c-Jun N-Terminal Kinase Mediated VEGFR2 Sustained Phosphorylation is Critical for VEGFA-Induced Angiogenesis In Vitro and In Vivo

c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) is involved in the regulation of various cellular functions including cell cycle, proliferation, apoptosis. However, whether JNK/SAPK directly regulates the angiogenesis of human umbilical vein endothelial cells (HUVECs) induced by vascular endothelial growth factor A (VEGFA) has not yet been fully elucidated. Our present study firstly demonstrated VEGFA-induced angiogenic responses including the increase of cell viability, migration, and tube formation with a concentration-dependent manner in HUVECs. Further results showed that VEGFA induced the activation of JNK/SAPK, p38 kinase and extracellular signal-regulated kinases 1 and 2 (ERK1/2), while JNK/SAPK inhibitor SP600125 and specific siRNA both blocked all those angiogenic effects induced by VEGFA. Furthermore, VEGFA induced the phosphorylation of ASK1, SEK1/MKK4, MKK7, and c-Jun, which are upstream or downstream signals of JNK/SAPK. In addition, in vivo matrigel plug assay further showed that SP600125 inhibited VEGFA-induced angiogenesis. Further results showed that SP600125 and JNK/SAPK siRNA decreased VEGFA-induced VEGFR2 (Flk-1/KDR) sustained phosphorylation in HUVECs. Taken together, all these results demonstrate that JNK/SAPK regulates VEGFA-induced VEGFR2 sustained phosphorylation, which plays important roles in VEGFA-induced angiogenesis in HUVECs.     

RP105 involved in activation of mouse macrophages via TLR2 and TLR4 signaling

RP105 is a member of the toll-like receptor family of proteins that transmits an activation signal in B cells, playing a role in regulation of B cell growth and death; in macrophages and dendritic cells, RP105 is a specific inhibitor of TLR4 signaling. RP105 is uniquely important for regulating TLR4-dependent signaling. It also proved that RP105 is closely related to TLR2 in macrophage activation by Mycobacterium tuberculosis lipoproteins. The aim of our study is to investigate the role of RP105 in mouse macrophages activation of TLR4 and TLR2 signaling by lipopolysaccharides (LPS) and Pam3CysSerLys4 (Pam3CSK4) alone or in combination, and the interaction between TLR2 and TLR4 signaling through RP105. Our results indicate that besides exhibiting negative regulation of TNF-α and IL12-p40 secretion in macrophage activated by LPS, RP105 is also involved in macrophages activation by Pam3CSK4 through TLR2 signaling and exhibited regulation to IL-10 and RANTES production by mouse peritoneal macrophage activated by Pam3CSK4. In macrophages activation by LPS and Pam3CSK4 in combination, TLR2 signaling can overcome RP105-mediated regulation of TLR4 signaling. Thus, our data demonstrate that not only TLR4 signaling, but also RP105 appears to be an essential accessory for immune responses through TLR2 signaling. The function of TLR2 and TLR4 in response to TLR ligands could be associated with each other by RP105. These results can help us understanding the unique role of RP105 in macrophages response to TLR ligands.     

Mutual dependency between lncRNA LETN and protein NPM1 in controlling the nucleolar structure and functions sustaining cell proliferation

Fundamental processes such as ribosomal RNA synthesis and chromatin remodeling take place in the nucleolus, which is hyperactive in fast-proliferating cells. The sophisticated regulatory mechanism underlying the dynamic nucleolar structure and functions is yet to be fully explored. The present study uncovers the mutual functional dependency between a previously uncharacterized human long non-coding RNA, which we renamed LETN, and a key nucleolar protein, NPM1. Specifically, being upregulated in multiple types of cancer, LETN resides in the nucleolus via direct binding with NPM1. LETN plays a critical role in facilitating the formation of NPM1 pentamers, which are essential building blocks of the nucleolar granular component and control the nucleolar functions. Repression of LETN or NPM1 led to similar and profound changes of the nucleolar morphology and arrest of the nucleolar functions, which led to proliferation inhibition of human cancer cells and neural progenitor cells. Interestingly, this inter-dependency between LETN and NPM1 is associated with the evolutionarily new variations of NPM1 and the coincidental emergence of LETN in higher primates. We propose that this human-specific protein–lncRNA axis renders an additional yet critical layer of regulation with high physiological relevance in both cancerous and normal developmental processes that require hyperactive nucleoli.Subject terms: Long non-coding RNAs, Cell division     

云南被子植物8个省级分布新记录种北大核心CSCD

首次报道了云南省被子植物的8个省级分布新记录种,分别为三白草科的白苞裸蒴(Gymnotheca involucrata C.Pei)、金虎尾科的花江盾翅藤(Aspidopterys esquirolii H.Lév.)、豆科的柱序杭子梢(Campylotropis teretiracemosa P.C.Li&C.J.Chen)、石竹科的四川卷耳(Cerastium szechuense F.N.Williams)、报春花科的齿萼报春[Primula odontocalyx(Franch.)Pax],苦苣苔科的白花大苞苣苔[Anna ophiorrhizoides(Hemsl.)B.L.Burtt&R.A.Davidson]、唇形科的石荠苎[Mosla scabra(Thunb.)C.Y.Wu&H.W.Li]和菊科的华漏芦[Rhaponticum chinense(S.Moore)L.Martins&Hidalgo];凭证标本保存于云南大学植物标本馆(YUKU)。     

Elevated Alanine Aminotransferase Is Strongly Associated with Incident Metabolic Syndrome: A Meta-Analysis of Prospective Studies

Background

The incidence of metabolic syndrome (MetS) is rapidly increasing worldwide and associated with alanine aminotransferase (ALT) activity. However, the impact of ALT activity on MetS incidence is inconsistent in published literature. We therefore estimated the association between elevated ALT activity and incident MetS through a meta-analysis of prospective cohort studies.

Methods/Principal Findings

All published prospective cohort studies on the association between elevated ALT activity and incident MetS were retrieved from Pubmed, Embase, and the Institute for Scientific Information (ISI). In all, seven prospective cohort studies, with 31545 participants and 2873 cases of incident MetS were recruited. If there was insignificant heterogeneity (P-value>0.05 and I²<50%), the fixed-effect model was used to calculate the pooled relative risks (RRs) of incident MetS induced by raised ALT. Otherwise, the random-effect model was used. The calculated RR was 1.81 (95% confidence interval [CI]: 1.49–2.14) when the incidence of MetS was compared between the highest versus the lowest classification of ALT activities. The pooled RR was 1.13 (95% CI: 1.11–1.16) in dose-response analysis with 5 units per liter (U/l) of ALT increment. Subgroup analysis suggested that gender disparity might be the main origin of heterogeneity in overall analysis (P = 0.007 between RRs of gender-specific subgroups evaluated with 5 U/l increments of ALT). Women had a higher dose-response risk of MetS incidence (1.38, 95% CI: 1.20–1.55) than men. Furthermore, sensitivity analysis confirmed the stability of results. No publication bias was found in our meta-analysis.

Conclusions/Significance

Current evidence from prospective studies supports the association between ALT elevation and increasing MetS incidence. This association is closer and more consistent in female population. Further studies are needed to confirm this association and to investigate the potential mechanism of ALT activity on MetS occurrence.     

南京地区药用植物资源调查

对南京地区的药用植物资源进行了初步调查,据植物分类学统计,南京地区有药用植物107科281属357种,其中蕨类植物12科12属12种,种子植物95科269属345种.对数种江苏特产和稀有的药用植物进行了介绍.     

不同产地丹参脂溶性成分指纹图谱的比较研究

目的：利用聚类分析对各地野生及家种丹参的指纹图谱数据进行分析。了解不同地理区域野生丹参以及同一地区家种丹参的遗传差异,为丹参药材优良品种的筛选提供依据。方法：采用高效液相色谱法,以甲醇-水系统为流动相进行梯度洗脱,流速1．0mL／min。检测波长254nm,使用SPSS11．0数据处理软件对所得指纹图谱中考察指标进行聚类分析。结果：采用无性繁殖的相同产地的家种丹参指纹图谱具有很好的相似性,相应的品系药材可以归入同一类;而野生丹参则不可按其地理区域归类。结论：采用无性繁殖丹参的遗传稳定性较好。     

眼镜蛇毒及其组分C对小鼠实验性肝癌抗癌作用的病理学研究

目的　观察眼镜蛇毒及其组分 Ｃ 抗小鼠肝癌的病理学改变。 方法　采用不同剂量眼镜蛇毒及其抗癌活性组分 Ｃ 与 Ｂ Ａ Ｌ Ａ／ｃ 小鼠腹水型肝癌细胞体外孵育, 空白对照组用生理盐水与肝癌细胞孵育, 然后取孵育液接种于小鼠前肢腋下, 接种后第 １０ｄ 处死, 解剖取出瘤结, 进行病理组织学研究。 结果　空白对照组瘤结较大, 显微镜下见瘤细胞生长活跃、核大、核仁明显、核分裂多见, 而坏死灶少见, 且瘤细胞向周围浸润扩散; 治疗组瘤体较小, 瘤细胞固缩、核仁不明显、核分裂少见, 而坏死灶多见, 瘤细胞周围有纤维组织增生围绕, 限制了瘤细胞向周围蔓延浸润。 结论　眼镜蛇毒及其组分 Ｃ 对小鼠实验性肝癌的体外抗癌作用是明显的, 不同剂量及不同孵育时间的抗癌作用亦显著不同, 其中组分 Ｃ 对抗癌作用最强。     

海岛生态保护红线划定技术方法

划定海岛生态保护红线是维护海岛生态安全,协调海岛开发与保护之间矛盾的重要方法。目前,海岛生态保护红线在概念内涵、划定内容、划定方法等方面尚未统一定性,且极易与海洋生态红线的概念混淆,不同类型和形态的海岛红线划定的方法及原则要求也有所区分,例如,单岛、列岛、群岛、有居民和无居民海岛等。论述了海岛生态保护红线概念、海岛生态保护红线与海洋生态红线的区别和联系;结合生态科学、地理科学和管理科学属性,基于发展观点和底线思维阐述了海岛生态保护红线划定原则;海岛生态保护红线类型主要包括:海岛重点生态功能区、海岛生态敏感区/脆弱区和海岛禁止开发区;筛选出海岛生态保护红线划定需要重点考量的指标,提出海岛生态保护红线划定的技术路线,同时针对海岛生态保护红线区划面临的若干问题进行探讨;最后对今后海岛生态保护红线划定研究进行了展望。     

F1C Fimbriae Play an Important Role in Biofilm Formation and Intestinal Colonization by the Escherichia coli Commensal Strain Nissle 1917

Bacterial biofilm formation is thought to enhance survival in natural environments and during interaction with hosts. A robust colonizer of the human gastrointestinal tract, Escherichia coli Nissle 1917, is widely employed in probiotic therapy. In this study, we performed a genetic screen to identify genes that are involved in Nissle biofilm formation. We found that F1C fimbriae are required for biofilm formation on an inert surface. In addition, these structures are also important for adherence to epithelial cells and persistence in infant mouse colonization. The data suggest a possible connection between Nissle biofilm formation and the survival of this commensal within the host. Further study of the requirements for robust biofilm formation may improve the therapeutic efficacy of Nissle 1917.