Analyses of the physiology and pathology of active biochemical species in their native contexts are critical for early diagnosis and therapy. Optical imaging has emerged as one of the promising modalities for noninvas...Analyses of the physiology and pathology of active biochemical species in their native contexts are critical for early diagnosis and therapy. Optical imaging has emerged as one of the promising modalities for noninvasive and real-time visualization of important biomolecules or biological events, and it has witnessed major advances in the field of imaging in vitro and in vivo. In this review, we present a survey of common approaches and tactics for enhanced targetability, response rate, and photostability in bioimaging applications. Recently developed and representative examples are illustrated on the cellular and tissue levels.展开更多
Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathologica...Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathological characteristics and molecular pathways associated with its progression.Advances in scientific research have increasingly highlighted the crucial role of non-coding RNAs in the progression of Alzheimer's disease.These non-coding RNAs regulate several biological processes critical to the advancement of the disease,offering promising potential as therapeutic targets and diagnostic biomarkers.Therefore,this review aims to investigate the underlying mechanisms of Alzheimer's disease onset,with a particular focus on microRNAs,long non-coding RNAs,and circular RNAs associated with the disease.The review elucidates the potential pathogenic processes of Alzheimer's disease and provides a detailed description of the synthesis mechanisms of the three aforementioned non-coding RNAs.It comprehensively summarizes the various non-coding RNAs that have been identified to play key regulatory roles in Alzheimer's disease,as well as how these noncoding RNAs influence the disease's progression by regulating gene expression and protein functions.For example,miR-9 targets the UBE4B gene,promoting autophagy-mediated degradation of Tau protein,thereby reducing Tau accumulation and delaying Alzheimer's disease progression.Conversely,the long non-coding RNA BACE1-AS stabilizes BACE1 mRNA,promoting the generation of amyloid-βand accelerating Alzheimer's disease development.Additionally,circular RNAs play significant roles in regulating neuroinflammatory responses.By integrating insights from these regulatory mechanisms,there is potential to discover new therapeutic targets and potential biomarkers for early detection and management of Alzheimer's disease.This review aims to enhance the understanding of the relationship between Alzheimer's disease and non-coding RNAs,potentially paving the way for early detection and novel treatment strategies.展开更多
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
Adolescent smoking constitutes a critical public health challenge as early initiation increases the risk of premature mortality and smoking-related chronic diseases due to longer exposure and higher cumulative tobacco...Adolescent smoking constitutes a critical public health challenge as early initiation increases the risk of premature mortality and smoking-related chronic diseases due to longer exposure and higher cumulative tobacco use^([1]).Adolescents are especially prone to developing persistent smoking habits,with many adult smokers having started before the age of 18.In China,16.7%of secondary school students have tried smoking and 4.7%are current smokers,highlighting the critical need for targeted tobacco control interventions among the youth.展开更多
Hebei Province has incorporated targeted assistance services for people with disabilities into livelihood projects,upgrading the quality and efficiency of support services for disadvantaged groups.THE living and nursi...Hebei Province has incorporated targeted assistance services for people with disabilities into livelihood projects,upgrading the quality and efficiency of support services for disadvantaged groups.THE living and nursing allowances provided by the Chinese government for people with disabilities who are unable to work are not only important components of China’s social security system which provide for the needs of its disabled,but also show China’s ability to guarantee the basic living standard and social fairness and justice for this group of people.展开更多
Ufmylation is an ubiquitin-like post-translational modification characterized by the covalent binding of mature UFM1 to target proteins.Although the consequences of ufmylation on target proteins are not fully understo...Ufmylation is an ubiquitin-like post-translational modification characterized by the covalent binding of mature UFM1 to target proteins.Although the consequences of ufmylation on target proteins are not fully understood,its importance is evident from the disorders resulting from its dysfunction.Numerous case reports have established a link between biallelic loss-of-function and/or hypomorphic variants in ufmylation-related genes and a spectrum of pediatric neurodevelopmental disorders.展开更多
Neural machine interface technology is a pioneering approach that aims to address the complex challenges of neurological dysfunctions and disabilities resulting from conditions such as congenital disorders,traumatic i...Neural machine interface technology is a pioneering approach that aims to address the complex challenges of neurological dysfunctions and disabilities resulting from conditions such as congenital disorders,traumatic injuries,and neurological diseases.Neural machine interface technology establishes direct connections with the brain or peripheral nervous system to restore impaired motor,sensory,and cognitive functions,significantly improving patients'quality of life.This review analyzes the chronological development and integration of various neural machine interface technologies,including regenerative peripheral nerve interfaces,targeted muscle and sensory reinnervation,agonist–antagonist myoneural interfaces,and brain–machine interfaces.Recent advancements in flexible electronics and bioengineering have led to the development of more biocompatible and highresolution electrodes,which enhance the performance and longevity of neural machine interface technology.However,significant challenges remain,such as signal interference,fibrous tissue encapsulation,and the need for precise anatomical localization and reconstruction.The integration of advanced signal processing algorithms,particularly those utilizing artificial intelligence and machine learning,has the potential to improve the accuracy and reliability of neural signal interpretation,which will make neural machine interface technologies more intuitive and effective.These technologies have broad,impactful clinical applications,ranging from motor restoration and sensory feedback in prosthetics to neurological disorder treatment and neurorehabilitation.This review suggests that multidisciplinary collaboration will play a critical role in advancing neural machine interface technologies by combining insights from biomedical engineering,clinical surgery,and neuroengineering to develop more sophisticated and reliable interfaces.By addressing existing limitations and exploring new technological frontiers,neural machine interface technologies have the potential to revolutionize neuroprosthetics and neurorehabilitation,promising enhanced mobility,independence,and quality of life for individuals with neurological impairments.By leveraging detailed anatomical knowledge and integrating cutting-edge neuroengineering principles,researchers and clinicians can push the boundaries of what is possible and create increasingly sophisticated and long-lasting prosthetic devices that provide sustained benefits for users.展开更多
Pericytes are multi-functional mural cells of the central nervous system that cover the capillary endothelial cells. Pericytes play a vital role in nervous system development, significantly influencing the formation, ...Pericytes are multi-functional mural cells of the central nervous system that cover the capillary endothelial cells. Pericytes play a vital role in nervous system development, significantly influencing the formation, maturation, and maintenance of the central nervous system. An expanding body of studies has revealed that pericytes establish carefully regulated interactions with oligodendrocytes, microglia, and astrocytes. These communications govern numerous critical brain processes, including angiogenesis, neurovascular unit homeostasis, blood–brain barrier integrity, cerebral blood flow regulation, and immune response initiation. Glial cells and pericytes participate in dynamic and reciprocal interactions, with each influencing and adjusting the functionality of the other. Pericytes have the ability to control astrocyte polarization, trigger differentiation of oligodendrocyte precursor cells, and initiate immunological responses in microglia. Various neurological disorders that compromise the integrity of the blood–brain barrier can disrupt these communications, impair waste clearance, and hinder cerebral blood circulation, contributing to neuroinflammation. In the context of neurodegeneration, these disruptions exacerbate pathological processes, such as neuronal damage, synaptic dysfunction, and impaired tissue repair. This article explores the complex interactions between pericytes and various glial cells in both healthy and pathological states of the central nervous system. It highlights their essential roles in neurovascular function and disease progression, providing important insights that may enhance our understanding of the molecular mechanisms underlying these interactions and guide potential therapeutic strategies for neurodegenerative disorders in future research.展开更多
In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,...In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,allowing them to target deep brain lesions.Recent studies have demonstrated that exosomes derived from different cell types may exert therapeutic effects by regulating the expression of various inflammatory cytokines,mRNAs,and disease-related proteins,thereby halting the progression of neurodegenerative diseases and exhibiting beneficial effects.However,exosomes are composed of lipid bilayer membranes and lack the ability to recognize specific target cells.This limitation can lead to side effects and toxicity when they interact with non-specific cells.Growing evidence suggests that surface-modified exosomes have enhanced targeting capabilities and can be used as targeted drug-delivery vehicles that show promising results in the treatment of neurodegenerative diseases.In this review,we provide an up-to-date overview of existing research aimed at devising approaches to modify exosomes and elucidating their therapeutic potential in neurodegenerative diseases.Our findings indicate that exosomes can efficiently cross the blood-brain barrier to facilitate drug delivery and can also serve as early diagnostic markers for neurodegenerative diseases.We introduce the strategies being used to enhance exosome targeting,including genetic engineering,chemical modifications(both covalent,such as click chemistry and metabolic engineering,and non-covalent,such as polyvalent electrostatic and hydrophobic interactions,ligand-receptor binding,aptamer-based modifications,and the incorporation of CP05-anchored peptides),and nanomaterial modifications.Research into these strategies has confirmed that exosomes have significant therapeutic potential for neurodegenerative diseases.However,several challenges remain in the clinical application of exosomes.Improvements are needed in preparation,characterization,and optimization methods,as well as in reducing the adverse reactions associated with their use.Additionally,the range of applications and the safety of exosomes require further research and evaluation.展开更多
A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation.This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiolog...A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation.This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiological mechanisms underlying hydrocephalus,one of the most common neurological conditions worldwide.In this review,we first outline the basic concepts and incidence of hydrocephalus along with the limitations of existing treatments for this condition.Then,we outline the definition,classification,and biological role of non-coding RNAs.Subsequently,we analyze the roles of non-coding RNAs in the formation of hydrocephalus in detail.Specifically,we have focused on the potential significance of non-coding RNAs in the pathophysiology of hydrocephalus,including glymphatic pathways,neuroinflammatory processes,and neurological dysplasia,on the basis of the existing evidence.Lastly,we review the potential of non-coding RNAs as biomarkers of hydrocephalus and for the creation of innovative treatments.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
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
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 first hemiterpene-quassinoid adducts,bruquass A and B(1 and 2),were rapidly isolated and identified from Brucea javanica using an integrated analytical strategy.They possessed unusual carbon skeletons formed by th...The first hemiterpene-quassinoid adducts,bruquass A and B(1 and 2),were rapidly isolated and identified from Brucea javanica using an integrated analytical strategy.They possessed unusual carbon skeletons formed by the coupling of quassinoids with hemiterpene units via vinylogous aldol reactions.Their structural configurations were determined through comprehensive spectroscopic analysis and electronic circular dichroism(ECD) calculations.Plausible biosynthetic pathways for 1 and 2 were proposed,and guided by these biogenetic insights,the biomimetic synthesis of compound 1 was successfully achieved.Furthermore,compounds 1 and 2 exhibited significant antifeedant activity against Plutella xylostella.The bioactivity assessment results open up the prospects of 1 and 2 as a promising new class of botanical insecticide.展开更多
Amyloid protein aggregation plays a major role in multiple neurodegenerative diseases and is likely the primary driving force for the progression of most of these diseases.Multiple recent studies have highlighted that...Amyloid protein aggregation plays a major role in multiple neurodegenerative diseases and is likely the primary driving force for the progression of most of these diseases.Multiple recent studies have highlighted that the DNAJ homolog subfamily B member 6(DNAJB6)chaperone is particularly interesting,when it comes to preventing amyloidogenic proteins from aggregating.It has been shown that DNAJB6 can prevent the aggregation of polyglutamine-expanded proteins in models of Huntington’s disease.Likewise,it can suppress aggregation ofα-synuclein in models of Parkinson’s disease and other synucleinopathies.Finally,it has been shown that DNAJB6 can block aggregation of multiple additional amyloid proteins involved in Alzheimer’s disease and other tauopathies as well.We believe there is yet much to learn about the protective role of DNAJB6 in the brain,but this focused review summarizes,what we know so far of this chaperone.It describes the biological role of DNAJB6 in the brain and its interaction with Hsp70,with particular emphasis on the studies that show its ability to prevent amyloid protein aggregation in vitro and in vivo.Moreover,recent work on dysregulation of the expression of DNAJB6 in brain clinical tissue is discussed.Finally,we discuss potential therapeutic perspectives as we believe this protein is a promising druggable target.展开更多
Aiming at the scale adaptation of automatic driving target detection algorithms in low illumination environments and the shortcomings in target occlusion processing,this paper proposes a YOLO-LKSDS automatic driving d...Aiming at the scale adaptation of automatic driving target detection algorithms in low illumination environments and the shortcomings in target occlusion processing,this paper proposes a YOLO-LKSDS automatic driving detection model.Firstly,the Contrast-Limited Adaptive Histogram Equalisation(CLAHE)image enhancement algorithm is improved to increase the image contrast and enhance the detailed features of the target;then,on the basis of the YOLOv5 model,the Kmeans++clustering algorithm is introduced to obtain a suitable anchor frame,and SPPELAN spatial pyramid pooling is improved to enhance the accuracy and robustness of the model for multi-scale target detection.Finally,an improved SEAM(Separated and Enhancement Attention Module)attention mechanism is combined with the DIOU-NMS algorithm to optimize the model’s performance when dealing with occlusion and dense scenes.Compared with the original model,the improved YOLO-LKSDS model achieves a 13.3%improvement in accuracy,a 1.7%improvement in mAP,and 240,000 fewer parameters on the BDD100K dataset.In order to validate the generalization of the improved algorithm,we selected the KITTI dataset for experimentation,which shows that YOLOv5’s accuracy improves by 21.1%,recall by 36.6%,and mAP50 by 29.5%,respectively,on the KITTI dataset.The deployment of this paper’s algorithm is verified by an edge computing platform,where the average speed of detection reaches 24.4 FPS while power consumption remains below 9 W,demonstrating high real-time capability and energy efficiency.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
In recent years,development of strategies to treat central nervous system(CNS) diseases has attracted extensive attention.A major obstacle in this field is the blood-brain barrier(BBB),which significantly limits the e...In recent years,development of strategies to treat central nervous system(CNS) diseases has attracted extensive attention.A major obstacle in this field is the blood-brain barrier(BBB),which significantly limits the efficient delivery of therapeutic agents to the brain and hinders the treatment of CNS diseases.Overcoming the restrictive nature of the BBB has thus emerged as a key objective in CNS drug development.Nanomaterials have garnered growing interest due to their unique physicochemical properties and potential to traverse the BBB,enabling targeted drug delivery to brain tissue and improving therapeutic efficacy.In this review,we present current insights into the structure and function of the BBB and highlight a range of nanomaterial-based strategies for BBB penetration,including receptor-mediated transport(RMT),adsorptive-mediated transcytosis,reversible BBB disruption,and intranasal administration.Finally,we summarize recent advances in enhancing BBB permeability for CNS therapeutics and discuss persisting challenges,offering perspectives for future research in this field.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
基金supported by National Natural Science Foundation of China for Science Center Program (21788102)National Key Research and Development Program (2016YFA0200300)+1 种基金Natural Science Foundation of China (21636002)National Postdoctoral Program for Innovative Talents (BX201700075)
文摘Analyses of the physiology and pathology of active biochemical species in their native contexts are critical for early diagnosis and therapy. Optical imaging has emerged as one of the promising modalities for noninvasive and real-time visualization of important biomolecules or biological events, and it has witnessed major advances in the field of imaging in vitro and in vivo. In this review, we present a survey of common approaches and tactics for enhanced targetability, response rate, and photostability in bioimaging applications. Recently developed and representative examples are illustrated on the cellular and tissue levels.
文摘Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathological characteristics and molecular pathways associated with its progression.Advances in scientific research have increasingly highlighted the crucial role of non-coding RNAs in the progression of Alzheimer's disease.These non-coding RNAs regulate several biological processes critical to the advancement of the disease,offering promising potential as therapeutic targets and diagnostic biomarkers.Therefore,this review aims to investigate the underlying mechanisms of Alzheimer's disease onset,with a particular focus on microRNAs,long non-coding RNAs,and circular RNAs associated with the disease.The review elucidates the potential pathogenic processes of Alzheimer's disease and provides a detailed description of the synthesis mechanisms of the three aforementioned non-coding RNAs.It comprehensively summarizes the various non-coding RNAs that have been identified to play key regulatory roles in Alzheimer's disease,as well as how these noncoding RNAs influence the disease's progression by regulating gene expression and protein functions.For example,miR-9 targets the UBE4B gene,promoting autophagy-mediated degradation of Tau protein,thereby reducing Tau accumulation and delaying Alzheimer's disease progression.Conversely,the long non-coding RNA BACE1-AS stabilizes BACE1 mRNA,promoting the generation of amyloid-βand accelerating Alzheimer's disease development.Additionally,circular RNAs play significant roles in regulating neuroinflammatory responses.By integrating insights from these regulatory mechanisms,there is potential to discover new therapeutic targets and potential biomarkers for early detection and management of Alzheimer's disease.This review aims to enhance the understanding of the relationship between Alzheimer's disease and non-coding RNAs,potentially paving the way for early detection and novel treatment strategies.
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 World Health Organization Global Youth Tobacco Survey(WPDHP1206671)the Global Health Capacity Building and Tobacco Control Project:Tobacco Epidemic Monitoring and Comprehensive Tobacco Control Intervention。
文摘Adolescent smoking constitutes a critical public health challenge as early initiation increases the risk of premature mortality and smoking-related chronic diseases due to longer exposure and higher cumulative tobacco use^([1]).Adolescents are especially prone to developing persistent smoking habits,with many adult smokers having started before the age of 18.In China,16.7%of secondary school students have tried smoking and 4.7%are current smokers,highlighting the critical need for targeted tobacco control interventions among the youth.
文摘Hebei Province has incorporated targeted assistance services for people with disabilities into livelihood projects,upgrading the quality and efficiency of support services for disadvantaged groups.THE living and nursing allowances provided by the Chinese government for people with disabilities who are unable to work are not only important components of China’s social security system which provide for the needs of its disabled,but also show China’s ability to guarantee the basic living standard and social fairness and justice for this group of people.
文摘Ufmylation is an ubiquitin-like post-translational modification characterized by the covalent binding of mature UFM1 to target proteins.Although the consequences of ufmylation on target proteins are not fully understood,its importance is evident from the disorders resulting from its dysfunction.Numerous case reports have established a link between biallelic loss-of-function and/or hypomorphic variants in ufmylation-related genes and a spectrum of pediatric neurodevelopmental disorders.
基金supported in part by the National Natural Science Foundation of China,Nos.81927804(to GL),82260456(to LY),U21A20479(to LY)Science and Technology Planning Project of Shenzhen,No.JCYJ20230807140559047(to LY)+3 种基金Key-Area Research and Development Program of Guangdong Province,No.2020B0909020004(to GL)Guangdong Basic and Applied Research Foundation,No.2023A1515011478(to LY)the Science and Technology Program of Guangdong Province,No.2022A0505090007(to GL)Ministry of Science and Technology,Shenzhen,No.QN2022032013L(to LY)。
文摘Neural machine interface technology is a pioneering approach that aims to address the complex challenges of neurological dysfunctions and disabilities resulting from conditions such as congenital disorders,traumatic injuries,and neurological diseases.Neural machine interface technology establishes direct connections with the brain or peripheral nervous system to restore impaired motor,sensory,and cognitive functions,significantly improving patients'quality of life.This review analyzes the chronological development and integration of various neural machine interface technologies,including regenerative peripheral nerve interfaces,targeted muscle and sensory reinnervation,agonist–antagonist myoneural interfaces,and brain–machine interfaces.Recent advancements in flexible electronics and bioengineering have led to the development of more biocompatible and highresolution electrodes,which enhance the performance and longevity of neural machine interface technology.However,significant challenges remain,such as signal interference,fibrous tissue encapsulation,and the need for precise anatomical localization and reconstruction.The integration of advanced signal processing algorithms,particularly those utilizing artificial intelligence and machine learning,has the potential to improve the accuracy and reliability of neural signal interpretation,which will make neural machine interface technologies more intuitive and effective.These technologies have broad,impactful clinical applications,ranging from motor restoration and sensory feedback in prosthetics to neurological disorder treatment and neurorehabilitation.This review suggests that multidisciplinary collaboration will play a critical role in advancing neural machine interface technologies by combining insights from biomedical engineering,clinical surgery,and neuroengineering to develop more sophisticated and reliable interfaces.By addressing existing limitations and exploring new technological frontiers,neural machine interface technologies have the potential to revolutionize neuroprosthetics and neurorehabilitation,promising enhanced mobility,independence,and quality of life for individuals with neurological impairments.By leveraging detailed anatomical knowledge and integrating cutting-edge neuroengineering principles,researchers and clinicians can push the boundaries of what is possible and create increasingly sophisticated and long-lasting prosthetic devices that provide sustained benefits for users.
文摘Pericytes are multi-functional mural cells of the central nervous system that cover the capillary endothelial cells. Pericytes play a vital role in nervous system development, significantly influencing the formation, maturation, and maintenance of the central nervous system. An expanding body of studies has revealed that pericytes establish carefully regulated interactions with oligodendrocytes, microglia, and astrocytes. These communications govern numerous critical brain processes, including angiogenesis, neurovascular unit homeostasis, blood–brain barrier integrity, cerebral blood flow regulation, and immune response initiation. Glial cells and pericytes participate in dynamic and reciprocal interactions, with each influencing and adjusting the functionality of the other. Pericytes have the ability to control astrocyte polarization, trigger differentiation of oligodendrocyte precursor cells, and initiate immunological responses in microglia. Various neurological disorders that compromise the integrity of the blood–brain barrier can disrupt these communications, impair waste clearance, and hinder cerebral blood circulation, contributing to neuroinflammation. In the context of neurodegeneration, these disruptions exacerbate pathological processes, such as neuronal damage, synaptic dysfunction, and impaired tissue repair. This article explores the complex interactions between pericytes and various glial cells in both healthy and pathological states of the central nervous system. It highlights their essential roles in neurovascular function and disease progression, providing important insights that may enhance our understanding of the molecular mechanisms underlying these interactions and guide potential therapeutic strategies for neurodegenerative disorders in future research.
基金supported by the National Natural Science Foundation of China,No.22103055(to JG)the Natural Science Foundation of Hebei Province,No.F2024110001(to HC)Open Project of Tianjin Key Laboratory of Optoelectronic Detection Technology and System,Nos.2024LODTS215(to NL),2024LODTS216(to XS).
文摘In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,allowing them to target deep brain lesions.Recent studies have demonstrated that exosomes derived from different cell types may exert therapeutic effects by regulating the expression of various inflammatory cytokines,mRNAs,and disease-related proteins,thereby halting the progression of neurodegenerative diseases and exhibiting beneficial effects.However,exosomes are composed of lipid bilayer membranes and lack the ability to recognize specific target cells.This limitation can lead to side effects and toxicity when they interact with non-specific cells.Growing evidence suggests that surface-modified exosomes have enhanced targeting capabilities and can be used as targeted drug-delivery vehicles that show promising results in the treatment of neurodegenerative diseases.In this review,we provide an up-to-date overview of existing research aimed at devising approaches to modify exosomes and elucidating their therapeutic potential in neurodegenerative diseases.Our findings indicate that exosomes can efficiently cross the blood-brain barrier to facilitate drug delivery and can also serve as early diagnostic markers for neurodegenerative diseases.We introduce the strategies being used to enhance exosome targeting,including genetic engineering,chemical modifications(both covalent,such as click chemistry and metabolic engineering,and non-covalent,such as polyvalent electrostatic and hydrophobic interactions,ligand-receptor binding,aptamer-based modifications,and the incorporation of CP05-anchored peptides),and nanomaterial modifications.Research into these strategies has confirmed that exosomes have significant therapeutic potential for neurodegenerative diseases.However,several challenges remain in the clinical application of exosomes.Improvements are needed in preparation,characterization,and optimization methods,as well as in reducing the adverse reactions associated with their use.Additionally,the range of applications and the safety of exosomes require further research and evaluation.
基金supported by the National Natural Science Foundation of China,Nos.82171347,82371362the Natural Science Foundation of Hunan Province,No.2022JJ30971the Scientific Research Project of Hunan Provincial Health Commission of China,No.202204040024(all to GX).
文摘A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation.This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiological mechanisms underlying hydrocephalus,one of the most common neurological conditions worldwide.In this review,we first outline the basic concepts and incidence of hydrocephalus along with the limitations of existing treatments for this condition.Then,we outline the definition,classification,and biological role of non-coding RNAs.Subsequently,we analyze the roles of non-coding RNAs in the formation of hydrocephalus in detail.Specifically,we have focused on the potential significance of non-coding RNAs in the pathophysiology of hydrocephalus,including glymphatic pathways,neuroinflammatory processes,and neurological dysplasia,on the basis of the existing evidence.Lastly,we review the potential of non-coding RNAs as biomarkers of hydrocephalus and for the creation of innovative treatments.
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.
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.
基金funded by the National Natural Science Foundation Regional Innovation and Development Joint Fund(No.U22A20381)National Key R&D Program of China (No.2024YFC3506600)+3 种基金Natural Science Foundation of Liaoning Province of China (No.2024-MS-086)Shenyang City Middle and Young Science and Technology Talents Cultivation Special U40 Outstanding Youth Project (No.RC230803)Science and Technology Planning Project of Liaoning Province (No.2021JH1/10400049)Song Shaojiang Expert Workstation of Yunnan Province (No.202305AF150030)。
文摘The first hemiterpene-quassinoid adducts,bruquass A and B(1 and 2),were rapidly isolated and identified from Brucea javanica using an integrated analytical strategy.They possessed unusual carbon skeletons formed by the coupling of quassinoids with hemiterpene units via vinylogous aldol reactions.Their structural configurations were determined through comprehensive spectroscopic analysis and electronic circular dichroism(ECD) calculations.Plausible biosynthetic pathways for 1 and 2 were proposed,and guided by these biogenetic insights,the biomimetic synthesis of compound 1 was successfully achieved.Furthermore,compounds 1 and 2 exhibited significant antifeedant activity against Plutella xylostella.The bioactivity assessment results open up the prospects of 1 and 2 as a promising new class of botanical insecticide.
文摘Amyloid protein aggregation plays a major role in multiple neurodegenerative diseases and is likely the primary driving force for the progression of most of these diseases.Multiple recent studies have highlighted that the DNAJ homolog subfamily B member 6(DNAJB6)chaperone is particularly interesting,when it comes to preventing amyloidogenic proteins from aggregating.It has been shown that DNAJB6 can prevent the aggregation of polyglutamine-expanded proteins in models of Huntington’s disease.Likewise,it can suppress aggregation ofα-synuclein in models of Parkinson’s disease and other synucleinopathies.Finally,it has been shown that DNAJB6 can block aggregation of multiple additional amyloid proteins involved in Alzheimer’s disease and other tauopathies as well.We believe there is yet much to learn about the protective role of DNAJB6 in the brain,but this focused review summarizes,what we know so far of this chaperone.It describes the biological role of DNAJB6 in the brain and its interaction with Hsp70,with particular emphasis on the studies that show its ability to prevent amyloid protein aggregation in vitro and in vivo.Moreover,recent work on dysregulation of the expression of DNAJB6 in brain clinical tissue is discussed.Finally,we discuss potential therapeutic perspectives as we believe this protein is a promising druggable target.
基金supported by the Key R&D Program of Shaanxi Province(No.2025CYYBXM-078).
文摘Aiming at the scale adaptation of automatic driving target detection algorithms in low illumination environments and the shortcomings in target occlusion processing,this paper proposes a YOLO-LKSDS automatic driving detection model.Firstly,the Contrast-Limited Adaptive Histogram Equalisation(CLAHE)image enhancement algorithm is improved to increase the image contrast and enhance the detailed features of the target;then,on the basis of the YOLOv5 model,the Kmeans++clustering algorithm is introduced to obtain a suitable anchor frame,and SPPELAN spatial pyramid pooling is improved to enhance the accuracy and robustness of the model for multi-scale target detection.Finally,an improved SEAM(Separated and Enhancement Attention Module)attention mechanism is combined with the DIOU-NMS algorithm to optimize the model’s performance when dealing with occlusion and dense scenes.Compared with the original model,the improved YOLO-LKSDS model achieves a 13.3%improvement in accuracy,a 1.7%improvement in mAP,and 240,000 fewer parameters on the BDD100K dataset.In order to validate the generalization of the improved algorithm,we selected the KITTI dataset for experimentation,which shows that YOLOv5’s accuracy improves by 21.1%,recall by 36.6%,and mAP50 by 29.5%,respectively,on the KITTI dataset.The deployment of this paper’s algorithm is verified by an edge computing platform,where the average speed of detection reaches 24.4 FPS while power consumption remains below 9 W,demonstrating high real-time capability and energy efficiency.
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funded by the Fundamental Research Funds for the Central Universities (No.2242022R42012)。
文摘In recent years,development of strategies to treat central nervous system(CNS) diseases has attracted extensive attention.A major obstacle in this field is the blood-brain barrier(BBB),which significantly limits the efficient delivery of therapeutic agents to the brain and hinders the treatment of CNS diseases.Overcoming the restrictive nature of the BBB has thus emerged as a key objective in CNS drug development.Nanomaterials have garnered growing interest due to their unique physicochemical properties and potential to traverse the BBB,enabling targeted drug delivery to brain tissue and improving therapeutic efficacy.In this review,we present current insights into the structure and function of the BBB and highlight a range of nanomaterial-based strategies for BBB penetration,including receptor-mediated transport(RMT),adsorptive-mediated transcytosis,reversible BBB disruption,and intranasal administration.Finally,we summarize recent advances in enhancing BBB permeability for CNS therapeutics and discuss persisting challenges,offering perspectives for future research in this field.
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.
