Development and validation of glycolysis-related prognostic score for prediction of prognosis and chemosensitivity of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with aggressive biological behaviour. Its rapid proliferation and tumour growth require reprogramming of glucose metabolism or the Warburg effect. However, the association between glycolysis-related genes with clinical features and prognosis of PDAC is still unknown. Here, we used the meta-analysis to correlate the hazard ratios (HR) of 106 glycolysis genes from MSigDB by the cox proportional hazards regression analysis in 6 clinical data sets of PDAC patients to form a training cohort, and a single group of PDAC patients from the TCGA, ICGC, Arrayexpress and GEO databases to form the validation cohort. Then, a glycolysis-related prognosis (GRP) score based on 29 glycolysis prognostic genes was established in 757 PDAC patients from the training composite cohort and validated in 267 ICGC-CA validation cohort (all P < .05). In addition, including PADC, the prognostic value was also confirmed in other 7 out of 30 pan-cancer cohorts. The GRP score was significantly related to specific metabolism pathways, immune genes and immune cells in the patients with PADC (all P < .05). Finally, by combining with immune cells, the GRP score also well-predicted the chemosensitivity of patients with PADC in the TCGA cohort (AUC = 0.709). In conclusion, this study developed a GRP score for patients with PDAC in predicting prognosis and chemosensitivity for PDAC.     

Molecular analysis of fungal diversity associated with three bryophyte species in the Fildes Region, King George Island, maritime Antarctica

The fungal communities associated with three bryophytes species (the liverwort Barbilophozia hatcheri, the mosses Chorisodontium aciphyllum and Sanionia uncinata) in the Fildes Region, King George Island, maritime Antarctica, were studied using clone library analysis. Fungal communities showed low diversity; the 680 clones belonged to 93 OTUs. Of these, 78 belonged to the phylum Ascomycota, 13 to the phylum Basidiomycota, 1 to the phylum Zygomycota, and 1 to an unknown phylum. Among the OTUs, the most common orders in the Ascomycota were Helotiales (42 OTUs) and Chaetothyriales (14 OTUs) and the most common orders in the Basidiomycota were Sebacinales (3 OTUs) and Platygloeales (3 OTUs). Most OTUs clustered within clades that contained phylotypes identified from samples in Antarctic or Arctic ecosystems or from bryophytes in other ecosystems. In addition, we found that host-related factor may shape the fungal communities associated with bryophytes in this region. This is the first systematic study of the fungal community in Antarctic bryophytes to be performed using culture-independent method and the results may improve understanding of the endophytic fungal evolution and ecology in the Antarctic ecosystem.     

正常妊娠大鼠的Th2型免疫反应

采用流式细胞仪,^3H-TdR掺入和酶联免疫打点(enzyme-linked immunospot,ELISPOT)方法研究妊娠免疫学指标的改变。妊娠晚期大鼠脾脏单个核细胞表面分子主要组织相容性抗原Ⅱ(MHCⅡ)明显下调,外周血单个核细胞表达CD11c明显减少,共激活分子B7-1和B7-2未见改变;脾脏和外周血单个核细胞中Th2细胞因子IL-10、IL-4表达增多,TGFD阳性细胞数也明显增加,而Th1细胞因子IFNγ的产生未受抑制。此外,脾脏和外周血中单个核细胞的抗原特异性增殖未见改变,而腹腔淋巴结细胞的增殖明显升高。脾脏单个核细胞在妊娠晚期分泌较少的抗原特异性抗体。提示妊娠期性激素具有免疫调节作用,可能与怀孕时Th1细胞介导的自身免疫性疾病得到缓解有关。     

Systematic analysis of the combinatorial nature of epitopes recognized by TCR leads to identification of mimicry epitopes for glutamic acid decarboxylase 65-specific TCRs

Accumulating evidence indicates that recognition by TCRs is far more degenerate than formerly presumed. Cross-recognition of microbial Ags by autoreactive T cells is implicated in the development of autoimmunity, and elucidating the recognition nature of TCRs has great significance for revelation of the disease process. A major drawback of currently used means, including positional scanning synthetic combinatorial peptide libraries, to analyze diversity of epitopes recognized by certain TCRs is that the systematic detection of cross-recognized epitopes considering the combinatorial effect of amino acids within the epitope is difficult. We devised a novel method to resolve this issue and used it to analyze cross-recognition profiles of two glutamic acid decarboxylase 65-autoreactive CD4(+) T cell clones, established from type I diabetes patients. We generated a DNA-based randomized epitope library based on the original glutamic acid decarboxylase epitope using class II-associated invariant chain peptide-substituted invariant chains. The epitope library was composed of seven sublibraries, in which three successive residues within the epitope were randomized simultaneously. Analysis of agonistic epitopes indicates that recognition by both TCRs was significantly affected by combinations of amino acids in the antigenic peptide, although the degree of combinatorial effect differed between the two TCRs. Protein database searching based on the TCR recognition profile proved successful in identifying several microbial and self-protein-derived mimicry epitopes. Some of the identified mimicry epitopes were actually produced from recombinant microbial proteins by APCs to stimulate T cell clones. Our data demonstrate the importance of the combinatorial nature of amino acid residues of epitopes in molecular mimicry.     

Tumor Invasiveness,Not Lymphangiogenesis,Is Correlated with Lymph Node Metastasis and Unfavorable Prognosis in Young Breast Cancer Patients (≤35 Years)

The morbidity rate of breast cancer is on the rise, and the age of onset appears to be trending toward a young age. Breast cancer in young women (BCYW) has a number of distinctive features that differ from breast cancer in middle-aged or elderly women (BCMEW). Lymphatic metastasis plays an important role in the spread of BCYW; however, the mechanisms of lymph node metastasis (LNM) in BCYW are not clear. This study aimed to investigate the mechanism of lymphatic metastasis in BCYW and to evaluate the relationships between lymphangiogenesis, the expression of matrix metalloproteinase 9 (MMP-9) and vascular endothelial growth factor C (VEGF-C) expression, clinicopathological characteristics, and prognosis. Using immunohistochemistry, MMP-9, VEGF-C and the level of lymphatic microvessel density (LMVD) were analyzed in 106 cases of breast invasive ductal carcinoma and 20 cases of breast proliferative lesions. Compared with BCMEW, BCYW had higher MMP-9 expression, higher LNM, and more adverse prognoses. In BCYW, high MMP-9 expression was positively correlated with LNM and impaired survival time. However, in BCMEW, MMP-9 expression was not correlated with LNM or survival time. In addition, high VEGF-C expression was positively correlated with a high level of LMVD in both BCYW and BCMEW. Nevertheless, a high level of LMVD was not correlated with LNM or survival time in the two groups. More importantly, univariate and multivariate survival analysis showed that MMP-9 expression and LNM were independent prognostic factors in BCYW. Our present study indicates that lymphangiogenesis induced by VEGF-C is augmented in breast cancer; however, a higher level of lymphangiogenesis has no significant impact on LNM or survival time. We suggest that tumor invasiveness, rather than lymphangiogenesis, plays an important role in LNM among BCYW. Moreover, MMP-9 and LNM were independent prognostic factors for BCYW.     

NF-κB决定小鼠胎肝激酶-1基因启动子的基本活性

为克隆小鼠胎肝激酶-1（fetal liver kinase-1,FLK-1）基因上游启动子序列,并观察其不同截短片段在小鼠血管内皮细胞中的启动子活性,以小鼠全基因组为模板,通过PCR扩增方法获得-258～+299 bp、-96～+299 bp、-71～+299 bp、-36～+299 bp大小的FLK-1启动子片段,将其定向克隆入pGL3 Basic,构建荧光素酶报告基因载体,并制备NF -κB结合位点的突变或缺失体.在阳离子脂质体介导下,报告基因载体瞬时转染小鼠血管内皮细胞株SVEC 4-10.结果发现,在小鼠血管内皮细胞中,各FLK-1启动子片段均有活性;－71～－36 bp区存在FLK-1启动子的核心调控元件.针对该区域NF-κB结合位点进行突变或缺失,能导致启动子活性显著降低;凝胶电泳迁移率实验表明该区段能结合转录因子NF-κB.结果提示,成功克隆了在血管内皮细胞中具有活性的FLK-1上游启动子序列,NF-κB是决定其基本活性的重要转录因子,为进一步研究FLK-1基因的转录调控机制奠定了基础.     

拟南芥核酸外切体亚基RRP41L与RRP42及RRP45B的互作关系

在真核生物中,核酸外切体(exosome)是一个由9个核心蛋白亚基组成的在进化上十分保守的大分子复合物,具有加工和降解RNA的重要功能。为了了解影响拟南芥生长发育的核酸外切体亚基RRP41-LIKE (RRP41L)与其他外切体亚基之间的互作关系,本文利用酵母双杂交和荧光素酶互补技术从体外和体内两个方面验证了RRP41L与另外两个核酸外切体亚基RRP42及RRP45B的互作关系。结果显示RRP41L不能与RRP42互作,而能与RRP45B互作。     

山西桑干河流域湿地植被优势种群分布格局研究

根据野外调查的样地资料,应用方差/均值比（扩散系数）的t检验、聚集指数、平均拥挤度、聚块性指数、Green指数和负二项分布的聚集强度等方法,研究了山西桑干河流域湿地植被优势种群的分布格局并分析格局形成的原因,并用相关分析比较了6个指数间的关系,结果表明：这些植物的分布格局皆属于聚集分布,但它们的聚集强度有差异。聚集强度最大的是沙棘和柽柳,聚集强度最小的是小车前和车前,由于它们均分布于河漫滩或者河床地势较高处,土壤水分含量较低,仅仅在洪水季节短时间有积水存在,不是典型的湿地植物。典型的水生植物泽泻、莎草、轮藻、芦苇、香蒲、慈姑,湿生植物水葱、藨草等,它们的聚集强度居中,对水分有着较强的依赖性,均分布于流水较缓的河道,或者濒临河道的积水处。此外,多年生的莎草、芦苇、香蒲、水葱、藨草等主要依靠无性繁殖扩大种群分布范围和密度,这也是它们服从聚集分布的原因之一。本研究还说明方差/均值比率法是一种较好的分析种群分布格局的方法。     

7号淀粉酶链霉菌M1033菌株木糖异构酶晶体结构研究

7号淀粉酶链霉菌M1033菌株木糖异构酶(SDXyI).19nm分辨率晶体结构已经解出.晶体空间群为I222,晶胞参数为a=9.884nm,b=9.393nm,c=8.798nm.参考锈赤链霉菌木糖异构酶(SRXyI)的晶体结构模型,通过分析晶体密堆积关系和晶体学R因子搜索,获得了SDXyI晶体结构的初始模型.采用PROLSQ软件包使用0.60～0.19nm分辨率衍射数据对模型进行了修正.最终模型的晶体学R因子为0.177,键长键角均方根偏差分别为0.0019nm和2.1°.与SRXyI相比较,SDXyI整体构象未发生明显变化,活性中心构象有显著差异.     

On the Evolution of the Palynoflora and Climatic Environment During Late Pleistocence in Tengger Desert,China

Palynoflora studies on the Duantouliang section, located at 39º40'N, 103º55'E in Northwestern Tengger Desert, China showed that, based on the spore-pollen assemblages, the major vegetation and climatic environment between 42 000 to 23 000 a BP could be divided into the following different periods: Ⅰ. From 42 000 to 38 000 a BP, the spore-pollen assemblages displayed that the mixed conifer/deciduous broad-leaved forests developed on the mountain and its foothill regions where the bare Gobi-desert are at present; At that time, Populus and Salix forests and grassland surrounded the Paleaolake, the climate condition was much warmer and humid than today; Ⅱ. From 38 000 to 37 000 a BP, the climate was warm and moist, it was the most suitable period for the plant growth, the studied area was dominated by the temperate and warm-temperate mixed broad-leaf deciduous and needleleaf forest, there was meadow spreaded on the river sides and lake beaches; Ⅲ. From 31 000 to 30000 a BP, the needleleaf forests and cold-temperate Salix oritrepha shrubs were flourishing, and the climate at that time was relatively cold;Ⅳ. From 30000 to 28000 a BP, the temperatures began increasing, the high lake levels was formed during this time, and the vegetations were meadows and swamps; V. From 28 000 to 23 000 a BP, temperate Cupressaceae and Betula mixed conifer/deciduous forests grew on mountain and foothill region, grassland developed on plain areas, Salix was on lake and river sides. This indicates a warm and moist climate condition but it was drier than the earliest period.