Antithrombotic effects of bromophenol, an alga-derived thrombin inhibitor

Thrombin, the ultimate proteinase of the coagulation cascade, is an attractive target for the treatment of a variety of cardiovascular diseases. A bromophenol derivative named (+)-3-(2,3-dibromo-4, 5-dihydroxy-phenyl)-4-bromo-5,6-dihydroxy-1,3-dihydroiso-benzofuran 1, isolated from the brown alga Leathesia nana exhibited significant thrombin inhibitory activity. In this study, we investigated the inhibition of human thrombin in vitro with this bromophenol derivative, and its antithrombotic efficacy in vivo using the arteriovenous shunt model and the ferric chloride-induced arterial thrombosis model in rats. The results show that the bromophenol derivative is a potential inhibitor of thrombin (IC₅₀=1.03 nmol/L). In antithrombotic experiments in vivo, the bromophenol derivative also shows good effect comparing with the control group. These data indicate that the bromophenol derivative is a potential drug for prophylaxis and the treatment of thrombotic diseases.     

The antitumor effect of bromophenol derivatives in vitro and Leathesia nana extract in vivo

To investigate the antitumor effect of bromophenol derivatives in vitro and Leathesia nana extract in vivo, six bromophenol derivatives 6-(2,3-dibromo-4,5-dihydroxybenzyl)-2,3-dibromo-4,5-dihydroxy benzyl methyl ether (1), (+)-3-(2,3-dibromo-4,5-dihydroxyphenyl)-4-bromo-5,6-dihydroxy-1,3-dihydroisobenzofuran (2), 3-bromo-4-(2,3-dibromo-4,5-dihydroxybenzyl)-5-methoxymethyl-pyrocatechol (3),2,2',3,3'-tetrabromo-4,4',5,5'-tetrahydroxy-diphenylmethane (4), bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (5), 2,2',3-tribromo-3',4,4',5-tetrahydroxy-6'-ethyloxymethyldiphenylmethane (6) were isolated from brown alga Leathesia nana, and their cytotoxicity were tested by MTr assays in human cancer cell lines A549, BGC-823, MCF-7, B16-BL6, HT-1080, A2780, Bel7402 and HCT-8. Their inhibitory activity against protein tyrosine kinase (PTK) with over-expression of c-kit was analyzed also by ELISA. The antitumor activity of ethanolic extraction of Leathesia nana (EELN) was evaluated on S180-bearing mice.All compounds showed very potent cytotoxicity against all of the eight cancer cell lines with IC50 below 10 μg/mL. In PTK inhibition study, all bromophenol derivatives showed moderate inhibitory activity and compounds 2, 5 and 6 showed significant bioactivity with the inhibition ratio of 77.5%, 80.1% and 71.4%,respectively. Pharmacological studies reveal that EELN could inhibit the growth of Sarcoma 180 tumor and increase the indices of thymus and spleen to improve the immune system remarkably in vivo. Results indicated that the bromophenoi derivatives and EELN can be used as potent antitumor agents for PTK over-expression of c-kit and considered in a new therapeutic strategy for treatment of cancer.     

The antitumor effect of bromophenol derivatives <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">Leathesia nana</Emphasis> extract <Emphasis Type="Italic">in vivo</Emphasis>

To investigate the antitumor effect of bromophenol derivatives in vitro and Leathesia nana extract in vivo, six bromophenol derivatives 6-(2,3-dibromo-4,5-dihydroxybenzyl)-2,3-dibromo-4,5-dihydroxy benzyl methyl ether (1), (+)-3-(2,3-dibromo-4,5-dihydroxyphenyl)-4-bromo-5,6-dihydroxy-1,3-dihydroisobenzofuran (2), 3-bromo-4-(2,3-dibromo-4,5-dihydroxybenzyl)-5-methoxymethyl-pyrocatechol (3), 2,2′,3,3′-tetrabromo-4,4′,5,5′-tetrahydroxy-diphenylmethane (4), bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (5), 2,2′,3-tribromo-3′,4,4′,5-tetrahydroxy-6′-ethyloxymethyldiphenylmethane (6) were isolated from brown alga Leathesia nana, and their cytotoxicity were tested by MTT assays in human cancer cell lines A549, BGC-823, MCF-7, B16-BL6, HT-1080, A2780, Bel7402 and HCT-8. Their inhibitory activity against protein tyrosine kinase (PTK) with over-expression of c-kit was analyzed also by ELISA. The antitumor activity of ethanolic extraction of Leathesia nana (EELN) was evaluated on S₁₈₀-bearing mice. All compounds showed very potent cytotoxicity against all of the eight cancer cell lines with IC₅₀ below 10 μg/mL. In PTK inhibition study, all bromophenol derivatives showed moderate inhibitory activity and compounds 2, 5 and 6 showed significant bioactivity with the inhibition ratio of 77.5%, 80.1% and 71.4%, respectively. Pharmacological studies reveal that EELN could inhibit the growth of Sarcoma 180 tumor and increase the indices of thymus and spleen to improve the immune system remarkably in vivo. Results indicated that the bromophenol derivatives and EELN can be used as potent antitumor agents for PTK over-expression of c-kit and considered in a new therapeutic strategy for treatment of cancer. Supported by the National High Technology Research and Development Program of China (863 Program, No. 2007AA09Z410) and Knowledge Innovation Program of Chinese Academy of Sciences (No. KZCX2-YW-209)     

Synthesis and protein tyrosine phosphatase 1B inhibition activities of two new synthetic bromophenols and their methoxy derivatives

3-bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol (1) is a natural bromophenol isolated from the red algae Rhodomela confervoides that exhibits significant inhibition against protein tyrosine phosphatase 1B (PTP1B). Based on its activity, we synthesized two new synthetic bromophenols and their methoxy derivatives from vanillin using the structure of natural bromophenol 1 as a scaffold. The structures of these bromophenols were elucidated from 1H NMR, 13C NMR, and high resolution electron ionization mass spectrometry as 2,3-dibromo-1-(2p-bromo-6p-(3q,4q-dimethoxybenzyl)- 3p,4p-dimethoxybenzyl)-4,5-dimethoxybenzene(2),2,3-dibromo-1-(2p-bromo-6p-(2q-bromo-4q,5q-dimethoxy-benzyl)-3p,4p-dimethoxybenzyl)-4,5-dimethoxybenzene(3),3,4-dibromo-5-(2p-bromo-6p-(2q-bromo-4q,5q-dihydroxybenzyl)-3p,4p-dihydroxybenzyl)pyrocatechol(4)and 3,4-dibromo-5-(2p-bromo-6p-(3q,4q-dihydroxybenzyl)-3p,4p-dihydroxybenzyl)pyrocatechol (5).PTP1B inhibition activities of these compounds were evaluated using a colorimetric assay,and compounds 3 and 4 demonstrated interesting activity against PTP1B.     

Synthesis of three bromophenols from red algae as PTP1B inhibitors

Bromophenols are a set of natural products widely distributed in seaweed, most of which exhibit interesting and useful biological activities. To develop a reliable and efficient synthetic route to these natural bromophenols, three of them, 3,4-dibromo-5-(2′-bromo-3′,4′-dihydroxy-6′-methoxymethyl-benzyl)-benzene-1,2-diol (compound 9), 3,4-dibromo-5-(2′-bromo-6′-ethoxy methyl-3′,4′-dihydroxybenzyl)-benzene-1,2-diol (compound 10), and 3-bromo-4-(3′-bromo-4′,5′-dihydroxy benzyl)-5-(ethoxymethyl)-benzene-1,2-diol (compound 14), isolated from red marine algae, have been synthesized in eight steps with an overall yield of 14.4%, 14.4%, and 18.2% respectively, via a practical approach employing bromination, Wolff-Kishner-Huang reduction and a Friedel-Crafts reaction as key steps. The protein tyrosine phosphatase 1B (PTP1B) inhibitory activities of the synthetic compounds were evaluated by the colorimetric assay. The results show that these compounds are moderate PTP1B inhibitors. The synthesis of these bromophenol derivatives makes in vivo studies of their structure-activity relationships and inhibition activity against PTP1B possible.     

具有任意阶非线性薛定谔方程的新行波解

对具有任意阶非线性薛定谔方程的行波解进行了研究。给出具有任意阶非线性薛定谔方程的精确解。利用行波变换和辅助函数法把具有任意阶非线性薛定谔方程最终转化为一个非线性常微分方程的解,通过对这个微分方程的研究可以得到具有任意阶非线性薛定谔方程的行波解。具有任意阶非线性薛定谔方程存在的孤立波解、三角孤立波解、扭孤立波解、Jacobi椭圆函数解。得到了具有任意阶非线性薛定谔方程新的Jacobi椭圆函数解。     

A new acyclic peroxide from Aspergillus nidulans SD-531, a fungus obtained from deep-sea sediment of cold spring in the South China Sea

A new acyclic peroxide derivative asperoxide A(1),along with 13 known compounds,namely,microperfuranone(2),9-hydroxymicroperfuranone(3),gibellulin A(4),lecanoric acid(5),terrequinone A(6),sterigmatocystin(7),isosecosterigmatocystin(8),arugo sin C(9),curvularin(10),3,3 '-diindolylmethane(11),austinol(12),austin(13),and dehydroaustin(14),were isolated and identified from the culture extract of Aspergillus nidulans SD-531,a fungus obtained from the deep-sea sediment of cold spring in the South China Sea.Their structures were determined based on detailed interpretation of nuclear magnetic resonance(NMR) spectroscopic and mass spectrometry data analysis.All the isolated compounds were evaluated for antimicrobial activities against human and aquatic bacteria as well as plant pathogenic fungi.Compounds1-8,10,and 11 exhibited antimicrobial activities against some of the te sted strains with minimum inhibitory concentration(MIC) values ranging from 2 to 64 μg/mL.Compounds 4 and 6 displayed strongest activities among the tested samples and might be used as promising molecules for the development of natural antimicrobial agents.     

Isolation and Neuroprotective Activity of Phenolic Derivatives from the Marine-Derived Fungus Penicillium janthinellum

A new phenolic compound, 6-(2-acetyl-3,5-dihydroxybenzyl)-4-hydroxy-3-methyl-2H-pyran-2-one(1), along with other six known phenolic derivatives(2-7), were isolated from the mangrove rhizosphere fungus Penicillium janthinellum HK1-6 cultured in potato dextrose broth medium containing 30 g L~(-1) of natural sea salt. The structure of the new compound(1) was elucidated by comprehensive analysis of spectroscopic data including 1D and 2D NMR spectra. The proposed biosynthetic pathway of compound 1 was also studied in this research. Interestingly, a brominated phenolic derivative, aryl bromide(compound 8), was obtained from this fungal strain cultured in medium containing 30 g L~(-1) of NaBr instead of natural sea salt. Compound 8 is proposed as a new natural product and formed through bromination of compound 7 when the fungus was cultured with NaBr. The neuroprotective effect of compound 1 on oxygen-glucose deprivation(OGD)-induced injury was investigated in rat spinal cord astrocytes. MTT assay demonstrated that compound 1 can attenuate OGD-induced cell viability loss in rat spinal cord astrocytes.     

Comparative analysis of fracture identification methods based on gravity anomaly in Heilongjiang

The identification of fractures is of great importance in gravity and magnetic data processing and interpretation.In this study,four fracture identification methods are applied,and widely used in processing and analysis of the gravity anomaly,including vertical second derivative method,tilt derivative method,theta map method and normalized differential method,for gravity data acquired in a given area in Heilongjiang.By comparing the distribution of the zero contour or maximum contour,we summarize the application effects,and both advantages and disadvantages of each method.It is found that tilt derivative method and normalized differential method provide better effects than other two methods:the narrower anomaly gradient belt and higher identification precision of fracture or geological boundary.The inferred fractures and geological boundaries have a great match with the results obtained from geologic map and remote sensing data interpretation.Those study results have definitely provided the theoretical foundation for identifying faults and the geological boundaries.     

单位圆内亚纯函数及其导数的公共Borel方向

证明了单位圆内的有究正级亚纯函数及其导数的Borel半径分布安全一致。     

一种新ⅡR分数阶微分滤波器

从频域角度出发,分析了几种基于典型微分算子的ⅡR分数阶微分滤波器的数字实现,提出一种频率响应更接近理想微分的新算子,在此基础上运用连续分数扩充方法实现了分数阶微分滤波器的设计,并详细推导基于新算子的ⅡR分数阶微分滤波器的数字实现。实验证明,基于新算子的ⅡR分数阶微分滤波器频率响应整体上优于Tustin和Simpson等其他ⅡR分数阶滤波器。     

磁法θ图方法在圈定磁性体边界中的应用

近几年提出的导数处理方法θ图法利用极大值圈定磁性体边界,其算法主要步骤为计算垂向一阶导数与总水平导数的比值。通过分析二维半情况下不同磁性体模型的θ图,总结了θ图极值与直立磁性体边界、倾斜磁性体边界、岩体及矽卡岩带边界的对应性规律。该方法对重力圈定断裂构造及地质界线也有借鉴意义。     

矿山废石淋溶对水环境的影响

为了研究废石堆砌对水环境的影响,通过对废石做淋溶实验,分析了出入水的水质变化规律,对废石衍生环境效应的过程、机制、影响因素方面进行讨论,揭示了人们容易忽视的酸性水中硫酸根、总硬度、微量金属离子的动力学变化机理,指出矿山废石对水环境的污染不至限于使水质酸化,硫酸根、总硬度也会大幅度提高,废石堆放应充分考虑当地的地理气候及水文条件,合理堆放,减少污染。     

重力异常反映的郯庐带中南段构造边界与应力场

为解决传统基于重力场数据一阶导数定义的总水平导数和解析信号振幅存在无法均衡深浅异常振幅的问题,应用重力全张量梯度数据,提出改进的倾斜导数地质体边界识别方法NTD_M。经模型验证,NTD_M在收敛性、抑噪性和边界识别精度方面均有提升。利用NTD_M将郯庐带中南段及邻区划分为14个边界较为清晰的构造单元,借助垂线偏差数据对郯庐带中南段的构造应力场和壳幔密度差进行反演。结果显示,二者在水平方向上存在显著差异,在空间上显著相关,构造应力最大差异值约为16 MPa,壳幔密度差约为0.2 g/cm³,构造应力等值线密集处与构造单元划分的边界以及地震分布情况对应较好。郯庐带中段最大主应力方向为NEE-EW,南段主应力方向以EW-NWW为主,总体呈EW向,与震源机制解、地应力测量和GPS反演结果具有较好的一致性。     

联合DInSAR与Offset-tracking技术监测高强度采区开采沉陷的方法

高强度煤炭开采产生巨大的地表形变,形变相位梯度过大导致干涉测量解缠错误,单一采用常规DInSAR及其衍生技术都无法获得地表沉陷主值。本文提出一种新的解决方案,即联合利用DInSAR与偏移量追踪技术（Offset-tracking）各自的技术优势,实现开采区大变形的准确提取,并基于GAUSS函数模型拟合恢复沉陷区剖面形态。基于2012年2月13日和2012年11月27日两景高分辨率SAR数据（RADARSAT-2,5 m精细波束模式（MF5））为数据源,以神东矿区布尔台矿、寸草塔一矿、二矿为研究区,采用常规DInSAR技术获得亚厘米级沉陷区边界,边界沉陷值处于-0.01~ -0.02 m;利用偏移量追踪方法获取米级地表沉陷中心主值,中心沉陷值集中在-1.0~ -4.0 m。将2种方法监测到沉陷信息分段融合,最后采用GAUSS函数模型重构矿区开采沉陷下沉特征曲线。结果表明,偏移量追踪方法可弥补DInSAR技术监测大量级形变信息的不足,联合技术可完整获取高强度采区的大形变沉陷。     

Several boundary identification methods of gravity data and application in Vientiane of Laos area

The authors studied the potential field boundary identification of the new technology in order to find out the possible fractures or contact zones using the following methods such as tilt derivative,horizontal deriva- tive of tilt derivative,normalized standard deviation and normalized differential method． Combined with Euler deconvolution and small subdomain filtering,the actual data processing results show that these methods are all a- ble to identify wider range extending fractures and obtain abundant geological information． The horizontal deriva- tive of tilt derivative and normalized differential method have a better resolution for the small cutting fractures and lacunae in the studied area． They provide a reliable basis for study of the cutting relationship between fractures．     

Optimized One-Step Preparation of a Bioactive Natural Product,Guaiazulene-2,9-dione

We previously isolated a natural product, namely guaiazulene-2,9-dione showing strong antibacterial activity against Vibrio anguillarum, from a gorgonian Muriceides collaris collected in South China Sea. In this experiment, guaiazulene-2,9-dione was quantitatively synthesized with an optimized one-step bromine oxidation method using guaiazulene as the raw material. The key reaction condition including reaction time and temperature, drop rate of bromine, concentration of aqueous THF solution, respective molar ratio of guaiazulene to bromine and acetic acid, and concentration of guaiazulene in aqueous THF solution, were investigated individually at five levels each for optimization. Combined with the verification test to show the absolute yield of each optimization step, the final optimal condition was determined as： when a solution of 0.025mmol mL-1 guaiazulene in 80% aqueous THF was treated with four volumes of bromine at a drop rate of 0.1 mL min 1 and four volumes of acetic acid at -5℃ for three hours, the yield of guaiazulene-2,9-dione was 23.72%. This was the first report concerning optimized one-step synthesis to provide a convenient method for the large preparation of guaiazulene-2,9-dione.     

几种规则形体的引力垂向导数及其应用

鉴于引力垂向导数在大地测量、地球物理中广泛应用,在许多情况下,异常体就是或接近于规则形体,为此推导、引入了球体、半球体、柱体、锥体和长方体的引力垂向导数公式。此外,还讨论了如何将它们用于绝对重力测量和精化大地水准面的实际中。     

新型壳聚糖季铵盐衍生物的合成与表征

采用甲磺酸作为溶剂兼作氨基保护试剂,对壳聚糖上的羟基选择性酯化,再游离出氨基并对其氯乙酰化,最后进行吡啶成盐,得到新型水溶性的壳聚糖季铵盐衍生物,产物的结构通过核磁共振氢谱和红外光谱进行了表征,从而为壳聚糖季铵盐衍生物的制备提供了一种新途径。     

代数体函数对数导数增长的估计

本文给出了代数体函数对数导数在整个复平面上除去一些小测度集外的增长估计。这些结果是Gary G.Gundersen 关于亚纯函数结果的推广,但在证明中使用了不同的方法。