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Objects: The purpose of this study was to quantitatively assess the effects of water-based Liuzijue exercise on patients with COPD and compare it with land-based Liuzijue exercise., Materials and Methods: Participants were randomly allocated to one of three groups: the water-based Liuzijue exercise group (WG), the land-based Liuzijue exercise group (LG), and the control group (CG). CG participants accepted no exercise intervention, while training groups performed Liuzijue exercise according to Health Qigong Liuzijue (People's Republic of China) in different environments for 60-min sessions twice a week for 3 months., Results: Of the 50 patients enrolled, 45 (90%) completed the 3-month intervention. The CG showed decreased expiratory muscle strength, extensor and flexor endurance ratio (ER) of the elbow joints and flexor peak torque (PT), total work (TW), and ER of the knee joints ( p <0.05). Both training groups showed improved respiratory muscle strength, which differed from the CG ( p <0.001). In addition, extensor and flexor TW of the elbow joints in the training groups were increased ( p <0.01), and the WG differed from the CG in extensor TW and ER and flexor TW ( p <0.01), while the LG differed from the CG in flexor TW and extensor ER ( p <0.05). PT, PT/body weight (BW), and TW in the knee joint extensor in the training groups were increased as well (PT and PT/BW: p <0.05, TW: p <0.01), and the WG differed from the CG in terms of knee joints outcomes, while the LG differed from the CG in flexor TW only ( p <0.05)., Conclusion: Water-based Liuzijue exercise has beneficial effects on COPD patients' respiratory muscle strength and peripheral skeletal muscle function, and additional benefits may exist in endurance of upper limbs and strength and endurance of lower limbs when compared with land-based Liuzijue exercise., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Lung cancer is one of the most common types of cancer worldwide, with the highest mortality rate of all types of cancer. In the present study, epidermal growth factor receptor (EGFR) mutations of 354 primary patients with non-small cell lung cancer (NSCLC) of Chinese ethnicity were detected following formalin-fixed and paraffin-embedded specimen DNA extraction, polymerase chain reaction amplification, and sanger sequencing. The total rate of occurrence of EGFR somatic mutation in these 354 patients was 48.02%. Of these detected EGFR mutations, 27.40% were located in exon 19 and 25.99% in exon 21. The most frequent mutation in exon 19 was E746-A750del (8.47%), and in exon 21, L858R (10.17%). EGFR mutation rates were significantly associated with sex [female vs. male: 60.13 vs. 38.81%; adjusted odds ratio (OR), 1.93, 95% confidence interval (CI), 1.07-3.51, P=0.029], age (<60 vs. ≥60; 58.62 vs. 40.67%; adjusted OR, 1.87; 95% CI, 1.20-2.92; P=0.006) and histology [adenocarcinoma (ADC) vs. non-ADC; 52.76 vs. 26.56%; adjusted OR, 2.35; 95% CI, 1.28-4.50; P=0.007]. The frequency of E746&#95;A750del, Q787Q and L858R mutations were significantly different in ADC patients compared with squamous cell carcinoma patients (P<0.001). Furthermore, a novel EGFR mutation, M793K, was detected in 7 NSCLC patients with possible gefitinib resistance. The present study analyzed the EGFR exon 18-21 mutation occurrence profile for Chinese patients with NSCLC and identified significant associations between different EGFR mutations with demographic and histological factors. These results may offer clinical benefits and potential novel treatments.

Evidences of oxidative stress and mitochondrial dysfunction have been recognized in most of clinical and experimental liver diseases. SIRT3, a member of NAD + -dependent deacetylases, is mainly localized in mitochondria. So far, the role of SIRT3 in protecting hepatocytes against oxidative stress remains elusive. Herein, we found SIRT3 protein expression is decreased in tert-butyl hydroperoxide (t-BHP)-treated AML12 cells in vitro and primary hepatocytes from CCl 4 -injured mice in vivo. To further verify the role of SIRT3 in protecting hepatocytes from t-BHP-induced injury, SIRT3 overexpressed AML12 cell line and primary hepatocytes were generated. SIRT3 overexpressed hepatocytes showed improved cell viability upon t-BHP challenge, with less intracellular reactive oxygen species (ROS) accumulation. SIRT3 overexpression reduced superoxide dismutase 2 acetylation level and stimulated nuclear factor erythroid 2-related factor 2 nuclear translocation to enhance anti-oxidative capacity. Moreover, SIRT3 deacetylated peroxisome proliferator-activated receptor γ coactivator 1α to promote mitochondrial biogenesis, and 8-oxoguanine DNA glycosylase 1 to orchestrate DNA repair, resulting in improved mitochondrial function. Through deacetylating Ku70, SIRT3 also abated mitochondrial translocation of dynamin-related protein 1, to attenuate mitochondrial fragmentation in t-BHP-injured hepatocytes. These results suggested that SIRT3 protected hepatocytes against oxidative stress by enhancing ROS scavenging and maintaining mitochondrial integrity.

Oxidative stress is important for the initiation and progression of cancers, which confers the cells with a survival advantage by inducing oxidative adaption and drug resistance. Therefore, developing strategies to promote oxidative stress-induced cytotoxicity could be important for cancer therapy. Herein, we found that H2O2-mediated oxidative stress increases TRPV2 expression in human hepatoma (HepG2 and Huh-7) cells. This occurred at the mRNA and protein levels in a dose-dependent manner. The significance of TRPV2 in promoting H2O2-induced cell death was demonstrated in gain and loss of function studies with overexpression and knockdown of TRPV2, respectively. Mechanistically, H2O2-induced cell death involves inhibition of pro-survival signaling proteins (Akt, Nrf2) and activation of pro-death signaling proteins (p38, JNK1). Overexpression of TRPV2 in H2O2-treated hepatoma cells aggravates the inhibition of Akt and Nrf2, while it enhances the activation of p38 and JNK1 at the early stage of cell death. Interestingly, increased expression of TRPV2 in HepG2 cells improved the efficacy of stress-associated chemicals to induce cell death. Our findings suggest that TRPV2 acts as an important enhancer for H2O2-induced cytotoxicity. This process occurred by the inhibition of Akt and Nrf2 as well as the early activation of p38 and JNK1. These findings have important implications for inhibition of oxidative adaption and drug resistance., (Copyright © 2015 Elsevier Inc. All rights reserved.)

P2X receptors are cation-permeable ion channels gated by extracellular adenosine triphosphate (ATP). Available crystallographic data suggest that ATP-binding ectodomain is connected to the transmembrane pore domain by three structurally conserved linker regions, which additionally frame the lateral fenestrations through which permeating ions enter the channel pore. The role of these linker regions in relaying the conformational change evoked by ATP binding of the ectodomain to the pore-forming transmembrane domain has not been investigated systematically. Using P2X4R as our model, we employed alanine and serine replacement mutagenesis to determine how the side chain structure of these linker regions influences gating. The mutants Y54A/S, F198A/S, and W259A/S all trafficked normally to the plasma membrane of transfected HEK293 cells but were poorly responsive to ATP. Nevertheless, the function of the F198A/S mutants could be recovered by pretreatment with the known positive allosteric modulator of P2X4R, ivermectin (IVM), although the IVM sensitivity of this mutant was significantly impaired relative to wild type. The functional mutants Y195A/S, F200A/S, and F330A/S exhibited ATP sensitivities identical to wild type, consistent with these side chains playing no role in ATP binding. However, Y195A/S, F200A/S, and F330A/S all displayed markedly changed sensitivity to the specific effects of IVM on current deactivation, suggesting that these positions influence allosteric modulation of gating. Taken together, our data indicate that conserved amino acids within the regions linking the ectodomain with the pore-forming transmembrane domain meaningfully contribute to signal transduction and channel gating in P2X receptors.

The aim of this study was to investigate the effects of Callistephus chinensis flower (CCF) polyphones on symptoms of metabolic syndrome in a newly developed high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) mouse model. C57BL/6J mice were fed a high fat diet (HFD; 50% energy as fat) with normal drinking fluid or HFD with CCF polyphones (50 mg L(-1) or 100 mg L(-1)) in drinking fluid for 12 weeks. As a comparison, mice fed a normal-fat (NFD; 10% energy as fat) and with normal drinking fluid were also included. The HFD group developed more severe symptoms of metabolic syndrome than the NFD group. CCF polyphones treatment significantly reduced fecal lipids compared to the HFD group, suggesting a strong indication of improved lipid metabolism. Liver damage and liver triglyceride levels were also decreased by CCF polyphones treatment. Moreover, both morphologic and histological detections indicated that CCF polyphones significantly reversed HFD-induced hepatic steatosis and liver injury. Furthermore, CCF polyphones significantly ameliorated both HFD-induced metabolic disorders, such as insulin resistance, and inflammatory cytokines, including interlukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Moreover, hepatic peroxisome proliferator-activated receptor (PPARα) and the gene involved in PPARα, Peroxisomal acyl-CoA oxidase (ACOX), were markedly up-regulated at protein levels by CCF polyphones. Our results demonstrate that the HFD produces metabolic syndrome of NAFLD, and CCF polyphones treatment can alleviate these symptoms. The beneficial effects of CCF polyphones are associated with improved lipid metabolism and reduced levels of inflammatory cytokines.

Human induced pluripotent stem cells (iPSC) can be used to understand the pathological mechanisms of human disease. These cells are a promising source for cell-replacement therapy. However, such studies require genetically defined conditions. Such genetic manipulations can be performed using the novel Transcription Activator-Like Effector Nucleases (TALENs), which generate site-specific double-strand DNA breaks (DSBs) with high efficiency and precision. Combining the TALEN and iPSC methods, we developed two iPS cell lines by generating the point mutation A5768G in the SCN1A gene, which encodes the voltage-gated sodium channel Nav1.1 α subunit. The engineered iPSC maintained pluripotency and successfully differentiated into neurons with normal functional characteristics. The two cell lines differ exclusively at the epilepsy-susceptibility variant. The ability to robustly introduce disease-causing point mutations in normal hiPS cell lines can be used to generate a human cell model for studying epileptic mechanisms and for drug screening.

Inhibitors of carbohydrate-hydrolysing enzymes play an important role for the treatment of diabetes. One of the therapeutic methods for decreasing of postprandial hyperglycemia is to retard absorption of glucose by the inhibition of carbohydrate- hydrolysing enzymes, such as α-glucosidase, in the digestive organs. To investigate the therapeutic potential of compounds from natural sources, Callistephus chinensis flowers (CCF) were tested for inhibition of α-glucosidase, and acarboes was used as the positive control. The 70 % ethanol extract of CCF exhibited significant α-glucosidase inhibitory activities with IC50 value of 8.14 μg/ml. The stepwise polarity fractions of CCF were tested further for in vitro inhibition of α-glucosidase. The ethyl acetate (EtOAc) fraction exhibited the most significant inhibitory activity. Eight pure compounds, apigenin, apigenin-7-O-β-D- glucoside, kaempferol, hyperin, naringenin, quercetin, luteolin, and kaempferol-7-O-β-D- glucoside, were isolated (using enzyme assay-guide fractionation method) from the EtOAc fraction. Among these, quercetin was the most active one (IC50 values 2.04 μg/ml), and it appears that the inhibiting percentages are close to acarbose (IC50 values 2.24 μg/ml), the positive control, on α-glucosidase inhibition. HPLC/UV analysis indicated that the major components of CCF are kaempferol, hyperin and quercetin. The presented results revealed that CCF containing these eight flavonoids could be a useful natural source in the development of a novel α-glucosidase inhibitory agent against diabetic complications.

Pd-catalytic C-S activation was successfully applied to initiate the cross-coupling of (2-methylthio-3-ester)benzofurans with 2-hydroxyphenylboronic acids and sequential intramolecular transesterification process under Liebeskind-Srogl conditions. Thus, a novel [3 + 3] annulation strategy for efficient synthesis of coumestan derivatives has been developed from readily available starting materials.

In previous studies, the Alfin1 gene, a transcription factor, enhanced salt tolerance in alfalfa, primarily through altering gene expression levels in the root. Here, we examined the molecular evolution of the Alfin-like (AL) proteins in two Arabidopsis species (A. lyrata and A. thaliana) and a salt-tolerant close relative Thellungiella halophila. These AL-like proteins could be divided into four groups and the two known DUF3594 and PHD-finger domains had co-evolved within each group of genes, irrespective of species, due to gene duplication events in the common ancestor of all three species while gene loss was observed only in T. halophila. To detect whether natural selection acted in the evolution of AL genes, we calculated synonymous substitution ratios (dn/ds) and codon usage statistics, finding positive selection operated on four branches and significant differences in biased codon usage in the AL family between T. halophila and A. lyrata or A. thaliana. Distinctively, only the AL7 branch was under positive selection on the PHD-finger domain and the three members on the branch showed the smallest difference when codon bias was evaluated among the seven clusters. Functional analysis based on transgenic overexpression lines and T-DNA insertion mutants indicated that salt-stress-induced AtAL7 could play a negative role in salt tolerance of A. thaliana, suggesting that adaptive evolution occurred in the members of AL gene family.

The title molecule (E)-2-[2-(2,6-dichlorophenyl)ethenyl]-8-hydroxyquinoline (DPEQ) was synthesized and characterized by FT-IR, UV-vis, NMR spectroscopy. The molecular geometry, vibrational frequencies and gauge independent atomic orbital (GIAO) 1H and 13C NMR chemical shift values of the compound in the ground state have been calculated by using the density functional theory (DFT) method. All the assignments of the theoretical frequencies were performed by potential energy distributions using VEDA 4 program. The calculated results indicate that the theoretical vibrational frequencies, 1H and 13C NMR chemical shift values show good agreement with experimental data. The electronic properties like UV-vis spectral analysis and HOMO-LUMO analysis of DPEQ have been reported and compared with experimental data. Information about the size, shape, charge density distribution and site of chemical reactivity of the molecule has been obtained by mapping electron density isosurface with molecular electrostatic potential (MEP)., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Palladium-catalyzed cyclization of β-alkylthio dienone derivatives affords 2-cyclopentenones in a regio- and stereoselective manner in the presence of silane. C-S activation, intramolecular carbopalladation and hydrogenolysis construct the cascade process.