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
Peripheral artery disease(PAD)remains a significant global health issue,with current treatments primarily focused on relieving symptoms and addressingmacrovascular issues.However,critical immunoinflammatory mechanisms...Peripheral artery disease(PAD)remains a significant global health issue,with current treatments primarily focused on relieving symptoms and addressingmacrovascular issues.However,critical immunoinflammatory mechanisms are often overlooked.Recent evidence suggests that monocyte phenotypic plasticity plays a central role in PAD development,affecting atherogenesis,plaque progression,ischemia-reperfusion injury,and chronic ischemic remodeling.This narrative review aims to summarize the latest advances(2023-2025)in understanding monocyte diversity,functional states,and their changes throughout different stages of PAD.We discuss both established and emerging biomarkers,such as circulating monocyte subset proportions,functional assays,immune checkpoint expression,and multi-omics signatures,highlighting their potential for prognosis and the challenges in translating them to clinical practice.We also present a stage-specific approach to mapping out potential therapies,linking monocyte phenotypes to molecular targets and possible interventions.Additionally,we address regulatory,economic,and implementation considerations for applying these findings in a clinical setting.The goal of this review is to facilitate the development of targeted immunomodulatory strategies to improve limb and cardiovascular outcomes in PAD by combining mechanistic understanding with therapeutic innovation.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
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.
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
Neutrophil extracellular traps(NETs)have emerged as key mediators of cardiovascular diseases(CVDs),linking innate immune activation to vascular injury,thrombosis,and maladaptive remodeling.This review synthesizes rece...Neutrophil extracellular traps(NETs)have emerged as key mediators of cardiovascular diseases(CVDs),linking innate immune activation to vascular injury,thrombosis,and maladaptive remodeling.This review synthesizes recent insights into the molecular and cellular pathways driving NET formation,including post-translational modifications,metabolic reprogramming,inflammasome signaling,and autophagy.It highlights the role of NETs in atherosclerosis,thrombosis,myocardial ischemia-reperfusion injury,and hypertension,emphasizing common control points such as peptidylarginine deiminase 4(PAD4)-dependent histone citrullination and nicotinamide adenine dinucleotide phosphate oxidases 2(NOX2)-mediated oxidative stress.Mechanistic interpretation of circulating biomarkers,includingmyeloperoxidase(MPO)-DNA complexes,citrullinated histoneH3,and cell-free DNA,provides a translational bridge between NET biology and patient stratification.Therapeutic strategies targeting NETs are examined through three main approaches:inhibition of NET initiation,enhancement of chromatin clearance,and neutralization of toxic extracellular components,with attention to both established and emerging interventions.In contrast to previous reviews,this study highlights the novelty of a mechano-therapeutic framework by providing a mechanistic roadmap linking NET formation pathways to therapeutic targeting in cardiovascular disease.Moving forward,integrating mechanistic information with biomarker discovery,precision profiling,and targeted therapies offers innovative strategies to reduce vascular inflammation and improve outcomes in cardiovascular disease.展开更多
Sphere-shape Eu（DBM）3Phen@Si02 nanoparticles were fabricated by employing a modified alkaline catalyzed hydrolysis and precipitation method. The silica coated on the particles surface was obtained by means of hydrol...Sphere-shape Eu（DBM）3Phen@Si02 nanoparticles were fabricated by employing a modified alkaline catalyzed hydrolysis and precipitation method. The silica coated on the particles surface was obtained by means of hydrolysis and condensation of tetraethyl orthosilicate （TEOS）. In this study, the particles morphology was analyzed by scanning electron microscopy （SEM） and the surface composition of samples was characterized by X-ray diffraction （XRD） and Fourier transform infrared spectroscopy （FT-IR）. It is confirmed that the Si02 shell has been coated on the rare earth complexes successfully. Moreover, the near-infrared photoluminescence emission analysis on the nanoparticles showed that the SiO2 shell would increase the luminescence intensity of Eu（DBM）3Phen. This is primarily due to the reason that SiO2 shell with chemical inertness can effectively reduce the ion Eu3~ non-radiation transition probabilities, as well as the probability of rare earth luminescence quenching caused by the external medium.展开更多
This paper reports that the film composed of flower-like ZnO micro-spheres, which consists of nano-sheets, is fab- ricated by chemical bath deposition. By adding hydrogen fluoride （HF） into the reaction solution, wh...This paper reports that the film composed of flower-like ZnO micro-spheres, which consists of nano-sheets, is fab- ricated by chemical bath deposition. By adding hydrogen fluoride （HF） into the reaction solution, which contains zinc nitrate hexahydrate and hexamethylenetetramine, the ZnO crystal growth process is changed and the film composed by ZnO micro-spheres is obtained after keeping the reaction solution at 95 ℃ for 2 h. The morphology, crystal phase and wettahility of the sample axe characterized by scanning electron microscope, x-ray diffraction and contact angle meter, respectively. The results show that the filrrl has the micro-nano compound structure. After modification with heptadecafluorodecyltrimethoxy-silane, the wettability of the film changed from superhydrophilicity to superhydropho-bicity, on which water contact angle and the sliding angle are 154° and less than 5° for 8-μL water droplet, respectively. Additionally, the formation mechanism of the ZnO micro-sphere is also discussed.展开更多
Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are ne...Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.展开更多
Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes...Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.展开更多
The YOLOv8 model faces challenges with dense target distribution and small size,resulting in lower accuracy in dense small target detection.To address these issues,an improved small target detection algorithm based on...The YOLOv8 model faces challenges with dense target distribution and small size,resulting in lower accuracy in dense small target detection.To address these issues,an improved small target detection algorithm based on the YOLOv8 model was proposed in this paper.Firstly,the Global Attention Module(GAM)was introduced to enhance data prediction capability and model expression ability.Secondly,the Space-to-Depth(SPD)module was incorporated into the backbone network for fine-grained feature information learning to mitigate feature information loss due to down-sampling.Finally,a 160 pixels×160 pixels feature layer was added to expand small target feature information and effectively reduce instances of missed targets.Experimental validation on the public VisDrone2019 UAV small target detaset demonstrated that the proposed model achieves significant performance improvement in small target detection tasks compared to existing models,exhibiting higher accuracy.展开更多
The application of deep learning for target detection in aerial images captured by Unmanned Aerial Vehicles(UAV)has emerged as a prominent research focus.Due to the considerable distance between UAVs and the photograp...The application of deep learning for target detection in aerial images captured by Unmanned Aerial Vehicles(UAV)has emerged as a prominent research focus.Due to the considerable distance between UAVs and the photographed objects,coupled with complex shooting environments,existing models often struggle to achieve accurate real-time target detection.In this paper,a You Only Look Once v8(YOLOv8)model is modified from four aspects:the detection head,the up-sampling module,the feature extraction module,and the parameter optimization of positive sample screening,and the YOLO-S3DT model is proposed to improve the performance of the model for detecting small targets in aerial images.Experimental results show that all detection indexes of the proposed model are significantly improved without increasing the number of model parameters and with the limited growth of computation.Moreover,this model also has the best performance compared to other detecting models,demonstrating its advancement within this category of tasks.展开更多
Peripheral immunity forms the foundation of tumor immunity,while tumor immunity represents a more refined adaptation of peripheral immune responses.The tumor microenvironment(TME),a localized niche surrounding tumor c...Peripheral immunity forms the foundation of tumor immunity,while tumor immunity represents a more refined adaptation of peripheral immune responses.The tumor microenvironment(TME),a localized niche surrounding tumor cells,is inherently immunosuppressive(1,2).Effective tumor therapy necessitates the dismantling of this microenvironment,aiming to eradicate tumors from the host system.展开更多
Chronic atrophic gastritis(CAG)is an important stage of precancerous lesions of gastric cancer.Effective treatment and regulation of CAG are essential to prevent its progression to malignancy.Traditional Chinese medic...Chronic atrophic gastritis(CAG)is an important stage of precancerous lesions of gastric cancer.Effective treatment and regulation of CAG are essential to prevent its progression to malignancy.Traditional Chinese medicine(TCM)has shown multi-targeted efficacy in CAG treatment,with advantages in enhancing gastric mucosal barrier defense,improving microcirculation,modulating inflammatory and immune responses,and promoting lesion healing,etc.Clinical studies and meta-analyses indicate that TCM provides significant benefits,with specific Chinese herbal compounds and monomers demonstrating protective effects on the gastric mucosa through mechanisms including anti-inflammation,antioxidation,and regulation of cellular proliferation and apoptosis,etc.Finally,it is pointed out that the efficacy of TCM in the treatment of CAG requires standardized research and unified standards,and constantly clarifies and improves the evaluation criteria of each dimension of gastric mucosal barrier function.展开更多
Natural products(NPs)have historically been a fundamental source for drug discovery.Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents,and corresponding targets.In the ...Natural products(NPs)have historically been a fundamental source for drug discovery.Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents,and corresponding targets.In the present study,an innovative natural product virtual screening-interaction-phenotype(NP-VIP)strategy that integrates virtual screening,chemical proteomics,and metabolomics to identify and validate the bioactive targets of NPs.This approach reduces false positive results and enhances the efficiency of target identification.Salvia miltiorrhiza(SM),a herb with recognized therapeutic potential against ischemic stroke(IS),was used to illustrate the workflow.Utilizing virtual screening,chemical proteomics,and metabolomics,potential therapeutic targets for SM in the IS treatment were identified,totaling 29,100,and 78,respectively.Further analysis via the NP-VIP strategy highlighted five high-confidence targets,including poly[ADP-ribose]polymerase 1(PARP1),signal transducer and activator of transcription 3(STAT3),amyloid precursor protein(APP),glutamate-ammonia ligase(GLUL),and glutamate decarboxylase 67(GAD67).These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM.The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research,proposing a comprehensive approach that could be adapted for broader pharmacological explorations.展开更多
Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central ...Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.展开更多
The paper presents a two-layer,disturbance-resistant,and fault-tolerant affine formation maneuver control scheme that accomplishes the surrounding of a dynamic target with multiple underactuated Quadrotor Unmanned Aer...The paper presents a two-layer,disturbance-resistant,and fault-tolerant affine formation maneuver control scheme that accomplishes the surrounding of a dynamic target with multiple underactuated Quadrotor Unmanned Aerial Vehicles(QUAVs).This scheme mainly consists of predefinedtime estimators and fixed-time tracking controllers,with a hybrid Laplacian matrix describing the communication among these QUAVs.At the first layer,we devise predefined time estimators for leading and following QUAVs,enabling accurate estimation of desired information.In the second layer,we initially devise a fixed-time hybrid observer to estimate unknown disturbances and actuator faults.Fixedtime translational tracking controllers are then proposed,and the intermediary control input from these controllers is used to extract the desired attitude and angular velocities for the fixed-time rotational tracking controllers.We employ an exact tracking differentiator to handle variables that are challenging to differentiate directly.The paper includes a demonstration of the control system stability through mathematical proof,as well as the presentation of simulation results and comparative simulations.展开更多
Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxyge...Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.展开更多
Microglia(MG)are immune effector cells in the central nervous system(CNS)and play a pivotal role in the pathogenesis of various CNS diseases.Alzheimer's disease(AD)is defined as a severe chronic degenerative neuro...Microglia(MG)are immune effector cells in the central nervous system(CNS)and play a pivotal role in the pathogenesis of various CNS diseases.Alzheimer's disease(AD)is defined as a severe chronic degenerative neurological disease in humans.The amyloid cascade hypothesis is a hypothesis on the pathogenesis of AD that suggests that abnormal extracellular aggregation ofβ-amyloid(Aβ)peptides is the main cause of the disease.Although this hypothesis has been found to be convincing,a growing body of evidence suggests that it does not fully explain the pathogenesis of AD.Neuroinflammation is a crucial element in the pathogenesis of AD,as evidenced by elevated levels of inflammatory markers and the identification of AD risk genes associated with innate immune function.This paper will first summarize the impact of microglia-mediated neuroinflammation on AD,exploring the phenotypic changes that follow microglia activation.Secondly,the interactions between microglia,Aβ,microtubule-associated protein,apolipoprotein E and neurons are thoroughly investigated,with particular focus on the interactive mechanisms.Furthermore,the recent progress and prospects of microglia as a diagnostic and therapeutic target for AD are analysed.A review of the literature on the mechanisms regulating MG for AD at home and abroad revealed that acupuncture modulation of microglia could help to delay the progression of AD.This was followed by an extensive discussion of the clinical possibilities and scientific validity of acupuncture treatment for AD,with the aim of providing new insights for acupuncture modulation of MG targeting for the treatment of AD.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Peripheral artery disease(PAD)remains a significant global health issue,with current treatments primarily focused on relieving symptoms and addressingmacrovascular issues.However,critical immunoinflammatory mechanisms are often overlooked.Recent evidence suggests that monocyte phenotypic plasticity plays a central role in PAD development,affecting atherogenesis,plaque progression,ischemia-reperfusion injury,and chronic ischemic remodeling.This narrative review aims to summarize the latest advances(2023-2025)in understanding monocyte diversity,functional states,and their changes throughout different stages of PAD.We discuss both established and emerging biomarkers,such as circulating monocyte subset proportions,functional assays,immune checkpoint expression,and multi-omics signatures,highlighting their potential for prognosis and the challenges in translating them to clinical practice.We also present a stage-specific approach to mapping out potential therapies,linking monocyte phenotypes to molecular targets and possible interventions.Additionally,we address regulatory,economic,and implementation considerations for applying these findings in a clinical setting.The goal of this review is to facilitate the development of targeted immunomodulatory strategies to improve limb and cardiovascular outcomes in PAD by combining mechanistic understanding with therapeutic innovation.
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Neutrophil extracellular traps(NETs)have emerged as key mediators of cardiovascular diseases(CVDs),linking innate immune activation to vascular injury,thrombosis,and maladaptive remodeling.This review synthesizes recent insights into the molecular and cellular pathways driving NET formation,including post-translational modifications,metabolic reprogramming,inflammasome signaling,and autophagy.It highlights the role of NETs in atherosclerosis,thrombosis,myocardial ischemia-reperfusion injury,and hypertension,emphasizing common control points such as peptidylarginine deiminase 4(PAD4)-dependent histone citrullination and nicotinamide adenine dinucleotide phosphate oxidases 2(NOX2)-mediated oxidative stress.Mechanistic interpretation of circulating biomarkers,includingmyeloperoxidase(MPO)-DNA complexes,citrullinated histoneH3,and cell-free DNA,provides a translational bridge between NET biology and patient stratification.Therapeutic strategies targeting NETs are examined through three main approaches:inhibition of NET initiation,enhancement of chromatin clearance,and neutralization of toxic extracellular components,with attention to both established and emerging interventions.In contrast to previous reviews,this study highlights the novelty of a mechano-therapeutic framework by providing a mechanistic roadmap linking NET formation pathways to therapeutic targeting in cardiovascular disease.Moving forward,integrating mechanistic information with biomarker discovery,precision profiling,and targeted therapies offers innovative strategies to reduce vascular inflammation and improve outcomes in cardiovascular disease.
基金financial support from the National Natural Science Foundation of China (No. 60972134, No. 51205137)the Fundamental Research Funds for the Central Universities with grant no. 2012ZM0067
文摘Sphere-shape Eu（DBM）3Phen@Si02 nanoparticles were fabricated by employing a modified alkaline catalyzed hydrolysis and precipitation method. The silica coated on the particles surface was obtained by means of hydrolysis and condensation of tetraethyl orthosilicate （TEOS）. In this study, the particles morphology was analyzed by scanning electron microscopy （SEM） and the surface composition of samples was characterized by X-ray diffraction （XRD） and Fourier transform infrared spectroscopy （FT-IR）. It is confirmed that the Si02 shell has been coated on the rare earth complexes successfully. Moreover, the near-infrared photoluminescence emission analysis on the nanoparticles showed that the SiO2 shell would increase the luminescence intensity of Eu（DBM）3Phen. This is primarily due to the reason that SiO2 shell with chemical inertness can effectively reduce the ion Eu3~ non-radiation transition probabilities, as well as the probability of rare earth luminescence quenching caused by the external medium.
基金Project supported by the National Natural Science Foundation of China (Grant No. 50872129)Natural Science Foundation of Anhui Province of China (Grant No. 070414187)
文摘This paper reports that the film composed of flower-like ZnO micro-spheres, which consists of nano-sheets, is fab- ricated by chemical bath deposition. By adding hydrogen fluoride （HF） into the reaction solution, which contains zinc nitrate hexahydrate and hexamethylenetetramine, the ZnO crystal growth process is changed and the film composed by ZnO micro-spheres is obtained after keeping the reaction solution at 95 ℃ for 2 h. The morphology, crystal phase and wettahility of the sample axe characterized by scanning electron microscope, x-ray diffraction and contact angle meter, respectively. The results show that the filrrl has the micro-nano compound structure. After modification with heptadecafluorodecyltrimethoxy-silane, the wettability of the film changed from superhydrophilicity to superhydropho-bicity, on which water contact angle and the sliding angle are 154° and less than 5° for 8-μL water droplet, respectively. Additionally, the formation mechanism of the ZnO micro-sphere is also discussed.
基金supported by the Natural Science Foundation of Fujian Province,No.2021J02035(to WX).
文摘Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.
基金supported by grants from the Natural Science Foundation of Tianjin(General Program),Nos.23JCYBJC01390(to RL),22JCYBJC00220(to XC),and 22JCYBJC00210(to QL).
文摘Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.
文摘The YOLOv8 model faces challenges with dense target distribution and small size,resulting in lower accuracy in dense small target detection.To address these issues,an improved small target detection algorithm based on the YOLOv8 model was proposed in this paper.Firstly,the Global Attention Module(GAM)was introduced to enhance data prediction capability and model expression ability.Secondly,the Space-to-Depth(SPD)module was incorporated into the backbone network for fine-grained feature information learning to mitigate feature information loss due to down-sampling.Finally,a 160 pixels×160 pixels feature layer was added to expand small target feature information and effectively reduce instances of missed targets.Experimental validation on the public VisDrone2019 UAV small target detaset demonstrated that the proposed model achieves significant performance improvement in small target detection tasks compared to existing models,exhibiting higher accuracy.
文摘The application of deep learning for target detection in aerial images captured by Unmanned Aerial Vehicles(UAV)has emerged as a prominent research focus.Due to the considerable distance between UAVs and the photographed objects,coupled with complex shooting environments,existing models often struggle to achieve accurate real-time target detection.In this paper,a You Only Look Once v8(YOLOv8)model is modified from four aspects:the detection head,the up-sampling module,the feature extraction module,and the parameter optimization of positive sample screening,and the YOLO-S3DT model is proposed to improve the performance of the model for detecting small targets in aerial images.Experimental results show that all detection indexes of the proposed model are significantly improved without increasing the number of model parameters and with the limited growth of computation.Moreover,this model also has the best performance compared to other detecting models,demonstrating its advancement within this category of tasks.
文摘Peripheral immunity forms the foundation of tumor immunity,while tumor immunity represents a more refined adaptation of peripheral immune responses.The tumor microenvironment(TME),a localized niche surrounding tumor cells,is inherently immunosuppressive(1,2).Effective tumor therapy necessitates the dismantling of this microenvironment,aiming to eradicate tumors from the host system.
基金Supported by the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences,No.CI2021A00806High Level Chinese Medical Hospital Promotion Project,No.HLCMHPP2023086the Fundamental Research Funds for the Central Public Welfare Research Institutes,No.ZZ17-XRZ-041.
文摘Chronic atrophic gastritis(CAG)is an important stage of precancerous lesions of gastric cancer.Effective treatment and regulation of CAG are essential to prevent its progression to malignancy.Traditional Chinese medicine(TCM)has shown multi-targeted efficacy in CAG treatment,with advantages in enhancing gastric mucosal barrier defense,improving microcirculation,modulating inflammatory and immune responses,and promoting lesion healing,etc.Clinical studies and meta-analyses indicate that TCM provides significant benefits,with specific Chinese herbal compounds and monomers demonstrating protective effects on the gastric mucosa through mechanisms including anti-inflammation,antioxidation,and regulation of cellular proliferation and apoptosis,etc.Finally,it is pointed out that the efficacy of TCM in the treatment of CAG requires standardized research and unified standards,and constantly clarifies and improves the evaluation criteria of each dimension of gastric mucosal barrier function.
基金supported by the National Natural Science Foundations of China(Grant No.:82204584)Liaoning Provincial Science and Technology Projects,China(Project No.:2021JH1/10400055).
文摘Natural products(NPs)have historically been a fundamental source for drug discovery.Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents,and corresponding targets.In the present study,an innovative natural product virtual screening-interaction-phenotype(NP-VIP)strategy that integrates virtual screening,chemical proteomics,and metabolomics to identify and validate the bioactive targets of NPs.This approach reduces false positive results and enhances the efficiency of target identification.Salvia miltiorrhiza(SM),a herb with recognized therapeutic potential against ischemic stroke(IS),was used to illustrate the workflow.Utilizing virtual screening,chemical proteomics,and metabolomics,potential therapeutic targets for SM in the IS treatment were identified,totaling 29,100,and 78,respectively.Further analysis via the NP-VIP strategy highlighted five high-confidence targets,including poly[ADP-ribose]polymerase 1(PARP1),signal transducer and activator of transcription 3(STAT3),amyloid precursor protein(APP),glutamate-ammonia ligase(GLUL),and glutamate decarboxylase 67(GAD67).These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM.The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research,proposing a comprehensive approach that could be adapted for broader pharmacological explorations.
基金supported by grants from National Key R&D Program of China,No.2023YFC2506100(to JZ)the National Natural Science Foundation of China,No.82171062(to JZ).
文摘Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.
基金supported by Natural Science Basic Research Plan in Shaanxi Province of China(No.2023-JC-QN-0733)Guangdong Basic and Applied Basic Research Foundation,China(No.2022A1515110753)+2 种基金China Postdoctoral Science Foundation(No.2022M722583)China Industry-UniversityResearch Innovation Foundation(No.2022IT188)National Key Laboratory of Air-based Information Perception and Fusion and the Aeronautic Science Foundation of China(No.20220001068001)。
文摘The paper presents a two-layer,disturbance-resistant,and fault-tolerant affine formation maneuver control scheme that accomplishes the surrounding of a dynamic target with multiple underactuated Quadrotor Unmanned Aerial Vehicles(QUAVs).This scheme mainly consists of predefinedtime estimators and fixed-time tracking controllers,with a hybrid Laplacian matrix describing the communication among these QUAVs.At the first layer,we devise predefined time estimators for leading and following QUAVs,enabling accurate estimation of desired information.In the second layer,we initially devise a fixed-time hybrid observer to estimate unknown disturbances and actuator faults.Fixedtime translational tracking controllers are then proposed,and the intermediary control input from these controllers is used to extract the desired attitude and angular velocities for the fixed-time rotational tracking controllers.We employ an exact tracking differentiator to handle variables that are challenging to differentiate directly.The paper includes a demonstration of the control system stability through mathematical proof,as well as the presentation of simulation results and comparative simulations.
基金support from the National Natural Science Foundation of China(Nos.22277056,21977052)the Distinguished Young Scholars of Jiangsu Province(No.BK20230006)+2 种基金the Natural Science Foundation of Jiangsu Province(Nos.BK20230977,BK20231090)the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(No.23KJB150020)the Jiangsu Excellent Postdoctoral Program(No.2022ZB758)。
文摘Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.
文摘Microglia(MG)are immune effector cells in the central nervous system(CNS)and play a pivotal role in the pathogenesis of various CNS diseases.Alzheimer's disease(AD)is defined as a severe chronic degenerative neurological disease in humans.The amyloid cascade hypothesis is a hypothesis on the pathogenesis of AD that suggests that abnormal extracellular aggregation ofβ-amyloid(Aβ)peptides is the main cause of the disease.Although this hypothesis has been found to be convincing,a growing body of evidence suggests that it does not fully explain the pathogenesis of AD.Neuroinflammation is a crucial element in the pathogenesis of AD,as evidenced by elevated levels of inflammatory markers and the identification of AD risk genes associated with innate immune function.This paper will first summarize the impact of microglia-mediated neuroinflammation on AD,exploring the phenotypic changes that follow microglia activation.Secondly,the interactions between microglia,Aβ,microtubule-associated protein,apolipoprotein E and neurons are thoroughly investigated,with particular focus on the interactive mechanisms.Furthermore,the recent progress and prospects of microglia as a diagnostic and therapeutic target for AD are analysed.A review of the literature on the mechanisms regulating MG for AD at home and abroad revealed that acupuncture modulation of microglia could help to delay the progression of AD.This was followed by an extensive discussion of the clinical possibilities and scientific validity of acupuncture treatment for AD,with the aim of providing new insights for acupuncture modulation of MG targeting for the treatment of AD.
