Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia

Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

The mechanism and relevant mediators associated with neuronal apoptosis and potential therapeutic targets in subarachnoid hemorrhage

Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro ns,which subsequently promotes a series of pathophysiological responses leading to neuronal death.Many previous experimental studies have reported that excitotoxicity,mitochondrial death pathways,the release of free radicals,protein misfolding,apoptosis,nec rosis,autophagy,and inflammation are involved solely or in combination in this disorder.Among them,irreversible neuronal apoptosis plays a key role in both short-and long-term prognoses after SAH.Neuronal apoptosis occurs through multiple pathways including extrinsic,mitochondrial,endoplasmic reticulum,p53 and oxidative stress.Meanwhile,a large number of blood contents enter the subarachnoid space after SAH,and the secondary metabolites,including oxygenated hemoglo bin and heme,further aggravate the destruction of the blood-brain barrier and vasogenic and cytotoxic brain edema,causing early brain injury and delayed cerebral ischemia,and ultimately increasing neuronal apoptosis.Even there is no clear and effective therapeutic strategy for SAH thus far,but by understanding apoptosis,we might excavate new ideas and approaches,as targeting the upstream and downstream molecules of apoptosis-related pathways shows promise in the treatment of SAH.In this review,we summarize the existing evidence on molecules and related drugs or molecules involved in the apoptotic pathway after SAH,which provides a possible target or new strategy for the treatment of SAH.

Pyrrole and Pyrimidine Derivatives as Possible Electron Donors for Colored Charge-Transfer Complexes with a Weakly Electrophilic Energetic Material,FOX-7:A Theoretical Study

A number of electron-rich heterocycles are studied as potential reagents for visual colorimetric detection of FOX-7 due to colored charge-transfer complexes formation.The obtained results suggest that pyrrole and pyrimidine derivatives can form such complexes playing the role of electron donors despite a low electrophilicity of FOX-7.Density functional theory calculations,as well as quantum theory of atoms in molecules analysis,suggest stacking binding mode as the most preferable one with the binding energy of about 21-36 kJ/mol.All the complexes demonstrate a clear single charge-transfer absorption band in the visible region and the expected colors of the complexes are varying from violet and blue to red and orange.The calculations of the crystalline state of the studied complexes indicate high lattice energies,which are higher than that of pure FOX-7 and are close to the recently reported hydrogen-bonded complex of FOX-7 with 1,10-phenanthroline.Additional analysis of the studied charge-transfer complexes using properties based on density difference grids clearly suggests the acceptor role of FOX-7 in the complexes.This analysis can be effectively applied to identify the nature of other possible complexes of FOX-7,in which its role is unclear because of the specific reactivity,namely,both weak electrophilic and nucleophilic properties at the same time.

Intraoperative Blood Pressure Lability Acts as a Key Mediator in the Impacts of Goal-Directed Fluid Therapy on Postoperative Complications in Patients Undergoing Major Spine Surgery

Objective Although goal-directed fluid therapy(GDFT)has been proven to be effective in reducing the incidence of postoperative complications,the underlying mechanisms remain unknown.The aim of this study was to examine the mediating role of intraoperative hemodynamic lability in the association between GDFT and the incidence of postoperative complications.We further tested the role of this mediation effect using mean arterial pressure,a hemodynamic indicator.Methods This secondary analysis used the dataset of a completed nonrandomized controlled study to investigate the effect of GDFT on the incidence of postoperative complications in patients undergoing posterior spine arthrodesis.We used a simple mediation model to test whether there was a mediation effect of average real variability between the association of GDFT and postoperative complications.We conducted mediation analysis using the mediation package in R(version 3.1.2),based on 5,000 bootstrapped samples,adjusting for covariates.Results Among the 300 patients in the study,40%(120/300)developed postoperative complications within 30 days.GDFT was associated with fewer 30-day postoperative complications after adjustment for confounders(odds ratio:0.460,95%CI:0.278,0.761;P=0.003).The total effect of GDFT on postoperative complications was-0.18(95%CI:-0.28,-0.07;P<0.01).The average causal mediation effect was-0.08(95%CI:-0.15,-0.04;P<0.01).The average direct effect was-0.09(95%CI:-0.20,0.03;P=0.17).The proportion mediated was 49.9%(95%CI:18.3%,140.0%).Conclusions The intraoperative blood pressure lability mediates the relationship between GDFT and the incidence of postoperative complications.Future research is needed to clarify whether actively reducing intraoperative blood pressure lability can prevent postoperative complications.

Association and potential mediators between socioeconomic status and childhood obesity in China:findings from a national cohort study

Objective:Socioeconomic status(SES)is associated with childhood obesity,but the underlying factors remain unknown.This study aimed to identify mediators that may explain SES disparities in childhood obesity in China.Methods:Nationally representative longitudinal data from the China Education Panel Survey of 11 o019 children(13.03±0.79)collected from 2013-2014 to 2016-2017 academic years.Overweight/obesity was defined using Chinese national body mass index cut-points.Principal component analysis was used to convert the four SES indicators(maternal and paternal education,and occupation)into one comprehensive variable.Mediation analysis for SES disparities in childhood obesity was conducted using structure equation models.Results:The prevalence of overweight/obesity was 12.8%,and was higher in boys than in girls(17.8%vs.7.6%,P<0.001)at baseline.Among boys,relative risk(RR)of obesity was 1.23(95%CI:1.09 to 1.40,P<O.001)for per unit change in SES.There was no significant association between obesity and SES among girls.Mediation analyses showed that among boys,birth weight,being the only child in the family and children's selfperceived weight status mediated 70.0%of the effects of SES on obesity.No mediation effect was detected in girls.Conclusions:Chinese boys are more likely to be overweight or obese than girls.SES may impact childhood obesity through birth weight,being the only child in the family and children's self-perceived body weight status in boys,but not in girls.More attention should be made to address childhood obesity in high SES families among boys.Interventions targeting at these mediators are needed.

Charge-Transfer and SERS Coupling on TiO2

We report the SERS enhancements of Raman forbidden surface modes of TiO2 in different sized TiO2 crystals. This current study utilizes the relationship between the vibronic coupling and the degree of charge-transfer to explain the differences of Surface Enhanced Raman Scattering (SERS) enhancements. Our study shows a direct correlation between the degree of charge-transfer and vibronic coupling. This relationship suggests that charge-transfer between the N-719 dye and TiO2 due to vibronic coupling plays a fundamental role in SERS enhancements. Furthermore, this study shows a strong dependence of the enhancements of the N-719 dye molecular modes to that of the surface modes. This indicates that the mechanism that governs the enhancements of the surface modes in TiO2 crystals most likely also dictates the enhancements of the N-719 dyes.

Linear paired electrolysis of furfural to furoic acid at both anode and cathode in a multiple redox mediated system

Implementing a new energy-saving electrochemical synthesis system with high commercial value is a strategy of the sustainable development for upgrading the bulk chemicals preparation technology in the future.Here,we report a multiple redox-mediated linear paired electrolysis system,combining the hydrogen peroxide mediated cathode process with the I2 mediated anode process,and realize the conversion of furfural to furoic acid in both side of the dividedflow cell simultaneously.By reasonably controlling the cathode potential,the undesired water splitting reaction and furfural reduction side reactions are avoided.Under the galvanostatic electrolysis,the two-mediated electrode processes have good compatibility,which reduce the energy consumption by about 22%while improving the electronic efficiency by about 125%.This system provides a green electrochemical synthesis route with commercial prospects.

Resilience provides mediating effect of resilience between fear of progression and sleep quality in patients with hematological malignancies

BACKGROUND Hematological tumors are common malignant tumors,with high morbidity and mortality rates.Most patients with hematological malignancies develop sleep disorders that seriously affect their life and health because of acute onset of disease,rapid progression,high recurrence rates,complex treatment methods,and treatment costs.AIM To explore the mediating effect of resilience on fear of disease progression and sleep quality in patients with hematological malignancies.METHODS A cross-sectional analysis of 100 patients with hematological malignancies,treated in the First Affiliated Hospital of Jinzhou Medical University between August 2022 and August 2023,was conducted.Patients were assessed using a general data survey,a simplified scale for the fear of progression(FoP)of disease,a resilience scale,and the Pittsburgh Sleep Quality Index.Statistical analysis was conducted to determine the relationship between various patient characteristics and FoP,resilience,and sleep quality.Spearman’s correlation analysis was used to examine the correlations between mental resilience,FoP,and sleep quality.RESULTS The total FoP score mean value in patients with hematological malignancies was 38.09±5.16;the total resilience score mean value was 40.73±7.04;and the Pittsburgh Sleep Quality Index score mean value was 10.72±1.90.FoP,resilience,and sleep quality of the patients were associated with family per capita monthly income and patient education level(P<0.05).Spearman correlation analysis revealed that FoP was negatively correlated with resilience and sleep quality scores(r=-0.560,-0.537,P<0.01),respectively,and resilience was significantly associated with sleep quality scores(r=0.688,P<0.01).Mediation analysis showed that the mediating effect of resilience between FoP and sleep quality in patients with hematological malignancies was-0.100 and accounted for 50.51%of the total effect.This indicated that FoP directly and indirectly affected sleep quality through the mesomeric effect of resilience.CONCLUSION Resilience is an intermediary variable between FoP and sleep quality in patients with hematological malignancies.Medical staff should evaluate and follow-up FoP and resilience to implement measures to improve sleep quality.

Mediating role of social support in dysphoria,despondency,and quality of life in patients undergoing maintenance hemodialysis

BACKGROUND Dysphoria and despondency are prevalent psychological issues in patients undergoing Maintenance Hemodialysis(MHD)that significantly affect their quality of life(QOL).High levels of social support can significantly improve the physical and mental well-being of patients undergoing MHD.Currently,there is limited research on how social support mediates the relationship between dysphoria,despondency,and overall QOL in patients undergoing MHD.It is imperative to investigate this mediating effect to mitigate dysphoria and despondency in patients undergoing MHD,ultimately enhancing their overall QOL.AIM To investigate the mediating role of social support in relationships between dysphoria,despondency,and QOL among patients undergoing MHD.METHODS Participants comprised 289 patients undergoing MHD,who were selected using a random sampling approach.The Social Support Rating Scale,Self-Rating Anxiety Scale,Self-Rating Depression Scale,and QOL Scale were administered.Correlation analysis was performed to examine the associations between social support,dysphoria,despondency,and QOL in patients undergoing MHD.To assess the mediating impact of social support on dysphoria,despondency,and QOL in patients undergoing MHD,a bootstrap method was applied.RESULTS Significant correlations among social support,dysphoria,despondency,and quality in patients undergoing MHD were observed(all P<0.01).Dysphoria and despondency negatively correlated with social support and QOL(P<0.01).Dysphoria and despondency had negative predictive impacts on the QOL of patients undergoing MHD(P<0.05).The direct effect of dysphoria on QOL was statistically significant(P<0.05).Social support mediated the relationship between dysphoria and QOL,and this mediating effect was significant(P<0.05).Similarly,the direct effect of despondency on QOL was significant(P<0.05).Moreover,social support played a mediating role between despondency and QOL,with a significant mediating effect(P<0.05).CONCLUSION These findings suggest that social support plays a significant mediating role in the relationship between dysphoria,despondency,and QOL in patients undergoing MHD.

基于Mediator的Web Services无回溯反向链动态合成

提出了一个基于Mediator的Webservices无回溯反向链动态合成框架,在该框架下提供了一种产生式建模方法和一种用于消除合成语义冲突的参数级本体,然后使用一种无回溯反向链算法进行合成.该合成方法避免了对合成方案的优化,它的参数级本体在合成语义处理上也比前向链合成中的属性级本体的效率高,特别适合于对同样的用户输入和Webservices进行多次合成以生成相同的或者不同的输出.

基于Mediator/Wrapper信息集成的查询优化研究

在对Mediator/Wrapper集成系统及其查询特点进行详细分析的基础上,针对涉及多个数据源的连接查询是使用频率较高且是查询代价最高的一种查询方式这一事实,确定了以全局连接查询为主要优化对象,并提出了用半连接方法来优化连接查询。在对半连接执行方案进行优化时,提出了半连接加权有向图的概念,并给出了针对半连接加权有向图的半连接执行方案的快速有效的优化算法。

棉铃虫天敌中红侧沟茧蜂Microplitis mediator对不同处理棉花的趋性行为反应

采用机械损伤(处理A)、棉铃虫取食为害(处理B)、棉铃虫取食棉花+棉铃虫复合物(处理B+H)、水杨酸诱导(处理C)、机械损伤加棉铃虫口腔分泌物(处理D)5种方式诱导现蕾期棉花植株,并应用Y型嗅觉仪测定处理后棉花对棉铃虫天敌中红侧沟茧蜂搜索寄主行为的影响.处理B、处理B+H和处理C棉花对中红侧沟茧蜂有显著的引诱作用.健康棉株、处理A及处理D棉花对中红侧沟茧蜂没有明显的吸引.中红侧沟茧蜂对处理C、处理B+H以及处理B棉花没有明显的趋性差异.利用气质联用系统对各处理棉花挥发性物质进行定性和定量分析.表明处理B、处理B+H、处理C棉花挥发物种类和含量均比对照棉花多,处理A及处理D棉花与对照棉花挥发物种类和含量差异不显著.处理C、处理B及处理B+H棉花中β-月桂烯、β-蒎烯、α-蒎烯的含量明显增加.处理C棉花柠檬烯的含量发生明显变化.

基于Mediator/Wrapper的VMI系统的研究

供应商管理库存(VMI)是一种新的供应链库存管理方法,通过应用VMI,可以提高企业的运作水平,降低供应商和生产商、零售商的成本。然而,在电子商务环境下,供应商与生产商或零售商是多对多的关系,VMI系统的数据间的通信变得十分庞大复杂,信息的管理也变得很困难。为此,本文提出使用Java和XML开发基于Mediator/Wrapper的VMI系统,通过Mediator构建一个以客户应用层、中介器层和数据源层三层VMI系统,使用XML作为中介器层的数据的标准以及客户应用层和中介器层的接口,并提供统一的描述数据的结构的框架,以便在Web上部署,同时Wrapper可以解决多个供应商和零售商之间的信息异构问题。

一种基于Mediator模式的角色实现方法

介绍一种基于Mediator模式的角色实现方法及其原型实现(Rava)。讨论了角色和面向方面程序设计(Aspect-Oriented Programming,AOP)中Aspect的异同点以及使用Rava实现动态AOP的方法,从而在实现层统一了角色和Aspect两个概念。

基于混合本体和Mediator/Wrapper的语义数据集成模型

分析数据集成中的语义异构问题和已有数据集成方法,提出一种基于混合本体和Mediator/Wrapper的语义数据集成模型,将数据元素作为领域数据概念标准引入到全局本体的构建中,并给出全局本体自动构建算法.设计并实现模型原型系统,系统运行结果证明,该模型能够有效地解决数据集成的语义异构问题,并可为各个领域的语义数据集成提供参考.

一种基于XML/Mediator的安全电子商务应用

使用Java Servlet和CORBA技术开发的基于XML／Mediator的安全电子商务,中介器作为组成客户应用程序和数据源之间的中间层,成功地应用于分布式信息系统,在基于Web的信息系统中,XML被用来为中介器开发自描述数据模型及提供通用接口.应用表明:采用中介器、XML技术使得系统具有易开发、易维护、易改进等优点.

基于Mediator平台的CAD与PDM集成

研究并验证了一种CAD与PDM集成的系统架构——Mediator平台。该平台采用星型拓扑结构,直接连接各个软件节点,为异构软件提供了统一的交互接口。该集成方式可提高系统的扩展性和稳定性,并将集成工作量降到最小。Mediator平台的可行性通过异构CAD几何共性和PDM数据交互共性进行论证,据此设计了基于XML的Mediator系统架构,并给出系统实例来验证这种集成方式的有效性。

B2B市场中基于Mediator调节的双边协商模型

随着电子商务的发展,基于Agent的智能协商得到广泛的关注。由于协商方不愿透漏更多的信息,传统交替式提议的协商方法容易陷于僵局,这需要中间方Mediator参与调节。针对B2B市场,提出了一种基于Mediator调节的双边协商模型。在该模型中,买卖双方同时向Mediator提交封闭提议以最大化本方效益,而Mediator根据调节策略确定每回合的让步度,以及最终的成交价和成交量。仿真实验验证了该模型在获得联合效益和维护公平方面是有效的。

基于Mediator模式的参数控制法

人机交互语言工具是电信网管的重要组成部分,是网管系统中使用频率最高的模块之一,命令参数的显示控制是它的实现难点.基于Mediator模式的参数控制法分离了参数表示和逻辑控制,它让每个参数专心处理自身表示,由中介者控制显示逻辑,解除了参数间的耦合关系.这种实现方法,集中了对参数的控制,减少了耦合,有利于各参数的复用,易于逻辑关系扩展,提高了命令解析效率.实际测试表明,在PIII 1.0 G CPU环境下,解析一条命令的平均时间只需0.14 s.该方法为开发网管人机交互语言工具或处理对象强耦合问题提供了一种有参考价值的实现方法.

Mediator模型的SystemC代码自动生成

Mediator是一种基于组件的建模语言,该语言主要通过自动机和系统对模型进行描述。将Mediator语言描述的模型自动生成为可执行代码,可以避免编码过程中由于人为疏忽而造成的错误,从而提高编码的可靠性,同时缩短模型开发周期。介绍一种从Mediator模型到SystemC代码的自动生成工具,该工具旨在将基于特定平台的模型转换为能直接仿真运行的代码。首先对Mediator语言的语法语义进行分析,选择合适的SystemC代码组织形式,然后针对Mediator模型的每一个组成部分设计生成规则,其中重点对类型生成、状态转移语句生成、同步语句的生成进行分析。最后,通过一个机器掉电检测系统说明该工具运行结果的正确性。