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.

Synthesis and stability evaluation of 5-FU-acetic podophyllic ester as anti-tumor agent

Aim To study a new anti-cancer drug 5-FU-acetic podophyllic ester derivatized from podophyllotoxin. Methods A novel derivative of podophyllotoxin was synthesized. Its inhibitory effects against P-388, A-549, Bel-7402 and HL-60 in vitro were tested. The stability tests under different kinds of conditions were carried out. Results The novel derivative showed stronger inhibitory activities against P-388, A-549 and Bel-7402 in vitro than VP-16. The novel derivative was found to be stable at 60 ℃ and 4500 1x light in solid-state, but was less stable in humid condition. It was more stable in methanol （4 ℃ ） and chloroform （25 ℃ ） than in methanol （25 ℃）, and less stable in artificial gastric juice （ AGJ, 37 ℃ ）. Its stabilities were decreased while increasing the pH of buffer solutions. Conclusion These results could provide useful information for further study of this compound.

Aging-induced memory loss due to decreased N1-acetyl-5-methoxykynuramine,a melatonin metabolite,in the hippocampus:a potential prophylactic agent for dementia

Melatonin(N-acetyl-5-methoxytryptamine)is known as the hormone of darkness because it is synthesized at night and involved in regulating the circadian clock.The hormone is primarily synthesized by the vertebrate pineal gland,but is ubiquitous among invertebrates,unicellular organisms,plants,and even cyanobacteria(Hattori and Suzuki,2024).Melatonin is well-conserved evolutionarily and possesses several physiological functions,such as immune response,bone and glucose metabolism,and memory formation besides regulating the circadian rhythm.

A functional cathode sodium compensation agent for stable sodium-ion batteries

Hard carbon(HC)is widely used in sodium-ion batteries(SIBs),but its performance has always been limited by lowinitial Coulombic efficiency(ICE)and cycling stability.Cathode compensation agent is a favorable strategy to make up for the loss of active sodium ions consumed byHCanode.Yet it lacks agent that effectively decomposes to increase the active sodium ions as well as regulate carbon defects for decreasing the irreversible sodium ions consumption.Here,we propose 1,2-dihydroxybenzene Na salt(NaDB)as a cathode compensation agent with high specific capacity(347.9 mAh g^(-1)),lower desodiation potential(2.4–2.8 V)and high utilization(99%).Meanwhile,its byproduct could functionalize HC with more C=O groups and promote its reversible capacity.Consequently,the presodiation hard carbon(pHC)anode exhibits highly reversible capacity of 204.7 mAh g^(-1) with 98%retention at 5 C rate over 1000 cycles.Moreover,with 5 wt%NaDB initially coated on the Na3V2(PO4)3(NVP)cathode,the capacity retention of NVP + NaDB|HC cell could increase from 22%to 89%after 1000 cycles at 1 C rate.This work provides a new avenue to improve reversible capacity and cycling performance of SIBs through designing functional cathode compensation agent.

Preparation and Performance of Ternary Early Strength Agent and Quercetin Composite Cement Sealing Material

A ternary early-strengthening agent consisting of calcium formate+triethanolamine+lithium sulfate was compounded with quercetin to shorten the setting time of cementitious materials while ensuring their early strength.The optimum ratio of the three early-strengthening agents was determined as 0.5%calcium formate+0.04%triethanolamine+0.4%lithium sulfate by response surface methodology.The effects of the ternary early-strengthening agent composed of calcium formate+triethanolamine(TEA)+lithium sulfate on cementitious pore sealing materials under the synergistic effect of quercetin were studied by means of the performance tests of compressive strength,fluidity,and setting time,and the microstructural characterizations of X-ray powder diffractometer(XRD),thermogravimetry(TG-DSC)and scanning electron microscopy(SEM).The study shows that the synergistic effect of ternary early-strengthening agent and quercetin forms a multi-performance composite admixture for cementitious materials.The best performance was obtained with the compounding scheme of 0.5%calcium formate+0.04%triethanolamine+0.4%lithium sulfate ternary early-strengthening agent and 0.05%quercetin.The compressive strength of 1,3,7,and 28 d are 94.8%,39.8%,42%,and 28%higher than those of the blank group,respectively.The initial time and final setting time are 41 and 57 minutes,respectively.According to the microscopic analysis,the network and fibrous C-S-H gels generated by ternary early-strengthening agents are attached to the surface promoted by quercetin,which forms skeleton support while thickening and solidifying the cement slurry,which enhances the early compressive strength of the cement-based materials.

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。

基于多Agent深度强化学习的无人机协作规划方法

人机协作控制是多无人机任务规划的重要方式。考虑多无人机任务环境协同解释和策略控制一致性需求,提出基于多Agent深度强化学习的无人机协作规划方法。依据任务知识和行为状态,构建基于任务分配Agent的任务规划器,生成人机交互的相互依赖关系;设计一种深度学习强化方法,解决群体行为最优策略和协同控制方法,并利用混合主动行为选择机制评估学习策略。实验结果表明:作为人机交互实例,所提方法通过深度强化学习使群体全局联合动作表现较好,学习速度和稳定性均能优于确定性策略梯度方法。同时,在跟随、自主和混合主动3种模式比较下,可以较好地控制无人机飞行路径和任务,为无人机集群任务执行提供了智能决策依据。

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。

Agent视域下的人工智能赋能作战系统

针对作战系统的智能化设计问题,提出了基于Agent的人工智能技术概念框架和应用方法。首先,阐述了Agent概念,讨论了在作战系统中研究Agent的重要意义。然后,介绍了基于Agent的人工智能研究框架,列举了Agent在作战系统中的多种应用方式。最后,分析了Agent技术发展趋势及其作战应用可能面临的风险与挑战。

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。

基于多Agent的服装可持续消费行为建模与仿真

“双碳”目标下,随着服装消费引起的气候变化和环境污染等生态问题日益严重,迫切需要重新思考和重塑服装消费模式,推动服装消费向质量型、低碳化转变,从而实现服装产业的绿色转型。文章运用多Agent建模方法,构建服装可持续消费行为仿真模型,采用Netlogo平台进行仿真实验,探求服装可持续消费行为的影响机理。结果表明,消费者可持续消费认知、产品可持续性和设施供应条件均显著促进可持续消费行为;但不同强度下,产品可持续性和设施供应条件的推动作用存在差异。基于此,从可持续消费认知和供应条件两方面提出了引导中国消费者服装可持续消费行为的建议和对策。

一种基于Agent的任务自生成方法

任务自生成是基于预先设定的业务工作流完成任务执行流程制定的一个过程,任务执行流程制定主要包括任务执行步骤选取与任务执行步骤相应的解决方案选取。提出一种基于Agent的任务自生成方法来解决基于传统的业务工作流的流程制定机制,在面对有差异性需求的不同任务时,因其不能做出任务执行流程制定的自适应性改变而在处理任务时出现处理速度慢、结果不准确等问题。利用Agent的环境感知能力实现对任务需求信息和任务自生成系统环境的感知,利用Agent的自主行为决策能力结合感知的信息实现对任务执行流程制定工作的自主管理,在真实应用场景测试中,通过一系列比较实验验证了这种方法在处理速度和准确度方面具有明显优势。

基于Multi-Agent的无人机集群体系自主作战系统设计

针对无人集群自主作战体系设计中的关键问题,提出基于Multi-Agent的无人集群自主作战系统设计方法。建立无人集群各节点的Agent模型及其推演规则;对于仿真系统模块化和通用化的需求,设计系统互操作式接口和无人集群自主作战的交互关系;开展无人集群系统仿真推演验证。仿真结果表明,所提设计方案不仅能够有效开展并完成自主作战网络生成-集群演化-效能评估的全过程动态演示验证,而且能够通过重复随机试验进一步评估无人集群的协同作战效能,最后总结了集群协同作战的策略和经验。

基于Multi-Agent的水电站变压器故障诊断系统

为了精准、快速完成水电站变压器的故障诊断,设计基于Multi-Agent的水电站变压器故障诊断系统。变压器状态监控agent将检测到的变压器故障信息发送给系统管理agent,系统管理agent通过通信agent将变压器故障信息发送给变压器故障诊断agent,变压器故障诊断agent利用小波变换方法提取变压器故障特征,并将其作为IFOA-SVM模型输入,完成变压器故障分类后,获取变压器故障诊断结果,该结果通过通信agent显示给用户。实验表明,该系统可有效诊断变压器故障诊断,诊断成功率受系统故障信息丢失率的影响较小,诊断耗时、耗能小,并具有较高故障诊断成功率。

基于多Agent传动关系的股市趋势预测

股市趋势预测是机器学习领域中一个具有挑战性的任务。由于一些因素对于股市的影响是动态且不确定的,导致股市趋势难以预测。针对已有方法在股市预测时存在的灵敏性差、适应力弱等问题,从快变量和慢变量的传动关系出发,利用Agent技术对股市中的快周期和慢周期进行联合建模,提出一种多Agent传动影响图(MATID)股市趋势预测方法。给出股市中快周期和慢周期的划分标准,并引入周期能量的概念;通过对相关趋势指标的特征融合,给出周期能量的量化计算方法;通过分析快周期和慢周期的动态作用过程,给出传动因子的表示方法;将快周期和慢周期分别对应成不同的Agent,利用多Agent影响图模型建模快周期和慢周期的传动过程;利用股市振子模型表示快Agent和慢Agent之间的传动效用,利用联合树的自动推理技术对股市趋势进行预测。在不同样本数量和不同股市趋势下进行实验,结果表明,与门控循环单元、S-LSTM和Hybrid-RNN预测方法相比,MATID方法预测精确率提升1.5%~7.0%,召回率提升5.4%~6.7%,F1值提升3.7%~6.2%,具有良好的灵敏性和适应力。

Herb pair of Huangqi-Danggui exerts anti-tumor immunity to breast cancer by upregulating PIK3R1

Background:According to traditional Chinese medicine(TCM),drugs supplementing the vital energy,Qi,can eliminate tumors by restoring host immunity.The objective of this study is to investigate the underlying immune mechanisms of anti-tumor activity associated with Qi-supplementing herbs,specifically the paired use of Huangqi and Danggui.Methods:Analysis of compatibility regularity was conducted to screen the combination of Qi-supplementing TCMs.Using the MTT assay and a transplanted tumor mice model,the anti-tumor effects of combination TCMs were investigated in vitro and in vivo.High content analysis and flow cytometry were then used to evaluate cellular immunity,followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms.Finally,the anti-tumor activity and the mechanism of the active ingredients were verified by molecular experiments.Results:There is an optimal combination of Huangqi and Danggui that,administered as an aqueous extract,can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo.Based on network pharmacology analysis,PIK3R1 is the core target for the anti-tumor immunity activity of combined Huangqi and Danggui.Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract(quercetin,jaranol,isorhamnetin,kaempferol,calycosin,and suchilactone)that bind to PIK3R1.Jaranol is the most important component against breast cancer.The suchilactone/jaranol combination and,especially,the suchilactone/kaempferol combination are key for immunity enhancement and the anti-tumor effects of the extract.Conclusions:The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone.

Extracellular vesicles in anti-tumor drug resistance: Mechanisms and therapeutic prospects

Drug resistance presents a significant challenge to achieving positive clinical outcomes in anti-tumor therapy.Prior research has illuminated reasons behind drug resistance,including increased drug efflux,alterations in drug targets,and abnormal activation of oncogenic pathways.However,there's a need for deeper investigation into the impact of drug-resistant cells on parental tumor cells and intricate crosstalk between tumor cells and the malignant tumor microenvironment(TME).Recent studies on extracellular vesicles(EVs)have provided valuable insights.EVs are membrane-bound particles secreted by all cells,mediating cell-to-cell communication.They contain functional cargoes like DNA,RNA,lipids,proteins,and metabolites from mother cells,delivered to other cells.Notably,EVs are increasingly recognized as regulators in the resistance to anti-cancer drugs.This review aims to summarize the mechanisms of EV-mediated anti-tumor drug resistance,covering therapeutic approaches like chemo-therapy,targeted therapy,immunotherapy and even radiotherapy.Detecting Ev-based biomarkers to predict drug resistance assists in bypassing anti-tumor drug resistance.Additionally,targeted inhibition of EV biogenesis and secretion emerges as a promising approach to counter drug resistance.We highlight the importance of conducting in-depth mechanistic research on EVs,their cargoes,and functional ap-proaches specifically focusing on EV subpopulations.These efforts will significantly advance the devel-opment of strategies to overcome drug resistance in anti-tumor therapy.