NADPH oxidase 2 plays a critical role in dysfunction and apoptosis of pancreatic β-cells induced by very low-density lipoprotein

In type 2 diabetes, pancreatic β-cells cannot secret enough insulin compensate for insulin resistance, which are often accompanied by abnormality in lipid metabolism such as hypertriglyceridemia. It is reported that oxidative stress is involved in pancreatic β-cell dysfunction. However, molecular mechanisms linking between excessive generations of reactive oxygen species (ROS) and β-cell dysfunction and apoptosis induced by high levels of very low-density lipoprotein (VLDL) are poorly understood. In this study, we test the hypothesis that NADPH oxidase 2 (NOX2)-derived ROS may play a key role in dysfunction and apoptosis of pancreatic β-cell induced by VLDL. Our results show that the ApoCIII transgenic mice displayed increased serum TG levels, enhanced generation of ROS and impaired insulin content in pancreatic β-cells. In vitro, the treatment of pancreatic NIT-1 cells with 1?mg/ml VLDL for 12?h stimulated NOX2-derived ROS generation, decreased expression and secretion of insulin. Furthermore, we found that VLDL induced dysfunction and apoptosis of pancreatic β-cells through JNK and p53 pathways, which were rescued by siRNA-mediated NOX2 reduction. In conclusion, our data demonstrate a critical role of NOX2-derived ROS in dysfunction and apoptosis through JNK and p53 pathways in pancreatic β-cells induced by VLDL.     

Molecular characterization, tissue distribution and expression analysis of interleukin-12 receptor β2 chain in sheep

Agnathia-otocephaly is a rare, often lethal malformation characterized by absence or hypoplasia of the mandible, microstomia, hypoglossia/aglossia, and variable anterior midline fusion of the ears (melotia, synotia). Etiologies have been linked to both genetic and teratogenic factors and to date, a definitive, commonly identifiable cause has not been recognized. Mouse and human genetic studies have implicated OTX2 and PRRX1 as potential candidate genes for agnathia-otocephaly. In this study we report a sporadic case of agnathia-otocephaly complex with associated features of maldevelopment and examine the roles of OTX2 and PRRX1. The proband, a male born at 31 weeks, displayed severe micrognathia, microstomia, posteriorly-rotated and low set ears, and downward slanting palpebral fissures. Mutation analysis was performed after sequencing the entire coding regions of OTX2 and PRRX1 genes isolated from the proband and his parents. After thorough analysis, no DNA variations were detected. This suggests that mutations in different genes or environmental causes are responsible.     

The migratory history of anadromous and non-anadromous tapertail anchovy Coilia nasus in the Yangtze River Estuary revealed by the otolith Sr:Ca ratio

The migratory history of tapertail anchovy Coilia nasus in the Yangtze River Estuary, China was investigated using otolith Sr:Ca ratios and two-dimensional images of the Sr level from an X-ray electron probe microanalyzer (EPMA). The results showed that 17 of the 22 young-of-the-year (YOY) specimens had low Sr:Ca ratios (1.2–2.4?×?10^?3;1.5?±?0.3?×?10^?3) at the central otolith area, indicating their riverine origin and initial freshwater residence. In addition, 11 of the 14 adult specimens had low Sr:Ca ratios (1.3–2.2?×?10^?3; 1.7?±?0.4?×?10^?3) at the central otolith area but showed alternating changes between high (>4.0?×?10^?3) and low (<2.5?×?10^?3) values outside of this region, reflecting their riverine origin and the migration between freshwater and estuarine habitats. These 28 specimens represented the anadromous population in this region. The other 5 YOY specimens had high Sr:Ca ratios (3.6–5.9?×?10^?3; 4.8?±?0.8?×?10^?3) throughout the life history. Similarly, the other 3 adult specimens had high Sr:Ca ratios (4.0–5.7?×?10^?3; 4.8?±?0.7?×?10^?3) at the central otolith area but showed alternating changes between low and high values outside this region, suggesting that estuarine-origin non-anadromous individuals occurred in this region. The average of the otolith Sr:Ca ratios and Sr level mapping along the life-history transects could be used as a scalar for charting the migratory history of the tapertail anchovy in the Yangtze River Estuary: <2.0?×?10^?3 for freshwater residence and 3.5–6.0?×?10^?3 for estuarine residence.     

Elemental signature in otolith nuclei for stock discrimination of anadromous tapertail anchovy (Coilia nasus) using laser ablation ICPMS

The elemental signature in otolith nuclei was determined using laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) for stock discrimination of adult anadromous tapertail anchovy, Coilia nasus, in five Chinese estuaries. Five elements (Na, Mg, K, Sr, and Ba) were well detected in the otolith nuclei of the adult fish. Results showed that the elemental composition in the otolith nuclei varied substantially among the estuaries. Age and fish length data showed no significant influences on the elemental concentration ratios across the sample sites. The Sr:Ca and Ba:Ca ratios were inter-site distinct and could be used as natal tags for discriminating among stocks. Discriminant function analyses (DFA) showed that these ratios can be used in discriminating the Liaohe River estuary (LD, 92.3?%), the Yangtze River estuary (CJ, 86.7?%), and the Yellow River estuary (HH, 76.9?%) samples with high classification accuracy, followed by the Haihe River estuary (BH, 58.3?%) and the Daguhe River estuary (JZ, 46.2?%) samples. An overall classification accuracy rate of 72.7?% from the discriminant functions indicated that elemental fingerprinting appeared to have the potential to discriminate between tapertail anchovy stocks in these estuaries.     

MOLECULAR CHARACTERIZATIONS OF TWO CYTOCHROME P450 GENES ENCODING CYP6A41 AND CYP6EK1 FROM THE ORIENTAL FRUIT FLY,Bactrocera dorsalis (DIPTERA: TEPHRITIDAE)

Two P450 genes encoding CYP6A41 and CYP6EK1 were cloned from the oriental fruit fly using polymerase chain reaction (PCR) and rapid amplification of cDNA ends (RACE) techniques. CYP6A41 and CYP6EK1 contained open reading frames of 1,530 and 1,524 nucleotides that encode 510 and 508 amino acid residues, respectively. The putative proteins shared 44% identity with each other. Phylogenetic analysis showed that CYP6A41 and CYP6EK1 were most closely related to Ceratitis capitata CYP6A10 and CYP6A subfamily. Expression patterns of the two genes in different geographical populations (Yunnan, Hainan, Dongguang, and Guangzhou), developmental stages (eggs, larvae, pupae, and adults), and tissues (midguts, fat bodies, and Malpighian tubules) were analyzed by real‐time quantitative PCR (RT‐qPCR) methods. The results showed that the expression levels of CYP6EK1 were significantly different among the four populations, but were not different for CYP6A41. Both the expressions of CYP6A41 and CYP6EK1 were development specific and had significantly higher levels in the larval stage. The expression of CYP6A41 did not vary among the midgut, fat body, or Malpighian tubules; however, CYP6EK1 expression was higher in the Malpighian tubules. The results suggest that CYP6A41 and CYP6EK1 might be involved in detoxification of xenobiotic compounds that were harmful to larval flies or development. Moreover, high expression of CYP6EK1 in the Malpighian tubules also implied participation in detoxification.     

Inhibition of noroviruses by piperazine derivatives

There is currently an unmet need for the development of small-molecule therapeutics for norovirus infection. The piperazine scaffold, a privileged structure embodied in many pharmacological agents, was used to synthesize an array of structurally-diverse derivatives which were screened for anti-norovius activity in a cell-based replicon system. The studies described herein demonstrate for the first time that functionalized piperazine derivatives possess anti-norovirus activity. Furthermore, these studies have led to the identification of two promising compounds (6a and 9l) that can be used as a launching pad for the optimization of potency, cytotoxicity, and drug-like characteristics.     

Inhibition of Dengue virus and West Nile virus proteases by click chemistry-derived benz[d]isothiazol-3(2H)-one derivatives

Two click chemistry-derived focused libraries based on the benz[d]isothiazol-3(2H)-one scaffold were synthesized and screened against Dengue virus and West Nile virus NS2B-NS3 proteases. Several compounds (4l, 7j-n) displayed noteworthy inhibitory activity toward Dengue virus NS2B-NS3 protease in the absence and presence of added detergent. These compounds could potentially serve as a launching pad for a hit-to-lead optimization campaign.     

Design, synthesis and CoMFA studies of N1-amino acid substituted 2,4,5-triphenyl imidazoline derivatives as p53-MDM2 binding inhibitors

A series of novel N1-amino-acid substituted 2,4,5-triphenyl imidazoline derivatives was designed and synthesized based on our previous studies. All synthesized target compounds were screened for their p53-MDM2 binding inhibitory activities and anti-proliferative activities against five cancer cell lines. Among them, twelve compounds displayed improved binding inhibitory activities and most compounds showed higher cell growth inhibition activities with IC(50) values in the low micromolar range. Compound 6c exhibited marked p53-MDM2 binding inhibitory activity (IC(50)=0.59 μM) which was eightfold more potent than that of Nutlin-1 (IC(50)=4.78 μM). CoMFA analysis was performed based on obtained biological data and resulted in a statistically significant CoMFA model with high predict abilities (q(2)=0.645, r(2)=0.979).     

水稻OsPR10A的表达特征及其在干旱胁迫应答过程中的功能

利用免疫印迹(WB)分析了水稻(Oryza sativa) OsPR10A在其不同生长时期、不同组织部位及多种非生物逆境胁迫下的表达特征, 发现OsPR10A在干旱、盐胁迫以及茉莉酸甲酯(MeJA)和脱落酸(ABA)诱导下表达量明显升高, 表明该蛋白可能在干旱和盐胁迫应答过程中发挥作用。为证明这一推测, 我们构建了OsPR10A超表达载体, 经农杆菌介导转化水稻, 获得超表达OsPR10A的纯合株系。田间表型观察表明, 转基因株系株高变矮、穗长变短、结实率降低。用20% PEG6000在水稻种子萌发过程中进行干旱处理, 结果显示, OsPR10A超表达株系的根长和芽长均显著高于野生型, 证明超表达OsPR10A可增强水稻萌发期耐旱性。该研究有助于增进人们对水稻OsPR10A功能的了解。