULTS: We demonstrate that ginsenoside compound K (CK) enhances SGLT1-mediated glucose uptake in mice and human intestinal Caco-2 cells. Transient transfection analysis using SGLT1 promoter-luciferase reporters demonstrated that the presence of an essential cAMP response element (CRE) is required for CK-mediated induction of SGLT1 gene expression. The ChIP assays indicated that increased CRE-binding protein (CREB) and CREB-binding protein (CBP) binding to the SGLT1 promoter in CK-treated cells is associated with an activated chromatin state. Our result showed that the increased CREB phosphorylation is directly correlated with SGLT1 expression in IECs. Further studies indicated that the epidermal growth factor receptor (EGFR) signaling pathway is involved in the CK-mediated effect. CONCLUSION: These findings provide a novel mechanism for the CK-mediated upregulation of SGLT1 expression through EGFR-CREB signaling activation, which could contribute to reducing gut inflammation.

High-yield synthesis of ZnO nanowire arrays and their opto-electrical properties.

In this article, ZnO nanostructures were synthesized via the hydrothermal method which used ZnCl(2) and HMTA mixed solution as the precursor. A multistep growth was adopted to improve the growth restriction of a closed system, not only the length but also the aspect ratio were increased with steps of growth, and the shape of nanorods maintained integrity. Furthermore, photoluminescence spectra which have the near-band-edge-emission (∼3.37 eV) and defect-related emission show the optical properties of ZnO nanostructures. The defect-related emission intensity was greatly enhanced with the increasing surface area of ZnO nanowires. The level of the OH group was attributed to the yellow-light emission (∼580 nm) and the red-shift phenomenon. In addition, we fabricated two types of ultraviolet photodetectors: a single nanowire device and a nanowire-array device, operating at a low bias (less than 5 mV). With the lower energy consumption and the weaker persistent photoconductive effect, our ultraviolet photodetectors have better performance, exhibiting a short response time and higher sensitivity.

Well-aligned ZnO nanowires with excellent field emission and photocatalytic properties.

Well-aligned ZnO nanowires (NWs) were successfully synthesized on Si(100) by the process of carbothermal reduction and vapor-liquid-solid method. Scanning electron microscopy and transmission electron microscopy results confirmed that ZnO NWs were single crystalline wurtzite structures and grew along the [0001] direction. The influences of substrate temperature and total pressure on the growth were discussed. The well-aligned ZnO NWs show good field emission properties, and the emitter constructed of pencil-like ZnO NWs exhibited a low turn-on field (3.82 V µm(-1)) and a high field enhancement factor (ß = 2303). Finally, we demonstrated that the as-prepared ZnO NWs with small diameter on the substrate have good photocatalytic activity toward degradation of methylene blue. Using ZnO NWs with Au nanoparticles (NPs) would decrease the recombination rate of hole-electron pairs due to the great shift of the Fermi level to the conduction band. Hence, adding Au NPs was a promising method to enhance the photocatalytic performance of ZnO NWs. It is significant that photocatalyst fabricated by ZnO NWs can apply to the degradation of organic pollution, and solve the environmental issues.

Resistive switching of Au/ZnO/Au resistive memory: an in situ observation of conductive bridge formation.

A special chip for direct and real-time observation of resistive changes, including set and reset processes based on Au/ZnO/Au system inside a transmission electron microscope (TEM), was designed. A clear conducting bridge associated with the migration of Au nanoparticles (NPs) inside a defective ZnO film from anode to cathode could be clearly observed by taking a series of TEM images, enabling a dynamic observation of switching behaviors. A discontinuous region (broken region) nearby the cathode after reset process was observed, which limits the flow of current, thus a high resistance state, while it will be reconnected to switch the device from high to low resistance states through the migration of Au NPs after set process. Interestingly, the formed morphology of the conducting bridge, which is different from the typical formation of a conducting bridge, was observed. The difference can be attributed to the different diffusivities of cations transported inside the dielectric layer, thereby significantly influencing the morphology of the conducting path. The current TEM technique is quite unique and informative, which can be used to elucidate the dynamic processes in other devices in the future.

Direct observation of melting behaviors at the nanoscale under electron beam and heat to form hollow nanostructures.

We report the melting behaviours of ZnO nanowire by heating ZnO-Al(2)O(3) core-shell heterostructures to form Al(2)O(3) nanotubes in an in situ ultrahigh vacuum transmission electron microscope (UHV-TEM). When the ZnO-Al(2)O(3) core-shell nanowire heterostructures were annealed at 600 °C under electron irradiation, the amorphous Al(2)O(3) shell became single crystalline and then the ZnO core melted. The average vanishing rate of the ZnO core was measured to be 4.2 nm s(-1). The thickness of the Al(2)O(3) nanotubes can be precisely controlled by the deposition process. Additionally, the inner geometry of nanotubes can be defined by the initial ZnO core. The result shows a promising method to obtain the biocompatible Al(2)O(3) nanotubes, which may be applied in drug delivery, biochemistry and resistive switching random access memory (ReRAM).