In vitro and in vivo effects of 3-bromopyruvate against Echinococcus metacestodes

International audienceAbstractWhile searching for novel anti-echinococcosis drugs, we have been focusing on glycolysis which is relied on by Echinococcus for energy production and intermediates for other metabolic processes. The aim of this study was to investigate the potential therapeutic implication of glycolytic inhibitors on Echinococcus. Our results demonstrate that at an initial concentration of 40 μM, all inhibitors of glycolysis used in the current experiment [3-bromopyruvate (3-BrPA), ornidazole, clorsulon (CLS), sodium oxamate and 2,6-dihydroxynaphthalene (NA-P2)] show considerable in vitro effects against Echinococcus granulosus protoscoleces and Echinococcus multilocularis metacestodes. Among them, 3-BrPA exhibited the highest activity which was similar to that of nitazoxanide (NTZ) and more efficacious than albendazole (ABZ). The activity of 3-BrPA was dose dependent and resulted in severe ultrastructural destructions, as visualized by electron microscopy. An additional in vivo study in mice infected with E. multilocularis metacestodes indicates a reduction in parasite weight after the twice-weekly treatment of 25 mg/kg 3-BrPA for 6 weeks, compared to that of the untreated control. In particular, in contrast to ABZ, the administration of 25 mg/kg 3-BrPA did not cause toxicity to the liver and kidney in mice. Similarly, at the effective dose against Echinococcus larvae, 3-BrPA showed no significant toxicity to human hepatocytes. Taken together, the results suggest that interfering with the glycolysis of the parasite may be a novel chemotherapeutical option and 3-BrPA, which exhibited a remarkable activity against Echinococcus, may be a promising potential drug against cystic echinococcosis (CE) and alveolar echinococcosis (AE)

Variability-driven module selection with joint design time optimization and post-silicon tuning

Abstract—Increasing delay and power variation are significant chal-lenges to the designers as technology scales to the deep sub-micron (DSM) regime. Traditional module selection techniques in high level synthesis use worst case delay/power information to perform the optimization, and therefore may be too pessimistic such that extra resources are used to guarantee design requirements. Parametric yield, which is defined as the probability of the synthesized hardware meeting the performance/power constraints, can be used to guide design space exploration. The para-metric yield can be effectively improved by combining both design-time variation-aware optimization and post silicon tuning techniques (such as adaptive body biasing (ABB)). In this paper, we propose a module selection algorithm that combines design-time optimization with post-silicon tuning (using ABB) to maximize design yield. A variation-aware module selection algorithm based on efficient performance and power yield gradient computation is developed. The post silicon optimization is formulated as an efficient sequential conic program to determine the optimal body bias distribution, which in turn affects design-time module selection. The experiment results show that significant yield can be achieved compared to traditional worst-case driven module selection technique. To the best of our knowledge, this is the first variability-driven high level synthesis technique that considers post-silicon tuning during design time optimization. 1 I

Phytoextraction potential of wetland plants for Copper in Water Bodies

Luo, Z., Yuan, X, Chen, X., & Cui, X. (March-April, 2017). Phytoextraction potential of wetland plants for Copper in Water Bodies. Water Technology and Sciences (in Spanish), 8(2), 43-50. Copper is the most common heavy metal contaminant in the environment. Wetland construction engineering and technology have been used to control water pollution due to their low cost and efficiency and the hydrophytes have been the most important constituents of wetland construction. In this experiment, during April of 2014, Cu2+ accumulation content in different parts of Acorus calamus and Phragmites australis were investigated based on hydroponic experiments of different Cu2+ concentration solutions. Cu2+ concentrations in the water body were 0, 10, 25, 60, 100, 200 and 500 mg/l, respectively. The results showed that there were significant Cu2+ concentration differences between the above- and below-ground parts of Acorus calamus and Phragmites australis. Cu2+ content in the above- and belowground parts of wetland plants increased with hydroponic solution Cu2+ concentrations, resulting in a significantly positive correlation between Cu2+ content and concentrations of hydroponic solutions. There was a significant difference in Cu2+ content in the wetland plants under all hydroponic solution Cu2+ concentrations. Acorus calamus exhibited the greatest Cu2+ accumulation in above- and below-ground parts. Acorus calamus and Phragmites australis can be selected for application on the phytoremediation of water polluted by heavy metals due to their excellent Cu2+ accumulation ability

Antimicrobial activity of <i>Laminaria japonica</i> extracts against bacterial canker of tomato disease agent <i>Clavibacter michiganensis</i> subsp. <i>michiganensis</i>

Laminaria japonica was extracted with ethanol, and tested for antimicrobial activity against Clavibacter michiganensis subsp. michiganensis (Cmm). This gram-positive bacterium is the agent of a serious tomato disease called bacterial canker. On in vitro antimicrobial assays, L. japonica extracts showed intensive antimicrobial activity to inhibit Cmm. Extracting parameters (time, temperature, and solid/liquid ratio) were investigated and further optimized integratedly with L27(313) orthogonal array design (OAD). Our data implied that the optimum extraction conditions were A3B3C3, that were extracting time 12 h, extracting temperature 80 °C, and solid/liquid ratio 1:30 (g:mL). Extracting temperature was the significant factor affecting extracting condition. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of L. japonica extracts against Cmm were 2.5 mg/mL and 5 mg/mL. Scanning electron microscopy (SEM) observation indicated L. japonica extracts caused considerable morphological alterations in Cmm cells, such as protoplast leakage, cell membrane disruption, cell clumped, and cell fragmented. Reactive oxygen species (ROS) level determination and ATPase activity assay revealed that L. japonica extracts did cause significant accumulation in ROS and reduce the intracellular ATPase activity rapidly. Accordingly, these results indicated that L. japonica extracts could open a new promising opportunity for this tomato disease control

Longitudinal in vivo Diffusion Tensor Imaging Detects Differential Microstructural Alterations in the Hippocampus of Chronic Social Defeat Stress-Susceptible and Resilient Mice

Background: Microstructural alterations in the hippocampus may underlie stress-related disorders and stress susceptibility. However, whether these alterations are pre-existing stress vulnerability biomarkers or accumulative results of chronic stress remain unclear. Moreover, examining the whole hippocampus as one unit and ignoring the possibility of a lateralized effect of stress may mask some stress effects and contribute to the heterogeneity of previous findings.Methods: After C57BL/6 mice were exposed to a 10-day chronic social defeat stress (CSDS) paradigm, different stress phenotypes, i.e., susceptible (n = 10) and resilient (n = 7) mice, were discriminated by the behavior of the mice in a social interaction test. With in vivo diffusion tensor imaging (DTI) scans that were conducted both before and after the stress paradigm, we evaluated diffusion properties in the left and right, dorsal (dHi) and ventral hippocampus (vHi) of experimental mice.Results: A significantly lower fractional anisotropy (FA) was found in the right vHi of the susceptible mice prior to the CSDS paradigm than that found in the resilient mice, suggesting that pre-existing microstructural abnormalities may result in stress susceptibility. However, no significant group differences were found in the post-stress FA values of any of the hippocampal regions of interest (ROIs). In addition, mean diffusivity (MD) and radial diffusivity (RD) values were found to be significantly greater only in the right dHi of the resilient group compared to those of the susceptible mice. Furthermore, a significant longitudinal decrease was only observed in the right dHi RD value of the susceptible mice. Moreover, the social interaction (SI) ratio was positively related to post-stress left MD, right dHi MD, and right dHi RD values and the longitudinal right dHi MD percent change. Meanwhile, a negative relationship was detected between the SI ratio and bilateral mean of the post-stress left relative to right vHi FA value, highlighting the important role of right hippocampus in stress-resilience phenotype.Conclusion: Our findings demonstrated different longitudinal microstructural alterations in the bilateral dHi and vHi between stress-susceptible and resilient subgroups and indicated a right-sided lateralized stress effect, which may be useful in the diagnosis and prevention of stress-related disorders as well as their intervention

Diverse and strain-specific metabolites patterns induced by fungal endophytes in grape cells of different varieties

The potential for endophytes to initiate changes in host secondary metabolism has been well documented. However, the mechanisms underlying endophyte-plant metabolic interactions are still poorly understood. Here, we analysed the effects of fungal endophytes on the metabolite profiles of grape cells from two cultivars: 'Cabernet Sauvignon' (CS) and 'Rose honey' (RH). Our results clearly showed that co-culture with endophytic fungi greatly modified the metabolic profiles in grape cells of both varieties. Treatments with endophytic fungal strains caused the numbers of detected metabolites to vary from 10 to 19 in CS cells and from 8 to 14 in RH cells. In addition, 5 metabolites were detected in all CS cell samples, while 4 metabolites were detected in all RH cell samples. Some endophytic fungal strains could even introduce novel metabolites into the co-cultured grape cells. The metabolic profiles of grape leaves shaped by endophytic fungi exhibited host selectivity and fungal strain specificity. In this assay, the fungal strains RH32 (Alternaria sp.) and MDR36 (Colletotrichum sp.) triggered an increased response of the detected metabolites, including the greatest increase in the metabolite contents in grape cells of both cultivars. No obvious effects in terms of metabolite numbers and contents in grape cells when co-cultured with fungal strains RH7 (Epicoccum sp.) and RH48 (Colletotrichum sp.) were observed. The results of this experiment suggest that endophytic fungi could be used to control the metabolic profiles of grapes and thus increase grape quality

Posttraumatic Stress Disorder Biomarker — p11

Post-traumatic stress disorder (PTSD) is a chronic and disabling anxiety disorder associated with a traumatic event [1]. It is linked to increased risk of suicide and deficits in social functioning [2, 3]. Despite extensive study in psychiatry, the underlying mechanisms of PTSD are still poorly understood [4, 5]. Currently, the diagnosis for PTSD is based on clinical observation and symptom checklist [4, 6-8] and no laboratory blood-based tests. Although biomarker discovery for PTSD is not easy [8], a reliable biomarker would significantly impact the diagnosis and therapeutic monitoring of PTSD. Developing interventions to identify and treat PTSD requires objective approaches to determining the presence of PTSD [8]. Substantial data indicate several potential biomarkers for PTSD. Of these candidate markers, p11 (S100A10) has been studied in PTSD animal models [7] and in human subjects with PTSD [6]. We found that p11 is over-expressed in both animal models and post-mortem brains of subjects with PTSD [7]. Incorporating testing of p11, a novel biomarker for PTSD, into clinical practice, along with more subjective measures, such as participants’ medical history, mental status, duration of symptoms, and symptom checklist or self-report, would provide additional power to predict impending PTSD. In this chapter, we discuss the biomarker concept and the potential clinical utility of PTSD biomarkers. We further discuss the potential of p11 as a PTSD biomarker and as a tool that may enhance PTSD diagnosis and intervention in health care practice

Epidemiological and etiological investigations of hand, foot, and mouth disease in Jiashan, northeastern Zhejiang Province, China, during 2016 to 2022

BackgroundHand, foot, and mouth disease (HFMD) is a common infectious disease in children. Enterovirus A71 (EV71) and coxsackievirus A16 (CA16) have been identified as the predominant pathogens for several decades. In recent years, coxsackievirus A6 (CA6) and coxsackievirus A10 (CA10) have played increasingly important roles in a series of HFMD outbreaks. We performed a retrospective analysis of the epidemiology of HFMD and the spectrum of different viral serotypes, to elucidate the genetic and phylogenetic characteristics of the main serotypes in the Jiashan area during 2016 to 2022.MethodsDescriptive epidemiological methods were used to analyze the time and population distribution of HFMD in Jiashan during 2016 to 2022 based on surveillance data. Molecular diagnostic methods were performed to identify the viral serotypes and etiological characteristics of HFMD. Phylogenetic analyses was based on VP1 region of CA16 and CA6.ResultsThe average annual incidence rate of HFMD fluctuated from 2016 to 2022. Children aged 1–5 years accounted for 81.65% of cases and boys were more frequently affected than girls. Except when HFMD was affected by the COVID-19 epidemic in 2020 and 2022, epidemics usually peak in June to July, followed by a small secondary peak from October to December and a decline in February. Urban areas had a high average incidence and rural areas had the lowest. Among 560 sample collected in Jiashan, 472 (84.29%) were positive for enterovirus. The most frequently identified serotypes were CA6 (296, 52.86%), CA16 (102, 18.21%), EV71 (16, 2.86%), CA10 (14, 2.50%) and other enteroviruses (44, 7.86%). There were 71 and 142 VP1 sequences from CA16 and CA6, respectively. Substitution of N218D, A220L and V251I was detected in CA16 and may have been related to viral infectivity. Phylogenetic analysis showed that CA16 could be assigned to two genogroups, B1a and B1b, while all the CA6 sequences belonged to the D3a genogroup.ConclusionCA6 and CA16 were the two major serotypes of enteroviruses circulating in the Jiashan area during 2016 to 2022. Continuous and comprehensive surveillance for HFMD is needed to better understand and evaluate the prevalence and evolution of the associated pathogens