Inhibitory effects of curcumin and piperine on fluorescent advanced glycation end products formation in a bovine serum albumin–fructose model

This study investigated the inhibitory effects of curcumin and piperine on fluorescent advanced glycation end products (fAGEs) formation in a bovine serum albumin (BSA)–fructose model. Model systems of BSA and fructose were prepared, and curcumin or piperine was added. fAGEs and BSA oxidation product (dityrosine, kynurenine and N'-formylkynurenine) contents were determined. The results showed that fAGEs content decreased with increasing concentration of curcumin and piperine (P < 0.05). Addition of curcumin and piperine at 160 µg mL⁻¹ could inhibit fluorescent AGEs by 100% and 93% respectively. Dityrosine and N'-formylkynurenine contents decreased as curcumin and piperine concentration increased (P < 0.05). Furthermore, the result of principal component analysis indicated that curcumin and piperine markedly impeded BSA oxidation, resulting in a lower level of fAGEs in model systems. Therefore, adding curcumin and piperine may facilitate reduced fAGEs levels in BSA–fructose model.     

Advancements in the Development of non-BET Bromodomain Chemical Probes

The bromodomain and extra terminal (BET) family of bromodomain-containing proteins (BCPs) have been the subject of extensive research over the past decade, resulting in a plethora of high-quality chemical probes for their tandem bromodomains. In turn, these chemical probes have helped reveal the profound biological role of the BET bromodomains and their role in disease, ultimately leading to a number of molecules in active clinical development. However, the BET subfamily represents just 8/61 of the known human bromodomains, and attention has now expanded to the biological role of the remaining 53 non-BET bromodomains. Rapid growth of this research area has been accompanied by a greater understanding of the requirements for an effective bromodomain chemical probe and has led to a number of new non-BET bromodomain chemical probes being developed. Advances since December 2015 are discussed, highlighting the strengths/caveats of each molecule, and the value they add toward validating the non-BET bromodomains as tractable therapeutic targets.     

Discovery of Affinity-Based Probes for Btk Occupancy Assays

Bruton's tyrosine kinase (Btk) is an attractive target for the treatment of a wide array of B-cell malignancies and autoimmune diseases. Small-molecule covalent irreversible Btk inhibitors targeting Cys481 have been developed for the treatment of such diseases. In clinical trials, probe molecules are required in occupancy studies to measure the level of engagement of the protein by these covalent irreversible inhibitors. The result of this pharmacodynamic (PD) activity provides guidance for appropriate dosage selection to optimize inhibition of the drug target and correlation of target inhibition with disease treatment efficacy. This information is crucial for successful evaluation of drug candidates in clinical trials. Based on the pyridine carboxamide scaffold of a novel solvent-accessible pocket (SAP) series of covalent irreversible Btk inhibitors, we successfully developed a potent and selective affinity-based biotinylated probe 12 (2-[(4-{4-[5-(1-{5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamido}-3,6,9,12-tetraoxapentadecan-15-amido)pentanoyl]piperazine-1-carbonyl}phenyl)amino]-6-[1-(prop-2-enoyl)piperidin-4-yl]pyridine-3-carboxamide). Compound 12 has been used in Btk occupancy assays for preclinical studies to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon.     

Quantum Sensing in a Physiological‐Like Cell Niche Using Fluorescent Nanodiamonds Embedded in Electrospun Polymer Nanofibers

Fluorescent nanodiamonds (fNDs) containing nitrogen vacancy (NV) centers are promising candidates for quantum sensing in biological environments. This work describes the fabrication and implementation of electrospun poly lactic‐co‐glycolic acid (PLGA) nanofibers embedded with fNDs for optical quantum sensing in an environment, which recapitulates the nanoscale architecture and topography of the cell niche. A protocol that produces uniformly dispersed fNDs within electrospun nanofibers is demonstrated and the resulting fibers are characterized using fluorescent microscopy and scanning electron microscopy (SEM). Optically detected magnetic resonance (ODMR) and longitudinal spin relaxometry results for fNDs and embedded fNDs are compared. A new approach for fast detection of time varying magnetic fields external to the fND embedded nanofibers is demonstrated. ODMR spectra are successfully acquired from a culture of live differentiated neural stem cells functioning as a connected neural network grown on fND embedded nanofibers. This work advances the current state of the art in quantum sensing by providing a versatile sensing platform that can be tailored to produce physiological‐like cell niches to replicate biologically relevant growth environments and fast measurement protocols for the detection of co‐ordinated endogenous signals from clinically relevant populations of electrically active neuronal circuits.     

荧光显示管直丝氧化物阴极有效逸出功的计算

阴极的逸出功是表征阴极发射能力的物理量，求定荧光显示管直丝氧化物阴极有效逸出功时，因其零场发射电流密度难于准确取值，温度无法直接测量，显得困难，须予解决，为此提出了一种计算阴极有产逸出功的办法，对某显示管的发射欠佳和“低温高效”的两种氧化物阴极的有效逸出功进行计算，有效逸出功率是靠测量相关物理量再同计算得出，精度不很高，文中所用办法也不例外，但所得结果能反映阴极发射能力，所需仪器少，是实用方法。     

Multi-functional biochip for medical diagnostics and pathogen detection

We describe a multi-functional biochip (MFB), which uses two different types of bioreceptors, including nucleic acid and antibody probes, on a single platform. The multi-functional capability of the MFB device for biomedical diagnostics is illustrated by measurements of DNA probes specific to gene fragments of Bacillus anthracis and antibody probes targeted to Escherichia coli. Calibration curves for monitoring pathogenic species using antibody probes against E. coli and DNA probes for B. anthracis illustrate the capability of the device for medical diagnostics and for quantitative detection of pathogenic agents.     

Signal analysis of total internal reflection fluorescent speckle microscopy (TIR-FSM) and wide-field epi-fluorescence FSM of the actin cytoskeleton and focal adhesions in living cells

Fluorescent speckle microscopy (FSM) uses low levels of fluorescent proteins to create fluorescent speckles on cytoskeletal polymers in high‐resolution fluorescence images of living cells. The dynamics of speckles over time encode subunit turnover and motion of the cytoskeletal polymers. We sought to improve on current FSM technology by first expanding it to study the dynamics of a non‐polymeric macromolecular assembly, using focal adhesions as a test case, and second, to exploit for FSM the high contrast afforded by total internal reflection fluorescence microscopy (TIR‐FM). Here, we first demonstrate that low levels of expression of a green fluorescent protein (GFP) conjugate of the focal adhesion protein, vinculin, results in clusters of fluorescent vinculin speckles on the ventral cell surface, which by immunofluorescence labelling of total vinculin correspond to sparse labelling of dense focal adhesion structures. This demonstrates that the FSM principle can be applied to study focal adhesions. We then use both GFP‐vinculin expression and microinjected fluorescently labelled purified actin to compare quantitatively the speckle signal in FSM images of focal adhesions and the actin cytoskeleton in living cells by TIR‐FM and wide‐field epifluorescence microscopy. We use quantitative FSM image analysis software to define two new parameters for analysing FSM signal features that we can extract automatically: speckle modulation and speckle detectability. Our analysis shows that TIR‐FSM affords major improvements in these parameters compared with wide‐field epifluorescence FSM. Finally, we find that use of a crippled eukaryotic expression promoter for driving low‐level GFP‐fusion protein expression is a useful tool for FSM imaging. When used in time‐lapse mode, TIR‐FSM of actin and GFP‐conjugated focal adhesion proteins will allow quantification of molecular dynamics within interesting macromolecular assemblies at the ventral surface of living cells.     

高扭曲向列液晶显示器件的特性研究

本文研究了高扭曲向列液晶显示器件（ＨＴＮＬＣＤ）（扭曲角９０～１８０°），此器件与扭曲向列液晶显示器件（ＴＮＬＣＤ）相比较，能够增加液晶显示器件扫描行数并改善视角特性，其制造技术与ＴＮ器件相似，具有很大的应用价值。     

Model for Nanoscopic Domain Formation in Dipalmitoyl-PC/Dilauroyl-PC/Cholesterol Mixture

We describe the lyotropic liquid crystalline phase transitions in the lipid mixture dipalmitoil-PC/dilauroy-PC/cholesterol by 3D spin-1 lattice model. The formation of nanoscale domains with the characteristic size about 300 nm was studied in experiments on confocal fluorescence microscopy (CFM) (G. V. Feigenson and J. T. Buboltz, Biophys. J. 80, 2775 (2001)). The structure parameters of the lamellar vesicle in dipalmitoil-PC-rich phase, corresponding to these regions, are verified by numerical Monte Carlo simulations on the lattice. We point its superconductivity analogy properties at the region of phase stability for composition-dependent nanoscopic region.     

New method for measuring an optical property of a sample treated by FWA

In this article, a new method for measuring a total spectral radiance factor of a FWA‐treated sample illuminated by a specific standard illuminant is introduced. The method replaces an unstable real fluorescent standard by a bi‐spectral luminescent radiance factor data, which works as a virtual fluorescent standard (VFS) by knowing spectral intensity distributions of illuminations applied to the sample. The method utilizes two illuminations I₁ and I₂ whose relative spectral intensity distributions are different from each other and synthesizes a virtual illumination presenting the identical fluorescent spectral radiance factor to that presented by the standard illuminant with the VFS of the specific bi‐spectral luminescent radiance factor by linearly combining I₁ and I₂ with the suitable weighting factors. The applicability of the method is examined in principle by comparing ISO brightness and CIE whiteness index of fluorescent standard paper as a test sample obtained by this new method to the assigned values. © 2007 Wiley Periodicals, Inc. Col Res Appl, 32, 195–200, 2007