Oridonin prevents oxidative stress-induced endothelial injury via promoting Nrf-2 pathway in ischaemic stroke

Oridonin, a natural diterpenoid compound extracted from a Chinese herb, has been proved to exert anti-oxidative stress effects in various disease models. The aim of the present study was to investigate the protective effects of oridonin on oxidative stress-induced endothelial injury in ischaemic stroke. We found oridonin repaired blood-brain barrier (BBB) integrity presented with upregulation of tight junction proteins (TJ proteins) expression, inhibited the infiltration of periphery inflammatory cells and neuroinflammation and thereby reduced infarct volume in ischaemic stroke mice. Furthermore, our results showed that oridonin could protect against oxidative stress-induced endothelial injury via promoting nuclear translocation of nuclear factor-erythroid 2 related factor 2 (Nrf-2). The specific mechanism could be the activation of AKT(Ser473)/GSK3β(Ser9)/Fyn signalling pathway. Our findings revealed the therapeutic effect and mechanism of oridonin in ischaemic stroke, which provided fundamental evidence for developing the extracted compound of Chinese herbal medicine into an innovative drug for ischaemic stroke treatment.     

Limited-Memory Fast Gradient Descent Method for Graph Regularized Nonnegative Matrix Factorization

Graph regularized nonnegative matrix factorization (GNMF) decomposes a nonnegative data matrix to the product of two lower-rank nonnegative factor matrices, i.e., and () and aims to preserve the local geometric structure of the dataset by minimizing squared Euclidean distance or Kullback-Leibler (KL) divergence between X and WH. The multiplicative update rule (MUR) is usually applied to optimize GNMF, but it suffers from the drawback of slow-convergence because it intrinsically advances one step along the rescaled negative gradient direction with a non-optimal step size. Recently, a multiple step-sizes fast gradient descent (MFGD) method has been proposed for optimizing NMF which accelerates MUR by searching the optimal step-size along the rescaled negative gradient direction with Newton''s method. However, the computational cost of MFGD is high because 1) the high-dimensional Hessian matrix is dense and costs too much memory; and 2) the Hessian inverse operator and its multiplication with gradient cost too much time. To overcome these deficiencies of MFGD, we propose an efficient limited-memory FGD (L-FGD) method for optimizing GNMF. In particular, we apply the limited-memory BFGS (L-BFGS) method to directly approximate the multiplication of the inverse Hessian and the gradient for searching the optimal step size in MFGD. The preliminary results on real-world datasets show that L-FGD is more efficient than both MFGD and MUR. To evaluate the effectiveness of L-FGD, we validate its clustering performance for optimizing KL-divergence based GNMF on two popular face image datasets including ORL and PIE and two text corpora including Reuters and TDT2. The experimental results confirm the effectiveness of L-FGD by comparing it with the representative GNMF solvers.     

基于长时间序列landsat数据的科尔沁沙地土地利用演变分析

以科尔沁沙地沙丘-草甸过渡带区域主要土地覆被类型为研究对象，以1987-2017年多时相Landsat TM/OLI遥感影像解译分类为基础，参考生态学植被演替研究方法，系统分析研究区30年来的土地利用/覆被动态演变规律，研究结果表明：（1）决策树法在复杂下垫面不同覆被类型的同步识别效果较好，所有影像分类精度均达到88%以上，分类效果较好，其中2017年分类精度最高为95.24%，达到了分类研究的要求；（2）研究区存在着"半灌丛-草甸地-灌丛"的植被结构特征，且整体表现为"南进北退"的变化趋势。结合土地利用动态度分析结果表明人类活动干涉下，研究区整体上遵循了半干旱区植被条件改善的一般规律，侧面反映该研究区域生态环境的持续不稳定性和脆弱性；（3）研究区覆被类型发生变化的总面积达到2623.59 hm²，总变化强度为63.76%。其中正向演替的比例为52.61%，以半灌丛面积的持续减小与沙地草甸面积的持续扩张为主要变化特征。但同时，半灌丛转为沙地的面积为184.95 hm²，表明以放牧为主的研究区同时发生着局部的逆行演变；（4）质心迁移结果反映了1987-2017年间，除人为影响较大的林地、草地以及耕地向北迁移外，其他植被类型的质心都有很明显的南迁，主要植被类型重心迁移距离依次由大到小为耕地 > 半灌丛 > 灌丛 > 沙地草甸 > 湿地草甸 > 林地。研究通过记录科尔沁沙地连续扩展的时空模式，展示了遥感-生态和时间序列影像在30 m分辨率下跟踪土地利用/覆被变化的潜力，为提高干旱半干旱区土地利用情况的动态监测效率，开展土地利用/覆被动态演变研究提供参考。     

低温下水稻幼苗形态生理应变研究

低温下水稻幼苗形态生理应变研究李太贵王磊（中国水稻研究所，杭州３１０００６）ＳｔｕｄｙｏｆＭｏｒｐｈｏＰｈｙｓｉｏｌｏｇｉｃａｌＳｔｒａｉｎｏｆＲｉｃｅＳｅｅｄｌｉｎｇＵｎｄｅｒＬｏｗＴｅｍｐｅｒａｔｕｒｅ．ＬｉＴａｉｇｕｉ，ＷａｎｇＬｅｉ（Ｃｈｉ...     

SKIL facilitates tumorigenesis and immune escape of NSCLC via upregulating TAZ/autophagy axis

Immune escape is an important mechanism in tumorigenesis. The aim of this study was to investigate roles of SKIL in tumorigenesis and immune escape of non-small-cell lung cancer (NSCLC). SKIL expression levels in NSCLC cell line, clinical sample, and adjacent normal tissue were measured by quantitative PCR, western blot, or immunohistochemistry. Lentivirus was used to overexpress/silence SKIL or TAZ expression. Malignant phenotypes of NSCLC cells were evaluated by colony formation, transwell, and MTT assays, and in xenograft mice model. Syngeneic mice model and flow cytometry were used to evaluate T cell infiltration. Quantitative PCR and western blot were applied to evaluate relevant mRNA and protein levels, respectively. Co-immunoprecipitation was applied to unveil the interaction between SKIL and TAZ. SKIL expression was higher in NSCLC tissue compared to adjacent normal tissue. Silencing of SKIL inhibited malignant phenotypes of NSCLC cells and promoted T cell infiltration. SKIL-knockdown inhibited autophagy and activated the STING pathway in NSCLC cells through down-regulation of TAZ. Silencing of TAZ cancelled the effects of SKIL overexpression on malignant phenotypes and autophagy of NSCLC cells. Inhibition of autophagy reversed the effects of SKIL/TAZ overexpression on the STING pathway. In conclusion, SKIL promoted tumorigenesis and immune escape of NSCLC cells through upregulation of TAZ/autophagy axis and inhibition on downstream STING pathway.Subject terms: Immunology, Cancer     

Sphingosine kinase 1 regulates HMGB1 translocation by directly interacting with calcium/calmodulin protein kinase II-δ in sepsis-associated liver injury

Previously, we confirmed that sphingosine kinase 1 (SphK1) inhibition improves sepsis-associated liver injury. High-mobility group box 1 (HMGB1) translocation participates in the development of acute liver failure. However, little information is available on the association between SphK1 and HMGB1 translocation during sepsis-associated liver injury. In the present study, we aimed to explore the effect of SphK1 inhibition on HMGB1 translocation and the underlying mechanism during sepsis-associated liver injury. Primary Kupffer cells and hepatocytes were isolated from SD rats. The rat model of sepsis-associated liver damage was induced by intraperitoneal injection with lipopolysaccharide (LPS). We confirmed that Kupffer cells were the cells primarily secreting HMGB1 in the liver after LPS stimulation. LPS-mediated HMGB1 expression, intracellular translocation, and acetylation were dramatically decreased by SphK1 inhibition. Nuclear histone deacetyltransferase 4 (HDAC4) translocation and E1A-associated protein p300 (p300) expression regulating the acetylation of HMGB1 were also suppressed by SphK1 inhibition. HDAC4 intracellular translocation has been reported to be controlled by the phosphorylation of HDAC4. The phosphorylation of HDAC4 is modulated by CaMKII-δ. However, these changes were completely blocked by SphK1 inhibition. Additionally, by performing coimmunoprecipitation and pull-down assays, we revealed that SphK1 can directly interact with CaMKII-δ. The colocalization of SphK1 and CaMKII-δ was verified in human liver tissues with sepsis-associated liver injury. In conclusion, SphK1 inhibition diminishes HMGB1 intracellular translocation in sepsis-associated liver injury. The mechanism is associated with the direct interaction of SphK1 and CaMKII-δ.Subject terms: Hepatotoxicity, Sepsis