CRISPR/Cas9-Mediated Generation of Pathogen-Resistant Tomato against Tomato Yellow Leaf Curl Virus and Powdery Mildew

Tomato is one of the major vegetable crops consumed worldwide. Tomato yellow leaf curl virus (TYLCV) and fungal Oidium sp. are devastating pathogens causing yellow leaf curl disease and powdery mildew. Such viral and fungal pathogens reduce tomato crop yields and cause substantial economic losses every year. Several commercial tomato varieties include Ty-5 (SlPelo) and Mildew resistance locus o 1 (SlMlo1) locus that carries the susceptibility (S-gene) factors for TYLCV and powdery mildew, respectively. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) is a valuable genome editing tool to develop disease-resistant crop varieties. In this regard, targeting susceptibility factors encoded by the host plant genome instead of the viral genome is a promising approach to achieve pathogen resistance without the need for stable inheritance of CRISPR components. In this study, the CRISPR/Cas9 system was employed to target the SlPelo and SlMlo1 for trait introgression in elite tomato cultivar BN-86 to confer host-mediated immunity against pathogens. SlPelo-knockout lines were successfully generated, carrying the biallelic indel mutations. The pathogen resistance assays in SlPelo mutant lines confirmed the suppressed accumulation of TYLCV and restricted the spread to non-inoculated plant parts. Generated knockout lines for the SlMlo1 showed complete resistance to powdery mildew fungus. Overall, our results demonstrate the efficiency of the CRISPR/Cas9 system to introduce targeted mutagenesis for the rapid development of pathogen-resistant varieties in tomato.     

Identification of Cyclophilin A as a Potential Anticancer Target of Novel Nargenicin A1 Analog in AGS Gastric Cancer Cells

We recently discovered a novel nargenicin A1 analog, 23-demethyl 8,13-deoxynargenicin (compound 9), with potential anti-cancer and anti-angiogenic activities against human gastric adenocarcinoma (AGS) cells. To identify the key molecular targets of compound 9, that are responsible for its biological activities, the changes in proteome expression in AGS cells following compound 9 treatment were analyzed using two-dimensional gel electrophoresis (2-DE), followed by MALDI/TOF/MS. Analyses using chemical proteomics and western blotting revealed that compound 9 treatment significantly suppressed the expression of cyclophilin A (CypA), a member of the immunophilin family. Furthermore, compound 9 downregulated CD147-mediated mitogen-activated protein kinase (MAPK) signaling pathway, including c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) by inhibiting the expression of CD147, the cellular receptor of CypA. Notably, the responses of AGS cells to CypA knockdown were significantly correlated with the anticancer and antiangiogenic effects of compound 9. CypA siRNAs reduced the expression of CD147 and phosphorylation of JNK and ERK1/2. In addition, the suppressive effects of CypA siRNAs on proliferation, migration, invasion, and angiogenesis induction of AGS cells were associated with G2/M cell cycle arrest, caspase-mediated apoptosis, inhibition of MMP-9 and MMP-2 expression, inactivation of PI3K/AKT/mTOR pathway, and inhibition of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression. The specific interaction between compound 9 and CypA was also confirmed using the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA) approaches. Moreover, in silico docking analysis revealed that the structure of compound 9 was a good fit for the cyclosporin A binding cavity of CypA. Collectively, these findings provide a novel molecular basis for compound 9-mediated suppression of gastric cancer progression through the targeting of CypA.     

贝叶斯项目反应模型及nimble实现

针对国际学生评估项目2015年数据(PISA),采用单参数、双参数和三参数的项目反应模型进行建模,在每个模型下,分别采用logistic连接函数和probit连接函数.针对6个模型,应用偏差信息准则(Deviance Information Criterion,DIC)和伪边际似然对数(Logarithm of Pseudo-Marginal Likelihood,LPML)进行模型评价和模型选择.结果表明,当连接函数为logistic双参数的项目反应模型表现最好,因为这个模型下的DIC值最小,并且LPML值最大.我们采用R软件nimble包进行编程.     

The Role of Chronic Inflammation in Various Diseases and Anti-inflammatory Therapies Containing Natural Products

Chronic inflammation represents a long-term reaction of the body's immune system to noxious stimuli. Such a sustained inflammatory response sometimes results in lasting damage to healthy tissues and organs. In fact, chronic inflammation is implicated in the development and progression of various diseases, including cardiovascular diseases, respiratory diseases, metabolic diseases, neurodegenerative diseases, and even cancers. Targeting nonresolving inflammation thus provides new opportunities for treating relevant diseases. In this review, we will go over several chronic inflammation-associated diseases first with emphasis on the role of inflammation in their pathogenesis. Then, we will summarize a number of natural products that exhibit therapeutic effects against those diseases by acting on different markers in the inflammatory response. We envision that natural products will remain a rich resource for the discovery of new drugs treating diseases associated with chronic inflammation.     

陕北±800 kV换流站高填方湿陷性黄土地基处理方案研究

陕北±800 kV换流站用地为原循环工业经济园区挖黄土梁卯、填深沟给出的一块台阶式场地,场地覆盖一层厚度0~50 m的素填土,密实度差异较大,土质极不均匀,填土完成约5年半时间,是一种欠固结土,在其自身重度和大气降水的入渗作用下有自行密实的特点,影响位于填方区建(构)筑物地基的承载力和稳定性。基于该工程特殊的岩土地质情况,除挖方区采用天然地基外,从处理填方区大面积欠固结土和消除部分地基土湿陷性、提高地基土承载力、减小场地沉降变形的角度,对不同地基处理及桩基方案进行技术经济综合比选,提出适合本工程的经济合理的地基处理方案。     

基于主成分分析与Wasserstein距离的低压用户相别识别

负载不平衡会导致电能质量差、功率损耗增加、变压器使用寿命缩短等问题,而准确识别用户相别可调整部分用户相别,尽可能达到三相负载平衡,因此提出一种基于主成分分析与Wasserstein距离的低压用户相别识别方法.首先利用主成分分析提取低压用户电压主成分进行聚类,然后计算聚类中值与关口各相电压Wasserstein距离进行相别归属.实测数据证明该方法对相别识别准确性较高,且相较于传统相似度算法在判别相别时具有明显区分度.     

Robust Superhydrophobic Fabric for Durability,Self-Cleaning,and Oil/Water Separation via Thiol–Acrylate Polymerization

In recent years, highly efficient oil/water separation materials have brought much attention. It requests superhydrophobic surfaces with a rapid and facile separation process, excellent durability, and large-scale fabrication. Herein, a facile vapor-liquid sol-gel, and free radical polymerization reaction method to prepare the durable and robust superhydrophobic cotton fabric is proposed. Moreover, the fabric can be used for highly efficient and various oil/water separation. It is prepared via a simple two-step process, including a vapor-liquid sol-gel process to deposit with thiols particles, and then followed a free radical polymerization reaction to graft 2,2,3,4,4,4-hexafluorobutyl methacrylate. Scanning electron microscopy and Fourier transform infrared spectrometry prove that the rough structures are generated from the hydrolysis condensation reaction between tetraethyl orthosilicate and 3-mercaptopropyltriethoxysilane. As a result, the synthetic chemical composition provided by the natural fabric and silica nanoparticles synergistically construct a superhydrophobic surface with water contact angles and shedding angle of 158° and 9°, respectively. Additionally, the treated fabric exhibits excellent chemical resistance and self-cleaning ability. Remarkably, the fabric still retains superhydrophobic and excellent mechanical robustness after 30 cycles of various oil/water separation. In summary, the resultant fabrics with excellent chemical resistance, remarkable mechanical robustness, and versatile separation abilities have potential applications in various oil/water separations.     

含砷氰化尾矿回填利用污染控制技术试验研究

针对某黄金生产企业含砷氰化尾矿污染特征,开展了搅拌洗涤法、臭氧氧化法、酸化溶砷法、铁盐固砷法等多种无害化方法联合处理试验研究,旨在将该含砷氰化尾矿处理至满足氰渣规范回填利用污染控制要求。结果表明：该含砷氰化尾矿回填利用污染控制技术工艺为压滤调浆搅拌洗涤+臭氧氧化+酸化溶砷+铁盐固砷,最佳参数为原矿浆压滤后加水调浆,矿浆浓度40%,臭氧投加量0.66 g/L,酸化溶砷pH值3、曝气量0.1 m³/h、反应时间2 h,铁盐固砷七水合硫酸亚铁投加量20.0 g/L、反应时间1 h。研究结果为该黄金生产企业含砷氰化尾矿回填利用提供了技术支撑。