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
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
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
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
After injury,bone tissue initiates a reparative response to restore its structure and function.The failure to initiate or delay this response could result in fracture nonunion.The molecular mechanisms underlying the o...After injury,bone tissue initiates a reparative response to restore its structure and function.The failure to initiate or delay this response could result in fracture nonunion.The molecular mechanisms underlying the occurrence of fracture nonunion are not yet established.We propose that hypoxia-triggered signaling pathways,mediated by reactive oxygen species(ROS)homeostasis,control Bmp2 expression and fracture healing initiation.The excessive ROS leads to oxidative stress and,ultimately,fracture nonunion.In this study,we silenced Apex1,the final ROS signaling transducer that mediates the activation of key transcription factors by their cysteines oxidoreduction,evaluating its role during endochondral ossification and fracture repair.Silencing Apex1 in limb bud mesenchyme results in transient metaphyseal dysplasia derived from impaired chondrocyte differentiation.During bone regeneration,Apex1 silencing induces a fracture nonunion phenotype,characterized by delayed fracture repair initiation,impaired periosteal response,and reduced chondrocyte and osteoblast differentiation.This compromised chondrocyte differentiation hampers callus vascularization and healing progression.Our findings highlight a critical mechanism where hypoxia-driven ROS signaling in mesenchymal progenitors through APEX1 is essential for fracture healing initiation.展开更多
In erasure-coded storage systems,updating data requires parity maintenance,which often leads to significant I/O amplification due to“write-after-read”operations.Furthermore,scattered parity placement increases disk ...In erasure-coded storage systems,updating data requires parity maintenance,which often leads to significant I/O amplification due to“write-after-read”operations.Furthermore,scattered parity placement increases disk seek overhead during repair,resulting in degraded system performance.To address these challenges,this paper proposes a Cognitive Update and Repair Method(CURM)that leverages machine learning to classify files into writeonly,read-only,and read-write categories,enabling tailored update and repair strategies.For write-only and read-write files,CURM employs a data-differencemechanism combined with fine-grained I/O scheduling to minimize redundant read operations and mitigate I/O amplification.For read-write files,CURM further reserves adjacent disk space near parity blocks,supporting parallel reads and reducing disk seek overhead during repair.We implement CURM in a prototype system,Cognitive Update and Repair File System(CURFS),and conduct extensive experiments using realworld Network File System(NFS)and Microsoft Research(MSR)workloads on a 25-node cluster.Experimental results demonstrate that CURMimproves data update throughput by up to 82.52%,reduces recovery time by up to 47.47%,and decreases long-term storage overhead by more than 15% compared to state-of-the-art methods including Full Logging(FL),ParityLogging(PL),ParityLoggingwithReservedspace(PLR),andPARIX.These results validate the effectiveness of CURM in enhancing both update and repair performance,providing a scalable and efficient solution for large-scale erasure-coded storage systems.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
Previous studies have shown that endoplasmic reticulum stress induces neuronal apoptosis,necrosis,and pro-inflammatory microenvironment after spinal cord injury.The JNK pathway is activated by endoplasmic reticulum st...Previous studies have shown that endoplasmic reticulum stress induces neuronal apoptosis,necrosis,and pro-inflammatory microenvironment after spinal cord injury.The JNK pathway is activated by endoplasmic reticulum stress and reactive oxygen species.Our previous research demonstrated that cerebral dopamine neurotrophic factor has anti-inflammatory effects and promotes the repair of the damaged spinal cord after injury.However,the molecular mechanism remains unclear.In this study,we found that cerebral dopamine neurotrophic factor binds JNK1 and regulates JNK1/2-c-Jun-p53 signaling in lipopolysaccharide-induced microglia.Cerebral dopamine neurotrophic factor also alleviated neuroinflammation by reducing the secretion of pro-inflammatory cytokines.Overexpression of cerebral dopamine neurotrophic factor in a mouse model of spinal cord injury promoted nerve regeneration and motor function recovery.These findings indicate the possibility for cerebral dopamine neurotrophic factor treating spinal cord injury by targeting the JNK1/2-c-Jun-p53 pathway.展开更多
We have previously shown the success of polyethylene glycol fusion repair of segmental-loss peripheral nerve injuries in rats using freshly harvested,viable peripheral nerve allografts that can conduct action potentia...We have previously shown the success of polyethylene glycol fusion repair of segmental-loss peripheral nerve injuries in rats using freshly harvested,viable peripheral nerve allografts that can conduct action potentials.Because clinical application of polyethylene glycol fusion with viable peripheral nerve allografts demands pre-transplant donor tissue storage,we developed a protocol for ex vivo storage of rat sciatic nerves as viable peripheral nerve allografts,preserving many axons for up to 5 days.The current study evaluated the in vivo use of these stored viable peripheral nerve allografts.We hypothesized that stored viable peripheral nerve allografts with viable axons would enable successful in vivo repair of segmental-loss peripheral nerve injuries via polyethylene glycol-fusion.Polyethylene glycol-fused viable peripheral nerve allografts were classified as successful if they produced significantly improved locomotor recovery,as evaluated by the sciatic functional index,within 8 weeks post-repair.Many Sprague-Dawley and Lewis rats with successfully polyethylene glycol-fused viable peripheral nerve allografts had significantly improved sciatic functional index scores beginning at 5 weeks post-operatively.There was no significant difference in the efficiency and extent of successful polyethylene glycol fusion between stored and freshly harvested viable peripheral nerve allografts.In contrast,rats with non-fused negative control viable peripheral nerve allografts showed no recovery by 8 weeks post-operatively.Additional confirmatory outcome measures included in vivo compound action potentials and assessments of axon morphometry.These results suggest that viable peripheral nerve allografts can be stored and later used for successful polyethylene glycol fusion repair of segmental-loss peripheral nerve injuries.展开更多
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
Irreversible fibrotic scarring after rotator cuff tear(RCT)compromises the mechanical properties of the healing tendon,yet the underlying mechanisms remain poorly understood.Here,we analyzed the histological features ...Irreversible fibrotic scarring after rotator cuff tear(RCT)compromises the mechanical properties of the healing tendon,yet the underlying mechanisms remain poorly understood.Here,we analyzed the histological features of human RCT scars,characterized by disruption of tendon architecture,disorganized collagen fibrils,and imbalance in type Ⅰ/Ⅲ collagen ratios and fibril diameters.Using single-cell RNA sequencing of tendon stumps from patients with RCT,we deconvolved the cellular and molecular landscape of the fibrotic scarring microenvironment.Heterogenous pro-fibrotic subclusters were identified and validated to participate into scar formation,including tendon stem cell,senescent tenocyte,SOX9-driven pro-fibrotic macrophage,and pro-fibrotic endothelial cells undergoing endothelial-mesenchymal transition(EndoMT).Furthermore,we found that osteopontin and TGF-βsignaling were key drivers of extracellular matrix deposition,and their blockade ameliorated fibrotic scarring after RCT.Collectively,our study dissected the dynamic scarring microenvironment in human RCT and highlights potential therapeutic targets for preventing pathological scar formation.展开更多
BACKGROUND The surgical management of bile duct injuries(BDIs)after laparoscopic cholecystectomy(LC)is challenging and the optimal timing of surgery remains unclear.The primary aim of this study was to systematically ...BACKGROUND The surgical management of bile duct injuries(BDIs)after laparoscopic cholecystectomy(LC)is challenging and the optimal timing of surgery remains unclear.The primary aim of this study was to systematically evaluate the evidence behind the timing of BDI repair after LC in the literature.AIM To assess timing of surgical repair of BDI and postoperative complications.METHODS The MEDLINE,EMBASE,and The Cochrane Library databases were systematically screened up to August 2021.Risk of bias was assessed via the Newcastle Ottawa scale.The primary outcomes of this review included the timing of BDI repair and postoperative complications.RESULTS A total of 439 abstracts were screened,and 24 studies were included with 15609 patients included in this review.Of the 5229 BDIs reported,4934(94%)were classified as major injury.Timing of bile duct repair was immediate(14%,n=705),early(28%,n=1367),delayed(28%,n=1367),or late(26%,n=1286).Standardization of definition for timing of repair was remarkably poor among studies.Definitions for immediate repair ranged from<24 h to 6 wk after LC while early repair ranged from<24 h to 12 wk.Likewise,delayed(>24 h to>12 wk after LC)and late repair(>6 wk after LC)showed a broad overlap.CONCLUSION The lack of standardization among studies precludes any conclusive recommendation on optimal timing of BDI repair after LC.This finding indicates an urgent need for a standardized reporting system of BDI repair.展开更多
CD47 is a ubiquitous and pleiotropic cell-surface receptor.Disrupting CD47 enhances injury repair in various tissues but the role of CD47 has not been studied in bone injuries.In a murine closed-fracture model,CD47-nu...CD47 is a ubiquitous and pleiotropic cell-surface receptor.Disrupting CD47 enhances injury repair in various tissues but the role of CD47 has not been studied in bone injuries.In a murine closed-fracture model,CD47-null mice showed decreased callus bone formation as assessed by microcomputed tomography 10 days post-fracture and increased fibrous volume as determined by histology.To understand the cellular basis for this phenotype,mesenchymal progenitors(MSC)were harvested from bone marrow.CD47-null MSC showed decreased large fibroblast colony formation(CFU-F),significantly less proliferation,and fewer cells in Sphase,although osteoblast differentiation was unaffected.However,consistent with prior research,CD47-null endothelial cells showed increased proliferation relative to WT cells.Similarly,in a murine ischemic fracture model,CD47-null mice showed reduced fracture callus size due to a reduction in bone relative to WT 15 days-post fracture.Consistent with our in vitro results,in vivo EdU labeling showed decreased cell proliferation in the callus of CD47-null mice,while staining for CD31 and endomucin demonstrated increased endothelial cell density.Finally,WT mice with ischemic fracture that were administered a CD47 morpholino,which blocks CD47 protein production,showed a callus phenotype similar to that of ischemic fractures in CD47-null mice,suggesting the phenotype was not due to developmental changes in the knockout mice.Thus,inhibition of CD47 during bone healing reduces both non-ischemic and ischemic fracture healing,in part,by decreasing MSC proliferation.Furthermore,the increase in endothelial cell proliferation and early blood vessel density caused by CD47 disruption is not sufficient to overcome MSC dysfunction.展开更多
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 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).
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.
文摘After injury,bone tissue initiates a reparative response to restore its structure and function.The failure to initiate or delay this response could result in fracture nonunion.The molecular mechanisms underlying the occurrence of fracture nonunion are not yet established.We propose that hypoxia-triggered signaling pathways,mediated by reactive oxygen species(ROS)homeostasis,control Bmp2 expression and fracture healing initiation.The excessive ROS leads to oxidative stress and,ultimately,fracture nonunion.In this study,we silenced Apex1,the final ROS signaling transducer that mediates the activation of key transcription factors by their cysteines oxidoreduction,evaluating its role during endochondral ossification and fracture repair.Silencing Apex1 in limb bud mesenchyme results in transient metaphyseal dysplasia derived from impaired chondrocyte differentiation.During bone regeneration,Apex1 silencing induces a fracture nonunion phenotype,characterized by delayed fracture repair initiation,impaired periosteal response,and reduced chondrocyte and osteoblast differentiation.This compromised chondrocyte differentiation hampers callus vascularization and healing progression.Our findings highlight a critical mechanism where hypoxia-driven ROS signaling in mesenchymal progenitors through APEX1 is essential for fracture healing initiation.
基金supported by the National Natural Science Foundation of China(Grant No.62362019)the Natural Science Foundation of Hainan Province(Grant No.624RC482)the Hainan Provincial Higher Education Teaching Reform Research Project(Grant Hnjg2024-27).
文摘In erasure-coded storage systems,updating data requires parity maintenance,which often leads to significant I/O amplification due to“write-after-read”operations.Furthermore,scattered parity placement increases disk seek overhead during repair,resulting in degraded system performance.To address these challenges,this paper proposes a Cognitive Update and Repair Method(CURM)that leverages machine learning to classify files into writeonly,read-only,and read-write categories,enabling tailored update and repair strategies.For write-only and read-write files,CURM employs a data-differencemechanism combined with fine-grained I/O scheduling to minimize redundant read operations and mitigate I/O amplification.For read-write files,CURM further reserves adjacent disk space near parity blocks,supporting parallel reads and reducing disk seek overhead during repair.We implement CURM in a prototype system,Cognitive Update and Repair File System(CURFS),and conduct extensive experiments using realworld Network File System(NFS)and Microsoft Research(MSR)workloads on a 25-node cluster.Experimental results demonstrate that CURMimproves data update throughput by up to 82.52%,reduces recovery time by up to 47.47%,and decreases long-term storage overhead by more than 15% compared to state-of-the-art methods including Full Logging(FL),ParityLogging(PL),ParityLoggingwithReservedspace(PLR),andPARIX.These results validate the effectiveness of CURM in enhancing both update and repair performance,providing a scalable and efficient solution for large-scale erasure-coded storage systems.
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.
基金National Natural Science Foundation of China,No.81601067(to HZ)Shandong Natural Science Foundation of Shandong Province,Nos.ZR2021MH134(to HZ)and ZR2020MH080(to PD).
文摘Previous studies have shown that endoplasmic reticulum stress induces neuronal apoptosis,necrosis,and pro-inflammatory microenvironment after spinal cord injury.The JNK pathway is activated by endoplasmic reticulum stress and reactive oxygen species.Our previous research demonstrated that cerebral dopamine neurotrophic factor has anti-inflammatory effects and promotes the repair of the damaged spinal cord after injury.However,the molecular mechanism remains unclear.In this study,we found that cerebral dopamine neurotrophic factor binds JNK1 and regulates JNK1/2-c-Jun-p53 signaling in lipopolysaccharide-induced microglia.Cerebral dopamine neurotrophic factor also alleviated neuroinflammation by reducing the secretion of pro-inflammatory cytokines.Overexpression of cerebral dopamine neurotrophic factor in a mouse model of spinal cord injury promoted nerve regeneration and motor function recovery.These findings indicate the possibility for cerebral dopamine neurotrophic factor treating spinal cord injury by targeting the JNK1/2-c-Jun-p53 pathway.
基金National Institutes of Health(NIH)R01-NS128086 grant(to GDB and JSB)Lone Star Paralysis Foundation(to GDB).
文摘We have previously shown the success of polyethylene glycol fusion repair of segmental-loss peripheral nerve injuries in rats using freshly harvested,viable peripheral nerve allografts that can conduct action potentials.Because clinical application of polyethylene glycol fusion with viable peripheral nerve allografts demands pre-transplant donor tissue storage,we developed a protocol for ex vivo storage of rat sciatic nerves as viable peripheral nerve allografts,preserving many axons for up to 5 days.The current study evaluated the in vivo use of these stored viable peripheral nerve allografts.We hypothesized that stored viable peripheral nerve allografts with viable axons would enable successful in vivo repair of segmental-loss peripheral nerve injuries via polyethylene glycol-fusion.Polyethylene glycol-fused viable peripheral nerve allografts were classified as successful if they produced significantly improved locomotor recovery,as evaluated by the sciatic functional index,within 8 weeks post-repair.Many Sprague-Dawley and Lewis rats with successfully polyethylene glycol-fused viable peripheral nerve allografts had significantly improved sciatic functional index scores beginning at 5 weeks post-operatively.There was no significant difference in the efficiency and extent of successful polyethylene glycol fusion between stored and freshly harvested viable peripheral nerve allografts.In contrast,rats with non-fused negative control viable peripheral nerve allografts showed no recovery by 8 weeks post-operatively.Additional confirmatory outcome measures included in vivo compound action potentials and assessments of axon morphometry.These results suggest that viable peripheral nerve allografts can be stored and later used for successful polyethylene glycol fusion repair of segmental-loss peripheral nerve injuries.
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 the National Natural Science Foundation of China(NO.82230085,82272572,82030071)National Key Research and Development Program of China(NO.2022YFC2010204)Natural Science Foundation of Hunan Province(NO.2024JJ6637)。
文摘Irreversible fibrotic scarring after rotator cuff tear(RCT)compromises the mechanical properties of the healing tendon,yet the underlying mechanisms remain poorly understood.Here,we analyzed the histological features of human RCT scars,characterized by disruption of tendon architecture,disorganized collagen fibrils,and imbalance in type Ⅰ/Ⅲ collagen ratios and fibril diameters.Using single-cell RNA sequencing of tendon stumps from patients with RCT,we deconvolved the cellular and molecular landscape of the fibrotic scarring microenvironment.Heterogenous pro-fibrotic subclusters were identified and validated to participate into scar formation,including tendon stem cell,senescent tenocyte,SOX9-driven pro-fibrotic macrophage,and pro-fibrotic endothelial cells undergoing endothelial-mesenchymal transition(EndoMT).Furthermore,we found that osteopontin and TGF-βsignaling were key drivers of extracellular matrix deposition,and their blockade ameliorated fibrotic scarring after RCT.Collectively,our study dissected the dynamic scarring microenvironment in human RCT and highlights potential therapeutic targets for preventing pathological scar formation.
文摘BACKGROUND The surgical management of bile duct injuries(BDIs)after laparoscopic cholecystectomy(LC)is challenging and the optimal timing of surgery remains unclear.The primary aim of this study was to systematically evaluate the evidence behind the timing of BDI repair after LC in the literature.AIM To assess timing of surgical repair of BDI and postoperative complications.METHODS The MEDLINE,EMBASE,and The Cochrane Library databases were systematically screened up to August 2021.Risk of bias was assessed via the Newcastle Ottawa scale.The primary outcomes of this review included the timing of BDI repair and postoperative complications.RESULTS A total of 439 abstracts were screened,and 24 studies were included with 15609 patients included in this review.Of the 5229 BDIs reported,4934(94%)were classified as major injury.Timing of bile duct repair was immediate(14%,n=705),early(28%,n=1367),delayed(28%,n=1367),or late(26%,n=1286).Standardization of definition for timing of repair was remarkably poor among studies.Definitions for immediate repair ranged from<24 h to 6 wk after LC while early repair ranged from<24 h to 12 wk.Likewise,delayed(>24 h to>12 wk after LC)and late repair(>6 wk after LC)showed a broad overlap.CONCLUSION The lack of standardization among studies precludes any conclusive recommendation on optimal timing of BDI repair after LC.This finding indicates an urgent need for a standardized reporting system of BDI repair.
基金supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases(NIAMS)of the National Institutes of Health(NIH)under award numbers F30AR071201(R.L.Z.)and R01 AR066028(K.D.H.)Additional research support is provided by the NIH under a training award T32TR004371(C.A.C.).
文摘CD47 is a ubiquitous and pleiotropic cell-surface receptor.Disrupting CD47 enhances injury repair in various tissues but the role of CD47 has not been studied in bone injuries.In a murine closed-fracture model,CD47-null mice showed decreased callus bone formation as assessed by microcomputed tomography 10 days post-fracture and increased fibrous volume as determined by histology.To understand the cellular basis for this phenotype,mesenchymal progenitors(MSC)were harvested from bone marrow.CD47-null MSC showed decreased large fibroblast colony formation(CFU-F),significantly less proliferation,and fewer cells in Sphase,although osteoblast differentiation was unaffected.However,consistent with prior research,CD47-null endothelial cells showed increased proliferation relative to WT cells.Similarly,in a murine ischemic fracture model,CD47-null mice showed reduced fracture callus size due to a reduction in bone relative to WT 15 days-post fracture.Consistent with our in vitro results,in vivo EdU labeling showed decreased cell proliferation in the callus of CD47-null mice,while staining for CD31 and endomucin demonstrated increased endothelial cell density.Finally,WT mice with ischemic fracture that were administered a CD47 morpholino,which blocks CD47 protein production,showed a callus phenotype similar to that of ischemic fractures in CD47-null mice,suggesting the phenotype was not due to developmental changes in the knockout mice.Thus,inhibition of CD47 during bone healing reduces both non-ischemic and ischemic fracture healing,in part,by decreasing MSC proliferation.Furthermore,the increase in endothelial cell proliferation and early blood vessel density caused by CD47 disruption is not sufficient to overcome MSC dysfunction.
