Regulation of insulin secretion and GLUT4 trafficking by the calcium sensor synaptotagmin VII

Insulin regulates blood glucose by promoting uptake by fat and muscle, and inhibiting production by liver. Insulin-stimulated glucose uptake is mediated by GLUT4, which translocates from an intracellular compartment to the plasma membrane. GLUT4 traffic and insulin secretion both rely on calcium-dependent, regulated exocytosis. Deletion of the voltage-gated potassium channel Kv1.3 results in constitutive expression of GLUT4 at the plasma membrane. Inhibition of channel activity stimulated GLUT4 translocation through a calcium dependent mechanism. The synaptotagmins (Syt) are calcium sensors for vesicular traffic, and Syt VII mediates lysosomal and secretory granule exocytosis. We asked if Syt VII regulates insulin secretion by pancreatic beta cells, and GLUT4 translocation in insulin-sensitive tissues mouse model. Syt VII deletion (Syt VII -/-) results in glucose intolerance and a marked decrease in glucose-stimulated insulin secretion in vivo. Pancreatic islet cells isolated from Syt VII -/- cells secreted significantly less insulin than islets of littermate controls. Syt VII deletion disrupted GLUT4 traffic as evidenced by constitutive expression of GLUT4 present at the plasma membrane of fat and skeletal muscle cells and unresponsiveness to insulin. These data document a key role for Syt VII in peripheral glucose homeostasis through its action on both insulin secretion and GLUT4 traffic.     

Cucurbitacin E Induces Cell Cycle G2/M Phase Arrest and Apoptosis in Triple Negative Breast Cancer

Triple negative breast cancer (TNBC) is a highly aggressive form of breast cancer resistant to many common treatments. In this study, we compared the effects of 12 phytochemical drugs on four cancer cell lines, and noticed that Cucurbitacin E (CuE) significantly inhibited TNBC cell growth by inducing cell cycle G2/M phase arrest and apoptosis. CuE reduced expression of Cyclin D1, Survivin, XIAP, Bcl2, and Mcl-1 in MDA-MB-468 and SW527, and within MDA-MB-468, CuE significantly increased activation of JNK and inhibited activation of AKT and ERK. Collectively, these results suggest that CuE may be a viable compound for developing novel TNBC therapeutics.     

基于视觉廊道的青藏铁路沿线旅游动态景观评价

青藏铁路作为一种重要的"线性"廊道,不仅起着重要的区域连接作用,促进着区域经济和社会发展,还具有旅游观光和体验的功能。基于游客视角对青藏铁路沿线10个自然景观段进行了青藏铁路沿线旅游动态景观评价研究。详细界定了铁路沿线动态景观评价的对象,构建了"游客眼"——青藏铁路沿线动态景观评价模型。动态景观评价是基于旅游列车在行进过程中以旅游者的眼睛感受到的景观质量高低——景观基底(包括地貌景观多样性、动植物点缀度、人文景观丰富度等),在列车行进过程中哪些景观能被游客捕捉到受到景观视域(包括相对坡度、景观在视域内出现几率、距离的远近等)的制约,哪些景观能被游客留下深刻印象要受到景观美感(包括色彩、奇异罕见景观、水体配置等)的影响。搭建了青藏铁路沿线旅游动态景观评价指标体系,青藏铁路沿线旅游动态景观评价指标体系包括沿线景观基底指标、景观视域评价指标和景观动态美感指标3个类指标和9个基础指标,动态景观评价指标的选择和权重确定主要采用层次分析法(Analytic Hierarchy Process,简称AHP),动态景观评价主要是基于模糊综合评判方法。通过对青藏铁路沿线10个自然景观段的各指标量化打分以及计算,结果发现:青藏铁路沿线不同景观带给游客的感受差异很大,10个旅游景观段的景观质量从高到低排序为:念青唐古拉宽谷盆地高寒草原草甸景观段、昆仑高山荒漠与荒漠草原景观段、可可西里—长江源宽谷高寒草原景观段、唐古拉极高山高寒草甸景观段、青海湖盆地草甸草原景观段、怒江源宽谷高寒草甸景观段、拉萨河谷灌丛草原景观段、柴达木盆地东北亚高山荒漠草原景观段、湟水谷地温性草原景观段、柴达木盆地盐湖戈壁荒漠景观段。其中旅游动态景观质量极高的有1个,旅游动态景观质量较高的有6个,旅游动态景观质量一般的有2个,旅游动态景观质量低的有1个。客观评估青藏铁路沿线各景观段的景观,有助于游客预知和了解青藏铁路途中旅游景观质量,对于地方相关部门指导青藏铁路旅游业的发展和景观管理、打造、开发、决策提供了参考依据。     

喜马拉雅山哺乳动物物种多样性垂直分布格局

生物多样性的空间分布及其相关机制一直是生态学、生物地理学和保护生物学研究的热点问题。山地生态系统生境异质性和生物多样性高, 适合研究生物多样性空间分布及其相关机制。喜马拉雅山脉位于青藏高原南缘, 是全球生态热点区域。其地形复杂, 海拔落差大(100-8,844 m), 具有明显的垂直气候带。本研究通过整合野外调查和文献资料, 系统地分析了10目23科160属313种喜马拉雅山地区哺乳动物物种多样性的垂直分布格局, 发现该区域哺乳动物总体及其子集的物种多样性垂直分布格局都为左偏倚的中峰格局, 物种多样性在海拔900-1,400 m之间最高, 不同物种子集的物种多样性垂直分布格局的模式有所不同。UPGMA聚类分析表明, 喜马拉雅山地区哺乳动物群落沿海拔梯度可以划分为5个聚类簇(海拔100-1,500 m、1,500-2,000 m、2,000-3,000 m、3,000-4,200 m以及4,200-6,000 m的地区), 大致与该地区植被的垂直带分布相吻合。喜马拉雅山地区哺乳动物物种多样性在中低海拔最为丰富, 可能跟东洋界与古北界生物群扩散后的交汇地带相关。喜马拉雅山区贯通南北的沟谷是生物扩散和迁移的通道, 沟谷内水热资源较好, 气候稳定性高, 为高山生态系统内各种生物创造了栖息条件。综上, 喜马拉雅山沟谷地区是生物多样性热点地区, 也是生物扩散和交流关键的“生态走廊”, 应加强对喜马拉雅山沟谷地区的保护, 以维系该区域较高的生物多样性。     

羌塘、可可西里无人区野牦牛种群数量和分布现状

野牦牛(Bos grunniens)是青藏高原特有的大型有蹄类动物, 主要分布在西藏羌塘, 青海可可西里、三江源, 新疆阿尔金山等地的高海拔生境。我们于2012-2014年在西藏羌塘和青海可可西里对野牦牛进行了较为全面的实地调查, 并且估算西藏羌塘地区野牦牛种群在11,222-21,072头之间, 可可西里野牦牛种群数量在659-1,793头之间。据本次野外调查和历史文献资料显示, 自20世纪90年代起, 中国野牦牛种群数量逐年增长, 但是其分布区面积却逐步缩减, 目前仅分布在几个相对孤立且远离人类居住地的高寒区域。随着全球气候变化与青藏高原人类活动的加强,野牦牛的生存现状依然严峻, 我们仍需加强对青藏高原特有物种的保护。     

RS-5645 attenuates inflammatory cytokine storm induced by SARS-CoV-2 spike protein and LPS by modulating pulmonary microbiota

An inflammatory cytokine storm is considered an important cause of death in severely and critically ill COVID-19 patients, however, the relationship between the SARS-CoV-2 spike (S) protein and the host''s inflammatory cytokine storm is not clear. Here, the qPCR results indicated that S protein induced a significantly elevated expression of multiple inflammatory factor mRNAs in peripheral blood mononuclear cells (PBMCs), whereas RS-5645 ((4-(thiophen-3-yl)-1-(p-tolyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)methanone) attenuated the expression of the most inflammatory factor mRNAs. RS-5645 also significantly reduced the cellular ratios of CD45+/IFNγ+, CD3+/IFNγ+, CD11b+/IFNγ+, and CD56+/IFNγ+ in human PBMCs. In addition, RS-5645 effectively inhibited the activation of inflammatory cells and reduced inflammatory damage to lung tissue in mice. Sequencing results of 16S rRNA v3+v4 in mouse alveolar lavage fluid showed that there were 494 OTUs overlapping between the alveolar lavage fluid of mice that underwent S protein+ LPS-combined intervention (M) and RS-5645-treated mice (R), while R manifested 64 unique OTUs and M exhibited 610 unique OTUs. In the alveoli of group R mice, the relative abundances of microorganisms belonging to Porphyromonas, Rothia, Streptococcus, and Neisseria increased significantly, while the relative abundances of microorganisms belonging to Psychrobacter, Shimia, and Sporosarcina were significantly diminished. The results of KEGG analysis indicated that the alveolar microbiota of mice in the R group can increase translation and reduce the activity of amino acid metabolism pathways. COG analysis results indicated that the abundance of proteins involved in ribosomal structure and biogenesis related to metabolism was augmented in the alveolar microbiota of the mice in the R group, while the abundance of proteins involved in secondary metabolite biosynthesis was significantly reduced. Therefore, our research results showed that RS-5645 attenuated pulmonary inflammatory cell infiltration and the inflammatory storm induced by the S protein and LPS by modulating the pulmonary microbiota.     

Exosomes as a messager to regulate the crosstalk between macrophages and cardiomyocytes under hypoxia conditions

Recent studies have confirmed that cardiomyocyte‐derived exosomes have many pivotal biological functions, like influencing the progress of coronary artery disease via modulating macrophage phenotypes. However, the mechanisms underlying the crosstalk between cardiomyocytes and macrophages have not been fully characterized. Hence, this study aimed to observe the interaction between cardiomyocytes under hypoxia and macrophages through exosome communication and further evaluate the ability of exosomes derived from cardiomyocytes cultured under hypoxic conditions (Hypo‐Exo) to polarize macrophages, and the effect of alternatively activated macrophages (M2) on hypoxic cardiomyocytes. Our results revealed that hypoxia facilitated the production of transforming growth factor‐beta (TGF‐β) in H9c2 cell‐derived exosomes. Moreover, exosomes derived from cardiomyocytes cultured under normal conditions (Nor‐Exo) and Hypo‐Exo could induce RAW264.7 cells into classically activated macrophages (M1) and M2 macrophages respectively. Likewise, macrophage activation was induced by circulating exosomes isolated from normal human controls (hNor‐Exo) or patients with acute myocardial infarction (hAMI‐Exo). Thus, our findings support that the profiles of hAMI‐Exo have been changed, which could regulate the polarization of macrophages and subsequently the polarized M2 macrophages reduced the apoptosis of cardiomyocytes in return. Based on our findings, we speculate that exosomes have emerged as important inflammatory response modulators regulating cardiac oxidative stress injury.     

12种酢浆草属植物核型分析

【目的】为了从细胞学角度明确12种酢浆草属（Oxalis）植物核型特征与亲缘关系,探究酢浆草属植物染色体的多样性,进一步为酢浆草种质资源鉴定与杂交育种亲本选择提供参考。【方法】应用根尖压片法对酢浆草属12个物种植物有丝分裂中期的染色体形态、数目及其核型进行观察分析。【结果】结果表明：（1）7个物种的染色体数目为首次报道,5种已报道物种中,兔耳酢浆草（O. fabaefolia）和黄花酢浆草（O. pes-caprae）染色体数目与前人报道一致,其余3种,与先前报道存在差异,其中2n=26为酢浆草属植物中首次报道的染色体数目,共发现7种染色体基数,其中x=13为首次报道,倍性范围从2x~6x;实际染色体大小范围为0.27~2.23 μm,着丝点位置为中部着丝点区（m）和亚中部着丝点区（sm）,核型类型共4种,核型不对称系数范围为56.31%~65.40%。（2）12种酢浆草属植物中兔耳酢浆草最为进化,扁平酢浆草（O. compressa）最为原始。（3）根据染色体核型相似性可将12个酢浆草属植物划分为4组。【结论】研究认为,12个酢浆草属物种具有广泛的核型多样性,核型分类结果与前人形态学分类不完全一致。