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In this study, a laboratory-scale sequencing biofilm batch reactor (SBBR) was employed to explore a fast start-up of completely autotrophic nitrogen removal over nitrite (CANON) process. Partial nitrification was achieved by controlling free ammonia concentration and operating at above 30 WC; then the reactor was immediately operatedwith alternating periods of aerobiosis and anaerobiosis to start the anammox process. The CANON processwas successfully achieved in less than 50 d, and the total-nitrogen removal efficiency and the nitrogen removal ratewere 81%and 0.14 kg-N m-3 d-1 respectively. Afterwards, with the increasing of ammonium loading rate a maximum nitrogen removal rate of 0.39 kg-N m-3 d-1 was achieved on day 94. DNA analysis showed that 'Candidatus Brocadia' was the dominant anammox species and Nitrosomonas was the dominant aerobic ammonium-oxidizing bacteria in the CANON reactor. This study revealed that due to shortening the persistent and stable nitrite accumulation period the long start-up time of the CANON process can be significantly reduced. [ABSTRACT FROM AUTHOR]

A simple and reliable ultra performance liquid chromatography method was established for determination of genistein, genistin, daidzein, daidzin, glycitein and glycitin content in different period fermentation of Semen sojae praeparatum. The chromatographic separation was performed on an ACQUITY UPLC BEH C18 (2.1*50 mm, 1.7 µm). The mobile phase was composed of acetonitrile (A), 0.1% formic acid in water (B). The gradient elution conditions were as follows: 0-8 min, 10-24% (A), 8-10 min, 24-50% (A), 10-12 min, 50% (A). The chromatogram was monitored at wavelength of 260 nm during the experiment. The result showed that the content of daidzin, glycitin and genistin were reduced, however the content of daidzein, glycitein and genistein were increased. The method is simple, accurate and reproducible. It can be used to provide the theory basis for the quality control of traditional Chinese medicine Semen sojae praeparatum. Finally, it provides an identification standard for production and market circulation of Semen sojae praeparatum. [ABSTRACT FROM AUTHOR]

In the Three Gorges Reservoir area, 78.1% of precipitation pH was measured below 5.6 by gathering 233 samples of precipitation in 2009-13. The forest ecological system in this area was threatened. In order to quantify the acid risk to the forest ecosystem, acid deposition and nutrient nitrogen critical loads in the area were estimated using simple mass balance equations based on the critical load concept. The values of acid deposition and nutrient nitrogen critical loads varied from 0 to 10.3 keq·ha-1·yr-1 and from 0 to 3.5 keq·ha-1·yr-1, respectively. Among them, acid critical loads were mostly sensitive to net nitrogen uptake and the ratio of Bc to Al. The accuracy of two parameters improved for reducing the evaluation error of critical loads. And then, exceedance of critical loads was calculated on the basis of critical loads. For the forest soil, exceedance of critical loads were predicted (0-2.1 keq·ha-1·yr-1). Acid critical loads were exceeded approximately 4.8% across the entire region, which affected nutrient pools in forested mineral soils. For the forest plants, 20.1% of the forests were predicted to exceed the empirical critical load. In addition, plant species diversity was significantly reduced with the increase of nitrogen deposition. This suggested that forest soil and plants have been adversely affected by acid deposition in some regions of the reservoir area. Thus, the impact of acid deposition on the forest ecosystem can provide key protection regions for the government and a basis for the implementation of emissions reduction policy. [ABSTRACT FROM AUTHOR]

Background: Associations between Arg399Gln single-nucleotide polymorphism (SNP) in the XRCC1 gene and leukemia susceptibility have been studied extensively, however, the results are inconsistent. The aim of this study was to determine these associations using metaanalytical methods. Methods: A meta-analysis was performed to examine the associations between XRCC1 Arg399- Gln SNP and leukemia risk. A literature search of PubMed and Web of Science databases was conducted to identify relevant studies published up to March 10, 2015. The references of the retrieved articles were also screened. All the statistical analyses were conducted using Review Manager software. Results: The XRCC1 Arg399Gln SNP was found to be associated with increased childhood risk of acute lymphoblastic leukemia among Asians under the dominant (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.50-2.97, P<0.0001), allele contrast (OR 1.72, 95% CI 1.33-2.23, P<0.0001), and homozygote contrast (OR 2.34, 95% CI 1.25-4.36, P=0.008) models. However, no association was found in Caucasians between the SNP and risk of either chronic myeloid leukemia or chronic lymphocytic leukemia under any contrast model. Conclusion: The findings of the current meta-analysis indicate that the XRCC1 Arg399Gln SNP is a risk factor for childhood lymphoblastic leukemia in Asians. [ABSTRACT FROM AUTHOR]

A popular application of propellant containing of aluminum powder is as fuel for solid rocket motors (SRMs). The combustion gas contains large amounts of alumina particles, which will worsen the SRM thermal protection system by inducing severe mechanical erosion on the surface of the insulation material exposed directly to the high-temperature and high-velocity gas and solid two-phase flow. To protect the structures of SRMs from being damaged, a thermal protection system is required, and it must be optimally designed to be as thin as possible, but thick enough to survive the SRM operating time. To optimize the thickness of insulation material, the particle erosion model should be set up. But most existing particle erosion models are the empirical expressions obtained by experiment or direct reference to pipeline particle erosion models, which limit the application of the model. The ablation process and the flow are coupled with one another. So, to optimize thickness, numerical calculation of dynamic ablation of the insulation material in SRMs should be carried out. In this work, the ethylene propylene diene monomer (EPDM) ablative composite used as heat shield was analyzed. The physical, chemical, and mechanical processes of ablation were expounded. Models for insulation thermal decomposition and thermochemical ablation were constructed, in which pyrolysis and carbonization temperature, pyrolysis rate, latent heat and pyrolysis products, and the main reaction chemical equation of the thermal chemical ablation were researched and confirmed. The coupling of physics, chemistry, and mechanics is through the charring layer in the process of ablation of the insulation material. The charring layer was treated as a porous medium. The ablation models and its numerical method were applied to calculate the ablation of insulation material in an experimental SRM. The computed result is in good agreement with that of the experiment, which shows that the model and numerical method have good accuracy. [ABSTRACT FROM AUTHOR]

Minks (Neovison vison) farming is under a threat of a variety of viral infections with increasingly growing number of breeding in Northeastern and Western China. While interferon is effective in controlling viral infection, IFN among different species rarely share high homology enough to provide cross protective effect on inhibition of virus replication. We cloned, sequenced, phlogenetically analyzed and expressed the miIFN-γ gene in prokaryotic and eukaryotic cells. The anti-vesicular stomatitis virus (VSV) activity of miIFN-γ protein was tested in MDCK cells using in vitro cytopathic inhibition assay. The recombinant miIFN-γ could inhibit VSV replication in MDCK cells, which was confirmed by that pre-incubation of rabbit anti-miIFN-γ antibodies with miIFN-γ abrogated the miIFN-γ protective effect. Our findings implicated that the miIFN-γ gene may be a potential counter measure against viral infection in the mink farming. [ABSTRACT FROM AUTHOR]

The metazoan Quadrapyrgites consists, from proximal to distal ends, of an oral area, a cone, a collar, and an apex from the Early Cambrian Fortunian Stage in Xixiang Zhangjiagou section, southern Shaanxi Province, South China. Three morphological types of the apex, the most characteristic feature of the taxon, are identified from hundreds of Quadrapyrgites specimens. The Quadrapyrgites growth zone is situated at the oral end, where 12 terminal lobes are generated, uplifted, enlarged, and evaginated to form a crest; A one-by-one of crest number from 2 to 13 has been recognized. The unique growth pattern and ontogenetic sequence refute a cubozoan or cycloneuralian affinity for Olivooides and Quadrapyrgites, and instead defend a coronate scyphozoan hypothesis. An embryonic development and ontogenetic sequence with embryo and crest is constructed. [ABSTRACT FROM AUTHOR]

The article discusses research that described the Campaign on Atmospheric Aerosol Research network of China (CARE-China). Topics covered include the physical, chemical and optical properties of atmospheric aerosols in China, the efforts of atmospheric aerosols on climate and the environment, and instrumentation, methodologies and experimental procedures used across CARE-China.

Dyslipidemia plays crucial roles in the progression of diabetic nephropathy (DN). This study investigated the effects of high glucose on lipid accumulation in podocytes and explored its underlying mechanisms. Male db/m and db/db mice were fed a normal chow diet for 8 wk. Immortalised mouse podocytes were treated with or without high glucose for 24 h. The changes to the morphology and ultramicrostructures of the kidneys in mice were examined using pathological staining and electron microscopy. Intracellular lipid accumulation was evaluated by Oil Red O staining and a free cholesterol quantitative assay. The expressions of the molecules involved in low-density lipoprotein receptor (LDLr) pathway and podocyte injury were examined using immunofluorescent staining, real-time PCR, and Western blot. There were increased levels of plasma lipid, serum creatinine, and proteinuria in db/db mice compared with db/m mice. Moreover, there was significant mesangial matrix expansion, basement membrane thickening, podocyte foot process effacement, and phenotypic alteration in the db/db group. Additionally, lipid accumulation in the kidneys of db/db mice was increased due to increased protein expressions of LDLr, sterol regulatory element-binding protein (SREBP) cleavageactivating protein, and SREBP-2. These effects were further confirmed by in vitro studies. Interestingly, the treatment with LDLr siRNA inhibited lipid accumulation in podocytes and decreased the protein expression of molecules associated with phenotypic alteration in podocytes. High glucose disrupted LDLr feedback regulation in podocytes, which may cause intracellular lipid accumulation and alteration of podocyte phenotype, thereby accelerating DN progression. [ABSTRACT FROM AUTHOR]

The inhibition of osteoblast proliferation by glucocorticoids (GCs) is very important in the etiology of GC-induced osteoporosis. The mechanisms of this process are still not fully understood. The results of recent studies have indicated an important role for microRNAs in GC-mediated responses in various cellular processes, including cell proliferation and apoptosis. Therefore, we developed the hypothesis that these regulatory molecules might be involved in GC-decreased osteoblast proliferation. Western blotting, quantitative realtime PCR, cell proliferation assays, and luciferase assays were employed to investigate the role of miRNAs in GC-inhibited osteoblast proliferation. microRNA-199a-5p was significantly increased in osteoblasts treated with dexamethasone (Dex). To delineate the role of microRNA-199a-5p, we silenced and overexpressed microRNA-199a-5p in osteoblasts. We found that overexpressing microRNA-199a-5p remarkably increased the inhibition effect of Dex on osteoblast proliferation, and depleting microRNA-199a-5p significantly attenuated Dex-inhibited osteoblast proliferation. Results of mechanistic studies indicated that microRNA-199a-5p inhibited FZD4 and WNT2 expression through a microRNA-199a-5p binding site within the 3'-UTR of FZD4 and WNT2. The post-transcriptional repression of FZD4 and WNT2 were further confirmed by luciferase reporter assay. These results indicated that microRNA-199a-5p may play a significant role in GC-inhibited osteoblast proliferation by regulating the WNT signaling pathway. [ABSTRACT FROM AUTHOR]

Background: As a key link between innate and adaptive immune responses, the interferon (IFN) system is the first line of defense against viral infection. IFN, and in particular, IFN-α, has been used clinically as an effective therapeutic agent for viral infections. However, different subtypes of IFN-α demonstrate distinct antiviral activity. Therefore, it is important to identify IFN-α subtypes with high antiviral activity for the development of genetically engineered antiviral drugs. Results: In this study, we cloned the genes for 13 IFN-α subtypes from peripheral blood lymphocytes of the mink. The homologies of the 13 mink IFN-α genes were 93.6-99.3% and 88.8-98.4% at the nucleotide and amino acid sequence levels, respectively. In contrast to human and canine IFN-α subtypes, most mink IFN-α subtypes contained two N-glycosylation sites. We expressed and purified 13 mink IFN-α subtypes in Escherichia coli. The cytopathic effect inhibition assay showed that all the 13 recombinant mink IFN-α subtypes inhibited the propagation of vesicular stomatitis virus in WISH cells, with IFN-α2 and IFN-α12 demonstrating the highest activities. Furthermore, recombinant mink IFN-α2 and IFN-α12 significantly suppressed the propagation of canine distemper virus in Vero cells, with IFN-α2 demonstrating the highest activity. Conclusions: We identified the mink IFN-α2 subtype as a promising candidate for the development of effective antiviral drugs. [ABSTRACT FROM AUTHOR]

It is challenging to investigate the magnetic anisotropy of Fe/Si(001) film in the case a limited magnetic field strength, when both coherent rotation and domain wall displacement coexist in the magnetization reversal process. Owing to the domain wall displacement, the magnetization reversal switching field is far lower than the magnetic anisotropy field, and, consequently, only the magnetization reversal process near easy axis can be treated as coherent rotation. Here, we record the slope of the magnetic torque curve of an iron film grown on a Si(001) substrate measured near the easy axis by anisotropic magnetoresistance (AMR) to separate the coherent rotation of magnetization reversal process from domain wall displacement. Furthermore, the magnitudes of various magnetic anisotropy constants were derived from the magnetic torque curves. Our work suggests that the AMR at low fields can clearly separate the detailed contributions of various magnetic anisotropies when domain wall displacement existed in Fe(001) ultrathin film. We also report on the hysteresis behavior of such films as measured by magneto-optic Kerr effect [ABSTRACT FROM AUTHOR]

Autologous tumor vaccine modified with nonlytic Newcastle disease virus (ATV-NDV) is a promising vaccine for cancer immunotherapy. IL-7 plays a critical role in lymphocyte development and homeostasis. To improve the efficacy of ATV-NDV, we inserted the murine IL-7 gene into the genome of nonlytic NDV strain LX using reverse genetic system. The insertion of the IL-7 gene neither affected the main features of NDV replication nor its tumor selectivity. The gene product was biologically active and stable. Then we tested the antitumor effects of the autologous tumor vaccine modified with LX/(IL-7) in the murine tumor models. We showed that tumor cells modified with LX/IL-7 induced a strong antitumor activity both in prophylaxis and therapeutic models. The IFN-γ production and the cytotoxicity of tumor-specific CD8+ T cells were significantly enhanced after immunization with tumor cells modified with LX/(IL-7) in both models. Although the tumor-infiltrating CD4+ T cells and CD8+ T cells were both increased and their IFN-γ productions also were upregulated, the antitumor activity of the tumor vaccine modified with LX/(IL-7) was dependent on CD8+ T cells. Our results demonstrated that the autologous tumor vaccine modified with NDV strain LX/(IL-7) could promote the antitumor immune responses mediated by CD8+ T cells and significantly improve the efficacy of the ATV-NDV. [ABSTRACT FROM AUTHOR]

Electrical stimulation of ventral division of medial geniculate body (MGBv) neurons evokes a shift of the frequency-tuning curves of auditory cortical (AC) neurons toward the best frequency (BF) of the stimulated MGBv neurons (frequencyspecific plasticity). The shift of BF is induced by inhibition of responses at the BF of the recorded AC neuron, with coincident facilitation of responses at the BF of the stimulated MGBv neuron. However, the synaptic mechanisms are not yet understood. We hypothesize that activation of thalamocortical synaptic transmission and receptor function may contribute to MGBv stimulation-induced frequency-specific auditory plasticity and the shift of BF. To test this hypothesis, we measured changes in the excitatory postsynaptic currents in pyramidal neurons of layer III/IV in the auditory cortex following high-frequency stimulation (HFS) of the MGBv, using whole cell recordings in an auditory thalamocortical slice. Our data showed that in response to the HFS of the MGBv the excitatory postsynaptic currents of AC neurons showed long-term bidirectional synaptic plasticity and long-term potentiation and depression. Pharmacological studies indicated that the long-term synaptic plasticity was induced through the activation of different sets of N-methyl-Daspartate- type glutamatergic receptors, γ-aminobutyric acid-type receptors, and type 5 metabotropic glutamate receptors. Our data further demonstrated that blocking of different receptors with specific antagonists significantly inhibited MGBv stimulation-induced long-term plasticity as well as the shift of BF. These data indicate that these receptors have an important role in mediating frequency-specific auditory cortical plasticity. [ABSTRACT FROM AUTHOR]

A total of 16 strains of canine distemper virus (CDV) were detected from vaccinated minks, foxes, and raccoon dogs in four provinces in North-Eastern China between the end of 2011 and 2013. Upon sequence analysis of the haemagglutinin gene and comparison with wild-type CDV from different species in the same geographical areas, two non-synonymous single nucleotide polymorphisms were identified in 10 CDV strains, which led to amino acid changes at positions 542 (isoleucine to asparagine) and 549 (tyrosine to histidine) of the haemagglutinin protein coding sequence. The change at residue 542 generated a potentially novel N-glycosylation site. Masking of antigenic epitopes by sugar moieties might represent a mechanism for evasion of virus neutralising antibodies and reduced protection by vaccination. [ABSTRACT FROM AUTHOR]

Two novel Zn and Cu complexes with 5-chlorhydroxybenzoate and imidazole ligands, C41 H 36Zn2N8O13Cl 4 (1) and C26H22Cl2Cu2N8O6 (2), were prepared by slow evaporation method. Single crystal X-ray di?raction analysis was used to determine their structures. The purity of the complexes was confirmed by powder X-ray diffraction analysis. In 1 the Zn2+ cation is tetracoordinated with 2 nitrogen atoms from 2 imidazoles and 2 oxygen atoms from the 2 carboxyl groups in 5-chlorhydroxybenzoate. In 2 the coordination polyhedrons of Cu2+ center can be described as distorted square pyramidal geometry sharing common edges, with an oxygen atom on the top of the pyramid. The hydrogen bonds and π - π interactions between the 2 ligands contribute to the presence of the infinite one-dimensional chain in the structure. Furthermore, solid-state fluorescence spectra indicate that both complexes show violet-blue fluorescence and can be potentially used as violet-blue fluorescence materials. [ABSTRACT FROM AUTHOR]

The magneto-optical Kerr effect susceptometry technique is proposed to determine the uniaxial magnetic anisotropy (UMA) constant Ku. The magnetic properties of Cu/Fe/SiO2/Si grown by dc magnetron sputtering were investigated. The in-plane uniaxial magnetic anisotropy was probed by the magneto-optical Kerr effect (MOKE). The value of UMA, Ku = 2.5 ×103 J/m3, was simulated from the field dependence of ac susceptibility along the hard axis according to the Stoner—Wohlfarth (S—W) model, which is consistent with Ku = 2.7 × 103 J/m3 calculated from the magnetic hysteresis loops. Our results show that the magneto-optical Kerr effect susceptometry can be employed to determine the magnetic anisotropy constant owing to its high sensitivity. [ABSTRACT FROM AUTHOR]

Accumulated soluble amyloid beta- (Aβ-) induced aberrant neuronal network activity may directly contribute to cognitive deficits, which are the most outstanding characteristics of Alzheimer's disease (AD).The entorhinal cortex (EC) is one of the earliest affected brain regions in AD. Impairments of EC neurons are responsible for the cognitive deficits in AD. However, little effort has been made to investigate the effects of soluble Aβ on the discharge properties of EC neurons in vivo. The present study was designed to examine the effects of soluble Aβ1-42 on the discharge properties of EC neurons, using in vivo extracellular single unit recordings. The protective effects of gastrodin (GAS) were also investigated against Aβ1-42-induced alterations in EC neuronal activities. The results showed that the spontaneous discharge of EC neurons was increased by local application of soluble Aβ1-42 and that GAS can effectively reverse Aβ1-42-induced facilitation of spontaneous discharge in a concentration-dependent manner. Moreover, whole-cell patch clamp results indicated that the protective function of GAS on abnormal hyperexcitability may be partially mediated by its inhibitory action on Aβ1-42-elicited inward currents in EC neurons. Our study suggested that GAS may provide neuroprotective effects on Aβ1-42-induced hyperactivity in EC neurons of rats. [ABSTRACT FROM AUTHOR]

The composting of sewage sludge and maize straw was investigated in forced-aeration composting systems at initial C/N ratios of 14, 20, and 25, respectively. The temperatures of composting mixture with initial C/N ratios of 25 and 20 could meet the requirement of destroying pathogens. The final electrical conductivity (EC) of composting mixture with initial C/N ratios of 20 and 25 did not exceed the limit value of 3000 μS cm−1, and the NH4+-N content of composting mixture with an initial C/N ratio of 14 did not meet the limit value of 400 mg kg−1. The final NO3−-N and germination index (GI) of composting mixture with an initial C/N ratio of 25 were higher than those of composting mixtures with initial C/N ratios of 14 and 20. The Fourier transform infrared (FTIR) spectra of composting mixtures in the three composting mixtures showed the same changing pattern during the composting. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the metabolic properties of maintenance hemodialysis patients treated with glucose-containing and glucose-free dialysate using metabonomics. Pre- and post-dialysis serum samples from group G (-) using glucose-free dialysate, and group G (+) using glucose-added dialysate (glucose levels were 5.5 mmol/L) were analyzed and tested with high performance liquid chromatography quadrupole time-of-flight mass spectrometry. Orthogonal signal correction-partial least squares discriminate analysis revealed a significant difference in the post-dialysis metabolic properties between samples from the G (-) and G (+) groups, and concentrations of leucine and dihydroxyprostaglandin F2α were higher in the G (+) group than in the G (-) group. However, markers of reactive lipid mobilization and amino acid release, such as bile acids, aspartate, and valine, were lower in the G (+) group than in the G (-) group. There were no significant differences in excitatory neurotransmitters aspartate and phosphorylated anandamide. Use of liquid chromatography-tandem mass spectrometry metabonomics indicated that using glucose-added dialysate was superior to glucose-free dialysate in the protection of the central nervous system of maintenance hemodialysis patients, but had potential risks in stimulating oxidative stress. [ABSTRACT FROM AUTHOR]

IMPORTANCE Blood pressure reduction and renin-angiotensin-aldosterone system inhibition are targets for treatment of atherosclerosis. The effect of renin inhibition on coronary disease progression has not been investigated. OBJECTIVE To determine the effects of renin inhibition with aliskiren on progression of coronary atherosclerosis. DESIGN, SETTING, AND PARTICIPANTS A double-blind, randomized, multicenter trial (Aliskiren Quantitative Atherosclerosis Regression Intravascular Ultrasound Study) comparing aliskiren with placebo in 613 participants with coronary artery disease, systolic blood pressure between 125 and 139 mm Hg (prehypertension range), and 2 additional cardiovascular risk factors conducted at 103 academic and community hospitals in Europe, Australia, and North and South America (enrollment from March 2009 to February 2011; end of follow-up: January 31, 2013). INTERVENTIONS Participants underwent coronary intravascular ultrasound (IVUS) imaging and were randomized to receive 300 mg of aliskiren (n = 305) or placebo (n = 308) taken orally daily for 104 weeks. Disease progression was measured by repeat IVUS examination after at least 72 weeks of treatment. MAIN OUTCOMES AND MEASURES The primary efficacy parameter was the change in percent atheroma volume (PAV) from baseline to study completion. Secondary efficacy parameters included the change in normalized total atheroma volume (TAV) and the percentage of participants with atheroma regression. Safety and tolerability were also assessed. RESULTS Evaluable imaging data were available at baseline and follow-up for 458 participants (74.7%). The primary IVUS efficacy parameter, PAV, did not differ between participants treated with aliskiren (-0.33%; 95% CI, -0.68% to 0.02%) and placebo (0.11%; 95% CI, -0.24% to 0.45%) (between-group difference, -0.43% [95% CI, -0.92% to 0.05%]; P = .08). The secondary IVUS efficacy parameter, TAV, did not differ between participants treated with aliskiren (-4.1 mm³; 95% CI, -6.27 to -1.94 mm³) and placebo (-2.1 mm³; 95% CI, -4.21 to 0.07 mm³) (between-group difference, -2.04 mm³ [95% CI, -5.03 to 0.95 mm³]; P = .18). There were no significant differences in the proportion of participants who demonstrated regression of PAV (56.9% vs 48.9%; P = .08) and TAV (64.4% vs 57.5%; P = .13) in the aliskiren and placebo groups, respectively. CONCLUSIONS AND RELEVANCE Among participants with prehypertension and coronary artery disease, the use of aliskiren compared with placebo did not result in improvement or slowing of progression of coronary atherosclerosis. These findings do not support the use of aliskiren for regression or prevention of progression of coronary atherosclerosis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00853827. [ABSTRACT FROM AUTHOR]

Inefficient gene delivery poses a challenge for non-viral gene therapy. Cytoplasmic and nuclear membrane barriers are responsible for the inefficiency as they restrict the import of exogenous genes. The present study aimed to improve the transfection efficiency using a novel gene delivery system, which consisted of two components: ultrasound microbubbles and the nuclear factor κB (NFκB) binding motif. Ultrasound-targeted microbubble destruction (UTMD) was used to enhance the cytoplasmic import of plasmids and the NFκB binding motif was added to promote the nuclear intake of the plasmid from the cytoplasm. In the present study, human umbilical vein endothelial cells were transfected using UTMD with two different Cy3-labeled plasmids, phSDF-1α and phSDF-1α-NFκB. phSDF-1α-NFκB was constructed by inserting a specific DNA targeting sequence (five optimal repeats of the binding motif for the inducible transcription factor NFκB) into phSDF-1α. The nuclear import and gene expression efficiency of phSDF-1α-NFκB were compared with those of phSDF-1α to investigate the effect of the NFκB binding motif on transfection. The results showed that UTMD significantly increased the cytoplasmic intake of pDNA and maintained high cell viability. The nuclear import and gene expression of phSDF-1α-NFκB-transfected cells were significantly higher than those transfected with phSDF-1α. Compared with the NFκB-free plasmids, the quantity of NFκB plasmids in the nucleus increased 6.5-fold and the expression of SDF-1α was 4.4-fold greater. These results suggest that UTMD combined with NFκB binding motif significantly improve transfection efficiency by enhancing the cytoplasmic and nuclear import of exogenous plasmid DNA. [ABSTRACT FROM AUTHOR]

Periplasmic flagella are essential for the distinctive morphology, motility, and infectious life cycle of the Lyme disease spirochete Borrelia burgdorferi. In this study, we genetically trapped intermediates in flagellar assembly and determined the 3D structures of the intermediates to 4-nm resolution by cryoelectron tomography. We provide structural evidence that secretion of rod substrates triggers remodeling of the central channel in the flagellar secretion apparatus from a closed to an open conformation. This open channel then serves as both a gateway and a template for flagellar rod assembly. The individual proteins assemble sequentially to form a modular rod. The hook cap initiates hook assembly on completion of the rod, and the filament cap facilitates filament assembly after formation of the mature hook. Cryoelectron tomography and mutational analysis thus combine synergistically to provide a unique structural blueprint of the assembly process of this intricate molecular machine in intact cells. [ABSTRACT FROM AUTHOR]

Tumor heterogeneity of high-grade glioma (HGG) is recognized by four clinically relevant subtypes based on core gene signatures. However, molecular signaling in glioma stem cells (GSCs) in individual HGG subtypes is poorly characterized. Here we identified and characterized two mutually exclusive GSC subtypes with distinct dysregulated signaling pathways. Analysis of mRNA profiles distinguished proneural (PN) from mesenchymal (Mes) GSCs and revealed a pronounced correlation with the corresponding PN or Mes HGGs. Mes GSCs displayed more aggressive phenotypes in vitro and as intracranial xenografts in mice. Further, Mes GSCs were markedly resistant to radiation compared with PN GSCs. The glycolytic pathway, comprising aldehyde dehydrogenase (ALDH) family genes and in particular ALDH1A3, were enriched in Mes GSCs. Glycolytic activity and ALDH activity were significantly elevated in Mes GSCs but not in PN GSCs. Expression of ALDH1A3 was also increased in clinical HGG compared with low-grade glioma or normal brain tissue. Moreover, inhibition of ALDH1A3 attenuated the growth of Mes but not PN GSCs. Last, radiation treatment of PN GSCs up-regulated Mes-associated markers and down-regulated PN-associated markers, whereas inhibition of ALDH1A3 attenuated an irradiation-induced gain of Mes identity in PN GSCs. Taken together, our data suggest that two subtypes of GSCs, harboring distinct metabolic signaling pathways, represent intertumoral glioma heterogeneity and highlight previously unidentified roles of ALDH1A3-associated signaling that promotes aberrant proliferation of Mes HGGs and GSCs. Inhibition of ALDH1A3-mediated pathways therefore might provide a promising therapeutic approach for a subset of HGGs with the Mes signature. [ABSTRACT FROM AUTHOR]

Phenotypic similarities have long been recognized between subpopulations of glioma and neural stem cells. Many of these similar properties, including the robust abilities to self-renew, migrate, and invade, are hallmarks of glioma cells that render them extremely aggressive. However, the molecular mechanisms underlying this character, particularly in glioma stem-like cells that drive this disease, remain poorly understood. Here, we report the results of a differential miRNA expression screen that compared glioma and neural stem cells, where we found that miR-204 was markedly downregulated in both types of cells. Mechanistic investigations revealed that miR-204 simultaneously suppressed self-renewal, stem cell-associated phenotype, and migration of glioma cells by targeting the stemness-governing transcriptional factor SOX4 and the migration-promoting receptor EphB2. Restoring miR-204 expression in glioma cells suppressed tumorigenesis and invasiveness in vivo and increased overall host survival. Further evaluation revealed that the miR-204 promoter was hypermethylated and that attenuating promoter methylation was sufficient to upregulate miR-204 in glioma cells. Together, our findings reveal miR-204 as a pivotal regulator of the development of stem cell-like phenotypes and cell motility in malignant glioma cells. [ABSTRACT FROM AUTHOR]

Angiogenesis in glioma is associated with the poor prognosis of the disease and closely correlates with the highly invasive phenotype of glioma cells, which represents the most challenging impediment against the currently glioma treatments. Bmi-1, an onco-protein, has been implicated in the progression of various human cancers, including gliomas, whereas its role in glioma angiogenesis remains unclear. Our current study examined the effects of Bmi-1 on glioma angiogenesis in vitro as well as in vivo. We found that overexpression of Bmi-1 enhanced, whereas knockdown of Bmi-1 diminished, the capability of glioma cells to induce tubule formation and migration of endothelial cells and neovascularization in chicken chorioallantoic membrane. In vivo, Bmi-1 overexpression and knockdown, respectively, promoted and inhibited angiogenesis in orthotopically transplanted human gliomas. Furthermore, NF-κB activity and VEGF-C expression was induced by Bmi-1 overexpression, whereas Bmi-1 knockdown attenuated NF-κB signaling and decreased VEGF-C expression. Additionally suppression of NF-κB activity using a specific chemical inhibitor abrogated the NF-κB activation and the proangiogenic activities of glioma cells. Together, our data suggest that Bmi-1 plays an important role in glioma angiogenesis and therefore could represent a potential target for anti-angiogenic therapy against the disease. [ABSTRACT FROM AUTHOR]

The strength and duration of NF-κB signaling are tightly controlled by multiple negative feedback mechanisms. However, in cancer cells, these feedback loops are overridden through unclear mechanisms to sustain oncogenic activation of NF-κB signaling. Previously, we demonstrated that overexpression of miR-30e* directly represses IκBá expression and leads to hyperactivation of NF-κB. Here, we report that miR-182 was overexpressed in a different set of gliomas with relatively lower miR-30e* expression and that miR-182 directly suppressed cylindromatosis (CYLD), an NF-κB negative regulator. This suppression of CYLD promoted ubiquitin conjugation of NF-κB signaling pathway components and induction of an aggressive phenotype of glioma cells both in vitro and in vivo. Furthermore, we found that TGF-β induced miR-182 expression, leading to prolonged NF-κB activation. Importantly, the results of these experiments were consistent with an identified significant correlation between miR-182 levels with TGF-β hyperactivation and activated NF-κB in a cohort of human glioma specimens. These findings uncover a plausible mechanism for sustained NF-κB activation in malignant gliomas and may suggest a new target for clinical intervention in human cancer. [ABSTRACT FROM AUTHOR]

LReBaCuO (LRe = Nd, Sm, Gd) single domains possess a superior superconducting performance and have exhibited potential applications in the fields of superconducting bearings and permanent magnets. Therefore, the requirement of a large size for LReBaCuO single domains with high values of TC and JC is desirable. However, it has been found that some unexpected spontaneous nucleation actions always take place, which interrupt the growing process of the single domains. In this paper, the behavior of spontaneous nucleation in SmBaCuO-Ag solution has been investigated systematically. Experimental results reveal that the spontaneous nucleation that frequently takes place during the growing process could be eliminated greatly by reducing the cooling rate to a proper level. Based on the framework of the constitutional super-cooling theory, combined with the results obtained in experiments, we discuss the possible explanations for the spontaneous nucleation behavior in SmBaCuO-Ag solution. An assumption that the distribution of solute concentration CL, as well as the solid-liquid phase transition temperature TL, in SmBaCuO-Ag solution might be of a time-dependent nature is put forward. A graph of temperature versus time has been worked out based on the assumption, which matches the growth process behavior satisfactorily with the experimental results. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed tumors worldwide and is known to be resistant to conventional chemotherapy. New therapeutic strategies are urgently needed for treating HCC. Osthole, a natural coumarin derivative, has been shown to have anti-tumor activity. However, the effects of osthole on HCC have not yet been reported. Methods and Findings: HCC cell lines were treated with osthole at various concentrations for 24, 48 and 72 hours. The proliferations of the HCC cells were measured by MTT assays. Cell cycle distribution and apoptosis were determined by flow cytometry. HCC tumor models were established in mice by subcutaneously injection of SMMC-7721 or Hepa1-6 cells and the effect of osthole on tumor growths in vivo and the drug toxicity were studied. NF-κB activity after osthole treatment was determined by electrophoretic mobility shift assays and the expression of caspase-3 was measured by western blotting. The expression levels of other apoptosis-related genes were also determined by real-time PCR (PCR array) assays. Osthole displayed a dose- and time-dependent inhibition of the HCC cell proliferations in vitro. It also induced apoptosis and caused cell accumulation in G2 phase. Osthole could significantly suppress HCC tumor growth in vivo with no toxicity at the dose we used. NF-κB activity was significantly suppressed by osthole at the dose- and time-dependent manner. The cleaved caspase-3 was also increased by osthole treatment. The expression levels of some apoptosis-related genes that belong to TNF ligand family, TNF receptor family, Bcl-2 family, caspase family, TRAF family, death domain family, CIDE domain and death effector domain family and CARD family were all increased with osthole treatment. Conclusion: Osthole could significantly inhibit HCC growth in vitro and in vivo through cell cycle arrest and inducing apoptosis by suppressing NF-κB activity and promoting the expressions of apoptosis-related genes. [ABSTRACT FROM AUTHOR]

Objective. To clarify the pathogenesis of rheumatoid arthritis (RA) by comparing protein expression in fibroblast‐like synoviocytes (FLS) from patients with RA with that in FLS from normal subjects, using proteomics analysis. Methods. Proteins extracted from primary cultures of FLS obtained from 50 patients with RA and 10 normal subjects were analyzed by automated 2‐dimensional nano–electrospray ionization liquid chromatography tandem mass spectometry. Differentially expressed proteins were screened by 2‐sample t‐test (P < 0.05) and fold change (>1.5), based on the bioinformatics analysis. The expression of vasculature development–related proteins (Thy‐1, connective tissue growth factor [CTGF], and thrombospondin 1 [TSP‐1]) and redox‐related proteins (superoxide dismutase 2 [SOD2]) in synovial tissue was confirmed by real‐time polymerase chain reaction and Western blotting. The effect of Thy‐1 and CTGF knockdown on Thy‐1, CTGF, TSP‐1, and vascular endothelial growth factor (VEGF) was analyzed by RNA interference experiments. Results. According to the criteria of having >1 unique peptide per protein present and a false discovery rate of ≤5%, 1,060 proteins were identified from patients with RA, and 1,292 proteins were identified from normal subjects, from which 100 differentially expressed proteins were screened out from the RA proteins. Of these, 46 proteins were up‐regulated, and the remaining 54 proteins were down‐regulated. Gene ontology and pathway analyses showed that 6 vasculature development–related proteins were up‐regulated, including Thy‐1, CTGF, and TSP‐1, while 11 redox‐related proteins were down‐regulated, including SOD2. The results were consistent with those obtained using mass spectrometry. Thy‐1, VEGF, CTGF, and TSP‐1 were down‐regulated after Thy‐1 knockdown, and VEGF and CTGF were down‐regulated after CTGF knockdown. Recombinant human CTGF could enhance proliferation and Transwell migration of human umbilical vein endothelial cells. Conclusion. Up‐regulation of vasculature development–related proteins and down‐regulation of redox‐related proteins in FLS are predominant factors that may contribute to the pathogenesis of RA. [ABSTRACT FROM AUTHOR]

Disruption of ionic homeostasis and neuronal hyperexcitability contribute to early brain injury after subarachnoid hemorrhage (SAH). The hyperpolarization-activated/cyclic nucleotide (HCN)-gated channels play critical role in the regulation of neuronal excitability in hippocampus CA1 region and neocortex, in which the abnormal neuronal activities are more readily provoked. This study was to investigate the interactions between HCN channels and hyperneuronal activity after experimental SAH. The present results from wholecell recordings in rat brain slices indicated that (1) perfusion of hemoglobin (Hb)-containing artificial CSF produced neuronal hyperexcitability and inhibited HCN currents in CA1 pyramidal neurons, (2) nitric oxide/Spermine (NO/Sp), a controlled releaser of nitric oxide, attenuated neuronal excitability and enhanced HCN currents in CA1 pyramidal neurons, while L-nitroarginine (L-NNA), an inhibitor of nitric oxide synthase, reduced theHCNcurrents;and(3) the inhibitory action ofHbonHCNcurrentswasreversed by application of NO/Sp, which also reduced neuronal hyperexcitability; conversely, L-NNA enhanced inhibitory action of Hb on HCN currents. Additionally, Hb perfusion scavengedtheproductionofnitricoxideanddecreasedtheexpressionofHCN1subunitsinCA1region. IntheratSAHmodel,theexpressionofHCN1, both at mRNA and protein level, decreased in hippocampus CA1 region at 24 h and more pronounced at 72 h after SAH. These observations demonstrated a reduction of HCN channels expression after SAH and Hb reduced HCN currents in hippocampus CA1 pyramidal neurons. Inhibition of HCN channels by Hb may be a novel pathway for inducing the hyperneuronal excitability after SAH. [ABSTRACT FROM AUTHOR]

A full-scale biosystem consisting of two anaerobic reactors (HA and BF1) and four aerobic ones (BF2-BF4 and OD) in succession and receiving antibiotic-bearing (mainly streptomycin) wastewater was used for studying the impacts of antibiotics on microbial community structures. Significant decreases of streptomycin (from 3955 ± 1910 to 23.1 ± 4.7 μg L-1) and CODCr were observed along the treatment process. Cloning results show that the anaerobic reactors (HA and BF1) were dominated with Deltaproteobacteria (51%) mainly affiliated with sulfate-reducing bacteria (SRB), while the aerobic BF2 receiving streptomycin of 408.6 ± 59.7 μg L-1 was dominated with Betaproteobacteria (34%), Deltaproteobacteria (31%) and Bacteroidetes (14%). Gammaproteobacteria (15.9-22.4%), Betaproteobacteria (10.0-20.3%), and Bacteroidetes (4.5-29.7%) became the major bacterial groups in aerobic BF3-OD receiving streptomycin of ≤83 ± 13 μg L-1. Archaea affiliated with Methanomethylovorans hollandica-like methylotroph was abundant in HA and BF1 (archaea/bacteria, 0.54-0.40; based on specific gene copy number), suggesting the coexistence of SRB and methanogens in degrading pollutants. Fungi were abundant (fungi/bacteria, 0.15; based on specific gene copy number) with the dominance of Ascomycota (clone ratio of Ascomycota/eukarya, 25.5%) in BF2, suggesting that fungi could be an important player in pollutant removal under high levels of antibiotics. This study demonstrates that under high antibiotic levels, wastewater treatment communities may maintain system stability through adjusting bacterial, archaeal, and eukaryal compositions. [ABSTRACT FROM AUTHOR]

The article discusses a study on the effects of the cholesteryl ester transfer protein (CETP) inhibitor evacetrapib when used as monotherapy or combined with statins to treat patients with dyslipidemia. The study was a randomized controlled trial involving 398 U.S. and European patients conducted between April 2010 and January 2011. The patients' low-density lipoprotein cholesterol (LDL-C) levels were high while their high-density lipoprotein cholesterol (HDL-C) levels were low at the start of the trial. They were randomized to receive placebo, evacetrapib monotherapy or statin therapy with or without evacetrapib. It was found that evacetrapib monotherapy raised HDL-C levels and reduced LDL-C levels. Also discussed are the safety and tolerability of evacetrapib.

The proinflammatory and catabolic cytokine IL-1β has been implicated in the pathogenesis of osteoarthritis (OA) by mediating synovial inflammation and cartilage degeneration. Although synovial macrophages are suggested to be the source of IL-1β, the mechanism remains unclear. Ectopic deposition of hydroxyapatite (HA) crystals in joints is closely associated with OA and other arthropathies, but the precise role of HA in arthritis pathogenesis has not been clearly demonstrated. Here we show that HA crystals of a particular size and shape can stimulate robust secretion of proinflammatory cytokines IL-1β and IL-18 from murine macrophages in a NLRP3 inflammasome-dependent manner. HA-induced inflammasome activation is dependent on potassium efflux, generation of reactive oxygen species (ROS), and lysosomal damage, but independent of cell death. Mice lacking the inflammasome components are protected against HA-induced neutrophilic inflammation in the air-pouch model of synovitis, and they show decreased joint pathology accompanying spontaneous HA deposition in the ank-deficient mouse model of arthritis. Moreover, calcium crystal positive synovial fluids from some OA patients exhibited inflammasome-stimulatory activity in vitro. These results demonstrate that the NLRP3 inflammasome mediates the pathological effect of HA crystals in vitro and in vivo and suggest a critical role for the inflammasome in the pathogenesis of OA. [ABSTRACT FROM AUTHOR]

The article presents a study on the overexpression of a NAC transcriptional factors from Arachis hypogaea to improve drought and salt tolerance in transgenic arabidopsis. The study utilizes several methods including stress treatment of peanut plants, northern blotting analysis and salt tolerance assays. It also revealed the gene structure and sequence analysis of Arachis hypogaea NAC2 (ahNAC2) and the effects of abiotic stress on gene expression of the ahNAC2 in peanut plant.

Recent collaborative efforts have subclassified malignant glioblastomas into 4 clinical relevant subtypes based on their signature genetic lesions. Platelet-derived growth factor receptor α (PDGFRA) overexpression is concomitant with a loss of cyclin-dependent kinase inhibitor 2A (CDKN2A) locus (encoding P16INK4A and P14ARF) in a large number of tumors within one subtype of glioblastomas. Here we report that activation of PDGFRα conferred tumorigenicity to Ink4a/Arf-deficient mouse astrocytes and human glioma cells in the brain. Restoration of p16INK4a but not p19ARF suppressed PDGFRα-promoted glioma formation. Mechanistically, abrogation of signaling modules in PDGFRα that lost capacity to bind to SHP-2 or PI3K significantly diminished PDGFRα-promoted tumorigenesis. Furthermore, inhibition of SHP-2 by shRNAs or pharmacological inhibitors disrupted the interaction of PI3K with PDGFRα, suppressed downstream AKT/mTOR activation, and impaired tumorigenesis of Ink4a/Arf-null cells, whereas expression of an activated PI3K mutant rescued the effect of SHP-2 inhibition on tumorigenicity. PDGFRα and PDGF-A are coexpressed in clinical glioblastoma specimens, and such co-expression is linked with activation of SHP-2/AKT/mTOR signaling. Together, our data suggest that in glioblastomas with Ink4a/Arf deficiency, overexpressed PDGFRα promotes tumorigenesis through the PI3K/AKT/mTOR-mediated pathway regulated by SHP-2 activity. These findings functionally validate the genomic analysis of glioblastomas and identify SHP-2 as a potential target for treatment of glioblastomas. [ABSTRACT FROM AUTHOR]

The recent energy crisis has triggered significant attention on the microbial synthesis of lipids, which comprise the raw material for biodiesel production. Microbial oil accumulation with filamentous fungi has great potential because filamentous fungi can form pellets during cell growth, and these pellets are much easier to harvest from cell broth. This paper focuses on the cell pelletization process of the oleaginous Mucor circinelloides. We have studied the effect of various cultural conditions on pelletized cell growth and lipid accumulation. This study is the first to report that pH adjustment during cell growth plays a key role in pellet formation of M. circinelloides and describes a handy method by which to induce cell pelletization in submerged fungal cultivation. Our study reveals that cell growth and lipid production are not significantly affected by pelletization and that lipid accumulation is triggered at stressed conditions, such as a high carbon-to-nitrogen ratio and high temperature. [ABSTRACT FROM AUTHOR]

Pseudomonas chlororaphis GP72 is a root-colonizing biocontrol strain isolated from the green pepper rhizosphere that synthesizes two phenazine derivatives: phenazine-1-carboxylic acid (PCA) and 2-hydroxyphenazine (2-OH-PHZ). The 2-OH-PHZ derivative shows somewhat stronger broad-spectrum antifungal activity than PCA, but its conversion mechanism has not yet been clearly revealed. The aim of this study was to clone and analyze the phenazine biosynthesis gene cluster in this newly found strain and to improve the production of 2-OH-PHZ by gene disruption and precursor addition. The conserved phenazine biosynthesis core operon in GP72 was cloned by PCR, and the unknown sequences located upstream and downstream of the core operon were detected by random PCR gene walking. This led to a complete isolation of the phenazine biosynthesis gene cluster phzIRABCDEFG and phzO in GP72. Gene rpeA and phzO were insertionally mutated to construct GP72AN and GP72ON, respectively, and GP72ANON collectively. The inactivation of rpeA resulted in a fivefold increase in the production of PCA, as well as 2-OH-PHZ. The addition of exogenous precursor PCA to the broth culture, to determine the conversion efficiency of PCA to 2-OH-PHZ under current culture conditions, revealed that PCA had a positive feedback effect on its own accumulation, leading to enhanced synthesis of both PCA and 2-OH-PHZ. The production of 2-OH-PHZ by GP72AN increased to about 170 μg ml, compared with just 5 μg ml for the wild type. The hypothesis of biosynthetic pathway for 2-OH-PHZ from PCA was confirmed by identification of 2-hydroxyphenazine-1-carboxylic acid as an intermediate in the culture medium of the high-phenazine producing GP72AN mutant. [ABSTRACT FROM AUTHOR]

The objective of this study was to identify the most effective treatment by evaluating the different therapies used to treat mild, moderate, and severe Henoch–Schönlein purpura (HSP) patients. We performed a retrospective study of children discharged with a diagnosis of HSP. The study group consisted of 425 children divided into mild, moderate, and severe condition groups. Different therapeutic protocols of hydrocortisone sodium succinate (HCSS) therapy, methylprednisolone (MP) pulse therapy, and MP combination with tripterygium glycoside (TG) therapy were used to treat the different groups. The evaluation of curative effect was performed. After 4 weeks, all patients with no obvious recovery were treated by strengthening the different treatment intervention. The remission time of skin, joint, and gastrointestinal manifestations was evaluated, and the results of the follow-up were analyzed (remission time of proteinuria, relapse, and side effects of therapy). After 4 weeks, in the mild group, the difference of the curative effect between HCSS and MP therapy was not statistically significant. Moderate HSP patients were more likely to respond to MP therapy than HCSS therapy ( P < 0.05). Severe HSP patients were more likely to respond to MP combination with TG than single MP therapy ( P < 0.05). At last follow-up, they all had normal urinalysis. In the moderate HSP group, the mean duration of proteinuria was shorter in the MP pulse therapy group than in the HCSS therapy group ( P < 0.05). In the mild group, the mean duration of purpura was shorter in HCSS therapy group than in the MP pulse therapy group ( P < 0.05). At last follow-up, 99 patients had recurrences of purpura and/or proteinuria and 41 patients had liver functional impairment and/or hypertension. The relapse and side effects were all satisfactorily controlled, and the rates of relapse and side effects did not differ between groups with different therapies ( P > 0.05). Our study has demonstrated a superior effect for HCSS therapy in patients with mild HSP disease, for MP therapy in patients with moderate disease, and for MP combined with TG therapy in patients with severe disease. MP therapy administered initially reduces the duration of urinary protein abnormality. The therapeutic protocols did not increase the risk of relapse and were safe. [ABSTRACT FROM AUTHOR]

We recently showed that increasing Wnt/β-catenin signalling in the bone marrow microenvironment or in multiple myeloma (MM) cells clearly suppresses osteoclastogenesis in SCID-hu mice; however, this regulation of osteoclastogenesis could result directly from activation of Wnt/β-catenin signalling in osteoclasts or indirectly from effects on osteoblasts. The present studies characterized Wnt/β-catenin signalling and its potential role in osteoclasts. Systematic analysis of expression of WNT, FZD, LRP and TCF gene families demonstrated that numerous Wnt-signalling components were expressed in human osteoclasts from patients with MM. Functional Wnt/β-catenin signalling was identified by accumulation of total and active β-catenin and increases in Dvl-3 protein in response to Wnt3a or LiCl. Furthermore, Wnt-induced increases in β-catenin and Dvl-3 were attenuated by Wnt antagonists Dkk1 and sFRP1. Finally, Wnt3a-induced TCF/LEF transcriptional activity suggests that canonical Wnt signalling is active in osteoclasts. Supernatants from dominant-negative-β-catenin–expressing osteoblast clones significantly stimulated tartrate-resistant acid phosphatase–positive osteoclast formation from primary MM-derived osteoclasts, compared with supernatants from control cells. These results suggested that Wnt/β-catenin signalling is active in osteoclasts in MM and is involved in osteoclastogenesis in bone marrow, where it acts as a negative regulator of osteoclast formation in an osteoblast-dependent manner in MM. [ABSTRACT FROM AUTHOR]

Background: Multiple subtypes of avian influenza viruses have crossed the species barrier to infect humans and have the potential to cause a pandemic. Therefore, new influenza vaccines to prevent the co-existence of multiple subtypes within a host and cross-species transmission of influenza are urgently needed. Methods: Here we report a multi-epitope DNA vaccine targeted towards multiple subtypes of the influenza virus. The protective hemagglutinin (HA) antigens from H5/H7/H9 subtypes were screened for MHC II class-restricted epitopes overlapping with predicted B cell epitopes. We then constructed a DNA plasmid vaccine, pV-H3-EHA-H1, based on HA antigens from human influenza H3/H1 subtypes combined with the H5/H7/H9 subtype Th/B epitope box. Results: Epitope-specific IFN-g ELISpot responses were significantly higher in the multi-epitope DNA group than in other vaccine and control groups (P < 0.05). The multi-epitope group significantly enhanced Th2 cell responses as determined by cytokine assays. The survival rate of mice given the multi-epitope vaccine was the highest among the vaccine groups, but it was not significantly different compared to those given single antigen expressing pVH1HA1 vaccine and dual antigen expressing pV-H3-H1 vaccine (P > 0.05). No measurable virus titers were detected in the lungs of the multi-epitope immunized group. The unique multi-epitope DNA vaccine enhanced virus-specific antibody and cellular immunity as well as conferred complete protection against lethal challenge with A/New Caledonia/20/99 (H1N1) influenza strain in mice. Conclusions: This approach may be a promising strategy for developing a universal influenza vaccine to prevent multiple subtypes of influenza virus and to induce long-term protective immune against cross-species transmission. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the fifth most common malignancy caused by environmental and genetic factors. MicroRNAs (miRNAs) are a class of short non-coding RNAs with posttranscriptional regulatory functions. They participate in diverse biological pathways and function as gene regulators. Genetic polymorphisms in 3′ untranslated regions (3′ UTRs) targeted by miRNAs alter the strength of miRNA binding, with consequences on regulation of target genes thereby affecting the individual's cancer risk. We have previously predicted polymorphisms falling in miRNA-binding regions of cancer genes. We selected an insertion/deletion (Indel) polymorphism (rs3783553) in the 3′ UTR of interleukin (IL)-1α (IL1A) for a case–control study in a Chinese population. With samples from 403 HCC patients and 434 healthy control individuals, strong evidence of association was observed for the variant homozygote. This association was validated in a second independent case–control study with 1074 HCC patients and 1239 healthy control individuals (odds ratio = 0.62; 95% confidence interval = 0.49–0.78). We further show that the ‘TTCA’ insertion allele for rs3783553 disrupts a binding site for miR-122 and miR-378, thereby increasing transcription of IL-1α in vitro and in vivo. These findings suggest that functional polymorphism rs3783553 in IL1A could contribute to HCC susceptibility. Considering IL-1α affects not only various phases of the malignant process, such as carcinogenesis, tumor growth and invasiveness, but also patterns of interactions between malignant cells and the host's immune system, our results indicated that IL-1α may be a promising target for immunotherapy, early diagnosis and intervention of HCC. [ABSTRACT FROM PUBLISHER]

A series of molybdenum/tungsten polyoxometalate compounds, namely, [(MII(HL)2)Mo3O10] (M = Mn (1), Co (2), Ni (3)), [CuII2(L)2(HL)2]2(Mo8O26) (4), [Zn(HL)2(MoO4)]2·HL·4H2O (5), [CuII4(L)6WO4)]·3H2O (6) (HL = 3-(2-pyridyl)pyrazole), were designed and synthesized under hydrothermal conditions. X-ray diffraction analyses reveal that compounds 1−3have an isostructural wavelike chain structure consisting of the asymmetric building blocks of [Mo3O10], in which the ratio of octahedron {MoO6} and square pyramid {MoO5} is 1:2. The hexacoordinated transitional metal cation, just like one “anchor” to fix the above wavelike chain, is linked by two terminal oxygen atoms belonging to two edged asymmetric molybdate [Mo3O10]2−units, and further chelated by two 3-(2-pyridyl)pyrazole ligands. Although a similar synthetic method in preparation of 1−5was employed, compounds 4and 5show a completely different structure compared to compounds 1−3. Compound 4is composed of two separate parts of the [CuII2(L)2(HL)2]2+dimer and the ε-[Mo8O26]4−unit. Compound 5consists of a bimetallic tetranuclear cluster that is constructed from corner-sharing {MoO4} tetrahedra and {ZnN4O2} distorted octahedron forming a cyclic {Zn2Mo2O4} core. For compound 6, a one-dimensional structure is composed of WO42−linked by the centrosymmetric tetranuclear copper grids, in which two approximately planar [CuII(L)]2units with an inversion center stack parallel and face-to-face linked by two additional deprotonated ligands of L−1perpendicularly. [ABSTRACT FROM AUTHOR]

Objectives: Sonic hedgehog (Shh) signaling pathway is associated with tumor development; however, the role of Shh signaling in the development of olfactory neuroblastoma (ONB) is unknown. This study aimed to investigate the relationship between the regulation of Shh signaling and the pathogenesis of ONB. Methods: The expression of Shh signaling components was characterized by immunohistochemistry in human non-tumor olfactory epithelium and ONB specimens, and by RT-PCR and immunoblotting in human ONB cell lines. The impact of the treatment with cyclopamine (a selective inhibitor of the Shh pathway) and/or exogenous Shh on ONB cell proliferation, cycle and apoptosis was examined by MTT, soft agar colony formation and flow cytometry assays, respectively. The influence of Shh signaling on the expression of Shh signaling components and cell cycle-related regulators was determined by immunoblotting and quantitative RT-PCR, respectively. Results: The expression of Pacthed1, Gli1 and Gli2 was detected in 70, 70, and 65% of human ONB specimens, respectively, and in proportion of ONB cell lines, but not in non-tumor olfactory epithelium. Treatment with cyclopamine inhibited the proliferation and colony formation of ONB cells, induced ONB cell cycle arrest and apoptosis, and down-regulated the expression of Pacthed1, Gli1 and cyclin D1, but up-regulated p21 expression in vitro. These regulatory effects of cyclopamine were partially or completely erased by exogenous Shh. Conclusion: These data suggest that the Shh signaling pathway is crucial for the growth of ONB. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background: Ruptured sinus of Valsalva aneurysm (RSVA) can be associated with ventricular septal defects or isolated lesions. Percutaneous transcatheter closure of RSVA has been an alternative strategy to surgery. The results of transcatheter closure of the RSVA in 10 patients were presented. Methods: From January 2000 to May 2006, 10 patients (4 males, 6 females) aged from 7 years to 69 years (mean ages 37±18.8 years) were involved in the present report. The diagnosis of RSVA was made based on a combination of several imaging modalities. Of them, 9 patients were identified as congenital cause and one did as acquired RSVA. Two-dimensional and color Doppler echocardiography revealed the rupture of right coronary sinus into right ventricle in 5 cases and into right atrium in 3 cases, while non-coronary sinus ruptured into right atrium in 2 cases. Aortogram showed that the estimated size of the defect was 6.2±2.3 mm (2–10 mm). After the establishment of the arterio-venous wire loop, Amplatzer duct occluder (ADO) was deployed by antegrade venous approach in all patients. Results: ADO with 1–3mm larger than the defect was used. All defects were successfully occluded without any complications. On the follow-up, echocardiography showed neither residual shunt nor aortic regurgitation, and there was also no device embolization, infective endocarditis in any of the patients. Conclusions: Transcatheter closure is a feasible and effective alternative for both congenital and acquired RSVA. However, long-term follow-up is mandatory. [Copyright &y& Elsevier]

The occurrence of unilateral flagellar phase variation was previously demonstrated in Escherichia coli strains carrying the non-fliC flagellin-specifying locus flk. In this study, we investigated the mechanism involved in this process. By using sequencing and sequence analysis, the flk region between the chromosomal genes yhaC and rnpB was characterized in all described flk-positive E. coli strains, including the H35 strain identified in this study (the other strains used are H3, H36, H47, and H53 strains), and this region was found to contain a putative integrase gene and flanking direct repeats in addition to the flk flagellin-specifying gene flkA and a fliC repressor gene, flkB, indicating that there is a typical genomic islet (GI), which was designated the flk GI. The horizontal transfer potential of the flk GI was indicated by detection of the excised extrachromosomal circular form of the flk GI. By generating fliC-expressing variants of H3 and H47 strains, unilateral flagellar phase variation in flk-positive strains was shown to be mediated by excision of the flk GI. The function of the proposed integrase gene was confirmed by deletion and a complementation test. The potential integration sites of the flk GI were identified. A general model for flagellar phase variation in flk-positive E. coli strains can be expressed as fliCoff + flkAon fliCon + flkAnone. This is the first time that a molecular mechanism for flagellar phase variation has been reported for E. coli. [ABSTRACT FROM AUTHOR]

A new converter transformer and an inductive filtering method are presented to solve the existing problems of the traditional converter transformer and the passive filtering method of the high-voltage direct current (HVDC) system. It adopts the ampere-turn balance of the transformer as the filtering mechanism. A tap at the linking point of the prolonged winding and the common winding of the secondary windings is connected with the LC resonance circuit. It can realize the goal that once the harmonic current flows into the prolonged winding, the common winding will induct the opposite harmonic current to balance it by the zero impedance design of the common winding and the proper configuration of LC parameters, so there will be no inductive harmonic current in the primary winding. Moreover, the reactive power that the converter needs can be partly compensated in the secondary winding. Simulation results have verified the correctness of the theoretical analysis. The new converter transformer can greatly reduce the harmonic content in the primary winding, loss, and noise generated by harmonics in the transformer, and the difficulty of the transformer's insulation design. [ABSTRACT FROM AUTHOR]

Abstract: The hepatoprotective effects of total flavonoids of Bidens pilosa L. (TFB), a traditional Chinese medicine were evaluated in carbon tetrachloride (CCl4)-induced liver injury in mice and rats. Total flavonoids of Bidens pilosa L. (25, 50 and 100mg/kg) were administered via gavage daily for 10 days to CCl4-treated mice as well as TFB (30, 60 and 90mg/kg) administered for 6 weeks to CCl4-treated rats. Liver index (liver weight/body weight), serum levels of transaminases (alanine aminotransferase, ALT and aspartate aminotransferase, AST), hepatic malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were evaluated following the 10 days treatment in mice. In addition histopathologic changes and nuclear factor-κB (NF-κB) expression of the liver were detected with hematoxylin–eosin (HE) and immunohistochemistry methods, respectively. The results showed that TFB (50 and 100mg/kg) effectively reduced the CCl4-induced elevated liver index, serum ALT, AST levels, hepatic MDA content, and restored hepatic SOD, GSH-Px activities in acute liver injury mice. TFB (60 and 90mg/kg) treatment significantly inhibited NF-κB activation in liver fibrosis of rats. The histopathological analysis suggested that TFB reduced the degree of liver injury in mice and severity of liver fibrosis in rats. These results suggested that TFB had a protective and therapeutic effect on animal liver injury, which might be associated with its antioxidant properties and inhibition of NF-κB activation. [Copyright &y& Elsevier]

A novel electrode was prepared by implanting NH2 + into an ITO film (NH2/ITO). Gold nanoparticles were deposited on the surface of NH2/ITO electrode. The NH2/ITO and Au/NH2/ITO electrodes were used to determine hemoglobin (Hb) immobilized on the electrodes surfaces. The relationship of the reductive peak current value of Hb among different electrodes was: Hb/ITO:Hb/Au/ITO:Hb/NH2/ITO:Hb/Au/NH2/ITO=1:1.5:2:4. The linkage between the –NH2 implanted into ITO film and the –COOH of Hb was recognized to be the reason for the increase of active Hb coverage on NH2/ITO electrode compared with the ITO electrode. Increase of active Hb coverage on Au/NH2/ITO compared with Au/ITO was attributed to the different amount of gold nanoparticles deposited. The determination of Hb at an Au/NH2/ITO electrode was optimized. Calibration curve was obtained over the range of 1.0 × 10−8 – 1.0 × 10−6 mol · L−1 with a detection limit of 1.0 × 10−8 mol · L−1. Results showed that the novel NH2/ITO and Au/NH2/ITO electrodes exhibited good stability, reproducibility besides better electrochemical performance. [ABSTRACT FROM AUTHOR]