Synthesis and biological evaluation of 18F labeled fluoro-oligo-ethoxylated 4-benzylpiperazine derivatives for sigma-1 receptor imaging

We report the synthesis and evaluation of a series of fluoro-oligo-ethoxylated 4-benzylpiperazine derivatives as potential σ₁ receptor ligands. In vitro competition binding assays showed that 1-(1,3-benzodioxol-5-ylmethyl)-4-(4-(2-fluoroethoxy)benzyl)piperazine (6) exhibits low nanomolar affinity for σ₁ receptors (K_i = 1.85 ± 1.59 nM) and high subtype selectivity (σ₂ receptor: K_i = 291 ± 111 nM; K_iσ₂/K_iσ₁ = 157). [¹⁸F]6 was prepared in 30–50% isolated radiochemical yield, with radiochemical purity of >99% by HPLC analysis after purification, via nucleophilic ¹⁸F^? substitution of the corresponding tosylate precursor. The log D_{pH 7.4} value of [¹⁸F]6 was found to be 2.57 ± 0.10, which is within the range expected to give high brain uptake. Biodistribution studies in mice demonstrated relatively high concentration of radiotracers in organs known to contain σ₁ receptors, including the brain, lungs, kidneys, heart, and spleen. Administration of haloperidol 5 min prior to injection of [¹⁸F]6 significantly reduced the concentration of radiotracers in the above-mentioned organs. The accumulation of radiotracers in the bone was quite low suggesting that [¹⁸F]6 is relatively stable to in vivo defluorination. The ex vivo autoradiography in rat brain showed high accumulation of radiotracers in the brain areas known to possess high expression of σ₁ receptors. These findings suggest that [¹⁸F]6 is a suitable radiotracer for imaging σ₁ receptors with PET in vivo.     

大型丝状藻类对城市河流甲烷排放的影响研究进展

温室气体排放导致的全球变暖受到广泛关注.近期研究发现,经由河流系统排放的二氧化碳（CO₂）和甲烷（CH₄）可部分抵消陆地生态系统的碳固定量,从而使人们开始重新思考河流对于全球碳平衡和温室气体排放清单的影响.作为城市河流系统中重要的初级生产者,大型丝状藻类通过改变水-沉积物界面物理、化学以及生物等环境因子,深刻影响着河流生态系统的碳循环过程.本文从3个方面阐述大型丝状藻类对于城市河流中CH₄排放的影响:城市化对河流生态系统及其CH₄排放通量的影响;大型丝状藻类对自然河流系统中CH₄产生与排放过程的影响;大型丝状藻类对城市河流系统初级生产力及CH₄产生过程的影响.最后对目前存在的问题和今后的研究方向进行了展望.     

胃肝样腺癌的临床病理特征

目的探讨胃肝样腺癌（hepatoid adenocarcinoma of the stomach,HAS）的临床病理学特点、发生机制和免疫组化特征,以提高诊断水平。方法收集并分析5例胃肝样腺癌的临床特征和病理资料,采用HE染色、免疫组化方法,并复习文献。结果组织学胃肝样腺癌具有管状腺癌、粘液性癌和肝样分化腺癌的移行过渡,肿瘤细胞呈小梁状、巢团状,间质为丰富的血窦。免疫表型胃肝样腺癌AAT（5／5）、ACT（5／5）、CEA（5／5）、AFP（4／5）均为阳性,Heppar1灶性阳性（2／5）。结论胃肝样腺癌是一种少见的高度恶性、侵袭性强的特殊类型胃癌,组织学呈肝细胞样腺癌,免疫表型AFP、AAT和ACT阳性有助诊断。     

Chiral discrimination and interaction mechanism between enantiomers and serum albumins

The chiral discrimination studies of biological system are theoretically and practically significant for the development of chiral drugs and life science. Our work has embarked upon the interaction between serum albumin (SA) (including human SA and bovine SA), R,S‐1‐(4‐methoxyphenyl)ethylamine, and R,S‐1‐(3‐methoxyphenyl)ethylamine. The formation of intermediate transition state, binding sites, and chiral discrimination ability can be investigated by ultraviolet‐visible spectra and fluorescence spectra. Moreover, both the changes of hydrophobic microenvironment and energy transfer can be detected by synchronous fluorescence spectra and fluorescence lifetime. Copyright © 2013 John Wiley & Sons, Ltd.     

Synergistic antitumor activity of reversine combined with aspirin in cervical carcinoma in vitro and in vivo

A recent report showed that reversine treatment could induce murine myoblasts dedifferentiation into multipotent progenitor cells and inhibit proliferation of some tumors, and other reports showed that apoptosis of lung adenocarcinoma cells could be induced by aspirin. The aim of the present study was to evaluate the synergistic antitumor effects of reversine and aspirin on cervical cancer. The inhibition rate of reversine and aspirin on cervical cancer cell lines’ (HeLa and U14) was determined by MTT method, cell cycle of HeLa and U14 cells was analyzed by FACS, mitochondrial membrane potential of HeLa and U14 was detected using a JC-1 kit. HeLa and U14 colony formation was analyzed by soft agar colony formation assay. The expression of caspase-3, Bcl-2/Bax, cyclin D1 and p21 was detected by qRT-PCR and Western Blotting. Moreover, tumor weight and tumor volume was assessed using a murine model of cervical cancer with U14 cells subcutaneously (s.c.) administered into the neck, separately or combined with drug administration via the intraperitoneal (i.p.) route. The inhibition rate of cells in the combination group (10 μmol/L reversine, 10 mmol/L aspirin) increased significantly in comparison to that when the drugs were used alone (P < 0.05); moreover, this combination could synergistically inhibit the proliferation of five cervical cancer cell lines (HeLa, U14, Siha, Caski and C33A). In the therapeutic mouse model, tumor weight and tumor volume of cervical cancer bearing mice was more reduced when compared with the control agents (P < 0.05) in tumor-bearing mice. The combination of reversine and aspirin exerts synergistic growth inhibition and apoptosis induction on cervical cancers cells.     

Vero细胞和脊髓灰质炎病毒在无血清条件下的培养探究

目的：探索Vero细胞和脊髓灰质炎病毒在无血清条件下的最佳培养条件,为无血清培养Vero细胞生产脊髓灰质炎疫苗奠定基础。方法选择直接适应（直降组）和序贯适应（驯化组）两种无血清培养方法,观察Vero细胞和脊髓灰质炎病毒在无血清条件下的生长情况,并检测脊髓灰质炎病毒及其病毒滴度。结果 Vero细胞在两种无血清条件下均生长良好,其中驯化组细胞生长速度更接近对照组。以脊髓灰质炎病毒Sabin株Ⅰ型分别感染直降组、驯化组和对照组细胞的病毒滴度平均值分别为8．94、8．81和8．94 LgCCID50/mL;Ⅱ型病毒滴度平均值分别为8．84、8．25和7．94 LgCCID50/mL;Ⅲ型病毒滴度平均值分别为8．91、8．57和8．63 LgCCID50/mL;且3组的变异系数（ CV）均小于10％。结论 Vero细胞在无血清条件下生长良好,无血清培养的Vero 细胞可用作脊髓灰质炎疫苗生产的基质。     

小儿下呼吸道感染痰培养标本病原菌构成分析

目的了解小儿下呼吸道感染病原菌的分布及对常用抗菌药物的耐药状况。方法对2710例小儿下呼吸道感染患者痰标本进行培养,用VITEK-2Compact微生物鉴定系统鉴定菌种和药敏试验,WHO-NET5．4软件对数据进行分析。结果共分离病原菌675株,革兰阴性杆菌457株,占67．7％,主要为大肠埃希菌、肺炎克雷伯菌;革兰阳性球菌159株,占23．5％,主要为金黄色葡萄球菌、肺炎链球菌;真菌59株,占8．7％,主要为白色假丝酵母菌。结论小儿下呼吸道感染病原菌以革兰阴性杆菌为主,耐药性较为严重,应不断加强耐药性监测,合理使用抗菌药物。     

南岳衡山藤本植物资源研究

根据野外调查,结合文献资料,对南岳衡山藤本植物的区系及其生态特征进行了初步的研究,结果表明:该区野生藤本植物共计59科129属282种(含变种),分别占该区维管植物科、属、种总数的29.35％、16.82％和15.60％.该区地里成分复杂,以热带性分布为主,温带成分亦占有较大比例,其中科、属以泛热带分布型最多,分别占科、属总数的38.98％和23.26％,而种以热带亚洲分布型最多,达25.89％,表明该区藤本植物区系是以热带性质为主的亚热带类型,同时也显示出该区藤本植物区系向温带渗透和过渡的性质;该区中国特有种丰富,共计106种,占种总数的37.59％,属华东区系,与华东、华中、华南及滇、黔、桂有着极密切的联系;该区藤本的生态分布是随着海拔的升高,温度的降低,藤本的种类与数量也相应地减少.树木和藤本无亲疏关系,未发现某些藤本偏爱某些树种胜于其他树种;在区系关系上,该区与康龙和庐山的关系最为密切,而与崀山和龙底的关系较为疏远.     

Development, characterization, genetic diversity and cross-species/genera transferability of ILP markers in rubber tree (Hevea brasiliensis)

To construct a linkage map enriched with tapping panel dryness (TPD)-related markers, we firstly utilized rubber tree ESTs associated with TPD to develop intron length polymorphism (ILP) markers. In this study, 52 new ILP markers were further developed. Together with the ILP markers previously reported, 102 ILP markers developed from TPD-related ESTs were analyzed within 39 Hevea germplasm in detail. The PCR success rate and polymorphism rate of ILP markers was 97.06 and 61.62 %, respectively. The results based on PCR amplification and sequence analyses provided the evidences on cross-species/genera transferability of rubber tree ILP markers. The average polymorphic information content (PIC) values of 39 Hevea germplasm were about 0.1719, indicating that the genetic base of Hevea germplasm selected in this study was very narrow. Among 39 Hevea germplasm, the PIC value of wild rubber tree accessions was the highest, followed by Hevea species and cultivated rubber tree clones. Based on the similarity coefficient of ILP markers, 39 Hevea germplasm were divided into three groups including cultivated clones, wild accessions and Hevea species, suggesting that the classification was generally related to the characterization of Hevea germplasm. The ILP markers developed in this study further enriches the number of molecular marker in rubber tree, and the ILP markers will have a wide application in DNA fingerprinting, genetic diversity, marker-assisted selection and genetic mapping, etc. Moreover, the ILP markers transferred cross-euphorbiaceae family might be utilized in cassava, castor bean and physic nut.