A Potent Anticancer Agent of Shikonin Derivative Targeting Tubulin

In this study, a shikonin ester derivative, compound 3g , was selected to evaluate its anticancer activities and we found that compound 3g exhibited better antitubulin activities against the human HepG2 cell line with an IC₅₀ value of 1.097 μM. Furthermore, the inhibition of tubulin polymerization results indicated that compound 3g demonstrated the most potent antitubulin activity (IC₅₀ = 13.88), which was compared with shikonin and colchicine as positive controls (IC₅₀ = 25.28 μM and 22.56 μM), respectively. Compound 3g was simulated to have good binding site with tubulin and arrested the cell cycle at G2/M phase, which also induces apoptosis in HepG2 cells, in which P53 and members of Bcl‐2 protein family were both involved in the progress of apoptosis revealed by western blot. Confocal microscopy observations revealed compound 3g targeted tubulin and altered its polymerization by interfering with microtubule organization. Based on these results, compound 3g functions as a potent anticancer agent targeting tubulin. Chirality 27:274–280, 2015.. © 2015 Wiley Periodicals, Inc.     

北京城市与西北远郊地表臭氧浓度梯度移动监测研究

北京城市与区域臭氧浓度逐年升高,对自然生态系统已经构成影响。但地表臭氧在北京城市与远郊梯度空间上的连续递变特征机制尚不清楚。采用移动监测车,搭载臭氧分析仪,选择夏季典型臭氧污染天气,以北京教学植物园为对照点,从北京城市中心向西北远郊方向,多点位连续测定地表臭氧浓度。通过分析臭氧浓度和采样点周围归一化植被指数(NDVI)的关系以及典型臭氧污染情况下的天气形势和气团轨迹,探讨北京城市和区域臭氧浓度连续空间变化特征及机制。结果表明:(1)北京西北山区森林区域臭氧浓度显著高于"城市区域",约为城市区域的2.00倍。十三陵是地表臭氧浓度的分界点,从十三陵开始臭氧浓度陡然升高,在西北山区方向保持在高水平。空间上从高到低的顺序是西北山区(254.68μg/m~3)对照点教学植物园(220.89μg/m~3)城市支路(162.84μg/m~3)城市快速路和高速路(103.24μg/m~3);(2)植被分布影响臭氧空间格局。在相同时间范围内,臭氧浓度和NDVI正相关,随NDVI增加臭氧浓度呈Logistic增长;(3)西北山区地表臭氧空间变异系数为0.11,城市支路上平均为0.28,城市快速路上为0.26,高速公路上为0.36。山区地表臭氧浓度的空间变异系数最小,高速公路最大,城市快速路、城市支路空间变异较大;(4)大范围均压场、高压后部、低压前部等稳定型天气型易造成南向弱气流,能够把空气污染物输送到西北远郊,但本研究中监测到的西北山区高浓度臭氧并非当天从城区输送而来。北京城市与区域臭氧格局与植被的关系及成因需要深入研究。     

Drug resistance‐related microRNAs in osteosarcoma: Translating basic evidence into therapeutic strategies

Although the application of multiple chemotherapy brought revolutionary changes to improve overall survival of osteosarcoma patients, the existence of multidrug resistance (MDR) has become a great challenge for successful osteosarcoma treatment in recent decades. Substantial studies have revealed various underlying mechanisms of MDR in cancers. As for osteosarcoma, evidence has highlighted that microRNAs (miRNAs) can mediate in the processes of DNA damage response, apoptosis avoidance, autophagy induction, activation of cancer stem cells, and signal transduction. Besides, these drug resistance‐related miRNAs showed much promise for serving as candidates for predictive biomarkers of poor outcomes and shorter survival time, and therapeutic targets to reverse drug resistance and overcome treatment refractoriness. This review aims to demonstrate the potential molecular mechanisms of miRNAs‐regulated drug resistance in osteosarcoma, and provide insight in translating basic evidence into therapeutic strategies.     

Targeting nucleolin to obstruct vasculature feeding with an intelligent DNA nanorobot

A prototype of DNA nanorobot with the ability to transport molecular payloads was designed to target cancer cells in tissue culture. Moreover, a further step was taken to succeed in the first in vivo application of the DNA nanorobot for cancer therapy. The robot was constructed using aptamer and DNA origami to fold a 90‐nm tubular device to carry the blood coagulation protease thrombin inside, shielded from circulating platelets and plasma fibrinogen. The recognition and binding of the aptamer to its tumour‐specific target molecule triggered the robot unfolding to expose thrombin to the blood, which in turn activated coagulation at the local tumour site, resulting in tumour necrosis and inhibition of tumour growth. Since all solid‐tumour feeding vessels are virtually the same, this strategy could be effective against many types of malignant diseases.     

北京地区油菜软腐病病原菌的鉴定

摘要:【目的】确定引发北京地区油菜［Brassica campestris L．ssp．chinensis (L.) Makino var． communis Tsen et Lee］软腐病的病原。【方法】结合病原菌形态、BIOLOG 及生理生化、16S rＲNA 基因序列及亚种IGS区特征分析,对从北京大兴和通州区油菜软腐病样中病原菌进行生物学鉴定。【结果】分离的40 个菌株均能引发 油菜软腐病,但分别为胡萝卜果胶杆菌(Pectobacterium carotovorum) 的2个不同亚种,其中13株为P．carotovorum subsp．carotovorum(Pcc),另27株为P．arotovorum subsp． brasiliensis(Pcb)。接种白菜(Brassica campestris L．ssp．pekinensis)致病力测定分析表明,亚种内、来源相同与16S rRNA基因序列相同的菌株间均存在明显的致病力分化。【结论】Pectobacterium carotovorum subsp．carotovorum和Pectobacterium carotovorum subsp. brasiliensis是引发北京地区油菜软腐病的致病菌,后者为首次报道能引起白菜类蔬菜软腐病的常见致病菌。     

Radially Oriented Single‐Crystal Primary Nanosheets Enable Ultrahigh Rate and Cycling Properties of LiNi0.8Co0.1Mn0.1O2 Cathode Material for Lithium‐Ion Batteries

Ni‐rich Li[Ni_xCo_yMn_1?x?y]O₂ (x ≥ 0.8) layered oxides are the most promising cathode materials for lithium‐ion batteries due to their high reversible capacity of over 200 mAh g^?1. Unfortunately, the anisotropic properties associated with the α‐NaFeO₂ structured crystal grains result in poor rate capability and insufficient cycle life. To address these issues, a micrometer‐sized Ni‐rich LiNi_0.8Co_0.1Mn_0.1O₂ secondary cathode material consisting of radially aligned single‐crystal primary particles is proposed and synthesized. Concomitant with this unique crystallographic texture, all the exposed surfaces are active {010} facets, and 3D Li⁺ ion diffusion channels penetrate straightforwardly from surface to center, remarkably improving the Li⁺ diffusion coefficient. Moreover, coordinated charge–discharge volume change upon cycling is achieved by the consistent crystal orientation, significantly alleviating the volume‐change‐induced intergrain stress. Accordingly, this material delivers superior reversible capacity (203.4 mAh g^?1 at 3.0–4.3 V) and rate capability (152.7 mAh g^?1 at a current density of 1000 mA g^?1). Further, this structure demonstrates excellent cycling stability without any degradation after 300 cycles. The anisotropic morphology modulation provides a simple, efficient, and scalable way to boost the performance and applicability of Ni‐rich layered oxide cathode materials.     

Overexpression of RYBP inhibits proliferation,invasion, and chemoresistance to cisplatin in anaplastic thyroid cancer cells via the EGFR pathway

Ring1 and YY1 binding protein (RYBP), a new member of the polycomb group protein family, has been reported to play an important role in various biological processes. Recently, more and more studies have demonstrated an implication of RYBP in cancer development. However, the specific role of RYBP in anaplastic thyroid cancer (ATC) remains unknown. In this study, we investigated for the first time the expression pattern and biological functions of RYBP in ATC. We showed that RYBP was lowly expressed in ATC tissues and cell lines. We also found that overexpression of RYBP inhibited ATC cell proliferation, invasion, and cisplatin resistance. Furthermore, we observed that upregulation of RYBP decreased the phosphorylation of EGFR and ERK1/2 in ATC cells. Taken together, our data indicated that RYBP might be considered as a promising therapeutic target for the treatment of ATC.     

Human serum and glucocorticoid-inducible kinase-like kinase (SGKL) phosphorylates glycogen syntheses kinase 3 beta (GSK-3beta) at serine-9 through direct interaction

Serum and glucocorticoid-inducible kinase-like kinase (SGKL) has been identified as a new integrator that decodes lipid signals produced by the activation of phosphoinositide 3-kinase (PI3K). SGKL is activated via its lipid-binding domain (phox homology domain) in response to PI3K signaling. However, downstream targets of SGKL as well as the role of SGKL as a mediator in PI3K signaling in human tissues remain to be established. In this study, we identified human glycogen synthase kinase 3 beta (GSK-3beta) as a specific interacting partner with SGKL in a yeast two-hybrid screening of human brain cDNA library. The association between these two proteins is confirmed independently in human embryonic kidney (HEK293) cells by co-immunoprecipitation. Furthermore, the kinase activity of wild-type SGKL was required for the in vitro phosphorylation of a GSK-3 crosstide fusion protein at serine-21/9 as demonstrated with a Phospho-GSK-3alpha/beta (Ser21/9) specific antibody. The present results provide strong evidences that SGKL could utilize GSK-3beta as a direct downstream target by phosphorylating GSK-3beta at serine-9.     

Comprehensive metabolomic,proteomic and physiological analyses of grain yield reduction in rice under abrupt drought–flood alternation stress

Abrupt drought–flood alternation (T1) is a meteorological disaster that frequently occurs during summer in southern China and the Yangtze river basin, often causing a significant loss of rice production. In this study, the response mechanism of yield decline under abrupt drought–flood alternation stress at the panicle differentiation stage was analyzed by looking at the metabolome, proteome as well as yield and physiological and biochemical indexes. The results showed that drought and flood stress caused a decrease in the yield of rice at the panicle differentiation stage, and abrupt drought–flood alternation stress created a synergistic effect for the reduction of yield. The main reason for the decrease of yield per plant under abrupt drought–flood alternation was the decrease of seed setting rate. Compared with CK0 (no drought and no flood), the net photosynthetic rate and soluble sugar content of T1 decreased significantly and its hydrogen peroxidase, superoxide dismutase, peroxidase activity increased significantly. The identified differential metabolites and differentially expressed proteins indicated that photosynthesis metabolism, energy metabolism pathway and reactive oxygen species response have changed strongly under abrupt drought–flood alteration stress, which are factors that leads to the rice grain yield reduction.     

雄性棉铃虫和烟青虫对雌性信息素的触角电生理反应

利用触角电位图(Electroantennogram,EAG)技术,比较研究了二近缘种棉铃虫、烟青虫对其性信息素主要成分Z—11—16：Ald、Z—9—16：Ald的触角电生理反应。剂量反应曲线表明,对Z—11—16：Ald,棉铃虫和烟青虫均有明显的EAG反应,且随浓度的增加而增强,但棉铃虫比烟青虫的反应较强;对Z—9—16：Ald,烟青虫有很强的EAG反应,棉铃虫的反应则很弱;对Z—11—16：Ald和Z—9—16：Ald以97：3和7：93比例形成的混合物,棉铃虫、烟青虫均有EAG反应,但二者之间没有显著差异[动物学报49(6)：795～799,2003]。