Anti-angiogenic agents in metastatic colorectal cancer

Colorectal cancer(CRC) is a major public health concern being the third leading cause of cancer mortality in the United States. The availability of better therapeutic options has led to a decline in cancer mortality in these patients. Surgical resection should be considered in all stages of the disease. The use of conversion therapy has made surgery a potentially curative option even in patients with initially unresectable metastatic disease. In this review we discuss the role of various antiangiogenic agents in patients with metastatic CRC(m CRC). We describe the mechanism of action of these agents, and the rationale for their use in combination with chemotherapy. We also review important clinical studies that have evaluated the safety and efficacy of these agents in m CRC patients. Despite the discovery of several promising anti-angiogenic agents, m CRC remains an incurable disease with a median overall survival of just over 2 years in patients exposed to all available treatment regimens. Further insights into tumor biology and tumor microenvironment may help improve outcomes in these patients.

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.

Anti-angiogenic drugs in cancer therapeutics:a review of the latest preclinical and clinical studies of anti-angiogenic agents with anticancer potential

Cancer is a group of diseases with significant morbidity and mortality.In cancer cells,where energy requirements are exceptionally high,angiogenesis,which is the sprouting of new blood vessels from pre-existing ones,is an important process for tumour survival and progression.Hence,extensive research in recent years focuses on the discovery of new anticancer drugs that target angiogenesis.Several methodologies have been developed preclinically,including the inhibition of pro-angiogenic factors and their receptors via micromolecular agents or monoclonal antibodies and the inhibition of other compensatory pathways beyond the traditional angiogenic ones.The purpose of the literature review is to present new anticancer drugs that target the process of angiogenesis and have been under preclinical or clinical investigation during the last five years.Many new anticancer drugs targeting angiogenesis are identified in the literature.The results of the in vitro and in vivo evaluation of these drugs show that,apart from inhibiting angiogenesis,they also affect cancer cell proliferation and tumour growth.Recent clinical studies show that these drugs increase the overall or disease-free survival of patients,even those with persistent,chemotherapy-resistant and metastatic types of cancer,although treatment-related side effects are not uncommon.Drugs that target the process of angiogenesis are likely to be the future of anticancer therapy,especially in cases where more traditional treatments do not produce the desired results and where combination regimens of anti-angiogenic agents with standard chemotherapeutics increase patient survival.

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。

Angiogenesis in hepatocellular carcinoma:mechanisms and anti-angiogenic therapies

Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-associated death worldwide.Angiogenesis,the process of formation of new blood vessels,is required for cancer cells to obtain nutrients and oxygen.HCC is a typical hypervascular solid tumor with an aberrant vascular network and angiogenesis that contribute to its growth,progression,invasion,and metastasis.Current anti-angiogenic therapies target mainly tyrosine kinases,vascular endothelial growth factor receptor(VEGFR),and plateletderived growth factor receptor(PDGFR),and are considered effective strategies for HCC,particularly advanced HCC.However,because the survival benefits conferred by these anti-angiogenic therapies are modest,new anti-angiogenic targets must be identified.Several recent studies have determined the underlying molecular mechanisms,including pro-angiogenic factors secreted by HCC cells,the tumor microenvironment,and cancer stem cells.In this review,we summarize the roles of pro-angiogenic factors;the involvement of endothelial cells,hepatic stellate cells,tumor-associated macrophages,and tumor-associated neutrophils present in the tumor microenvironment;and the regulatory influence of cancer stem cells on angiogenesis in HCC.Furthermore,we discuss some of the clinically approved anti-angiogenic therapies and potential novel therapeutic targets for angiogenesis in HCC.A better understanding of the mechanisms underlying angiogenesis may lead to the development of more optimized anti-angiogenic treatment modalities for HCC.

Numerical simulation of inhibiting effects on solid tumour cells in anti-angiogenic therapy: application of coupled mathematical model of angiogenesis with tumour growth

To investigate the inhibiting effects of the anti-angiogenic factor andostatin and the anti-angiogenic drug endostatin on turnout angiogenesis and turnout cells, a coupled mathematical model of tumor angiogenesis with tumour growth and blood perfusion is developed. Simulation results show that angiostatin and endostatin can improve the abnormal microenvironment inside the tumour tissue by effectively inhibiting the process of tumor angiogenesis and decreasing tumour cells. The present model can be used as a valid theoretical method in the investigation of the tumour anti-angiogenic therapy.

Identification of bioactive anti-angiogenic constitutes targeting tumor endothelial cells in Shenmai Injection using multidimensional pharmacokinetics

OBJECTIVE To identify the bioactive anti-angiogenic constitutes targeting tumor endothelial cells(TECs)in Shenmai Injection(SMI).METHEODS For pharmacokinetic(PK)studies,Balb/c mice harboring human colorectal cancer(LoVo)xenografts were treated with SMI 10 mL·kg^-1 daily for 1 or 8 d.Multidimensional PK profiles of ginsenosides in plasma,subcutaneous tumors,and TECs were investigated.For PD studies,the tumor-bearing mice Intravital multi-photon imaging and CD31 immunofluorescence staining were used to evaluate the number of microves⁃sels and braches.Double staining of CD31 and α-SMA was performed to evaluate pericytes coverage ratios around vessels.ELISA was performed to determine the concentrations of VEGF and FGF in tumor tissues.For synergistic anti-tumor study,the tumor-bearing mice were treated with SMI 10 mL·kg^-1 daily,Rd 5 mg·kg^-1 daily with or without 5-FU 15 mg·kg^-1 every 3 d for 20 d.HPLC-MS/MS was used to determine the concentrations of 5-FU in plasma and tumor tissues.RESULTS SMI decreased the number of microvessels(P<0.05)and vessel branches(P<0.05)and improved vascular pericytes coverage(P<0.05).PK studies showed that the concentrations of protopanaxadiol-type(PPD)ginsenosides(Rb1,Rb2/Rb3,Rc,and Rd)in both,plasma and tumors,were higher than those of protopanaxatriol-type(Rg1 and Re)and oleanane-type(Ro)ginsenosides.Among PPD ginsenosides,Rd exhibited the greatest concentrations in tumors and TECs after repeated injection.In fact,the proportion of Rd in the detectable components of SMI gradually increased in the following order:SMI formula(2.8%),plasma(16.0%),tumor tissues(34.3%),and TECs(40.3%).In vivo bioactivity results showed that Rd 5 mg·kg^-1 daily significantly decreased the number of microvessels(P<0.05)and vessel branches(P<0.05)and increased pericytes coverage(P<0.05)while Rd 0.5 mg·kg^-1 daily,Rb1 and Rg1 had no significant effect on them.Rd 5 mg·kg^-1 suppressed the expression of VEGF and FGF simultaneously.Rd 5 mg·kg^-1 enhanced the antitumor effect of 5-FU via increasing the distribution of 5-FU in tumor tissues(P<0.05)in xenograft mice.CONCLUSION Ginsenoside Rd may be the major bioactive anti-angiogenic constituent targeting TECs after SMI treatment.

Challenges and opportunities of using stereotactic body radiotherapy with anti-angiogenesis agents in tumor therapy

Microvessels promote proliferation of tumor cells by delivering oxygen and nutrients, but rapid growth of tumors results in unmet demands for oxygen and nutrients, thereby creating a hypoxia microenvironment. Under hypoxic conditions, vascular endothelial cells（ECs） initiate the formation of immature and abnormal microvasculature. This results in leakage and tortuosity that facilitates tumor cell invasion, metastasis and resistance to cytotoxic treatment.Radiotherapy（RT） is a vital tumor treatment modality. Currently, more than 60% of patients with malignant tumors receive RT at certain points during their treatment. Hypoxia induced by abnormal microvessels can hamper the cytotoxic effect of ionizing radiation, particularly, stereotactic body radiotherapy（SBRT）. Anti-angiogenesis（AA） agents are known to reduce and renormalize microvessels in tumors, and hence alleviate hypoxia. The combination of AA agents with SBRT may have a synergistic role in inhibiting the growth of tumors. On the contrary, large doses of irradiation may affect tumor microvessels itself. In this review, we aim to clarify the relationship between SBRT and microvessel formation in tumors. In addition, we provide a retrospective analysis of the combination therapy involving SBRT and AA agents in preclinical and clinical practice to define its role in antitumor treatment.

Vascular damage and anti-angiogenic effects of tumor vessel-targeted adenovirus-mediated herpes simplex virus thymidine kinase gene

AIM： To explore the therapeutic efficacy and mechanism of herpes simplex virus-thymidine kinase （HSV-tk） targeting angiogenesis against hepatocellular carcinoma in vivio and in vitro. METHODS： Recombinant adenovirus containing kinase domain insert with receptor （KDR） or cytomegalovirus （CMV） promoter-controlled HSV-tk gene （AdKDR-tk and AdCMV-tk） was constructed using pAdeasy system. The expression of KDR antigen in human umbilical venous endothelial cells （HUVEC） and HepG2 was detected with histological analysis of cells. The virus was used to infect HUVEC and HepG2. Following administration of ganciclovir （GCV）, the survival rate of gene-transfected HUVEC and HepG2 was evaluated by MTT method. To develop hepatocarcinomas in 32 Balb/C mice with HepG2 cells, the mice were divided into four groups： ganciclovir group （Ⅰ）, Ad group （Ⅱ）, AdCMV-tk group （Ⅲ） and AdKDR-tk group （Ⅳ）. Then selective administration of recombinant adenovirus or Ad via the intratumorial was given to all rats. Ganciclovir （GCV） was given at a dose of 100 mg·kg^-1·d^-1 （ip） started on the following day and lasted 10 d. Microvessel density （MVD） of tumor in all the treated animals were examined by the immunohistochemical methods and tumor burden was evaluated 10 d before and alter the last GCV dose.RESULTS： Immunocytochemical staining indicated the expression of KDR antigen in HUVEC. Under adenovirus infection index of 100, with increasing GCV concentration from 0 up to 50 mg/L, the survival rate of AdKDR-tk- transfected HUVEC and HepG2 decreased from 100% to （28.94 ± 5.67）% and （75.45 ± 2.91）% at proper order, respectively （P 〈 0.01）, while the survival rate of AdCMV- tk-transfected HUVEC and HepG2 declined from 100% to （17.56 ± 2.48）% and （23.15± 5.72）%, respectively （P 〉 0.05）. Compared with group I, there was a decrease of tumor weight by 14.7% in group Ⅲ and by 23.6% in group Ⅳ. And there was a distinct difference between group M and Ⅳ （P 〈 0.05）. The median MVD for all groups was 37.4 ± 8.6, 30.6 ± 7.8, 27.6 ± 7.1, and 10.7 ± 4.1 （microvessels/mm^2） in group Ⅰ, Ⅱ, M and IV, respectively. And there was a marked difference between group M and Ⅱ （P 〈 0.05）, Ⅳ and Ⅱ （P 〈 0.01）, and Ⅳ and M （P 〈 0.01）. CONCLUSION： KDR promoter-HSV-tk gene may effectually restrain the growth of tumor via targeting angiogenesis for hepatocellular carcinoma with treatment of GCV.

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。

Patent-based technological developments and surfactants application of lithium-ion batteries fire-extinguishing agent

While newer,more efficient Lithium-ion batteries(LIBs)and extinguishing agents have been developed to reduce the occurrence of thermal runaway accidents,there is still a scarcity of research focused on the application of surfactants in different LIBs extinguishing agents,particularly in terms of patented technologies.The aim of this review paper is to provide an overview of the technological progress of LIBs and LIBs extinguishing agents in terms of patents in Korea,Japan,Europe,the United States,China,etc.The initial part of this review paper is sort out LIBs technology development in different regions.In addition,to compare LIBs extinguishing agent progress and challenges of liquid,solid,combination of multiple,and microencapsulated.The subsequent section of this review focuses on an in-depth analysis dedicated to the efficiency and challenges faced by the surfactants corresponding design principles of LIBs extinguishing agents,such as nonionic and anionic surfactants.A total of 451,760 LIBs-related patent and 20 LIBs-fire-extinguishing agent-related patent were included in the analyses.The extinguishing effect,cooling performance,and anti-recombustion on different agents have been highlighted.After a comprehensive comparison of these agents,this review suggests that temperature-sensitive hydrogel extinguishing agent is ideal for the effective control of LIBs fire.The progress and challenges of surfactants have been extensively examined,focusing on key factors such as surface activity,thermal stability,foaming properties,environmental friendliness,and electrical conductivity.Moreover,it is crucial to emphasize that the selection of a suitable surfactant must align with the extinguishing strategy of the extinguishing agent for optimal firefighting effectiveness.