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41.
Yun-Ting He Xiao-Hong Huang Yue-Yi Fang Qing-Sheng Zeng Lai-De Li Le Luo Ying-Si Lai 《PLoS neglected tropical diseases》2022,16(5)
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. 相似文献
42.
Ennian Li Kai Wang Bei Zhang Siqi Guo Senhao Xiao Qi Pan Xiaowan Wang Weiying Chen Yunshan Wu Hesong Xu Xiangqian Kong Cheng Luo Shijie Chen Bo Liu 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1537
The DNA methyltransferases (DNMTs) were found in mammals to maintain DNA methylation. Among them, DNMT1 was the first identified, and it is an attractive target for tumour chemotherapy. DC_05 and DC_517 have been reported in our previous work, which is non-nucleoside DNMT1 inhibitor with low micromolar IC50 values and significant selectivity towards other S-adenosyl-L-methionine (SAM)-dependent protein methyltransferases. In this study, through a process of similarity-based analog searching, a series of DNMT1 inhibitors were designed, synthesized, and evaluated as anticancer agents. SAR studies were conducted based on enzymatic assays. And most of the compounds showed strong inhibitory activity on human DNMT1, especially WK-23 displayed a good inhibitory effect on human DNMT1 with an IC50 value of 5.0 µM. Importantly, the pharmacokinetic (PK) profile of WK-23 was obtained with quite satisfying oral bioavailability and elimination half-life. Taken together, WK-23 is worth developing as DNMT1-selective therapy for the treatment of malignant tumour. 相似文献
43.
Lifang Guo Xingchao Geng Li Liu Yufa Miao Zhi Lin Min Yu Yan Fu Lihong Liu Bo Li Yongzhang Luo 《Journal of biochemical and molecular toxicology》2019,33(3)
Endostar, a potent endogenous antiangiogenic factor, is wildly used in clinics. However, it was easily degraded by enzymes and rapidly cleared by the kidneys. To overcome these shortcomings, PEGylated recombinant human endostatin was developed. In this study, the purity of M2ES was evaluated by silver stain and reversed‐phase high‐performance liquid chromatography. Ultraviolet spectrum was used to examine the structural of M2ES and endostar. The bioactivity and antitumor efficacy of M2ES were evaluated using an in vitro endothelial cell migration model and athymic nude mouse xenograft model of a heterogeneous lung adenocarcinoma, respectively. A preclinical study was performed to evaluate the acute toxicity and safety pharmacology in rhesus monkeys. The purity of M2ES was more than 98%; PEG modification has no effect on endostatin structure. Compared with the control group, M2ES dramatically retards endothelial cell migration and tumor growth. After intravenous (IV) infusions of M2ES at a dose level of three and 75 mg/kg in rhesus monkeys, there was no observable serious adverse event in both acute toxicity and safety pharmacology study. On the basis of the quality and bioactivity study data of M2ES and the absence of serious side effect in rhesus monkeys, M2ES was authorized to initiate a phase I clinical trial. 相似文献
44.
45.
Junna Wang Chong Li Xinbin Duan Daqing Chen Shunxin Feng Huihuang Luo Qidong Peng Wengen Liao 《Freshwater Biology》2014,59(7):1343-1360
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46.
山姜属(Alpinia L.)植物的花柱具卷曲运动的能力,该属植物的野生种群有两种表型的个体,其花柱运动方向相反。该文通过观察马来良姜(Alpinia mutica Roxb.)花柱的显微和超微结构来研究花柱卷曲运动的结构基础。结果表明两种表型的花柱解剖结构相同。花柱仅形态学上端区域(约占花柱总长度的25%)有卷曲运动能力,其它区域不能运动。运动区近轴侧分布着几层直径较大、形状不规则、相对较短且细胞壁较薄的细胞,远轴侧的细胞直径较小、狭长;非运动区近轴和远轴侧的细胞都呈狭长形。花柱运动区域近轴侧和远轴侧细胞结构和细胞层数的不对称可能是导致花柱卷曲运动的结构原因。 相似文献
47.
Jinshan Yang Xiang Luo Xiaojiang Huang Qin Ning Minjie Xie Wei Wang 《Journal of neurochemistry》2014,131(3):383-394
Increasing evidence indicates that the Eph receptors and their ephrin ligands are involved in the regulation of interactions between neurons and astrocytes. Moreover, astrocytic ephrin‐A3 reverse signaling mediated by EphA4 receptors is necessary for controlling the abundance of glial glutamate transporters. However, the role of ephrin‐A3 reverse signaling in astrocytic function and neuronal death under ischemic conditions remains unclear. In the present study, we found that the EphA4 receptor and its ephrin‐A3 ligand, which were distributed in neurons and astrocytes, respectively, in the hippocampus showed a coincident up‐regulation of protein expression in the early stage of ischemia. Application of clustered EphA4 decreased the expressions of astrocytic glutamate transporters together with astrocytic glutamate uptake capacity through activating ephrin‐A3 reverse signaling. In consequence, neuronal loss was aggravated in the CA1 region of the hippocampus accompanied by impaired hippocampus‐dependent spatial memory when clustered EphA4 treatment was administered prior to transient global ischemia. These findings indicate that EphA4‐mediated ephrin‐A3 reverse signaling is a crucial mechanism for astrocytes to control glial glutamate transporters and prevent glutamate excitotoxicity under pathological conditions.
48.
贺兰山马鹿冬春季生境的选择 总被引:4,自引:2,他引:4
2007年12月~2008年1月和2008年4~5月,在贺兰山利用痕迹检验法和直接观察法对马鹿阿拉善亚种冬春季生境选择进行研究.通过在选定的15条沟段里进行调查,冬春季各测定了131个和181个样方的18种生态因子.结果表明,冬春季贺兰山马鹿在植被类型、优势乔木、灌木密度、灌木高度、灌木距离、坡向、坡位、海拔高度、距裸岩距离和隐蔽级10种生态因子上差异极显著(P < 0.001),其余生态因子无显著差异(P < 0.05),相对于冬季生境而言,马鹿春季更偏爱选择以油松和青海云杉为优势乔木的山地针叶林带,灌木密度大、高度高、距离近,半阴半阳坡的中坡位,海拔较高,距裸岩较近,隐蔽程度高的生境.典则判别系数显示冬春季马鹿在生境选择上存在一定程度的重叠,但春季马鹿的分布范围要比冬季更广一些,Wilk's λ值显示冬春季马鹿的生境选择具有较高的差异性(Wilk's λ = 0.683,x2 = 116.995,df = 13,P < 0.001).逐步判别分析表明在区分冬春季马鹿生境方面有一系列生态因子发挥作用,依照贡献值的大小依次为:乔木密度、灌木距离、坡度、海拔高度、距水源距离、距裸岩距离和隐蔽级,由这7个变量构成的方程对冬春季马鹿生境的正确区分率达到79.9%,其中对春季的误判率为22.1%,对冬季的误判率为20.6%. 相似文献
49.
甘肃矿产资源丰富,矿区酸性矿坑水(acid mine drainage,AMD)及周边土壤中嗜酸微生物种类丰富,具有相当大的研究价值.本研究通过Illumina高通量测序方法,对甘肃省4个矿区AMD及周边土壤中的细菌群落组成、相似性及功能组成进行分析.结果 表明,煤矿样品GNM细菌物种组成最为丰富,金矿样品LNJ1与紫金矿样品LNZJK细菌组成最相似,与属于铜矿的BYT物种较相近,与LNJ1同地区的LNJ2样品细菌组成相比较远.所有样品细菌主要分为放线菌门(Actinobacteria)、拟杆菌门(Bacteriodetes)、厚壁菌门(Firmicutes)和变形菌门(Proteobacteria)四大门,其中变形菌门(Proteobacteria)丰度最高.放线菌门(Actinobacteria)中不动杆菌属(Acinetobacter)、类诺卡氏属(Nocardioides)和芽球菌属(Blastococcus)表现出较高丰度;厚壁菌门(Firmicutes)中微小杆菌属(Exiguobacterium)和芽孢杆菌属(Bacillus)表现出较高丰度,且微小杆菌属(Exiguobacterium)丰度极高.通过功能预测发现,与煤矿样品GNM相比,LNJ1、LNJ2、BYT和LNZJK4个金属矿区样品中的微生物具有较强的氨基酸与碳源的转运与代谢、转录等功能以及较低的能量生产与转运、无机离子转运与代谢能力.通过探究AMD中的细菌多样性及其与重金属之间的相互关系,了解AMD采样区微生物群落结构,以期挖掘出更为丰富的具有重金属抗性的菌株资源,以应用于生物浸矿和环境修复等领域. 相似文献
50.
Excess copper is toxic to life. Copper has been shown to induce apoptosis in various cell lines and tissues. However, due to the lack of appropriate gene knockout animal models, data concerning the underlying pathways of copper-induced apoptosis are insufficient, especially with regards to in vivo systems. The nematode Caenorhabditis elegans is a good model to study basic biological processes, including stress responses and apoptosis. In the present study, we investigated copper-induced germline apoptosis in the C. elegans strains carrying mutated alleles of homologs to known mammalian genes that are involved in apoptosis regulation. We show here that exposing C. elegans to copper causes dose- and time-dependent germline apoptosis. The knockout of checkpoint genes hus-1, clk-2, the Bcl-2 homolog ced-9, and the BH3-only domain egl-1 did not prevent cells of the germline from copper-induced apoptosis. The loss-of-function of the tumor suppressor gene, p53/cep-1, caused a significant increase in germline apoptosis with exposure to copper, and the depletion of p53 antagonist ABL1 significantly enhanced apoptosis. The knockout of the caspase gene ced-3 and the Apaf-1 homolog ced-4 abrogated both copper-induced and physiological germline apoptosis. Germline apoptosis stopped increase in the strains lin-45(ku51), mek-2(n1989), mpk-1(ku1) under copper stresses, respectively. Copper-induced apoptosis was blocked in the loss-of-function alleles of both JNK and p38 MAPK cascades excepting pmk-3, one of the three p38 MAPK components. Together, the results of this study suggest that caspase and Apaf-1 are required for copper-induced germline apoptosis while DNA damage response genes are not essential, and that the Raf-MEK-ERK, ASK1/2-MKK7-JNK, ASK1/2-MKK3/6-p38 signaling pathways are indispensable in mediating this apoptotic response. 相似文献