Exploring a new ligand binding site of G protein-coupled receptors.

Identifying a target ligand binding site is an important step for structure-based rational drug design as shown here for G protein-coupled receptors (GPCRs), which are among the most popular drug targets. We applied long-time scale molecular dynamics simulations, coupled with mutagenesis studies, to two prototypical GPCRs, the M3 and M4 muscarinic acetylcholine receptors. Our results indicate that unlike synthetic antagonists, which bind to the classic orthosteric site, the endogenous agonist acetylcholine is able to diffuse into a much deeper binding pocket.

Biosynthesis of advanced biofuel farnesyl acetate using engineered Escherichia coli.

Diminishing petroleum reserves and the rapid accumulation of greenhouse gases lead to increasing interest in microbial biofuels. In this study, a heterologous farnesyl acetate biosynthesis pathway was constructed in Escherichia coli for the first time. Firstly, the AtoB, ERG13, tHMG1, ERG12, ERG8, MVD1, Idi, IspA and PgpB were expressed to accumulate farnesol in the E.

Mechanical Properties Study of Fe-Mn-Si Shape Memory Alloys Welding Seam Formed by Laser Welding with Filler Powder.

To reduce the residual stress and improve the fatigue property of the laser weldment by using the stress self-accommodation characteristic of Fe-Mn-Si shape memory alloys (SMAs), a Fe15Mn5Si12Cr6Ni memory alloy welding seam was formed inside 304 stainless steel by laser welding with filler powder. The combination of the hole-drilling method and the ANSYS software was used to research the distribution law of residual stress inside the laser welding specimen. The fatigue strength of the laser welded specimens with the Fe-Mn-Si SMAs welding seam (experimental materials) and 304 stainless steel welding seam (comparative materials) was measured by cycle bending fatigue test.

Molecular detection and genetic diversity of Theileria orientalis in cattle in China.

The apicomplexan parasite Theileria orientalis is a tick-borne intracellular protozoan parasite that is widely distributed throughout China. It causes bovine theileriosis in infected cattle, which results in huge economic losses to the cattle industry. In this study, the infection status of T.

Parallel Control of Distributed Parameter Systems.

In this paper, we study the control problems of distributed parameter systems, and discuss the limitations of traditional control methods. In recent years, social factors have gradually become an essential parameter of system modeling. For complex distributed parameter systems, the accurate modeling becomes difficult.

Crystal Structure of ATP-Bound Human ABCF1 Demonstrates a Unique Conformation of ABC Proteins.

Gene translation requires the correct selection of start codon AUG in mRNA. ATP-binding cassette subfamily F member 1 (ABCF1) plays a key role in the accuracy of start codon selection. However, the function of human ABCF1 is not clearly understood.

Correction: Adsorption properties of NO molecules on the hexagonal LaCoO (0 0 1) surface: a density functional theory study.

[This corrects the article DOI: 10.1039/C7RA03213G.].

[Evaluation of the Combined Removal of Heavy Metals by Saponin and Citric Acid from Municipal Sewage Sludges and Metal Stability Features].

Sewage sludge contains a high level of nutrients, such as nitrogen, phosphorus, potassium and organic matter, with a high recovery value. The presence of heavy metals in sludges has become a major limiting factor in the utilization of these sludges. Therefore, the removal of heavy metals before land application of sewage sludge has become very necessary.

First detection and molecular identification of Borrelia species in Bactrian camel (Camelus bactrianus) from Northwest China.

Comprehensive epidemiological surveys for Lyme disease have not been conducted for the Bactrian camel in China. In this study, a total of 138 blood specimens collected from Bactrian camels from Zhangye City in Gansu Province and Yili and Aksu in Xinjiang Province, China, were examined for the presence of Borrelia spp. Species-specificity nested PCR based on the 5S-23S rRNA, OspA, flaB and 16S rRNA genes revealed that the total positive rate of Borrelia spp.

Computational design of thermostabilizing point mutations for G protein-coupled receptors.

Engineering of GPCR constructs with improved thermostability is a key for successful structural and biochemical studies of this transmembrane protein family, targeted by 40% of all therapeutic drugs. Here we introduce a comprehensive computational approach to effective prediction of stabilizing mutations in GPCRs, named CompoMug, which employs sequence-based analysis, structural information, and a derived machine learning predictor. Tested experimentally on the serotonin 5-HT receptor target, CompoMug predictions resulted in 10 new stabilizing mutations, with an apparent thermostability gain ~8.

Metabolic Engineering of Escherichia coli for Production of 2-Phenylethanol and 2-Phenylethyl Acetate from Glucose.

Rose-like odor 2-phenylethanol (2-PE) and its more fruit-like ester 2-phenylethyl acetate (2-PEAc) are two important aromatic compounds and have wide applications. In the past, 2-PE and 2-PEAc were mainly produced from l-phenylalanine. In this study, Escherichia coli was engineered to de novo biosynthesis of 2-PE and 2-PEAc from glucose: first, overexpression of deregulated 3-deoxy-d-arabinoheptulosonate-7-phosphate synthase aroG and chorismate mutase/prephenate dehydratase pheA for increasing phenylpyruvate production in E.

High-throughput identification of G protein-coupled receptor modulators through affinity mass spectrometry screening.

G protein-coupled receptors (GPCRs) represent the largest class of cell surface proteins and thus constitute an important family of therapeutic targets. Therefore, significant effort has been put towards the identification of novel ligands that can modulate the activity of a GPCR target with high efficacy and selectivity. However, due to limitations inherent to the most common techniques for GPCR ligand discovery, there is a pressing need for more efficient and effective ligand screening methods especially for the identification of potential allosteric modulators.

Cold atmospheric plasma as a potential tool for multiple myeloma treatment.

Multiple myeloma (MM) is a fatal and incurable hematological malignancy thus new therapy need to be developed. Cold atmospheric plasma, a new technology that could generate various active species, could efficiently induce various tumor cells apoptosis. More details about the interaction of plasma and tumor cells need to be addressed before the application of gas plasma in clinical cancer treatment.

Gas Plasma Pre-treatment Increases Antibiotic Sensitivity and Persister Eradication in Methicillin-Resistant .

Methicillin-resistant (MRSA) is a major cause of serious nosocomial infections, and recurrent MRSA infections primarily result from the survival of persister cells after antibiotic treatment. Gas plasma, a novel source of ROS (reactive oxygen species) and RNS (reactive nitrogen species) generation, not only inactivates pathogenic microbes but also restore the sensitivity of MRSA to antibiotics. This study further found that sublethal treatment of MRSA with both plasma and plasma-activated saline increased the antibiotic sensitivity and promoted the eradication of persister cells by tetracycline, gentamycin, clindamycin, chloramphenicol, ciprofloxacin, rifampicin, and vancomycin.

Sanyang Xuedai enhances the radiosensitivity of human non-small cell lung cancer cells via increasing iNOS/NO production.

Objective: In this research, we aimed at finding out how San Yang Xue Dai (SYKT) promotes the radiosensitivity of non-small cell lung cancer (NSCLC) cell line NCI-H460.

Methods: Survival rate of NSCLC cells (A549, NCI-H460, NCI-H1650 and NCI-H1975) after the SYKT treatment or irradiation (IR) was calculated by the MTT assay. The radiosensitization of SYKT (0.

Identification of natural products as novel ligands for the human 5-HT receptor.

G protein-coupled receptors (GPCRs) constitute the largest human protein family with over 800 members, which are implicated in many important medical conditions. Serotonin receptors belong to the aminergic GPCR subfamily and play important roles in physiological and psychological activities. Structural biology studies have revealed the structures of many GPCRs in atomic details and provide the basis for the identification and investigation of the potential ligands, which interact with and modulate the receptors.

Alteration of metabolite profiling by cold atmospheric plasma treatment in human myeloma cells.

Background: Despite new progress of chemotherapy in multiple myeloma (MM) clinical treatment, MM is still a refractory disease and new technology is needed to improve the outcomes and prolong the survival. Cold atmospheric plasma is a rapidly developed technology in recent years, which has been widely applied in biomedicine. Although plasma could efficiently inactivate various tumor cells, the effects of plasma on tumor cell metabolism have not been studied yet.

Population Genetic Analysis of from Six Geographical Regions in China, Determined on the Basis of Micro- and Mini-satellite Markers.

, a tick-borne apicomplexan protozoan, causes a lymphoproliferative disease of cattle with high prevalence in tropical and sub-tropical regions. Understanding the genetic diversity and structure of local populations will provide more fundamental knowledge for the population genetics and epidemics of protozoa. In this study, 78 samples of collected from cattle/yaks representing 6 different geographic populations in China were genotyped using eight micro- and mini-satellite markers.

5-HT Receptor Structures Reveal the Structural Basis of GPCR Polypharmacology.

Drugs frequently require interactions with multiple targets-via a process known as polypharmacology-to achieve their therapeutic actions. Currently, drugs targeting several serotonin receptors, including the 5-HT receptor, are useful for treating obesity, drug abuse, and schizophrenia. The competing challenges of developing selective 5-HT receptor ligands or creating drugs with a defined polypharmacological profile, especially aimed at G protein-coupled receptors (GPCRs), remain extremely difficult.

Expression of Wnt/β-catenin related genes after skeletal muscle contusion.

Background: It was aimed to determine expressions of genes related to Wnt/β-catenin signaling for evaluating time duration after skeletal muscle contusion.

Methods: Pathological change of skeletal muscle was observed after H-E staining. mRNA of respective genes was quantified with real-time quantitative PCR.

Quercetin suppresses breast cancer stem cells (CD44/CD24) by inhibiting the PI3K/Akt/mTOR-signaling pathway.

Aims: Cancer stem cells (CSCs) are considered the prime source of cancer recurrence, metastasis, and progression and represent important targets for developing novel anticancer agents and therapeutic strategies. The aim of this study was to investigate the effect of treating breast CSCs with the anticancer flavonoid, quercetin.

Main Methods: We examined changes in the cluster of differentiation CD44/CD24CSC population and behavior using the breast cancer cell line MCF-7.

Single-Cell RNA-seq Reveals a Subpopulation of Prostate Cancer Cells with Enhanced Cell-Cycle-Related Transcription and Attenuated Androgen Response.

Increasing evidence suggests the presence of minor cell subpopulations in prostate cancer that are androgen independent and poised for selection as dominant clones after androgen deprivation therapy. In this study, we investigated this phenomenon by stratifying cell subpopulations based on transcriptome profiling of 144 single LNCaP prostate cancer cells treated or untreated with androgen after cell-cycle synchronization. Model-based clustering of 397 differentially expressed genes identified eight potential subpopulations of LNCaP cells, revealing a previously unappreciable level of cellular heterogeneity to androgen stimulation.

Long non-coding RNA (LncRNA) RMST in triple-negative breast cancer (TNBC): Expression analysis and biological roles research.

Microarray showed that lncRNA RMST was differentially expressed in cervical cancer. Further experiments were conducted to detect the expression and biological function of RMST in triple-negative breast cancer (TNBC). Microarray was used to screen the differentially expressed lncRNAs in TNBC.

Comparison of graphical optimization or IPSA for improving brachytheraphy plans associated with inadequate target coverage for cervical cancer.

Many studies have reported that inverse planning by simulated annealing (IPSA) can improve the quality of brachytherapy plans, and we wanted to examine whether IPSA could improve cervical cancer brachytherapy plans giving D < 6 Gy (with 7 Gy per fraction) at our institution. Various IPSA plans involving the tandem and ovoid applicators were developed for 30 consecutive cervical cancer patients on the basis of computed tomography: IPSA1, with a constraint on the maximum dose in the target volume; IPSA1-0, identical to IPSA1 but without a dwell-time deviation constraint; IPSA2, without a constraint on the maximum dose; and IPSA2-0, identical to IPSA2 but without a dwell-time deviation constraint. IPSA2 achieved similar results as graphical optimization, and none of the other IPSA plans was significantly better than graphical optimization.

Insight into the genetic diversity of Anaplasma marginale in cattle from ten provinces of China.

Background: Anaplasma marginale is an important tick-transmitted rickettsial pathogen of cattle, with worldwide distribution and an important economic impact. The genetic diversity of A. marginale strains has been extensively characterized in different geographical regions throughout the world, while information is limited on studies in China.