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It is urgently necessary to develop more effective anti-influenza agents due to the continuous emergence of drug-resistant strains of influenza virus. Our earlier studies have identified that certain pentacyclic triterpene derivatives are effective inhibitors of influenza virus infection. In the present study, a series of C-28 modified pentacyclic triterpene derivatives via conjugation with a series of polyphenols were synthesized, and their antiviral activities against influenza A/WSN/33 (H1N1) virus in MDCK (Madin-Darby canine kidney) cells were evaluated. Four compounds 23m, 23o, 23q and 23s displayed robust anti-influenza potency with averaged IC50 values at the low-micromole level, surpassing the potency of oseltamivir. In addition, the in vitro cytotoxic activity of the four conjugates against MDCK cells showed no toxicity at 100 μM. Further mechanism studies of compound 23s, one of the best representative conjugates with IC50 value of 5.80 μM and a selective index (SI) value of over 17.2, by hemagglutination inhibition (HI), surface plasmon resonance and molecular modeling indicated that this conjugate bound tightly to the viral envelope hemagglutinin (KD = 15.6 μM), thus blocking the invasion of influenza viruses into host cells.

This paper describes a novel design and a simple, low cost fabrication method of concentration gradient generator which can generate the approximate linear and quadratic concentration gradient curves output. The concentration gradient generators were fabricated in polymethyl-methacrylate (PMMA). The gradient curves can be controlled by the flow velocities. The generator is designed and simulated using CAXA and COMSOL multiphysics, and the concentration gradient generated in the simulation and experiment was analyzed through Origin 8.0 software. The generator was fabricated with the CO2 laser processing machine and thermocompressor. We have carried out a deep research on the processing parameters of laser machine and got an ideal microchannel effect and the microchannels are processed using the CO2 laser processing machine on PMMA substrate. In addition, we also proposed a method of multiple bond to bond chip. Finally, the feasibility of simulation was clearly verified by a mixing experiment with blue ink and yellow ink. This simple microfluidic device can help the study of high-throughput concentration gradient applications such as cell biology of chemotaxis or hypotaxis.

In this study, the traditional hot rolling to fabricate Al/Ti laminated metal composites (LMCs) was improved by using a pre-rolling diffusion process. The effect of the pre-rolling diffusion on microstructure and mechanical properties of Al/Ti LMCs were investigated by various methods, such as optical microscope (OM), scanning electron microscope (SEM), energy dispersive spectrometer (EDS) and tensile tests. The results show that, with increasing diffusion temperature, the thickness in diffusion layer was increased and the mechanical properties of LMCs were improved obviously, which was attributed to the optimized interfacial structure after diffusion process. In addition, the formation of TiAl3 intermetallic compounds (IMCs) was detected in the bonding interface, which played an important role in improving the mechanical properties for Al/Ti LMCs. The predicted results of stress-strain curves from rule of mixture (ROM) indicated that, there existed an extra interfacial strengthening in Al/Ti LMCs beside the mechanical properties provided by the contribution of constituent layers. The pre-rolling diffusion process is effective for the optimization of interfacial structure and improvement of mechanical properties in Al/Ti LMCs.

Oleanolic acid (OA) and echinocystic acid (EA), two naturally occurring pentacyclic oleanane triterpenes, are gaining increasing attention due to their promising pharmacological activities. Conjugation with amphiphilic α(β)-cyclodextrin (CD) via “click chemistry” can improve their solubility and anti-HCV entry potency. In the present work, four water-soluble β-CD-pentacyclic triterpene conjugates were designed and synthesized, in which OA and EA was coupled to one of the primary hydroxyl groups of β-CD via ester and amide bonds. The structures of the conjugates were unambiguously determined by 1H NMR, 13C NMR and HRMS or MALDI-TOF-MS. All the conjugates showed lower hydrophobicity (AlogP) than their parent compounds and no significant cytotoxicity was found to HL-60, A549, Hela and Bel-7402 cells at concentrations up to 10 μmol/L. Further anti-HCV entry activity and mechanism studies are under way in our laboratory.

Titanium dioxide (TiO2) aerogels were prepared with sol–gel ambient pressure drying method by using titanium tetrachloride (TiCl4) as precursor and tetraethoxysilane as modifier, calcinated at different temperature and characterized by X-ray diffraction, transmission electron microscopy and small angle X-ray scattering. The results showed that the TiO2 aerogels remained amorphous under 500 °C, changed to anatase from 600 °C and further changed to rutile from 900 °C. Between 60 °C and 500 °C, the primary particles within the samples concentrated mainly upon small sizes, enlarged and diverged remarkably above 600 °C. The crystalline grains grew and agglomerated with the rise of the calcination temperature. The TiO2 aerogels at a temperature higher than 800 °C have better stability than anatase because of the formation of partial Ti―O―Si bonds. Copyright © 2016 John Wiley & Sons, Ltd.

The emergence of drug resistant variants of the influenza virus has led to a great need to identify novel and effective antiviral agents. In our previous study, a series of sialic acid (C-2 and C-4)-pentacyclic triterpene conjugates have been synthesized, and a five-fold more potent antiviral activity was observed when sialic acid was conjugated with pentacyclic triterpene via C-4 than C-2. It was here that we further reported the synthesis and anti-influenza activity of novel sialic acid (C-5 and C-9)-pentacyclic triterpene conjugates. Their structures were confirmed by ESI-HRMS, 1H-NMR, and 13C-NMR spectroscopic analyses. Two conjugates (26 and 42) showed strong cytotoxicity to MDCK cells in the CellTiter-Glo assay at a concentration of 100 μM. However, they showed no significant cytotoxicity to HL-60, Hela, and A549 cell lines in MTT assay under the concentration of 10 μM (except compound 42 showed weak cytotoxicity to HL-60 cell line (10 μM, ~53%)). Compounds 20, 28, 36, and 44 displayed weak potency to influenza A/WSN/33 (H1N1) virus (100 μM, ~20–30%), and no significant anti-influenza activity was found for the other conjugates. The data suggested that both the C-5 acetylamide and C-9 hydroxy of sialic acid were important for its binding with hemagglutinin during viral entry into host cells, while C-4 and C-2 hydroxy were not critical for the binding process and could be replaced with hydrophobic moieties. The research presented herein had significant implications for the design of novel antiviral inhibitors based on a sialic acid scaffold.

Toroidal Alfven eigenmodes (TAE) and ellipticity induced Alfven eigenmodes (EAE) driven by fast electrons are observed for the first time in steady-state EAST plasmas heated by lower hybrid wave (LHW). For the analyzed discharge four modes appear after the injection of LHW. Comparing experimental observations with simulation, high frequency modes are located near and low frequency mode is near . The two positions are very close to where most of the heating power is deposited and population inversion occurs. Analysis of resonance condition between particles and waves indicates that barely-passing, deeply trapped and barely-trapped electrons can drive the mode.

We report on current profile evolution in EAST NBI driven plasmas where two neutral beams are injected, one during the current ramp phase and the second during flattop. At the end of the current ramp phase, it is found that a flat q profile with q 0 ~ 1 is achieved with low magnetic shear in the core. It is observed that plasma current and density both relax much faster than resistive time, even in the absence of sawtooth activity when H–L transition occurs. Density fluctuations associated with magnetic perturbations (3/2) as a precursor to the H–L transition are observed. It is likely that these modes play a role in fast current transport.

A set of in-vessel resonant magnetic perturbation (RMP) coil has been recently installed in EAST. It can generate a range of spectrum, and there is a relatively large window for edge localized mode (ELM) control according to the vacuum field modeling of the edge magnetic island overlapping area. Observation of mitigation and suppression of ELM in slow rotating plasmas during the application of an n = 1 RMP is presented in this paper. Strong ELM mitigation effect is observed in neutral beam injection heating plasmas. The ELM frequency increases by a factor of 5, and the crash amplitude and the particle flux are effectively reduced by a similar factor. Clear density pump-out and magnetic braking effects are observed during the application of RMP. Footprint splitting is observed during ELM mitigation and agrees well with vacuum field modelling. Strong ELM mitigation happens after a second sudden drop of plasma density, which indicates the possible effect due to field penetration of the resonant harmonics near the pedestal top, where the electron perpendicular rotation becomes flat and close to zero after the application of RMP. ELM suppression is achieved in a resonant window during the scan of the n = 1 RMP spectrum in radio-frequency (RF) dominant heating plasmas. The best spectrum for ELM suppression is consistent with the resonant peak of RMP by taking into account of linear magnetohydrodynamics plasma response. There is no mode locking during the application of n = 1 RMP in ELMy H-mode plasmas, although the maximal coil current is applied.

In the experimental advanced superconducting tokamak, density pump-out phenomena were observed by using a multi-channel polarimeter-interferometer system under different heating schemes of ion cyclotron resonant heating, electron cyclotron resonance heating, and neutral beam injection. The density pump-out was also induced with application of resonant magnetic perturbation, accompanied with a degradation of particle confinement. For the comparison analysis in all heating schemes, the typical plasma parameters are plasma current 400 kA, toroidal field 2 T, and line average density 2 × 1019 m−3. The experimental results show that the degree of pump-out is concerned with electron density and heating power. Low density deuterium low confinement (L-mode) plasmas (

Increasing the density in a tokamak is limited by the so-called density limit, which is generally performed as an appearance of disruption causing loss of plasma confinement, or a degradation of high confinement mode which could further lead to a H → L transition. The L-mode and H-mode density limit has been investigated in EAST tokamak. Experimental results suggest that density limits could be triggered by either edge cooling or excessive central radiation. The L-mode density limit disruption is generally triggered by edge cooling, which leads to the current profile shrinkage and then destabilizes a 2/1 tearing mode, ultimately resulting in a disruption. The L-mode density limit scaling agrees well with the Greenwald limit in EAST. The observed H-mode density limit in EAST is an operational-space limit with a value of . High density H-mode heated by neutral beam injection (NBI) and lower hybrid current drive (LHCD) are analyzed, respectively. The constancy of the edge density gradients in H-mode indicates a critical limit caused perhaps by e.g. ballooning induced transport. The maximum density is accessed at the H → L transition which is generally caused by the excessive core radiation due to high Z impurities (Fe, Cu). Operating at a high density () is favorable for suppressing the beam shine through NBI. High density H-mode up to could be sustained by 2 MW 4.6 GHz LHCD alone, and its current drive efficiency is studied. Statistics show that good control of impurities and recycling facilitate high density operation. With careful control of these factors, high density up to 0.93 stable H-mode operation was carried out heated by 1.7 MW LHCD and 1.9 MW ion cyclotron resonance heating with supersonic molecular beam injection fueling.