戊型肝炎病毒感染激活补体系统

为了探究补体系统与戊型肝炎病毒复制的相关性,分别在HEV感染的A549细胞和BALB/c小鼠中检测C3aR、CD55和CD59蛋白的表达.利用RT-qPCR定量检测细胞和组织中补体的表达,采用免疫组化法检测HEV感染BALB/c小鼠中补体CD59及C5b-9的表达,ELISA检测补体相关炎症因子的变化.HEV感染可以激活补体蛋白C3aR、C5b-9、CD55和CD59的表达,引起补体蛋白相关炎症因子IL-10表达水平下降,IL-12和TNF-α的表达水平的上升,从而导致机体的炎症反应,加剧组织损伤.HEV感染激活补体系统并参与早期的抗病毒反应,HEV感染对补体的持续激活导致炎症因子过度表达,加重机体损伤.     

A Novel PEGylated Liposome-Encapsulated SANT75 Suppresses Tumor Growth through Inhibiting Hedgehog Signaling Pathway

The Hedgehog (Hh) pathway inhibitors have shown great promise in cancer therapeutics. SANT75, a novel compound we previously designed to specially inhibit the Smoothened (SMO) protein in the Hh pathway, has greater inhibitory potency than many of commonly used Hh inhibitors. However, preclinical studies of SANT75 revealed water insolubility and acute toxicity. To overcome these limitations, we developed a liposomal formulation of SANT75 and investigated its antitumor efficacy in vitro and in vivo. We encapsulated SANT75 into PEGylated liposome and the mean particle size distribution and zeta-potential (ZP) of liposomes were optimized. Using the Shh-light2 cell and Gli-GFP or Flk-GFP transgenic reporter zebrafish, we confirmed that liposome-encapsulated SANT75 inhibited Hh activity with similar potency as the original SANT75. SANT75 encapsulated into liposome exerted strong tumor growth-inhibiting effects in vitro and in vivo. In addition, the liposomal SANT75 therapy efficiently improved the survival time of tumor-bearing mice without obvious systemic toxicity. The pathological morphology and immunohistochemistry staining revealed that liposomal SANT75 induced tumor cell apoptosis, inhibited tumor angiogenesis as assessed by CD31 and down-regulated the expression of Hh target protein Gli-1 in tumor tissues. Our findings suggest that liposomal formulated SANT75 has improved solubility and bioavailability and should be further developed as a drug candidate for treating tumors with abnormally high Hh activity.     

Germination,Viability and Clearance of Stachybotrys chartarum in the Lungs of Infant Rats

Observing that the conidia of Stachybotrys chartarum can germinate in the lung of infant rats, it became important to ascertain whether an infection can ensue. Viable conidia of S. chartarum were instilled into the lungs of 4 and 14 day-old rat pups. Germination was observed frequently in the lungs of 4 day-old but rarely in the 14 day-old pups. In the 4 day-old pups, pulmonary inflammation with hemorrhagic exudates was observed and resulted in about 15% mortality rate compared to 0% for the controls instilled with phosphate buffered saline. Acute neutrophilic inflammation and intense interstitial pneumonia with poorly formed granulomas observed three days following exposure were associated with fungal hyphae and conidia. The surviving experimental pups showed significantly slower weight gain for seven days. Dilution plating and quantitative PCR analysis were used to follow total fungal load in the rat pups lung homogenates. In the 4 day-old rat pups viable fungi decreased rapidly and were less than 1% by day seven. Similarly, fungal DNA decreased exponentially and was only 0.03% by fourteen days after exposure. However, 14 day-old rat pups showed neither the lethal effects of exposures to viable conidia of S. chartarum nor the slower weight gain, and the fungal load decreased even more rapidly. We conclude that S. chartarum conidia can initially germinate and form hyphae but even in the immature rat pups do not establish an effective infection, although a very limited persistence cannot be excluded.This revised version was published online in October 2005 with corrections to the Cover Date.     

Infant animal model of pulmonary mycotoxicosis induced by Stachybotrys chartarum

In recent years cases of often fatal pulmonary hemorrhage in infants have been associated with water damaged homes and the toxigenic fungusStachybotrys chartarum. The fungal spores contain mycotoxins which could be injurious to the rapidly developing lung. In order to understand the developmental pathophysiology of this disease we developed an infant rat model of stachybotrytoxicosis describing the effects of fungal spores on survival, growth, histopathology of the lung and respiration. Conidia ofS. chartarum were instilled intratracheally (1.0–8.0 × 10⁵/gm wt.) in 4-dold Sprague-Dawley rat pups. Two control groups received either sterile PBS or a suspension of spores extensively extracted with ethanol to remove toxins. Lethal dose response was determined (LD₅₀ = 2.7 × 10⁵ spores/gm wt.). All dead pups had extensively hemorrhagic lungs. Growth of surviving animals was impaired in a dose-dependent manner. Changes of pulmonary function parameters in rats treated with 1.1 × 10⁵ spores/g were consistent with an increased respiratory resistance. Histology of lungs revealed fresh hemorrhage, sparse hemosiderin-laden macrophages, and evidence of inflammation including thickened alveolar septa infiltrated by lymphocytes and mononuclear cells and intra-alveolar macrophages. Significant increases (p = 0.001) in numbers of macrophages (2-fold), lymphocytes (5-fold) and neutrophils (7-fold) were found in BAL fluid. Hemoglobin was elevated 2-fold (p = 0.004). Proinflammatory mediator IL-1β increased more than 6-fold and TNF-α30-fold (p = 0.001). Extracted spores had a minimal effect on all examined parameters in BAL fluid indicating that mycotoxins are primarily responsible for the hemorrhagic and inflammatory response. This revised version was published online in June 2006 with corrections to the Cover Date.     

Clinical Outcomes with Alternative Dosing Strategies for Piperacillin/Tazobactam: A Systematic Review and Meta-Analysis

Objectives

A better dosing strategy can improve clinical outcomes for patients. We sought to compare the extended or continuous infusion with conventional intermittent infusion of piperacillin/tazobactam, investigating which approach is better and worthy of recommendation for clinical use.

Methods

Articles were gathered from PubMed, Web of Science, ProQuest, Science Direct, Cochrane, two Chinese literature databases (CNKI, Wan Fang Data) and related ICAAC and ACCP conferences. Randomized controlled and observational studies that compared extended or continuous infusion with conventional intermittent infusion of piperacillin/tazobactam were identified from the databases above and analyzed. Two reviewers independently extracted and investigated the data. A meta-analysis was performed using Revman 5.2 software. The quality of each study was assessed. Sensitivity analysis and publication bias were evaluated.

Results

Five randomized controlled trials and nine observational studies were included in this study. All included studies had high quality and no publication bias was found. Compared to the conventional intermittent infusion approach, the extended or continuous infusion group had a significantly higher clinical cure rate (OR 1.88, 95% CI 1.29-2.73, P = 0.0009) and a lower mortality rate (OR 0.67, 95% CI 0.50-0.89, P = 0.005). No statistical difference was observed for bacteriologic cure (OR 1.40, 95% CI 0.82-2.37, P = 0.22) between the two dosing regimens. The sensitivity analysis showed the results were stable.

Conclusions

Our systematic review and meta-analysis suggested that the extended or continuous infusion strategy of piperacillin/tazobactam should be recommended for clinical use considering its higher clinical cure rate and lower mortality rate in comparison with conventional intermittent strategy. Data from this study could be extrapolated for other β-lactam antimicrobials. Therefore, this dosing strategy could be considered in clinical practice.     

Effects of different photoperiods on flower opening,flower closing and circadian expression of clock-related genes in Iris domestica and I. dichotoma

Journal of Plant Research - The circadian clock can entrain to forced light-dark cycles by adjusting the phases and periods of flower opening and closing in ephemeral flowers. The responses of...     

Identification and SAR of a new series of thieno[3,2-d]pyrimidines as Tpl2 kinase inhibitors

We report here the synthesis and SAR of a new series of thieno[3,2-d]pyrimidines as potent Tpl2 kinase inhibitors. The proposed binding mode suggests the potential flipped binding mode depending on the substitution. Biacore studies show evidence of binding of these molecules to the protein kinase. The kinome inhibition profile of these molecules suggests good selectivity.     

城市山地保护：美国俄亥俄州辛辛那提市案例研究

记录了辛辛那提市自成立以来的发展历史,包括那些成为城市及其居民的长期财政负担的资源开发型的土地利用模式和不理智的工程实践。强调了过去40年里该市为缓解坡地不稳定性而采取的步骤,并提出了其他一些该市可以采取的关于未来山地开发的更为积极的措施。还记录了山地信托基金会（Hillside Trust）的工作,该基金会是一个成立于1976年的非营利组织,旨在倡导慎重利用和保护辛辛那提地区的山地。     

不同龄阶梭梭根区土壤水分时空变化特征

土壤水是荒漠植被发育最主要的制约因子。不仅影响植物的生长和发育,还限制着植被的种类、数量和分布。梭梭作为北方荒漠区重要的固沙植物,研究梭梭林地土壤水分动态对其植被生存或恢复以及群落稳定性维持具有重要意义。鉴于少有学者研究过不同龄阶梭梭根区的土壤含水率差异,于2014年2月至2014年11月,采用中子仪法和烘干法对0—400 cm沙层土壤含水率进行了原位观测,分析了不同龄阶梭梭根区土壤水分的时空变化规律。结果表明:(1)梭梭根区土壤水分时间变化可分为4个阶段:2月下旬—3月下旬是土壤水分快速补给期,4月上旬—5月下旬是土壤水分均衡期,6月上旬—10月下旬是土壤水分耗损期,11月上旬—次年2月中旬是土壤水分稳定期;(2)梭梭根区0—50 cm土层,受降雨、融雪水入渗补给和蒸发的影响较大,土壤水分变异系数较大且随深度增加迅速减小,50 cm以下土层变异系数较小且随深度变化微小;(3)不同龄阶梭梭根区剖面平均土壤含水率全年与春、夏、秋季均表现为:枯树成熟梭梭中龄梭梭裸地;(4)随距梭梭树干距离的增大(0—5 m范围内),土壤含水率整体呈减小趋势;降雨前后,梭梭根区浅层(0—10 cm)土壤含水率增量大于裸地土壤含水率增量。