Rapid (<5 min) identification of pathogen in human blood by electrokinetic concentration and surface-enhanced Raman spectroscopy.

This study reports a novel microfluidic platform for rapid and long-ranged concentration of rare-pathogen from human blood for subsequent on-chip surface-enhanced Raman spectroscopy (SERS) identification/discrimination of bacteria based on their detected fingerprints. Using a hybrid electrokinetic mechanism, bacteria can be concentrated at the stagnation area on the SERS-active roughened electrode, while blood cells were excluded away from this region at the center of concentric circular electrodes. This electrokinetic approach performs isolation and concentration of bacteria in about three minutes; the density factor is increased approximately a thousand fold in a local area of ~5000 μm(2) from a low bacteria concentration of 5 × 10(3) CFU/ml. Besides, three genera of bacteria, S. aureus, E. coli, and P. aeruginosa that are found in most of the isolated infections in bacteremia were successfully identified in less than one minute on-chip without the use of any antibody/chemical immobilization and reaction processes

A Bayesian measurement error model for two-channel cell-based RNAi data with replicates

RNA interference (RNAi) is an endogenous cellular process in which small double-stranded RNAs lead to the destruction of mRNAs with complementary nucleoside sequence. With the production of RNAi libraries, large-scale RNAi screening in human cells can be conducted to identify unknown genes involved in a biological pathway. One challenge researchers face is how to deal with the multiple testing issue and the related false positive rate (FDR) and false negative rate (FNR). This paper proposes a Bayesian hierarchical measurement error model for the analysis of data from a two-channel RNAi high-throughput experiment with replicates, in which both the activity of a particular biological pathway and cell viability are monitored and the goal is to identify short hair-pin RNAs (shRNAs) that affect the pathway activity without affecting cell activity. Simulation studies demonstrate the flexibility and robustness of the Bayesian method and the benefits of having replicates in the experiment. This method is illustrated through analyzing the data from a RNAi high-throughput screening that searches for cellular factors affecting HCV replication without affecting cell viability; comparisons of the results from this HCV study and some of those reported in the literature are included.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS496 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Protective effect of liquiritin on corticosterone-induced neurotoxicity in PC12 cells

Purpose: To determine the protective effects of liquiritin on corticosterone-induced neurotoxicity in rat pheochromocytoma (PC12) cells.Methods: Neurotoxicity in PC12 cells was induced by different concentrations of corticosterone. Proliferation of PC12 cells was evaluated using CCK8 assay kits, while apoptosis was determined by flow cytometry.Results: The results indicate that corticosterone inhibited the proliferation of PC12 cells time- and dosedependently. The inhibitory effect (0.2 mM) was ameliorated by liquiritin. Furthermore, the cell apoptosis rate and protein level of caspase 3 in PC12 cells induced by corticosterone were ameliorated by liquiritin (1 and 2 mg/mL) treatment. Moreover, the protective effect of liquiritin (2 mg/mL) on corticosterone induced neurotoxicity in PC12 cells was weakened by K252a (the specific TrkB inhibitor) treatment. In addition, the protein level of brain-derived neurotrophic factor (BDNF) and (tyrosine-kinase receptor) TrkB showed a reverse trend to caspase 3.Conclusion: Liquiritin shows protective effects against neurotoxicity induced by corticosterone in PC12 cells, and these effects are exerted via up-regulating BDNF/TrkB signaling.Keywords: Liquiritin, Antidepressant, Corticosterone, Neuroprotection, PC12 cells, BDNF/TrkB signalin

浅析中药学与民族药学对木香的临床应用异同

Costusroot is commonly used in traditional medicine,Mongolian medicine,Tibetan medicine,Dai medicine and Uighur medicine. We discuss similarities and differences in clinical applications of costusroot in traditional medicine,Mongolian medicine,Tibetan medicine,Dai medicine and Uighur medicine, from aspects of its property and flavor,functions and indications ,and clinical applications. For sake of retaining their own features, the authors intended to integrate the essences of the two, broaden its clinical applications, make costusroot to play its role fully and fully understand the natural medicinal plants ,which is more conducive to modernize the traditional medicine.木香是中、蒙、藏、傣以及维医药学的常用药。本文从木香的性味、功效主治及临床应用等方面，比较探讨木香在中医药学、蒙医药学、藏医药学、傣医药学及维医药学中的临床应用异同，希冀在保留各自特色的基础上，相互借鉴，拓宽临床应用，使之发挥其更全面的作用，同时全面认识自然界药用植物，更有利于促进中药现代化

Structures of Darunavir-Resistant HIV‑1 Protease Mutant Reveal Atypical Binding of Darunavir to Wide Open Flaps

The molecular basis for high resistance to clinical inhibitors of HIV-1 protease (PR) was examined for the variant designated PRP51 that was selected for resistance to darunavir (DRV). High resolution crystal structures of PRP51 with the active site D25N mutation revealed a ligand-free form and an inhibitor-bound form showing a unique binding site and orientation for DRV. This inactivating mutation is known to increase the dimer dissociation constant and decrease DRV affinity of PR. The PRP51‑D25N dimers were in the open conformation with widely separated flaps, as reported for other highly resistant variants. PRP51‑D25N dimer bound two DRV molecules and showed larger separation of 8.7 Å between the closest atoms of the two flaps compared with 4.4 Å for the ligand-free structure of this mutant. The ligand-free structure, however, lacked van der Waals contacts between Ile50 and Pro81′ from the other subunit in the dimer, unlike the majority of PR structures. DRV is bound inside the active site cavity; however, the inhibitor is oriented almost perpendicular to its typical position and exhibits only 2 direct hydrogen bond and two water-mediated interactions with atoms of PRP51‑D25N compared with 11 hydrogen bond interactions seen for DRV bound in the typical position in wild-type enzyme. The atypical location of DRV may provide opportunities for design of novel inhibitors targeting the open conformation of PR drug-resistant mutants

Advance on rock-breaking cutter steels: A review of characteristics, failure modes, molding processes and strengthening technology

Rock breaking has always been a challenging problem that must be solved in projects such as excavating mountains, drilling wells, and constructing railways. Among the rock-breaking cutter steels, AISI H13 steel and wear-resistant high manganese steel have become the best choices. From the characteristics and failure modes of the two, rock-breaking cutter steels should simultaneously have high strength, high toughness and high wear resistance to avoid short-term fracture/damage and cost increase. Analyzing the problems existing in the molding process of rock-breaking cutter steels such as die casting, forging, and hot stamping, traditional strengthening technologies such as alloying optimization, heat treatment, and surface treatment can achieve certain performance enhancement. After reaching the limits of traditional strengthening technologies, a series of nanoparticle strengthening technologies came into being. The selection, addition amount, and addition method of nanoparticles all affect the microstructure, mechanical properties and wear. To this end, this article summarizes the research progress and challenges of rock-breaking cutter steels, and discusses traditional strengthening technologies and mainstream nanoparticle strengthening technologies. It provides a reference for the future development of high-quality and high-performance rock-breaking cutter steels, with aim to simultaneously expand their application potentials to other fields