Synthesis and anti-tumor activity of novel ethyl 3-aryl-4-oxo-3,3a,4,6-tetrahydro-1H-furo[3,4-c]pyran-3a-carboxylates

A series of ethyl 3-aryl-4-oxo-3,3a,4,6-tetrahydro-1H-furo[3,4-c]pyran-3a-carboxylates were prepared through the metal-catalyzed domino reaction of alkylidene malonates and 1,4-butynediol under a one-pot reaction condition at room temperature. Their in vitro anti-proliferative activities were subsequently evaluated in A549, QGY and HeLa cells. The majority of the compounds showed potent anti-tumor activity against HeLa cells. In particular, compound 3l was the most potent compound with IC₅₀ value of 5.4 μM. For the first time, the X-ray structure of the anti-tumor ethyl 3-aryl-4-oxo-3,3a,4,6-tetrahydro-1H-furo[3,4-c]pyran-3a-carboxylates is determined.     

Slit-Robo signaling induces malignant transformation through Hakai-mediated E-cadherin degradation during colorectal epithelial cell carcinogenesis

The Slit family of guidance cues binds to Roundabout (Robo) receptors and modulates cell migration. We report here that ectopic expression of Slit2 and Robo1 or recombinant Slit2 treatment of Robo1-expressing colorectal epithelial carcinoma cells recruited an ubiquitin ligase Hakai for E-cadherin (E-cad) ubiquitination and lysosomal degradation, epithelial-mesenchymal transition (EMT), and tumor growth and liver metastasis, which were rescued by knockdown of Hakai. In contrast, knockdown of endogenous Robo1 or specific blockade of Slit2 binding to Robo1 prevented E-cad degradation and reversed EMT, resulting in diminished tumor growth and liver metastasis. Ectopic expression of Robo1 also triggered a malignant transformation in Slit2-positive human embryonic kidney 293 cells. Importantly, the expression of Slit2 and Robo1 was significantly associated with an increased metastatic risk and poorer overall survival in colorectal carcinoma patients. We conclude that engagement of Robo1 by Slit2 induces malignant transformation through Hakai-mediated E-cad ubiquitination and lysosomal degradation during colorectal epithelial cell carcinogenesis.     

MLD-STZ诱导1型糖尿病小鼠胰腺比较蛋白质组学研究

目的：通过对小剂量多次链脲佐菌素（multiple low doses of streptozotocin MLD-STZ）诱导的1型糖尿病模型小鼠胰腺与正常小鼠胰腺蛋白的比较分析,拟从蛋白水平上对1型糖尿病发病机制进行探讨。方法：将20只雄性昆明鼠,按体重随机分为MLD-STE模型组和正常对照组（n=10）,应用二维凝胶电泳技术获得胰腺的二维电泳图谱,经ImageMaster2D 5．0软件分析获得差异蛋白,结合质谱（MALDI-TOF-MS）与MASCOT网络数据库进行匹配鉴定蛋白。结果：与正常对照组比较,模型组胰腺中有23个蛋白表达改变,其中15个蛋白表达下调,8个蛋白表达上调。经肽质量指纹图谱分析及蛋白数据库检索,最终鉴定出15个差异蛋白,根据其功能可分为：①代谢相关蛋白;②氧化应激相关蛋白;③催化酶类;④细胞骨架蛋白;⑤伴侣蛋白;⑥免疫相关蛋白;⑦其他蛋白。结论：研究结果表明模型组胰腺蛋白表达存在明显改变,提示1型糖尿病的发生是多途径多靶点的共同作用,同时这些改变蛋白为研究和治疗糖尿病等相关疾病提供了新靶标。     

杜鹃花属植物扦插繁殖研究进展

我国有着丰富的杜鹃花资源,但有关其繁殖应用的研究还具有一定的局限。种子育苗耗时长,组培育苗成本和技术要求高,都不适于杜鹃花属植物的大面积生产。扦插繁殖快,还可保持母本的优良性状。从插条的选择,准备,插条的生根激素处理,扦插基质的选择,外界环境条件对扦插成活率的影响及扦插后的养护管理等六个方面对杜鹃的扦插繁殖技术的研究进行综述,以期推进杜鹃花属植物,尤其是中国野生杜鹃的引种驯化和大面积的推广应用。     

Artificial gravity with ergometric exercise preserves the cardiac, but not cerebrovascular, functions during 4 days of head-down bed rest

Cardiovascular and musculoskeletal deconditioning occurring in long-term spaceflight requires new strategies to counteract these adverse effects. We previously reported that a short-arm centrifuge produced artificial gravity (AG), together with ergometer, has an approving effect on promoting cardiovascular function. The current study sought to investigate whether the cardiac and cerebrovascular functions were maintained and improved using a strategy of AG combined with exercise training on cardiovascular function during 4-day head-down bed rest (HDBR). Twelve healthy male subjects were assigned to a control group (CONT, n=6) and an AG combined with ergometric exercise training group (CM, n=6). Simultaneously, cardiac pumping and systolic functions, cerebral blood flow were measured before, during, and after HDBR. The results showed that AG combined with ergometric exercise caused an increase trend of number of tolerance, however, there was no significant difference between the two groups. After 4-day HDBR in the CONT group, heart rate increased significantly (59±6 vs 66±7 beats/min), while stroke volume (98±12 vs 68±13 mL) and cardiac output (6±1 vs 4±1 L/min) decreased significantly (p<0.05). All subjects had similar drops on cerebral vascular function. Volume regulating hormone aldosterone increased in both groups (by 119.9% in CONT group and 112.8% in the CM group), but only in the CONT group there were a significant changes (p<0.05). Angiotensin II was significantly increased by 140.5% after 4-day HDBR in the CONT group (p<0.05), while no significant changes were observed in the CM group. These results indicated that artificial gravity with ergometric exercise successfully eliminated changes induced by simulated weightlessness in heart rate, volume regulating hormones, and cardiac pumping function and partially maintained cardiac systolic function. Hence, a daily 1h alternating +1.0 and +2.0 Gz with 40 W exercise training appear to be an effective countermeasure against cardiac deconditioning.     

Gene expression profiling-based identification of CD28 and PI3K as new biomarkers for chronic graft-versus-host disease

Chronic graft-versus-host disease (cGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Currently, no reliable biomarkers are available to predict the onset or progression of cGVHD. Therefore, in this study, we collected peripheral blood mononuclear cells from four patients with cGVHD and four ones with non-GVHD after hematopoietic stem cell transplantation and employed Affymetrix GeneChip Human U133 Plus 2.0 microarrays to screen the genes differentially expressed in cGVHD versus non-GVHD groups, with the aim to identify potential clinical biomarkers to predict cGVHD risk or progression. Microarray analysis demonstrated that the expression of 3180 genes changed significantly in cGVHD versus non-GVHD, with 879 genes upregulated and 2301 genes downregulated. Among them we chose CD28 and PI3K as candidates for further verification. Flow cytometry and quantitative real-time polymerase chain reaction analysis confirmed the significant upregulation of CD28 and PI3K in samples from patients with cGVHD compared with patients with non-GVHD, respectively. In conclusion, our study suggested that the upregulation of CD28 and PI3K contributed to the onset and progression of cGVHD and provided evidence that CD28 and PI3K may serve as promising biomarkers for cGVHD.     

Sequence Conservation in the Prediction of Catalytic Sites

Predicting catalytic sites of a given enzyme is an important open problem of Bioinformatics. Recently, many machine learning-based methods have been developed which have the advantage that they can account for many sequential or structural features. We found that although many kinds of features are incorporated, protein sequence conservation is the main part of information they used and should play an important role in the future. So we tested several conservation features in their ability to predict catalytic sites by using the Support Vector Machine classifier. Our results suggest that position specific scoring matrix performs better than other features and incorporating conservation information of sequentially adjacent sites is more effective than that of structurally adjacent ones. Moreover, although conservation information is effective in predicting catalytic sites, it is a difficult problem to optimize the combination of conservation features and other ones.     

Structural variation in two human genomes mapped at single-nucleotide resolution by whole genome de novo assembly

Here we use whole-genome de novo assembly of second-generation sequencing reads to map structural variation (SV) in an Asian genome and an African genome. Our approach identifies small- and intermediate-size homozygous variants (1-50 kb) including insertions, deletions, inversions and their precise breakpoints, and in contrast to other methods, can resolve complex rearrangements. In total, we identified 277,243 SVs ranging in length from 1-23 kb. Validation using computational and experimental methods suggests that we achieve overall <6% false-positive rate and <10% false-negative rate in genomic regions that can be assembled, which outperforms other methods. Analysis of the SVs in the genomes of 106 individuals sequenced as part of the 1000 Genomes Project suggests that SVs account for a greater fraction of the diversity between individuals than do single-nucleotide polymorphisms (SNPs). These findings demonstrate that whole-genome de novo assembly is a feasible approach to deriving more comprehensive maps of genetic variation.     

Three novel species of Stemphylium from Sinkiang, China: their morphological and molecular characterization

Three new species of Stemphylium were isolated from diseased leaves of Luffa cylindrica, Lycium chinense and Cucumis melo growing in the Sinkiang province of Northwest China. Stemphylium luffae, S. lycii and S. cucumis are described by morphological and molecular phylogenetic analyses. The principal morphological characteristics of these three species are congruent with those of Stemphylium. They are distinguished from morphologically similar Stemphylium species based on characteristics of their conidia and conidiophores. In order to establish the molecular phylogenetic status of these species, DNA loci including the internal transcribed spacer (ITS) nuclear rDNA region and the glyceraldehyde-3-phosphate dehydrogenase (gpd) genes were amplified and sequenced. Phylogenetic analyses using Maximum-Parsimony (MP) and Neighbor-Joining (NJ) were performed on the combined DNA sequences of ITS and gpd gene regions. Both morphological observations and molecular analyses support S. luffae, S. lycii and S. cucumis as three new taxa.