Synthesis of Pyrroles and Condensed Pyrroles as Anti-Inflammatory Agents with Multiple Activities and Their Molecular Docking Study

We herein disclose a series of novel pyrrole derivatives as well as fused pyrrolopyridines 6a,b and 7a,b, pyrrolopyrazoles 8a, b, pyrrolo[2,3-d]pyrimidine derivatives 10a-d, 12a,b, 14a,b, 18a,b, 20a,b, 21a,b, 22a,b, 23a,b, 24a,b, 31a,b, 36a,b, 40a,b, pyrrolo[1,2,6]thiadiazine derivatives 19a,b, pyrrolotriazolopyrimidines 25a,b, 26a,b, 27a,b and 28a,b, pyrrolo[2,3-d][1,2,3]triazine derivatives 32a,b and pyrrolo[2,3-d][1,3]oxazine derivatives 39a,b as novel compounds. All compounds were evaluated for their anti-inflammatory, analgesic (compared to the reference drug Indomethacin) and antimicrobial activities (compared to the reference drug Ampicillin and Fluconazole). Compounds 4d, 5b-d, 6a,b, 9c,d, 10d, 12ab, 13b, 19a,b, 21b, 23b, 31a,b, 38b and 40a were found to be the most active anti-inflammatory drugs exhibiting potency ranging from 1 - 1.01 compared to the reference drug indomethacin. In addition to docking study of these highly active twenty compounds against the active site of cyclooxygenase-2 enzyme (COX-2), among the tested compounds, compounds 5d, 9d, 11b, 12a, 13b and 32a showed multiple activities;anti-inflammatory, analgesic and anti-bacterial activities.

New innovation of moisturizers containing non-steroidal anti-inflammatory agents for atopic dermatitis

Atopic dermatitis is a chronic, relapsing and extremely pruritic eczematous disease which commonly affects children. The standard management consists of a combination of anti-inflammatory drugs in adjunctive with skin care management particular moisturizer application. A concern for the side effects associated with long term use of corticosteroids has also been considered. There has been an emerging interest in moisturizer containing non-steroidal anti-inflammatory agents such as herbal extracts, vitamins, mineral and lipids. The in vitro and the in vivo studies of each agent were reviewed. The clinical study on the efficacy of moisturizers containing these agents were also demonstrated including the author's studies and clinicalexperience. These moisturizers might be considered as an alternative treatment in acute flare of mild to moderate atopic dermatitis.

Intelligent Agent Based Mapping of Software Requirement Specification to Design Model

Automatically mapping a requirement specification to design model in Software Engineering is an open complex problem. Existing methods use a complex manual process that use the knowledge from the requirement specification/modeling and the design, and try to find a good match between them. The key task done by designers is to convert a natural language based requirement specification (or corresponding UML based representation) into a predominantly computer language based design model—thus the process is very complex as there is a very large gap between our natural language and computer language. Moreover, this is not just a simple language conversion, but rather a complex knowledge conversion that can lead to meaningful design implementation. In this paper, we describe an automated method to map Requirement Model to Design Model and thus automate/partially automate the Structured Design (SD) process. We believe, this is the first logical step in mapping a more complex requirement specification to design model. We call it IRTDM (Intelligent Agent based requirement model to design model mapping). The main theme of IRTDM is to use some AI (Artificial Intelligence) based algorithms, semantic representation using Ontology or Predicate Logic, design structures using some well known design framework and Machine Learning algorithms for learning over time. Semantics help convert natural language based requirement specification (and associated UML representation) into high level design model followed by mapping to design structures. AI method can also be used to convert high level design structures into lower level design which then can be refined further by some manual and/or semi automated process. We emphasize that automation is one of the key ways to minimize the software cost, and is very important for all, especially, for the “Design for the Bottom 90% People” or BOP (Base of the Pyramid People).

Optimizing Grey Wolf Optimization: A Novel Agents’ Positions Updating Technique for Enhanced Efficiency and Performance

Grey Wolf Optimization (GWO) is a nature-inspired metaheuristic algorithm that has gained popularity for solving optimization problems. In GWO, the success of the algorithm heavily relies on the efficient updating of the agents’ positions relative to the leader wolves. In this paper, we provide a brief overview of the Grey Wolf Optimization technique and its significance in solving complex optimization problems. Building upon the foundation of GWO, we introduce a novel technique for updating agents’ positions, which aims to enhance the algorithm’s effectiveness and efficiency. To evaluate the performance of our proposed approach, we conduct comprehensive experiments and compare the results with the original Grey Wolf Optimization technique. Our comparative analysis demonstrates that the proposed technique achieves superior optimization outcomes. These findings underscore the potential of our approach in addressing optimization challenges effectively and efficiently, making it a valuable contribution to the field of optimization algorithms.

Long-Term Fate of Agent Orange and Dioxin TCDD Contaminated Soils and Sediments in Vietnam Hotspots

The soils, tropical climate, and network of canals and rivers of southern Vietnam have created one of the most diverse tropical jungles and intensely cultivated landscapes of Southeast Asia. This paradise has a long history of numerous wars, foreign occupations, and most recently the Second Indochina War (aka the Vietnam War 1965-1972) which defoliated rain forests and ancient wetland mangroves and left behind contaminated soil and sediment hotspots. During this war, the United States (US) military sprayed 80 million liters of Agent Orange contaminated with the dioxin TCDD in a guerrilla war against communist insurgents. Agent Orange was a synthetic plant growth regulator comprised of equal amounts of two herbicides 2,4-dichloro phenoxyacetic acid C8H6Cl2O3 (2,4-D) and 2,4,5-trichlorophenoxyacetic acid C8H5Cl3O3 (2,4,5-T). TCDD, the dioxin, 2,3,7,8-tetrachlorodibenzodioxin (C12H4Cl4O2) was an unintended byproduct of the accelerated combustion process used in the manufacture of herbicides containing 2,4,5-T. Agent Orange has frequently been blamed for soil and sediment contamination and long-term human health problems;however, the true source of harm is the dioxin TCDD. Agent Orange has a short half-life of days and weeks after application to vegetation, and has not been found to persist, after 50 years, in the water or soils of southern Vietnam. However, the half-life of dioxin TCDD depends on where it is deposited and varies from 1 to 3 years on soil surfaces that have been fully exposed to sunlight, to as long as 20 to 50 years or more when buried in tropical subsoils, and more than 100 years in river and sea sediments. Dioxin TCDD was heavily concentrated in the US Air Force bases in Vietnam where the herbicides were stored, loaded on planes and helicopters for aerial spraying, and used extensively around military base perimeter fences as a security measure to prevent surprise attacks. Bien Hoa Air Force base, 40 km northeast of Ho Chi Minh City, continues to be one of the mega-hotspots where after 48 years the dioxin TCDD levels in fish and shrimp are still high and fishing is banned in ponds and lakes adjacent to the airbase. Although expensive, one of the most effective remediation to dioxin TCDD contaminated soils is incineration which is the recommended method of dioxin TCDD disposal.

时序Agent程序设计语言TAOPLID的离线解释器

AOPLID是一种面向agent程序设计语言。本文旨在对AOPLID语言进行时序扩充,使之能表达并处理带时间参数的并发行动,基于离线方式下AOPLID程序的语义,用Prolog语言实现时序AOPLID语言(TAOPLID)的离线解释器。首先,我们对经典情境演算进行适当改造,使之能描述含时间变元的行动,因为持续行动一般可认为是具有瞬时开始行动和瞬时终止行动的过程,所以可以将一个持续动作分解为两个时间上互不相交的瞬时动作,再引入一个新的关系流刻画这两个瞬时动作的执行情况,从而可在扩充后的情境演算中表达带时间参数的并发行动。其次,为使TAOPLID离线解释器方便处理以集合方式表示的TAOPLID程序,设计并实现了TAOPLID预处理器,它将TAO-PLID程序的集合形式转换成Prolog子句形式,然后通过TAPOLID离线解释器对其解释生成一可执行的原子行动序列。

按需装配Agent系统的构件安全机制研究

按需装配Agent是一种能够在运行过程中根据系统当时的需求,动态地加载相应功能构件,更好地完成任务的Agent。构件是按需装配Agent的重要组成部分。它的安全性将直接影响到Agent的自身安全性、其任务结果的正确性以及对被访问的主机的安全性,也成为按需装配Agent系统安全的重要问题。笔者在研究按需装配Agent的概念和系统模型的基础上,提出了影响构件安全的主要环节:构件在传输环节安全和构件在主机中驻留环节安全;利用IDEA算法、RSA算法和MD5算法的各自特性,使用组合链式加密算法,设计了Agent构件的安全机制,有效地解决了按需装配Agent系统的构件的安全性问题。

Parasitoid wasps as effective biological control agents

Biological control(biocontrol) is a safe, sustainable approach that takes advantage of natural enemies such as predators, parasitic insects or pathogens to manage pests in agroecosystems. Parasitoid wasps, a very large evolutionary group of hymenopteran insects, are well-known biological control agents for arthropod pests in agricultural and forest ecosystems. Here, we summarize the recent progress on the application of parasitoid wasps in biocontrol in China for the last five years. These include species diversity of parasitoid wasps, identification of dominant parasitoid wasps associated with insect pests and biocontrol practices(three types of biological control, i.e., classical, augmentative and conservation biological control) in several Chinese agroecosystems. We then treat different mass-rearing and release technologies and the commercialization of several parasitoid wasp species. We also summarize other work that may have a potential use in biocontrol, including the effect of plant volatiles on parasitoids and recent advance in the molecular mechanisms underlying the host regulation by parasitoid wasps. Future research area and applied perspectives are also discussed, noting that advances in biocontrol technologies in Chinese agriculture informs research at the global level.

A Device to Improve Collaborative Practices of Sanitation Department Agents of a Territory: The Case of the Lamkansa District in Casablanca

The aim of this article is to strengthen and improve the collaboration between professional agents of a service that manages one of the technical processes acting on a given territory by synchronizing the spatio-temporal dimensions including all agents assembled for the task. This proposal was tested in the Lamkansa neighborhood in Casablanca, Morocco. The employed approach is based GIS resources and on systemic analysis of communication present in a territory. We were inspired by several methodological developments that carried multi-actor processes in land use planning. We focused our work on strengthening the collaboration between professionals, field agents and office agents, in the process of design and monitoring the liquid sanitation system. The device is based on geolocation and synchronous feedback of topological, geographical, and multimedia data related to the liquid sanitation network. Thanks to a geo-collaborative, participative, and motivating logic, we reduced the management costs of the network and made it faster and more efficient by equally mobilizing another type of non-specialized actors (the inhabitants). This device uses spatial and temporal dimensions to consolidate collaborative work tools through ICT and GIS technologies that thematize and exchange information collected in the field. Furthermore, this device raises great interest as it entails the concept of integration of several actors in a geo-collaborative mode while combining geomatics with communication and information sciences.

Effects of Water-retaining Agents on Growth, Development, Yield and Quality of Soybean under Drought Stress

[Objectives]The paper was to explore the effects of different doses of water-retaining agent on the growth and development indicators,yield and quality of soybean plants subjected to drought stress.[Methods]The effects of drought stress(MDS)and drought stress with low(MDS-L),medium(MDS-M)and high doses(MDS-H)of the water-retaining agent on the growth and development indicators,root activity,MDA content,antioxidant enzyme activity,yield and quality of soybean were studied by field plot test,with the normal water supply serving as the control(CK).[Results]In response to drought stress,the plant height,stem diameter,and yield of soybean exhibited a notable decline.Additionally,the contents of protein,fat,linoleic acid,and linolenic acid in seeds demonstrated a significant reduction.Conversely,the root activity and antioxidant enzyme activity exhibited a noticeable decline,while the MDA content exhibited an increase.The application of varying doses of the water-retaining agent was found to significantly enhance soybean growth,stimulate root activity,and elevate antioxidant enzyme activity,while concurrently reducing MDA content.The observed effects were found to be dose-dependent,with the greatest effects observed at the highest dose.In comparison to MDS,the yields of soybean in the MDS-L,MDS-M,and MDS-H treatments exhibited a 18.38%,25.58%,and 46.26%increase,respectively.Additionally,the content of protein,fat,linoleic acid,and linolenic acid in seeds demonstrated a notable enhancement.[Conclusions]The application of the water-retaining agent has been demonstrated to significantly promote the growth of soybean plants under conditions of drought stress,resulting in an improvement in both the yield and the quality of the soybean crop.The recommended dosage of the water-retaining agent is 3.3 kg/667 m 2.

Causality Is Logically Definable—Toward an Equilibrium-Based Computing Paradigm of Quantum Agent and Quantum Intelligence (QAQI) (Survey and Research)

A survey on agents, causality and intelligence is presented and an equilibrium-based computing paradigm of quantum agents and quantum intelligence (QAQI) is proposed. In the survey, Aristotle’s causality principle and its historical extensions by David Hume, Bertrand Russell, Lotfi Zadeh, Donald Rubin, Judea Pearl, Niels Bohr, Albert Einstein, David Bohm, and the causal set initiative are reviewed;bipolar dynamic logic (BDL) is introduced as a causal logic for bipolar inductive and deductive reasoning;bipolar quantum linear algebra (BQLA) is introdused as a causal algebra for quantum agent interaction and formation. Despite the widely held view that causality is undefinable with regularity, it is shown that equilibrium-based bipolar causality is logically definable using BDL and BQLA for causal inference in physical, social, biological, mental, and philosophical terms. This finding leads to the paradigm of QAQI where agents are modeled as quantum enssembles;intelligence is revealed as quantum intelligence. It is shown that the enssemble formation, mutation and interaction of agents can be described as direct or indirect results of quantum causality. Some fundamental laws of causation are presented for quantum agent entanglement and quantum intelligence. Applicability is illustrated;major challenges are identified in equilibriumbased causal inference and quantum data mining.

Intelligent Agent Technologies: The Work Horse of ERP E-Commerce

Agents are the new defacto standard for inclusion in modules of today’s software systems such as ERP systems, mobile applications and operating systems. Agents are an integral part of today’s software design. The question is how do intelligent agents work in the specific area of ERP credit card processing e-commerce models? To answer this question, a specific area of ERP systems will be analyzed: credit card processing for merchants. One specific merchant credit card processor will be specifically investigated: EVO Merchants. This paper will research how exactly does ERP systems interact using Application Programing Interface or “API” specified by a credit card clearing house. Secure Socket Layers or SSL, and XML are discussed and elaborated on specifically how intelligent agents play such a pivotal role in ERP e-commerce systems for credit card processing.

Determination of Fragmentation Schemes and Metabolites of Fluorinated Histone Deacetylase Inhibitors for Use as Positron Emission Tomography Imaging Agents Using HPLC-MS/MS

High performance liquid chromatography coupled with tandem mass spectrometry was developed and validated as a method for the analysis of fluorinated histone deacetylase inhibitors (F-HDACi), and then employed to study their metabolism in biosystems. Four HDACi analogs labeled with the positron emission nuclide 18F constitute a group of potential positron emission tomography imaging agents, which were developed by the Institute of Nuclear Energy Research (INER) and coded as INER-1577 #1, #2, #3, and #4 during animal studies for the diagnosis of dementia. The performance of the method was found to be suitable for the determination of analog #3, and it was employed to determine the structures and fragmentation mechanisms of all four analogs and to study the biotransformations of analogs #3 and #4. The results indicated that the method used for the determination of analog #3 was suitable for determining the abundance of the analogs in chemical and biochemical tests with high precision, accuracy, reproducibility, and recovery. Weaknesses in the chemical bonding of the analogs were found to involve the fluoro, dimethylamino, and benzamide groups in a fragmentation mechanism deduced via tandem mass spectrometry. The metabolites of analogs #3 and #4 in rat liver microsomes and rat plasma were also identified to clarify their characteristic behaviors in biosystems. The major product of analogs #3 in liver microsomes was produced by hydroxylation of the benzylic carbon atom, but in rat plasma the metabolites of analog #3 were produced by hydrolysis of the benzamide group to give a diaminobiphenyl compound with the simultaneous replacement of a fluorine atom by a hydroxyl group. The metabolites of analog #4 in liver microsomes were produced by hydroxylation of the benzylic carbon atom and hydrolysis of the benzamide bond. The results of the studies characterized the chemical and biochemical behaviors of the series F-HADCi analogs.

基于FIPA-Agent的变电站故障诊断系统研究

通过引入Multi-Agent系统,提出了一个完全符合FIPA标准的基于多Agent的变电站故障诊断系统体系,该体系参与的Agent包括:系统管理Agent、服务管理Agent、界面管理Agent、故障监测Agent、故障诊断Agent和故障决策Agent。在此基础上,提出了基于JADE中间件的变电站故障诊断MAS系统实现模型,最后给出了一个基于模糊融合的多Agent的变压器故障诊断实例,仿真结果表明该模型的合理性和可行性。

General anesthetic agents induce neurotoxicity through oligodendrocytes in the developing brain

General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells.Oligodendrocytes perform essential roles in the central nervous system,including myelin sheath formation,axonal metabolism,and neuroplasticity regulation.They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation,differentiation,and apoptosis.Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes.These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways,but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function.In this review,we summarize the effects of general anesthetic agents on oligodendrocytes.We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.

Increasing Incidence of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae (ESBL) and the Relation to Consumption of Broad-Spectrum Antimicrobial Agents 2003-2011 in a Large Area of Copenhagen, Denmark

Purpose: To investigate 1) the development in the incidence of ESBL-producing bacteria in hospitals and primary health care, 2) the contribution of primary health care to the incidence of ESBL-producing bacteria, and 3) the development in resistance patterns for all Escherichia coli and Klebsiella pneumoniae isolates in relation to antimicrobial consumption in hospitals and primary health care. Methods: ESBL-data were retrospectively collected from bacterial isolates from all specimens received at the Department of Clinical Microbiology from 2003 to 2011 together with the corresponding patient data. ESBL-production was detected in isolates from 1067 of 59,373 patients (1.8%) with an E. coli infection and in 263 of 8660 patients (3.0%) with a K. pneumoniae infection. Results: From 2003 to 2009, an increase in patients with an ESBL-producing isolate occurred in both hospitals and primary health care at the same time as an increased consumption of broad-spectrum antimicrobial agents was seen. Interventions to reduce prescription of cephalosporins and ciprofloxacin at the hospitals from 2010 resulted in a remarkable decrease in patients with ESBL-producing K. pneumoniae whereas a continuing increase was seen in patients with ESBL-producing E. coli both at hospitals and in primary health care. The proportion of patients with community-acquired ESBL-producing E. coli was stable with an increase of only 1.4% from 2007 to 2011. Conclusions: Reduction in prescription of broad-spectrum antimicrobial agents at the hospital level had an important impact on the incidence of ESBL-producing K. pneumoniae, but not on ESBL-producing E. coli.

Pharmacological Adjuvants to Limit Erythropoietin Stimulating Agents Exposure

Anemia in chronic kidney disease (CKD) is common, causing morbidity and mortality, and is primarily due to reduced erythropoietin (EPO) release and, to a lesser degree, shortened red cell survival. Erythropoietin Stimulating Agents like epoetin Alfa and darbepoetin alpha are used commonly to treat this form of anemia. Recent evidence suggests increased morbidity and mortality associated with higher hemoglobin in the setting of these agents use. Whether these complications are due to higher dose of erythropoietin or its resistance (i.e. inflammation), or achieving a higher hemoglobin remains unclear. Tightening restrictions on these agents has led to increase interest in the use of non-ESA adjuvants to improve erythropoiesis. This review will highlight the most promising of these agents.

Agent技术在Web数据仓库结构中的应用研究

针对基于Web的数据仓库体系结构存在的问题,在该体系结构中引入软件Agent技术,运用移动Agent技术来解决传统方法难以解决的一些主要问题,提出了一种基于Agent的Web数据仓库系统体系结构。文中发挥数据仓库技术和Web技术结合的优势,重点研究了Agent技术在Web服务器端的应用,在把有用的Web数据集成并入到数据仓库中这一目前的研究热点问题中,提出了基于Agent技术将HTML页面转化为XML数据源的解决方案。此外,文章分别研究了应用服务器端和数据仓库系统中的Agent技术的应用,并提出了将Agent技术引入后实现基于Web的数据仓库体系的关键技术。

Sustained virologic response to direct-acting antiviral agents predicts better outcomes in hepatitis C virus-infected patients: A retrospective study

BACKGROUND Direct-acting antiviral agents(DAAs)are extremely effective in eradicating hepatitis C virus(HCV)in chronically infected patients.However,the protective role of the sustained virologic response(SVR)achieved by second-and thirdgeneration DAAs against the onset of hepatocellular carcinoma(HCC)and mortality is less well established.AIM To examine the occurrence of HCC or death from any cause in a retrospectiveprospective study of patients treated with DAAs.METHODS Patients were enrolled from a tertiary academic hospital center for liver disease management that collects subject data mainly from northeastern Italy.The study was conducted in 380 patients(age:60±13 years,224 males,32%with cirrhosis)treated with DAAs with or without SVR(95/5%),with a median follow up of 58 wk(interquartile range:38-117).The baseline anthropometric features,HCV viral load,severity of liver disease,presence of extra-hepatic complications,coinfection with HIV and/or HBV,alcohol consumption,previous interferon use,alphafetoprotein levels,and renal function were considered to be confounders.RESULTS The incidence rate of HCC in patients with and without SVR was 1.3 and 59 per 100 person-years,respectively(incidence rate ratio:44,95%CI:15-136,P<0.001).Considering the combined endpoint of HCC or death from any cause,the hazard ratio(HR)for the SVR patients was 0.070(95%CI:0.025-0.194,P<0.001).Other independent predictors of HCC or death were low HCV viremia(HR:0.808,P=0.030),low platelet count(HR:0.910,P=0.041),and presence of mixed cryoglobulinemia(HR:3.460,P=0.044).Considering SVR in a multi-state model,the independent predictors of SVR achievement were absence of cirrhosis(HR:0.521,P<0.001)and high platelet count(HR:1.019,P=0.026).Mixed cryoglobulinemia predicted the combined endpoint in patients with and without SVR(HR:5.982,P=0.028 and HR:5.633,P=0.047,respectively).CONCLUSION DAA treatment is effective in inducing SVR and protecting against HCC or death.A residual risk of HCC persists in patients with advanced liver disease or with complications,such as mixed cryoglobulinemia or renal failure.

Anti-inflammatory Effect of Polysaccharide from Embelia parviflora Wall.on Rheumatoid Arthritis in Rats

[Objectives]To investigate the anti-inflammatory effect of Embelia parviflora Wall.polysaccharide on rheumatoid arthritis(RA)in rats.[Methods]RA rat model was induced by type II collagen.After successful modeling,the rats were divided into model group,positive group,low,medium and high dose of E.parviflora Wall.polysaccharide groups,and normal control group.Body mass,toe volume and arthritis index were measured,and thymus index and spleen index were calculated.The levels of interleukin-1β,interleukin-6 and tumor necrosis factor-αin serum and synovial tissue of ankle joint were detected by ELISA.[Results]Compared with the normal control group,the pathological changes such as synovial hyperplasia and unclear layer were observed in the model group,the body mass was decreased(P<0.05),the toe volume,arthritis index,thymus and spleen index were increased(P<0.05),and the levels of IL-1β,IL-6 and TNF-αin serum and ankle synovial tissue were increased(P<0.05).Compared with the model group,the histopathological changes in synovium of ankle joint in the positive group and the medium and high dose groups of E.parviflora Wall.polysaccharide were significantly improved,and the body mass was increased(P<0.05).The toe volume,arthritis index,thymus index and spleen index were decreased(P<0.05).The levels of IL-Iβ,IL-6 and TNF-αin serum and synovial tissue of ankle joint were increased(P<0.05),while there was no significant difference between the low dose group of E.parviflora Wall.polysaccharide and the model group(P>0.05).[Conclusions]E.parviflora Wall.polysaccharide can reduce the body's inflammatory response and improve RA,which may be related to the inhibition of the activation of inflammatory cytokines IL-1β,IL-6 and TNF-α.