Synthesis and biological evaluation of a folate-targeted rhaponticin conjugate

To improve the therapeutic effect of rhaponticin (RHA), a folate receptor (FR) targeted RHA conjugate was synthesized by utilizing a hydrophilic peptide spacer linked to folic acid (FA) via a releasable disulfide linker. This water-soluble conjugate was found to retain high affinity for FR-positive cells, and it produced specific, dose-responsive activity in vitro. Treatment of FRHA with a reducing agent indicated that the amino-reactive derivative of RHA would be released spontaneously following disulfide bond reduction within the endosomes. FRHA also proved to be active predominantly specific against FR-positive syngeneic and xenograft models in vivo, and possible curative activity resulted with minimal to moderate toxicity. The FRHA conjugate greatly enhanced the therapeutic effects and reduced the toxicity of RHA. In conclusion, FRHA represents a folate-targeted chemotherapeutic that can produce potent activity against established sc tumors. Hence, this report has a great significance in pharmacology and clinical medicine as well as methodology.     

深圳兽类物种资源调查及其影响因素分析

2014年4月至2015年10月对深圳市不同区域的兽类进行实地调查,共调查到8目15科32属49种,其中翼手目4科12属24种占比达49.0%,啮齿目3科8属13种占比26.5%,食肉目3科5属5种占比10.2%,鼩形目1科3属3种占比6.1%,其他4个目各1种,分别占比2.0%;发现1种广东省兽类新纪录,8种深圳市兽类新纪录。按景观生态以及生境情况,将深圳市划分为11个区域,通过相关性分析发现,不同区域兽类物种丰富度与其人口密度呈负相关,与植被条件以及距市区距离呈显著正相关,但是与生境斑块面积没有显著相关性;多元回归分析表明,植被条件为最主要的影响因素,且植被条件、距市区距离、人口密度三者间具有相关性。与此同时,对所调查到兽类的栖息生活类型、区系特征、濒危现状等进行了分析。     

Synthesis and spectroscopic characterization of 4-butoxyethoxy-N-octadecyl-1,8-naphthalimide as a new fluorescent probe for the determination of proteins

A novel 4-butoxyethoxy-N-octadecyl-1,8-naphthalimide (BON) was synthesized as a fluorescent probe for the determination of proteins. The interactions between BON and bovine serum albumin (BSA) were studied by fluorescence spectroscopy and UV-vis absorption spectroscopy. Fluorescence data revealed that the fluorescence quenching of BSA by BON was likely the result of the formation of the BON-BSA complex. According to the modified Stern-Volmer equation, the binding constants of BON with BSA at four different temperatures were obtained. The thermodynamic parameters, enthalpy change (ΔH) and entropy change (ΔS) for the reaction were calculated to be −23.27 kJ mol⁻¹ and 10.40 J mol⁻¹ K⁻¹ according to van’t Hoff equation, indicating that the hydrogen bonds and hydrophobic interactions played a dominant role in the binding of BON to BSA. Furthermore, displacement experiments using warfarin indicated that BON could bind to site I of BSA. The effect of BON on the conformation of BSA was also analyzed by synchronous fluorescence and three-dimensional fluorescence spectra. A new fluorescence quenching assay of the proteins BSA using BON in the HCl-Tris (pH 7.4) buffer solution was developed with maximum excitation and emission wavelengths of 373 and 489 nm, respectively. The linear range was 0.1-10.0 × 10⁻⁵ mol L⁻¹ with detection limits were determined to be 1.76 × 10⁻⁸ mol L⁻¹. The effect of metal cations on the fluorescence spectra of BON in ethanol was also investigated. Determination of protein in human serum by this method gave results which were very close to those obtained by using Coomassie Brilliant Blue G-250 colorimetry.     

Synthesis,discovery and preliminary SAR study of benzofuran derivatives as angiogenesis inhibitors

A series of benzofuran derivatives were synthesized and evaluated against HUVEC proliferation. Among these compounds, compound 32 exhibited good inhibitory activity and remarkable selectivity to HUVEC. Our current data suggested that array order of methyl, acrylate and carboxylate groups in benzofuran scaffold is the basic requirement for inhibitory activity against HUVEC proliferation. These results demonstrated that benzofuran scaffold represents a promising structural core to discover a new class of active and selective angiogenesis inhibitors.     

Molecular dynamics simulation of shear- and stretch-induced dissociation of P-selectin/PSGL-1 complex

By mediating the tethering and rolling of leukocytes on vascular surfaces, the interactions between P-selectin and the P-selectin glycoprotein ligand 1 (PSGL-1) play crucial roles during inflammation cascade. Tensile stretch produced by rolling leukocytes and shear stress exerted by blood flow constitute the two types of mechanical forces that act on the P-selectin/PSGL-1 bond. These forces modulate not only dissociation kinetics of this bond, but also the leukocyte adhesion dynamics. However, the respective contribution of the two forces to bond dissociation and to the corresponding microstructural bases remains unclear. To mimic the mechanical microenvironment, we developed two molecular dynamics approaches; namely, an approach involving the shear flow field with a controlled velocity gradient, and the track dragging approach with a defined trajectory. With each approach or with both combined, we investigate the microstructural evolution and dissociation kinetics of the P-LE/SGP-3 construct, which is the smallest functional unit of the P-selectin/PSGL-1 complex. The results demonstrate that both shear flow and tensile stretch play important roles in the collapse of the construct and that, before bond dissociation, the former causes more destruction of domains within the construct than the latter. Dissociation of the P-LE/SGP-3 construct features intramolecular destruction of the epidermal-growth-factor (EGF) domain and the breaking of hydrogen-bond clusters at the P-selectin-lectin/EGF interface. Thus, to better understand how mechanics impacts the dissociation kinetics of the P-selectin/PSGL-1 complex, we propose herein two approaches to mimic its physiological mechanical environment.     

New Distribution Records for Sphenomorphus tonkinensis(Lacertilia: Scincidae) with Notes on Its Variation and Diagnostic Characters

Sphenomorphus tonkinensis is a recently described new species based on specimens collected from northern Vietnam and Hainan, China. Herein, we report 13 additional specimens of S. tonkinensis from five new localities in Guangxi, Guangdong and Jiangxi, southern China. These specimens were compared with the type specimens of S. tonkinensis, which allows us to revise the diagnostic characteristics of this newly described species. Additional information on morphological variation, distribution and reproductive biology are provided, which extends our understanding of the natural history of S. tonkinensis.     

Morphology,Molecular Genetics,and Bioacoustics Support Two New Sympatric Xenophrys Toads (Amphibia: Anura: Megophryidae) in Southeast China

Given their recent worldwide declines and extinctions, characterization of species-level diversity is of critical importance for large-scale biodiversity assessments and conservation of amphibians. This task is made difficult by the existence of cryptic species complexes, species groups comprising closely related and morphologically analogous species. The combination of morphology, genetic, and bioacoustic analyses permits robust and accurate species identification. Using these methods, we discovered two undescribed Xenophrys species, namely Xenophrys lini sp. nov. and Xenophrys cheni sp. nov. from the middle range of Luoxiao Mountains, southeast China. These two new species can be reliably distinguished from other known congeners by morphological and morphometric differences, distinctness in male advertisement calls, and substantial genetic distances (>3.6%) based on the mitochondrial 16s and 12s rRNA genes. The two new species, together with X. jinggangensis, are sympatric in the middle range of Luoxiao Mountains but may be isolated altitudinally and ecologically. Our study provides a first step to help resolve previously unrecognized cryptic biodiversity and provides insights into the understanding of Xenophrys diversification in the mountain complexes of southeast China.     

Prognostic Implications of SLIT and ROBO1 Expression in Gallbladder Cancer

SLIT, a secretory glycoprotein, and its receptor roundabout (ROBO) are expressed in several types of cancer and have been implicated in tumor angiogenesis. The purpose of this study was to determine the prognostic implications of SLIT and ROBO1 expression and their association with clinicopathologic characteristics in gallbladder cancer. A retrospective analysis of 109 consecutive patients who underwent primary gallbladder cancer resection was conducted. Univariate and multivariate models were used to analyze the effect of clinicopathologic factors on survival. Expression of SLIT and ROBO1 was evaluated by immunohistochemistry, and their association with clinicopathologic characteristics was analyzed using mean testing. Multivariate linear regression analysis was also applied to investigate the independent predictors of ROBO1 expression. Seventy-five patients were included in the post-resection survival analysis, with 1-year and 3-year overall survival rates of 60 and 40 %, respectively. Univariate analysis revealed that pN classification, pT classification, pM classification, liver involvement, perineural invasion, TNM staging, Nevin staging, and microscopic resection margins affect prognosis. Multivariate analysis confirmed that pN classification, liver involvement, and perineural invasion are independent prognostic factors. In the mean tests of 109 cases, the mean difference of SLIT immunoreactivity was significant according to the presence of gallstones (P = 0.003) and liver involvement (P = 0.005), while the mean difference of ROBO1 immunoreactivity was significant according to liver involvement (P < 0.001), TNM staging (P < 0.001), and Nevin staging (P < 0.001). Multivariate analysis of ROBO1 immunoreactivity showed that SLIT immunoreactivity and TNM stage (adjusted R ² = 0.203) or SLIT immunoreactivity and Nevin stage (adjusted R ² = 0.195) were independent predictors of ROBO1 expression. pN classification, liver involvement, perineural invasion, and pathologic stage are significant prognostic factors for gallbladder cancer survival. SLIT expression is associated with cholelithiasis and liver involvement, and ROBO1 expression is associated with liver involvement and pathologic stage. In addition, SLIT expression and pathologic stage predict ROBO1 expression independently.     

中国两栖、爬行动物更新名录

本文在2015年发表的爬行动物名录及同年《中国两栖类信息系统》发布的两栖动物名录的基础上, 通过整理新发表的分类学研究及先前名录遗漏的部分早期文献, 更新了截至2019年底中国现生本土两栖、爬行动物物种名录。2015-2019年间, 中国两栖动物新记录1科, 新描述2属, 恢复1属有效性, 新记录1属, 新描述或恢复有效种74种, 新增国家纪录18种; 另6属、8种的有效性未得到近年研究证据支持(在此视为次定同物异名而未做收录, 后同)。同期, 中国爬行动物新恢复5科, 新描述1亚科, 新描述1属, 恢复3属有效性, 新记录3属, 新描述、恢复或提升有效种43个, 新增国家纪录10种; 另有5属、4种的有效性未得到近年研究证据支持, 并移除1属、4种在我国的分布纪录。此外, 通过整理2015年前文献, 爬行动物增补3属, 提升3亚种至种级地位, 增补国家新纪录3种, 另有3属、2种的有效性未得到近年研究证据支持, 同时移除1种在我国的分布纪录。综上, 截至2019年底, 我国共记录现生本土两栖动物3目13科62属515种(蚓螈目1科1属1种, 有尾目3科14属82种, 无尾目9科47属431种), 爬行动物3目35科135属511种(鳄形目1科1属1种, 龟鳖目6科18属34种, 有鳞目蛇亚目18科73属265种、蜥蜴亚目10科43属211种)。此外, 本文还对先前名录中部分爬行动物的中文名提出了修改建议, 建议恢复部分物种的惯用中文名。2015-2019年, 新物种及新纪录已知物种数量占现两栖、爬行动物物种总数的17.1%和10.2%。近年来, 我国发表的两栖、爬行动物新物种和已知物种的新纪录数量持续增加, 分类体系也在研究中不断完善, 建议今后及时地进行阶段性总结, 同时对存在的问题提出讨论, 以推动中国两栖、爬行动物分类学研究工作的进一步开展。     

纳米银对小麦赤霉病菌的抑制

采用化学还原法制备纳米银,以小麦赤霉病菌为受试菌株,研究纳米银对小麦赤霉病菌抗菌活性、对细胞内3种保护酶:超氧化物歧化酶(SOD)、过氧化物酶(POD)、过氧化氢酶(CAT)活性和对细胞渗透调节物质:丙二醛(MDA)、可溶性蛋白、可溶性糖含量的影响。结果表明:纳米银能显著抑制小麦赤霉病菌的生长,抑制作用随着浓度的增加而不断增大,10μg/mL的纳米银对病原菌的抑制率达90%以上,有效中浓度(EC_(50))为0.59μg/mL。随着纳米银处理时间(2、4、6、8和10 h)的增长,3种酶的活性均出现先增加后降低的变化。SOD、POD和CAT均在4 h出现最高值,10 h降至最低。纳米银使得菌体内丙二醛含量增加,可溶性蛋白和可溶性糖含量降低。纳米银破坏了病原真菌体内细胞的完整性,这可能是纳米银抑制病原菌生长的机理之一。