Design and synthesis of diarylamines and diarylethers as cytotoxic antitumor agents

Based on a shared structural core of diarylamine in several known anticancer drugs as well as a new cytotoxic hit 6-chloro-2-(4-cyanophenyl)amino-3-nitropyridine (7), 30 diarylamines and diarylethers were designed, synthesized, and evaluated for cytotoxic activity against A549, KB, KB-vin, and DU145 human tumor cell lines (HTCL). Four new leads 11e, 12, 13a, and 13b were discovered with GI(50) values ranging from 0.33 to 3.45μM. Preliminary SAR results revealed that a diarylamine or diarylether could serve as an active structural core, meta-chloro and ortho-nitro groups on the A-ring (either pyridine or phenyl ring) were necessary and crucial for cytotoxic activity, and the para-substituents on the other phenyl ring (B-ring) were related to inhibitory selectivity for different tumor cells. In an investigation of potential biological targets of the new leads, high thoughput kinase screening discovered that new leads 11e, 12 and 13b especially inhibit Mer tyrosine kinase, a proto-oncogene associated with munerous tumor types, with IC(50) values of 2.2-3.0μM. Therefore, these findings provide a good starting point to optimize a new class of compounds as potential anticancer agents, particularly targeting Mer tyrosine kinase.     

Molecular characterization of avian-like H1N1 swine influenza a viruses isolated in Eastern China, 2011

Currently, three predominant subtypes of influenza virus are prevalent in pig populations worldwide: H1N1, H3N2, and H1N2. European avian-like H1N1 viruses, which were initially detected in European pig populations in 1979, have been circulating in pigs in eastern China since 2007. In this study, six influenza A viruses were isolated from 60 swine lung samples collected from January to April 2011 in eastern China. Based on whole genome sequencing, molecular characteristics of two isolates were determined. Phylogenetic analysis showed the eight genes of the two isolates were closely related to those of the avian-like H1N1 viruses circulating in pig populations, especially similar to those found in China. Four potential glycosylation sites were observed at positions 13, 26, 198, 277 in the HA1 proteins of the two isolates. Due to the presence of a stop codon at codon 12, the isolates contained truncated PB1-F2 proteins. In this study, the isolates contained 591Q, 627E and 701N in the polymerase subunit PB2, which had been shown to be determinants of virulence and host adaptation. The isolates also had a D rather than E at position 92 of the NS1, a marker of mammalian adaptation. Both isolates contained the GPKV motif at the PDZ ligand domain of the 3′ end of the NS1, a characteristic marker of the European avian-like swine viruses since about 1999, which is distinct from those of avian, human and classical swine viruses. The M2 proteins of the isolates have the mutation (S31N), a characteristic marker of the European avian-like swine viruses since about 1987, which may confer resistance to amantadine and rimantadine antivirals. Our findings further emphasize the importance of surveillance on the genetic diversity of influenza A viruses in pigs, and raise more concerns about the occurrence of cross-species transmission events.     

荧光定量PCR检测家蚕核型多角体病毒在其宿主体内的增殖动态

为了研究家蚕核型多角体病毒(Bombyx mori nuclear polyhedrosis virus,BmNPV)在其宿主幼虫体内不同组织中的增殖动态,对敏感性家蚕品种306幼虫进行经口定量滴注病毒。在接种后9个时间点,对中肠、血淋巴和脂肪体进行取样。以BmNPV DNA 聚合酶基因(dnapol)指示病毒拷贝数,同时以家蚕细胞质肌动蛋白A3(actin A3)基因作为参比基因,用荧光定量PCR的方法分别检测各个时间点的中肠、血淋巴和脂肪体中病毒的拷贝数。结果表明经口感染2 h,病毒进入中肠;12 h,病毒已经到达血淋巴和脂肪体;再经过约12 h的潜伏期,病毒在各组织中开始快速增殖,到84 h各组织中病毒增殖达到平台期。     

Aspergillus niger DLFCC-90 rhamnoside hydrolase, a new type of flavonoid glycoside hydrolase

A novel rutin-α-L-rhamnosidase hydrolyzing α-L-rhamnoside of rutin, naringin, and hesperidin was purified and characterized from Aspergillus niger DLFCC-90, and the gene encoding this enzyme, which is highly homologous to the α-amylase gene, was cloned and expressed in Pichia pastoris GS115. The novel enzyme was classified in glycoside-hydrolase (GH) family 13.     

rmlB基因在单核细胞增生李斯特菌耐药性、生物被膜形成和毒力方面的作用

【目的】探究单核细胞增生李斯特菌(Listeria monocytogenes,Lm)rmlB基因在细菌耐药、生物被膜形成和毒力方面的作用。【方法】通过同源重组的方法敲除Lm染色体上的rmlB基因,比较野生株与rmlB缺失株在耐药性方面的差异;利用微孔板法观测rmlB缺失菌株生物被膜形成能力的变化;利用RT-PCR检测缺失菌株中主要毒力基因转录表达,并观察rmlB缺失对细菌溶血活性的影响。【结果】同野生菌株相比,rmlB缺失菌株对头孢菌素和杆菌肽等作用位点在细菌细胞壁和细胞膜的敏感性显著增加(P≤0.01),生物被膜形成能力显著降低(P≤0.01),细菌主要毒力基因hly的转录表达及溶血活性也发生显著降低(P≤0.01)。【结论】rmlB基因在Lm生物被膜形成和耐受作用位点位于细胞壁和细胞膜的抗生素及细菌毒力方面具有重要作用。     

Lipids,lipid metabolism and Kaposi’s sarcoma-associated herpesvirus pathogenesis

Lipids are essential for mammalian cells to maintain many physiological functions. Emerging evidence has shown that cancer cells can develop specific alterations in lipid biosynthesis and metabolism to facilitate their survival and various malignant behaviors. To date, the precise role of cellular lipids and lipid metabolism in viral oncogenesis is still largely unclear with only a handful of literature covering this topic to implicate lipid metabolism in oncogenic virus associated pathogenesis. In this review, we focus on the role of lipid biosynthesis and metabolism in the pathogenesis of the Kaposi’s sarcoma-associated herpesvirus, a common causative factor for cancers arising in the immunocompromised settings.

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In Situ TEM Study of Volume Expansion in Porous Carbon Nanofiber/Sulfur Cathodes with Exceptional High‐Rate Performance

Although lithium sulfur batteries (LSBs) have attracted much interest owing to their high energy densities, synthesis of high‐rate cathodes and understanding their volume expansion behavior still remain challenging. Herein, electrospinning is used to prepare porous carbon nanofiber (PCNF) hosts, where both the pore volume and surface area are tailored by optimizing the sacrificial agent content and the activation temperature. Benefiting from the ameliorating functional features of high electrical conductivity, large pore volume, and Li ion permselective micropores, the PCNF/A550/S electrode activated at 550 °C exhibits a high sulfur loading of 71 wt%, a high capacity of 945 mA h g^?1 at 1 C, and excellent high‐rate capability. The in situ transmission electron microscope examination reveals that the lithiation product, Li₂S, is contained within the electrode with only ≈35% volume expansion and the carbon host remains intact without fracture. In contrast, the PCNF/A750/S electrode with damaged carbon spheres exhibits sulfur sublimation, a larger volume expansion of over 61%, and overflowing of Li₂S, a testament to its poor cyclic stability. These findings provide, for the first time, a new insight into the correlation between volume expansion and electrochemical performance of the electrode, offering a potential design strategy to synthesize high‐rate and stable LSB cathodes.     

芝麻愈伤组织诱导与植株再生体系的建立

以芝麻栽培种(Sesamum indicum, 2n=26)、野生种(S. radiatum, 2n=64; S. schinzianum, 2n=64)及其远源杂交后代(S. schinzianum × S. indicum)为材料, 研究了不同基因型、外植体类型、激素种类及其浓度对芝麻愈伤组织诱导及植株再生的影响, 建立了芝麻愈伤组织诱导及高频植株再生的技术体系。结果表明, 6-BA/NAA激素组合有利于绿色紧密型愈伤组织的形成及分化; 最佳愈伤组织诱导及分化培养基为MS+ 0.1 mg·L^–1NAA + 2.0 mg·L^–16-BA+ 30 g·L^–1蔗糖。在该培养条件下, 野生种下胚轴愈伤组织的诱导率最高为97.50%, 分化率为94.02%; 栽培种下胚轴愈伤组织的诱导率最高为40.60%, 分化率为8.16%; 远缘杂交后代幼胚外植体愈伤组织的诱导率最高为46.67%, 分化率为89.29%。该研究结果为芝麻转基因技术体系的建立及新种质创制奠定了基础。