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.

Heterostructured nickel-cobalt metal alloy and metal oxide nanoparticles as a polysulfide mediator for stable lithium-sulfur full batteries with lean electrolyte

Batteries that utilize low-cost elemental sulfur and light metallic lithium as electrodes have great potential in achieving high energy density.However,building a lithium-sulfur(Li-S)full battery by controlling the electrolyte volume generally produces low practical energy because of the limited electrochemical Li-S redox.Herein,the high energy/high performance of a Li-S full battery with practical sulfur loading and minimum electrolyte volume is reported.A unique hybrid architecture configured with Ni-Co metal alloy(NiCo)and metal oxide(NiCoO_(2))nanoparticles heterogeneously anchored in carbon nanotube-embedded selfstanding carbon matrix is fabricated as a host for sulfur.This work demonstrates the considerable improvement that the hybrid structure's high conductivity and satisfactory porosity promote the transport of electrons and lithium ions in Li-S batteries.Through experimental and theoretical validations,the function of NiCo and NiCoO_(2) nanoparticles as an efficient polysulfide mediator is established.These particles afford polysulfide anchoring and catalytic sites for Li-S redox reaction,thus improving the redox conversion reversibility.Even at high sulfur loading,the nanostructured Ni-Co metal alloy and metal oxide enable to have stable cycling performance under lean electrolyte conditions both in half-cell and full-cell batteries using a graphite anode.

Scarcity and Mental Health—Multiple Mediators of Sleep Quality and Life Satisfaction

Background:In the current social environment,scarcity,as a universally present objective state,profoundly impacts individuals’decision-making and health through the subjective feeling it induces,known as a“scarcity mindset.”Particularly,the feeling of scarcity related to money and sleep time is not only widespread but also directly linked to an individual’s mental health.Purpose:This study aims to delve into the relationship between the feeling of scarcity and mental health,with a specific focus on the relationship between the feeling of money scarcity or sleep time scarcity and mental health,as well as the role of sleep quality or life satisfaction in this relationship.Procedure:We determined the sampling quotas based on the population and economic development levels of each province in the“China Statistical Yearbook(2021)”(National Bureau of Statistics,2021).Participants were selected using the Probability Proportional to Size(PPS)sampling method.Data was collected by distributing online questionnaires to participants,and the relationships between the main variables were explored using structural equation modeling.Results:1.In China,the feeling of sleep time scarcity is stronger than the feeling of money scarcity among the public.2.The feeling of money scarcity is positively correlated with depression and anxiety,whereas the feeling of sleep time scarcity is only positively correlated with depression.3.The feeling of scarcity mainly leads to depression and self-denial through reducing life satisfaction,and it leads to anxiety through reducing sleep quality.Conclusion:The feeling of scarcity in money and sleep time is related to different dimensions of mental health.Therefore,reasonably planning financial allocation and ensuring an adequate amount of sleep can reduce the sense of scarcity,thereby improving mental health.Additionally,improving sleep quality and increasing life satisfaction can alleviate the adverse effects of scarcity on mental health.

Observation on Therapeutic Effect of Lotus Needle Cupping Therapy for Removing Blood Stasis in Zhuang Medicine on PHN and Its Influ-ence on Inflammatory Mediators

[Objectives]To observe the clinical effect of the lotus needle cupping therapy for removing blood stasis in Zhuang medicine in treating PHNand its influence on inflammatory factors.[Methods]96 patients with PHN were randomly divided into three groups:lotus nee-dle cupping therapy group,TCM surrounding acupuncture group and gabapentin group.Venous blood and acupoint blood were collected at 0,21 and 42 d of treatment,and the expression levels of 5-HT,SP and CGRPinflammatory mediators were detected before and after treatment.The changes of VAS scores before,during and after treatment and the clinical efficacy were observed.[Results]The total effective rate of the lotus needle cupping group was 87.50%,which was better than that of the TCM acupuncture group(81.25%)and the gabapentin group(62.50%);after treatment,the VAS scores and the expression of inflammatory mediators in the three groups of patients were lower than those before treatment,and the decrease was more significant in the treatment group(P<0.05).[Conclusions]The lotus needle cupping therapy for removing blood stasis in Zhuang medicine is effective in treating PHN,and its mechanism is to reduce the release of inflammatory media-tors,reduce hyperalgesia,relieve pain and improve the quality of life of patients.

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.

Development of High Areal Capacity Electrolytic MnO_(2)-Zn Battery via an Iodine Mediator

The commercialization of electrolytic MnO_(2)-Zn batteries is highly applauded owing to the advantages of cost-effectiveness,high safety,high energy density,and durable working performance.However,due to the low reversibility of the cathode MnO_(2)/Mn^(2+)chemistry at high areal capacities and the severe Zn anode corrosion,the practical application of MnO_(2)-Zn batteries is hampered by inadequate lifespan.Leveraging the full advantage of an iodine redox mediator,here we design a highly rechargeable electrolytic MnO_(2)-Zn battery with a high areal capacity.The MnO_(2)-Zn battery coupled with an iodine mediator in a mild electrolyte shows a high discharge voltage of 1.85 V and a robust areal capacity of 10 mAh cm^(-2)under a substantial discharge current density of 160 mA cm^(-2).The MnO_(2)/I_(2)-Zn battery with an areal capacity of 10 mAh cm^(-2)exhibits prolonged stability of over 950 cycles under a high-capacity retention of~94%.The scaled-up MnO_(2)/I_(2)-Zn battery reveals a stable cycle life under a cell capacity of~600 mAh.Moreover,our constructed MnO_(2)/I_(2)-Zn battery demonstrates a practical energy density of~37 Wh kg^(-1)and a competitive energy cost of<18 US$kWh^(-1)by taking into account the cathode,anode,and electrolyte.The MnO_(2)/I_(2)-Zn battery,with its remarkable reversibility and reasonable energy density,enlightens a new arena of large-scale energy storage devices.

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.

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.

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。

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。

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.

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。

Inflammatory mediators and microcirculatory disturbance in acute pancreatitis

BACKGROUND: Inflammatory mediators are not only initiation factors of acute pancreatitis (AP) but also key factors causing pancreatic hemorrhage and necrosis, which damage important organs such as the heart, brain, liver, kidney and lung. Microcirculatory disturbance in AP has attracted widespread attention. In order to provide a theoretical basis for clinical therapy of AP, it is very important to explore the effect of inflammatory mediators on microcirculatory disturbance in this disease. DATA SOURCES: In this review, the impact of inflammatory mediators on microcirculatory disturbance in AP was reviewed according to the literature, especially the articles indexed in PubMed and books published in China and reports from websites. RESULTS: At present, inflammatory mediation and microcirculatory disturbance are the two major hypotheses to explain the development of AP. Although experimental studies have shown that inflammatory mediators induce or aggravate microcirculatory disturbance, the clinical application of these findings is still difficult because the inflammatory mediators are diverse and their research is not comprehensive and thorough. CONCLUSION: It is very important to explore the influence of inflammatory mediators on microcirculatory disturbance in AP.

Effects of large dose of dexamethasone on inflammatory mediators and pancreatic cell apoptosis of rats with severe acute pancreatitis

AIM: To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP). METHODS: SAP rats were randomly assigned to the model group and treatment group while the normal rats were assigned to the sham operation group. The mortality,ascite volumes,ascites/body weight ratio and pancreas pathological changes of all rats were observed at 3,6 and 12 h after operation. Their contents of amylase and endotoxin in plasma and contents of tumor necrosis factor (TNF-α),phospholipase A2 (PLA2) and IL-6 in serum were also determined. The microarray sections of their pancreatic tissues were prepared,terminal transferase dUTP nick end labeling (TUNEL) staining was performed and apoptotic indexes were calculated. RESULTS: There was no marked difference between treatment group and model group in survival. The contents of amylase and endotoxin in plasma and contents of TNF-α,PLA2 and IL-6 in serum,ascite volumes,ascites/body weight ratio and pancreas pathological scores were all lower in treatment group than in model group to different extents at different time points P < 0.05,58.3 (26.4) ng/L vs 77.535 (42.157) ng/L in TNF-α content,8.00 (2.00) points vs 9.00 (2.00) points in pathological score of pancreas respectively; P < 0.01,0.042 (0.018) EU/mL vs 0.056 (0.0195) EU/mL in endotoxin content,7791 (1863) U/L vs 9195 (1298) U/L in plasma amylase content,1.53 (0.79) vs 2.38 (1.10) in ascites/body weight ratio,8.00 (1.00) points vs 11.00 (1.50) points in pathological score of pancreas; P < 0.001,3.36 (1.56) ng/L vs 5.65 (1.08) ng/L in IL-6 content,4.50 (2.00) vs 7.20 (2.00),4.20 (1.60) vs 6.40 (2.30),3.40 (2.70) vs 7.90 (1.70) in ascite volumes,respectively. The apoptotic indexes of pancreas head and pancreas tail were all higher in treatment group than in model group at 6 h P < 0.01,0.00 (2.00)% vs 0.00 (0.00)%,0.20 (1.80) vs 0.00 (0.00) in apoptosis indexes,respectively. CONCLUSION: The mechanism of dexamethasone treatment in acute pancreatitis is related to its inhibition of inflammatory mediator generation and induction of pancreatic acinar cell apoptosis.

Value of inflammatory mediator profiles and procalcitonin in predicting postoperative infection in patients with hypertensive cerebral hemorrhage

BACKGROUND Hypertensive cerebral hemorrhage(HICH)is a common clinical cerebrovascular disease and one of the most serious complications of hypertension.Early warning of the occurrence of infection during treatment and timely anti-infective treatment are of great significance for the early prevention and treatment of postoperative infection in patients with HICH.Changes in the levels of inflammatory mediators,which are closely related to the occurrence and development of postoperative infection,and procalcitonin(PCT),which is a sensitive indicator for diagnosing bacterial infections,are widely used in clinical practice.AIM To explore the application value of inflammatory mediator profiles and PCT in predicting postoperative infection in patients with HICH.METHODS A total of 271 patients who underwent HICH surgery at our hospital between March 2019 and March 2021 were selected and divided into the infection(n=80)and non-infection(n=191)groups according to whether postoperative infection occurred.The postoperative infection status and etiological characteristics of the infective pathogens in the infection group were analyzed.Changes in inflammatory mediator profile indices and PCT levels were compared between the two groups,pre-and postoperatively.RESULTS A total of 109 strains of pathogenic bacteria were detected in the infection group,including 67 strains(61.47%)of gram-negative bacteria,32 strains(29.36%)of gram-positive bacteria,and 10 strains(9.17%)of fungi.The main infection site of the patients in the infection group was the respiratory system(63.75%).Preoperative interleukin(IL)-4,IL-6,IL-10,tumor necrosis factor-α,interferon-γ,and PCT levels were higher in the infection group than in the non-infection group(P<0.05),and there were no significant differences in the IL-2 Levels between the two groups(P>0.05).The inflammatory mediator profile indices and PCT levels were higher in the two groups of patients on the first postoperative day than preoperatively(P<0.05),and were higher than those in the non-infection group(P<0.05).Logistic regression analysis showed that preoperative IL-6 and PCT levels correlated with postoperative infection(P<0.05).Operating characteristic curve analysis results showed that the area under the curve(AUC)values of preoperative IL-6 and PCT levels in predicting postoperative infection in patients with HICH were 0.755 and 0.824,respectively.The AUC value of joint detection was 0.866,which was significantly higher than that of the single index(P<0.05).CONCLUSION Preoperative IL-6 and PCT levels are correlated with postoperative infection in patients with HICH.Their detection is clinically significant for early identification of patients at high risk for postoperative infection.

Bone marrow-derived mesenchymal stem cell transplantation attenuates overexpression of inflammatory mediators in rat brain after cardiopulmonary resuscitation

Emerging evidence suggests that bone marrow-derived mesenchymal stem cell transplantation improves neurological function after cardiac arrest and cardiopulmonary resuscitation;however, the precise mechanisms remain unclear. This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cell treatment on expression profiles of multiple cytokines in the brain after cardiac arrest and cardiopulmonary resuscitation. Cardiac arrest was induced in rats by asphyxia and cardiopulmonary resuscitation was initiated 6 minutes after cardiac arrest. One hour after successful cardiopulmonary resuscitation, rats were injected with either phosphate-buffered saline(control) or 1 × 10~6 bone marrow-derived mesenchymal stem cells via the tail vein. Serum S100 B levels were measured by enzyme-linked immunosorbent assay and neurological deficit scores were evaluated to assess brain damage at 3 days after cardiopulmonary resuscitation. Serum S100 B levels were remarkably decreased and neurological deficit scores were obviously improved in the mesenchymal stem cell group compared with the phosphate-buffered saline group. Brains were isolated from the rats and expression levels of 90 proteins were determined using a RayBio Rat Antibody Array, to investigate the cytokine profiles. Brain levels of the inflammatory mediators tumor necrosis factor-α, interferon-γ, macrophage inflammatory protein-1α, macrophage inflammatory protein-2, macrophage inflammatory protein-3α, macrophage-derived chemokine, and matrix metalloproteinase-2 were decreased ≥ 1.5-fold, while levels of the anti-inflammatory factor interleukin-10 were increased ≥ 1.5-fold in the mesenchymal stem cell group compared with the control group. Donor mesenchymal stem cells were detected by immunofluorescence to determine their distribution in the damaged brain, and were primarily observed in the cerebral cortex. These results indicate that bone marrow-derived mesenchymal stem cell transplantation attenuates brain damage induced by cardiac arrest and cardiopulmonary resuscitation, possibly via regulation of inflammatory mediators. This experimental protocol was approved by the Institutional Animal Care and Use Committee of Fujian Medical University, China in January 2016(approval No. 2016079).