Cost-effectiveness evaluation of different control strategies for Clonorchis sinensis infection in a high endemic area of China: A modelling study

Clonorchiasis is an important food-borne parasitic disease caused by Clonorchis sinensis infection. The evaluation of long-term cost-effectiveness of control strategies is important for disease control and prevention. The present study aimed to assess the cost-effectiveness of the three recommended strategies (i.e., WHO, Chinese and Guangdong strategies) and different combinations of commonly used measures (i.e., preventive chemotherapy, information, education, and communication (IEC) and environmental improvement) on clonorchiasis. The study area, Fusha town in Guangdong Province, was a typical high endemic area in China. The analysis was based on a multi-group transmission model of C. sinensis infection. We set the intervention duration for 10 years and post-intervention period for 50 years. The corresponding costs and DALYs were estimated. Strategies with incremental cost-effectiveness ratios (ICERs) less than 1/5 of the willingness-to-pay threshold were identified as highly cost-effective strategies. The optimal control strategy was obtained using the next best comparator method. The ICERs of Guangdong strategy were $172 (95% CI: $143-$230) US for praziquantel and $106 (95% CI: $85-$143) US for albendazole, suggesting the highest cost-effectiveness among the three recommended strategies. For praziquantel, 470 sets of control strategies were identified as highly cost-effective strategies for achieving infection control (prevalence<5%). The optimal strategy consisted of chemotherapy targeted on at-risk population, IEC and environmental improvement, with coverages all being 100%, and with the ICER of $202 (95% CI: $168-$271) US. The results for transmission control (prevalence<1%) and albendazole were obtained with the same procedures. The findings may help to develop control policies for C. sinensis infection in high endemic areas. Moreover, the method adopted is applicable for assessment of optimal strategies in other endemic areas.     

Genetic validation of Aspergillus fumigatus phosphoglucomutase as a viable therapeutic target in invasive aspergillosis

Aspergillus fumigatus is the causative agent of invasive aspergillosis, an infection with mortality rates of up to 50%. The glucan-rich cell wall of A. fumigatus is a protective structure that is absent from human cells and is a potential target for antifungal treatments. Glucan is synthesized from the donor uridine diphosphate glucose, with the conversion of glucose-6-phosphate to glucose-1-phosphate by the enzyme phosphoglucomutase (PGM) representing a key step in its biosynthesis. Here, we explore the possibility of selectively targeting A. fumigatus PGM (AfPGM) as an antifungal treatment strategy. Using a promoter replacement strategy, we constructed a conditional pgm mutant and revealed that pgm is required for A. fumigatus growth and cell wall integrity. In addition, using a fragment screen, we identified the thiol-reactive compound isothiazolone fragment of PGM as targeting a cysteine residue not conserved in the human ortholog. Furthermore, through scaffold exploration, we synthesized a para-aryl derivative (ISFP10) and demonstrated that it inhibits AfPGM with an IC₅₀ of 2 μM and exhibits 50-fold selectivity over the human enzyme. Taken together, our data provide genetic validation of PGM as a therapeutic target and suggest new avenues for inhibiting AfPGM using covalent inhibitors that could serve as tools for chemical validation.     

界面发酵红曲霉的图像解析*

利用计算机视觉技术研究了红曲霉界面发酵过程中菌体形态变化与菌体生长的关系。在界面培养中通过检测前期菌落面积,后期隆起部分的表征体积——基于颜色变化的生长点分布,可以有效表示菌体生长状况。基于此建立了含有相应形态参数的动力学模型,该模型与常规动力学模型具有相似的表达形式。     

土壤矿物与微生物相互作用的机理及其环境效应

土壤矿物与微生物相互作用是地球表层系统中重要的生态过程.微生物或生物分子与矿物间的吸附(粘附)是两者相互作用的基础.吸附(粘附)是一个由分子间力、静电力、疏水作用力、氢键和空间位阻效应等多种作用力或作用因素共同决定、影响的物理化学过程.因此,微生物和矿物的表面性质如表面电荷、疏水性和它们所处的环境条件如pH、电解质浓度、温度等,都影响着矿物-微生物吸附(粘附)过程.微生物细胞或酶可吸附于矿物表面,其结果是细胞代谢或酶活性会发生明显变化,并进一步影响土壤中诸多相关的生态、环境过程.结合4种典型的初始吸附理论:表面自由能热力学理论、DLVO理论、吸附等温线理论和表面复合物理论及本课题组近年来的研究成果,对土壤矿物与微生物相互作用的类型、机理、作用力和现代研究技术等方面的最新研究进展进行了较为全面的论述,对土壤矿物-微生物相互作用的环境效应进行了讨论,并就该领域今后研究工作的特点及应关注的问题进行了展望.     

九龙江口底栖生物生态研究

本文研究了九龙江口底栖生物种类组成、数量分布、季节变化及其与环境因子的关系等生态特点。结果表明,九龙江口底栖生物种类丰富(计440种)。其分布具有三种生态类型:河口种、海水种和近岸广盐种。平均总生物量为56.17克/米~2,平均栖息密度为358个/米~2。底栖生物与环境因子的关系密切:河口区底栖生物种群和数量的分布趋势是随着盐度的增高而增多;局部区域的水动力特点以及不同的沉积物类型也影响底栖生物种类和数量的分布。     

弱氧化醋杆菌阿拉伯糖醇脱氢酶基因克隆及其在大肠杆菌中的表达

The partial genomic library of Acetobacter suboxydans was constructed using Yeast\| E.coli shuttle plasmid YEp352 as vector.Two positive transformants,designated as DH5α(pAD91) and DH5α(pAD98),were obtained by screening the growth of transformants on the agar plate in which D\|arabitol was used as the sole carbon source.The results of Southern blot and restriction endonuclease analysis showed that the two recombinants are identical.The insert is about 2.3kb.Arabitol dehydrogenase activity assay indic…     

新疆苦豆子根瘤菌的数值分类研究

苦豆子(Sophora alopecuroides)对于干旱荒漠地区的畜牧业发展有着非常重要的意义,其生长特性与根瘤菌有密切关系。我们对分离自新疆苦豆子根瘤的67株根瘤菌及36个模式菌株进行了118项表型性状的测定,包括唯一碳源利用、唯一氮源利用、对抗生素和染料的抗性、耐盐性、初始pH值生长范围、生长温度范围及石蕊牛奶反应、氧化酶、过氧化氢酶和脲酶。对测定结果用聚类分析方法进行了分析,获得数值分类树状图。结果表明：新疆苦豆子根瘤菌在碳氮源利用、抗生素敏感性以及对染料的抗性程度等方面存在着差异。新疆苦豆子根瘤菌能耐受低温,并具有较强的耐盐、碱能力,所有供试菌株均能在初始pH值为9－12的YMA培养基上生长,92.5％的菌株能耐受3.0％的NaCl,91.0％的菌株能耐受4.0％的NaCl,有18株菌甚至能耐受5.0％和6.0％的NaCl。聚类结果表明, 在84.8%的相似性水平上,67个供试菌株构成了4个新的表观群,第Ⅰ、Ⅱ、Ⅲ、Ⅳ类群分别有21、7、4、3个菌株,中心菌株分别为NWBC152、NWTKX101、NWYJS12、NWLP112。此外,数值分类结果还表明,苦豆子根瘤菌与模式菌株的相似性较低,它们所形成的4个独立群可能有新种出现。     

Dynamics of fertilizer-derived organic nitrogen fractions in an arable soil during a growing season

Background

Inorganic fertilizer is one of the most important anthropogenic inputs which influences soil nutrient turnover in agricultural ecosystems. However, as the key process involved in the maintenance, transformation and stability of soil nitrogen (N), the incorporation and allocation of fertilizer N between different soil organic N (SON) fractions in a growing season remains largely unknown.

Methods

In this study, a field experiment was conducted in triplicate of micro-plots and a total of 200 kg N ha^?1 (¹⁵?N-labeled (NH₄)₂SO₄, 98 atom %) was applied as a basal dressing and two top dressings, at jointing and filling stages, respectively, to a maize crop during one growing season. The distribution and seasonal dynamics of fertilizer N in different SON fractions (i.e., amino acids, amino sugars, hydrolyzable ammonium N and acid insoluble-N) were measured by liquid/gas chromatography–mass spectrometry (LC/GC-MS) and element analysis-combustion-isotope ratio mass spectrometry (EA-C-IRMS) techniques. Path analysis was used to evaluate the transformation processes between organic N fractions derived from fertilizer and N supply strategy in soil-plant system.

Results

The accumulation of fertilizer-derived N in different organic fractions was season-specific. At jointing stage, preferential enrichment of ¹⁵?N was found in soil amino acids plus amino sugars, indicating the active biological immobilization of basal dressing fertilizer N. Nevertheless, there is still a small proportion of fertilizer N stabilized in the acid insoluble fraction. The accumulation of the residual fertilizer N in hydrolyzable ammonium N reached a maximum at filling stage and then declined significantly, implying the rapid release of the fertilizer N remained in mineral forms. The contents of amino acids changed slightly, but they played a very important role in mediating SON transformation.

Conclusion

The hydrolyzable ammonium N was a temporary pool for rapid fertilizer N retention and simultaneously was apt to release N for crop uptake in the current season. In contrast, the amino acids could serve as a transitional pool of available N in the soil-crop system, while the acid insoluble fraction was as a stable pool of fertilizer N. Importantly, there is an interim shift among different pools to maintain soil N turnover; hence N in the amino acid fraction mediates N supply and the depolymerization of SON constituents controls the proceeding of fertilizer N cycling in the soil-plant system.     

超抗原SEA增强小鼠对HBV DNA 疫苗的免疫反应

观察超抗原SEA(D227A)的真核表达载体(pmSEA),对HBVDNA疫苗诱导Balbc小鼠(H2d)免疫应答的调节作用。肌内注射空载体pcDNA3、HBVDNA疫苗加pmSEA佐剂(pHBVS2S+pmSEA)或不加佐剂(pHBVS2S);ELISA法测定血清抗HBs;ELISPOT检测分泌IFNγ的脾淋巴细胞;4h51Cr释放法检测小鼠脾细胞CTL活性。HBVDNA佐剂组免疫小鼠抗HBsAg抗体滴度明显高于不加佐剂组,其IgG1IgG2a的比例不同于多肽免疫组,二者分别为0.282与10。HBVDNA佐剂组均能增强IgG1和IgG2a的产生,是不加佐剂组的1.36、1.73倍。佐剂组小鼠脾淋巴细胞IFNγ的分泌量是不加佐剂组2～3倍。CTL细胞杀伤活性(E:T=100)佐剂组与不加佐剂组分别为:69.77%±7.5%、42.81%±7.7%,差异显著(P<0.05)。HBVDNA疫苗具有较强的免疫原性,能够诱导机体产生特异性的抗体及CTL反应;pmSEA佐剂能够提高小鼠对DNA疫苗的免疫应答,有望成为DNA疫苗的免疫佐剂。     

冀西北坝上半干旱区南瓜油葵间作的水分效应

针对冀西北高原水源匮乏、利用低效问题,于2009-2010年在农业部张北农业资源与生态环境重点野外观测试验站通过南瓜//油葵不同间作群体结构试验,探讨了该区南瓜水分高效的种植方式。试验设南瓜单作（Sp）,南瓜行间作1行油葵（IC1）,南瓜行间作2行油葵（IC2）和油葵单作（So）4个处理。结果表明,南瓜行间种植两行油葵（IC2）在南瓜生长中后期出现了油葵与南瓜争夺水分的现象,而南瓜行间种植一行油葵（IC1）无此现象。各处理间水量平衡各分量有较大的差异,在整个生育时期降雨量为201.6mm的情况下,渗漏量占的比重非常小,并且土壤蓄水量变化均为负值,绝大部分水分都是以气态水蒸散掉,但不同间作方式蒸散失水量不同,其中IC1较So、Sp和IC2分别少散失土壤水分36.33%、19.00%和34.87%。得益于油葵的偏利效应使南瓜经济产量下降30.00% ~71.42%,而间种油葵单株产量相对单作田提高190.71%~ 241.26%,虽其土地当量比LER和水分当量比WER分别达1.08~1.22和1.07~1.26,但IC1复合群体的经济效益只能与南瓜单作田持平,其他处理明显低于单作南瓜。在冀西北高原雨养背景下,稀植高效的南瓜单作生产能够实现对区域水资源的高效利用。