In vivo self-assembled small RNAs as a new generation of RNAi therapeutics

RNAi therapy has undergone two stages of development, direct injection of synthetic siRNAs and delivery with artificial vehicles or conjugated ligands; both have not solved the problem of efficient in vivo siRNA delivery. Here, we present a proof-of-principle strategy that reprogrammes host liver with genetic circuits to direct the synthesis and self-assembly of siRNAs into secretory exosomes and facilitate the in vivo delivery of siRNAs through circulating exosomes. By combination of different genetic circuit modules, in vivo assembled siRNAs are systematically distributed to multiple tissues or targeted to specific tissues (e.g., brain), inducing potent target gene silencing in these tissues. The therapeutic value of our strategy is demonstrated by programmed silencing of critical targets associated with various diseases, including EGFR/KRAS in lung cancer, EGFR/TNC in glioblastoma and PTP1B in obesity. Overall, our strategy represents a next generation RNAi therapeutics, which makes RNAi therapy feasible.Subject terms: RNAi, siRNAs     

试论福建海岛植物资源的保护、改造及合理开发利用

本文阐述了福建沿海海岛植被及植物资源的现状;指出其存在的资源严重衰退、树种组成简单、森林生态效益差、果林生产落后、农业植被单一等问题;针对这些问题提出了切实有效的保护现有各类植被,发展针闲叶混交防护林,加快沙荒及荒山绿化,积极发展经济果林及旅游林业等建议,为各地开发海岛资源、振兴海岛经济提供参考。     

短序十大功劳基因组总DNA提取方法研究

以短序大功劳嫩叶为材料,采用CTAB法、CTAB改良法1、CTAB改良法2、SDS法和试剂盒法五种方法提取短序十大功劳基因组总DNA,用分光光度计和琼脂糖凝胶电泳方法检测所得总DNA的纯度和得率,用ISSR-PCR扩增的方法检测所得总DNA的质量。结果表明,五种方法均能从短序大功劳叶片中提取到基因组DNA,但不同方法提取得的基因组DNA的纯度、浓度和得率存在明显的差异。CTAB改良法2和试剂盒法提取的DNA纯度高,可直接用于下游分子生物学实验,CTAB法、CTAB改良法1和SDS法提取的总DNA质量较差,不利于下游的分子生物学实验;五种方法提取的总DNA的得率在10.836~451.709μg/g之间,呈CTAB法>SDS法>CTAB改良法1>CTAB改良法2>试剂盒法的现象。此实验获得的结果可以为短序十大功劳分子生物学研究提供基础。     

利用数值模拟重构物种多样性格局的形成过程

生命形成的过程极其漫长, 经历了地球系统复杂的沧海桑田变化。当前人类所观察到的物种分布格局的形成除了由物种本身特征决定外, 还受到环境变化、人类活动以及各种随机事件的影响。受限于实验条件、时间、经费、人力等诸多因素, 我们尚无法完整地观察并记录到物种多样性形成的全过程, 只能通过片段化数据来推测该过程。信息科学中包括数值模拟在内的仿真技术以其高效、可控及全过程记录等优势, 能从某种程度上解决物种多样性格局形成过程中的部分数据黑箱问题。本文介绍了数值模拟的概念和工作原理及在物种多样性研究中应用的特点, 列举了物种生态位、扩散模式、种间互作及物种分布应对气候变化等方面的数值模拟研究, 基于已有研究系统地介绍了如何综合上述数值模拟研究构建虚拟物种、气候和场景来解释物种多样性的形成与维持机制, 并阐述了数值模拟在物种多样性研究中的优缺点及应用前景。     

Thermal and Solvent-Isotope Effects on the Flagellar Rotary Motor near Zero Load

In Escherichia coli, the behavior of the flagellar rotary motor near zero load can be studied by scattering light from nanogold spheres attached to proximal hooks of cells lacking flagellar filaments. We used this method to monitor changes in speed when cells were subjected to changes in temperature or shifted from a medium made with H₂O to one made with D₂O. In H₂O, the speed increased with temperature in a near-exponential manner, with an activation enthalpy of 52 ± 4 kJ/mol (12.0 ± 1.0 kcal/mol). In D₂O, the speed increased in a similar manner, with an activation enthalpy of 50 ± 4 kJ/mol. The speed in H₂O was higher than that in D₂O by a factor of 1.53 ± 0.14. We performed comparison studies of variations in temperature and solvent isotope, using motors operating at high loads. The variations were small, consistent with previous observations. The implications of these results for proton translocation are discussed.     

Tongxinluo Protects against Hypertensive Kidney Injury in Spontaneously-Hypertensive Rats by Inhibiting Oxidative Stress and Activating Forkhead Box O1 Signaling

Hypertension is an independent risk factor for the progression of chronic renal failure, and oxidative stress plays a critical role in hypertensive renal damage. Forkbox O1(FoxO1) signaling protects cells against oxidative stress and may be a useful target for treating oxidative stress-induced hypertension. Tongxinluo is a traditional Chinese medicine with cardioprotective and renoprotective functions. Therefore, this study aimed to determine the effects of Tongxinluo in hypertensive renal damage in spontaneously hypertensive rats(SHRs)and elucidate the possible involvement of oxidative stress and FoxO1 signaling in its molecular mechanisms. SHRs treated with Tongxinluo for 12 weeks showed a reduction in systolic blood pressure. In addition to increasing creatinine clearance, Tongxinluo decreased urinary albumin excretion, oxidative stress injury markers including malondialdehyde and protein carbonyls, and expression of nicotinamide adenine dinucleotide phosphate oxidase subunits and its activity in SHR kidneys. While decreasing phosphorylation of FoxO1, Tongxinluo also inhibited the phosphorylation of extracellular signal-regulated kinase1/2 and p38 and enhanced manganese superoxide dismutase and catalase activities in SHR kidneys. Furthermore, histology revealed attenuation of glomerulosclerosis and renal podocyte injury, while Tongxinluo decreased the expression of α-smooth muscle actin, extracellular matrixprotein, transforming growth factor β1 and small mothers against decapentaplegic homolog 3,and improved tubulointerstitial fibrosis in SHR kidneys. Finally, Tongxinluo inhibited inflammatory cell infiltration as well as expression of tumor necrosis factor-α and interleukin-6. In conclusion, Tongxinluo protected SHRs against hypertension-induced renal injury by exerting antioxidant, antifibrotic, and anti-inflammatory activities. Moreover, the underlying mechanisms of these effects may involve inhibition of oxidative stress and functional activation of FoxO1 signaling.     

Inhibition Ability of Food Cues between Successful and Unsuccessful Restrained Eaters: A Two-Choice Oddball Task

BackgroundPrevious studies have presented mixed findings on the inhibition ability in restrained eaters (REs) due to the limited amount of neural evidence and limitations of behavioral measures. The current study explores the neural correlations of the specific inhibition ability among successful restrained eaters (S-REs), unsuccessful restrained eaters (US-REs), and unrestrained eaters (UREs).ConclusionResults indicate that S-REs and US-REs differ in terms of specific inhibition ability and that enhanced inhibition is essential to a successful diet.     

Identification of chalcone synthase genes and their expression patterns reveal pollen abortion in cotton

Chalcone synthase (CHS) is a key enzyme and producing flavonoid derivatives as well play a vital roles in sustaining plant growth and development. However, the systematic and comprehensive analysis of CHS genes in island cotton (G. barbadense) has not been reported yet especially response to cytoplasmic male sterility (CMS). To fill this knowledge gap, a genome-wide investigation of CHS genes were studied in island cotton. A total of 20 GbCHS genes were identified and grouped into five GbCHSs. The gene structure analysis revealed that most of GbCHS genes consisted of two exons and one intron, and 20 motifs were identified. Twenty five pairs duplicated events (12 GbCHS genes) were identified including 23 segmental duplication pairs and two tandem duplication events, representing that GbCHS gene family amplification mainly owned to segmental duplication events and evolving slowly. Gene expression analysis exhibited that the GbCHS family genes presented a diversity expression patterns in various organs of cotton. Coupled with functional predictions and gene expression, the abnormal expression of GbCHS06, 10, 16 and 19 might be associated with pollen abortion of CMS line in island cotton. Conclusively, GbCHS genes exhibited diversity and conservation in many aspects, which will help to better understand functional studies and a reference for CHS research in island cotton and other plants.