Synthesis and biological evaluation of N-Alkylamide derivatives as anti-tumor agents

Background:N-Alkylamides(NAAs),derived from Anacyclus pyrethrum(L.)DC,have potential anti-tumor effects.To explore the molecular mechanism and chemo-preventive capacity of NAAs,we synthesized an NAA(H-10)and evaluated whether it could inhibit the proliferation of B16,HepG2,HeLa,and HCT116 cancer cells in 2D culture.Methods:To evaluate the antiproliferative activity of H-10 in 2D and 3D culture of BD,HepG2,HeLa,and HCT116 cells,multicellular tumor spheroids were constructed to more accurately reflect the cell tumor environment.To visualize nuclear changes related to apoptosis,Hoechst 33258 staining and propidium iodide-Annexin V double staining were performed.Results:Compound H-10 strongly inhibited the growth of all tested cell lines.Hoechst 33258 staining and propidium iodide-Annexin V double staining revealed that H-10 did not cause morphological alterations in the nuclei and moderately induced late apoptosis only when treated at 180 mM.The strongest inhibitory effect was observed in HCT116 cells.Flow cytometry analysis indicated that treatment of HCT116 cells with compound H-10 resulted in robust cell growth arrest in G2 phase in 2D and 3D cell culture;in 3D-cultured HCT116 cells,growth arrest occurred in G1 phase.Treatment with compound H-10 also significantly suppressed angiogenesis of chick chorioallantoic membrane in vivo.Conclusion:Treatment with compound H-10 strongly affected clonogenic survival(in the long-term)and migration of HCT116 cells.Therefore,H-10,a compound of NAAs may be useful for treating cancer because of its anti-neoplastic effect and easy synthesis.

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.

General anesthetic agents induce neurotoxicity through astrocytes

Neuroscientists have recognized the importance of astrocytes in regulating neurological function and their influence on the release of glial transmitters.Few studies,however,have focused on the effects of general anesthetic agents on neuroglia or astrocytes.Astrocytes can also be an important target of general anesthetic agents as they exert not only sedative,analgesic,and amnesic effects but also mediate general anesthetic-induced neurotoxicity and postoperative cognitive dysfunction.Here,we analyzed recent advances in understanding the mechanism of general anesthetic agents on astrocytes,and found that exposure to general anesthetic agents will destroy the morphology and proliferation of astrocytes,in addition to acting on the receptors on their surface,which not only affect Ca^(2+)signaling,inhibit the release of brain-derived neurotrophic factor and lactate from astrocytes,but are even involved in the regulation of the pro-and anti-inflammatory processes of astrocytes.These would obviously affect the communication between astrocytes as well as between astrocytes and neighboring neurons,other neuroglia,and vascular cells.In this review,we summarize how general anesthetic agents act on neurons via astrocytes,and explore potential mechanisms of action of general anesthetic agents on the nervous system.We hope that this review will provide a new direction for mitigating the neurotoxicity of general anesthetic agents.

Improvement Mechanism of Adhesion Performance of Anti-stripping Agents and Coupling Agents on Asphalt-Aggregate Interface Based on Molecular Dynamics

This study examined the mechanisms for improving the adhesion performance of the asphalt-aggregate interface with two anti-stripping agents and two coupling agents.The investigation of contact behavior between various asphalt-aggregate surfaces was conducted using molecular dynamics(MD)simulations.The interaction energy and the relative concentration distribution were employed as the parameters to analyze the enhancement mechanisms of anti-stripping agents and coupling agents on the asphalt-aggregate interface.Results indicated that the adhesion at the asphalt-aggregate interface could be strengthened by both anti-stripping agents and coupling agents.Anti-stripping agents primarily improve adhesion through the reinforcement of electrostatic attraction,while coupling agents primarily upgrade adhesion by strengthening the van der Waals.Hence,the molecular dynamics modeling and calculation techniques presented in this study can be utilized to elucidate the development mechanism of the asphalt-aggregate interface through the use of anti-stripping agents and coupling agents.

Progress in the Use of Glucocorticoids and Biological Agents in Non-Infectious Uveitis

One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing promise in the management of this condition. The description of glucocorticoid and biologic usage in non-infectious uveitis is the main topic of this paper.

Near-Infrared Fluorescence Imaging Contrast Agents for Clinical Research: Limitations and Alternatives

Introduction: Near-infrared fluorescence imaging is a technique that will establish itself in the short term at the international level because it is recognized for its potential to improve the performance of surgical interventions, its moderate investment and operating costs and its portability. Although the technology is now mature, there is currently the problem of the availability of contrast agents to be injected IV. The aim of this methodology article is to propose an alternative solution to the need for contrast agents for clinical research, particularly in oncology. Methodology: They consist of coupling a fluorescent marker in the form of an NHS derivative, such as IR DYE manufactured in compliance with GMP, with therapeutic monoclonal antibodies having marketing authorization for molecular imaging. For a given antibody, the marking procedure must be the subject of a validation file on the final preparation filtered on a sterilizing membrane at 0.22 μm. Once the procedure has been validated, it would be unnecessary to repeat the tests before each clinical research examination. A check of the marking by thin-layer chromatography (TLC) and place it in a sample bank at +4˚C for 1 month of each injected formulation would be sufficient for additional tests if necessary. Conclusion: Molecular near-infrared fluorescence imaging is experiencing development, the process of which could be accelerated by greater availability of clinical contrast agents. Alternative solutions are therefore necessary to promote clinical research in this area. These methods must be shared to make it easier for researchers.

Pharmacological effects of bioactive agents in earthworm extract:A comprehensive review

This review compiles information from the literature on the chemical composition,pharmacological effects,and molecular mechanisms of earthworm extract(EE)and suggests possibilities for clinical translation of EE.We also consider future trends and concerns in this domain.We summarize the bioactive components of EE,including G-90,lysenin,lumbrokinase,antimicrobial peptides,earthworm serine protease(ESP),and polyphenols,and detail the antitumor,antithrombotic,antiviral,antibacterial,anti-i nflammatory,analgesic,antioxidant,wound-healing,antifibrotic,and hypoglycemic activities and mechanisms of action of EE based on existing in vitro and in vivo studies.We further propose the potential of EE for clinical translation in anticancer and lipid-modifying therapies,and its promise as source of a novel agent for wound healing and resistance to antibiotic tolerance.The earthworm enzyme lumbrokinase embodies highly effective anticoagulant and thrombolytic properties and has the advantage of not causing bleeding phenomena due to hyperfibrinolysis.Its antifibrotic properties can reduce the excessive accumulation of extracellular matrix.The glycolipoprotein extract G-90 can effectively scavenge reactive oxygen groups and protect cellular tissues from oxidative damage.Earthworms have evolved a well-developed defense mechanism to fight against microbial infections,and the bioactive agents in EE have shown good antibacterial,fungal,and viral properties in in vitro and in vivo experiments and can alleviate inflammatory responses caused by infections,effectively reducing pain.Recent studies have also highlighted the role of EE in lowering blood glucose.EE shows high medicinal value and is expected to be a source of many bioactive compounds.

Effects of virtual agents on interaction efficiency and environmental immersion in MR environments

Background Physical entity interactions in mixed reality(MR)environments aim to harness human capabilities in manipulating physical objects,thereby enhancing virtual environment(VEs)functionality.In MR,a common strategy is to use virtual agents as substitutes for physical entities,balancing interaction efficiency with environmental immersion.However,the impact of virtual agent size and form on interaction performance remains unclear.Methods Two experiments were conducted to explore how virtual agent size and form affect interaction performance,immersion,and preference in MR environments.The first experiment assessed five virtual agent sizes(25%,50%,75%,100%,and 125%of physical size).The second experiment tested four types of frames(no frame,consistent frame,half frame,and surrounding frame)across all agent sizes.Participants,utilizing a head mounted display,performed tasks involving moving cups,typing words,and using a mouse.They completed questionnaires assessing aspects such as the virtual environment effects,interaction effects,collision concerns,and preferences.Results Results from the first experiment revealed that agents matching physical object size produced the best overall performance.The second experiment demonstrated that consistent framing notably enhances interaction accuracy and speed but reduces immersion.To balance efficiency and immersion,frameless agents matching physical object sizes were deemed optimal.Conclusions Virtual agents matching physical entity sizes enhance user experience and interaction performance.Conversely,familiar frames from 2D interfaces detrimentally affect interaction and immersion in virtual spaces.This study provides valuable insights for the future development of MR systems.

Travel Agents Around the World Praising the Trip to China

Foreign tourists'trips to China recently reached a new height,both online and offline.Travel agents around the world also made trips to China,generating more thoughts for the development of new routes and the design of innovative tourist products,and contributing to the development of China's inbound tourism.

Effectiveness of Chromated Copper Arsenate against Deteriorating Agents of Eucalyptus Poles and Posts in Four Eco-Regions in Kenya

Previous studies done elsewhere have shown that Eucalyptus poles treated with chromated copper arsenate (CCA) can last over 30 years. Kenya is exceptional because in some eco-regions, the Eucalyptus poles’ life span has greatly reduced to 5 years. The current study was designed to evaluate wood deteriorating agents of CCA-treated Eucalyptus poles and variability in four eco-regions of Kenya, namely, dryland, coastal, highland and humid lake. A total of 360 Eucalyptus pole samples were used for this experiment. Three CCA treatments were used to treat transmission poles at 20 kg/cm3 fencing posts samples at 6 kg/cm3, and a control group. Results indicated that termites and wood-decay fungi attacks caused wood deterioration in the four eco-regions. The proportion of power transmission pole degradation by wood deteriorating agents varied across eco-regions, between treatments and control and between time after treatments. Dryland eco-regions had the highest termite-related degradation (41.82%) while wood-decay fungi attack was highest in the highland eco-regions (9.20%). Samples treated with 6 kg/cm3 recorded the lowest level of wood deterioration, manifested by minimal superficial termite and wood-decay fungi attack. Samples treated with 20 kg/cm3 were characterized by moderate termite and wood-decay fungi attacks observed around the heartwood region, unlike sapwood. This study concluded that the deterioration of Eucalyptus CCA-treated poles is a question of climatic variability and hence, to increase the poles’ lifespan, CCA treatment should be tailored according to the characteristics of the ecoregion of use. Further investigations will inform the diversity of termites and decay-fungi across different eco-regions.

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.

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.

Factors Influencing Compliance with Safe Handling Requirements of Anticancer Agents by Nurses in a Tertiary Hospital-A Secondary Publication

Purpose:This research aimed to identify leading factors that affect nurses’compliance with the safe handling of anticancer agents.Methods:Data were collected from 114 nurses working in the university hospital and were analyzed through independent t-test,one-way ANOVA,Pearson’s correlation coefficient,and multiple regression analysis using SPSS25.0.Results:The average level of compliance with the safe handling of anticancer agents was 3.73±0.33 out of 5 points.Workplace safety culture(β=0.40,P<0.001)and knowledge of safe handling(β=0.18,P=0.030)had significant influences on nurses’compliance with the safe handling of anticancer agents.The explained variance for compliance was 28.3%.Conclusion:To enhance the implementation of safety management for anticancer agents,each institution should strive to support human and material resources and enhance specialization in the workplace safety culture through system improvement.Based on the results of this study,we suggest research for the development of a training program for anticancer agent safety management.

Anti-Cancer Agents Associated Diarrhea:Current Status and Prospects

Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is a common clinical adverse event,and despite the absence of specific anti-diarrhea drugs,there is a pressing need for improvement.This article aims to provide a valuable reference for researchers in clinical drug use and scientific tumor treatment.It summarizes recent advancements in drug mechanisms and adverse reactions,whether in preclinical research or clinical diagnosis and therapy.

Synthesis and in vitro biological evaluation of nitric oxide-releasing derivatives of hydroxylcinnamic acids as anti-tumor agents

Novel furoxan-based nitric oxide-releasing derivatives 6a-p of hydroxylcinnamic acids were synthesized by coupling the carboxyl group of hydroxylcinnamic acids with furoxan through various alkylol amines.Compounds 6a,e-i and m-p displayed more potent anti-tumor activities superior to control 5-fluorouracil（5-FU） in most cancer cells tested.Furthermore,6f could selectively inhibit tumor cells,but not non-tumor cell proliferation.This inhibition was attributed to high levels of NO released in cancer cells and potentially synergistic effect of NO donor moieties and the bioactivity of hydroxylcinnamic acids.

Synthesis and in vitro biological evaluation of novel 2-aminoimidazolone derivatives as anti-tumor agents

Novel 2-aminoimidazolone derivatives were synthesized.Most compounds displayed strong anticancer activities against human carcinoma cells in vitro.Compounds 8a,8b and 8j exhibited optimal activity superior to 5-FU in most cancer cells tested.Especially,the lC_（50）s of 8b（12.6-21.5μmol/L） against five tumor cells were 1 -4 fold less than those of 5-FU（18.4-56.1μmol/L） in vitro.Furthermore,comp以ound 8b could induce SMMC-7721 cell apoptosis in a dose-dependent manner.Therefore,our novel findings may provide a new framework for the design of new 2-aminoimidazolone derivatives for the treatment of cancer.

基于Agent人工智能的异构网络多重覆盖节点入侵检测系统设计

异构网络具有结构复杂、多重覆盖面积大等特征,使得网络入侵检测较为隐蔽,威胁网络运行的安全性;为此,对基于Agent人工智能的异构网络多重覆盖节点入侵检测系统进行了研究;通过检测Agent和通信Agent装设主机Agent,以Cisco Stealthwatch流量传感器作为异构网络传感器检测攻击行为,采用STM32L151RDT664位微控制器传输批量数据,由MAX3232芯片实现系统电平转化,实现硬件系统设计;软件部分设计入侵检测标准,采用传感器设备捕获网络实时数据,通过Agent技术解析异构网络协议并提取数据运行特征,综合考虑协议解析结果及与检测标准匹配度,实现异构网络多重覆盖节点入侵检测;经实验测试表明,基于Agent人工智能的异构网络多重覆盖节点入侵检测系统入侵行为的漏检率和入侵类型误检率的平均值仅为6%和5%,能够有效提高检测精度,减小检测误差。

流程型生产安全数据流的多Agent节点协同分流优化方法

为实现流程型生产安全监测系统的及时、准确决策,结合数据流采集与隐患识别过程,分析非关键数据的冗余、关键数据的缺失和数据计算时延较大的问题,提出基于多Agent的流程型生产安全数据流网络分流调度规划方法和节点流量划分识别机制。研究结果表明:相较于分簇传输方法,数据流网络分流调度方法可以实现关键隐患数据更高的传输成功率;相较于常规的复杂事件处理方法,本文提出的流量划分识别机制在2种类型数据集上实现隐患事件识别均有更低的计算时延。研究结果可为流程行业安全生产数字化管控模式和数据高质量获取提供参考。

基于AI agent的6G内生智能技术框架及其应用

未来6G网络将内生支持通信和AI一体化服务,赋能丰富多彩的新业务,支撑社会高效可持续发展。为此,借鉴了IT行业AI Agent的应用范式,基于电信应用场景创新地提出了6G AI Agent技术框架的三大设计理念,包括多模型融合、定制化Agent和插件式环境交互,并基于该理念构建了6G AI Agent技术框架。通过环境交互层、Agent引擎层、模型调度层、模型基座层交互协同,实现了自主环境感知、自主任务生成和自主执行任务的能力。此外,以移动网络的智能感知任务为例,探索了AI Agent的使用场景及价值,为AI新技术在电信领域发展提供了新的思路和技术支撑。

基于免疫Agent的电力电缆线路故障检测系统

为区别故障信号、非故障信号,实现对电缆线路故障的准确检测,设计了基于免疫Agent的电力电缆线路故障检测系统。利用前端检测电路为故障分析模块、测距方式切换模块提供电量传输信号,完成系统前端检测装置的连接。按照免疫Agent检测原理提取电力电缆线路故障信号的特征,联合已获取信号对象,求解检测插值指标的具体数值。结合各级硬件设备结构,完成系统设计。实验结果表明,该系统可同时检测波频为10~20 Hz、40~50 Hz、60~70 Hz的故障信号与波频为20~30 Hz、30~40 Hz、50~60 Hz的非故障信号,可以在精准辨别故障与非故障信号的同时,实现对电力电缆线路故障的准确检测。