Darunavir-Resistant HIV-1 Protease Constructs Uphold a Conformational Selection Hypothesis for Drug Resistance.

Multidrug resistance continues to be a barrier to the effectiveness of highly active antiretroviral therapy in the treatment of human immunodeficiency virus 1 (HIV-1) infection. Darunavir (DRV) is a highly potent protease inhibitor (PI) that is oftentimes effective when drug resistance has emerged against first-generation inhibitors. Resistance to darunavir does evolve and requires 10-20 amino acid substitutions.

Ripening of avocado fruits studied by spectroscopic techniques.

Avocados are considered very healthy due to the high content mono-unsaturated lipid, essential vitamins and minerals, minimal sugar and no cholesterol and are therefore sometimes referred to as "the perfect fruits". Avocados, mainly grown in Latin-America, are harvested unripe and sent overseas. However, the ripening process is very difficult to assess visually and tactilely.

Non-intrusive studies of gas contents and gas diffusion in hen eggs.

A detailed study of the condition of eggs was performed using tunable diode lasers to monitor free gas in hen eggs. We detected oxygen and water vapor signals from 13 unfertilized eggs and studied the growth of the egg air cell over a time period of 3 weeks. We also studied the gas exchange through the egg shell, which is of particular interest for fertilized eggs.

Towards an optical diagnostic system for otitis media using a combination of otoscopy and spectroscopy.

An improved method, where conventional otoscope investigation of human suspicious otitis media is combined with diffuse reflectance spectroscopy and gas in scattering media absorption spectroscopy (GASMAS) is being developed. Otitis media is one of the most common infectious diseases in children, whose Eustachian tube connecting the middle ear with the nasal cavity is more horizontal than for adults, which leads to impaired fluid drainage. At present, the use of an otoscope to visually observe possible changes in the tympanic membrane appearance is the main diagnostics method for otitis media.

LGALS3 Promotes Treatment Resistance in Glioblastoma and Is Associated with Tumor Risk and Prognosis.

Background: LGALS3 promotes tumor progression in diverse cancers. However, the involvement of LGALS3 in glioblastoma has not yet been broadly illuminated.

Methods: Microarray was performed to detect the gene expression profiles of radioresistance in T98G cells and identified a universally upregulated gene, .

Intracellular generation of single-strand template increases the knock-in efficiency by combining CRISPR/Cas9 with AAV.

Targeted integration of transgenes facilitates functional genomic research and holds prospect for gene therapy. The established microhomology-mediated end-joining (MMEJ)-based strategy leads to the precise gene knock-in with easily constructed donor, yet the limited efficiency remains to be further improved. Here, we show that single-strand DNA (ssDNA) donor contributes to efficient increase of knock-in efficiency and establishes a method to achieve the intracellular linearization of long ssDNA donor.

New applications of CRISPR/Cas9 system on mutant DNA detection.

The detection of mutant DNA is critical for precision medicine, but low-frequency DNA mutation is very hard to be determined. CRISPR/Cas9 is a robust tool for in vivo gene editing, and shows the potential for precise in vitro DNA cleavage. Here we developed a DNA mutation detection system based on CRISPR/Cas9 that can detect gene mutation efficiently even in a low-frequency condition.

Whole exome-wide association study identifies a missense variant in SLC2A4RG associated with glioblastoma risk.

In this study, we conducted a genome-wide scan of single nucleotide polymorphisms (SNPs) to identify coding variants that is associated with the risk of glioblastoma (GBM), the most common and most malignant subtype of glioma. We genotyped 1038 GBM cases and 1008 controls in a Chinese Han population using Illumina HumanExome Beadchip v1.0.

Effects of Hinge-region Natural Polymorphisms on Human Immunodeficiency Virus-Type 1 Protease Structure, Dynamics, and Drug Pressure Evolution.

Multidrug resistance to current Food and Drug Administration-approved HIV-1 protease (PR) inhibitors drives the need to understand the fundamental mechanisms of how drug pressure-selected mutations, which are oftentimes natural polymorphisms, elicit their effect on enzyme function and resistance. Here, the impacts of the hinge-region natural polymorphism at residue 35, glutamate to aspartate (E35D), alone and in conjunction with residue 57, arginine to lysine (R57K), are characterized with the goal of understanding how altered salt bridge interactions between the hinge and flap regions are associated with changes in structure, motional dynamics, conformational sampling, kinetic parameters, and inhibitor affinity. The combined results reveal that the single E35D substitution leads to diminished salt bridge interactions between residues 35 and 57 and gives rise to the stabilization of open-like conformational states with overall increased backbone dynamics.

Development of risk prediction models for glioma based on genome-wide association study findings and comprehensive evaluation of predictive performances.

Over 14 common single nucleotide polymorphisms (SNP) have been consistently identified from genome-wide association studies (GWAS) as associated with glioma risk in European background. The extent to which and how these genetic variants can improve the prediction of glioma risk has was not been investigated. In this study, we employed three independent case-control datasets in Chinese populations, tested GWAS signals in dataset1, validated association results in dataset2, developed prediction models in dataset2 for the consistently replicated SNPs, refined the consistently replicated SNPs in dataset3 and developed tailored models for Chinese populations.

Development of background-free tame fluorescent probes for intracellular live cell imaging.

Fluorescence labelling of an intracellular biomolecule in native living cells is a powerful strategy to achieve in-depth understanding of the biomolecule's roles and functions. Besides being nontoxic and specific, desirable labelling probes should be highly cell permeable without nonspecific interactions with other cellular components to warrant high signal-to-noise ratio. While it is critical, rational design for such probes is tricky.

High expression of N-myc (and STAT) interactor predicts poor prognosis and promotes tumor growth in human glioblastoma.

Glioma is the most malignant brain tumor and glioblastoma (GBM) is the most aggressive type. The involvement of N-myc (and STAT) interactor (NMI) in tumorigenesis was sporadically reported but far from elucidation. This study aims to investigate roles of NMI in human glioma.

VAMP8 facilitates cellular proliferation and temozolomide resistance in human glioma cells.

Background: Malignant glioma is a common and lethal primary brain tumor in adults. Here we identified a novel oncoprotein, vesicle-associated membrane protein 8 (VAMP8), and investigated its roles in tumorigenisis and chemoresistance in glioma.

Methods: The expression of gene and protein were determined by quantitative PCR and Western blot, respectively.

Erlotinib promotes endoplasmic reticulum stress-mediated injury in the intestinal epithelium.

Erlotinib, a popular drug for treating non-small cell lung cancer (NSCLC), causes diarrhea in approximately 55% of patients receiving this drug. In the present study, we found that erlotinib induced barrier dysfunction in rat small intestine epithelial cells (IEC-6) by increasing epithelial permeability and down-regulating E-cadherin. The mRNA levels of various pro-inflammatory cytokines (Il-6, Il-25 and Il-17f) were increased after erlotinib treatment in IEC-6 cells.

Membrane assisted micro-solid phase extraction of pharmaceuticals with amino and urea-grafted silica gel.

Individual polar sorbents with surface-displayed amino groups (APS) and non-nucleophilic urea-groups (UPS), were prepared by chemical modification of granular silica gel with bifunctional silane coupling reagents. In this preliminary study, they were separately employed for micro-solid phase extraction (μ-SPE) of the quarternary salt of Amitriptyline (Ami), Carbamazepine (Cbz), Ketoprofen (Ket) and Diclofenac (Dfn) from aqueous samples in conjunction with high performance liquid chromatography. The resulting enrichment factors for both APS and UPS are comparable and exceeded those of μ-SPE involving commercial C18-silica gel sorbents.