Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of H. pylori and AGS Cell Line

Following a similar approach on carvacrol-based derivatives, we investigated the synthesis and the microbiological screening against eight strains of H. pylori, and the cytotoxic activity against human gastric adenocarcinoma (AGS) cells of a new series of ether compounds based on the structure of thymol. Structural analysis comprehended elemental analysis and ¹H/¹³C/¹⁹F NMR spectra. The analysis of structure–activity relationships within this molecular library of 38 structurally-related compounds reported that some chemical modifications of the OH group of thymol led to broad-spectrum growth inhibition on all isolates. Preferred substitutions were benzyl groups compared to alkyl chains, and the specific presence of functional groups at para position of the benzyl moiety such as 4-CN and 4-Ph endowed the most anti-H. pylori activity toward all the strains with minimum inhibitory concentration (MIC) values up to 4 µg/mL. Poly-substitution on the benzyl ring was not essential. Moreover, several compounds characterized by the lowest minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) values against H. pylori were also tested in order to verify a cytotoxic effect against AGS cells with respect to 5-fluorouracil and carvacrol. Three derivatives can be considered as new lead compounds alternative to current therapy to manage H. pylori infection, preventing the occurrence of severe gastric diseases. The present work confirms the possibility to use natural compounds as templates for the medicinal semi-synthesis.     

Thiazole Analogues of the Marine Alkaloid Nortopsentin as Inhibitors of Bacterial Biofilm Formation

Anti-virulence strategy is currently considered a promising approach to overcome the global threat of the antibiotic resistance. Among different bacterial virulence factors, the biofilm formation is recognized as one of the most relevant. Considering the high and growing percentage of multi-drug resistant infections that are biofilm-mediated, new therapeutic agents capable of counteracting the formation of biofilms are urgently required. In this scenario, a new series of 18 thiazole derivatives was efficiently synthesized and evaluated for its ability to inhibit biofilm formation against the Gram-positive bacterial reference strains Staphylococcus aureus ATCC 25923 and S. aureus ATCC 6538 and the Gram-negative strain Pseudomonas aeruginosa ATCC 15442. Most of the new compounds showed a marked selectivity against the Gram-positive strains. Remarkably, five compounds exhibited BIC₅₀ values against S. aureus ATCC 25923 ranging from 1.0 to 9.1 µM. The new compounds, affecting the biofilm formation without any interference on microbial growth, can be considered promising lead compounds for the development of a new class of anti-virulence agents.     

Design,Synthesis, Molecular Docking,and Tumor Resistance Reversal Activity Evaluation of Matrine Derivative with Thiophene Structure

Nasopharyngeal carcinoma (NPC) frequently occurs in Southern China. The main treatments of NPC are chemotherapy and radiotherapy. However, chemo-resistance arises as a big obstacle in treating NPC. Therefore, there is a great need to develop new compounds that could reverse tumor drug resistance. In this study, eight matrine derivatives containing thiophene group were designed and synthesized. Structures of these 8 compounds were characterized by ¹H-NMR, ¹³C-NMR, and high-resolution mass spectrometer (HRMS). The cytotoxicity and preliminary synergistic effects of these 8 compounds were detected against nasopharyngeal carcinoma (NPC) cells and cisplatin-resistant NPC cells (CNE2/CDDP), respectively. Furthermore, the in vivo and in vitro tumor resistance reversal effects of compound 3f were evaluated. Moreover, docking studies were performed in Bclw (2Y6W). The results displayed that compound 3f showed synergistic inhibitory effects with cisplatin against CNE2/CDDP cells proliferation via apoptosis induction. Docking results revealed that compound 3f may exert its effects via inhibiting anti-apoptosis protein Bcl-w.     

Laminarin Induces Defense Responses and Efficiently Controls Olive Leaf Spot Disease in Olive

Olive leaf spot (OLS) caused by Fusicladium oleagineum is mainly controlled using copper fungicides. However, the replacement of copper-based products with eco-friendly alternatives is a priority. The use of plant resistance-inducers (PRIs) or biological control agents (BCAs) could contribute in this direction. In this study we investigated the potential use of three PRIs (laminarin, acibenzolar-S-methyl, harpin) and a BCA (Bacillus amyloliquefaciens FZB24) for the management of OLS. The tested products provided control efficacy higher than 68%. In most cases, dual applications provided higher (p < 0.05) control efficacies compared to that achieved by single applications. The highest control efficacy of 100% was achieved by laminarin. Expression analysis of the selected genes by RT-qPCR revealed different kinetics of induction. In laminarin-treated plants, for most of the tested genes a higher induction rate (p < 0.05) was observed at 3 days post application. Pal, Lox, Cuao and Mpol were the genes with the higher inductions in laminarin-treated and artificially inoculated plants. The results of this study are expected to contribute towards a better understanding of PRIs in olive culture and the optimization of OLS control, while they provide evidence for potential contributions in the reduction of copper accumulation in the environment.     

Solid-Phase Synthesis of an Insect Pyrokinin Analog Incorporating an Imidazoline Ring as Isosteric Replacement of a trans Peptide Bond

A facile solid-phase synthetic method for incorporating the imidazoline ring motif, a surrogate for a trans peptide bond, into bioactive peptides is reported. The example described is the synthesis of an imidazoline peptidomimetic analog of an insect pyrokinin neuropeptide via a cyclization reaction of an iminium salt generated from the preceding amino acid and 2,4-diaminopropanoic acid (Dap).     

Combined nanosuspensions from two natural active ingredients for cancer therapy with reduced side effects

Tumor drug resistance and systemic side effects of chemotherapeutic drugs are the main reasons for the failure of cancer treatment. In recent years, it was found that some natural active ingredients can reverse MDR and regulate body immunity to enhance the efficacy and reduce toxicity of chemotherapeutic drugs. In this paper, a new nanosuspensions, HCPT and QUR hybrid nanosuspensions (HQ-NPs), was prepared by the microprecipitation-high pressure homogenization method to reverse tumor drug resistance, reduce toxicity, and increase therapeutic efficacy. The in vitro investigation results showed that HQ-NPs had a unique shape (particle size was about 216.3 ± 5.9 nm), changed crystalline, and different dissolution rates compared with HCPT-NPs and QUR-NPs, which is attributed to the strong intermolecular forces between HCPT and QUR as indicated by the results of the molecule dock. It was verified that the HQ-NPs could double the retention of HCPT in cells and enhance the cytotoxicity to A549/PTX cells in vitro tests compared with HCPT-NPs. We also found that HQ-NPs can significantly enhance the accumulation of HCPT in tumor sites, improve the antitumor activity of HCPT, and protect the immune organs and other normal tissues (P < 0.01), compared with HCPT-NPs. Therefore, hybrid nanosuspensions can offer promising potential as the drug delivery system for HCPT and QUR to increase the therapeutic efficacy and reduce the toxicity of HCPT.     

三功能策略设计制备具有优异低温抗积碳性能的Ni-CeO2@SiO2催化剂催化甲烷干重整反应

随着全球人为温室气体排放量(主要是甲烷和二氧化碳)的增加,全球变暖的趋势逐渐增加,因此,迫切需要通过各种技术来捕获和利用这些温室气体.甲烷干气重整反应(DRM)可以有效地将甲烷和二氧化碳这两种资源丰富、价格低廉的温室气体转化为高附加值化学品,减少它们向大气排放.尽管DRM工艺的应用具有许多优势,但是反应期间碳沉积和活性组分的烧结是阻碍其工业应用的两个主要原因.这些碳沉积物可能覆盖活性中心或阻塞催化剂的孔道,从而导致催化剂活性降低.镍基催化剂因其价格低廉、初始活性高和资源丰富而得到广泛的应用.但应用于DRM反应的Ni基催化剂在反应中容易烧结和积碳,导致催化剂迅速失活.为解决上述问题,本文从三功能策略角度出发,即SiO2壳层的限域作用和Ni-Ce之间的协同作用以及CeO2的消除积碳作用,采用原位一锅法设计合成了一种限域型Ni-CeO2核壳结构催化剂(Ni-CeO2@SiO2).通过X射线衍射、透射电子显微镜、能量色散X射线光谱、N2吸附/脱附、氢气程序升温还原和脱附、氧气程序升温脱附、拉曼光谱、热重分析和原位漫反射红外傅里叶变换光谱测试对催化剂进行了系统的表征,来揭示催化剂的理化性质和反应机理.催化剂应用于甲烷干气重整反应结果表明,在温度区间为550～800℃时,与传统浸渍法合成的催化剂相比,Ni-CeO2@SiO2催化剂具有更高的活性.高温800℃下的稳定性测试结果显示,传统浸渍法合成的催化剂在反应20 h后就出现了大量的积碳且活性下降明显;而Ni-CeO2@SiO2催化剂在800℃下反应100 h后未检测到积碳,并且催化剂中的Ni纳米颗粒的平均粒径从5.01 nm仅增长到5.77 nm,表现出很好的高温抗积碳和耐烧结性能.值得注意的是,Ni-CeO2@SiO2催化剂在低温600℃(形成碳沉积的最可能温度区域)下反应20h后也未检测到积碳的形成,表现出催化剂良好的低温稳定性和抗积碳性能.这可能归因于对Ni-CeO2@SiO2催化剂的三功能作用,即多孔二氧化硅壳层的限域作用、Ni与CeO2之间强的金属-金属氧化物相互作用以及具有丰富活性氧物种CeO2的消除积碳的作用.通过原位漫反射红外傅里叶变换光谱测试来探究反应机理.结果 表明,DRM反应在Ni-CeO2@SiO2催化剂上遵循L-H机理,添加CeO2可以消除碳沉积并促进CO2活化.该三功能策略为设计其他应用于DRM的高性能催化剂提供了指导,有望加快该工艺的工业化.     

2′,4′-BNA/LNA with 9-(2-Aminoethoxy)-1,3-diaza-2-oxophenoxazine Efficiently Forms Duplexes and Has Enhanced Enzymatic Resistance**

Artificial nucleic acids are widely used in various technologies, such as nucleic acid therapeutics and DNA nanotechnologies requiring excellent duplex-forming abilities and enhanced nuclease resistance. 2′-O,4′-C-Methylene-bridged nucleic acid/locked nucleic acid (2′,4′-BNA/LNA) with 1,3-diaza-2-oxophenoxazine (BNAP ( B^H )) was previously reported. Herein, a novel B^H analogue, 2′,4′-BNA/LNA with 9-(2-aminoethoxy)-1,3-diaza-2-oxophenoxazine (G-clamp), named BNAP-AEO ( B^AEO ), was designed. The B^AEO nucleoside was successfully synthesized and incorporated into oligodeoxynucleotides (ODNs). ODNs containing B^AEO possessed up to 10⁴-, 152-, and 11-fold higher binding affinities for complementary (c) RNA than those of ODNs containing 2′-deoxycytidine ( C ), 2′,4′-BNA/LNA with 5-methylcytosine ( L ), or 2′-deoxyribonucleoside with G-clamp ( P^AEO ), respectively. Moreover, duplexes formed by ODN bearing B^AEO with cDNA and cRNA were thermally stable, even under molecular crowding conditions induced by the addition of polyethylene glycol. Furthermore, ODN bearing B^AEO was more resistant to 3′-exonuclease than ODNs with phosphorothioate linkages.     

避雷器电阻片测试系统设计

采用工业PC机与可编程控制器、示波器、直流仪等设备设计了避雷器电阻片测试系统,阐述了本系统的控制流程及逻辑关系,用图形化编程语言编写了上位机软件,完成了避雷器电阻片在 U_1mA及0.75U_1mA下的漏电流等参数的测试,并对电阻片测试过程中的电压峰值、电流峰值进行采集存储,还存储了电阻片在整个测试过程中的能量,方便以后对测试过程中损坏的阀片进行能量、电流峰值、电压峰值方面的分析,对系统进行了初步的试验,结果表明该系统运行效果良好,实现了避雷器电阻片出厂前的测试,提高了测试效率。     

Analytical and empirical studies on the characteristic resistances of no-insulation GdBCO racetrack pancake coil under various operating currents

This paper presents the effects of the Lorentz force on the electrical behaviors of the no-insulation (NI) GdBCO racetrack pancake (RP) coil without turn-to-turn insulation by performing charging/discharging and sudden-discharging tests. The simulation results of the 2-dimensional finite element method showed that the Lorentz forces were generated towards the center of the winding pack consisting of 60-turn GdBCO CCs, which could enhanced the turn-to-turn contact within the RP coil. The charging/discharging test results indicated that the characteristic resistance (R_c) of the NI RP coil decreased with increasing operating current, which was caused by an increase of the Lorentz force. Further, the results of the sudden-discharging tests exhibited that the Lorentz force was dissipated instantly during the sudden-discharge of the coil, since the operating current immediately decreased to zero. Overall, this study clearly demonstrated that the Lorentz force induced by the operating current exerts the electrical behaviors of an NI RP coil.