气候变化下中国八种梧桐属树种潜在适生区模拟

中国梧桐属（Firmiana）在世界梧桐属中占比较大，且除梧桐外其余种均为中国特有且分布范围狭窄的植物种，灭绝风险大，研究气候变化对中国梧桐属树种的影响对于维护生物多样性具有重要的意义。结合多时期第六次国际气候耦合模式比较计划（CMIP6）气候变量数据和中国八种梧桐属树种的分布数据，基于R语言kuenm程序包优化的最大熵（Maxent）模型模拟分析中国八种梧桐属树种在多尺度下的潜在适生区，得出梧桐属最适宜的模拟尺度、潜在适生区的面积变化和迁移方向、梧桐属多样性保护关键区域及保护空缺。结果表明：（1）梧桐属最适宜的模拟尺度为亚洲；（2） Maxent模型的接收者操作特征曲线下面积（AUC）值均大于0.9，表明模型对梧桐属潜在适生区预测结果具有较高准确度；（3）气候变化影响下除云南梧桐（Firmiana major）外其它树种的潜在适生区都将在未来有所扩大；（4）中国八种梧桐属树种潜在适生区迁移方向主要为东西向，南北向大跨度迁移较少，纬度变化不大；（5）丹霞梧桐（Firmiana danxiaensis）的稳定潜在适生区最小；（6）中国梧桐属多样性保护关键区域主要分布于广西壮族自治区及云南、广东、海南等省区；（7）中国梧桐属多样性保护空缺区域主要分布于广西壮族自治区中部及海南省北部；（8）梧桐属多样性保护关键区域正在为人造地表所侵蚀。研究分析气候变化对中国八种梧桐属树种的影响及其潜在适生区变化、中国梧桐属多样性保护状态，可为中国梧桐属建立多样性保护廊道提供相关建议，为制定多样性保护规划及相应措施提供参考。     

Cucurbitacin I Induces Protective Autophagy in Glioblastoma in Vitro and in Vivo

There is an urgent need for new therapeutic avenues to improve the outcome of patients with glioblastoma multiforme (GBM). Current studies have suggested that cucurbitacin I, a natural selective inhibitor of JAK2/STAT3, has a potent anticancer effect on a variety of cancer cell types. This study showed that autophagy and apoptosis were induced by cucurbitacin I. Exposure of GBM cells to cucurbitacin I resulted in pronounced apoptotic cell death through activating bcl-2 family proteins. Cells treatment with cucurbitacin I up-regulated Beclin 1 and triggered autophagosome formation and accumulation as well as conversion of LC3I to LC3II. Activation of the AMP-activated protein kinase/mammalian target of rapamycin/p70S6K pathway, but not the PI3K/AKT pathway, occurred in autophagy induced by cucurbitacin I, which was accompanied by decreased hypoxia-inducible factor 1α. Stable overexpression of hypoxia-inducible factor 1α induced by FG-4497 prevented cucurbitacin I-induced autophagy and down-regulation of bcl-2. Knockdown of beclin 1 or treatment with the autophagy inhibitor 3-methyladenine also inhibited autophagy induced by cucurbitacin I. A coimmunoprecipitation assay showed that the interaction of Bcl-2 and Beclin 1/hVps34 decreased markedly in cells treated with cucurbitacin I. Furthermore, knockdown of beclin 1 or treatment with the lysosome inhibitor chloroquine sensitized cancer cells to cucurbitacin I-induced apoptosis. Finally, a xenograft model provided additional evidence for the occurrence of cucurbitacin I-induced apoptosis and autophagy in vitro. Our findings provide new insights into the molecular mechanisms underlying cucurbitacin I-mediated GBM cell death and may provide an efficacious therapy for patients harboring GBM.     

eEF-2 Phosphorylation Down-Regulates P-Glycoprotein Over-Expression in Rat Brain Microvessel Endothelial Cells

ObjectiveWe investigated whether glutamate, NMDA receptors, and eukaryote elongation factor-2 kinase (eEF-2K)/eEF-2 regulate P-glycoprotein expression, and the effects of the eEF-2K inhibitor NH125 on the expression of P-glycoprotein in rat brain microvessel endothelial cells (RBMECs).MethodsCortex was obtained from newborn Wistar rat brains. After surface vessels and meninges were removed, the pellet containing microvessels was resuspended and incubated at 37°C in culture medium. Cell viability was assessed by the MTT assay. RBMECs were identified by immunohistochemistry with anti-vWF. P-glycoprotein, phospho-eEF-2, and eEF-2 expression were determined by western blot analysis. Mdr1a gene expression was analyzed by RT-PCR.ResultsMdr1a mRNA, P-glycoprotein and phospho-eEF-2 expression increased in L-glutamate stimulated RBMECs. P-glycoprotein and phospho-eEF-2 expression were down-regulated after NH125 treatment in L-glutamate stimulated RBMECs.ConclusionseEF-2K/eEF-2 should have played an important role in the regulation of P-glycoprotein expression in RBMECs. eEF-2K inhibitor NH125 could serve as an efficacious anti-multidrug resistant agent.     

JSI-124 Suppresses Invasion and Angiogenesis of Glioblastoma Cells In Vitro

Glioblastoma multiforme (GBM) is one of the utmost malignant tumors. Excessive angiogenesis and invasiveness are the major reasons for their uncontrolled growth and resistance toward conventional strategies resulting in poor prognosis. In this study, we found that low-dose JSI-124 reduced invasiveness and tumorigenicity of GBM cells. JSI-124 effectively inhibited VEGF expression in GBM cells. In a coculture study, JSI-124 completely prevented U87MG cell–mediated capillary formation of HUVECs and the migration of HUVECs when cultured alone or cocultured with U87MG cells. Furthermore, JSI-124 inhibited VEGF-induced cell proliferation, motility, invasion and the formation of capillary-like structures in HUVECs in a dose-dependent manner. JSI-124 suppressed VEGF-induced p-VEGFR2 activity through STAT3 signaling cascade in HUVECs. Immunohistochemistry analysis showed that the expression of CD34, Ki67, p-STAT3 and p-VEGFR2 protein in xenografts was remarkably decreased. Taken together, our findings provide the first evidence that JSI-124 effectively inhibits tumor angiogenesis and invasion, which might be a viable drug in anti-angiogenesis and anti-invasion therapies.     

Host-Parasite Interactions and Purifying Selection in a Microsporidian Parasite of Honey Bees

To clarify the mechanisms of Nosema ceranae parasitism, we deep-sequenced both honey bee host and parasite mRNAs throughout a complete 6-day infection cycle. By time-series analysis, 1122 parasite genes were significantly differently expressed during the reproduction cycle, clustering into 4 expression patterns. We found reactive mitochondrial oxygen species modulator 1 of the host to be significantly down regulated during the entire infection period. Our data support the hypothesis that apoptosis of honey bee cells was suppressed during infection. We further analyzed genome-wide genetic diversity of this parasite by comparing samples collected from the same site in 2007 and 2013. The number of SNP positions per gene and the proportion of non-synonymous substitutions per gene were significantly reduced over this time period, suggesting purifying selection on the parasite genome and supporting the hypothesis that a subset of N. ceranae strains might be dominating infection.     

Isolation and characterization of 16 tetranucleotide microsatellite loci in the red panda (Ailurus fulgens)

A total of 15 polymorphic tetranucleotide microsatellite loci in the red panda, Ailurus fulgens, were characterized in this study. Based on evaluations of 33 red pandas, the number of observed alleles for each locus ranged from seven to 17 and the expected and observed heterozygosities were 0.412–0.897 and 0.121–0.909, respectively. The mean polymorphic information content was 0.721. These markers would greatly strengthen the utilization of microsatellite tools in genetic variation studies in red panda populations.     

溶瘤病毒载体研究进展

溶瘤病毒(oncolytic virus,OVs)疗法是治疗肿瘤的一种新方法,它可通过直接杀死肿瘤细胞并引起机体的免疫反应发挥作用.然而天然溶瘤病毒有一定的局限性,因此需将各种不同的病毒作为载体,通过基因修饰的方法增强或减弱病毒毒力并导入新的功能性基因,以提高其溶瘤作用.目前可以作为溶瘤病毒载体的有单纯疱疹病毒、腺病毒、牛痘病毒、水泡性口炎病毒、麻疹病毒、腮腺炎病毒、脊髓灰质炎病毒等.这些病毒载体均可通过不同的基因修饰方法,靶向性感染并杀死不同的肿瘤细胞,获得较好的溶瘤作用.本文综述了几种溶瘤病毒载体的基因修饰方法,以及修饰后的溶瘤效果.