Theoretical Localized Electric Field Enhancement in Tip-Enhanced Spectroscopy Using Multi-Order Radially Polarized Modes

Multi-order radially polarized modes (RPMs), including Bessel-Gaussian, Gaussian, Super Gaussian, and multi-order hollow Gaussian are respectively utilized as the illumination laser to achieve tip-enhanced spectroscopy (TES). Based on the vector diffraction theory and finite difference time domain (FDTD) analysis, we achieve the optimization of RPM illuminated TES system, including the focal spot size, focal depth, and electric field enhancement factor, in which the focal spot size of 5th order hollow Gaussian RPM is smallest (0.54λ) and the focusing depth of super Gaussian RPM is longest (4.71λ). Specially, it is found that the multi-order hollow Gaussian RPM illuminated TES system with the tip cone angle of 45^° reveals better focusing ability and 40~60-fold electric field enhancement factor compared to the linearly polarized mode (LPM) illuminated TES system. These results will supply a useful reference for spectral signal enhancement of TES system.     

Mechanism of gold nanoparticles-induced trypsin inhibition: a multi-technique approach

The binding interactions of gold nanoparticles with trypsin were investigated using multi-spectra methods and molecular modeling. The experiment data showed that trypsin modified the surface of gold nanoparticles. The fluorescence intensity of trypsin was quenched by gold nanoparticles that strongly associated with protein and induced the inhibition of enzyme activity. The electrostatic and hydrophobic interactions were the primary contributors to the binding forces between trypsin and gold nanoparticles. The covalent interactions might be also involved in the binding process. The modeling calculated results indicated that the binding site was near to the primary substrate-binding pocket and the active site of the enzyme substrate. This work elucidated the interaction mechanism of trypsin with gold nanoparticles from the theoretical and experimental angle.     

Synthesis and evaluation of (2-phenethyl-2H-1,2,3-triazol-4-yl)(phenyl)methanones as Kv1.5 channel blockers for the treatment of atrial fibrillation

A series of novel (2-phenethyl-2H-1,2,3-triazol-4-yl)(phenyl)methanones were prepared and examined for utility as Kv1.5 channel blockers for the treatment of atrial fibrillation.     

Evolution of thiazolidine-based blockers of human Kv1.5 for the treatment of atrial arrhythmias

Blockade of the Kv1.5 ion channel is a potentially atrial-selective avenue for the treatment of atrial fibrillation and atrial flutter. The development and biological evaluation of a series of thiazolidine-based blockers of Kv1.5 is described.     

大肠杆菌工程菌ptsG基因敲除及其缺陷株混合糖同型乙醇发酵

为实现可同时利用木糖和葡萄糖进行生产发酵,以产乙醇的大肠杆菌工程菌SZ470为出发菌株(△pflB,△frdABCD,△ackA,△ldhA),采用同源重组技术,敲除葡萄糖转运基因ptsG,以构建不受葡萄糖抑制效应影响的菌株SZ470P.SZ470P在5％混合糖(2.5％木糖和2.5％葡萄糖)培养基中能同时利用葡萄糖和木糖进行发酵,葡萄糖消耗量是13 g/L,为对照菌株SZ470的一半;木糖消耗量是20 g/L,是SZ470的3.8倍;乙醇的最高产量为15.01 g/L,转化率为89.13％,比SZ470提高了14.32％.结果表明,工程菌SZ470P可同时利用葡萄糖和木糖发酵生产高产量的乙醇.     

Extension temperature of 60°C required for PCR amplification of large DNA fragments (>5 kb) from a low GC bacterium Clostridium acetobutylicum

PCR amplification of DNA fragments has been routinely used in gene cloning and engineering of microbial strains for biotechnological purposes such as production of biofuels and green chemicals. However, it is often a challenge to amplify large DNA fragments (>5 kb) from low GC microorganisms using the standard PCR protocols. In this brief communication, we report a modified PCR method with an extension temperature of 60°C, which efficiently amplified a 5.3 and a 5.5 kb DNA fragment (an extension time of 6 min) from a low GC bacterium Clostridium acetobutylicum (~30% GC). A lower than normal extension temperature (72°C) approach may also facilitate PCR amplification of large DNA fragments (>5 kb) from other low GC microorganisms.     

A novel series of imidazo[1,2-a]pyridine derivatives as HIF-1alpha prolyl hydroxylase inhibitors

Utilizing modeling information from a recently resolved structure of human HIF-1alpha prolyl hydroxylase (EGLN1) and structure-based design, a novel series of imidazo[1,2-a]pyridine derivatives was prepared. The activity of these compounds was determined in a human EGLN1 assay and a limited SAR was developed.     

Design and synthesis of substituted pyridine derivatives as HIF-1alpha prolyl hydroxylase inhibitors

Structure-guided de novo drug design led to the identification of a novel series of substituted pyridine derivatives as HIF-1alpha prolyl hydroxylase inhibitors. Pyridine carboxyamide derivatives bearing a substituted aryl group at the 5-position of the pyridine ring show appreciable activity, while constraining the side chain by placing a pyrazole carboxylic acid generated a potent lead series with consistent activity against EGLN-1.