Artificial intelligence(AI)is reshaping financial systems and services,as intelligent AI agents increasingly form the foundation of autonomous,goal-driven systems capable of reasoning,learning,and action.This review s...Artificial intelligence(AI)is reshaping financial systems and services,as intelligent AI agents increasingly form the foundation of autonomous,goal-driven systems capable of reasoning,learning,and action.This review synthesizes recent research and developments in the application of AI agents across core financial domains.Specifically,it covers the deployment of agent-based AI in algorithmic trading,fraud detection,credit risk assessment,roboadvisory,and regulatory compliance(RegTech).The review focuses on advanced agent-based methodologies,including reinforcement learning,multi-agent systems,and autonomous decision-making frameworks,particularly those leveraging large language models(LLMs),contrasting these with traditional AI or purely statistical models.Our primary goals are to consolidate current knowledge,identify significant trends and architectural approaches,review the practical efficiency and impact of current applications,and delineate key challenges and promising future research directions.The increasing sophistication of AI agents offers unprecedented opportunities for innovation in finance,yet presents complex technical,ethical,and regulatory challenges that demand careful consideration and proactive strategies.This review aims to provide a comprehensive understanding of this rapidly evolving landscape,highlighting the role of agent-based AI in the ongoing transformation of the financial industry,and is intended to serve financial institutions,regulators,investors,analysts,researchers,and other key stakeholders in the financial ecosystem.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithel...BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.展开更多
This study constructs a reflective feedback model based on a pedagogical agent(PA)and explores its impact on students’problem-solving ability and cognitive load.A quasi-experimental design was used in the study,with ...This study constructs a reflective feedback model based on a pedagogical agent(PA)and explores its impact on students’problem-solving ability and cognitive load.A quasi-experimental design was used in the study,with 84 students from a middle school selected as the research subjects(44 in the experimental group and 40 in the control group).The experimental group used the reflective feedback model,while the control group used the factual feedback model.The results show that,compared with factual feedback,the reflective feedback model based on the pedagogical agent significantly improves students’problem-solving ability,especially at the action and thinking levels.In addition,this model effectively reduces students’cognitive load,especially in terms of internal and external load.展开更多
Nanolipid carriers and traditional emulsion containing chemical sunscreens were prepared using emulsification combined with ultrasonic technology.The nanolipid carriers showed superior performance in sunscreen encapsu...Nanolipid carriers and traditional emulsion containing chemical sunscreens were prepared using emulsification combined with ultrasonic technology.The nanolipid carriers showed superior performance in sunscreen encapsulation,slow release and skin impermeability,and provided an excellent nanolipid slow-release encapsulation system for sunscreens.As observed by transmission electron microscopy,the nanolipid carriers were spherical shape,with smooth surface and uniform distribution,and the particle sizes were mainly concentrated in the range of 230 to 250 nm without agglomeration.The nanolipid carriers significantly improved the sunscreen performance through the synergistic effect of scattering and chemical absorption,and showed better UV stability than traditional sunscreen,indicating their photoprotective function.In vitro release experiments showed that the nano-lipidic carriers exhibited better release control when loaded with octyl methoxycinnamate(OMC)and butylmethoxydibenzoylmethane(BDFM)sunscreens than traditional traditional emulsions,with the cumulative release rate of OMC in the nano-lipidic carriers decreasing by 17.17% to 30.24% within 12 hours,and that of BDFM decreasing by 26.67% to 44.67%.26.67% to 44.16%.The results of the in vitro permeation experiment further confirmed that the nanolipid carriers could effectively encapsulate the sunscreens and prevent them from penetrating the skin barrier,thus reducing the skin irritation.Compared with traditional traditional emulsion,the cumulative penetration of OMC in nanostructured lipid carriers was 2.24μg/cm^(2)in 4 hours,while the cumulative penetration was reduced by 68.05%.The cumulative penetration of BDFM in the nanostructured lipid carrier was 3.24μg/cm^(2),with a 64.04%reduction in cumulative penetration.展开更多
【Objectives】Si and microbial application could relieve the crop replanting problems(CRPs).We further studied the change of key microorganisms that are related to the beneficial effects,aiming at provide reference fo...【Objectives】Si and microbial application could relieve the crop replanting problems(CRPs).We further studied the change of key microorganisms that are related to the beneficial effects,aiming at provide reference for the manufacture and application of both microbial agents and Si fertilizer in food lily production.【Methods】A field experiment was conducted over a three-year period,from March 2019 to March 2022.The experimental field had been continuously cultivated with lily for 9 years.Three treatments were established:silicon fertilizer(SF),microbial agents(“Special 8^(TM)”,MF),and combined application of silicon fertilizer and microbial agents(SMF).A control group with blank soil(CK)was also included.At seedling stage of Lanzhou lilies in 2020 and 2021,the shoot and bulb dry weight,and the plant height and stem diameter of Lanzhou lilies were investigated for calculation of seedling index.In July 2020,20 plants were selected in each plot,and root zone soils were sampled at a depth of 20 cm,10 cm away from the roots,and then mixed to form a composite sample.The soil available Si and organic matter content were analyzed,and the fungal community structure and some specific microbial groups in soils were determined with high-throughput sequencing of ITS.【Results】All the three treatments significantly enhanced the lily plant growth and the seedling index,compared to CK.Besides,SF and MF treatments increased the relative abundances(RA)and diversity of fungal communities,and altered the community structures.The RA of some specific groups were found to be significantly correlated with the seedling index and/or soil available Si.Of them,the RA of the genera Fusarium,Dactylonectria,Humicola,Stilbella,and the species Humicola_grisea showed a positive correlation,while that of the genera Mortierella,Stilbella,Holtermanniella,and the species Mortierella_fatshederae showed a negative correlation with seedling index.The genera Fusarium,Stilbella,the species Humicola_grisea,and Dactylonectria_estremocensis showed a positive correlation,while the genura Stilbella,and the species Mortierella fatshederae showed a negative correlation with available Si content.In the co-occurence network of top twenty fungal genera and top sixteen bacterial genera(RA>0.2%),Holtermanniella was the only genus that interacted with the bacteria and negatively correlated with bacterial genus Blastococcus.Holtermanniella was also the most densely connected genera,followed by the genus Fusarium,Didymella and Humicola.In addition,the genus Holtermanniella was the key species connecting fungal and bacterial community in soil.Fungal functional prediction revealed that SF,MF and SMF treatments decreased plant pathogens guilds and increased the beneficial guilds Ectomycorrhizal,plant saprophyte,leaf saprophyte,and arbuscular mycorrhizal compared to CK.【Conclusions】Combined application of silicon fertilizer and microbial agents can alleviate continuous replanting problems of Lanzhou lilies through restoring the fungal community diversity,and promoting plant residue depredation,thus reducing soil born disease incidence.The beneficial genus Humicola and its one species H.grisea acts as bioconversion,and the genus Acremonium acts as plant pathogen inhibitor.展开更多
Given that the citrus psyllid is the primary vector of citrus Huanglongbing(HLB),there is an urgent need to control this pest to mitigate the spread of the disease.This paper reviews the current research on two predom...Given that the citrus psyllid is the primary vector of citrus Huanglongbing(HLB),there is an urgent need to control this pest to mitigate the spread of the disease.This paper reviews the current research on two predominant control strategies:chemical control and biological control agents,in managing the citrus psyllid.It emphasizes the mechanisms of action,efficacy,and application advancements of these control methods.Finally,the paper analyzes the principal challenges associated with the sustainable management of citrus psyllids and offers perspectives for future research.展开更多
Conventional echocardiography can sometimes pose a challenge to diagnosis due to sub-optimal images.Ultrasound contrast agents(UCAs)have been shown to drastically enhance imaging quality,particularly depicting the lef...Conventional echocardiography can sometimes pose a challenge to diagnosis due to sub-optimal images.Ultrasound contrast agents(UCAs)have been shown to drastically enhance imaging quality,particularly depicting the left ventricular endocardial borders.Their use during echocardiography has become a valuable tool in non-invasive diagnostics.UCAs provide higher-quality images that may ultimately reduce the length of hospital stays and improve patient care.The higher cost associated with UCAs in many situations has been an impediment to frequent use.However,when used as an initial diagnostic test,UCA during rest echocardiogram is more cost-effective than the traditional diagnostic approach,which frequently includes multiple tests and imaging studies to make an accurate diagnosis.They can be easily performed across multiple patient settings and provide optimal images that allow clinicians to make sound medical decisions.This consequently allows for better diagnostic accuracies and improvement in patient care.展开更多
Acquired immune deficiency syndrome(AIDS)is the name used to describe several potentially life-threatening infections and disorders that happen when HIV has severely compromised the immune system.The primary effect of...Acquired immune deficiency syndrome(AIDS)is the name used to describe several potentially life-threatening infections and disorders that happen when HIV has severely compromised the immune system.The primary effect of HIV is to decrease host immunity,exposing the host to external pathogens.The development of pharmaceutical drugs that directly cure the infection is crucial because of the current wide-ranging epidemic of HIV.Most therapeutic anti-HIV drugs are nucleosides.However,their high toxicity and potential for drug resistance restrict their use.Many of the most effective clinical drugs used to inhibit HIV,the activation of latent HIV,and AIDS have been obtained from natural sources.This review focuses on potential natural medicinal products for treating and managing HIV and AIDS.Notwithstanding,further clinical research studies are needed to understand the subject and its dynamics.展开更多
Objectives:This review aimed to systematically analyze the technological frameworks,application scenarios,and outcomes of large language model-driven agents(LLMDAs)in nursing practice,and to summarize ethical,technolo...Objectives:This review aimed to systematically analyze the technological frameworks,application scenarios,and outcomes of large language model-driven agents(LLMDAs)in nursing practice,and to summarize ethical,technological,and practical challenges,guiding future research and clinical implementation.Methods:This scoping review was conducted following the JBI guidelines.Five databases(PubMed,Embase,Web of Science,APA PsycNet,Cochrane Library)were systematically searched for peer-reviewed English-language studies from inception until September 9,2025.Eligible studies were screened by title and abstract,with full-text assessments conducted independently by two reviewers.Results:Twenty-five studies published between 2023 and 2025 were included,involving nine countries,primarily China(n=9)and the United States(n=9).Technological architectures were categorized into three types:collaborative models for solving complex tasks through multi-agent division of labor;augmentative models to enhance the accuracy of information outputs;and interactive models focusing on natural interactions and robotic task execution.Application scenarios included clinical,home-based,and community care.Studies indicated that LLMDAs can enhance diagnostic accuracy,optimize resource allocation,and improve patient experience.Primary ethical challenges identified included data privacy,reliability of generated content,and ambiguous attribution of responsibility.Conclusions:LLMDAs offer a novel paradigm for intelligent transformation in nursing care through integrative technological frameworks.They demonstrate considerable potential in enhancing clinical decision-making accuracy,efficiency of care delivery,and patient satisfaction.Addressing existing ethical,technical,and practical challenges is essential for facilitating broader clinical adoption.展开更多
Energy security is the association between national security and the availability of natural resources for energy consumption.Access to cheaper energy has become essential to the functioning of modern economies.Howeve...Energy security is the association between national security and the availability of natural resources for energy consumption.Access to cheaper energy has become essential to the functioning of modern economies.However,the uneven distribution of energy supplies among countries has led to significant challenges.International energy relations have contributed to the globalization of the world,leading to energy security and energy vulnerability at the same time.The first article in Science Direct for energy security appeared in 1993 with authors from USA.Gradually the number of articles and their origin increases.In 2024 we observe a boom of these publications-30(not only in Science Direct)and one planned for 2025.The recent article explores these publications and sorts them by origin and content.The content is distributed in five topics:computer technologies impact,artificial intelligence applications,environmental management and energy security,economics and policy for energy security,and emerging technologies for energy security.Since the share of AI usage is relatively small the author suggests scenarios for AI agents’application in various situations concerning environmental decisions,failures,cyber-attacks,performance,and pricing.展开更多
Clinical pharmacy is on the cusp of exponential change powered by artificial intelligence agents,automation,data analytics,and robotics.Blockchain will enhance data integrity and transparency,and Augmented and Virtual...Clinical pharmacy is on the cusp of exponential change powered by artificial intelligence agents,automation,data analytics,and robotics.Blockchain will enhance data integrity and transparency,and Augmented and Virtual Reality technologies will revolutionise training,patient education,and simulation-based care planning.Clinical pharmacists need to be ready and upskill to prepare for emerging technologies.The ethical,regulatory,and educational frameworks surrounding artificial intelligence and precision medicine will require constant attention,but the potential benefits for patient outcomes are unprecedented.Clinical pharmacists are in a prime position to design a new era in precision medicine,where technology works hand in hand with humans to transform healthcare.展开更多
Domain randomization is a widely adopted technique in deep reinforcement learning(DRL)to improve agent generalization by exposing policies to diverse environmental conditions.This paper investigates the impact of diff...Domain randomization is a widely adopted technique in deep reinforcement learning(DRL)to improve agent generalization by exposing policies to diverse environmental conditions.This paper investigates the impact of different reset strategies,normal,non-randomized,and randomized,on agent performance using the Deep Deterministic Policy Gradient(DDPG)and Twin Delayed DDPG(TD3)algorithms within the CarRacing-v2 environment.Two experimental setups were conducted:an extended training regime with DDPG for 1000 steps per episode across 1000 episodes,and a fast execution setup comparing DDPG and TD3 for 30 episodes with 50 steps per episode under constrained computational resources.A step-based reward scaling mechanism was applied under the randomized reset condition to promote broader state exploration.Experimental results showthat randomized resets significantly enhance learning efficiency and generalization,with DDPG demonstrating superior performance across all reset strategies.In particular,DDPG combined with randomized resets achieves the highest smoothed rewards(reaching approximately 15),best stability,and fastest convergence.These differences are statistically significant,as confirmed by t-tests:DDPG outperforms TD3 under randomized(t=−101.91,p<0.0001),normal(t=−21.59,p<0.0001),and non-randomized(t=−62.46,p<0.0001)reset conditions.The findings underscore the critical role of reset strategy and reward shaping in enhancing the robustness and adaptability of DRL agents in continuous control tasks,particularly in environments where computational efficiency and training stability are crucial.展开更多
This paper discusses the importance of standards in the fire extinguishing agent industry,and highlights the vital role of the standards in promoting technological innovation.China’s standards for fire extinguishing ...This paper discusses the importance of standards in the fire extinguishing agent industry,and highlights the vital role of the standards in promoting technological innovation.China’s standards for fire extinguishing agent products have evolved significantly,aligning with industrial development,market demands,regulatory requirements,to respond to the great impact of international competition in the industry.The paper analyzes the current state of China’s standards,including their composition and integration with industry growth,green development strategies,and international harmonization.Future development strategies for the standards framework should focus on valid period estimation,fire test model development,and raw material selection guidelines.By implementing these strategies,China’s fire protection industry can enhance product quality,contribute to public safety,and maintain a competitive edge in the global market.展开更多
The integration of Green Artificial Intelligence(AI)technologies into educational systems offers a promising avenue to enhance operational efficiency while addressing sustainability challenges.Through a rigorous three...The integration of Green Artificial Intelligence(AI)technologies into educational systems offers a promising avenue to enhance operational efficiency while addressing sustainability challenges.Through a rigorous three-phase methodology combining literature review,AI agent development,and participatory workshop-based case analysis,this paper highlights the pivotal role of AI agents,as applications of Green AI technologies,in driving transformative outcomes within schools.By directly improving self-learning efficiency and reducing learning costs for students,enhancing management and service efficiency,reducing labor costs for schools,as well as minimizing resource dependence for both teachers and students,AI agents create a foundation for sustainable operations.These direct effects generate positive spillover effects,cascading into broader outcomes,including innovation performance,economic efficiency,and environmental sustainability,aligning with the United Nations Sustainable Development Goals(SDGs).By presenting a comprehensive conceptual model,this study demonstrates the pathways through which Green AI contributes to sustainable development in education and emphasizes its critical role in bridging technological innovation with sustainability.This framework provides significant theoretical insights for further empirical research while offering actionable strategies for policymakers and educators to harness Green AI for building sustainable schools with a student-centered approach.展开更多
Exploration of immunosuppressive agents for the treatment of diabetes is a burgeoning field that has captured the attention of the medical community.The innovative approach of using these agents to combat diabetes is ...Exploration of immunosuppressive agents for the treatment of diabetes is a burgeoning field that has captured the attention of the medical community.The innovative approach of using these agents to combat diabetes is driven by their diverse capabilities to regulate the immune system,which is pivotal for disease pathogenesis.The primary objective is to enhance the management of blood glucose levels,which is a critical factor in the daily life of diabetic patients.This comprehensive review delves into the therapeutic horizons opened by immunosuppressive agents,particularly their potential impact on type 1 and type 2 diabetes mellitus,and their utility in the transplantation process.The complex etiology of diabetes,which involves a delicate interplay of genetic,environmental,and immunological factors,presents a multifaceted target landscape for these therapies.The agents discussed in the review,including CD3 inhibitors,cytotoxic T-lymphocyte-associated protein 4-immunoglobulin G,Janus kinase inhibitors,anti-thymocyte globulin,tumor necrosis factor-αinhibitors,CD20 inhibitors,alefacept,and alemtuzumab,each bring a unique mechanism to the table,offering a tailored approach to immune modulation.As research progresses,emphasis is being placed on evaluating the long-term efficacy and safety of these agents to pave the way for more personalized and effective diabetes management strategies.展开更多
For the purpose of satisfying high demands for taste,color,flavor,and storage of meat products,water retention agents(WRAs)play an important role.Phosphate has been widely used as an attractive functional material for...For the purpose of satisfying high demands for taste,color,flavor,and storage of meat products,water retention agents(WRAs)play an important role.Phosphate has been widely used as an attractive functional material for water retention in current practical applications.However,excessive phosphate addition and longterm consumption may be harmful impacts on health and the environment.Therefore,it is vital to develop safe and efficient phosphate-free WRAs for further improving water-holding capacity(WHC)efficacy and edible safety,especially in meat products.In particular,sugar water retention agents(SWRAs)are increasingly popular because of their perfect safety,excellent WHC,and superior biological properties.This review discusses the inducements and mechanisms underlying water loss in meat products.In addition,we focused on the research progresses and related mechanisms of SWRAs in the WHC of meat products and its unique biological functions,as well as the extraction technology.Finally,the future application and development of SWRA were prospected.展开更多
Plants have long served as a cornerstone for drug discovery,offering a vast repertoire of bioactive compounds with proven efficacy in combating oxidative stress,a pivotal driver of chronic diseases such as cancer,diab...Plants have long served as a cornerstone for drug discovery,offering a vast repertoire of bioactive compounds with proven efficacy in combating oxidative stress,a pivotal driver of chronic diseases such as cancer,diabetes,cardiovascular disorders,and neurodegenerative conditions.This review synthesizes current knowledge on plant-derived antioxidants,emphasizing their mechanisms,therapeutic potential,and quantitative efficacy validated through standardized assays.Key phytochemicals,including polyphenols,carotenoids,flavonoids,and terpenoids,neutralize reactive oxygen species(ROS)through radical scavenging,enzyme modulation,and gene regulation.For instance,lutein,a carotenoid found in leafy greens,demonstrates potent antioxidant activity with IC50 values of 1.75μg/mL against hydroxyl radicals and 2.2μg/mL in lipid peroxidation inhibition,underscoring its role in mitigating cardiovascular and ocular diseases.Similarly,quercetin,a ubiquitous flavonoid in onions and berries,exhibits remarkable ROS-scavenging capacity,with IC50 values of 0.55μg/mL,2,2-Diphenyl-1-picrylhydrazyl(DPPH)and 1.17μg/mL,2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),supporting its use in reducing inflammation and neurodegeneration.The therapeutic promise of these compounds extends to disease-specific applications.Limonoids from citrus fruits,such as limonin(IC_(50)15-31μg/mL),enhance Phase II detoxification enzymes,offering protection against chemical carcinogens.Sulforaphane,a glucosinolate derived from cruciferous vegetables,shows potent anticancer activity with an IC50 of 85.66 mg in DPPH radical scavenging,whileβ-sitosterol(IC_(50)1.43-2.42 mM)inhibits tumor proliferation and cholesterol synthesis.Synergistic interactions further amplify their efficacy:phytoestrogens like genistein(IC_(50)13.00 ppm)and terpenoids such asα-pinene(IC_(50)12.57 mg/mL)collectively enhance antiinflammatory and antimicrobial responses,illustrating the multi-targeted nature of plant-based therapies.Beyond disease prevention,these compounds address age-related decline.Ascorbic acid(vitamin C),with an IC50 of 11.81μg/mL for antioxidant activity,mitigates skin aging and accelerates wound healing,while seleniumnanoparticles(IC_(50)0.437μg/mL)bolster immune function and reduce chemotherapy-induced toxicity.Dietary fibers,exemplified by sugar beet fibers(IC_(50)52.32μg/mL for DPPH scavenging),further contribute to cardiovascular health by lowering Low-Density Lipoprotein(LDL)cholesterol.This review not only catalogs the antioxidant prowess of phytochemicals but also highlights their translational potential.Advances in nanotechnology,such as nano-formulated curcumin,have overcome bioavailability challenges,enhancing clinical applicability.By integrating quantitative metrics(e.g.,IC50,radical scavenging rates)with mechanistic insights,this work bridges the gap between traditional knowledge and modern pharmacology.展开更多
Natural products are the important sources in cardiovascular drug development.In this study,twenty-nine buthutin derivatives were designed,synthesized,and evaluated for their NHE-1 inhibition and protective effects on...Natural products are the important sources in cardiovascular drug development.In this study,twenty-nine buthutin derivatives were designed,synthesized,and evaluated for their NHE-1 inhibition and protective effects on cardiomyo-cyte injury.The structure of the newly synthesized compounds had been confirmed by 1H-NMR,13C-NMR,and HR-ESI-MS spectra.Among all target compounds at 1μM,compounds 9d,9f,9k,9m,and 9n,with a protection ratio exceeding 30%,exerted stronger protective effects on H9c2 cardiomyocyte than positive control dexrazoxane and buthutin A.Meanwhile,compounds 9k,9m,and 9o showed the significant NHE-1 inhibitory activities on H9c2 cardiomyocyte,all with a dpHi/min value less than 0.23.What is more,compounds 9k,9m,9o and buthutin A all exhibited the specificity on NHE-1 inhibition.Molecular modelling studies suggested the ability of compounds 9m and 9o to establish interactions with three hydrogen bonds to Asp267 and Glu346 of NHE-1,but also the ability with much lower CDOCKER energies than positive control cariporide and buthutin A.The structure-activity relationship(SAR)studies suggested that the presences of amide group,four-carbon linker,and para hydroxyl benzene ring were advantageous pharmacophores for above two pharmacological actions.This research would open new avenues for developing amide-guanidine-based cardioprotective agents.展开更多
Objectives:SLFN11(Schlafen-11)enhances sensitivity to DNA-damaging agents(DDAs)and DNA damage response(DDR)inhibitors in various cancer types.However,its function in pancreatic cancer(PC)remains largely unknown.This r...Objectives:SLFN11(Schlafen-11)enhances sensitivity to DNA-damaging agents(DDAs)and DNA damage response(DDR)inhibitors in various cancer types.However,its function in pancreatic cancer(PC)remains largely unknown.This research aims to investigate the expression patterns of SLFN11 and other SLFN family members in PC and their correlation with drug sensitivity.Methods:SLFN11 expression and genetic alterations were analyzed using publicly available datasets(TCGA and GTEx).Functional studies,including cell cycle,apoptosis assays,and proliferation assays,were performed in SLFN11-knockdown and SLFN11-knockout(KO)PC cells.The relationship between SLFN11 expression and drug responsiveness was assessed via the CellMiner Cross-Database.Results:Analysis of multiple public datasets demonstrated that elevated SLFN11 expression is significantly linked with poor survival outcomes in PC,supporting its function as a predictive marker.Functional assays in PC cell lines demonstrated that SLFN11 knockdown disrupted G1 phase progression and increased apoptosis,indicating its involvement in tumor cell survival.Moreover,while elevated SLFN11 expression correlated with improved sensitivity to gemcitabine in some cell lines,CRISPR/Cas9-mediated SLFN11 knockout resulted in notable gemcitabine resistance.Importantly,this resistance was partially reversed when gemcitabine was combined with cisplatin and DDR inhibitors(Poly(ADP-ribose)polymerase(PARP),ataxia telangiectasia and Rad3 related(ATR),and Wee1 inhibitors),suggesting that SLFN11 modulates the reaction to both DNA-damaging agents and DDR-targeted therapies.Conclusion:Our findings indicate that SLFN11 plays a dual role in PC:as a prognostic marker,with high expression linked to poor clinical outcomes,and as a predictor of drug sensitivity,where its presence is associated with increased gemcitabine efficacy.However,the development of chemoresistance upon SLFN11 loss(and its partial reversal by DDR inhibitors)highlights the complexity of its function.These results underscore that SLFN11 expression alone may not fully determine gemcitabine response,and additional factors are likely involved.Further clinical validation is therefore essential to establish SLFN11 as a reliable biomarker for guiding DDR-targeted therapeutic strategies in PC.展开更多
基金supported by the Ministry of Education and Science of the Republic of North Macedonia through the project“Utilizing AI and National Large Language Models to Advance Macedonian Language Capabilties”。
文摘Artificial intelligence(AI)is reshaping financial systems and services,as intelligent AI agents increasingly form the foundation of autonomous,goal-driven systems capable of reasoning,learning,and action.This review synthesizes recent research and developments in the application of AI agents across core financial domains.Specifically,it covers the deployment of agent-based AI in algorithmic trading,fraud detection,credit risk assessment,roboadvisory,and regulatory compliance(RegTech).The review focuses on advanced agent-based methodologies,including reinforcement learning,multi-agent systems,and autonomous decision-making frameworks,particularly those leveraging large language models(LLMs),contrasting these with traditional AI or purely statistical models.Our primary goals are to consolidate current knowledge,identify significant trends and architectural approaches,review the practical efficiency and impact of current applications,and delineate key challenges and promising future research directions.The increasing sophistication of AI agents offers unprecedented opportunities for innovation in finance,yet presents complex technical,ethical,and regulatory challenges that demand careful consideration and proactive strategies.This review aims to provide a comprehensive understanding of this rapidly evolving landscape,highlighting the role of agent-based AI in the ongoing transformation of the financial industry,and is intended to serve financial institutions,regulators,investors,analysts,researchers,and other key stakeholders in the financial ecosystem.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.
基金023 Zhejiang Provincial Department of Education General Project:Research on an interdisciplinary teaching model to promote the development of computational thinking in the context of the new curriculum standards[Grant NO:Y202351596]Key Project of Zhejiang Provincial Education Science Planning:Research on an interdisciplinary teaching model to promote students’computational thinking from multiple analytical perspectives[Grant NO:2025SB103].
文摘This study constructs a reflective feedback model based on a pedagogical agent(PA)and explores its impact on students’problem-solving ability and cognitive load.A quasi-experimental design was used in the study,with 84 students from a middle school selected as the research subjects(44 in the experimental group and 40 in the control group).The experimental group used the reflective feedback model,while the control group used the factual feedback model.The results show that,compared with factual feedback,the reflective feedback model based on the pedagogical agent significantly improves students’problem-solving ability,especially at the action and thinking levels.In addition,this model effectively reduces students’cognitive load,especially in terms of internal and external load.
文摘Nanolipid carriers and traditional emulsion containing chemical sunscreens were prepared using emulsification combined with ultrasonic technology.The nanolipid carriers showed superior performance in sunscreen encapsulation,slow release and skin impermeability,and provided an excellent nanolipid slow-release encapsulation system for sunscreens.As observed by transmission electron microscopy,the nanolipid carriers were spherical shape,with smooth surface and uniform distribution,and the particle sizes were mainly concentrated in the range of 230 to 250 nm without agglomeration.The nanolipid carriers significantly improved the sunscreen performance through the synergistic effect of scattering and chemical absorption,and showed better UV stability than traditional sunscreen,indicating their photoprotective function.In vitro release experiments showed that the nano-lipidic carriers exhibited better release control when loaded with octyl methoxycinnamate(OMC)and butylmethoxydibenzoylmethane(BDFM)sunscreens than traditional traditional emulsions,with the cumulative release rate of OMC in the nano-lipidic carriers decreasing by 17.17% to 30.24% within 12 hours,and that of BDFM decreasing by 26.67% to 44.67%.26.67% to 44.16%.The results of the in vitro permeation experiment further confirmed that the nanolipid carriers could effectively encapsulate the sunscreens and prevent them from penetrating the skin barrier,thus reducing the skin irritation.Compared with traditional traditional emulsion,the cumulative penetration of OMC in nanostructured lipid carriers was 2.24μg/cm^(2)in 4 hours,while the cumulative penetration was reduced by 68.05%.The cumulative penetration of BDFM in the nanostructured lipid carrier was 3.24μg/cm^(2),with a 64.04%reduction in cumulative penetration.
基金Key Research project of Gansu Province of China(22YF7NA108)National Natural Science Foundation of China(31860549)+1 种基金Industry Supporting Project from Education Department of Gansu Province(2023CYZC-49)Major Science and Technology project of Gansu province(24ZDNA006)。
文摘【Objectives】Si and microbial application could relieve the crop replanting problems(CRPs).We further studied the change of key microorganisms that are related to the beneficial effects,aiming at provide reference for the manufacture and application of both microbial agents and Si fertilizer in food lily production.【Methods】A field experiment was conducted over a three-year period,from March 2019 to March 2022.The experimental field had been continuously cultivated with lily for 9 years.Three treatments were established:silicon fertilizer(SF),microbial agents(“Special 8^(TM)”,MF),and combined application of silicon fertilizer and microbial agents(SMF).A control group with blank soil(CK)was also included.At seedling stage of Lanzhou lilies in 2020 and 2021,the shoot and bulb dry weight,and the plant height and stem diameter of Lanzhou lilies were investigated for calculation of seedling index.In July 2020,20 plants were selected in each plot,and root zone soils were sampled at a depth of 20 cm,10 cm away from the roots,and then mixed to form a composite sample.The soil available Si and organic matter content were analyzed,and the fungal community structure and some specific microbial groups in soils were determined with high-throughput sequencing of ITS.【Results】All the three treatments significantly enhanced the lily plant growth and the seedling index,compared to CK.Besides,SF and MF treatments increased the relative abundances(RA)and diversity of fungal communities,and altered the community structures.The RA of some specific groups were found to be significantly correlated with the seedling index and/or soil available Si.Of them,the RA of the genera Fusarium,Dactylonectria,Humicola,Stilbella,and the species Humicola_grisea showed a positive correlation,while that of the genera Mortierella,Stilbella,Holtermanniella,and the species Mortierella_fatshederae showed a negative correlation with seedling index.The genera Fusarium,Stilbella,the species Humicola_grisea,and Dactylonectria_estremocensis showed a positive correlation,while the genura Stilbella,and the species Mortierella fatshederae showed a negative correlation with available Si content.In the co-occurence network of top twenty fungal genera and top sixteen bacterial genera(RA>0.2%),Holtermanniella was the only genus that interacted with the bacteria and negatively correlated with bacterial genus Blastococcus.Holtermanniella was also the most densely connected genera,followed by the genus Fusarium,Didymella and Humicola.In addition,the genus Holtermanniella was the key species connecting fungal and bacterial community in soil.Fungal functional prediction revealed that SF,MF and SMF treatments decreased plant pathogens guilds and increased the beneficial guilds Ectomycorrhizal,plant saprophyte,leaf saprophyte,and arbuscular mycorrhizal compared to CK.【Conclusions】Combined application of silicon fertilizer and microbial agents can alleviate continuous replanting problems of Lanzhou lilies through restoring the fungal community diversity,and promoting plant residue depredation,thus reducing soil born disease incidence.The beneficial genus Humicola and its one species H.grisea acts as bioconversion,and the genus Acremonium acts as plant pathogen inhibitor.
基金Supported by National Undergraduate Training Programs for Innovation and Entrepreneurship(202510580009)Special Project for Promoting the Coordinated Development of Urban and Rural Areas and Regions by Introducing Scientific and Technological Achievements of Guangdong Province into Counties and Towns(2025B0202010051)Project of High-quality Development in Hundred Counties,Thousands Towns and Ten Thousand Villages of Guangdong Provincial Department of Science and Technology:Key Dispatch Project for Rural Science and Technology Commissioners(KTP20240704).
文摘Given that the citrus psyllid is the primary vector of citrus Huanglongbing(HLB),there is an urgent need to control this pest to mitigate the spread of the disease.This paper reviews the current research on two predominant control strategies:chemical control and biological control agents,in managing the citrus psyllid.It emphasizes the mechanisms of action,efficacy,and application advancements of these control methods.Finally,the paper analyzes the principal challenges associated with the sustainable management of citrus psyllids and offers perspectives for future research.
文摘Conventional echocardiography can sometimes pose a challenge to diagnosis due to sub-optimal images.Ultrasound contrast agents(UCAs)have been shown to drastically enhance imaging quality,particularly depicting the left ventricular endocardial borders.Their use during echocardiography has become a valuable tool in non-invasive diagnostics.UCAs provide higher-quality images that may ultimately reduce the length of hospital stays and improve patient care.The higher cost associated with UCAs in many situations has been an impediment to frequent use.However,when used as an initial diagnostic test,UCA during rest echocardiogram is more cost-effective than the traditional diagnostic approach,which frequently includes multiple tests and imaging studies to make an accurate diagnosis.They can be easily performed across multiple patient settings and provide optimal images that allow clinicians to make sound medical decisions.This consequently allows for better diagnostic accuracies and improvement in patient care.
基金funding this work through the Large Research Group Project under grant number RGP.02/513/45.
文摘Acquired immune deficiency syndrome(AIDS)is the name used to describe several potentially life-threatening infections and disorders that happen when HIV has severely compromised the immune system.The primary effect of HIV is to decrease host immunity,exposing the host to external pathogens.The development of pharmaceutical drugs that directly cure the infection is crucial because of the current wide-ranging epidemic of HIV.Most therapeutic anti-HIV drugs are nucleosides.However,their high toxicity and potential for drug resistance restrict their use.Many of the most effective clinical drugs used to inhibit HIV,the activation of latent HIV,and AIDS have been obtained from natural sources.This review focuses on potential natural medicinal products for treating and managing HIV and AIDS.Notwithstanding,further clinical research studies are needed to understand the subject and its dynamics.
文摘Objectives:This review aimed to systematically analyze the technological frameworks,application scenarios,and outcomes of large language model-driven agents(LLMDAs)in nursing practice,and to summarize ethical,technological,and practical challenges,guiding future research and clinical implementation.Methods:This scoping review was conducted following the JBI guidelines.Five databases(PubMed,Embase,Web of Science,APA PsycNet,Cochrane Library)were systematically searched for peer-reviewed English-language studies from inception until September 9,2025.Eligible studies were screened by title and abstract,with full-text assessments conducted independently by two reviewers.Results:Twenty-five studies published between 2023 and 2025 were included,involving nine countries,primarily China(n=9)and the United States(n=9).Technological architectures were categorized into three types:collaborative models for solving complex tasks through multi-agent division of labor;augmentative models to enhance the accuracy of information outputs;and interactive models focusing on natural interactions and robotic task execution.Application scenarios included clinical,home-based,and community care.Studies indicated that LLMDAs can enhance diagnostic accuracy,optimize resource allocation,and improve patient experience.Primary ethical challenges identified included data privacy,reliability of generated content,and ambiguous attribution of responsibility.Conclusions:LLMDAs offer a novel paradigm for intelligent transformation in nursing care through integrative technological frameworks.They demonstrate considerable potential in enhancing clinical decision-making accuracy,efficiency of care delivery,and patient satisfaction.Addressing existing ethical,technical,and practical challenges is essential for facilitating broader clinical adoption.
文摘Energy security is the association between national security and the availability of natural resources for energy consumption.Access to cheaper energy has become essential to the functioning of modern economies.However,the uneven distribution of energy supplies among countries has led to significant challenges.International energy relations have contributed to the globalization of the world,leading to energy security and energy vulnerability at the same time.The first article in Science Direct for energy security appeared in 1993 with authors from USA.Gradually the number of articles and their origin increases.In 2024 we observe a boom of these publications-30(not only in Science Direct)and one planned for 2025.The recent article explores these publications and sorts them by origin and content.The content is distributed in five topics:computer technologies impact,artificial intelligence applications,environmental management and energy security,economics and policy for energy security,and emerging technologies for energy security.Since the share of AI usage is relatively small the author suggests scenarios for AI agents’application in various situations concerning environmental decisions,failures,cyber-attacks,performance,and pricing.
文摘Clinical pharmacy is on the cusp of exponential change powered by artificial intelligence agents,automation,data analytics,and robotics.Blockchain will enhance data integrity and transparency,and Augmented and Virtual Reality technologies will revolutionise training,patient education,and simulation-based care planning.Clinical pharmacists need to be ready and upskill to prepare for emerging technologies.The ethical,regulatory,and educational frameworks surrounding artificial intelligence and precision medicine will require constant attention,but the potential benefits for patient outcomes are unprecedented.Clinical pharmacists are in a prime position to design a new era in precision medicine,where technology works hand in hand with humans to transform healthcare.
基金supported by the Deputyship for Research&Innovation,Ministry of Education in Saudi Arabia(Project No.MoE-IF-UJ-R2-22-04220773-1).
文摘Domain randomization is a widely adopted technique in deep reinforcement learning(DRL)to improve agent generalization by exposing policies to diverse environmental conditions.This paper investigates the impact of different reset strategies,normal,non-randomized,and randomized,on agent performance using the Deep Deterministic Policy Gradient(DDPG)and Twin Delayed DDPG(TD3)algorithms within the CarRacing-v2 environment.Two experimental setups were conducted:an extended training regime with DDPG for 1000 steps per episode across 1000 episodes,and a fast execution setup comparing DDPG and TD3 for 30 episodes with 50 steps per episode under constrained computational resources.A step-based reward scaling mechanism was applied under the randomized reset condition to promote broader state exploration.Experimental results showthat randomized resets significantly enhance learning efficiency and generalization,with DDPG demonstrating superior performance across all reset strategies.In particular,DDPG combined with randomized resets achieves the highest smoothed rewards(reaching approximately 15),best stability,and fastest convergence.These differences are statistically significant,as confirmed by t-tests:DDPG outperforms TD3 under randomized(t=−101.91,p<0.0001),normal(t=−21.59,p<0.0001),and non-randomized(t=−62.46,p<0.0001)reset conditions.The findings underscore the critical role of reset strategy and reward shaping in enhancing the robustness and adaptability of DRL agents in continuous control tasks,particularly in environments where computational efficiency and training stability are crucial.
基金supported by the specialized fund project for the fundamental research operation of central-level public welfare scientific research institutes,titled“Research on the International Standards System Construction and Updates in the Field of Fire Protection(Project No.2023SJ09)”.
文摘This paper discusses the importance of standards in the fire extinguishing agent industry,and highlights the vital role of the standards in promoting technological innovation.China’s standards for fire extinguishing agent products have evolved significantly,aligning with industrial development,market demands,regulatory requirements,to respond to the great impact of international competition in the industry.The paper analyzes the current state of China’s standards,including their composition and integration with industry growth,green development strategies,and international harmonization.Future development strategies for the standards framework should focus on valid period estimation,fire test model development,and raw material selection guidelines.By implementing these strategies,China’s fire protection industry can enhance product quality,contribute to public safety,and maintain a competitive edge in the global market.
基金2024 Academic Research of Zhejiang Technical Institute of Economics:“Spillover Effects of Multimodal AI Agents on Green School Development”(Project No.:X2024038)2024-2025 Research and Creative Project,Department of Culture and Tourism:“The Application of Digital Information Technology in Safety Early Warning and Supervision of Cultural Relics in Zhejiang,China”(Project No.:2024KYY045)2024 General Research Project of Zhejiang Provincial Department of Education:“Empirical Research on Low-Carbon Economy Driving the Development of New Quality Productivity:A Case Study of Zhejiang Province”(Project No.:Y202456145)。
文摘The integration of Green Artificial Intelligence(AI)technologies into educational systems offers a promising avenue to enhance operational efficiency while addressing sustainability challenges.Through a rigorous three-phase methodology combining literature review,AI agent development,and participatory workshop-based case analysis,this paper highlights the pivotal role of AI agents,as applications of Green AI technologies,in driving transformative outcomes within schools.By directly improving self-learning efficiency and reducing learning costs for students,enhancing management and service efficiency,reducing labor costs for schools,as well as minimizing resource dependence for both teachers and students,AI agents create a foundation for sustainable operations.These direct effects generate positive spillover effects,cascading into broader outcomes,including innovation performance,economic efficiency,and environmental sustainability,aligning with the United Nations Sustainable Development Goals(SDGs).By presenting a comprehensive conceptual model,this study demonstrates the pathways through which Green AI contributes to sustainable development in education and emphasizes its critical role in bridging technological innovation with sustainability.This framework provides significant theoretical insights for further empirical research while offering actionable strategies for policymakers and educators to harness Green AI for building sustainable schools with a student-centered approach.
基金Supported by The National Natural Science Foundation of China,No.82273986Natural Science Foundation of Zhejiang Province,No.LYY22H310014.
文摘Exploration of immunosuppressive agents for the treatment of diabetes is a burgeoning field that has captured the attention of the medical community.The innovative approach of using these agents to combat diabetes is driven by their diverse capabilities to regulate the immune system,which is pivotal for disease pathogenesis.The primary objective is to enhance the management of blood glucose levels,which is a critical factor in the daily life of diabetic patients.This comprehensive review delves into the therapeutic horizons opened by immunosuppressive agents,particularly their potential impact on type 1 and type 2 diabetes mellitus,and their utility in the transplantation process.The complex etiology of diabetes,which involves a delicate interplay of genetic,environmental,and immunological factors,presents a multifaceted target landscape for these therapies.The agents discussed in the review,including CD3 inhibitors,cytotoxic T-lymphocyte-associated protein 4-immunoglobulin G,Janus kinase inhibitors,anti-thymocyte globulin,tumor necrosis factor-αinhibitors,CD20 inhibitors,alefacept,and alemtuzumab,each bring a unique mechanism to the table,offering a tailored approach to immune modulation.As research progresses,emphasis is being placed on evaluating the long-term efficacy and safety of these agents to pave the way for more personalized and effective diabetes management strategies.
基金funded by National Natural Science Foundation of China(51901160)。
文摘For the purpose of satisfying high demands for taste,color,flavor,and storage of meat products,water retention agents(WRAs)play an important role.Phosphate has been widely used as an attractive functional material for water retention in current practical applications.However,excessive phosphate addition and longterm consumption may be harmful impacts on health and the environment.Therefore,it is vital to develop safe and efficient phosphate-free WRAs for further improving water-holding capacity(WHC)efficacy and edible safety,especially in meat products.In particular,sugar water retention agents(SWRAs)are increasingly popular because of their perfect safety,excellent WHC,and superior biological properties.This review discusses the inducements and mechanisms underlying water loss in meat products.In addition,we focused on the research progresses and related mechanisms of SWRAs in the WHC of meat products and its unique biological functions,as well as the extraction technology.Finally,the future application and development of SWRA were prospected.
基金funded by the project of Scientific Research Start-up Funds for Doctoral Talents of Zhaotong University-Mingzheng Duan,Grant number:202406Young Talent Project of Talent Support Program for the Development of Yunnan,Grant number:210604199008271015.
文摘Plants have long served as a cornerstone for drug discovery,offering a vast repertoire of bioactive compounds with proven efficacy in combating oxidative stress,a pivotal driver of chronic diseases such as cancer,diabetes,cardiovascular disorders,and neurodegenerative conditions.This review synthesizes current knowledge on plant-derived antioxidants,emphasizing their mechanisms,therapeutic potential,and quantitative efficacy validated through standardized assays.Key phytochemicals,including polyphenols,carotenoids,flavonoids,and terpenoids,neutralize reactive oxygen species(ROS)through radical scavenging,enzyme modulation,and gene regulation.For instance,lutein,a carotenoid found in leafy greens,demonstrates potent antioxidant activity with IC50 values of 1.75μg/mL against hydroxyl radicals and 2.2μg/mL in lipid peroxidation inhibition,underscoring its role in mitigating cardiovascular and ocular diseases.Similarly,quercetin,a ubiquitous flavonoid in onions and berries,exhibits remarkable ROS-scavenging capacity,with IC50 values of 0.55μg/mL,2,2-Diphenyl-1-picrylhydrazyl(DPPH)and 1.17μg/mL,2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),supporting its use in reducing inflammation and neurodegeneration.The therapeutic promise of these compounds extends to disease-specific applications.Limonoids from citrus fruits,such as limonin(IC_(50)15-31μg/mL),enhance Phase II detoxification enzymes,offering protection against chemical carcinogens.Sulforaphane,a glucosinolate derived from cruciferous vegetables,shows potent anticancer activity with an IC50 of 85.66 mg in DPPH radical scavenging,whileβ-sitosterol(IC_(50)1.43-2.42 mM)inhibits tumor proliferation and cholesterol synthesis.Synergistic interactions further amplify their efficacy:phytoestrogens like genistein(IC_(50)13.00 ppm)and terpenoids such asα-pinene(IC_(50)12.57 mg/mL)collectively enhance antiinflammatory and antimicrobial responses,illustrating the multi-targeted nature of plant-based therapies.Beyond disease prevention,these compounds address age-related decline.Ascorbic acid(vitamin C),with an IC50 of 11.81μg/mL for antioxidant activity,mitigates skin aging and accelerates wound healing,while seleniumnanoparticles(IC_(50)0.437μg/mL)bolster immune function and reduce chemotherapy-induced toxicity.Dietary fibers,exemplified by sugar beet fibers(IC_(50)52.32μg/mL for DPPH scavenging),further contribute to cardiovascular health by lowering Low-Density Lipoprotein(LDL)cholesterol.This review not only catalogs the antioxidant prowess of phytochemicals but also highlights their translational potential.Advances in nanotechnology,such as nano-formulated curcumin,have overcome bioavailability challenges,enhancing clinical applicability.By integrating quantitative metrics(e.g.,IC50,radical scavenging rates)with mechanistic insights,this work bridges the gap between traditional knowledge and modern pharmacology.
基金supported by the National Natural Science Foundation of China(NSFC)Youth Project(No.82204397).
文摘Natural products are the important sources in cardiovascular drug development.In this study,twenty-nine buthutin derivatives were designed,synthesized,and evaluated for their NHE-1 inhibition and protective effects on cardiomyo-cyte injury.The structure of the newly synthesized compounds had been confirmed by 1H-NMR,13C-NMR,and HR-ESI-MS spectra.Among all target compounds at 1μM,compounds 9d,9f,9k,9m,and 9n,with a protection ratio exceeding 30%,exerted stronger protective effects on H9c2 cardiomyocyte than positive control dexrazoxane and buthutin A.Meanwhile,compounds 9k,9m,and 9o showed the significant NHE-1 inhibitory activities on H9c2 cardiomyocyte,all with a dpHi/min value less than 0.23.What is more,compounds 9k,9m,9o and buthutin A all exhibited the specificity on NHE-1 inhibition.Molecular modelling studies suggested the ability of compounds 9m and 9o to establish interactions with three hydrogen bonds to Asp267 and Glu346 of NHE-1,but also the ability with much lower CDOCKER energies than positive control cariporide and buthutin A.The structure-activity relationship(SAR)studies suggested that the presences of amide group,four-carbon linker,and para hydroxyl benzene ring were advantageous pharmacophores for above two pharmacological actions.This research would open new avenues for developing amide-guanidine-based cardioprotective agents.
基金supported by the 8th AstraZeneca-KHIDI(Korea Health Industry Development Institute)oncology research programa research grant was supported by AstraZeneca and by Grant No.02-2022-0020 from the Seoul National University Hospital(SNUBH)Research Fund.
文摘Objectives:SLFN11(Schlafen-11)enhances sensitivity to DNA-damaging agents(DDAs)and DNA damage response(DDR)inhibitors in various cancer types.However,its function in pancreatic cancer(PC)remains largely unknown.This research aims to investigate the expression patterns of SLFN11 and other SLFN family members in PC and their correlation with drug sensitivity.Methods:SLFN11 expression and genetic alterations were analyzed using publicly available datasets(TCGA and GTEx).Functional studies,including cell cycle,apoptosis assays,and proliferation assays,were performed in SLFN11-knockdown and SLFN11-knockout(KO)PC cells.The relationship between SLFN11 expression and drug responsiveness was assessed via the CellMiner Cross-Database.Results:Analysis of multiple public datasets demonstrated that elevated SLFN11 expression is significantly linked with poor survival outcomes in PC,supporting its function as a predictive marker.Functional assays in PC cell lines demonstrated that SLFN11 knockdown disrupted G1 phase progression and increased apoptosis,indicating its involvement in tumor cell survival.Moreover,while elevated SLFN11 expression correlated with improved sensitivity to gemcitabine in some cell lines,CRISPR/Cas9-mediated SLFN11 knockout resulted in notable gemcitabine resistance.Importantly,this resistance was partially reversed when gemcitabine was combined with cisplatin and DDR inhibitors(Poly(ADP-ribose)polymerase(PARP),ataxia telangiectasia and Rad3 related(ATR),and Wee1 inhibitors),suggesting that SLFN11 modulates the reaction to both DNA-damaging agents and DDR-targeted therapies.Conclusion:Our findings indicate that SLFN11 plays a dual role in PC:as a prognostic marker,with high expression linked to poor clinical outcomes,and as a predictor of drug sensitivity,where its presence is associated with increased gemcitabine efficacy.However,the development of chemoresistance upon SLFN11 loss(and its partial reversal by DDR inhibitors)highlights the complexity of its function.These results underscore that SLFN11 expression alone may not fully determine gemcitabine response,and additional factors are likely involved.Further clinical validation is therefore essential to establish SLFN11 as a reliable biomarker for guiding DDR-targeted therapeutic strategies in PC.
