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Showing papers by "Yu Huang published in 2012"


Journal ArticleDOI
TL;DR: The versatility of graphene-based devices goes beyond conventional transistor circuits and includes flexible and transparent electronics, optoelectronics, sensors, electromechanical systems, and energy technologies.
Abstract: Graphene, a single layer of carbon atoms in a honeycomb lattice, offers a number of fundamentally superior qualities that make it a promising material for a wide range of applications, particularly in electronic devices. Its unique form factor and exceptional physical properties have the potential to enable an entirely new generation of technologies beyond the limits of conventional materials. The extraordinarily high carrier mobility and saturation velocity can enable a fast switching speed for radio-frequency analog circuits. Unadulterated graphene is a semi-metal, incapable of a true off-state, which typically precludes its applications in digital logic electronics without bandgap engineering. The versatility of graphene-based devices goes beyond conventional transistor circuits and includes flexible and transparent electronics, optoelectronics, sensors, electromechanical systems, and energy technologies. Many challenges remain before this relatively new material becomes commercially viable, but laboratory prototypes have already shown the numerous advantages and novel functionality that graphene provides.

740 citations


Journal ArticleDOI
TL;DR: The accelerated durability test (ADT) demonstrates that the hybrid supporting material can dramatically enhance the durability of the catalyst and retain the electrochemical surface area (ECSA) of Pt: the final ECSA of the Pt nanocrystal on the hybrid support after 20 000 ADT cycles is retained at >95%, much higher than the commercially available catalyst.
Abstract: Oxygen reduction reaction (ORR) catalyst supported by hybrid composite materials is prepared by well-mixing carbon black (CB) with Pt-loaded reduced graphene oxide (RGO). With the insertion of CB particles between RGO sheets, stacking of RGO can be effectively prevented, promoting diffusion of oxygen molecules through the RGO sheets and enhancing the ORR electrocatalytic activity. The accelerated durability test (ADT) demonstrates that the hybrid supporting material can dramatically enhance the durability of the catalyst and retain the electrochemical surface area (ECSA) of Pt: the final ECSA of the Pt nanocrystal on the hybrid support after 20 000 ADT cycles is retained at >95%, much higher than the commercially available catalyst. We suggest that the unique 2D profile of the RGO functions as a barrier, preventing leaching of Pt into the electrolyte, and the CB in the vicinity acts as active sites to recapture/renucleate the dissolved Pt species. We furthermore demonstrate that the working mechanism can ...

436 citations


Journal ArticleDOI
TL;DR: This study defines a unique pathway to large-scale fabrication of high-performance graphene transistors, and holds significant potential for future application of graphene-based devices in ultra–high-frequency circuits.
Abstract: Graphene has attracted enormous attention for radio-frequency transistor applications because of its exceptional high carrier mobility, high carrier saturation velocity, and large critical current density. Herein we report a new approach for the scalable fabrication of high-performance graphene transistors with transferred gate stacks. Specifically, arrays of gate stacks are first patterned on a sacrificial substrate, and then transferred onto arbitrary substrates with graphene on top. A self-aligned process, enabled by the unique structure of the transferred gate stacks, is then used to position precisely the source and drain electrodes with minimized access resistance or parasitic capacitance. This process has therefore enabled scalable fabrication of self-aligned graphene transistors with unprecedented performance including a record-high cutoff frequency up to 427 GHz. Our study defines a unique pathway to large-scale fabrication of high-performance graphene transistors, and holds significant potential for future application of graphene-based devices in ultra–high-frequency circuits.

350 citations


Journal ArticleDOI
TL;DR: Stable hemin-graphene conjugates formed by immobilization of monomeric hemin on graphene, showed excellent catalytic activity, more than 10 times better than that of the recently developedhemin-hydrogel system and 100 times betterthan that of unsupported hemin.
Abstract: Using synthetic systems to mimic natural enzymes with high catalytic activity and distinct substrate selectivity has been a challenge for the last several decades. Hemin, the catalytic center for many protein families including cytochromes, peroxidases, myoglobins and hemoglobins, can catalyze a variety of oxidation reactions like peroxidase enzymes.[1] However, direct application of hemin as an oxidation catalyst is of significant challenge because of its molecular aggregation in aqueous solution to form catalytic inactive dimers and oxidative self-destruction in the oxidizing media, which causes passivation of its catalytic activity.[2] A potential solution to this problem is to synthetically modify the porphyrin structure to achieve a variety of iron porphyrin derivatives for improved catalytic activity or stability.[3] An alternative approach is to use high surface area materials such as zeolites, nanoparticles, silica or natural clay to support hemin to achieve improved stability or activity in epoxidation or other reactions in organic solutions.[4] For reactions in aqueous solutions, hydrogel-embedded hemin[5] or more elaborate hemin complex obtained by conjugating with specific antibodies[6] have shown activity significantly better than free molecules, which is, however, still orders of magnitude inferior to natural enzymes, not to mention the difficulties in the synthesis of such kinds of complex hemin conjugates. Therefore, the discovery and development of novel materials as supports to achieve biomimetic catalysts with enzyme-like activity is highly desired.

345 citations


Journal ArticleDOI
24 Aug 2012-ACS Nano
TL;DR: It is shown that the self-limiting effect of graphene growth on Cu foil can be broken by using a high H(2)/CH(4) ratio in a low-pressure CVD process to enable the continued growth of bilayer graphene.
Abstract: Bernal-stacked (AB-stacked) bilayer graphene is of significant interest for functional electronic and photonic devices due to the feasibility to continuously tune its band gap with a vertical electric field. Mechanical exfoliation can be used to produce AB-stacked bilayer graphene flakes but typically with the sizes limited to a few micrometers. Chemical vapor deposition (CVD) has been recently explored for the synthesis of bilayer graphene but usually with limited coverage and a mixture of AB- and randomly stacked structures. Herein we report a rational approach to produce large-area high-quality AB-stacked bilayer graphene. We show that the self-limiting effect of graphene growth on Cu foil can be broken by using a high H2/CH4 ratio in a low-pressure CVD process to enable the continued growth of bilayer graphene. A high-temperature and low-pressure nucleation step is found to be critical for the formation of bilayer graphene nuclei with high AB stacking ratio. A rational design of a two-step CVD process...

251 citations


Journal ArticleDOI
TL;DR: A facile synthetic strategy to single-crystalline PtPd nanocrystals with controllable shapes and tunable compositions is reported, which exhibit high activity in the hydrogenation of nitrobenzene and their performance is highly shape- and composition-dependent.
Abstract: We report a facile synthetic strategy to single-crystalline PtPd nanocrystals with controllable shapes and tunable compositions. In the developed synthesis, the molar ratio of the starting precursors determines the composition in the final PtPd nanocrystals, while the halides function as the shape-directing agent to induce the formation of PtPd nanocrystals with cubic or octahedral/tetrahedral morphology. These obtained PtPd nanocrystals exhibit high activity in the hydrogenation of nitrobenzene, and their performance is highly shape- and composition-dependent with Pt in ∼50% showing the optimum activity and the {100}-facet-enclosed PtPd nanocrystals demonstrating a higher activity than the {111}-facet-bounded PtPd nanocrystals.

225 citations


Journal ArticleDOI
TL;DR: This facile fabrication of centimeter-scale colloidal PCs with narrow stopbands will offer significant insights into the design and creation of novel optical devices.
Abstract: This article presents a facile approach to centimeter-scale colloidal photonic crystals (PCs) with narrow stopbands assembled on low-adhesive superhydrophobic substrates. The full-width-at-half-maxima of the stopbands are just 12 nm. The narrow stopbands of colloidal PCs are ascribed to the combined effects of perfectly ordered assembly structure, large-scale crack elimination, decreased void fraction, and sufficient thickness of the colloidal PCs. These properties result from a self-assembly process on a low-adhesive superhydrophobic substrate. Latex suspension on this substrate displays a receding three-phase contact line during evaporation, which releases tensile stress induced by latex shrinkage and results in complete elimination of cracks in the colloidal PCs. Furthermore, the simultaneous assembly of latex particles on the outermost layer of a spread liquid film contributes to the perfectly ordered assembly structure. This facile fabrication of centimeter-scale colloidal PCs with narrow stopbands w...

201 citations


Journal ArticleDOI
TL;DR: It is elucidate that upregulation of GLP-1 and related agents improve endothelial function in hypertension by restoring NO bioavailability, suggesting that GLp-1 signaling could be a therapeutic target in hypertension-related vascular events.
Abstract: Sitagliptin, a selective dipeptidyl peptidase 4 inhibitor, inhibits the inactivation and degradation of glucagon like peptide 1 (GLP-1), which is used for the treatment of type 2 diabetes mellitus. However, little is known about the role of GLP-1 in hypertension. This study investigated whether the activation of GLP-1 signaling protects endothelial function in hypertension. Two-week sitagliptin treatment (10 mg/kg per day, oral gavage) improved endothelium-dependent relaxation in renal arteries, restored renal blood flow, and reduced systolic blood pressure in spontaneously hypertensive rats. In vivo sitagliptin treatment elevated GLP-1 and GLP-1 receptor expressions, increased cAMP level, and subsequently activated protein kinase A, liver kinase B1, AMP-activated protein kinase-α and endothelial NO synthase in spontaneously hypertensive rat renal arteries. Inhibition of GLP-1 receptor, adenylyl cyclase, protein kinase A, AMP-activated protein kinase-α, or NO synthase reversed the protective effects of sitagliptin. We also demonstrate that GLP-1 receptor agonist exendin 4 in vitro treatment had similar vasoprotective effects in spontaneously hypertensive rat renal arteries and increased NO production in spontaneously hypertensive rat aortic endothelial cells. Studies using transient expressions of wild-type and dominant-negative AMP-activated protein kinase-α2 support the critical role of AMP-activated protein kinase-α in mediating the effect of GLP-1 in endothelial cells. Ex vivo exendin 4 treatment also improved endothelial function of renal arteries from hypertensive patients. Our results elucidate that upregulation of GLP-1 and related agents improve endothelial function in hypertension by restoring NO bioavailability, suggesting that GLP-1 signaling could be a therapeutic target in hypertension-related vascular events.

173 citations


Journal ArticleDOI
TL;DR: In vivo and in vitro activation of VDR with calcitriol improves endothelial function by normalizing the expressions of AT(1)R and radical generating and scavenging enzymes and thus preventing ROS over-production.
Abstract: Aims The present study investigated whether or not calcitriol, an active form of vitamin D, protects against renovascular dysfunction in hypertension and, if so, whether or not such protection alters the expression of key proteins involved in that dysfunction. Methods and results Changes in isometric tension showed that the impaired endothelium-dependent relaxations in renal arteries of hypertensive patients were enhanced by 12 h in vitro treatment with calcitriol. Dihydroethidium fluorescence revealed an elevated level of reactive oxygen species (ROS) in these arteries which was reduced by calcitriol. Immunofluorescence showed that calcitriol treatment reduced the expression of AT1R, NOX-2, NOX-4, and p67 phox and increased that of superoxide dismutase (SOD)-1. Twelve-hour exposure to calcitriol prevented angiotensin (Ang) II-induced increases in ROS and the over-expression of NOX-2, NOX-4, and p67 phox in renal arteries from normotensive patients. A specific antagonist of the human vitamin D receptor (VDR), TEI-9647, abolished these effects of calcitriol. Both in vitro exposure to and chronic in vivo administration of calcitriol enhanced relaxations to acetylcholine and abolished exaggerated endothelium-dependent contractions in renal arteries of normotensive rats pre-exposed to Ang II or harvested from spontaneously hypertensive rats (SHR). Reactive oxygen species levels and expressions of AT1R, NAD(P)H oxidase subunits, SOD-1, and SOD-2 in SHR arteries were normalized by the chronic treatment with calcitriol. Conclusion In vivo and in vitro activation of VDR with calcitriol improves endothelial function by normalizing the expressions of AT1R and radical generating and scavenging enzymes and thus preventing ROS over-production. The present findings suggest that calcitriol is effective in preserving endothelial function in hypertension.

156 citations


Journal ArticleDOI
TL;DR: It is concluded that TRPV1 activation by dietary capsaicin improves energy metabolism and exercise endurance by upregulating PGC-1α in skeletal muscles by a novel therapeutic strategy for managing metabolic diseases and improving exercise endurance.
Abstract: Impaired aerobic exercise capacity and skeletal muscle dysfunction are associated with cardiometabolic diseases. Acute administration of capsaicin enhances exercise endurance in rodents, but the long-term effect of dietary capsaicin is unknown. The capsaicin receptor, the transient receptor potential vanilloid 1 (TRPV1) cation channel has been detected in skeletal muscle, the role of which remains unclear. Here we report the function of TRPV1 in cultured C2C12 myocytes and the effect of TRPV1 activation by dietary capsaicin on energy metabolism and exercise endurance of skeletal muscles in mice. In vitro, capsaicin increased cytosolic free calcium and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression in C2C12 myotubes through activating TRPV1. In vivo, PGC-1α in skeletal muscle was upregulated by capsaicin-induced TRPV1 activation or genetic overexpression of TRPV1 in mice. TRPV1 activation increased the expression of genes involved in fatty acid oxidation and mitochondrial respiration, promoted mitochondrial biogenesis, increased oxidative fibers, enhanced exercise endurance and prevented high-fat diet-induced metabolic disorders. Importantly, these effects of capsaicin were absent in TRPV1-deficient mice. We conclude that TRPV1 activation by dietary capsaicin improves energy metabolism and exercise endurance by upregulating PGC-1α in skeletal muscles. The present results indicate a novel therapeutic strategy for managing metabolic diseases and improving exercise endurance.

140 citations


Journal ArticleDOI
TL;DR: UCP2 preserves endothelial function through increasing nitric oxide bioavailability secondary to the inhibition of ROS production in the endothelium of obese diabetic mice.
Abstract: Rationale:Previous studies indicate uncoupling protein-2 (UCP2) as an antioxidant defense against endothelial dysfunction in hypertension. UCP2 also regulates insulin secretion and action. However, the role of UCP2 in endothelial dysfunction associated with diabetes and obesity is unclear. Objective:UCP2 protects against endothelial dysfunction induced by high-fat diet through inhibition of reactive oxygen species (ROS) production, and subsequent increase of nitric oxide bioavailability. Methods and Results:Endothelium-dependent relaxation (EDR) in aortae and mesenteric arteries in response to acetylcholine was measured in wire myograph. Flow-mediated vasodilatation in 2nd-order mesenteric arteries was measured in pressure myograph. ROS production is measured by CM-H2DCFDA and DHE fluorescence. High-glucose exposure reduced EDR in mouse aortae, which was exaggerated in UCP2 knockout (KO) mice, whereas UCP2 overexpression by adenoviral infection (AdUCP2) restored the impaired EDR. Impairment of EDR and flo...

Journal ArticleDOI
TL;DR: It was concluded that the lifespan-prolonging activity of blueberry extracts was at least partially associated with its interactions with MTH, Rpn11, and endogenous antioxidant enzymes SOD and CAT.

Journal ArticleDOI
TL;DR: In this article, a colloidal photonic crystal (PC) microdot was fabricated by inkjet printing, which demonstrated a fastest response of ca. 1.2 s to water vapor, which was attributed to the combined effects of the intrinsic small size of the inkjet microdots and the hydrophobic transition of poly(N-isopropyl acrylamide) above its lower critical solution temperature (LCST).
Abstract: This paper presents rapid response colloidal photonic crystal (PC) microdots fabricated by inkjet printing, which demonstrate a fastest response of ca. 1.2 s to water vapor. This remarkable improvement of response rate could be attributed to the combined effects of the intrinsic small size of the inkjet microdots and the hydrophobic transition of poly(N-isopropyl acrylamide) (PNIPAm) above its lower critical solution temperature (LCST). The reversible phase transition of PNIPAm modifies the hydrophilic–hydrophobic balance of the polymer interface, which leads to the modulation of wetting states/adhesion properties of adsorbed water on the polymer segments, resulting in the remarkable improvement of response rate. Moreover, the optimal response performance (including signal strength and response sensitivity) of the printed PC microdot is achieved by the coordination of a well-ordered latex assembly and full infiltration of the responsive polymer in the latex interstices. This simple fabrication of functional colloidal PC microdots opens new avenues for the construction of advanced microanalysis and microsensing devices. In addition, improving the response rate by the phase transition of the polymer segments is promising for the creation of high-performance sensors.

Journal ArticleDOI
TL;DR: A scalable approach is reported to fabricate self-aligned graphene transistors with the extrinsic cutoff frequency exceeding 50 GHz and graphene circuits that can operate in the 1-10 GHz regime, a significant advancement over previous reports.
Abstract: Graphene transistors are of considerable interest for radio frequency (rf) applications. High-frequency graphene transistors with the intrinsic cutoff frequency up to 300 GHz have been demonstrated. However, the graphene transistors reported to date only exhibit a limited extrinsic cutoff frequency up to about 10 GHz, and functional graphene circuits demonstrated so far can merely operate in the tens of megahertz regime, far from the potential the graphene transistors could offer. Here we report a scalable approach to fabricate self-aligned graphene transistors with the extrinsic cutoff frequency exceeding 50 GHz and graphene circuits that can operate in the 1–10 GHz regime. The devices are fabricated on a glass substrate through a self-aligned process by using chemical vapor deposition (CVD) grown graphene and a dielectrophoretic assembled nanowire gate array. The self-aligned process allows the achievement of unprecedented performance in CVD graphene transistors with a highest transconductance of 0.36 m...

Journal ArticleDOI
03 Aug 2012-PLOS ONE
TL;DR: In this article, the authors showed that H(2)S exerts vasodilatory effects by opening KCNQ-type voltage-dependent (K(v)) K(+) channels and showed that CSE-producing cystathionine-gamma-lyase in perivascular adipose tissue plays a major role in this pathway.
Abstract: BACKGROUND: Hydrogen sulfide (H(2)S) is a potent vasodilator. However, the complex mechanisms of vasoregulation by H(2)S are not fully understood. We tested the hypotheses that (1) H(2)S exerts vasodilatory effects by opening KCNQ-type voltage-dependent (K(v)) K(+) channels and (2) that H(2)S-producing cystathionine-gamma-lyase (CSE) in perivascular adipose tissue plays a major role in this pathway. METHODOLOGY/PRINCIPAL FINDINGS: Wire myography of rat and mouse aortas was used. NaHS and 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADTOH) were used as H(2)S donors. KCNQ-type K(v) channels were blocked by XE991. 4-Propargylglycine (PPG) and beta-cyano-l-alanine (BCA), or 2-(aminooxy)-acetic acid (AOAA) were used as inhibitors of CSE or cystathionine-s-synthase (CBS), respectively. NaHS and ADTOH produced strong vasorelaxation in rat and mouse aortas, which were abolished by KCNQ channel inhibition with XE991. Perivascular adipose tissue (PVAT) exerted an anticontractile effect in these arteries. CSE inhibition by PPG and BCA reduced this effect in aortas from rats but not from mice. CBS inhibition with AOAA did not inhibit the anticontractile effects of PVAT. XE991, however, almost completely suppressed the anticontractile effects of PVAT in both species. Exogenous l-cysteine, substrate for the endogenous production of H(2)S, induced vasorelaxation only at concentrations >5 mmol/l, an effect unchanged by CSE inhibition. CONCLUSIONS/SIGNFICANCE: Our results demonstrate potent vasorelaxant effects of H(2)S donors in large arteries of both rats and mice, in which XE991-sensitive KCNQ-type channel opening play a pivotal role. CSE-H(2)S seems to modulate the effect of adipocyte-derived relaxing factor in rat but not in mouse aorta. The present study provides novel insight into the interaction of CSE-H(2)S and perivascular adipose tissue. Furthermore, with additional technical advances, a future clinical approach targeting vascular H(2)S/KCNQ pathways to influence states of vascular dysfunction may be possible.

Journal ArticleDOI
TL;DR: These findings demonstrate the functional importance of oxidative stress, and that COX-2-derived PGF(2α) plays an important role in mediating endothelial dysfunction in RH.
Abstract: Aims: The role of endothelium-derived contracting factors (EDCFs) in regulating renovascular function is yet to be elucidated in renovascular hypertension (RH). The current study investigated whether oxidative stress-dependent cyclooxygenase (COX)-2-derived prostaglandin F2α (PGF2α) impairs endothelial function in renal arteries of renovascular hypertensive rats (RHR). Results: Renal hypertension was induced in rats by renal artery stenosis of both kidneys using the 2-kidney 2-clip model. Acute treatment with reactive oxygen species (ROS) scavengers, COX-2 inhibitors, and thromboxane-prostanoid receptor antagonists, but not COX-1 inhibitors, improved endothelium-dependent relaxations and eliminated endothelium-dependent contractions in RHR renal arteries. Five weeks of treatment with celecoxib or tempol reduced blood pressure, increased renal blood flow, and restored endothelial function in RHRs. Increased ROS production in RHR arteries was inhibited by ROS scavengers, but unaffected by COX-2 inhibitors; whereas increased PGF2α release was reduced by both ROS scavengers and COX-2 inhibitors. ROS also induced COX-2-dependent contraction in RHR renal arteries, which was accompanied by the release of COX-2-derived PGF2α. Further, chronic tempol treatment reduced COX-2 and BMP4 upregulation, p38MAPK phosphorylation, and the nitrotyrosine level in RHR renal arteries. Conclusion: These findings demonstrate the functional importance of oxidative stress, which serves as an initiator of increased COX-2 activity, and that COX-2-derived PGF2α plays an important role in mediating endothelial dysfunction in RH. Innovation: The current study, thus, suggests that drugs targeting oxidative stress-dependent COX-2-derived PGF2α may be useful in the prevention and management of RH. Antioxid. Redox Signal. 16, 363–373.

Journal ArticleDOI
TL;DR: A two-step synthetic process with higher initial annealing temperature but lower growth temperature is developed to reduce domain density and achieve high quality full-surface coverage of monolayer graphene films.
Abstract: Graphene has attracted considerable interest as a potential material for future electronics. Although mechanical peel is known to produce high quality graphene flakes, practical applications require continuous graphene layers over a large area. The catalyst-assisted chemical vapor deposition (CVD) is a promising synthetic method to deliver wafer-sized graphene. Here we present a systematic study on the nucleation and growth of crystallized graphene domains in an atmospheric pressure chemical vapor deposition (APCVD) process. Parametric studies show that the mean size of the graphene domains increases with increasing growth temperature and CH4 partial pressure, while the density of domains decreases with increasing growth temperature and is independent of the CH4 partial pressure. Our studies show that nucleation of graphene domains on copper substrate is highly dependent on the initial annealing temperature. A two-step synthetic process with higher initial annealing temperature but lower growth temperature is developed to reduce domain density and achieve high quality full-surface coverage of monolayer graphene films. Electrical transport measurements demonstrate that the resulting graphene exhibits a high carrier mobility of up to 3000 cm2 V−1 s−1 at room temperature.

Journal ArticleDOI
TL;DR: It is delineated that BMP4 causes EC apoptosis through activation of caspase-3 in a ROS/p38MAPK/JNK-dependent signaling cascade.

Journal ArticleDOI
TL;DR: In this article, a facile and reliable approach for the assembly of crack-free single-crystalline photonic crystals (PCs) with centimeter scale by the synergistic effects of substrate deformation and monomer infiltration/polymerization is presented.
Abstract: We present a facile and reliable approach for the assembly of crack-free single-crystalline photonic crystals (PCs) with centimeter scale by the synergistic effects of substrate deformation and monomer infiltration/polymerization. The critical thickness of crack-free PCs is ∼5.6 μm, below which crack-free PCs can be fabricated on proper substrate. The co-assembling monomer infiltrates and polymerizes in the interstices of the colloidal spheres to form an elastic polymer network, which could lower the tensile stress generated from colloid shrinkage and strengthen the long range interactions of the colloidal spheres. Otherwise, the timely transformation of the flexible substrate releases the residual stress. This approach to centimeter-scale crack-free single-crystalline PCs will not only prompt the practical applications of PCs in high-performance optic devices, but also have great implications for the fabrication of crack-free thin films in other fields, such as wet clays, coating and ceramic industry.

Journal ArticleDOI
20 Aug 2012-PLOS ONE
TL;DR: Findings strongly suggest that TRPM2 channel mediates cellular Ca2+ overload in response to H2O2 and contribute to oxidant-induced apoptotic cell death in vascular endothelial cells.
Abstract: Melastatin-like transient receptor potential channel 2 (TRPM2) is an oxidant-sensitive and cationic non-selective channel that is expressed in mammalian vascular endothelium. Here we investigated the functional role of TRPM2 channels in hydrogen peroxide (H2O2)-induced cytosolic Ca2+ ([Ca2+]i) elavation, whole-cell current increase, and apoptotic cell death in murine heart microvessel endothelial cell line H5V. A TRPM2 blocking antibody (TM2E3), which targets the E3 region near the ion permeation pore of TRPM2, was developed. Treatment of H5V cells with TM2E3 reduced the [Ca2+]i rise and whole-cell current change in response to H2O2. Suppressing TRPM2 expression using TRPM2-specific short hairpin RNA (shRNA) had similar inhibitory effect. H2O2-induced apoptotic cell death in H5V cells was examined using MTT assay, DNA ladder formation analysis, and DAPI-based nuclear DNA condensation assay. Based on these assays, TM2E3 and TRPM2-specific shRNA both showed protective effect against H2O2-induced apoptotic cell death. TM2E3 and TRPM2-specific shRNA also protect the cells from tumor necrosis factor (TNF)-α-induced cell death in MTT assay. In contrast, overexpression of TRPM2 in H5V cells resulted in an increased response in [Ca2+]i and whole-cell currents to H2O2. TRPM2 overexpression also aggravated the H2O2-induced apoptotic cell death. Downstream pathways following TRPM2 activation was examined. Results showed that TRPM2 activity stimulated caspase-8, caspase-9 and caspase-3. These findings strongly suggest that TRPM2 channel mediates cellular Ca2+ overload in response to H2O2 and contribute to oxidant-induced apoptotic cell death in vascular endothelial cells. Down-regulating endogenous TRPM2 could be a means to protect the vascular endothelial cells from apoptotic cell death.

Journal ArticleDOI
TL;DR: This work reports here a facile strategy that allows the one-pot synthesis of uniform dumbbell-like Cu-Ag nanostructures for the first time in which both metal precursors are present simultaneously.
Abstract: Because of their intriguing properties and broad applications in a number of areas, such as catalysis, electronics, photonics, sensing, labeling, imaging and photothermal therapy, the controlled synthesis of noble metal nanostructures has been a research theme for many years. Fundamental studies have revealed that the properties of noble metal nanostructures are highly dependent on their size, shape, and composition. In the past several years, increasing attention has been paid to the controlled synthesis of noble bimetal (or trimetal) nanostructures including core-shell nanostructures, hierarchical nanodendrites, and alloy nanostructures. As a result of coupling the physical/chemical properties or even possible synergistic effects between different metals, noble bimetal (or trimetal) nanostructures are generally more active toward specific reactions than their corresponding single component nanostructures. d,e] Thanks to the great efforts from a large number of research groups, noble bimetal (or trimetal) nanostructures in a wide range of compositions, such as PtPd, PtAu, PtAg, PdAu, d, 5c,9] PdAg, AuAg, and AuCu, have been successfully prepared. However, the strategies developed so far in controlling these nanostructures are mainly based on seed-mediated synthesis, 6,9b–d,10, 11] although some bimetal nanostructures have been prepared by simultaneous or successive reduction of metal precursors. 9e, 11b] Furthermore, the resulting nanostructures are often limited to core-shell nanostructures, nanodendrites, or alloys. It remains a significant challenge to find a seed-free approach to direct prepare dumbbell-like nanostructures, which are expected to have unique properties or advantages that are hard to achieve with single-metal nanostructures. We report here a facile strategy that allows the one-pot synthesis of uniform dumbbell-like Cu-Ag nanostructures. To the best of our knowledge, it is the first time that dumbbell-like Cu-Ag nanostructures have been prepared in which both metal precursors are present simultaneously. In contrast to the typical two-step seed-mediated growth strategies, which use the premade seeds, the proposed synthesis strategy exhibits remarkable simplicity, which is a significant breakthrough in the synthesis of dumbbell-like structures. The influences of the important synthesis parameters on the final product evolution were investigated through controlled studies on the growth of Cu-Ag nanostructures. With respect to the single copper/silver nanostructures, the obtained dumbbell-like Cu-Ag nanostructures show enhanced catalytic activity in the hydrogenation of 4-nitrophenol. To prepare the dumbbell-like Cu-Ag nanostructures, CuCl2·2 H2O, AgNO3, hexadecylamine, glucose and water were added into a vial (see the Experimental Section for details). After the vial had been capped, the mixture was magnetically stirred at room temperature for around 5 h. The resulting homogeneous mixture was then immerged in an oil bath of 100 8C for 3 h under vigorous stirring before it was cooled to room temperature. As the reaction proceeded, the mixture displayed a significant color change from blue to yellow, yellow brown and finally red (digital photographs are shown in Figure S1 in the Supporting Information). The resulting colloidal products were collected by centrifugation and washed several times with hot water. The representative electron microscopic images of the asprepared colloidal products are shown in Figure 1. The images show that the product consisted of uniform elongat-

Journal ArticleDOI
27 Aug 2012-Diabetes
TL;DR: An endothelial-protective effect of PPARδ agonists in diabetic mice through PI3K/Akt/eNOS signaling is demonstrated, suggesting the therapeutic potential of PPARI agonists for diabetic vasculopathy.
Abstract: Recent evidence highlights the therapeutic potential of peroxisome proliferator–activated receptor-δ (PPARδ) agonists to increase insulin sensitivity in diabetes. However, the role of PPARδ in regulating vascular function is incompletely characterized. We investigate whether PPARδ activation improves endothelial function in diabetic and obese mice. PPARδ knockout (KO) and wild-type (WT) mice fed with high-fat diet and db/db mice were used as diabetic mouse models, compared with PPARδ KO and WT mice on normal diet and db/m+ mice. Endothelium-dependent relaxation (EDR) was measured by wire myograph. Flow-mediated vasodilatation (FMD) was measured by pressure myograph. Nitric oxide (NO) production was examined in primary endothelial cells from mouse aortae. PPARδ agonist GW1516 restored EDRs in mouse aortae under high-glucose conditions or in db/db mouse aortae ex vivo. After oral treatment with GW1516, EDRs in aortae and FMDs in mesenteric resistance arteries were improved in obese mice in a PPARδ-specific manner. The effects of GW1516 on endothelial function were mediated through phosphatidylinositol 3-kinase (PI3K) and Akt with a subsequent increase of endothelial nitric oxide synthase (eNOS) activity and NO production. The current study demonstrates an endothelial-protective effect of PPARδ agonists in diabetic mice through PI3K/Akt/eNOS signaling, suggesting the therapeutic potential of PPARδ agonists for diabetic vasculopathy.

Journal ArticleDOI
TL;DR: This study shows for the first time the systematic investigation of effects of Pd atomic shells on Pt-Pd bimetallic nanocatalysts, providing valuable guidelines for designing high-performance catalysts for fuel cell applications.
Abstract: Bimetallic Pt-Pd core-shell nanocrystals (NCs) are synthesized through a two-step process with controlled Pd thickness from sub-monolayer to multiple atomic layers. The oxygen reduction reaction (ORR) catalytic activity and methanol oxidation reactivity of the core-shell NCs for fuel cell applications in alkaline solution are systematically studied and compared based on different Pd thickness. It is found that the Pd shell helps to reduce the over-potential of ORR by up to 50mV when compared to commercial Pd black, while generating up to 3-fold higher kinetic current density. The carbon monoxide poisoning test shows that the bimetallic NCs are more resistant to the CO poisoning than Pt NCs and Pt black. It is also demonstrated that the bimetallic Pt-Pd core-shell NCs can enhance the current density of the methanol oxidation reaction, lowering the over-potential by 35 mV with respect to the Pt core NCs. Further investigation reveals that the Pd/Pt ratio of 1/3, which corresponds to nearly monolayer Pd deposition on Pt core NCs, gives the highest oxidation current density and lowest over-potential. This study shows for the first time the systematic investigation of effects of Pd atomic shells on Pt-Pd bimetallic nanocatalysts, providing valuable guidelines for designing high-performance catalysts for fuel cell applications.

Journal ArticleDOI
TL;DR: It is found that atrial natriuretic peptide, nitric oxide, and cyclic guanosine monophosphate (cGMP) act through protein kinase G (PKG) to inhibit flow-induced increases in [Ca(2+)](i) in M1-CCD cells.
Abstract: The renal cortical collecting duct (CCD) contributes to the maintenance of K + homeostasis by modulating renal K + secretion. Cytosolic Ca 2+ ([Ca 2+ ]i )m ediatesflow-induced K + secretion in the CCD, but the mechanisms regulating flow-induced Ca 2+ entry into renal epithelial cells are not well understood. Here, we found that atrial natriuretic peptide, nitric oxide, and cyclic guanosine monophosphate (cGMP) act

Journal ArticleDOI
TL;DR: It was concluded that all three fatty acids were beneficial in improving lipoprotein profile with DPA n-3 and DHA having better effect on aortic function.


Journal ArticleDOI
TL;DR: NaHS dilates rat cerebral arteries by reducing l-type Ca(2+) currents and suppressing [Ca(2+)](i) of arterial myocyte, indicating that NaHS relaxes cerebral arteries primarily through inhibiting Ca( 2+) influx via Ca(1+) channels.

Journal ArticleDOI
TL;DR: Activation of the EP3 receptor raises baseline blood pressure and contributes to Ang II–dependent hypertension at least partially via enhancing Ca2+ sensitivity and intracellular calcium concentration in vascular smooth muscle cells.
Abstract: Objective— The present studies aimed at elucidating the role of prostaglandin E2 receptor subtype 3 (E-prostanoid [EP] 3) in regulating blood pressure. Methods and Results— Mice bearing a genetic disruption of the EP3 gene (EP3−/−) exhibited reduced baseline mean arterial pressure monitored by both tail-cuff and carotid arterial catheterization. The pressor responses induced by EP3 agonists M&B28767 and sulprostone were markedly attenuated in EP3−/− mice, whereas the reduction of blood pressure induced by prostaglandin E2 was comparable in both genotypes. Vasopressor effect of acute or chronic infusion of angiotensin II (Ang II) was attenuated in EP3−/− mice. Ang II-induced vasoconstriction in mesenteric arteries decreased in EP3−/− group. In mesenteric arteries from wild-type mice, Ang II-induced vasoconstriction was inhibited by EP3 selective antagonist DG-041 or L798106. The expression of Arhgef-1 is attenuated in EP3 deficient mesenteric arteries. EP3 antagonist DG-041 diminished Ang II-induced phosphorylation of myosin light chain 20 and myosin phosphatase target subunit 1 in isolated mesenteric arteries. Furthermore, in vascular smooth muscle cells, Ang II–induced intracellular Ca2+ increase was potentiated by EP3 agonist sulprostone but inhibited by DG-041. Conclusion— Activation of the EP3 receptor raises baseline blood pressure and contributes to Ang II–dependent hypertension at least partially via enhancing Ca2+ sensitivity and intracellular calcium concentration in vascular smooth muscle cells. Selective targeting of the EP3 receptor may represent a potential therapeutic target for the treatment of hypertension.

Journal Article
TL;DR: Recent findings which are summarized in this paper provide new insights into molecular mechanisms of hydrogen sulfide that are crucial for understanding vascular dysfunction in cardiovascular disease and possibly angiogenesis.
Abstract: Hydrogen sulfide is the "third" gasotransmitter on the rise in cardiovascular research. Recent studies show that hydrogen sulfide has a great potential in the regulation of vascular tone of systemic arteries and many molecular targets are discussed. However, the complex mechanism of vascular tone regulation by hydrogen sulfide is only incompletely understood. It seems that a potent interaction of hydrogen sulfide with vascular endothelial growth factor (VEGF) becomes important in angiogenesis, in the process of wound healing, but also in tumor angiogenesis. Hydrogen sulfide exerts anti-inflammatory effects and it could be a pharmacological target in vascular dysfunction in association with obesity-related hypertension as well as in tumor development and progression. However, the underlying molecular pathways still need to be revealed. This review primarily focuses on the regulatory role of hydrogen sulfide in controlling vascular tone. We attempt to provide recent insights into mechanisms by which CSE-dependent hydrogen sulfide plays a role in the regulation of vascular tone by perivascular adipose tissue. The role of KCNQ channels and other ionic permeation pathways as key targets will be discussed. Recent findings which are summarized in this paper provide new insights into molecular mechanisms of hydrogen sulfide that are crucial for understanding vascular dysfunction in cardiovascular disease and possibly angiogenesis. Future research will be extended to investigate the therapeutic potential of hydrogen sulfide and their targets such as KCNQ channels in cardiovascular diseases, angiogenesis and tumor genesis.

Journal ArticleDOI
TL;DR: The measured compositions of formaldehyde were much higher than the theoretical compositions in summer, demonstrating that photochemical reactions significantly contributed to the formaldehyde production in the roadsides.
Abstract: Vehicular emission (VE) is one of the important anthropogenic sources for airborne carbonyls in urban area. Six types of VE-dominated samples were collected at representative locations in Hong Kong where polluted by a particular fueled type of vehicles, including (i) a gas refilling taxis station (liquefied petroleum gas [LPG] emission); (ii) a light-duty passenger car park (gasoline emission); (iii) a minibus station (diesel emission); (iv) a single-deck-bus depot (diesel emission); (v) a double-deck-bus depot (diesel emission); and (vi) a whole-food market entrance for light- and heavy-duty vehicles (diesel emission). A total of 15 carbonyls in the samples were quantified. Formaldehyde was the most abundant carbonyl among the VE-dominated samples, and its contribution to the total quantified amount on a molar basis ranged from 54.8% to 60.8%. Acetaldehyde and acetone were the next two abundant carbonyls. The carbonyls were quantified at three roadside locations in Hong Kong. The highest concentrations o...