The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of th...The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.展开更多
A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an or...A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.展开更多
Considering the impact of terminal impact time constraints and the state information of maneuvering targets on the guidance accuracy in multi-UAV cooperative guidance,this paper proposes an impact time cooperative con...Considering the impact of terminal impact time constraints and the state information of maneuvering targets on the guidance accuracy in multi-UAV cooperative guidance,this paper proposes an impact time cooperative control guidance law(ITCCG)that combines the optimal error dynamics with an improved adaptive cubature Kalman filter(IACKF)algorithm.First,a terminal impact time feedback term is introduced into proportional navigation guidance based on the relative virtual guidance model,and terminal time control is achieved through optimal error dynamics.Then,the Huber loss function is used to reduce the impact of measurement outliers,and the diagonal decomposition is applied to address the issue of non-positive definite matrices that cannot undergo Cholesky decomposition.Finally,the ITCCG and IACKF algorithms combined achieve multi-UAV time-cooperated guidance based on maneuvering target state estimation.Simulation results show that the proposed algorithm effectively reduces the target state estimation error and achieves cooperative guidance within the desired time frame.展开更多
Naphthalene,anthracene and pyridone endoperoxides are known to thermally release singlet oxygen.However,in the cycloreversion reaction,singlet oxygen is produced stoichiometrically;therefore,multiple singlet oxygen re...Naphthalene,anthracene and pyridone endoperoxides are known to thermally release singlet oxygen.However,in the cycloreversion reaction,singlet oxygen is produced stoichiometrically;therefore,multiple singlet oxygen releasing modules are expected to be very useful in inducing apoptosis of cancer cells.Herein,we present a potential therapeutic agent presenting three-pyridone endoperoxide modules and a mitochondria targeting group.Compared to previously reported pyridone-based monofunctional endoperoxides,the triple endoperoxide is highly effective as evidenced by assays and fluorescence microscopy.展开更多
Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-through...Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.展开更多
In recent years,proteolysis-targeting chimeras(PROTACs)have gained widespread attention as an emerging therapeutic approach.PROTACs are bifunctional molecules composed of a target protein-binding ligand,an E3 ubiquiti...In recent years,proteolysis-targeting chimeras(PROTACs)have gained widespread attention as an emerging therapeutic approach.PROTACs are bifunctional molecules composed of a target protein-binding ligand,an E3 ubiquitin ligase ligand,and a linker connecting these ligands.By harnessing the cell’s intrinsic ubiquitin-proteasome system(UPS),they promote the ubiquitination of specific target proteins,leading to their degradation and therapeutic effects.PROTACs show exceptional promise in targeting conventional“undruggable”targets compared to traditional small-molecule inhibitors.This review provides an overview of PROTACs,including their molecular mechanism of action,therapeutic benefits,development history,key design aspects,current research and development challenges,and future trends in nextgeneration PROTAC technology.展开更多
The published article titled“MicroRNA-133b Inhibits Proliferation,Cellular Migration,and Invasion via Targeting LASP1 in Hepatocarcinoma Cells”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1269–1282.
Food-grade biopolymers and nanotechnology have been increasingly used to revolutionize the delivery of bioactive compounds by enhancing stability,bioavailability,and controlled release.Within the scope of nanoencapsul...Food-grade biopolymers and nanotechnology have been increasingly used to revolutionize the delivery of bioactive compounds by enhancing stability,bioavailability,and controlled release.Within the scope of nanoencapsulation systems,this review explores food-derived polymers such as vicilin,zein,gluten,cruciferin,inulin,and others.These biopolymers are ideal since they encapsulate numerous functional compounds,such as vitamins,probiotics,essential oils,and polyphenols,because they are biocompatible,amphiphilic,and biodegradable.The specific physical and chemical properties of each polymer,extraction procedures,and nanoencapsulation techniques applied therein(e.g.,ionic gelation and spray drying)are described.The review highlights advanced targeting systems like pH-sensitive,magnetic delivery.Additional applications include those in synergistic nutraceutical systems,oral administration of vaccination,and intelligent food packaging.All these findings demonstrate that food polymers are increasingly more viable as functional nanocarriers by way of increasing bioactive delivery and the shifting requirements of personalized and health-based dietary regimes.展开更多
Delivery carriers serve as a highly efficient approach for precision nutrition and medicine;however,artificial delivery carriers are prone to triggering the immune response and have the disadvantages of poor stability...Delivery carriers serve as a highly efficient approach for precision nutrition and medicine;however,artificial delivery carriers are prone to triggering the immune response and have the disadvantages of poor stability and low bioavailability.Extracellular vesicles(EVs),nucleus-free biological particles composed of phospholipid bilayers secreted by living cells,are a new generation of targeted delivery carriers.In recent years,an increasing number of species have been reported to contain EVs.Among them,food-derived extracellular vesicles(FDEVs)show outstanding comprehensive properties.FDEVs are considered to have great application potential due to their wide range of sources,high yields,absence of human pathogenic pathogens,and ethical concerns.In this review,the preparation,nomenclature,physicochemical characteristics,and preservation methods of FDEVs are discussed,as well as their potential protein markers,bioactivities,and applications as novel targeted delivery carriers of FDEVs from animals,plants,and microorganisms.We also summarized the adverse consequences of FDEVs in current studies,and put forward the problems and challenges in the process of FDEVs research and commercialization.In short,the importance of FDEVs has been highlighted,and FDEVs have good application prospects as a new class of targeted delivery carriers.The current problems should be paid attention to and actively solved.展开更多
Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through...Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through integration of large-scale multi-omics datasets.Methods:We constructed a multi-stage analytical framework encompassing 32 proteomic datasets(covering 2914 unique plasma proteins)and 6 transcriptomic datasets.Multi-omics integration strategies,including two-sample Mendelian randomization,colocalization analysis,and functional enrichment analysis,were employed to identify and validate causal relationships between candidate targets and GCA risk across 4 independent European-ancestry GCA cohorts.Single-cell RNA sequencing analysis of peripheral blood mononuclear cells from untreated GCA patients was performed to characterize hub gene-immune cell relationships.Results:We identified 43 plasma proteins causally associated with GCA[false discovery rate(FDR)<0.05],with 17 representing novel therapeutic targets.Through dual validation using proteome-wide association studies and transcriptome-wide association studies,we identified 13 high-confidence candidate targets with distinct tissue-specific expression patterns.Unc-51 like kinase 3(ULK3)emerged as the strongest protective factor(odds ratio=0.47,95%confidence interval:0.37–0.71)through autophagy regulation,while SLAMF7 represents an immediate drug repositioning opportunity as the target of food and drug administration-approved elotuzumab.Five targets have existing approved drugs(SLAMF7,ICAM1,IL18,IL6ST,CTSS).Single-cell analysis revealed profound disruption of hub gene-immune cell relationships in untreated GCA patients,with cell-type-specific alterations in inflammatory gene expression,and TYMP as the most critical hub gene.Conclusions:This study provides a clinically-actionable atlas of 43 potential therapeutic targets in GCA,identifying novel mechanisms including autophagy modulation and metabolic reprogramming,with immediate drug repositioning opportunities and precision medicine strategies based on tissue-specific and cell-type-specific expression patterns.These findings require experimental validation before clinical translation.展开更多
To address the challenges of small target detection and significant scale variations in unmanned aerial vehicle(UAV)aerial imagery,which often lead to missed and false detections,we propose Multi-scale Feature Fusion ...To address the challenges of small target detection and significant scale variations in unmanned aerial vehicle(UAV)aerial imagery,which often lead to missed and false detections,we propose Multi-scale Feature Fusion YOLO(MFF-YOLO),an enhanced algorithm based on YOLOv8s.Our approach introduces a Multi-scale Feature Fusion Strategy(MFFS),comprising the Multiple Features C2f(MFC)module and the Scale Sequence Feature Fusion(SSFF)module,to improve feature integration across different network levels.This enables more effective capture of fine-grained details and sequential multi-scale features.Furthermore,we incorporate Inner-CIoU,an improved loss function that uses auxiliary bounding boxes to enhance the regression quality of small object boxes.To ensure practicality for UAV deployment,we apply the Layer-adaptive Magnitude-based pruning(LAMP)method to significantly reduce model size and computational cost.Experiments on the VisDrone2019 dataset show that MFF-YOLO achieves a 5.7% increase in mean average precision(mAP)over the baseline,while reducing parameters by 8.5 million and computation by 17.5%.The results demonstrate that our method effectively improves detection performance in UAV aerial scenarios.展开更多
Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensiv...Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensively explores how cancer cells rewire BCAA metabolism to enhance proliferation,survival,and therapy resistance.Tumors manipulate BCAA uptake and catabolism via high expression of transporters like L-type amino acid transporter 1(LAT1)and enzymes including branched chain amino acid transaminase 1(BCAT1),branched chain amino acid transaminase 2(BCAT2),branched-chain alpha-keto acid dehydrogenase(BCKDH),and branched chain alpha-keto acid dehydrogenase kinase(BCKDK).These alterations sustain energy production,biosynthesis,redox homeostasis,and oncogenic signaling(especially mammalian target of rapamycin complex 1[mTORC1]).Crucially,tumor-driven BCAA depletion also shapes an immunosuppressive microenvironment,impairing anti-tumor immunity by limiting essential nutrients for T cells and natural killer(NK)cells.Innovative therapeutic strategies targeting BCAA pathways—ranging from selective small-molecule inhibitors(e.g.,LAT1 and BCAT1/2)to dietary modulation—have shown promising preclinical and early clinical efficacy,highlighting their potential to exploit metabolic vulnerabilities in cancer cells while bolstering immune responses.By integrating multi-omics data and precision targeting approaches,this review underscores the translational significance of BCAA metabolic reprogramming,positioning it as a novel frontier in cancer treatment.展开更多
Human Resource(HR)operations increasingly rely on cloud-based platforms that provide hiring,payroll,employee management,and compliance services.These systems,typically built on multi-tenant microservice architectures,...Human Resource(HR)operations increasingly rely on cloud-based platforms that provide hiring,payroll,employee management,and compliance services.These systems,typically built on multi-tenant microservice architectures,offer scalability and efficiency but also expand the attack surface for adversaries.Ransomware has emerged as a leading threat in this domain,capable of halting workflows and exposing sensitive employee records.Traditional defenses such as static hardening and signature-based detection often fail to address the dynamic requirements of HR Software as a Service(SaaS),where continuous availability and privacy compliance are critical.This paper presents a Moving Target Defense(MTD)framework for HR SaaS that combines container mutation,IP hopping,and node reassignment to randomize the attack surface without pausing services.Many prior defenses for cloud or IoT rely on static hardening or signature-driven detection and do not meet HR SaaS needs such as uninterrupted sessions,privacy compliance,and live service continuity.This paper presents a MTD framework for HR SaaS that combines container mutation,IP hopping,and node reassignment to randomize the attack surface without pausing services.The framework runs on Kubernetes and uses a KL-divergence-based anomaly detector that monitors HR access logs across five modules(onboarding,employee records,leave,payroll,and exit).In simulation with realistic HR traffic,the approach reaches 96.9% average detection accuracy with AUC 0.94-0.98,cuts mean time to containment to 91.4 s,and lowers the ransomware encryption rate to 13.2%.Measured overheads for CPU,memory,and per-mutation latency remainmodest.Comparedwith priorMTDand non-MTD baselines,the design provides stronger containment without service interruption and aligns with zero-trust and compliance goals.Its modular implementation and control-plane orchestration support stepwise,enterprise-scale deployment in HR SaaS environments.展开更多
Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,ta...Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,tau is not an easy target because it dynamically interacts with microtubules and other cellular components,which presents a challenge for tau-targeted drugs.New cellular models could aid the development of mechanism-based tau-targeted therapies.展开更多
In this article,the unit of total distance in Fig.2B was misused.In fact,the unit of total distance exported by the system was"pixels".After correction,the data in Fig.2B were not changed.The Fig.2B should h...In this article,the unit of total distance in Fig.2B was misused.In fact,the unit of total distance exported by the system was"pixels".After correction,the data in Fig.2B were not changed.The Fig.2B should have appeared as shown below.展开更多
Hepatic fibrosis is regulated by the synergistic actions of various cells and cytokines,with the activation and proliferation of hepatic stellate cells(HSCs) being considered the central event in this process.To achie...Hepatic fibrosis is regulated by the synergistic actions of various cells and cytokines,with the activation and proliferation of hepatic stellate cells(HSCs) being considered the central event in this process.To achieve specific targeting of activated hepatic stellate cells(a HSCs) and precise treatment of hepatic fibrosis,this study developed a dual-functional drug delivery system(SIL/c RGD-PEG-PPS PMs) with both targeting and responsive release capabilities.It aims to target the αvβ 3 receptor specifically expressed on the surface of a HSCs using the cyclic peptide c(RGDyk),and to exploit the high reactive oxygen species(ROS) level in the cellular microenvironment to achieve concentrated burst release of drugs at the pathological sites of hepatic fibrosis.Based on multiple assessments,SIL/c RGD-PEG-PPS PMs specifically enhanced the targeted delivery of silybin(SIL) to a HSCs,inhibited the proliferation and migration of a HSCs,and exhibited good biosafety.Additionally,it demonstrated excellent anti-fibrotic activity in fibrotic mice.In summary,this study shows great potential in targeted treatment of hepatic fibrosis and provides a multifunctional tool for advancing the research and therapeutic strategies of hepatic fibrosis.展开更多
Alzheimer’s disease(AD)remains an incurable neurodegenerative disorder with devastating societal and personal impacts.Despite decades of intensive research,therapeutic efforts targeting the clinical stages of AD have...Alzheimer’s disease(AD)remains an incurable neurodegenerative disorder with devastating societal and personal impacts.Despite decades of intensive research,therapeutic efforts targeting the clinical stages of AD have largely failed to halt or reverse disease progression.This has prompted a critical shift in focus toward the earlier,preclinical stages of AD,where interventions may hold greater promise for altering the disease trajectory.展开更多
Recently,Tian et al.published a research paper with significant breakthroughs in Cell[1].The study found that targeting the signalling pathways named Serpine2-lowdensity lipoprotein receptor-related protein 1(Lrp1)and...Recently,Tian et al.published a research paper with significant breakthroughs in Cell[1].The study found that targeting the signalling pathways named Serpine2-lowdensity lipoprotein receptor-related protein 1(Lrp1)and ectonucleoside triphosphate diphosphohydrolase 1(CD39)-adenosine A_(3)receptor(A_(3)AR)is a promising strategy for the treatment of vascular dementia.The Serpine2-Lrp1 signalling pathway primarily exerts its therapeutic effects on myelin regeneration by regulating the differentiation of oligodendrocyte precursor cells.Serpine2 is a secretory serine protease inhibitor regulates proteolytic homeostasis.It may also bind to cell surface receptors such as Lrp1 to directly activate signalling pathways.As a transmembrane glycoprotein receptor,Lrpl mediates the endocytic clearance of ligands.展开更多
Within the domain of Intelligent Group Systems(IGSs),this paper develops a resourceaware multitarget Constant False Alarm Rate(CFAR)detection framework for multisite MIMO radar systems.It underscores the necessity of ...Within the domain of Intelligent Group Systems(IGSs),this paper develops a resourceaware multitarget Constant False Alarm Rate(CFAR)detection framework for multisite MIMO radar systems.It underscores the necessity of managing finite transmit and receive antennas and transmit power systematically to enhance detection performance.To tackle the multidimensional resource optimization challenge,we introduce a Cooperative Transmit-Receive Antenna Selection and Power Allocation(CTRSPA)strategy.It employs a perception-action cycle that incorporates uncertain external support information to optimize worst-case detection performance with multiple targets.First,we derive a closed-form expression that incorporates uncertainty for the noncoherent integration squared-law detection probability using the Neyman-Pearson criterion.Subsequently,a joint optimization model for antenna selection and power allocation in CFAR detection is formulated,incorporating practical radar resource constraints.Mathematically,this represents an NPhard problem involving coupled continuous and Boolean variables.We propose a three-stage method—Reformulation,Node Picker,and Convex Power Allocation—that capitalizes on the independent convexity of the optimization model for each variable,ensuring a near-optimal result.Simulations confirm the approach's effectiveness,efficiency,and timeliness,particularly for large-scale radar networks,and reveal the impact of threat levels,system layout,and detection parameters on resource allocation.展开更多
Transient receptor potential vanilloid subtype 1(TRPV1),a polymodally activated,calcium-permeable non-selective cation channel,is broadly present in all parts of the body,with notable expression in the nociceptive neu...Transient receptor potential vanilloid subtype 1(TRPV1),a polymodally activated,calcium-permeable non-selective cation channel,is broadly present in all parts of the body,with notable expression in the nociceptive neurons.Both physiological and pathological functions rely heavily on this ion channel,mediating responses to a variety of stimuli and contributing to the maintenance of bodily homeostasis.Its unique ability to respond to temperature changes,chemical ligands,and voltage fluctuations positions TRPV1 as a key target in understanding and modulating normal bodily functions,in addition to diagnosing and treating diseases.This review synthesizes current knowledge on the structure,gating mechanisms,and physiological and pathological roles of TRPV1,highlighting its potential as a therapeutic target across multiple disease states.By providing a comprehensive overview of the multifaceted functions of TRPV1,this review aims to inform and inspire future research,finally contributing to the advancement of new therapeutic techniques focusing on TRPV1 to enhance human health.展开更多
基金partly supported by the Yan’an University Qin Chuanyuan“Scientist+Engineer”Team Special Fund,No.2023KXJ-012(to YL)Yan’an University Transformation of Scientific and Technological Achievements Fund,No.2023CGZH-001(to YL)+2 种基金College Students Innovation and Entrepreneurship Training Program,Nos.D2023158,202410719056(to XS,JM)Yan’an University Production and Cultivation Project,No.CXY202001(to YL)Kweichow Moutai Hospital Research and Talent Development Fund Project,No.MTyk2022-25(to XO)。
文摘The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.
文摘A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.
基金supported by the Fundamental Research Funds for the Central Universities of China(FRF-TP-24-058A)with additional support from the National Key Laboratory of Helicopter Aeromechanics(2024-ZSJ-LB-02-02).
文摘Considering the impact of terminal impact time constraints and the state information of maneuvering targets on the guidance accuracy in multi-UAV cooperative guidance,this paper proposes an impact time cooperative control guidance law(ITCCG)that combines the optimal error dynamics with an improved adaptive cubature Kalman filter(IACKF)algorithm.First,a terminal impact time feedback term is introduced into proportional navigation guidance based on the relative virtual guidance model,and terminal time control is achieved through optimal error dynamics.Then,the Huber loss function is used to reduce the impact of measurement outliers,and the diagonal decomposition is applied to address the issue of non-positive definite matrices that cannot undergo Cholesky decomposition.Finally,the ITCCG and IACKF algorithms combined achieve multi-UAV time-cooperated guidance based on maneuvering target state estimation.Simulation results show that the proposed algorithm effectively reduces the target state estimation error and achieves cooperative guidance within the desired time frame.
基金supported by the National Natural Science Foundation of China(22007008,22178048).
文摘Naphthalene,anthracene and pyridone endoperoxides are known to thermally release singlet oxygen.However,in the cycloreversion reaction,singlet oxygen is produced stoichiometrically;therefore,multiple singlet oxygen releasing modules are expected to be very useful in inducing apoptosis of cancer cells.Herein,we present a potential therapeutic agent presenting three-pyridone endoperoxide modules and a mitochondria targeting group.Compared to previously reported pyridone-based monofunctional endoperoxides,the triple endoperoxide is highly effective as evidenced by assays and fluorescence microscopy.
基金the Deanship of Research and Graduate Studies at King Khalid University,KSA,for funding this work through the Large Research Project under grant number RGP2/164/46.
文摘Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.
文摘In recent years,proteolysis-targeting chimeras(PROTACs)have gained widespread attention as an emerging therapeutic approach.PROTACs are bifunctional molecules composed of a target protein-binding ligand,an E3 ubiquitin ligase ligand,and a linker connecting these ligands.By harnessing the cell’s intrinsic ubiquitin-proteasome system(UPS),they promote the ubiquitination of specific target proteins,leading to their degradation and therapeutic effects.PROTACs show exceptional promise in targeting conventional“undruggable”targets compared to traditional small-molecule inhibitors.This review provides an overview of PROTACs,including their molecular mechanism of action,therapeutic benefits,development history,key design aspects,current research and development challenges,and future trends in nextgeneration PROTAC technology.
文摘The published article titled“MicroRNA-133b Inhibits Proliferation,Cellular Migration,and Invasion via Targeting LASP1 in Hepatocarcinoma Cells”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1269–1282.
文摘Food-grade biopolymers and nanotechnology have been increasingly used to revolutionize the delivery of bioactive compounds by enhancing stability,bioavailability,and controlled release.Within the scope of nanoencapsulation systems,this review explores food-derived polymers such as vicilin,zein,gluten,cruciferin,inulin,and others.These biopolymers are ideal since they encapsulate numerous functional compounds,such as vitamins,probiotics,essential oils,and polyphenols,because they are biocompatible,amphiphilic,and biodegradable.The specific physical and chemical properties of each polymer,extraction procedures,and nanoencapsulation techniques applied therein(e.g.,ionic gelation and spray drying)are described.The review highlights advanced targeting systems like pH-sensitive,magnetic delivery.Additional applications include those in synergistic nutraceutical systems,oral administration of vaccination,and intelligent food packaging.All these findings demonstrate that food polymers are increasingly more viable as functional nanocarriers by way of increasing bioactive delivery and the shifting requirements of personalized and health-based dietary regimes.
基金supported by the National Natural Science Foundation of China(82373277).
文摘Delivery carriers serve as a highly efficient approach for precision nutrition and medicine;however,artificial delivery carriers are prone to triggering the immune response and have the disadvantages of poor stability and low bioavailability.Extracellular vesicles(EVs),nucleus-free biological particles composed of phospholipid bilayers secreted by living cells,are a new generation of targeted delivery carriers.In recent years,an increasing number of species have been reported to contain EVs.Among them,food-derived extracellular vesicles(FDEVs)show outstanding comprehensive properties.FDEVs are considered to have great application potential due to their wide range of sources,high yields,absence of human pathogenic pathogens,and ethical concerns.In this review,the preparation,nomenclature,physicochemical characteristics,and preservation methods of FDEVs are discussed,as well as their potential protein markers,bioactivities,and applications as novel targeted delivery carriers of FDEVs from animals,plants,and microorganisms.We also summarized the adverse consequences of FDEVs in current studies,and put forward the problems and challenges in the process of FDEVs research and commercialization.In short,the importance of FDEVs has been highlighted,and FDEVs have good application prospects as a new class of targeted delivery carriers.The current problems should be paid attention to and actively solved.
基金supported by grants from the Fundamental Research Funds for the Central Universities(No.2025ZFJH03)the Central Guidance Fund for Local Science and Technology Development(No.2024ZY01054)the CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-045).
文摘Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through integration of large-scale multi-omics datasets.Methods:We constructed a multi-stage analytical framework encompassing 32 proteomic datasets(covering 2914 unique plasma proteins)and 6 transcriptomic datasets.Multi-omics integration strategies,including two-sample Mendelian randomization,colocalization analysis,and functional enrichment analysis,were employed to identify and validate causal relationships between candidate targets and GCA risk across 4 independent European-ancestry GCA cohorts.Single-cell RNA sequencing analysis of peripheral blood mononuclear cells from untreated GCA patients was performed to characterize hub gene-immune cell relationships.Results:We identified 43 plasma proteins causally associated with GCA[false discovery rate(FDR)<0.05],with 17 representing novel therapeutic targets.Through dual validation using proteome-wide association studies and transcriptome-wide association studies,we identified 13 high-confidence candidate targets with distinct tissue-specific expression patterns.Unc-51 like kinase 3(ULK3)emerged as the strongest protective factor(odds ratio=0.47,95%confidence interval:0.37–0.71)through autophagy regulation,while SLAMF7 represents an immediate drug repositioning opportunity as the target of food and drug administration-approved elotuzumab.Five targets have existing approved drugs(SLAMF7,ICAM1,IL18,IL6ST,CTSS).Single-cell analysis revealed profound disruption of hub gene-immune cell relationships in untreated GCA patients,with cell-type-specific alterations in inflammatory gene expression,and TYMP as the most critical hub gene.Conclusions:This study provides a clinically-actionable atlas of 43 potential therapeutic targets in GCA,identifying novel mechanisms including autophagy modulation and metabolic reprogramming,with immediate drug repositioning opportunities and precision medicine strategies based on tissue-specific and cell-type-specific expression patterns.These findings require experimental validation before clinical translation.
基金supported by the National Natural Science Foundation of China(No.61976028).
文摘To address the challenges of small target detection and significant scale variations in unmanned aerial vehicle(UAV)aerial imagery,which often lead to missed and false detections,we propose Multi-scale Feature Fusion YOLO(MFF-YOLO),an enhanced algorithm based on YOLOv8s.Our approach introduces a Multi-scale Feature Fusion Strategy(MFFS),comprising the Multiple Features C2f(MFC)module and the Scale Sequence Feature Fusion(SSFF)module,to improve feature integration across different network levels.This enables more effective capture of fine-grained details and sequential multi-scale features.Furthermore,we incorporate Inner-CIoU,an improved loss function that uses auxiliary bounding boxes to enhance the regression quality of small object boxes.To ensure practicality for UAV deployment,we apply the Layer-adaptive Magnitude-based pruning(LAMP)method to significantly reduce model size and computational cost.Experiments on the VisDrone2019 dataset show that MFF-YOLO achieves a 5.7% increase in mean average precision(mAP)over the baseline,while reducing parameters by 8.5 million and computation by 17.5%.The results demonstrate that our method effectively improves detection performance in UAV aerial scenarios.
基金supported by a grant from the Dalian Science and Technology Innovation Fund Program(No.2024JJ13PT070)United Foundation for Dalian Institute of Chemical Physics,Chinese Academy of Sciences and the Second Hospital of Dalian Medical University(No.DMU-2&DICP UN202410)Dalian Life and Health Field Guidance Program Project(No.2024ZDJH01PT084).
文摘Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensively explores how cancer cells rewire BCAA metabolism to enhance proliferation,survival,and therapy resistance.Tumors manipulate BCAA uptake and catabolism via high expression of transporters like L-type amino acid transporter 1(LAT1)and enzymes including branched chain amino acid transaminase 1(BCAT1),branched chain amino acid transaminase 2(BCAT2),branched-chain alpha-keto acid dehydrogenase(BCKDH),and branched chain alpha-keto acid dehydrogenase kinase(BCKDK).These alterations sustain energy production,biosynthesis,redox homeostasis,and oncogenic signaling(especially mammalian target of rapamycin complex 1[mTORC1]).Crucially,tumor-driven BCAA depletion also shapes an immunosuppressive microenvironment,impairing anti-tumor immunity by limiting essential nutrients for T cells and natural killer(NK)cells.Innovative therapeutic strategies targeting BCAA pathways—ranging from selective small-molecule inhibitors(e.g.,LAT1 and BCAT1/2)to dietary modulation—have shown promising preclinical and early clinical efficacy,highlighting their potential to exploit metabolic vulnerabilities in cancer cells while bolstering immune responses.By integrating multi-omics data and precision targeting approaches,this review underscores the translational significance of BCAA metabolic reprogramming,positioning it as a novel frontier in cancer treatment.
文摘Human Resource(HR)operations increasingly rely on cloud-based platforms that provide hiring,payroll,employee management,and compliance services.These systems,typically built on multi-tenant microservice architectures,offer scalability and efficiency but also expand the attack surface for adversaries.Ransomware has emerged as a leading threat in this domain,capable of halting workflows and exposing sensitive employee records.Traditional defenses such as static hardening and signature-based detection often fail to address the dynamic requirements of HR Software as a Service(SaaS),where continuous availability and privacy compliance are critical.This paper presents a Moving Target Defense(MTD)framework for HR SaaS that combines container mutation,IP hopping,and node reassignment to randomize the attack surface without pausing services.Many prior defenses for cloud or IoT rely on static hardening or signature-driven detection and do not meet HR SaaS needs such as uninterrupted sessions,privacy compliance,and live service continuity.This paper presents a MTD framework for HR SaaS that combines container mutation,IP hopping,and node reassignment to randomize the attack surface without pausing services.The framework runs on Kubernetes and uses a KL-divergence-based anomaly detector that monitors HR access logs across five modules(onboarding,employee records,leave,payroll,and exit).In simulation with realistic HR traffic,the approach reaches 96.9% average detection accuracy with AUC 0.94-0.98,cuts mean time to containment to 91.4 s,and lowers the ransomware encryption rate to 13.2%.Measured overheads for CPU,memory,and per-mutation latency remainmodest.Comparedwith priorMTDand non-MTD baselines,the design provides stronger containment without service interruption and aligns with zero-trust and compliance goals.Its modular implementation and control-plane orchestration support stepwise,enterprise-scale deployment in HR SaaS environments.
文摘Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,tau is not an easy target because it dynamically interacts with microtubules and other cellular components,which presents a challenge for tau-targeted drugs.New cellular models could aid the development of mechanism-based tau-targeted therapies.
文摘In this article,the unit of total distance in Fig.2B was misused.In fact,the unit of total distance exported by the system was"pixels".After correction,the data in Fig.2B were not changed.The Fig.2B should have appeared as shown below.
基金supported by the financial assistance from Natural Science Fund Project of Science and Technology Department of Jilin Province (Nos.YDZJ202301ZYTS141,YDZJ202501ZYTS793)。
文摘Hepatic fibrosis is regulated by the synergistic actions of various cells and cytokines,with the activation and proliferation of hepatic stellate cells(HSCs) being considered the central event in this process.To achieve specific targeting of activated hepatic stellate cells(a HSCs) and precise treatment of hepatic fibrosis,this study developed a dual-functional drug delivery system(SIL/c RGD-PEG-PPS PMs) with both targeting and responsive release capabilities.It aims to target the αvβ 3 receptor specifically expressed on the surface of a HSCs using the cyclic peptide c(RGDyk),and to exploit the high reactive oxygen species(ROS) level in the cellular microenvironment to achieve concentrated burst release of drugs at the pathological sites of hepatic fibrosis.Based on multiple assessments,SIL/c RGD-PEG-PPS PMs specifically enhanced the targeted delivery of silybin(SIL) to a HSCs,inhibited the proliferation and migration of a HSCs,and exhibited good biosafety.Additionally,it demonstrated excellent anti-fibrotic activity in fibrotic mice.In summary,this study shows great potential in targeted treatment of hepatic fibrosis and provides a multifunctional tool for advancing the research and therapeutic strategies of hepatic fibrosis.
基金supported by the Canadian Institutes of Health Research Project grant (PJT-169197) to QYsupported by a CGS-M fellowship from the Canadian Institutes of Health Research
文摘Alzheimer’s disease(AD)remains an incurable neurodegenerative disorder with devastating societal and personal impacts.Despite decades of intensive research,therapeutic efforts targeting the clinical stages of AD have largely failed to halt or reverse disease progression.This has prompted a critical shift in focus toward the earlier,preclinical stages of AD,where interventions may hold greater promise for altering the disease trajectory.
基金support from the Sichuan Science and Technology Program(2024JDHJ0043 and 2025YFHZ0121).
文摘Recently,Tian et al.published a research paper with significant breakthroughs in Cell[1].The study found that targeting the signalling pathways named Serpine2-lowdensity lipoprotein receptor-related protein 1(Lrp1)and ectonucleoside triphosphate diphosphohydrolase 1(CD39)-adenosine A_(3)receptor(A_(3)AR)is a promising strategy for the treatment of vascular dementia.The Serpine2-Lrp1 signalling pathway primarily exerts its therapeutic effects on myelin regeneration by regulating the differentiation of oligodendrocyte precursor cells.Serpine2 is a secretory serine protease inhibitor regulates proteolytic homeostasis.It may also bind to cell surface receptors such as Lrp1 to directly activate signalling pathways.As a transmembrane glycoprotein receptor,Lrpl mediates the endocytic clearance of ligands.
基金supported by the National Natural Science Foundation of China(Nos.62071482 and 62471348)the Shaanxi Association of Science and Technology Youth Talent Support Program Project,China(No.20230137)+1 种基金the Innovative Talents Cultivate Program for Technology Innovation Team of Shaanxi Province,China(No.2024RS-CXTD-08)the Youth Innovation Team of Shaanxi Universities,China。
文摘Within the domain of Intelligent Group Systems(IGSs),this paper develops a resourceaware multitarget Constant False Alarm Rate(CFAR)detection framework for multisite MIMO radar systems.It underscores the necessity of managing finite transmit and receive antennas and transmit power systematically to enhance detection performance.To tackle the multidimensional resource optimization challenge,we introduce a Cooperative Transmit-Receive Antenna Selection and Power Allocation(CTRSPA)strategy.It employs a perception-action cycle that incorporates uncertain external support information to optimize worst-case detection performance with multiple targets.First,we derive a closed-form expression that incorporates uncertainty for the noncoherent integration squared-law detection probability using the Neyman-Pearson criterion.Subsequently,a joint optimization model for antenna selection and power allocation in CFAR detection is formulated,incorporating practical radar resource constraints.Mathematically,this represents an NPhard problem involving coupled continuous and Boolean variables.We propose a three-stage method—Reformulation,Node Picker,and Convex Power Allocation—that capitalizes on the independent convexity of the optimization model for each variable,ensuring a near-optimal result.Simulations confirm the approach's effectiveness,efficiency,and timeliness,particularly for large-scale radar networks,and reveal the impact of threat levels,system layout,and detection parameters on resource allocation.
基金supported by the Natural Science Foundation of Xinjiang Uyghur Autonomous Region(No.2022D01C721)the Tianchi Young Talent Program of Xinjiang Uyghur Autonomous Region,and the General Program of the National Natural Science Foundation of China(NSFC)(No.32571328).
文摘Transient receptor potential vanilloid subtype 1(TRPV1),a polymodally activated,calcium-permeable non-selective cation channel,is broadly present in all parts of the body,with notable expression in the nociceptive neurons.Both physiological and pathological functions rely heavily on this ion channel,mediating responses to a variety of stimuli and contributing to the maintenance of bodily homeostasis.Its unique ability to respond to temperature changes,chemical ligands,and voltage fluctuations positions TRPV1 as a key target in understanding and modulating normal bodily functions,in addition to diagnosing and treating diseases.This review synthesizes current knowledge on the structure,gating mechanisms,and physiological and pathological roles of TRPV1,highlighting its potential as a therapeutic target across multiple disease states.By providing a comprehensive overview of the multifaceted functions of TRPV1,this review aims to inform and inspire future research,finally contributing to the advancement of new therapeutic techniques focusing on TRPV1 to enhance human health.
