Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in hu...Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear,including cell viability,distribution,migration,and fate.Conventional cell tracing methods cannot be used in the clinic.The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging.In 2016,the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle,Ruicun,for use as a contrast agent in clinical trials.In the present study,an acute hemi-transection spinal cord injury model was established in beagle dogs.The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells.The results indicated that Ruicunlabeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury.T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord.The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks.These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.展开更多
Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response pla...Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury.Neuroinflammation,a key player in the pathophysiology of stroke,has a dual role.In the acute phase of stroke,neuroinflammation exacerbates brain injury,contributing to neuronal damage and blood–brain barrier disruption.This aspect of neuroinflammation is associated with poor neurological outcomes.Conversely,in the recovery phase following stroke,neuroinflammation facilitates brain repair processes,including neurogenesis,angiogenesis,and synaptic plasticity.The transition of neuroinflammation from a harmful to a reparative role is not well understood.Therefore,this review seeks to explore the mechanisms underlying this transition,with the goal of informing the development of therapeutic interventions that are both time-and context-specific.This review aims to elucidate the complex and dual role of neuroinflammation in stroke,highlighting the main actors,biomarkers of the disease,and potential therapeutic approaches.展开更多
Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted t...Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.展开更多
Background:Rats are often used to prepare skin defect models.However,the skin defect sizes of the models prepared by researchers are different,and the lack of consensus on the critical-size defect makes it difficult t...Background:Rats are often used to prepare skin defect models.However,the skin defect sizes of the models prepared by researchers are different,and the lack of consensus on the critical-size defect makes it difficult to compare their research results.Methods:The time for wound closure was evaluated and recorded through gross observation.The regression equation between the healing time and the diameter of skin defect was established,which can be used to predict the healing time for a certain skin defect size in rats.Histochemical and immunohistochemical staining was used to observe the regeneration and reconstruction of skin appendages,and the functional skin repair was quantitatively scored.Results:The critical-size defect of rats was determined based on the maximum capacity of structural skin repair,and the functional skin repair was quantitatively scored based on the regeneration and reconstruction of skin appendages.The allowable range of critical-size skin defect of SD rats lies between 45 and 50 mm in diameter.The concept of structural repair and the category of functional repair of injured skin are put forward.The regression equation between the structural skin healing time and defect diameters is established.Conclusion:The allowable range of skin critical-size defect of SD rats lies between 45 and 50 mm in diameter.The regression equation between the structural skin healing time and defect diameters can be used to predict the healing time for a certain skin defect size in rats.展开更多
In ultraviolet cured-in-place-pipe(UV-CIPP)pipeline rehabilitation,resin performance critically determines repair effectiveness.Current UV-curable resins exhibit high volatile organic compound(VOC)emissions and inadeq...In ultraviolet cured-in-place-pipe(UV-CIPP)pipeline rehabilitation,resin performance critically determines repair effectiveness.Current UV-curable resins exhibit high volatile organic compound(VOC)emissions and inadequate post-cure toughness,which compromise fatigue resistance during service.To address these issues,we synthesized hydroxyl-terminated polyurethane acrylate prepolymers using diphenylmethane diisocyanate(MDI),polypropylene glycol(PPG),and hydroxyethyl methacrylate(HEMA).Fourier transform infrared spectroscopy(FTIR)confirmed successful prepolymer synthesis.We developed UV-curable resins by incorporating various crosslinking monomers and optimized the formulations through mechanical property analysis.Testing revealed that the polyurethane-acrylic UV-cured resin system combines polyurethane's mechanical excellence with acrylics'high UV-curing activity.The PPG200/MDI/HEMA formulation achieved superior performance,with a tensile strength of 55.31 MPa,an impact toughness of 22.7 kJ/m^(2),and a heat deflection temperature(HDT)of 132℃.The optimized system eliminates volatile components while maintaining high reactivity,addressing critical limitations in trenchless pipeline rehabilitation.The improved mechanical properties meet the operational demands of underground pipes,suggesting practical applicability in trenchless pipeline repair.展开更多
The increasing occurrence of corrosion-related damage in steel pipelines has led to the growing use of composite-based repair techniques as an efficient alternative to traditional replacement methods.Computer modeling...The increasing occurrence of corrosion-related damage in steel pipelines has led to the growing use of composite-based repair techniques as an efficient alternative to traditional replacement methods.Computer modeling and structural analysis were performed for the repair reinforcement of a steel pipeline with a composite bandage.A preliminary analysis of possible contact interaction schemes was implemented based on the theory of cylindrical shells,taking into account transverse shear deformations.The finite element method was used for a detailed study of the stress state of the composite bandage and the reinforced section of the pipeline.The limit state of the reinforced section was assessed based on the von Mises criterion for steel and the Tsai-Wu criterion for composites.The effectiveness of the repair was demonstrated on a pipeline whose wall thickness had decreased by 20%as a result of corrosion damage.At a nominal pressure of P=6 MPa,the maximum normal stress in the weakened area reached 381 MPa.The installation of a composite bandage reduced this stress to 312 MPa,making the repaired section virtually as strong as the undamaged pipeline.Due to the linearity of the problem,the results obtained can be easily used to find critical internal pressure values.展开更多
Planning in lexical-prior-free environments presents a fundamental challenge for evaluating whether large language models(LLMs)possess genuine structural reasoning capabilities beyond lexical memorization.When predica...Planning in lexical-prior-free environments presents a fundamental challenge for evaluating whether large language models(LLMs)possess genuine structural reasoning capabilities beyond lexical memorization.When predicates and action names are replaced with semantically irrelevant random symbols while preserving logical structures,existing direct generation approaches exhibit severe performance degradation.This paper proposes a symbol-agnostic closed-loop planning pipeline that enables models to construct executable plans through systematic validation and iterative refinement.The system implements a complete generate-verify-repair cycle through six core processing components:semantic comprehension extracts structural constraints,language planner generates text plans,symbol translator performs structure-preserving mapping,consistency checker conducts static screening,Stanford Research Institute Problem Solver(STRIPS)simulator executes step-by-step validation,and VAL(Validator)provides semantic verification.A repair controller orchestrates four targeted strategies addressing typical failure patterns including first-step precondition errors andmid-segment statemaintenance issues.Comprehensive evaluation on PlanBench Mystery Blocksworld demonstrates substantial improvements over baseline approaches across both language models and reasoning models.Ablation studies confirm that each architectural component contributes non-redundantly to overall effectiveness,with targeted repair providing the largest impact,followed by deep constraint extraction and stepwise validation,demonstrating that superior performance emerges from synergistic integration of these mechanisms rather than any single dominant factor.Analysis reveals distinct failure patterns betweenmodel types—languagemodels struggle with local precondition satisfaction while reasoning models face global goal achievement challenges—yet the validation-driven mechanism successfully addresses these diverse weaknesses.A particularly noteworthy finding is the convergence of final success rates across models with varying intrinsic capabilities,suggesting that systematic validation and repair mechanisms play a more decisive role than raw model capacity in lexical-prior-free scenarios.This work establishes a rigorous evaluation framework incorporating statistical significance testing and mechanistic failure analysis,providingmethodological contributions for fair assessment and practical insights into building reliable planning systems under extreme constraint conditions.展开更多
Background:Cartilage repair remains a considerable challenge in regenerative medicine.Despite extensive research on biomaterials for cartilage repair in recent years,issues such as prolonged repair cycles and suboptim...Background:Cartilage repair remains a considerable challenge in regenerative medicine.Despite extensive research on biomaterials for cartilage repair in recent years,issues such as prolonged repair cycles and suboptimal outcomes persist.Organoids,miniature three-dimensional(3D)tissue structures derived from the directed differentiation of stem or progenitor cells,mimic the structure and function of natural organs.Therefore,the construction of cartilage organoids(COs)holds great promise as a novel strategy for cartilage repair.Methods:This study employed a digital light processing system to perform 3D bioprinting of a DNA-silk fibroin(DNA-SF)hydrogel sustained-release system(DSRGT)with bone-marrow mesenchymal stem cells(BMSCs)to construct millimeter-scale CO.COs at different developmental stages were characterized,and the COs with the best cartilage phenotype were selected for in vivo cartilage repair in a rat articular cartilage defect model.Results:This study developed a DSRGT by covalently grafting glucosamine(which promotes cartilage matrix synthesis)and TD-198946(which promotes chondrogenic differentiation)onto a hydrogel using acrylic acid-polyethylene glycolN-hydroxysuccinimide(AC-PEG-NHS).In vitro,4-week COs exhibited higher SRY-box transcription factor 9(SOX9),typeⅡcollagen(ColⅡ),and aggrecan(ACAN)expression and lower typeⅠcollagen(ColⅠ)and typeⅩcollagen(ColⅩ)expression,indicating that 4 weeks is the optimal culture duration for hyaline cartilage development.In vivo,the mitogen-activated protein kinase(MAPK)signaling pathway was upregulated in 4-week COs,enabling cartilage repair within 8 weeks.Transcriptomic analysis revealed that cartilage regenerated with 4-week COs presented gene expression profiles resembling those of healthy cartilage.Conclusion:This study employs DSRGT to construct COs,providing an innovative strategy for the regeneration of cartilage defects.展开更多
The central nervous system(CNS)does not function in isolation-it engages in continuous molecular dialogue with the vascular and immune systems.Traditionally,the blood-brain barrier(BBB)was portrayed solely as an imper...The central nervous system(CNS)does not function in isolation-it engages in continuous molecular dialogue with the vascular and immune systems.Traditionally,the blood-brain barrier(BBB)was portrayed solely as an impermeable wall,safeguarding the CNS by excluding blood-derived molecules and circulating cells.However,this view has evolved.The BBB is now recognized as a dynamic interface that selectively regulates the exchange of signals,cells.展开更多
Robotic inguinal hernia repair remains in the early stages of implementation,and its potential advantages over the laparoscopic approach are still a matter of debate.This narrative review aims to summarize the finding...Robotic inguinal hernia repair remains in the early stages of implementation,and its potential advantages over the laparoscopic approach are still a matter of debate.This narrative review aims to summarize the findingsof major systematic reviews and randomized controlled trials and explore variables not adequately addressed in those studies.The literature review indicates that robotic inguinal hernia repair is associated with longer operative times but has improved ergonomics compared with laparoscopy.It is a safe procedure that results in a reduced inflammatory response,similar complication rates,and no significantdifference in acute postoperative pain.Although it involves higher direct costs,its cost-effectiveness remains unclear owing to a lack of analysis including indirect costs.Ongoing controversy continues regarding long-term benefits.The most recent systematic review pointed towards lower recurrence rates with robotic surgery,although randomized controlled trials have not validated this finding.Data on chronic pain are currently insufficientto draw firmconclusions.Further studies are needed to assess its use in complex cases and the role of novel techniques.展开更多
The blood-spinal cord barrier is crucial for preserving homeostasis of the central nervous system.After spinal cord injury,autophagic flux within endothelial cells is disrupted,compromising the integrity of the blood-...The blood-spinal cord barrier is crucial for preserving homeostasis of the central nervous system.After spinal cord injury,autophagic flux within endothelial cells is disrupted,compromising the integrity of the blood-spinal cord barrier.This disruption facilitates extensive infiltration of inflammatory cells,resulting in exacerbated neuroinflammatory responses,neuronal death,and impaired neuronal regeneration.Previous research has demonstrated that photobiomodulation promotes the regeneration of damaged nerves following spinal cord injury by inhibiting the recruitment of inflammatory cells to the injured site and restoring neuronal mitochondrial function.However,the precise mechanisms by which photobiomodulation regulates neuroinflammation remain incompletely elucidated.In this study,we established a mouse model of spinal cord injury and assessed the effects of photobiomodulation treatment.Photobiomodulation effectively cleared damaged mitochondria from endothelial cells in mice,promoting recovery of hindlimb motor function.Using microvascular endothelial bEnd.3 cells subjected to oxygen-glucose deprivation,we found that the effects of photobiomodulation were mediated through activation of the PINK1/Parkin pathway.Additionally,photobiomodulation reduced mitochondrial oxidative stress levels and increased the expression of tight junction proteins within the blood-spinal cord barrier.Our findings suggest that photobiomodulation activates mitochondrial autophagy in endothelial cells through the PINK1/Parkin pathway,thereby promoting repair of the blood-spinal cord barrier following spinal cord injury.展开更多
Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process...Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.展开更多
Fissured rocks are prevalent in geotechnical engineering and can significantlyimpact the stability of engineering structures.Microbial-induced carbonate precipitation(MICP)technology provides an ecofriendly solution f...Fissured rocks are prevalent in geotechnical engineering and can significantlyimpact the stability of engineering structures.Microbial-induced carbonate precipitation(MICP)technology provides an ecofriendly solution for repairing fissuredrocks.To optimize repair effectiveness,this study firstinvestigated the effects of environmental factors on bacterial growth,urease activity,and calcium carbonate yield.The optimal MICP scheme was determined to be a pH of 9,a temperature of 25℃,and a cementation solution concentration of 0.5 mol/L.Subsequently,the sandstone specimens with various fissureapertures were repaired using MICP with different bacterial concentrations.Dynamic tests were carried out on the repaired specimens using a split Hopkinson pressure bar system.The experimental results indicate that the dynamic strength of the MICP-repaired specimens positively correlates with strain rate,but decreases with increasing bacterial concentration and fissureaperture.These factors have little effect on the progressive failure behavior.Surface cracks were mainly compression-shear cracks in the repair area and tensile-shear cracks at the end of the specimen.Moreover,the crystal morphology observed by scanning electron microscope indicates that MICP primarily produces vaterite crystals,and lower bacterial concentrations favor the formation of more stable calcite crystals,thereby enhancing the cementitious properties.Furthermore,X-ray computed tomography demonstrates an uneven distribution of calcium carbonate within fissures,with higher fillingrates observed at the injection end and at the bottom of the fissures.Lower bacterial concentrations and smaller fissureapertures are conducive to more uniform distribution and increased fillingrate of calcium carbonate,with fissureaperture exerting a more dominant influence.展开更多
Spinal cord injury(SCI)is a debilitating ailment that leads to the loss of motor and sensory functions,often leaving the patient paralyzed below the injury site(Chen et al.,2013).Globally around 250,000-300,000 people...Spinal cord injury(SCI)is a debilitating ailment that leads to the loss of motor and sensory functions,often leaving the patient paralyzed below the injury site(Chen et al.,2013).Globally around 250,000-300,000 people are diagnosed with SCI annually(Singh et al.,2014),and while this number appears quite low,the effect that an SCI has on the patient’s quality of life is drastic,due to the current difficulties to comprehensively treat this illness.The cost of patient care can also be quite costly,amounting to an estimated$1.69 billion in healthcare costs in the USA alone(Mahabaleshwarkar and Khanna,2014).展开更多
Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kines...Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.展开更多
Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after inju...Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.展开更多
Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue en...Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue engineering scaffolds is of great significance for bone repair.This study synthesized copper(Cu)-doped mesoporous silica nanoparticles(Cu@MSN)modified with hydroxyethyl methacrylate to obtain methacrylated Cu@MSN(Cu@MSNMA).Furtheremore,bio-mimetic nanocomposite hydrogels were prepared by adding Cu@MSNMA to a GelMA/gelatin solution.This hydrogel achieves multi-modal bone tissue biomimicry:(ⅰ)GelMA/gelatin mimics the matrix components in bone ECM,ensuring biocompatibility while promoting cellular behavior(such as adhesion,proliferation,and differentiation);(ⅱ)GelMA/gela-tin and the crosslinking sites introduced by Cu@MSNMA form a stable porous network structure,achieving structural and mechanical biomimicry to provide necessary support for bone defects;(ⅲ)The elemental biomimicry of Si and Cu in Cu@MSNMA achieves efficient osteogenic induction.The effect of different proportions of Cu@MSNMA on the physi-cal properties of the composite hydrogels was investigated to determine the optimal proportion.The results indicated that the mechanical properties of hydrogel were enhanced with the increasing Cu@MSNMA mass ratio.Notably,5%NPs/GelMA/gelatin hydrogel exhibited excellent mechanical property compared to the GelMA/gelatin hydrogel.In vitro and vivo cellular experiments demonstrated a significant enhancement in antibacterial and osteogenic induction with Cu@MSNMA addition.In conclusion,the proposed nanocomposite hydrogel with biomimetic components and ion-regulating properties can serve as a multifunctional scaffold,offering antimicrobial properties for infected bone regeneration,and guide for future research in bone regeneration and three-dimensional printing.展开更多
The presence or absence of adult neural stem cells in the mammalian forebrain ependyma has been debated for two decades.In this study,we performed single-cell RNA sequencing to investigate the cellular composition of ...The presence or absence of adult neural stem cells in the mammalian forebrain ependyma has been debated for two decades.In this study,we performed single-cell RNA sequencing to investigate the cellular composition of the ependymal surface of the adult mouse forebrain using whole mounts of lateral walls of lateral ventricles.We identified 12 different cell subtypes in the ependymal surface.Immunocytochemical analyses revealed that CD133^(+)multi-ciliated cells comprised 67.6%of ependymal cells,while the remaining 32.4%were CD133^(-).CD133^(+)ependymal cells can be further classified into FOXJ1^(+)/SOX2^(+)/ACTA2^(+)cells,FLT1^(+)/CD31^(+)/CLDN5^(+)endothelial-like cells,and PDGFRB^(+)/VTN^(+)/NG2^(+)pericyte-like cells,as well as endothelial-pericyte-like cells and Foxj1^(+)endothelial-like cells.CD133^(-)ependymal cells can be further divided into endothelial-like cells,Foxj1^(+)ependymal cells,Foxj1^(+)endothelial-like cells,pericyte-like cells,endothelial-pericyte-like cells,VIM^(+)cells,and cells negative for all of these markers.This comprehensive profiling confirms the heterogeneity of the ependymal surface in the adult mouse forebrain.Debate regarding whether adult ependymal cells contain neural stem cells has arisen because different researchers have examined different populations of ependymal cells.Our study provides a new perspective for investigation of clinical endogenous neural stem cells,ultimately paving the way for stem cell therapies in neurological diseases.展开更多
The application of DNA hybridization technology,grounded in Watson-Crick base pairing,has facilitated the rational design of framework nucleic acids(FNAs)featuring adaptable shapes and dimensions.These nanostructures ...The application of DNA hybridization technology,grounded in Watson-Crick base pairing,has facilitated the rational design of framework nucleic acids(FNAs)featuring adaptable shapes and dimensions.These nanostructures exhibit remarkable stability and reproducibility,making them promising candidates for biomedical applications.Among various FNAs,tetrahedral FNAs(tFNAs),first introduced by Turberfield,are nanoscale assemblies of oligonucleotides that possess unique physical,chemical,and biological properties.Previous studies have demonstrated that tFNAs exhibit excellent cellular uptake,enhanced tissue permeability,and strong capabilities to promote cell migration,proliferation,and differentiation.Moreover,the intrinsic ability of tFNAs to efficiently penetrate cell membranes allows tFNAs to serve as versatile carriers for small-molecule drugs or functional oligonucleotides,thereby exerting significant anti-inflammatory,antioxidant,antibacterial,and immunomodulatory effects.These features highlight the therapeutic potential of tFNA-based complexes in skin,mucosal,and barrier tissue repair and regeneration.This review provides a comprehensive analysis of recent advances in the application of tFNAs for the prevention and treatment of skin,mucosal,and barrier tissue diseases,with a focus on their mechanisms of action and future prospects in regenerative medicine and targeted therapies.展开更多
Automated Program Repair(APR)techniques have shown significant potential in mitigating the cost and complexity associated with debugging by automatically generating corrective patches for software defects.Despite cons...Automated Program Repair(APR)techniques have shown significant potential in mitigating the cost and complexity associated with debugging by automatically generating corrective patches for software defects.Despite considerable progress in APR methodologies,existing approaches frequently lack contextual awareness of runtime behaviors and structural intricacies inherent in buggy source code.In this paper,we propose a novel APR approach that integrates attention mechanisms within an autoencoder-based framework,explicitly utilizing structural code affinity and execution context correlation derived from stack trace analysis.Our approach begins with an innovative preprocessing pipeline,where code segments and stack traces are transformed into tokenized representations.Subsequently,the BM25 ranking algorithm is employed to quantitatively measure structural code affinity and execution context correlation,identifying syntactically and semantically analogous buggy code snippets and relevant runtime error contexts from extensive repositories.These extracted features are then encoded via an attention-enhanced autoencoder model,specifically designed to capture significant patterns and correlations essential for effective patch generation.To assess the efficacy and generalizability of our proposed method,we conducted rigorous experimental comparisons against DeepFix,a state-of-the-art APR system,using a substantial dataset comprising 53,478 studentdeveloped C programs.Experimental outcomes indicate that our model achieves a notable bug repair success rate of approximately 62.36%,representing a statistically significant performance improvement of over 6%compared to the baseline.Furthermore,a thorough K-fold cross-validation reinforced the consistency,robustness,and reliability of our method across diverse subsets of the dataset.Our findings present the critical advantage of integrating attentionbased learning with code structural and execution context features in APR tasks,leading to improved accuracy and practical applicability.Future work aims to extend the model’s applicability across different programming languages,systematically optimize hyperparameters,and explore alternative feature representation methods to further enhance debugging efficiency and effectiveness.展开更多
基金supported by the National Key R&D Program of China,Nos.2017YFA0104302(to NG and XM)and 2017YFA0104304(to BW and ZZ)
文摘Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear,including cell viability,distribution,migration,and fate.Conventional cell tracing methods cannot be used in the clinic.The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging.In 2016,the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle,Ruicun,for use as a contrast agent in clinical trials.In the present study,an acute hemi-transection spinal cord injury model was established in beagle dogs.The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells.The results indicated that Ruicunlabeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury.T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord.The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks.These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.
基金supported by European Union-NextGeneration EU under the Italian University and Research(MUR)National Innovation Ecosystem grant ECS00000041-VITALITY-CUP E13C22001060006(to MdA)。
文摘Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury.Neuroinflammation,a key player in the pathophysiology of stroke,has a dual role.In the acute phase of stroke,neuroinflammation exacerbates brain injury,contributing to neuronal damage and blood–brain barrier disruption.This aspect of neuroinflammation is associated with poor neurological outcomes.Conversely,in the recovery phase following stroke,neuroinflammation facilitates brain repair processes,including neurogenesis,angiogenesis,and synaptic plasticity.The transition of neuroinflammation from a harmful to a reparative role is not well understood.Therefore,this review seeks to explore the mechanisms underlying this transition,with the goal of informing the development of therapeutic interventions that are both time-and context-specific.This review aims to elucidate the complex and dual role of neuroinflammation in stroke,highlighting the main actors,biomarkers of the disease,and potential therapeutic approaches.
基金supported by the National Natural Science Foundation of China,Nos.32271389,31900987(both to PY)the Natural Science Foundation of Jiangsu Province,No.BK20230608(to JJ)。
文摘Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.
基金National Key Research and Development Program of China,Grant/Award Number:2023YFC2410403。
文摘Background:Rats are often used to prepare skin defect models.However,the skin defect sizes of the models prepared by researchers are different,and the lack of consensus on the critical-size defect makes it difficult to compare their research results.Methods:The time for wound closure was evaluated and recorded through gross observation.The regression equation between the healing time and the diameter of skin defect was established,which can be used to predict the healing time for a certain skin defect size in rats.Histochemical and immunohistochemical staining was used to observe the regeneration and reconstruction of skin appendages,and the functional skin repair was quantitatively scored.Results:The critical-size defect of rats was determined based on the maximum capacity of structural skin repair,and the functional skin repair was quantitatively scored based on the regeneration and reconstruction of skin appendages.The allowable range of critical-size skin defect of SD rats lies between 45 and 50 mm in diameter.The concept of structural repair and the category of functional repair of injured skin are put forward.The regression equation between the structural skin healing time and defect diameters is established.Conclusion:The allowable range of skin critical-size defect of SD rats lies between 45 and 50 mm in diameter.The regression equation between the structural skin healing time and defect diameters can be used to predict the healing time for a certain skin defect size in rats.
基金Funded by the National Natural Science Foundation of China(No.52473077)China Three Gorges Corporation(No.202403190)。
文摘In ultraviolet cured-in-place-pipe(UV-CIPP)pipeline rehabilitation,resin performance critically determines repair effectiveness.Current UV-curable resins exhibit high volatile organic compound(VOC)emissions and inadequate post-cure toughness,which compromise fatigue resistance during service.To address these issues,we synthesized hydroxyl-terminated polyurethane acrylate prepolymers using diphenylmethane diisocyanate(MDI),polypropylene glycol(PPG),and hydroxyethyl methacrylate(HEMA).Fourier transform infrared spectroscopy(FTIR)confirmed successful prepolymer synthesis.We developed UV-curable resins by incorporating various crosslinking monomers and optimized the formulations through mechanical property analysis.Testing revealed that the polyurethane-acrylic UV-cured resin system combines polyurethane's mechanical excellence with acrylics'high UV-curing activity.The PPG200/MDI/HEMA formulation achieved superior performance,with a tensile strength of 55.31 MPa,an impact toughness of 22.7 kJ/m^(2),and a heat deflection temperature(HDT)of 132℃.The optimized system eliminates volatile components while maintaining high reactivity,addressing critical limitations in trenchless pipeline rehabilitation.The improved mechanical properties meet the operational demands of underground pipes,suggesting practical applicability in trenchless pipeline repair.
文摘The increasing occurrence of corrosion-related damage in steel pipelines has led to the growing use of composite-based repair techniques as an efficient alternative to traditional replacement methods.Computer modeling and structural analysis were performed for the repair reinforcement of a steel pipeline with a composite bandage.A preliminary analysis of possible contact interaction schemes was implemented based on the theory of cylindrical shells,taking into account transverse shear deformations.The finite element method was used for a detailed study of the stress state of the composite bandage and the reinforced section of the pipeline.The limit state of the reinforced section was assessed based on the von Mises criterion for steel and the Tsai-Wu criterion for composites.The effectiveness of the repair was demonstrated on a pipeline whose wall thickness had decreased by 20%as a result of corrosion damage.At a nominal pressure of P=6 MPa,the maximum normal stress in the weakened area reached 381 MPa.The installation of a composite bandage reduced this stress to 312 MPa,making the repaired section virtually as strong as the undamaged pipeline.Due to the linearity of the problem,the results obtained can be easily used to find critical internal pressure values.
基金supported by the Information,Production and Systems Research Center,Waseda University,and partly supported by the Future Robotics Organization,Waseda Universitythe Humanoid Robotics Institute,Waseda University,under the Humanoid Project+1 种基金the Waseda University Grant for Special Research Projects(grant numbers 2024C-518 and 2025E-027)was partly executed under the cooperation of organization between Kioxia Corporation andWaseda University.
文摘Planning in lexical-prior-free environments presents a fundamental challenge for evaluating whether large language models(LLMs)possess genuine structural reasoning capabilities beyond lexical memorization.When predicates and action names are replaced with semantically irrelevant random symbols while preserving logical structures,existing direct generation approaches exhibit severe performance degradation.This paper proposes a symbol-agnostic closed-loop planning pipeline that enables models to construct executable plans through systematic validation and iterative refinement.The system implements a complete generate-verify-repair cycle through six core processing components:semantic comprehension extracts structural constraints,language planner generates text plans,symbol translator performs structure-preserving mapping,consistency checker conducts static screening,Stanford Research Institute Problem Solver(STRIPS)simulator executes step-by-step validation,and VAL(Validator)provides semantic verification.A repair controller orchestrates four targeted strategies addressing typical failure patterns including first-step precondition errors andmid-segment statemaintenance issues.Comprehensive evaluation on PlanBench Mystery Blocksworld demonstrates substantial improvements over baseline approaches across both language models and reasoning models.Ablation studies confirm that each architectural component contributes non-redundantly to overall effectiveness,with targeted repair providing the largest impact,followed by deep constraint extraction and stepwise validation,demonstrating that superior performance emerges from synergistic integration of these mechanisms rather than any single dominant factor.Analysis reveals distinct failure patterns betweenmodel types—languagemodels struggle with local precondition satisfaction while reasoning models face global goal achievement challenges—yet the validation-driven mechanism successfully addresses these diverse weaknesses.A particularly noteworthy finding is the convergence of final success rates across models with varying intrinsic capabilities,suggesting that systematic validation and repair mechanisms play a more decisive role than raw model capacity in lexical-prior-free scenarios.This work establishes a rigorous evaluation framework incorporating statistical significance testing and mechanistic failure analysis,providingmethodological contributions for fair assessment and practical insights into building reliable planning systems under extreme constraint conditions.
基金supported by the National Key Research and Development Program of China(2022YFB3804300)the National Natural Science Foundation of China(82230071,32471395,82427809,82472479)+2 种基金the Shanghai Science and Technology Innovation Action Plan(23141900600)the Research Physician Training Program of Shanghai Hospital Development Center(SHDC2023CRT013)the Shanghai Municipal Demonstration Project for Innovative Medical Device Applications(23SHS05700)。
文摘Background:Cartilage repair remains a considerable challenge in regenerative medicine.Despite extensive research on biomaterials for cartilage repair in recent years,issues such as prolonged repair cycles and suboptimal outcomes persist.Organoids,miniature three-dimensional(3D)tissue structures derived from the directed differentiation of stem or progenitor cells,mimic the structure and function of natural organs.Therefore,the construction of cartilage organoids(COs)holds great promise as a novel strategy for cartilage repair.Methods:This study employed a digital light processing system to perform 3D bioprinting of a DNA-silk fibroin(DNA-SF)hydrogel sustained-release system(DSRGT)with bone-marrow mesenchymal stem cells(BMSCs)to construct millimeter-scale CO.COs at different developmental stages were characterized,and the COs with the best cartilage phenotype were selected for in vivo cartilage repair in a rat articular cartilage defect model.Results:This study developed a DSRGT by covalently grafting glucosamine(which promotes cartilage matrix synthesis)and TD-198946(which promotes chondrogenic differentiation)onto a hydrogel using acrylic acid-polyethylene glycolN-hydroxysuccinimide(AC-PEG-NHS).In vitro,4-week COs exhibited higher SRY-box transcription factor 9(SOX9),typeⅡcollagen(ColⅡ),and aggrecan(ACAN)expression and lower typeⅠcollagen(ColⅠ)and typeⅩcollagen(ColⅩ)expression,indicating that 4 weeks is the optimal culture duration for hyaline cartilage development.In vivo,the mitogen-activated protein kinase(MAPK)signaling pathway was upregulated in 4-week COs,enabling cartilage repair within 8 weeks.Transcriptomic analysis revealed that cartilage regenerated with 4-week COs presented gene expression profiles resembling those of healthy cartilage.Conclusion:This study employs DSRGT to construct COs,providing an innovative strategy for the regeneration of cartilage defects.
基金supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number K02NS110973 and R01NS126498(to MAP).
文摘The central nervous system(CNS)does not function in isolation-it engages in continuous molecular dialogue with the vascular and immune systems.Traditionally,the blood-brain barrier(BBB)was portrayed solely as an impermeable wall,safeguarding the CNS by excluding blood-derived molecules and circulating cells.However,this view has evolved.The BBB is now recognized as a dynamic interface that selectively regulates the exchange of signals,cells.
文摘Robotic inguinal hernia repair remains in the early stages of implementation,and its potential advantages over the laparoscopic approach are still a matter of debate.This narrative review aims to summarize the findingsof major systematic reviews and randomized controlled trials and explore variables not adequately addressed in those studies.The literature review indicates that robotic inguinal hernia repair is associated with longer operative times but has improved ergonomics compared with laparoscopy.It is a safe procedure that results in a reduced inflammatory response,similar complication rates,and no significantdifference in acute postoperative pain.Although it involves higher direct costs,its cost-effectiveness remains unclear owing to a lack of analysis including indirect costs.Ongoing controversy continues regarding long-term benefits.The most recent systematic review pointed towards lower recurrence rates with robotic surgery,although randomized controlled trials have not validated this finding.Data on chronic pain are currently insufficientto draw firmconclusions.Further studies are needed to assess its use in complex cases and the role of novel techniques.
基金supported by the National Natural Science Foundation of China,No.82471411(to ZW and TD)the Key Research and DevelopmentProgram of Shaanxi Province,No.2023-ZDLSF-12(to TD).
文摘The blood-spinal cord barrier is crucial for preserving homeostasis of the central nervous system.After spinal cord injury,autophagic flux within endothelial cells is disrupted,compromising the integrity of the blood-spinal cord barrier.This disruption facilitates extensive infiltration of inflammatory cells,resulting in exacerbated neuroinflammatory responses,neuronal death,and impaired neuronal regeneration.Previous research has demonstrated that photobiomodulation promotes the regeneration of damaged nerves following spinal cord injury by inhibiting the recruitment of inflammatory cells to the injured site and restoring neuronal mitochondrial function.However,the precise mechanisms by which photobiomodulation regulates neuroinflammation remain incompletely elucidated.In this study,we established a mouse model of spinal cord injury and assessed the effects of photobiomodulation treatment.Photobiomodulation effectively cleared damaged mitochondria from endothelial cells in mice,promoting recovery of hindlimb motor function.Using microvascular endothelial bEnd.3 cells subjected to oxygen-glucose deprivation,we found that the effects of photobiomodulation were mediated through activation of the PINK1/Parkin pathway.Additionally,photobiomodulation reduced mitochondrial oxidative stress levels and increased the expression of tight junction proteins within the blood-spinal cord barrier.Our findings suggest that photobiomodulation activates mitochondrial autophagy in endothelial cells through the PINK1/Parkin pathway,thereby promoting repair of the blood-spinal cord barrier following spinal cord injury.
基金supported by the National Natural Science Foundation of China,Nos.82171344(to ZY),82471313(to CKT)the Guangdong Basic and Applied Basic Research Foundation,China,Nos.2023B1515120035,2024A1515012035(to CKT)The Science and Technology Projects in Guangzhou Nos.2025A03J4169(to ZY)。
文摘Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.
基金support from the National Key R&D Program of China(Grant No.2023YFC3081500)the National Natural Science Foundation of China(Grant Nos.52225904 and 52039007).
文摘Fissured rocks are prevalent in geotechnical engineering and can significantlyimpact the stability of engineering structures.Microbial-induced carbonate precipitation(MICP)technology provides an ecofriendly solution for repairing fissuredrocks.To optimize repair effectiveness,this study firstinvestigated the effects of environmental factors on bacterial growth,urease activity,and calcium carbonate yield.The optimal MICP scheme was determined to be a pH of 9,a temperature of 25℃,and a cementation solution concentration of 0.5 mol/L.Subsequently,the sandstone specimens with various fissureapertures were repaired using MICP with different bacterial concentrations.Dynamic tests were carried out on the repaired specimens using a split Hopkinson pressure bar system.The experimental results indicate that the dynamic strength of the MICP-repaired specimens positively correlates with strain rate,but decreases with increasing bacterial concentration and fissureaperture.These factors have little effect on the progressive failure behavior.Surface cracks were mainly compression-shear cracks in the repair area and tensile-shear cracks at the end of the specimen.Moreover,the crystal morphology observed by scanning electron microscope indicates that MICP primarily produces vaterite crystals,and lower bacterial concentrations favor the formation of more stable calcite crystals,thereby enhancing the cementitious properties.Furthermore,X-ray computed tomography demonstrates an uneven distribution of calcium carbonate within fissures,with higher fillingrates observed at the injection end and at the bottom of the fissures.Lower bacterial concentrations and smaller fissureapertures are conducive to more uniform distribution and increased fillingrate of calcium carbonate,with fissureaperture exerting a more dominant influence.
基金supported by the Irish Research Council under the Government of Ireland Postdoctoral Fellowship Project ID-GOIPD/2023/1431(to AS).
文摘Spinal cord injury(SCI)is a debilitating ailment that leads to the loss of motor and sensory functions,often leaving the patient paralyzed below the injury site(Chen et al.,2013).Globally around 250,000-300,000 people are diagnosed with SCI annually(Singh et al.,2014),and while this number appears quite low,the effect that an SCI has on the patient’s quality of life is drastic,due to the current difficulties to comprehensively treat this illness.The cost of patient care can also be quite costly,amounting to an estimated$1.69 billion in healthcare costs in the USA alone(Mahabaleshwarkar and Khanna,2014).
基金supported by the Portuguese Foundation for Science and Technology(FCT),Centro 2020 and Portugol2020 and the EU FEDER program,via the project GoBack to SIV(PTDC/CVT-CVT/32261/2017,CENTRO-01-0145-FEDER-032261)the doctoral grants of PDC(SFRH/BD/139974/2018)and BMS(2020.06525.BD and DOI 10.54499/2020.06525.BD)+5 种基金the post-doctoral grant to JPF(SFRH/BPD/113359/2015-program-contract described in paragraphs 4,5,6 of art.23 of Law no.100157/2016,of August 29,as amended by Law no.57/2017 of July 2019),the project PTDC/MED-NEU/1677/2021 to JBRthe Institute of Biomedicine iBiMED(UIDB/04501/2020 and DOI 10.54499/UIDB/04501/2020,UIDP/04501/2020 and DOI 10.54499/UIDP/04501/2020)its LiM Bioimaging Facility-a PPBI node(POCI-01-0145-FEDER-022122)supported by the Research Commission of the Medical Faculty of the Heinrich-Heine-University(HHU)Düsseldorf,of the Biologisch-Medizinisches Forschungszentrum(BMFZ)of HHUfinanced by the Spanish"Plan Nacional de Investigacion Cientifica,Desarrollo e Innovacion Tecnologica,Ministerio de Economia y Competitividad(Instituto de Salud CarlosⅢ)",co-financed by the European Union(FEDER program),(grant FIS P/20/00318 and FIS P23/00337 to VC)grant CPP2021-009070 to VC by the"Proyectos de colaboracion publico-privada,Plan de Investigacion Cientifica,Tecnica y de inovacion 2021-2023,Ministerio de Ciencia e Innovacion,Union Europea,Agencia Estatal de Investigacion,Espana"。
文摘Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.
文摘Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.
基金National Key R&D Program of China(grant number 2022YFA1207500)National Natural Science Foundation of China(grant number 82072412).
文摘Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue engineering scaffolds is of great significance for bone repair.This study synthesized copper(Cu)-doped mesoporous silica nanoparticles(Cu@MSN)modified with hydroxyethyl methacrylate to obtain methacrylated Cu@MSN(Cu@MSNMA).Furtheremore,bio-mimetic nanocomposite hydrogels were prepared by adding Cu@MSNMA to a GelMA/gelatin solution.This hydrogel achieves multi-modal bone tissue biomimicry:(ⅰ)GelMA/gelatin mimics the matrix components in bone ECM,ensuring biocompatibility while promoting cellular behavior(such as adhesion,proliferation,and differentiation);(ⅱ)GelMA/gela-tin and the crosslinking sites introduced by Cu@MSNMA form a stable porous network structure,achieving structural and mechanical biomimicry to provide necessary support for bone defects;(ⅲ)The elemental biomimicry of Si and Cu in Cu@MSNMA achieves efficient osteogenic induction.The effect of different proportions of Cu@MSNMA on the physi-cal properties of the composite hydrogels was investigated to determine the optimal proportion.The results indicated that the mechanical properties of hydrogel were enhanced with the increasing Cu@MSNMA mass ratio.Notably,5%NPs/GelMA/gelatin hydrogel exhibited excellent mechanical property compared to the GelMA/gelatin hydrogel.In vitro and vivo cellular experiments demonstrated a significant enhancement in antibacterial and osteogenic induction with Cu@MSNMA addition.In conclusion,the proposed nanocomposite hydrogel with biomimetic components and ion-regulating properties can serve as a multifunctional scaffold,offering antimicrobial properties for infected bone regeneration,and guide for future research in bone regeneration and three-dimensional printing.
基金supported by the State Key Program of the National Natural Science Foundation of China,No.82030035(to YES)Peak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai(to LZ).
文摘The presence or absence of adult neural stem cells in the mammalian forebrain ependyma has been debated for two decades.In this study,we performed single-cell RNA sequencing to investigate the cellular composition of the ependymal surface of the adult mouse forebrain using whole mounts of lateral walls of lateral ventricles.We identified 12 different cell subtypes in the ependymal surface.Immunocytochemical analyses revealed that CD133^(+)multi-ciliated cells comprised 67.6%of ependymal cells,while the remaining 32.4%were CD133^(-).CD133^(+)ependymal cells can be further classified into FOXJ1^(+)/SOX2^(+)/ACTA2^(+)cells,FLT1^(+)/CD31^(+)/CLDN5^(+)endothelial-like cells,and PDGFRB^(+)/VTN^(+)/NG2^(+)pericyte-like cells,as well as endothelial-pericyte-like cells and Foxj1^(+)endothelial-like cells.CD133^(-)ependymal cells can be further divided into endothelial-like cells,Foxj1^(+)ependymal cells,Foxj1^(+)endothelial-like cells,pericyte-like cells,endothelial-pericyte-like cells,VIM^(+)cells,and cells negative for all of these markers.This comprehensive profiling confirms the heterogeneity of the ependymal surface in the adult mouse forebrain.Debate regarding whether adult ependymal cells contain neural stem cells has arisen because different researchers have examined different populations of ependymal cells.Our study provides a new perspective for investigation of clinical endogenous neural stem cells,ultimately paving the way for stem cell therapies in neurological diseases.
基金supported by the National Natural Science Foundation of China(No.81960199)Clinical Translational Innovation Cultivating Fund 550 Project of Hainan General Hospital,Joint Program on Health Science&Technology Innovation of Hainan Province(No.WSJK2024MS127)Academic Enhancement Support Program of Hainan Medical University(No.XSTS2025093).
文摘The application of DNA hybridization technology,grounded in Watson-Crick base pairing,has facilitated the rational design of framework nucleic acids(FNAs)featuring adaptable shapes and dimensions.These nanostructures exhibit remarkable stability and reproducibility,making them promising candidates for biomedical applications.Among various FNAs,tetrahedral FNAs(tFNAs),first introduced by Turberfield,are nanoscale assemblies of oligonucleotides that possess unique physical,chemical,and biological properties.Previous studies have demonstrated that tFNAs exhibit excellent cellular uptake,enhanced tissue permeability,and strong capabilities to promote cell migration,proliferation,and differentiation.Moreover,the intrinsic ability of tFNAs to efficiently penetrate cell membranes allows tFNAs to serve as versatile carriers for small-molecule drugs or functional oligonucleotides,thereby exerting significant anti-inflammatory,antioxidant,antibacterial,and immunomodulatory effects.These features highlight the therapeutic potential of tFNA-based complexes in skin,mucosal,and barrier tissue repair and regeneration.This review provides a comprehensive analysis of recent advances in the application of tFNAs for the prevention and treatment of skin,mucosal,and barrier tissue diseases,with a focus on their mechanisms of action and future prospects in regenerative medicine and targeted therapies.
文摘Automated Program Repair(APR)techniques have shown significant potential in mitigating the cost and complexity associated with debugging by automatically generating corrective patches for software defects.Despite considerable progress in APR methodologies,existing approaches frequently lack contextual awareness of runtime behaviors and structural intricacies inherent in buggy source code.In this paper,we propose a novel APR approach that integrates attention mechanisms within an autoencoder-based framework,explicitly utilizing structural code affinity and execution context correlation derived from stack trace analysis.Our approach begins with an innovative preprocessing pipeline,where code segments and stack traces are transformed into tokenized representations.Subsequently,the BM25 ranking algorithm is employed to quantitatively measure structural code affinity and execution context correlation,identifying syntactically and semantically analogous buggy code snippets and relevant runtime error contexts from extensive repositories.These extracted features are then encoded via an attention-enhanced autoencoder model,specifically designed to capture significant patterns and correlations essential for effective patch generation.To assess the efficacy and generalizability of our proposed method,we conducted rigorous experimental comparisons against DeepFix,a state-of-the-art APR system,using a substantial dataset comprising 53,478 studentdeveloped C programs.Experimental outcomes indicate that our model achieves a notable bug repair success rate of approximately 62.36%,representing a statistically significant performance improvement of over 6%compared to the baseline.Furthermore,a thorough K-fold cross-validation reinforced the consistency,robustness,and reliability of our method across diverse subsets of the dataset.Our findings present the critical advantage of integrating attentionbased learning with code structural and execution context features in APR tasks,leading to improved accuracy and practical applicability.Future work aims to extend the model’s applicability across different programming languages,systematically optimize hyperparameters,and explore alternative feature representation methods to further enhance debugging efficiency and effectiveness.
