Anomalous Resistivity and Electron Heating by Lower Hybrid Drift Waves during Magnetic Reconnection with a Guide Field.

The lower hybrid drift wave (LHDW) has been a candidate for anomalous resistivity and electron heating inside the electron diffusion region of magnetic reconnection. In a laboratory reconnection layer with a finite guide field, quasielectrostatic LHDW (ES-LHDW) propagating along the direction nearly perpendicular to the local magnetic field is excited in the electron diffusion region. ES-LHDW generates large density fluctuations (δn_{e}, about 25% of the mean density) that are correlated with fluctuations in the out-of-plane electric field (δE_{Y}, about twice larger than the mean reconnection electric field). With a small phase difference (∼30°) between two fluctuating quantities, the anomalous resistivity associated with the observed ES-LHDW is twice larger than the classical resistivity and accounts for 20% of the mean reconnection electric field. After we verify the linear relationship between δn_{e} and δE_{Y}, anomalous electron heating by LHDW is estimated by a quasilinear analysis. The estimated electron heating is about 2.6±0.3 MW/m^{3}, which exceeds the classical Ohmic heating of about 2.0±0.2 MW/m^{3}. This LHDW-driven heating is consistent with the observed trend of higher electron temperatures when the wave amplitude is larger. Presented results provide the first direct estimate of anomalous resistivity and electron heating power by LHDW, which demonstrates the importance of wave-particle interactions in magnetic reconnection.

De-wetting of evaporating drops on regular patterns of triangular posts.

Directional wicking and spreading of liquids can be achieved by regular micro-patterns of specifically designed topographic features that break the reflection symmetry of the underlying pattern. The present study aims to understand the formation and stability of wetting films during the evaporation of volatile liquid drops on surfaces with a micro-pattern of triangular posts arranged in a rectangular lattice. Depending on the density and aspect ratio of the posts, we observe either spherical-cap shaped drops with a mobile three-phase contact line or the formation of circular or angular drops with a pinned three-phase contact line. Drops of the latter class eventually evolve into a liquid film extending to the initial footprint of the drop and a shrinking cap-shaped drop sitting on the film. The drop evolution is controlled by the density and aspect ratio of the posts, while no influence of the orientation of the triangular posts on the contact line mobility becomes evident. Our experiments corroborate previous results of systematic numerical energy minimization, predicting that conditions for a spontaneous retraction of a wicking liquid film depend weakly on the orientation of the film edge relative to the micro-pattern.

Molecular Dynamics Study of Clathrate-like Ordering of Water in Supersaturated Methane Solution at Low Pressure.

Using molecular dynamics, the evolution of a metastable solution for "methane + water" was studied for concentrations of 3.36, 6.5, 9.45, 12.2, and 14.8 mol% methane at 270 K and 1 bar during 100 ns. We have found the intriguing behavior of the system containing over 10,000 water molecules: the formation of hydrate-like structures is observed at 6.5 and 9.45 mol% concentrations throughout the entire solution volume. This formation of "blobs" and the following amorphous hydrate were studied. The creation of a metastable methane solution through supersaturation is the key to triggering the collective process of hydrate formation under low pressure. Even the first stage (0-1 ns), before the first fluctuating cavities appear, is a collective process of H-bond network reorganization. The formation of fluctuation cavities appears before steady hydrate growth begins and is associated with a preceding uniform increase in the water molecule's tetrahedrality. Later, the constantly presented hydrate cavities become the foundation for a few independent hydrate nucleation centers, this evolution is consistent with the labile cluster and local structure hypotheses. This new mechanism of hydrogen-bond network reorganization depends on the entropy of the cavity arrangement of the guest molecules in the hydrate lattice and leads to hydrate growth.

Unsteady Magnetopause Reconnection Under Quasi-Steady Solar Wind Driving.

The intrinsic temporal nature of magnetic reconnection at the magnetopause has been an active area of research. Both temporally steady and intermittent reconnection have been reported. We examine the steadiness of reconnection using space-ground conjunctions under quasi-steady solar wind driving. The spacecraft suggests that reconnection is first inactive, and then activates. The radar further suggests that after activation, reconnection proceeds continuously but unsteadily. The reconnection electric field shows variations at frequencies below 10 mHz with peaks at 3 and 5 mHz. The variation amplitudes are ∼10-30 mV/m in the ionosphere, and 0.3-0.8 mV/m at the equatorial magnetopause. Such amplitudes represent 30%-60% of the peak reconnection electric field. The unsteadiness of reconnection can be plausibly explained by the fluctuating magnetic field in the turbulent magnetosheath. A comparison with a previous global hybrid simulation suggests that it is the foreshock waves that drive the magnetosheath fluctuations, and hence modulate the reconnection.

Magnetopause Reconnection and Indents Induced by Foreshock Turbulence.

Based on global hybrid simulation results, we predict that foreshock turbulence can reach the magnetopause and lead to reconnection as well as Earth-sized indents. Both the interplanetary magnetic field (IMF) and solar wind are constant in our simulation, and hence, all dynamics are generated by foreshock instabilities. The IMF in the simulation is mostly Sun-Earth aligned with a weak northward and zero dawn-dusk component, such that subsolar magnetopause reconnection is not expected without foreshock turbulence modifying the magnetosheath fields. We show a reconnection example to illustrate that the turbulence can create large magnetic shear angles across the magnetopause to induce local bursty reconnection. Magnetopause reconnection and indents developed from the impact of foreshock turbulence can potentially contribute to dayside loss of planetary plasmas.

Direct observation of wetting behavior of water drops on single micro-scale roughness surfaces of rose petal effect.

HYPOTHESIS: It has been verified that a surface of single micro-scale structures with certain roughness could exhibit petal effect. That is, water drops with a contact angle larger than 150° would pin on the petal effect surface. It is conjectured that the water drop could pin on the single micro-scale roughness petal effect surface by totally infiltrating into spaces (or grooves) between micro-pillars. EXPERIMENTS: An inverted optical microscopy system is synchronically applied in the process of advancing/receding contact angle (ACA/RCA) measurements to directly observe the wetting behavior of water droplets on hydrophobic patterned surfaces with regular arrays of square micro-pillars. FINDINGS: A sequence of wetting behavior evolution, Wenzel â†’ petal â†’ pseudo-lotus â†’ lotus, is observed on the hydrophobic patterned surfaces along with increasing surface roughness. It is interesting to observe a Cassie-Wenzel transition for water drops on a petal substrate during the ACA measurement (embedded needle method), leading to two ACAs, one before (in Cassie state) and one after the transition (in Wenzel state). Thus, the petal substrates have large contact angle hysteresis (CAH) (with both ACA and RCA in Wenzel state) to pin the water drop in Wenzel state. A Cassie-Wenzel transition is consistently observed during the evaporation process of water drops on pseudo-lotus substrates, leading to two RCAs: one in Cassie state and one in Wenzel state. The pseudo-lotus substrates have CAH (with both ACA and RCA in Cassie state) small enough to make water drops easily slide off.

Effect of Small Cage Guests on Dissociation Properties of Tetrahydrofuran Hydrates.

It is well understood that tetrahydrofuran (THF) molecules are able to stabilize the large cages (51264) of structure II to form the THF hydrate with empty small cages even at atmospheric pressure. This leaves the small cages to store gas molecules at relatively lower pressures and higher temperatures. The dissociation enthalpy and temperature strongly depend on the size of gas molecules enclathrated in the small cages of structure II THF hydrate. A high-pressure microdifferential scanning calorimeter was applied to measure the dissociation enthalpies and temperatures of THF hydrates pressurized by helium and methane under a constant pressure ranging from 0.10 to 35.00 MPa and a wide THF concentration ranging from 0.25 to 8.11 mol %. The dissociation temperature of binary He + THF and methane + THF hydrates increases along with an increase in the THF concentration in the liquid phase at a fixed pressure (e.g., 30 MPa), reaching a maximum value of 280.8 and 312.8 K, respectively, at stoichiometric concentration (5.56 mol % THF), and then remains nearly constant for even higher THF concentrations (>5.56 mol %). The effect of gas occupancy in the small cages on the dissociation enthalpy of He + THF and methane + THF mixed hydrates was further examined by using molecular dynamics (MD) simulations. The dissociation enthalpy of the He-THF mixed hydrates is independent of pressure with an average of 5.68 kJ/mol H2O over the pressure ranging from 0.10 to 30.0 MPa, consistent with the MD results of the He-THF mixed hydrates with low single occupancy (<23%) of helium molecules in the small cages. Consequently, the heat of adsorption of helium molecules in the small cages of the He-THF mixed hydrates is rather too weak to be identified. On the other hand, the dissociation enthalpy of the methane-THF hydrates increases from 9.11 to 10.01 kJ/mol H2O along with an increase in methane pressure over the pressure ranging from 5.0 to 30.0 MPa, consistent with the MD results of the methane-THF mixed hydrates with full occupancy of methane molecules in the small cages. These findings provide important information for the design of a potential medium of gas storage and transportation.

Dynamic Behavior of the Structural Phase Transition of Hydrogel Formation Induced by Temperature Ramp and Addition of Ibuprofen.

Understanding the dynamic behavior of hydrogel formation induced by a temperature ramp is essential for the design of gel-based injectable formulation as drug-delivery vehicles. In this study, the dynamic behavior of the hydrogel formation of Pluronic F108 aqueous solutions within different heating rates was explored in both macroscopic and microscopic views. It was discovered that when the heating rate is increased, the gelation temperature window (hard gel region) shrinks and the mechanical strength of the hydrogel decreases. A given system at different heating rates would lead to different crystalline structural evolutions. The time-resolved small-angle X-ray scattering (SAXS) experiments at a heating rate of 10 °C/min disclose that the crystalline structure of micelle packing in the hydrogel exhibits a series of transitions: hexagonal close-packed (HCP) to face-centered cubic (FCC) and body-centered cubic (BCC) structures coexisting and then to the BCC structure along with the increasing temperature. For the system at equilibrium, the BCC structure exclusively dominates the system. Furthermore, the addition of a hydrophobic model drug (ibuprofen) to the F108 aqueous solution promotes hard gel formation at even lower temperatures and concentrations of F108. The SAXS results for the system with ibuprofen at a heating rate of 10 °C/min demonstrate a mixture of FCC and BCC structures coexisting over the whole gelation window compared to the BCC structure that exclusively dominates the system at equilibrium. The addition of ibuprofen would alter the structural evolution to change the delivery path of the encapsulated drug, which is significantly related to the performance of drug release.

Self-pinning of silica suspension droplets on hydrophobic surfaces.

HYPOTHESIS: Self-pinning induced by the aggregation of particles at the edge of a pinned drop is a pre-requisite for the coffee ring formation. The edge (three-phase contact line) of a suspension drop on a hydrophobic surface would depin and shrink in the early stage of evaporation process. It is plausible to conjecture that the self-pinning of silica suspension drops depends on the particle size and surface property. EXPERIMENTS: Two substrate materials, the alkylsilane coated surfaces and the polydimethylsiloxane surfaces, and three different sizes of silica particles are used to explore the criterion of self-pinning of silica suspension drops on these hydrophobic surfaces. The evaporation process of droplets is recorded and further analyzed. FINDINGS: The pinning concentration of silica suspensions of a fixed size linearly depends on the receding contact angle of the surface, irrelevant to the substrate material and initial particle concentration. The pinning concentration decreases along with an increase in particle size. In addition, the pinning concentrations of bi-dispersed silica (e.g. 400 + 1000 nm) suspensions have an excellent agreement with that of larger size (1000 nm) particle system. That implies that the larger particle dominates the system of bi-dispersed silica suspensions to initiate the self-pinning, further verified by SEM images.

Electron Energy Partition across Interplanetary Shocks. I. Methodology and Data Product.

Analyses of 15,314 electron velocity distribution functions (VDFs) within ±2 hr of 52 interplanetary (IP) shocks observed by the Wind spacecraft near 1 au are introduced. The electron VDFs are fit to the sum of three model functions for the cold dense core, hot tenuous halo, and field-aligned beam/strahl component. The best results were found by modeling the core as either a bi-kappa or a symmetric (or asymmetric) bi-self-similar VDF, while both the halo and beam/strahl components were best fit to bi-kappa VDF. This is the first statistical study to show that the core electron distribution is better fit to a self-similar VDF than a bi-Maxwellian under all conditions. The self-similar distribution deviation from a Maxwellian is a measure of inelasticity in particle scattering from waves and/or turbulence. The ranges of values defined by the lower and upper quartiles for the kappa exponents are κ ec ~ 5.40-10.2 for the core, κ eh ~ 3.58-5.34 for the halo, and κ eb ~ 3.40-5.16 for the beam/strahl. The lower-to-upper quartile range of symmetric bi-self-similar core exponents is s ec ~ 2.00-2.04, and those of asymmetric bi-self-similar core exponents are p ec ~ 2.20-4.00 for the parallel exponent and q ec ~ 2.00-2.46 for the perpendicular exponent. The nuanced details of the fit procedure and description of resulting data product are also presented. The statistics and detailed analysis of the results are presented in Paper II and Paper III of this three-part study.

Directional Liquid Wicking in Regular Arrays of Triangular Posts.

Wicking of wetting liquids into micropatterns of posts with homogeneous triangular cross section is studied in experiments and by numerical energy minimizations. To test for directional wicking, we fabricated regular arrays of posts with various combinations of line fractions and aspect ratios using standard photolithography processes. In agreement with numerical energy minimizations of the liquid film morphology, we find spontaneous wicking in the experiments only for line fractions and aspect ratios where the homogeneous liquid film represents the state of lowest interfacial free energy and where no local energy minimum could be detected in our numerical energy minimizations. The numerical results further demonstrate that the stability of a certain morphology of the terminal meniscus controls the direction of wicking relative to the orientation of the triangular posts. The observed selectivity of spontaneous wicking with respect to the meniscus orientation can be exploited to build a microfluidic rectifier for partially wetting liquids.

Role of molecular weight and hydrophobicity of amphiphilic tri-block copolymers in temperature-dependent co-micellization process and drug solubility.

The binary P123 + F108, + F98, + F88, + F68, + F87 and + P84 systems were used to systematically explore the effect of molecular weight and hydrophobicity of Pluronic on the tendency of cooperative binding between parent copolymers and solubility of drug (ibuprofen) in these mixed Pluronic systems. Temperature-dependent co-micellization process in these systems was carefully investigated by using high sensitivity differential scanning calorimeter (HSDSC), dynamic light scattering (DLS) and small angle X-ray scattering (SAXS). All the HSDSC thermograms for these systems consistently exhibit two endothermic (micellization) peaks apart by at least 13.3 °C. It was evidenced that micelles are mainly formed by P123, the copolymer with a lower critical micelle temperature (CMT), at low temperatures. Raising temperature would dehydrate the other Pluronic with a higher CMT to be integrated into the neat P123 micelles developed at low temperatures. When the temperature is further increased beyond the second endothermic peak, the mixed micelles with a two-shell structure and characteristic corona lengths of their parent copolymers are observed to prove the existence of cooperative binding between parent copolymers. All the binary mixed Pluronic systems used in this study exhibit cooperative binding to form unimodal distribution of mixed micelles, except the P123 + F68 system. The SAXS results show that P123 + F68 system at 65 °C exhibits bimodal distribution of aggregates with coexisting of neat F68 micelles (65% in number) and P123 + F68 mixed micelles (35% in number). It is interesting to find out that P123 and F68 with distinct polypropylene oxide (PPO) moieties (i.e., a difference of 37 PO units) would exhibit very weak cooperative binding to partially form mixed micelles. Addition of ibuprofen in the P123 + F68 system would substantially enhance the cooperative binding between P123 and F68 to form bimodal distribution of aggregates with coexisting of neat F68 micelles (drops down to 30% in number) and P123 + F68 mixed micelles (increases up to 70% in number). For the systems with ibuprofen incorporated, SAXS results demonstrate that the drug is mainly encapsulated in the core of neat micelles developed at low temperatures. The solubility of ibuprofen in the 0.5 wt% P123 + 0.368 wt% P84 system is as high as 2.62 mg/ml, which is 114 times more than that in pure water at 37 °C.

Synthesis of Methane Hydrate from Ice Powder Accelerated by Doping Ethanol into Methane Gas.

Clathrate hydrate is considered to be a potential medium for gas storage and transportation. Slow kinetics of hydrate formation is a hindrance to the commercialized process development of such applications. The kinetics of methane hydrate formation from the reaction of ice powder and methane gas doped with/without saturated ethanol vapor at constant pressure of 16.55 ± 0.20 MPa and constant temperature ranging from -15 to -1.0 °C were investigated. The methane hydrate formation can be dramatically accelerated by simply doping ethanol into methane gas with ultralow ethanol concentration (<94 ppm by mole fraction) in the gas phase. For ethanol-doped system 80.1% of ice powder were converted into methane hydrate after a reaction time of 4 h, while only 26.6% of ice powder was converted into methane hydrate after a reaction time of 24 h when pure methane gas was used. Furthermore, this trace amount of ethanol could also substantially suppress the self-preservation effect to enhance the dissociation rate of methane hydrate (operated at 1 atm and temperatures below the ice melting point). In other words, a trace amount of ethanol doped in methane gas can act as a kinetic promoter for both the methane hydrate formation and dissociation.

The Protective Role of Garlic on Allergen-Induced Airway Inflammation in Mice.

Asthma is the most prevalent chronic respiratory disease worldwide. Garlic extracts have long been used as a food source and in traditional medicine. Crude extracts of garlic are used as an anti-inflammatory agent and have been reported to exhibit antiasthmatic properties. However, molecular mechanisms of garlic extracts in the context of antiasthmatic airway inflammation are still unclear. In this study, the antiasthmatic effect of garlic extracts on Th1, Th2, and Th3 cytokine profiles and immunoregulatory mechanism were explored using an animal model of allergic asthma. Garlic extracts significantly reduced total inflammatory cell counts and eosinophil infiltration and decreased the production of Dermatophagoides pteronyssinus IgE in serum and Th1/Th2/Th3 cytokine in bronchoalveolar fluid. Enzyme-linked immunosorbent assay analysis demonstrated that garlic extracts downregulated the levels of cytokines and chemokines, namely Th2-related IL-4, IL-5, and IL-13; but they simultaneously upregulated Th1-related IFN-γ, IL-12, and Th3-related IL-10 and TGF-ß expression in BALF. The mechanism may be ascribed to the modulation of Th1-, Th2-, and Th3-related cytokine imbalance.

Synergistic Effect of Binary Mixed-Pluronic Systems on Temperature Dependent Self-assembly Process and Drug Solubility.

Mixed Pluronic micelles from very hydrophobic and very hydrophilic copolymers were selected to scrutinize the synergistic effect on the self-assembly process as well as the solubilization capacity of ibuprofen. The tendency of mixing behavior between parent copolymers was systematically examined from two perspectives: different block chain lengths at same hydrophilicity (L92 + F108, +F98, +F88, and +F68), as well as various hydrophobicities at the same PPO moiety (L92 + F88, +F87, and +P84). Temperature-dependent micellization in these binary systems was clearly inspected by the combined use of high sensitivity differential scanning calorimeter (HSDSC) and dynamic light scattering (DLS). Changes in heat capacity and size of aggregates at different temperatures during the whole micellization process were simultaneously observed and examined. While distinction of block chain length between parent copolymers increases, the monodispersity of the binary Pluronic systems decreases. However, parent copolymers with distinct PPO moieties do not affirmatively lead to non-cooperative binding, such as the L92 + P84 system. The addition of ibuprofen promotes micellization as well as stabilizes aggregates in the solution. The partial replacement of the hydrophilic Pluronic by a more hydrophobic Pluronic L92 would increase the total hydrophobicity of mixed Pluronics used in the system to substantially enhance the solubility of ibuprofen. The solubility of ibuprofen in the 0.5 wt % L92 + 0.368 wt % P84 system is as high as 4.29 mg/mL, which is 1.4 times more than that of the 0.868 wt % P84 system and 147 times more than that in pure water at 37 °C.

Erratum: Synergistic Effect of Binary Mixed-Pluronic Systems on Temperature Dependent Self-Assembly Process and Drug Solubility. Polymers 2018, 10, 105.

The authors wish to make changes to the above-mentioned published paper [1].[...].

Increase of human prostate cancer cell (DU145) apoptosis by telmisartan through PPAR-delta pathway.

The effect of telmisartan on prostate cancer DU145 cell survival and the underlying mechanism of apoptosis involving peroxisome proliferator-activated receptor (PPAR) pathway were investigated. Cultured DU145 cells were treated pharmacologically with telmisartan and GSK0660 (a PPAR-delta antagonist); or by RNA interference with siRNA of PPAR-delta. The treatment effects on cell survival were evaluated with cell viability assay, life and dead cell staining and flow cytometry. Western blot analysis for PPAR-delta protein expression was also performed. The results showed that telmisartan (0-80 µm) dose-dependently reduced DU145 cell survival. Flow cytometry demonstrated cancer cell cycle arrest with increase of sub-G1 phase. GSK0660 partially but significantly restored the telmisartan-treated cell viability. Similarly, siRNA of PPAR-delta significantly reversed the telmisartan-induced apoptosis. Western blot showed that telmisartan significantly increased DU145 cell PPAR-delta protein expression. Co-incubation with siRNA of PPAR-delta inhibited the telmisartan effect of PPAR-delta up-regulation. In conclusion, telmisartan induces prostate cancer DU145 cells apoptosis through the up-regulation of PPAR-delta protein expression. Pharmacological inhibition or genetic silencing of PPAR-delta activity can both reverse the telmisartan-induced apoptotic effect. Thus the PPAR-delta pathway might be a potential target for the treatment of prostate cancer.

Molecular dynamics study on the nucleation of methane + tetrahydrofuran mixed guest hydrate.

The nucleation of methane (CH4), tetrahydrofuran (THF), and CH4 + THF hydrates are investigated by microsecond MD simulations. These three systems exhibit distinct structural developments in the aqueous phase quantified by the formation of cage structures of hydrogen bonded water molecules. The development of a cluster of cages in the CH4 system is limited by the scarce CH4 molecules in the solution, while in the THF system it is limited by the short lifetime of cages. In the CH4 + THF mixed guest system, a small cluster of caged CH4 molecules can be rapidly stabilized by abundant neighboring cages of THF molecules. Therefore, the induction time of the CH4 + THF mixed guest system is found to be significantly shorter than that of the pure CH4 and pure THF systems. Furthermore, the structure of cages found in the initially formed cage clusters are often different from the typical 5(12)6(n) (n = 0, 2, 3, 4) cages observed in clathrate hydrate systems. The cluster of cages may grow or transform into structure I or II clathrate hydrate in the later stages.

Canavanine activates imidazoline I-2 receptors to reduce hyperglycemia in type 1-like diabetic rats.

Canavanine is a guanidinium derivative that has the basic structure of a ligand for the imidazoline receptor (I-R). Furthermore, canavanine is found in an herb that has been shown to improve diabetic disorders. Thus, the present study was designed to investigate the anti-hyperglycemic action of canavanine in rats with streptozotocin (STZ)-induced type 1-like diabetes. Canavanine decreased hyperglycemia in the STZ-induced diabetic rats, and this action was blocked by the antagonist specific to imidazoline I-2 receptors (I-2R), BU224, in a dose-dependent manner. Additionally, canavanine increased the plasma ß-endorphin level, as measured using enzyme-linked immunosorbent assay (ELISA), and this increase was also blocked by BU224 in the same manner. Moreover, amiloride at a dose sufficient to block I-2AR attenuated the actions of canavanine, including the increased ß-endorphin level and the antihyperglycemic effect. Otherwise, canavanine increased the radioactive glucose uptake into skeletal muscles isolated from the diabetic rats. Furthermore, canavanine increased the phosphorylation of AMPK measured using Western blot analysis in these isolated skeletal muscles in a dose-dependent manner. Additionally, the insulin sensitivity of the diabetic rats was markedly increased by canavanine, and this action was also blocked by BU224. Overall, canavanine is capable of activating imidazoline I-2R; I-2AR is linked to an increase in the plasma level of ß-endorphin, and I-2BR is related to effects on the glucose uptake by skeletal muscle that reduces hyperglycemia in type 1-like diabetic rats. Therefore, canavanine can be developed as effective agent to treat the diabetic disorders in the future.

Canavanine increases glucose uptake in C2 C12 cells through the activation of imidazoline I-2B receptors.

Canavanine is a guanidinium derivative that contains the basic structure of the ligand(s) of imidazoline receptor (I-R). Canavanine has been reported to activate the imidazoline I-3 receptor (I-3R) both in vivo and in vitro. Additionally, the activation of the imidazoline I-2B receptor (I-2BR) by guanidinium derivatives may increase glucose uptake. Therefore, the effect of canavanine on the I-2BR was investigated in the present study. Glucose uptake into cultured C2 C12 cells was determined using the radio-ligated tracer 2-[(14) C]-deoxy-glucose. The changes in 5' AMP-activated protein kinase (AMPK) expression were also identified using Western blotting analysis. The canavanine-induced glucose uptake was inhibited in a dose-dependent manner by BU224 (0.01-1 µmol/L), which is a specific I-2BR antagonist, in the C2 C12 cells. Additionally, the canavanine-stimulated AMPK phosphorylation and glucose transporter (GLUT4) expression were also sensitive to BU224 inhibition in the C2 C12 cells. Moreover, both canavanine-stimulated glucose uptake and AMPK phosphorylation were attenuated by high concentrations of amiloride (1-2 µmol/L), which is another established I-2BR inhibitor, in a dose-dependent manner in C2 C12 cells. Additionally, compound C abolished the canavanine-induced glucose uptake and AMPK phosphorylation at a concentration (0.1 µmol/L) sufficient to inhibit AMPK. In conclusion, these data demonstrated that canavanine has an ability to activate I-2BR through the AMPK pathway to increase glucose uptake, which indicates I-2BR as a new target for diabetic therapy.