摘要：
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>Malaria transmission depends on infected mosquitoes and can be controlled by transmission-blocking drugs. The recently discovered FREP1-mediated malaria transmission pathway is an excellent target to screen drugs for limiting transmission.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<jats:p>To identify candidate small molecules, we used an ELISA-based approach to analyze extracts from a fungal library for inhibition of the FREP1–parasite interaction. We isolated and determined one active compound by chromatography and crystallography, respectively. We measured the effects of the bioactive compound on malaria transmission to mosquitoes through standard membrane-feeding assays (SMFA) and on parasite proliferation in blood by culturing.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>We discovered the ethyl acetate extract of the fungus <jats:italic>Purpureocillium lilacinum</jats:italic> that inhibited <jats:italic>Plasmodium falciparum</jats:italic> transmission to mosquitoes. Pre-exposure to the extract rendered <jats:italic>Anopheles gambiae</jats:italic> resistant to <jats:italic>Plasmodium</jats:italic> infection. Furthermore, we isolated one novel active compound from the extract and identified it as 3-amino-7,9-dihydroxy-1-methyl-6H-benzo[c]chromen-6-one, or “pulixin.” Pulixin prevented FREP1 from binding to <jats:italic>P. falciparum</jats:italic>-infected cell lysate. Pulixin blocked the transmission of the parasite to mosquitoes with an EC<jats:sub>50</jats:sub> (the concentration that gave half-maximal response)of 11µM based on SMFA. Notably, pulixin also inhibited the proliferation of asexual-stage <jats:italic>P. falciparum</jats:italic> with an EC<jats:sub>50</jats:sub> of 47nM. The compound did not show cytotoxic effects at a concentration of 116µM or lower.</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusion</jats:title>
<jats:p>By targeting the FREP1–<jats:italic>Plasmodium</jats:italic> interaction, we discovered that <jats:italic>Purpureocillium lilacinum</jats:italic> extract blocked malaria transmission. We isolated and identified the bioactive agent pulixin as a new compound capable of stopping malaria transmission to mosquitoes and inhibiting parasite proliferation in blood culture.</jats:p>
</jats:sec><jats:sec>
<jats:title>Graphical Abstract</jats:title>
</jats:sec>
摘要：
目的建立华支睾吸虫的免疫胶体金（ICT）和实时荧光定量PCR检测体系,比较两者检测华支睾吸虫的效果。方法以华支睾吸虫成虫抗原包被胶体金,检测血液样本中的相应抗体,建立华支睾吸虫ICT检测方法;以华支睾吸虫18S r RNA基因作为靶基因,设计RT-PCR的特异性引物和探针,检测粪便样本中的核酸实时荧光定量PCR方法;以两种检测体系与商品化的酶联免疫（ELISA）检测试剂盒平行测定比较,考核检测体系的应用价值。结果对200份华支睾吸虫重点人群样本进行检测,ELISA法检出的华支睾吸虫Ig G抗体阳性例数为20例,阳性率为10.0%;ICT法为16例,阳性率为8.0%,灵敏度为80.0%,特异度为100.0%,符合率为98.0%,ICT和ELISA两种检测方法差异无统计学意义（χ^2=2.25,P〉0.05）;RT-PCR法检出的粪便样本中华支睾吸虫核酸阳性例数为18例,阳性率为9.0%,灵敏度为90.0%,特异度为100.0%,符合率为99.0%,RT-PCR和ELISA两种检测方法差异无统计学意义（χ^2=0.05,P〉0.05）。说明ICT、RT-PCR两种检测方法与ELISA的测定结果比较一致。结论建立的ICT及RT-PCR两种检测方法特异性好、灵敏度高,两种检测方法均适用于华支睾吸虫现场的快速检测及定量分析。
期刊：
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY,2016年169:208-215 ISSN：1386-1425
通讯作者：
Li, Guirong
作者机构：
[Han, Qian; Li, Guirong; Li, Jiekang] Univ South China, Coll Publ Hlth, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Li, Guirong] U;Univ South China, Coll Publ Hlth, Hengyang 421001, Hunan, Peoples R China.
关键词：
Uranyl;[UO22+-salophen] complex;Photo-catalytic resonance fluorescence method;Dual cloud point extraction
摘要：
In this paper, two kinds of salophens (Sal) with different solubilities, Sal1 and Sal2, have been respectively synthesized, and they all can combine with uranyl to form stable complexes: [UO22+-Sal1] and [UO22+-Sal2]. Among them, [UO22+-Sal1] was used as ligand to extract uranium in complex samples by dual cloud point extraction (dCPE), and [UO22+-Sal2] was used as catalyst for the determination of uranium by photocatalytic resonance fluorescence (RF) method. The photocatalytic characteristic of [UO22+-Sal2] on the oxidized pyronine Y (PRY) by potassium bromate which leads to the decrease of RF intensity of PRY were studied. The reduced value of RF intensity of reaction system (Delta F) is in proportional to the concentration of uranium (c), and a novel photo-catalytic RF method was developed for the determination of trace uranium (VI) after dCPE. The combination of photo catalytic RF techniques and dCPE procedure endows the presented methods with enhanced sensitivity and selectivity. Under optimal conditions, the linear calibration curves range for 0.067 to 6.57 ng mL(-1), the linear regression equation was Delta F = 438.0 c (ng mL(-1)) + 175.6 with the correlation coefficient r = 0.9981. The limit of detection was 0.066 ng mL(-1). The proposed method was successfully applied for the separation and determination of uranium in real samples with the recoveries of 95.0-103.5%. The mechanisms of the indicator reaction and dCPE are discussed. (C) 2016 Elsevier B.V. All rights reserved.
摘要：
Exposure to trihalomethanes (THMs) and haloacetic acids (HAAs) has been individually associated with adverse male reproductive effects; however, their joint male reproductive toxicity is largely unknown. This study aimed to explore the joint effects of THMs and trichloroacetic acid (TCAA) on semen quality in a Chinese population. A total of 337 men presenting to the Reproductive Center of Tongjing Hospital, in Wuhan, China to seek semen analysis were included this study. Baseline blood THMs [chloroform (TCM), bromodichloromethane (BDCM), dibromochioromethane (DBCM), and bromoform (TBM)] and urinary TCAA were analyzed and dichotomized at their median levels. The joint effects of THMs and TCAA on below-reference semen quality parameters were evaluated by calculating the relative excess risk due to interaction (RERI). After adjusting for potential confounders, we found a suggestive synergistic effect between Br-THMs (sum of BDCM, DBCM, and TBM) and TCAA for below-reference sperm count (RERI = 2.14, 95% CI:-0.37, 4.91) (P = 0.076); men with high Br-THMs and TCAA levels (above the median) had 3.31 times (95% CI: 1.21, 9.07) elevated risk of having below-reference sperm count than men with low Br-THMs and TCAA levels (below the median). No apparent joint effects were observed between THMs and TCAA for other semen quality parameters. Our results suggest that co-exposure to Br-THMs and TCAA is associated with additive effects on decreased semen quality. However, further studies in a larger sample size and mechanistic studies are needed to confirm the findings. (C) 2016 Elsevier Ltd. All rights reserved.
