63 research outputs found

    The relationship between IGF1 and the expression spectrum of miRNA in the placenta of preeclampsia patients

    Get PDF
    Objectives: Pre-eclampsia (PE) affects many women worldwide and remains the leading cause of morbidity and mortality in neonatal and maternal settings. Abnormal expression of placental microRNAs (miRNAs) may be associated with PE. Material and methods: This study was conducted to the relationship between IGF1 and the expression spectrum of miRNA in the placenta of preeclampsia patient. The expression of miRNA in placental tissue was compared between pre-eclampsia (n = 6) and normal pregnant women (n = 5) miRNA targets were studied by computer simulation and functional assays. The role of miRNA was verified in trophoblast cell lines by apoptosis assay and invasion assay. Results: There was a significant increase in miRNAs in the placenta of women with pre-eclampsia compared with patients with normal pregnancy. Luciferase assay confirmed direct regulation of miRNA. Conclusions: The expression of IGF1 and miRNA was significantly increased in the placenta of patients with pre-eclampsia

    Pathologically Activated Neuroprotection via Uncompetitive Blockade of \u3cem\u3eN\u3c/em\u3e-Methyl-d-aspartate Receptors with Fast Off-rate by Novel Multifunctional Dimer Bis(propyl)-cognitin

    Get PDF
    Uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists with fast off-rate (UFO) may represent promising drug candidates for various neurodegenerative disorders. In this study, we report that bis(propyl)-cognitin, a novel dimeric acetylcholinesterase inhibitor and γ-aminobutyric acid subtype A receptor antagonist, is such an antagonist of NMDA receptors. In cultured rat hippocampal neurons, we demonstrated that bis(propyl)-cognitin voltage-dependently, selectively, and moderately inhibited NMDA-activated currents. The inhibitory effects of bis(propyl)-cognitin increased with the rise in NMDA and glycine concentrations. Kinetics analysis showed that the inhibition was of fast onset and offset with an off-rate time constant of 1.9 s. Molecular docking simulations showed moderate hydrophobic interaction between bis(propyl)-cognitin and the MK-801 binding region in the ion channel pore of the NMDA receptor. Bis(propyl)-cognitin was further found to compete with [3H]MK-801 with a Ki value of 0.27 μm, and the mutation of NR1(N616R) significantly reduced its inhibitory potency. Under glutamate-mediated pathological conditions, bis(propyl)-cognitin, in contrast to bis(heptyl)-cognitin, prevented excitotoxicity with increasing effectiveness against escalating levels of glutamate and much more effectively protected against middle cerebral artery occlusion-induced brain damage than did memantine. More interestingly, under NMDA receptor-mediated physiological conditions, bis(propyl)-cognitin enhanced long-term potentiation in hippocampal slices, whereas MK-801 reduced and memantine did not alter this process. These results suggest that bis(propyl)-cognitin is a UFO antagonist of NMDA receptors with moderate affinity, which may provide a pathologically activated therapy for various neurodegenerative disorders associated with NMDA receptor dysregulation

    Development of an Infectious Cell Culture System for Hepatitis C Virus Genotype 6a Clinical Isolate Using a Novel Strategy and Its Sensitivity to Direct-Acting Antivirals

    Get PDF
    Hepatitis C virus (HCV) is classified into seven major genotypes, and genotype 6 is commonly prevalent in Asia, thus reverse genetic system representing genotype 6 isolates in prevalence is required. Here, we developed an infectious clone for a Chinese HCV 6a isolate (CH6a) using a novel strategy. We determined CH6a consensus sequence from patient serum and assembled a CH6a full-length (CH6aFL) cDNA using overlapped PCR product-derived clones that shared the highest homology with the consensus. CH6aFL was non-infectious in hepatoma Huh7.5 cells. Next, we constructed recombinants containing Core-NS5A or 5′UTR-NS5A from CH6a and the remaining sequences from JFH1 (genotype 2a), and both were engineered with 7 mutations identified previously. However, they replicated inefficiently without virus spread in Huh7.5 cells. Addition of adaptive mutations from CH6a Core-NS2 recombinant, with JFH1 5′UTR and NS3-3′UTR, enhanced the viability of Core-NS5A recombinant and acquired replication-enhancing mutations. Combination of 22 mutations in CH6a recombinant with JFH1 5′UTR and 3′UTR (CH6aORF) enabled virus replication and recovered additional four mutations. Adding these four mutations, we generated two efficient recombinants containing 26 mutations (26m), CH6aORF_26m and CH6aFL_26m (designated “CH6acc”), releasing HCV of 104.3–104.5 focus-forming units (FFU)/ml in Huh7.5.1-VISI-mCherry and Huh7.5 cells. Seven newly identified mutations were important for HCV replication, assembly, and release. The CH6aORF_26m virus was inhibited in a dose- and genotype-dependent manner by direct-acting-antivirals targeting NS3/4A, NS5A, and NS5B. The CH6acc enriches the toolbox of HCV culture systems, and the strategy and mutations applied here will facilitate the culture development of other HCV isolates and related viruses

    Dynamic stability of a nonlinear multiple-nanobeam system

    Get PDF
    We use the incremental harmonic balance (IHB) method to analyse the dynamic stability problem of a nonlinear multiple-nanobeam system (MNBS) within the framework of Eringen’s nonlocal elasticity theory. The nonlinear dynamic system under consideration includes MNBS embedded in a viscoelastic medium as clamped chain system, where every nanobeam in the system is subjected to time-dependent axial loads. By assuming the von Karman type of geometric nonlinearity, a system of m nonlinear partial differential equations of motion is derived based on the Euler–Bernoulli beam theory and D’ Alembert’s principle. All nanobeams in MNBS are considered with simply supported boundary conditions. Semi-analytical solutions for time response functions of the nonlinear MNBS are obtained by using the single-mode Galerkin discretization and IHB method, which are then validated by using the numerical integration method. Moreover, Floquet theory is employed to determine the stability of obtained periodic solutions for different configurations of the nonlinear MNBS. Using the IHB method, we obtain an incremental relationship with the frequency and amplitude of time-varying axial load, which defines stability boundaries. Numerical examples show the effects of different physical and material parameters such as the nonlocal parameter, stiffness of viscoelastic medium and number of nanobeams on Floquet multipliers, instability regions and nonlinear amplitude–frequency response curves of MNBS. The presented results can be useful as a first step in the study and design of complex micro/nanoelectromechanical systems

    Exploration of a New Task-driven Model for Botany Field Practice

    No full text
    In the present context of increasing social demands for natural science education, increasing people's awareness of environmental biodiversity protection, and ecological civilization lifting to the state strategy, it is just the time to explore a new botany field practice model. The attempt of a new task-driven model for botany field practice will greatly enhance students' thinking about plants and nature, plants and environment, and plant and ecological civilization, and will inevitably enhance students' initiative awareness and practical ability to protect and rationally utilize plant resources

    Etching Behavior of GaN/GaAs(001) Epilayers Grown by MOVPE

    No full text
    Wet etching characteristics of cubic GAN (c-GaN) thin films grown on GaAs(001) by metalorganic vapor phase epitaxy (MOVPE) are investigated. The samples are etched in HCl, H_3PO_4, KOH aqueous solutions, and molten KOH at temperatures in the range of 90~300 ℃. It is found that different solution produces different etch figure on the surfaces of a sample. KOH-based solutions produce rectangular pits rather than square pits. The etch pits elongate in [1(1-bar)0] direction, indicating asymmetric etching behavior in the two orthogonal directions. An explanation based on relative reactivity of the various crystallographic planes is employed to interpret qualitatively the asymmetric etching behavior. In addition, it is found that KOH aqueous solution would be more suitable than molten KOH and the two acids for the evaluation of stacking faults in c-GaN epilayers

    Growth of Cubic GaN by MOCVD at High Temperature

    No full text
    High quality cubic GaN (c-GaN) is grown by metalorganic vapor deposition (MOCVD) at an increased growth temperature of 900 ℃, with the growth rate of 1.6 μm/h. The full width at half maximum (FWHM) of room temperature photoluminescence (PL) for the high temperature grown GaN film is 48meV. It is smaller than that of the sample grown at 830 ℃. In X-ray diffraction (XRD) measurement, the high temperature grown GaN shows a (002) peak at 20° with a FWHM of 21'. It can be concluded that, although c-GaN is of metastable phase, high growth temperature is still beneficial to the improvement in its crystal quality. The relationship between the growth rate and growth temperature is also discussed

    Optimization of CNTs and SiO2 for thermostability and mechanical properties of PF microcapsules : used for self-healing of closed wall cracks in goaf

    No full text
    Air leakage of closed wall in coal mine goaf would cause spontaneous combustion of remained coal. Most of measures to repair cracks are carried out after cracks are penetrated, which is not conducive to early prevention of spontaneous combustion. Repairing damage at the initial stage of cracking makes prevention effect to the best. Phenol-formaldehyde resin (PF) microcapsules embedded in closed wall to achieve self-healing of initial cracks, but the actual repair effect is often less than expected. PF microcapsules (PFM) of carbon nanotubes (CNTs) and silicon dioxide (SiO2) decorated shell for self-healing of closed wall cracks were prepared by in-situ polymerization. The effects of nanomaterials on morphology, chemical constitution, thermal performance and mechanical properties of PF microcapsules were characterized by scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and nanoindentation test. The test results indicated that nanomaterials were successfully introduced into the shell of PF microcapsules. The CNTs-SiO2@PF microcapsules were uniformly dispersed, the thermal decomposition was delayed, and the residual carbon was significantly increased, and the brittleness of PF microcapsules was significantly enhanced. The 0.2CNTs-SiO2@PF microcapsules (0.2CNTs-SiO2@PFM) had a uniform and full particle size, the initial decomposition temperature was 267.6℃, the residual mass was 41.3%, the maximum load on the capsule wall reached 94.79 mN, and the load dropped sharply after the capsule wall rupture. Finally, the self-healing mechanism of closed wall doped with microcapsules was discussed. The exploration of modified phenolic microcapsules provides a new idea for the repair of closed wall in goaf
    corecore