Screening an In-House Isoquinoline Alkaloids Library for New Blockers of Voltage-Gated Na+ Channels Using Voltage Sensor Fluorescent Probes: Hits and Biases

Voltage-gated Na⁺ (Na_V) channels are significant therapeutic targets for the treatment of cardiac and neurological disorders, thus promoting the search for novel Na_V channel ligands. With the objective of discovering new blockers of Na_V channel ligands, we screened an In-House vegetal alkaloid library using fluorescence cell-based assays. We screened 62 isoquinoline alkaloids (IA) for their ability to decrease the FRET signal of voltage sensor probes (VSP), which were induced by the activation of Na_V channels with batrachotoxin (BTX) in GH3b6 cells. This led to the selection of five IA: liriodenine, oxostephanine, thalmiculine, protopine, and bebeerine, inhibiting the BTX-induced VSP signal with micromolar IC₅₀. These five alkaloids were then assayed using the Na⁺ fluorescent probe ANG-2 and the patch-clamp technique. Only oxostephanine and liriodenine were able to inhibit the BTX-induced ANG-2 signal in HEK293-hNa_V1.3 cells. Indeed, liriodenine and oxostephanine decreased the effects of BTX on Na⁺ currents elicited by the hNa_V1.3 channel, suggesting that conformation change induced by BTX binding could induce a bias in fluorescent assays. However, among the five IA selected in the VSP assay, only bebeerine exhibited strong inhibitory effects against Na⁺ currents elicited by the hNav1.2 and hNav1.6 channels, with IC₅₀ values below 10 µM. So far, bebeerine is the first BBIQ to have been reported to block Na_V channels, with promising therapeutical applications.     

The Antioxidant and Hypolipidemic Effects of Mesona Chinensis Benth Extracts

In this study, the antioxidant and hypolipidemic effects of Mesona Chinensis Benth (MCB) extracts were evaluated. Seven fractions (F0, F10, F20, F30, F40, F50 and MTF) were obtained from the MCB ethanol extracts. Compared to the commercial antioxidants (vitamin C), MTF and F30 exhibited higher antioxidant activities in the antiradical activity test and the FRAP assay. The half-inhibition concentration (IC50) for MTF and F30 were 5.323 µg/mL and 5.278 µg/mL, respectively. MTF at 200 µg/mL significantly decreased the accumulation of TG in oleic acid (OA)-induced HepG2 cells and reversed the inhibitory effect of Compound C on AMPK (MTF and F30 significantly increased the glucose utilization of insulin-induced HepG2 cells). In addition, the components of MTF were identified by HPLC-MS, which were caffeic acid, quercetin 3-O-galactoside, isoquercetin, astragalin, rosmarinic acid, aromadendrin-3-O-rutinoside, rosmarinic acid-3-O-glucoside and kaempferol-7-O-glucoside. Through statistical correlations by Simca P software, it was found that the main antioxidant and hypolipidemic components of MCB might be caffeic acid, kaempferol-7-O-glucoside, rosmarinic acid-3-O-glucoside and aromadendrin-3-O-rutinoside, which may play important roles in the AMPK pathway. MTF and F30 in MCB could be potential health products for the treatment of hyperlipidemia.     

硅烷化磁铁粉固定胰蛋白酶的研究

分别以硅烷化磁铁粉、硅烷磁化脱乙酰几丁质及脱乙酰几丁质作载体,甲醛或戊二醛为交联剂,对胰蛋白酶的固定化条件及所制备的固定化酶的性质进行了研究．研究了载体种类、交联剂和ｐＨ值以及载体与酶比例等因素对胰蛋白酶固定化的影响．研究了不同载体固定胰蛋白酶的特点,证明以硅烷化试剂和甲醛作交联剂的硅烷化磁铁粉作胰蛋白酶固定化的载体具有明显优点,所制备的硅烷化磁铁粉固定化胰蛋白酶酶学性质明显优于可溶性胰蛋白酶     

Laser–Induced Fluorescence Detection of Carbamates Traces in Water

The absorption and fluorescence spectra of carbaryl (CB), carbofuran (CF) and carbendazim (MBC) have been studied. Fluorescence lifetime and fluorescence quantum yields are also reported as well as the influence of pH, solvent and presence of humic acids on fluorescence. The limit of detection (LD) of the three compounds has been measured by direct analysis by laser-induced fluorescence (LIF) using a pulsed YAG laser with an Optical Parametric Oscillator (OPO) as excitation source and an Intensified Charged Coupled Device (ICCD) camera for the fluorescence detection. Instrumental LD found for CB, for MBC and for CF are respectively 4, 50 and 1000 ng L⁻¹. In tap water, the LD obtained is 800 ng L⁻¹ for MBC and 20,000 ng L⁻¹ for CF. For CB, the use of a time shift between excitation and emission allows to reach a LD of 20 ng L⁻¹ in tap water.     

斑头雁不同组织氨基酸的组成和含量分析

采用高效液相色谱法对斑头雁卵、肌肉和羽毛中17种氨基酸进行了含量的测定,并分析其中必需氨基酸的含量,为斑头雁的保护和利用提供依据。结果表明,斑头雁的卵、腿肌、胸肌和羽毛中均含有17种氨基酸,必需氨基酸含量较高,配比合理,有较高的营养价值。     

基于光谱解调的对称波导型表面等离子体共振传感研究

表面等离子体共振(SPR)传感系统有角度谱、光谱、强度、相位等解调方式,其中光谱型的(SPR)传感系统因可以使用光纤导光,将传感部分独立出来,可进行远距离传感和现场检测,并能有效缩小系统的体积。对称光波导型(SOW)SPR因金属膜层两边的折射率完全相同,表面等离子体波传播距离更长,穿透深度更深,比传统的SPR系统具有更高的灵敏度和分辨率。对对称波导型(SOW)SPR进行光谱解调研究,以MgF₂-Au-MgF₂结构的SOW-SPR为传感单元,同时以光纤输出的卤素灯为光源, 搭建了一套光谱解调的SOW-SPR检测系统,以不同浓度的葡萄糖溶液对系统折射率分辨率进行测量,得到2.8×10-7 RIU的分辨率。为SOW-SPR系统小型化、现场检测以及远距离探测提出一种可能实现的手段,具有很好的应用前景。     

A proposal for preparation of cluster states with linear optics

Measurement-based quantum computation in an optical setup shows great promise towards the implementation oflarge-scale quantum computation. The difficulty of measurement-based quantum computation lies in the preparation ofcluster state. In this paper, we propose the method of generating the large-scale cluster state, which is a platform formeasurement-based quantum computation. In order to achieve more complex quantum circuits, the preparation protocolof N-photon cluster state will be proposed as a generalization of the preparation of four- and five-photon cluster states.Furthermore, our proposal is experimentally feasible.     

Acetylenic and diacetylenic liquid-crystalline monomers: towards ordered conjugated polymers

Abstract

Acetylenic and diacetylenic mesomorphic monomers have been prepared in order to obtain long conjugated polymers able to give high non-linear optical hyperpolarizabilities. Here we report the synthesis of such monomers incorporating cholesteryl and methoxybiphenyl groups; their structural and thermal behaviour are described. The occurrence of mesophases in the acetylenic and diacetylenic derivatives is discussed as a function of the spacer length and of the size of the mesogen moiety. The diacetylenic derivatives containing the methoxybiphenyl groups do not exhibit any liquid-crystalline behaviour but are able to polymerize under U.V. radiation.     

On one possibility of determining the atom position in the crystal unit cell

The possibility of the determination of the position of an atom incorporated in the crystal unit cell by measuring the yield of characteristic radiation of this atom, excited by an X-ray wave nonuniform over the cell cross section, is shown. Such a wave can appear, in particular, in the mode of dynamical diffraction of an ordinary plane wave.     

Fracture and debonding of a thin film on a stiff substrate: analytical and numerical solutions of a one-dimensional variational model

We study multi-fissuration and debonding phenomena of a thin film bonded to a stiff substrate using the variational approach to fracture mechanics. We consider a reduced one-dimensional membrane model where the loading is introduced through uniform inelastic (e.g., thermal) strains in the film or imposed displacements of the substrate. Fracture phenomena are accounted for by adopting a Griffith model for debonding and transverse fracture. On the basis of energy minimization arguments, we recover the key qualitative properties of the experimental evidences, like the periodicity of transverse cracks and the peripheral debonding of each regular segment. Phase diagrams relate the maximum number of transverse cracks that may be created before debonding takes place, as a function of the material properties and the sample’s geometry. The theoretical results are illustrated with numerical simulations obtained through a finite element discretization and a regularized variational formulation of the Ambrosio–Tortorelli type, which is suited to further extensions in two-dimensional settings.