Design,synthesis and evaluation of constrained tetrahydroimidazopyrimidine derivatives as antagonists of corticotropin-releasing factor type 1 receptor (CRF1R)

Several tetrahydroimidazopyrimidines were prepared using silver assisted cyclization as the key step. The binding affinities of compounds thus prepared were evaluated in vitro toward hCRF₁R. Initial lead compound 16 (K_i = 32 nM) demonstrated modest putative anxiolytic effects in the mouse canopy test. Further optimization using parallel synthesis provided compounds with K_i’s <50 nM.     

A Network Centrality Method for the Rating Problem

We propose a new method for aggregating the information of multiple users rating multiple items. Our approach is based on the network relations induced between items by the rating activity of the users. Our method correlates better than the simple average with respect to the original rankings of the users, and besides, it is computationally more efficient than other methods proposed in the literature. Moreover, our method is able to discount the information that would be obtained adding to the system additional users with a systematically biased rating activity.     

Is Yield Increase Sufficient to Achieve Food Security in China?

Increasing demand for food, driven by unprecedented population growth and increasing consumption, will keep challenging food security in China. Although cereal yields have substantially improved during the last three decades, whether it will keep thriving to meet the increasing demand is not known yet. Thus, an integrated analysis on the trends of crop yield and cultivated area is essential to better understand current state of food security in China, especially on county scale. So far, yield stagnation has extensively dominated the main cereal-growing areas across China. Rice yield is facing the most severe stagnation that 53.9% counties tracked in the study have stagnated significantly, followed by maize (42.4%) and wheat (41.9%). As another important element for production sustainability, but often neglected is the planted area patterns. It has been further demonstrated that the loss in productive arable land for rice and wheat have dramatically increased the pressure on achieving food security. Not only a great deal of the planted areas have stagnated since 1980, but also collapsed. 48.4% and 54.4% of rice- and wheat-growing counties have lost their cropland areas to varying degrees. Besides, 27.6% and 35.8% of them have retrograded below the level of the 1980s. The combined influence (both loss in yield and area) has determined the crop sustainable production in China to be pessimistic for rice and wheat, and consequently no surprise to find that more than half of counties rank a lower level of production sustainability. Therefore, given the potential yield increase in wheat and maize, as well as substantial area loss of rice and wheat, the possible targeted adaptation measures for both yield and cropping area is required at county scale. Moreover, policies on food trade, alongside advocation of low calorie diets, reducing food loss and waste can help to enhance food security.     

基于三种叶绿体基因序列的证据分析阴石粉背蕨和金粉背蕨的关系

选择阴石粉背蕨(Aleuritopteris humatifolia)和金粉背蕨(A.chrysophylla)及其相关类群共27种植物,提取基因组DNA,通过聚合酶链式反应(PCR)扩增其叶绿体rbc L,trn L-F和mat K序列,所得序列利用Clustal X软件进行对位排列,用MEGA6.0软件计算种内及种间遗传距离,并采用最大简约法(MP)构建系统发育树。结果显示:阴石粉背蕨1个样品和金粉背蕨2个样品的rbc L,trn L-F和mat K序列间差异很小,最大遗传距离均小于其与其它近缘种的种间最小遗传距离,结合两个种叶片形态、孢子、囊群盖和根状茎鳞片等形态学特征的对比研究,作者认为阴石粉背蕨应该作为金粉背蕨的异名处理。     

What Do Pneumocystis Organisms Tell Us about the Phylogeography of Their Hosts? The Case of the Woodmouse Apodemus sylvaticus in Continental Europe and Western Mediterranean Islands

Pneumocystis fungi represent a highly diversified biological group with numerous species, which display a strong host-specificity suggesting a long co-speciation process. In the present study, the presence and genetic diversity of Pneumocystis organisms was investigated in 203 lung samples from woodmice (Apodemus sylvaticus) collected on western continental Europe and Mediterranean islands. The presence of Pneumocystis DNA was assessed by nested PCR at both large and small mitochondrial subunit (mtLSU and mtSSU) rRNA loci. Direct sequencing of nested PCR products demonstrated a very high variability among woodmouse-derived Pneumocystis organisms with a total number of 30 distinct combined mtLSU and mtSSU sequence types. However, the genetic divergence among these sequence types was very low (up to 3.87%) and the presence of several Pneumocystis species within Apodemus sylvaticus was considered unlikely. The analysis of the genetic structure of woodmouse-derived Pneumocystis revealed two distinct groups. The first one comprised Pneumocystis from woodmice collected in continental Spain, France and Balearic islands. The second one included Pneumocystis from woodmice collected in continental Italy, Corsica and Sicily. These two genetic groups were in accordance with the two lineages currently described within the host species Apodemus sylvaticus. Pneumocystis organisms are emerging as powerful tools for phylogeographic studies in mammals.     

MiR-26a enhances the radiosensitivity of glioblastoma multiforme cells through targeting of ataxia–telangiectasia mutated

Glioblastoma multiforme (GBM) is notoriously resistant to radiation, and consequently, new radiosensitizers are urgently needed. MicroRNAs are a class of endogenous gene modulators with emerging roles in DNA repair. We found that overexpression of miR-26a can enhance radiosensitivity and reduce the DNA repair ability of U87 cells. However, knockdown miR-26a in U87 cells could act the converse manner. Mechanistically, this effect is mediated by direct targeting of miR-26a to the 3′UTR of ATM, which leads to reduced ATM levels and consequent inhibition of the homologous recombination repair pathway. These results suggest that miR-26a may act as a new radiosensitizer of GBM.     

The state and conservation of Southeast Asian biodiversity

Southeast Asia is a region of conservation concern due to heavy losses of its native habitats. In this overview, we highlight the conservation importance of Southeast Asia by comparing its degree of species endemism and endangerment, and its rate of deforestation with other tropical regions (i.e., Meso-America, South America, and Sub-Saharan Africa). Southeast Asia contains the highest mean proportion of country-endemic bird (9%) and mammal species (11%). This region also has the highest proportion of threatened vascular plant, reptile, bird, and mammal species. Furthermore, not only is Southeast Asia’s annual deforestation rate the highest in the tropics, but it has also increased between the periods 1990–2000 and 2000–2005. This could result in projected losses of 13–85% of biodiversity in the region by 2100. Secondary habitat restoration, at least in certain countries, would allow for some amelioration of biodiversity loss and thus potentially lower the currently predicted extinction rates. Nonetheless, urgent conservation actions are needed. Conservation initiatives should include public education, sustaining livelihoods, and ways to enhance the sustainability of agriculture and increase the capacity of conservation institutions. Furthermore, these actions should be country-specific and not ignore areas heavily populated by humans, as they can also harbour high numbers of threatened species. We urge that cooperative conservation initiatives be undertaken and support (e.g., capacity-building) be given by more developed countries in the region and beyond.     

桥小脑角区脑膜瘤显微外科手术17例分析

目的:探讨桥小脑角脑膜瘤的临床表现及相应的手术治疗方案,提高显微外科手术治疗效果.方法:回顾分析我院近5年来收治的17例桥小脑角脑膜瘤患者,均采用枕下乙状窦后手术入路.结果:本组肿瘤全切率为88.3%面神经和位听神经功能大部分保留,无死亡病例.结论:术前详细的检查和完善的手术方案制订对桥小脑角区脑膜瘤的手术治疗至关重要,显微外科手术是治疗桥小脑角区脑膜瘤安全有效的方法     

PTEN和EGFR在胃癌中的表达及相关性研究

目的:检测第10号染色体缺失的磷酸酶和张力蛋白同源物基因PTEN及表皮生长因子受体EGFR在胃癌组织中的表达,探讨两者与胃癌肿瘤行为的关系及意义。方法:采用免疫组织化学染色法(S-P法)检测105例胃癌组织及癌旁正常胃组织中EGFR和PTEN蛋白的表达水平,并将检测结果与临床病理参数进行综合分析。结果:胃癌组织PTEN的表达56.19%明显低于正常组织中的表达的表达92.3%,而胃癌组织EGFR的表达46.67%明显高于正常组织7.62%,(P<0.01)。二者的表达与性别和年龄无相关性(P>0.05),与胃癌的分化程度、浸润深度、淋巴结转移及临床分期有相关性(P<0.05)。结论:PTEN在胃癌组织中呈低表达,EGFR在胃癌组织中存在高表达,与胃癌的发生、发展有一定关系,并与胃癌的分化程度、浸润深度、淋巴结转移及临床分期密切相关,二者呈负相关。