Synthesis of novel substituted N-aryl benzamides as hA3G stabilizers and their inhibitory activities against hepatitis C virus replication

AbstractA series of novel amino-substituted N-aryl benzamide analogs were synthesized and evaluated for their ability to inhibit hepatitis C virus (HCV) replication in acutely infected Huh7.5 cells. Most of the substituted N-aryl benzamide compounds showed convincing anti-HCV activities. Compounds 1f, 1g and 4c exhibited potent anti-replicative activity at low micromolar levels (IC50=1.0–2.0μM) with selective indices (SI) greater than 40. Mechanistic analysis indicated that the active compounds increased intracellular hA3G protein levels and inhibited HCV replication in a dose-dependent manner. The results demonstrate that this series of substituted N-aryl benzamide compounds warrant further investigation as inhibitors of HCV replication

Color Control and White Light Generation of Upconversion Luminescence by Operating Dopant Concentrations and Pump Densities in Yb\u3csup\u3e3+\u3c/sup\u3e, Er\u3csup\u3e3+\u3c/sup\u3e, and Tm\u3csup\u3e3+\u3c/sup\u3e Tri-Doped Lu\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e3\u3c/sub\u3e Nanocrystals

We synthesized a series of Yb3+, Er3+ and Tm3+ tri-doped Lu2O3 nanocrystals with various dopant concentrations by the hydrothermal approach. Due to a unique electronic state at the top of the valence band, Lu2O3 based materials exhibit intense upconversion luminescence involving 1G4 → 3H6 of Tm3+ in blue, (2H11/2, 4S3/2) → 4I15/2 in green and 4F9/2 → 4I15/2 in red of Er3+ upon near infrared excitation at 980 nm. The variation of upconversion spectra and color points with dopant concentrations and pump densities are studied in detail on the basis of energy transfer processes. An ideal white upconversion light with color coordinates of (0.327, 0.339) is obtained by controlling the intensity of red, green, and blue emission in Lu1.906Yb0.08Er0.008Tm0.006O3nanocrystals under a pump density of 8 W cm−2. Based on the present experimental data, we may predict the dopant concentrations and pump densities for any color point within or around the white light region in the tri-doped Lu2O3 nanocrystals

Double Dome and Reemergence of Superconductivity in Pristine 6R-TaS2 under Pressure

Investigating the implications of interlayer coupling on superconductivity is essential for comprehending the intrinsic mechanisms of high temperature superconductors. Van der Waals heterojunctions have attracted extensive research due to their exotic interlayer coupling. Here, we present a natural heterojunction superconductor of 6R-TaS2 that demonstrates a double-dome of superconductivity, in addition to, the reemergence of superconducting under high pressures. Our first principles calculation shows that the first dome of superconductivity in 6R-TaS2 can be attributed to changes in interlayer coupling and charge transfer. The second superconducting dome and the reemergence of superconductivity can be ascribed to changes in the density of states resulting from Fermi surface reconstruction, in which the DOS of T-layer and S p-orbitals play a crucial role. We have reported the first observation in TMDs that non-metallic atoms playing a dominant role in the reemergence of superconducting and the influence of two Lifshitz transitions on superconducting properties

A two-dimensional hybrid with molybdenum disulfide nanocrystals strongly coupled on nitrogen-enriched graphene via mild temperature pyrolysis for high performance lithium storage

A novel 2D hybrid with MoS₂ nanocrystals strongly coupled on nitrogen-enriched graphene (MoS₂/NGg-C₃N₄) is realized by mild temperature pyrolysis (550 °C) of a self-assembled precursor (MoS₃/g-C₃N₄–H⁺/GO). With rich active sites, the boosted electronic conductivity and the coupled structure, MoS₂/NGg₋C₃N₄ achieves superior lithium storage performance

Regulation of non-classical immune parameters in immune thrombocytopenic purpura mice by a spleen-invigorating, qi-replenishing and blood-containing formula

AbstractObjectiveThis study investigated the regulatory effect of non-classical immune parameters on immune thrombocytopenic purpura (ITP) mice by a spleen-invigorating, qi-replenishing and blood-containing formula (SQBF).MethodA total of 80 BALB/c mice were randomly divided into four equal groups (20 mice each): control group, model group, prednisone group and spleen-invigorating, qi-replenishing and blood-containing (SQBF) group. Mice in the model group, prednisone group, and SQBF group were administered anti-platelet serum to induce ITP. The dynamic variations of platelet counts in ITP mice were measured with an automatic blood analyzer before modeling and 48 h, and 8, 12 and 15 days following APS injection. Levels of β-endorphin (β-EP), vasoactive intestinal peptide (VIP) and salivary IgA (SIgA) were detected by enzyme-linked immunosorbent assay (ELISA) on 15th day of experiment.ResultsSQBF enhanced peripheral blood platelet counts in ITP mice similar to that of prednisone, and both groups showed a statistically significant response compared with the model group (P < .01). The SQBF significantly decreased β-EP levels compared with the model and prednisone intervention groups (P < .05), significantly increased the levels of VIP and SIgA in ITP mice compared with the model group (P < .05) and had significant protective effects on the thymus of ITP mice compared with the model group (P < .01).ConclusionsThe SQBF had a similar effect to prednisone with regards to enhancing peripheral blood platelet counts in ITP mice. Furthermore, it decreased β-EP levels and increased VIP and SIgA, and protected the thymus. This shows that, on base of the brain-gut axis functions, some non-classical immune vascular active factors or neurotransmitters are also involved in immune responses, and also have relationship with the onset of ITP and bleeding and/or hemostasis. It needs further study to determine whether a change in these active factors is related to immediate hemostasis

Superconducting Zirconium Polyhydrides at Moderate Pressures.

Highly compressed hydrides have been at the forefront of the search for high-Tc superconductivity. The recent discovery of record-high Tc's in H3S and LaH10±x under high pressure fuels the enthusiasm for finding good superconductors in similar hydride groups. Guided by first-principles structure prediction, we successfully synthesized ZrH3 and Zr4H15 at modest pressures (30-50 GPa) in diamond anvil cells by two different reaction routes: ZrH2 + H2 at room temperature and Zr + H2 at ∼1500 K by laser heating. From the synchrotron X-ray diffraction patterns, ZrH3 is found to have a Pm3̅n structure corresponding to the familiar A15 structure, and Zr4H15 has an I4̅3d structure isostructural to Th4H15. Electrical resistance measurement and the dependence of Tc on the applied magnetic field of the sample showed the emergence of two superconducting transitions at 6.4 and 4.0 K at 40 GPa, which correspond to the two Tc's for ZrH3 and Zr4H15.This work was supported by the National Key R&D Program of China (No. 2018YFA0305900), National Natural Science Foundation of China (Nos. 51632002, 11674122, 51572108, and 11504127), Program for Changjiang Scholars and Innovative Research Team in University (No. IRT_15R23), the 111 Project (No. B12011), and the Natural Sciences and Engineering Research Council of Canada (NSERC). C.J.P. acknowledges financial support from the Engineering and Physical Sciences Research Council (Grant EP/P022596/1) and a Royal Society Wolfson Research Merit award

Selection of Reference Genes for Gene Expression Studies in Porcine Whole Blood and Peripheral Blood Mononuclear Cells under Polyinosinic:Polycytidylic Acid Stimulation

Investigating gene expression of immune cells of whole blood or peripheral blood mononuclear cells (PBMC) under polyinosinic:polycytidylic acid (poly I:C) stimulation is valuable for understanding the immune response of organism to RNA viruses. Quantitative real-time PCR (qRT-PCR) is a standard method for quantification of gene expression studies. However, the reliability of qRT-PCR data critically depends on proper selection of reference genes. In the study, using two different analysis programs, geNorm and NormFinder, we systematically evaluated the gene expression stability of six candidate reference genes (GAPDH, ACTB, B2M, RPL4, TBP, and PPIA) in samples of whole blood and PBMC with or without poly I:C stimulation. Generally, the six candidate genes performed a similar trend of expression stability in the samples of whole blood and PBMC, but more stably expressed in whole blood than in PBMC. geNorm ranked B2M and PPIA as the best combination for gene expression normalization, while according to NormFinder, TBP was ranked as the most stable reference gene, followed by B2M and PPIA. Comprehensively considering the results from the two programs, we recommended using the geometric mean of the three genes, TBP, PPIA and B2M, to normalize the gene expression of whole blood and PBMC with poly I:C stimulation. Our study is the first detailed survey of the gene expression stability in whole blood and PBMC with or without poly I:C stimulation and should be helpful for investigating the molecular mechanism involved in porcine whole blood and PBMC in response to poly I:C stimulation

Ternary composite phase change materials (PCMs) towards low phase separation and supercooling: eutectic behaviors and application

Salt hydrates have been used as phase change materials (PCMs) for various types of Thermal Energy Storage (TES) especially for cold storage. In this project, a novel composite phase change material (PCM) consisted of mixed solution of inorganic salt and organic salt was developed and characterized. Firstly, the PCM solutions containing sodium formate, potassium chloride and water with various weight percentage were evaluated to understand their solidification temperature, melting temperature, the supercooling degree and the latent heat. Then a PCM with mass fractions at weight percentages of 22%/12%/66% with better performance was selected for further study to restrain the supercooling. Different gelling agents and nucleate agents were employed in this PCM. The results show that the addition of 0.6 wt% xanthan gum can effectively prevent the phase separation and leakage, while 0.6 wt% of nano-TiO2 is the best nucleating agent since the supercooling can be reduced to 2.6 °C, which is 67.9% lower than that of the original PCM without any nucleating agent. Finally, the novel PCM was tested for frozen food storage application, in which the food temperature could be maintained below -18 °C for over 10 hours in the insulated box. This indicated the suitability of developed PCM for frozen food storage and transportation

The Involvement of the Cas9 Gene in Virulence of Campylobacter jejuni

Campylobacter jejuni is considered as the leading cause of gastroenteritis all over the world. This bacterium has the CRISPR–cas9 system, which is used as a gene editing technique in different organisms. However, its role in bacterial virulence has just been discovered; that discovery, however, is just the tip of the iceberg. The purpose of this study is to find out the relationship between cas9 and virulence both phenotypically and genotypically in C. jejuni NCTC11168. Understanding both aspects of this relationship allows for a much deeper understanding of the mechanism of bacterial pathogenesis. The present study determined virulence in wild and mutant strains by observing biofilm formation, motility, adhesion and invasion, intracellular survivability, and cytotoxin production, followed by the transcriptomic analysis of both strains. The comparative gene expression profile of wild and mutant strains was determined on the basis of De-Seq transcriptomic analysis, which showed that the cas9 gene is involved in enhancing virulence. Differential gene expression analysis revealed that multiple pathways were involved in virulence, regulated by the CRISPR-cas9 system. Our findings help in understanding the potential role of cas9 in regulating the other virulence associated genes in C. jejuni NCTC11168. The findings of this study provide critical information about cas9's potential involvement in enhancing the virulence of C. jejuni, which is a major public health threat