Pharmacophore features for machine learning in pharmaceutical virtual screening

Molecular Diversity - Methods of three-dimensional molecular alignment generally treat all pharmacophore features equally when superimposing. However, some pharmacophore features can be more...     

A Stochastic Method for Modelling the Geometry of a Single Fracture: Spatially Controlled Distributions of Aperture,Roughness and Anisotropy

Transport in Porous Media - We describe a simple but effective stochastic method to model the void structure of a single fracture in a form of voxel representation. A fracture void is delineated by...     

Development of Optogenetic Dual-Switch System for Rewiring Metabolic Flux for Polyhydroxybutyrate Production

Several strategies, including inducer addition and biosensor use, have been developed for dynamical regulation. However, the toxicity, cost, and inflexibility of existing strategies have created a demand for superior technology. In this study, we designed an optogenetic dual-switch system and applied it to increase polyhydroxybutyrate (PHB) production. First, an optimized chromatic acclimation sensor/regulator (RBS10–CcaS#10–CcaR) system (comprising an optimized ribosomal binding site (RBS), light sensory protein CcaS, and response regulator CcaR) was selected for a wide sensing range of approximately 10-fold between green-light activation and red-light repression. The RBS10–CcaS#10–CcaR system was combined with a blue light-activated YF1–FixJ–PhlF system (containing histidine kinase YF1, response regulator FixJ, and repressor PhlF) engineered with reduced crosstalk. Finally, the optogenetic dual-switch system was used to rewire the metabolic flux for PHB production by regulating the sequences and intervals of the citrate synthase gene (gltA) and PHB synthesis gene (phbCAB) expression. Consequently, the strain RBS34, which has high gltA expression and a time lag of 3 h, achieved the highest PHB content of 16.6 wt%, which was approximately 3-fold that of F34 (expressed at 0 h). The results indicate that the optogenetic dual-switch system was verified as a practical and convenient tool for increasing PHB production.     

The Biological Fate of Pharmaceutical Excipient β-Cyclodextrin: Pharmacokinetics,Tissue Distribution,Excretion, and Metabolism of β-Cyclodextrin in Rats

β-cyclodextrin has a unique annular hollow ultrastructure that allows encapsulation of various poorly water-soluble drugs in the resulting cavity, thereby increasing drug stability. As a bioactive molecule, the metabolism of β-cyclodextrin is mainly completed by the flora in the colon, which can interact with API. In this study, understanding the in vivo fate of β-cyclodextrin, a LC-MS/MS method was developed to facilitate simultaneous quantitative analysis of pharmaceutical excipient β-cyclodextrin and API dextromethorphan hydrobromide. The established method had been effectively used to study the pharmacokinetics, tissue distribution, excretion, and metabolism of β-cyclodextrin after oral administration in rats. Results showed that β-cyclodextrin was almost wholly removed from rat plasma within 36 h, and high concentrations of β-cyclodextrin distributed hastily to organs with increased blood flow velocities such as the spleen, liver, and kidney after administration. The excretion of intact β-cyclodextrin to urine and feces was lower than the administration dose. It can be speculated that β-cyclodextrin metabolized to maltodextrin, which was further metabolized, absorbed, and eventually discharged in the form of CO₂ and H₂O. Results proved that β-cyclodextrin, with relative low accumulation in the body, had good safety. The results will assist further study of the design and safety evaluation of adjuvant β-cyclodextrin and promote its clinical development.     

Joint Detection of Community and Structural Hole Spanner of Networks in Hyperbolic Space

Community detection and structural hole spanner (the node bridging different communities) identification, revealing the mesoscopic and microscopic structural properties of complex networks, have drawn much attention in recent years. As the determinant of mesoscopic structure, communities and structural hole spanners discover the clustering and hierarchy of networks, which has a key impact on transmission phenomena such as epidemic transmission, information diffusion, etc. However, most existing studies address the two tasks independently, which ignores the structural correlation between mesoscale and microscale and suffers from high computational costs. In this article, we propose an algorithm for simultaneously detecting communities and structural hole spanners via hyperbolic embedding (SDHE). Specifically, we first embed networks into a hyperbolic plane, in which, the angular distribution of the nodes reveals community structures of the embedded network. Then, we analyze the critical gap to detect communities and the angular region where structural hole spanners may exist. Finally, we identify structural hole spanners via two-step connectivity. Experimental results on synthetic networks and real networks demonstrate the effectiveness of our proposed algorithm compared with several state-of-the-art methods.     

An Encryption Algorithm for Region of Interest in Medical DICOM Based on One-Dimensional eλ-cos-cot Map

Today, with the rapid development of the Internet, improving image security becomes more and more important. To improve image encryption efficiency, a novel region of interest (ROI) encryption algorithm based on a chaotic system was proposed. First, a new 1D eλ-cos-cot (1D-ECC) with better chaotic performance than the traditional chaotic system is proposed. Second, the chaotic system is used to generate a plaintext-relate keystream based on the label information of a medical image DICOM (Digital Imaging and Communications in Medicine) file, the medical image is segmented using an adaptive threshold, and the segmented region of interest is encrypted. The encryption process is divided into two stages: scrambling and diffusion. In the scrambling stage, helical scanning and index scrambling are combined to scramble. In the diffusion stage, two-dimensional bi-directional diffusion is adopted, that is, the image is bi-directionally diffused row by column to make image security better. The algorithm offers good encryption speed and security performance, according to simulation results and security analysis.     

基于FTIR和XRD的降低连铸保护渣红外辐射传热研究

根据常用工业保护渣的成分范围配制出含有TiO2的连铸结晶器保护渣,通过实验检测并分析了渣样FTIR光谱及X射线衍射图谱,探讨了熔渣辐射传热特性随TiO2变化的规律.FTIR分析结果表明,在1～6 μm波段范围内,TiO2具有明显降低渣膜红外透过率的作用.X射线衍射结果表明渣中枪晶石的含量减少,析出CaTiO3等晶体,枪晶石的大量减少有利于铸坯的润滑.通过辐射传热模型计算得到铸坯与结晶器之间的辐射热流密度.TiO2的加入使渣样热流密度大为降低,并随其含量增加而降低,最高达30%.由于试样表面及晶界强烈的折射和散射,结晶态试样对辐射传热的降低作用比玻璃态试样更明显.     

Preparative high-speed counter-current chromatography for purification of shikonin from the Chinese medicinal plant Lithospermum erythrorhizon

The bioactive compound shikonin was successfully isolated and purified from the crude extract of the traditional Chinese medicinal plant Lithospermum erythrorhizon Sieb. et Zucc. by preparative high-speed counter-current chromatography (HSCCC). The preparative HSCCC was performed using a two-phase solvent system composed of n-hexane-ethylacetate-ethanol-water (16:14:14:5 (v/v)). A total amount of 19.6 mg of shikonin at 98.9% purity was obtained from 52 mg of the crude extract (containing 38.9% shikonin) with 96.9% recovery. The preparative isolation and purification of shikonin by HSCCC was completed in 200 min in a one-step separation.     

Applications of Raman-based techniques to on-site and in-vivo analysis

Raman-based technologies have proved to be excellent tools for on-site and in-vivo analysis, due to the non-invasive nature of their detection, their capability of providing structure information, their high tolerance to aqueous samples, the ultra-sensitivity of surface-enhanced Raman scattering (SERS) and resonance Raman scattering (RRS), the high spatial resolution of tip-enhanced Raman scattering (TERS), and the ultrashort spectra-acquisition time for coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering (SRS).In this review, we highlight the recent success of Raman-based technologies in various applications, including:

• (1) 

  on-site surface analysis and chemical-reaction monitoring;

• (2) 

  on-site identification of cultural objects, archeological studies and planetary science;

• (3) 

  in-vivo analysis of cells and microorganisms;

• (4) 

  in-vivo diagnosis inside human and animal bodies;

• (5) 

  in-vivo fast Raman imaging and mapping;

• (6) 

  the study of SERS processes; and,

• (7) 

  assessment of nanomaterial safety.