Autotomy of appendages is a self-protection mechanism in crustaceans,which is defined as the reflexive loss of a limb in response to predation,competition,or other environmental factors.Single-limb injuries were the m...Autotomy of appendages is a self-protection mechanism in crustaceans,which is defined as the reflexive loss of a limb in response to predation,competition,or other environmental factors.Single-limb injuries were the most common among the species surveyed in the present study,and the chelicerae were the most frequently lost appendages.After autotomy,hormones and signaling pathways are altered.Loss of limbs can affect foraging efficiency,although cheliped loss may be compensated by shifting to alternative prey or using both motor and oral appendages.In heterogeneous species,the loss of the major chelae may affect the selectivity of feeding.Autotomy can affect crustacean growth by reducing size increases at molting and altering the timing of ecdysis.In commercial production,removing chelicerae is an effective strategy to reduce cannibalism,and production of soft-shell crabs can be increased via autotomy.After autotomy,a new limb will regrow through regeneration and molting.This process involves the regulation of hormones,regrowth of nerves,and a number of signaling pathways that include the Wnt/β-catenin signaling pathway and transforming growth factorβsignaling pathway.Crustaceans are somewhat different from vertebrates in terms of regeneration.This review provides theoretical guidance about autotomy and regeneration applied in artificial aquaculture,and we offer several suggestions for future research on autotomy and regeneration in crustaceans.展开更多
BACKGROUND The success of liver resection relies on the ability of the remnant liver to regenerate.Most of the knowledge regarding the pathophysiological basis of liver regeneration comes from rodent studies,and data ...BACKGROUND The success of liver resection relies on the ability of the remnant liver to regenerate.Most of the knowledge regarding the pathophysiological basis of liver regeneration comes from rodent studies,and data on humans are scarce.Additionally,there is limited knowledge about the preoperative factors that influence postoperative regeneration.AIM To quantify postoperative remnant liver volume by the latest volumetric software and investigate perioperative factors that affect posthepatectomy liver regenera-tion.METHODS A total of 268 patients who received partial hepatectomy were enrolled.Patients were grouped into right hepatectomy/trisegmentectomy(RH/Tri),left hepa-tectomy(LH),segmentectomy(Seg),and subsegmentectomy/nonanatomical hepatectomy(Sub/Non)groups.The regeneration index(RI)and late rege-neration rate were defined as(postoperative liver volume)/[total functional liver volume(TFLV)]×100 and(RI at 6-months-RI at 3-months)/RI at 6-months,respectively.The lower 25th percentile of RI and the higher 25th percentile of late regeneration rate in each group were defined as“low regeneration”and“delayed regeneration”.“Restoration to the original size”was defined as regeneration of the liver volume by more than 90%of the TFLV at 12 months postsurgery.RESULTS The numbers of patients in the RH/Tri,LH,Seg,and Sub/Non groups were 41,53,99 and 75,respectively.The RI plateaued at 3 months in the LH,Seg,and Sub/Non groups,whereas the RI increased until 12 months in the RH/Tri group.According to our multivariate analysis,the preoperative albumin-bilirubin(ALBI)score was an independent factor for low regeneration at 3 months[odds ratio(OR)95%CI=2.80(1.17-6.69),P=0.02;per 1.0 up]and 12 months[OR=2.27(1.01-5.09),P=0.04;per 1.0 up].Multivariate analysis revealed that only liver resection percentage[OR=1.03(1.00-1.05),P=0.04]was associated with delayed regeneration.Furthermore,multivariate analysis demonstrated that the preoperative ALBI score[OR=2.63(1.00-1.05),P=0.02;per 1.0 up]and liver resection percentage[OR=1.02(1.00-1.05),P=0.04;per 1.0 up]were found to be independent risk factors associated with volume restoration failure.CONCLUSION Liver regeneration posthepatectomy was determined by the resection percentage and preoperative ALBI score.This knowledge helps surgeons decide the timing and type of rehepatectomy for recurrent cases.展开更多
Neuro regeneration is a very complex phenomenon characterized by the generation of new neurons and synapses,involving connections between adjacent cells and axonal projections.Neuroregeneration supplies additional lon...Neuro regeneration is a very complex phenomenon characterized by the generation of new neurons and synapses,involving connections between adjacent cells and axonal projections.Neuroregeneration supplies additional longterm resources to replace those altered by the injury and ensure lasting functional recovery.展开更多
Inflammatory skin disorders can cause chronic scarring and functional impairments,posing a significant burden on patients and the healthcare system.Conventional therapies,such as corticosteroids and nonsteroidal anti-...Inflammatory skin disorders can cause chronic scarring and functional impairments,posing a significant burden on patients and the healthcare system.Conventional therapies,such as corticosteroids and nonsteroidal anti-inflammatory drugs,are limited in efficacy and associated with adverse effects.Recently,nanozyme(NZ)-based hydrogels have shown great promise in addressing these challenges.NZ-based hydrogels possess unique therapeutic abilities by combining the therapeutic benefits of redox nanomaterials with enzymatic activity and the water-retaining capacity of hydrogels.The multifaceted therapeutic effects of these hydrogels include scavenging reactive oxygen species and other inflammatory mediators modulating immune responses toward a pro-regenerative environment and enhancing regenerative potential by triggering cell migration and differentiation.This review highlights the current state of the art in NZ-engineered hydrogels(NZ@hydrogels)for anti-inflammatory and skin regeneration applications.It also discusses the underlying chemo-mechano-biological mechanisms behind their effectiveness.Additionally,the challenges and future directions in this ground,particularly their clinical translation,are addressed.The insights provided in this review can aid in the design and engineering of novel NZ-based hydrogels,offering new possibilities for targeted and personalized skin-care therapies.展开更多
Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public hea...Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.展开更多
In the medical and dental field, the importance and need for the study of materials and drugs for use as bone grafts or regeneration in injured areas due to the presence of fractures, infections or tumors that cause e...In the medical and dental field, the importance and need for the study of materials and drugs for use as bone grafts or regeneration in injured areas due to the presence of fractures, infections or tumors that cause extensive loss of bone tissue is observed. Bone is a specialized, vascularized and dynamic connective tissue that changes throughout the life of the organism. When injured, it has a unique ability to regenerate and repair without the presence of scars, but in some situations, due to the size of the defect, the bone tissue does not regenerate completely. Thus, due to its importance, there is a great development in therapeutic approaches for the treatment of bone defects through studies that include autografts, allografts and artificial materials used alone or in association with bone grafts. Pharmaceuticals composed of biomaterials and osteogenic active substances have been extensively studied because they provide potential for tissue regeneration and new strategies for the treatment of bone defects. Statins work as specific inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoAreductase). They represent efficient drugs in lowering cholesterol, as they reduce platelet aggregation and thrombus deposition;in addition, they promote angiogenesis, reduce the β-amyloid peptide related to Alzheimer’s disease and suppress the activation of T lymphocytes. Furthermore, these substances have been used in the treatment of hypercholesterolemia and coronary artery disease. By inhibiting HMG-CoAreductase, statins not only inhibit cholesterol synthesis, but also exhibit several other beneficial pleiotropic effects. Therefore, there has been increasing interest in researching the effects of statins, including Simvastatin, on bone and osteometabolic diseases. However, statins in high doses cause inflammation in bone defects and inhibit osteoblastic differentiation, negatively contributing to bone repair. Thus, different types of studies with different concentrations of statins have been studied to positively or negatively correlate this drug with bone regeneration. In this review we will address the positive, negative or neutral effects of statins in relation to bone defects providing a comprehensive understanding of their application. Finally, we will discuss a variety of statin-based drugs and the ideal dose through a theoretical basis with preclinical, clinical and laboratory work in order to promote the repair of bone defects.展开更多
On an agrosilvopastoral farm in central Italy where Maremmana cattle graze in Turkey oak forests,we evaluated the impact of different livestock densities on stand structure,tree diversity and natural regeneration in f...On an agrosilvopastoral farm in central Italy where Maremmana cattle graze in Turkey oak forests,we evaluated the impact of different livestock densities on stand structure,tree diversity and natural regeneration in four types of grazed areas based on the grazing regime adopted:calf-grazed,high-intensity-grazed,low-intensity-grazed,ungrazed control.For each area,we set up three permanent circular plots(radius of 15 m)to survey the structural and dasometric characteristics of the overstorey,understorey,and regeneration layer.The results showed that grazing negatively affected the complexity of the forest structure and its potential to regenerate and maintain a high level of biodiversity.The differences in stand structure observed between the grazing areas were closely related to livestock density.The most sensitive components of the system were the understorey and the regeneration layers.Contrarily,the current grazing management did not affect the dominant tree structure or its composition.Our findings identified medium-term monitoring and regeneration management as the two significant aspects to consider when assessing sustainable livestock.New forests can be established by excluding graz-ing for about 20–25 years.展开更多
Skeletal muscle has a robust regeneration ability that is impaired by severe injury,disease,and aging.resulting in a decline in skeletal muscle function.Therefore,improving skeletal muscle regeneration is a key challe...Skeletal muscle has a robust regeneration ability that is impaired by severe injury,disease,and aging.resulting in a decline in skeletal muscle function.Therefore,improving skeletal muscle regeneration is a key challenge in treating skeletal muscle-related disorders.Owing to their significant role in tissue regeneration,implantation of M2 macrophages(M2MФ)has great potential for improving skeletal muscle regeneration.Here,we present a short-wave infrared(SWIR)fluorescence imaging technique to obtain more in vivo information for an in-depth evaluation of the skeletal muscle regeneration effect after M2MФtransplantation.SWIR fluorescence imaging was employed to track implanted M2MФin the injured skeletal muscle of mouse models.It is found that the implanted M2MФaccumulated at the injury site for two weeks.Then,SWIR fluorescence imaging of blood vessels showed that M2MФimplantation could improve the relative perfusion ratio on day 5(1.09±0.09 vs 0.85±0.05;p=0.01)and day 9(1.38±0.16 vs 0.95±0.03;p=0.01)post-injury,as well as augment the degree of skeletal muscle regencration on day 13 post-injury.Finally,multiple linear regression analyses determined that post-injury time and relative perfusion ratio could be used as predictive indicators to evaluate skeletal muscle regeneration.These results provide more in vivo details about M2MФin skeletal muscle regeneration and confirm that M2MФcould promote angiogenesis and improve the degree of skeletal muscle repair,which will guide the research and development of M2MФimplantation to improve skeletal muscle regeneration.展开更多
Spent battery recycling has received considerable attention because of its economic and environmental potential.A large amount of retired graphite has been produced as the main electrode material,accompanied by a deta...Spent battery recycling has received considerable attention because of its economic and environmental potential.A large amount of retired graphite has been produced as the main electrode material,accompanied by a detailed exploration of the repair mechanism.However,they still suffer from unclear repair mechanisms and physicochemical evolution.In this study,spent graphite was repaired employing three methodologies:pickling-sintering,pyrogenic-recovery,and high-temperature sintering.Owing to the catalytic effect of the metal-based impurities and temperature control,the as-obtained samples displayed an ordered transformation,including the interlayer distance,crystalline degree,and grain size.As anodes of lithium ions batteries,the capacity of repaired samples reached up to 310 mA h g^(-1)above after 300loops at 1.0 C,similar to that of commercial graphite.Meanwhile,benefitting from the effective assembly of carbon atoms in internal structure of graphite at>1400℃,their initial coulombic efficiency were>87%.Even at 2.0 C,the capacity of samples remained approximately 244 mA h g^(-1)after 500 cycles.Detailed electrochemical and kinetic analyses revealed that a low temperature enhanced the isotropy,thereby enhancing the rate properties.Further,economic and environmental analyses revealed that the revenue obtained through suitable pyrogenic-recovering manners was approximately the largest value(5500$t^(-1)).Thus,this study is expected to clarify the in-depth effect of different repair methods on the traits of graphite,while offering all-round evaluations of repaired graphite.展开更多
The recycling of spent batteries has become increasingly important owing to their wide applications,abundant raw material supply,and sustainable development.Compared with the degraded cathode,spent anode graphite ofte...The recycling of spent batteries has become increasingly important owing to their wide applications,abundant raw material supply,and sustainable development.Compared with the degraded cathode,spent anode graphite often has a relatively intact structure with few defects after long cycling.Yet,most spent graphite is simply burned or discarded due to its limited value and inferior performance on using conventional recycling methods that are complex,have low efficiency,and fail in performance restoration.Herein,we propose a fast,efficient,and“intelligent”strategy to regenerate and upcycle spent graphite based on defect‐driven targeted remediation.Using Sn as a nanoscale healant,we used rapid heating(~50 ms)to enable dynamic Sn droplets to automatically nucleate around the surface defects on the graphite upon cooling owing to strong binding to the defects(~5.84 eV/atom),thus simultaneously achieving Sn dispersion and graphite remediation.As a result,the regenerated graphite showed enhanced capacity and cycle stability(458.9 mAh g^(−1) at 0.2 A g^(−1) after 100 cycles),superior to those of commercial graphite.Benefiting from the self‐adaption of Sn dispersion,spent graphite with different degrees of defects can be regenerated to similar structures and performance.EverBatt analysis indicates that targeted regeneration and upcycling have significantly lower energy consumption(~99%reduction)and near‐zero CO2 emission,and yield much higher profit than hydrometallurgy,which opens a new avenue for direct upcycling of spend graphite in an efficient,green,and profitable manner for sustainable battery manufacture.展开更多
The structure of plant communities at local scales depends on both the spatial heterogeneity of abiotic environmental factors and the biotic interactions within the community.However,although environmental filtering d...The structure of plant communities at local scales depends on both the spatial heterogeneity of abiotic environmental factors and the biotic interactions within the community.However,although environmental filtering due to microtopographic heterogeneity and resource competition among plants caused by spatial variation in tree density and size are considered to be very important in explaining the mechanisms of community assembly,their effects on the processes of individual mortality and recruitment in natural forest regeneration,as well as their relative contributions,are still poorly understood.To address this,we established a 12-ha permanent plot in a subtropical evergreen broad-leaved forest area and measured microtopographic variables such as elevation,slope,aspect,and terrain position index(TPI)using a total station.We monitored the individual mortality and recruitment in forest natural regeneration through repeated surveys at 5-year intervals.We fitted spatial covariance models to jointly use multiple factors from three groups of variables(microtopographic effect,neighborhood density effects,neighborhood size effects)as explanatory variables to analyze their roles in driving the mortality and recruitment of all individual and 12 dominant species in forest natural regeneration at the neighborhood scale.Our results show that:(1)In the crucial early stages of secondary forest restoration,natural regeneration is influenced by a synergy of environmental filtering,due to microtopographic heterogeneity,and resource competition among plants.(2)For distinct species responses,evergreen dominant species'mortality is largely explained by neighborhood effects,while deciduous species are more affected by topographic factors.Furthermore,the adverse effects of larger conspecific trees on younger trees indicate a pattern of competitive pressure leading to mortality among regenerating trees,such pattern emphasis the influence of parent trees on natural regeneration.(3)As trees grow,their interaction with these stressors evolves,suggesting a shift in their resource acquisition strategies and response to neighborhood effects and environmental factors.Despite these changes,the relative importance of topographic factors in determining survival and recruitment success remains constant.This research highlights the importance of considering both environmental and neighborhood effects in forest management,particularly in early secondary forest restoration.展开更多
From the perspective of a community energy operator,a two-stage optimal scheduling model of a community integrated energy system is proposed by integrating information on controllable loads.The day-ahead scheduling an...From the perspective of a community energy operator,a two-stage optimal scheduling model of a community integrated energy system is proposed by integrating information on controllable loads.The day-ahead scheduling analyzes whether various controllable loads participate in the optimization and investigates the impact of their responses on the operating economy of the community integrated energy system(IES)before and after;the intra-day scheduling proposes a two-stage rolling optimization model based on the day-ahead scheduling scheme,taking into account the fluctuation of wind turbine output and load within a short period of time and according to the different response rates of heat and cooling power,and solves the adjusted output of each controllable device.The simulation results show that the optimal scheduling of controllable loads effectively reduces the comprehensive operating costs of community IES;the two-stage optimal scheduling model can meet the energy demand of customers while effectively and timely suppressing the random fluctuations on both sides of the source and load during the intra-day stage,realizing the economic and smooth operation of IES.展开更多
Light olefins is the incredibly important materials in chemical industry.Methanol to olefins(MTO),which provides a non-oil route for light olefins production,received considerable attention in the past decades.However...Light olefins is the incredibly important materials in chemical industry.Methanol to olefins(MTO),which provides a non-oil route for light olefins production,received considerable attention in the past decades.However,the catalyst deactivation is an inevitable feature in MTO processes,and regeneration,therefore,is one of the key steps in industrial MTO processes.Traditionally the MTO catalyst is regenerated by removing the deposited coke via air combustion,which unavoidably transforms coke into carbon dioxide and reduces the carbon utilization efficiency.Recent study shows that the coke species over MTO catalyst can be regenerated via steam,which can promote the light olefins yield as the deactivated coke species can be essentially transferred to industrially useful synthesis gas,is a promising pathway for further MTO processes development.In this work,we modelled and analyzed these two MTO regeneration methods in terms of carbon utilization efficiency and technology economics.As shown,the steam regeneration could achieve a carbon utilization efficiency of 84.31%,compared to 74.74%for air combustion regeneration.The MTO processes using steam regeneration can essentially achieve the near-zero carbon emission.In addition,light olefins production of the MTO processes using steam regeneration is 12.81%higher than that using air combustion regeneration.In this regard,steam regeneration could be considered as a potential yet promising regeneration method for further MTO processes,showing not only great environmental benefits but also competitive economic performance.展开更多
Runx2 is a major regulator of osteoblast differentiation and function;however,the role of Runx2 in peripheral nerve repair is unclea r.Here,we analyzed Runx2expression following injury and found that it was specifical...Runx2 is a major regulator of osteoblast differentiation and function;however,the role of Runx2 in peripheral nerve repair is unclea r.Here,we analyzed Runx2expression following injury and found that it was specifically up-regulated in Schwann cells.Furthermore,using Schwann cell-specific Runx2 knocko ut mice,we studied peripheral nerve development and regeneration and found that multiple steps in the regeneration process following sciatic nerve injury were Runx2-dependent.Changes observed in Runx2 knoc kout mice include increased prolife ration of Schwann cells,impaired Schwann cell migration and axonal regrowth,reduced re-myelination of axo ns,and a block in macrophage clearance in the late stage of regeneration.Taken together,our findings indicate that Runx2 is a key regulator of Schwann cell plasticity,and therefore peripheral nerve repair.Thus,our study shows that Runx2 plays a major role in Schwann cell migration,re-myelination,and peripheral nerve functional recovery following injury.展开更多
Stem cell regeneration is an essential biological process in the maintenance of tissue homeostasis;dysregulation of stem cell regeneration may result in dynamic diseases that show oscillations in cell numbers.Cell het...Stem cell regeneration is an essential biological process in the maintenance of tissue homeostasis;dysregulation of stem cell regeneration may result in dynamic diseases that show oscillations in cell numbers.Cell heterogeneity and plasticity are necessary for the dynamic equilibrium of tissue homeostasis;however,how these features may affect the oscillatory dynamics of the stem cell regeneration process remains poorly understood.Here,based on a mathematical model of heterogeneous stem cell regeneration that includes cell heterogeneity and random transition of epigenetic states,we study the conditions to have oscillation solutions through bifurcation analysis and numerical simulations.Our results show various model system dynamics with changes in different parameters associated with kinetic rates,cellular heterogeneity,and plasticity.We show that introducing heterogeneity and plasticity to cells can result in oscillation dynamics,as we have seen in the homogeneous stem cell regeneration system.However,increasing the cell heterogeneity and plasticity intends to maintain tissue homeostasis under certain conditions.The current study is an initiatory investigation of how cell heterogeneity and plasticity may affect stem cell regeneration dynamics,and many questions remain to be further studied both biologically and mathematically.展开更多
Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong disability.Currently,there are no FDA-approved therapies a...Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong disability.Currently,there are no FDA-approved therapies available to promote nerve regeneration.Tacrolimus accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve surgery.The authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug exposure.Tacrolimus is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 days.Size and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible byproducts.Tacrolimus released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic delivery.Given its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.展开更多
Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. ...Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the introduction of applications based on biochemistry and cell molecules, and discuss the emerging role of biomaterials in promoting neural regeneration. Further, we summarize the adaptive biomaterials infused with exosomes produced from stem cells and stem cells themselves for the treatment of traumatic brain injury. Finally, we present the main limitations of biomaterials for the treatment of traumatic brain injury and offer insights into their future potential.展开更多
Transition metal carbides and nitrides(MXenes)are crystal nanomaterials with a number of surface functional groups such as fluorine,hydroxyl,and oxygen,which can be used as carriers for proteins and drugs.MXenes have ...Transition metal carbides and nitrides(MXenes)are crystal nanomaterials with a number of surface functional groups such as fluorine,hydroxyl,and oxygen,which can be used as carriers for proteins and drugs.MXenes have excellent biocompatibility,electrical conductivity,surface hydrophilicity,mechanical properties and easy surface modification.However,at present,the stability of most MXenes needs to be improved,and more synthesis methods need to be explored.MXenes are good substrates for nerve cell regeneration and nerve reconstruction,which have broad application prospects in the repair of nervous system injury.Regarding the application of MXenes in neuroscience,mainly at the cellular level,the long-term in vivo biosafety and effects also need to be further explored.This review focuses on the progress of using MXenes in nerve regeneration over the last few years;discussing preparation of MXenes and their biocompatibility with different cells as well as the regulation by MXenes of nerve cell regeneration in two-dimensional and three-dimensional environments in vitro.MXenes have great potential in regulating the proliferation,differentiation,and maturation of nerve cells and in promoting regeneration and recovery after nerve injury.In addition,this review also presents the main challenges during optimization processes,such as the preparation of stable MXenes and long-term in vivo biosafety,and further discusses future directions in neural tissue engineering.展开更多
Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside a...Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration.These effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so far.The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers.Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632.Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity.In contrast,the same dose showed toxic effects on the regeneration of myelinated fibers.Interestingly,scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632.Overall,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody.Our findings open the possibility of therapeutic pharmacological intervention targeting Rho A/Rock pathway in immune neuropathies associated with the presence of anti-ganglioside antibodies and delayed or incomplete clinical recovery after injury in the peripheral nervous system.展开更多
The technique of Farmer Managed Natural Regeneration (FMNR) is being promoted as a cost-effective approach for restoring degraded arable dry lands. Its effectiveness has been observed in many countries across the glob...The technique of Farmer Managed Natural Regeneration (FMNR) is being promoted as a cost-effective approach for restoring degraded arable dry lands. Its effectiveness has been observed in many countries across the globe, where it is a traditional practice, and is now being encouraged across the African continent. This study aimed to evaluate the impact of FMNR on floristic Composition, Vegetation Structure, and Regeneration Status of woody Plant Species in the severely degraded Central Rift, Kenya. The study systematically assessed how FMNR influenced species composition, vegetation structure and regeneration status from two sample plots involved in FMNR practices. Transect lines and quadrats methods were utilized to collect data, specifically regarding the floristic composition, vegetation structure, and regeneration status of woody plant species. Quadrats and sub-quadrats of varying sizes (10 m by 10 m, 5 m by 5 m, and 1 m by 1 m) were nested along the transect lines for data collection. Furthermore, measurements of tree growth and development, including root collar diameter, diameter at breast height (D<sub>130</sub>) and heights within the study blocks, were taken. The data was then analyzed using R-software. Results showed a marked progressive increase in numbers of trees, saplings, seedlings, shrubs and herbs in all FMNR sites and reductions in all non-FMNR sites. The study advocates for widespread promotion of the FMNR practice both as an environmental conservation and restoration strategy.展开更多
基金funded by the National Natural Science Foundation of China(Nos.32172993,42106104)the Ningbo Provincial Natural Science Foundation of China(No.202003N4181).
文摘Autotomy of appendages is a self-protection mechanism in crustaceans,which is defined as the reflexive loss of a limb in response to predation,competition,or other environmental factors.Single-limb injuries were the most common among the species surveyed in the present study,and the chelicerae were the most frequently lost appendages.After autotomy,hormones and signaling pathways are altered.Loss of limbs can affect foraging efficiency,although cheliped loss may be compensated by shifting to alternative prey or using both motor and oral appendages.In heterogeneous species,the loss of the major chelae may affect the selectivity of feeding.Autotomy can affect crustacean growth by reducing size increases at molting and altering the timing of ecdysis.In commercial production,removing chelicerae is an effective strategy to reduce cannibalism,and production of soft-shell crabs can be increased via autotomy.After autotomy,a new limb will regrow through regeneration and molting.This process involves the regulation of hormones,regrowth of nerves,and a number of signaling pathways that include the Wnt/β-catenin signaling pathway and transforming growth factorβsignaling pathway.Crustaceans are somewhat different from vertebrates in terms of regeneration.This review provides theoretical guidance about autotomy and regeneration applied in artificial aquaculture,and we offer several suggestions for future research on autotomy and regeneration in crustaceans.
文摘BACKGROUND The success of liver resection relies on the ability of the remnant liver to regenerate.Most of the knowledge regarding the pathophysiological basis of liver regeneration comes from rodent studies,and data on humans are scarce.Additionally,there is limited knowledge about the preoperative factors that influence postoperative regeneration.AIM To quantify postoperative remnant liver volume by the latest volumetric software and investigate perioperative factors that affect posthepatectomy liver regenera-tion.METHODS A total of 268 patients who received partial hepatectomy were enrolled.Patients were grouped into right hepatectomy/trisegmentectomy(RH/Tri),left hepa-tectomy(LH),segmentectomy(Seg),and subsegmentectomy/nonanatomical hepatectomy(Sub/Non)groups.The regeneration index(RI)and late rege-neration rate were defined as(postoperative liver volume)/[total functional liver volume(TFLV)]×100 and(RI at 6-months-RI at 3-months)/RI at 6-months,respectively.The lower 25th percentile of RI and the higher 25th percentile of late regeneration rate in each group were defined as“low regeneration”and“delayed regeneration”.“Restoration to the original size”was defined as regeneration of the liver volume by more than 90%of the TFLV at 12 months postsurgery.RESULTS The numbers of patients in the RH/Tri,LH,Seg,and Sub/Non groups were 41,53,99 and 75,respectively.The RI plateaued at 3 months in the LH,Seg,and Sub/Non groups,whereas the RI increased until 12 months in the RH/Tri group.According to our multivariate analysis,the preoperative albumin-bilirubin(ALBI)score was an independent factor for low regeneration at 3 months[odds ratio(OR)95%CI=2.80(1.17-6.69),P=0.02;per 1.0 up]and 12 months[OR=2.27(1.01-5.09),P=0.04;per 1.0 up].Multivariate analysis revealed that only liver resection percentage[OR=1.03(1.00-1.05),P=0.04]was associated with delayed regeneration.Furthermore,multivariate analysis demonstrated that the preoperative ALBI score[OR=2.63(1.00-1.05),P=0.02;per 1.0 up]and liver resection percentage[OR=1.02(1.00-1.05),P=0.04;per 1.0 up]were found to be independent risk factors associated with volume restoration failure.CONCLUSION Liver regeneration posthepatectomy was determined by the resection percentage and preoperative ALBI score.This knowledge helps surgeons decide the timing and type of rehepatectomy for recurrent cases.
基金supported by PIAno di inCEntivi per la Rlcerca di Ateneo 2020/2022 Linea di In tervento3"Starting Grant""REPAIR"(to GM)。
文摘Neuro regeneration is a very complex phenomenon characterized by the generation of new neurons and synapses,involving connections between adjacent cells and axonal projections.Neuroregeneration supplies additional longterm resources to replace those altered by the injury and ensure lasting functional recovery.
基金supported by the grants from National Research Foundation(NRF,#2021R1A5A2022318,#RS-2023-00220408,#RS-2023-00247485),Republic of Korea.
文摘Inflammatory skin disorders can cause chronic scarring and functional impairments,posing a significant burden on patients and the healthcare system.Conventional therapies,such as corticosteroids and nonsteroidal anti-inflammatory drugs,are limited in efficacy and associated with adverse effects.Recently,nanozyme(NZ)-based hydrogels have shown great promise in addressing these challenges.NZ-based hydrogels possess unique therapeutic abilities by combining the therapeutic benefits of redox nanomaterials with enzymatic activity and the water-retaining capacity of hydrogels.The multifaceted therapeutic effects of these hydrogels include scavenging reactive oxygen species and other inflammatory mediators modulating immune responses toward a pro-regenerative environment and enhancing regenerative potential by triggering cell migration and differentiation.This review highlights the current state of the art in NZ-engineered hydrogels(NZ@hydrogels)for anti-inflammatory and skin regeneration applications.It also discusses the underlying chemo-mechano-biological mechanisms behind their effectiveness.Additionally,the challenges and future directions in this ground,particularly their clinical translation,are addressed.The insights provided in this review can aid in the design and engineering of novel NZ-based hydrogels,offering new possibilities for targeted and personalized skin-care therapies.
基金supported by the Natural Science Foundation of Beijing,China(7214223,7212027)the Beijing Hospitals Authority Youth Programme(QML20210601)+3 种基金the Chinese Scholarship Council(CSC)scholarship(201706210415)the National Key Research and Development Program of China(2017YFC0908800)the Beijing Municipal Health Commission(PXM2020_026272_000002,PXM2020_026272_000014)the National Natural Science Foundation of China(82070293).
文摘Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.
文摘In the medical and dental field, the importance and need for the study of materials and drugs for use as bone grafts or regeneration in injured areas due to the presence of fractures, infections or tumors that cause extensive loss of bone tissue is observed. Bone is a specialized, vascularized and dynamic connective tissue that changes throughout the life of the organism. When injured, it has a unique ability to regenerate and repair without the presence of scars, but in some situations, due to the size of the defect, the bone tissue does not regenerate completely. Thus, due to its importance, there is a great development in therapeutic approaches for the treatment of bone defects through studies that include autografts, allografts and artificial materials used alone or in association with bone grafts. Pharmaceuticals composed of biomaterials and osteogenic active substances have been extensively studied because they provide potential for tissue regeneration and new strategies for the treatment of bone defects. Statins work as specific inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoAreductase). They represent efficient drugs in lowering cholesterol, as they reduce platelet aggregation and thrombus deposition;in addition, they promote angiogenesis, reduce the β-amyloid peptide related to Alzheimer’s disease and suppress the activation of T lymphocytes. Furthermore, these substances have been used in the treatment of hypercholesterolemia and coronary artery disease. By inhibiting HMG-CoAreductase, statins not only inhibit cholesterol synthesis, but also exhibit several other beneficial pleiotropic effects. Therefore, there has been increasing interest in researching the effects of statins, including Simvastatin, on bone and osteometabolic diseases. However, statins in high doses cause inflammation in bone defects and inhibit osteoblastic differentiation, negatively contributing to bone repair. Thus, different types of studies with different concentrations of statins have been studied to positively or negatively correlate this drug with bone regeneration. In this review we will address the positive, negative or neutral effects of statins in relation to bone defects providing a comprehensive understanding of their application. Finally, we will discuss a variety of statin-based drugs and the ideal dose through a theoretical basis with preclinical, clinical and laboratory work in order to promote the repair of bone defects.
基金This research is related to the project GO NEWTON“Agroforestry Network in Tuscany”,financed by the Tuscany Region through the Measure 16.2 of Rural Development Plan 2014-2020 to promote agroforestry systems by spreading knowledge to farmers and promoting innovation in the Tuscan territory.
文摘On an agrosilvopastoral farm in central Italy where Maremmana cattle graze in Turkey oak forests,we evaluated the impact of different livestock densities on stand structure,tree diversity and natural regeneration in four types of grazed areas based on the grazing regime adopted:calf-grazed,high-intensity-grazed,low-intensity-grazed,ungrazed control.For each area,we set up three permanent circular plots(radius of 15 m)to survey the structural and dasometric characteristics of the overstorey,understorey,and regeneration layer.The results showed that grazing negatively affected the complexity of the forest structure and its potential to regenerate and maintain a high level of biodiversity.The differences in stand structure observed between the grazing areas were closely related to livestock density.The most sensitive components of the system were the understorey and the regeneration layers.Contrarily,the current grazing management did not affect the dominant tree structure or its composition.Our findings identified medium-term monitoring and regeneration management as the two significant aspects to consider when assessing sustainable livestock.New forests can be established by excluding graz-ing for about 20–25 years.
基金supported by Shanghai Sailing Program(22YF1438700)National Key Research and Development Program of China(2021YFA1201303)+5 种基金National Natural Science Foundation of China(82172511,81972121,81972129,82072521,82011530023,and 82111530200)Sanming Project of Medicine in Shenzhen(SZSM201612078)the Introduction Project of Clinical Medicine Expert Team for Suzhou(SZYJTD201714)Shanghai Talent Development Funding Scheme 2020080Shanghai Sailing Program(21YF1404100 and 22YF1405200)Research Project of Shanghai Science and Technology Commission(22DZ2204900)。
文摘Skeletal muscle has a robust regeneration ability that is impaired by severe injury,disease,and aging.resulting in a decline in skeletal muscle function.Therefore,improving skeletal muscle regeneration is a key challenge in treating skeletal muscle-related disorders.Owing to their significant role in tissue regeneration,implantation of M2 macrophages(M2MФ)has great potential for improving skeletal muscle regeneration.Here,we present a short-wave infrared(SWIR)fluorescence imaging technique to obtain more in vivo information for an in-depth evaluation of the skeletal muscle regeneration effect after M2MФtransplantation.SWIR fluorescence imaging was employed to track implanted M2MФin the injured skeletal muscle of mouse models.It is found that the implanted M2MФaccumulated at the injury site for two weeks.Then,SWIR fluorescence imaging of blood vessels showed that M2MФimplantation could improve the relative perfusion ratio on day 5(1.09±0.09 vs 0.85±0.05;p=0.01)and day 9(1.38±0.16 vs 0.95±0.03;p=0.01)post-injury,as well as augment the degree of skeletal muscle regencration on day 13 post-injury.Finally,multiple linear regression analyses determined that post-injury time and relative perfusion ratio could be used as predictive indicators to evaluate skeletal muscle regeneration.These results provide more in vivo details about M2MФin skeletal muscle regeneration and confirm that M2MФcould promote angiogenesis and improve the degree of skeletal muscle repair,which will guide the research and development of M2MФimplantation to improve skeletal muscle regeneration.
基金financially supported by National Natural Science Foundation of China(52374288,52204298)Young Elite Scientists Sponsorship Program by China Association for Science and Technology(2022QNRC001)+2 种基金National Key Research and Development Program of China(2022YFC3900805-4/7)Hunan Provincial Education Office Foundation of China(No.21B0147)Collaborative Innovation Centre for Clean and Efficient Utilization of Strategic Metal Mineral Resources,Found of State Key Laboratory of Mineral Processing(BGRIMM-KJSKL-2017-13)。
文摘Spent battery recycling has received considerable attention because of its economic and environmental potential.A large amount of retired graphite has been produced as the main electrode material,accompanied by a detailed exploration of the repair mechanism.However,they still suffer from unclear repair mechanisms and physicochemical evolution.In this study,spent graphite was repaired employing three methodologies:pickling-sintering,pyrogenic-recovery,and high-temperature sintering.Owing to the catalytic effect of the metal-based impurities and temperature control,the as-obtained samples displayed an ordered transformation,including the interlayer distance,crystalline degree,and grain size.As anodes of lithium ions batteries,the capacity of repaired samples reached up to 310 mA h g^(-1)above after 300loops at 1.0 C,similar to that of commercial graphite.Meanwhile,benefitting from the effective assembly of carbon atoms in internal structure of graphite at>1400℃,their initial coulombic efficiency were>87%.Even at 2.0 C,the capacity of samples remained approximately 244 mA h g^(-1)after 500 cycles.Detailed electrochemical and kinetic analyses revealed that a low temperature enhanced the isotropy,thereby enhancing the rate properties.Further,economic and environmental analyses revealed that the revenue obtained through suitable pyrogenic-recovering manners was approximately the largest value(5500$t^(-1)).Thus,this study is expected to clarify the in-depth effect of different repair methods on the traits of graphite,while offering all-round evaluations of repaired graphite.
基金The Fundamental Research Funds for the Central Universities,HUST,Grant/Award Number:2021GCRC046The Open Fund of State Key Laboratory of New Textile Materials and Advanced Processing Technologies,Grant/Award Number:FZ2022005Natural Science Foundation of Hubei Province,China,Grant/Award Number:2022CFA031。
文摘The recycling of spent batteries has become increasingly important owing to their wide applications,abundant raw material supply,and sustainable development.Compared with the degraded cathode,spent anode graphite often has a relatively intact structure with few defects after long cycling.Yet,most spent graphite is simply burned or discarded due to its limited value and inferior performance on using conventional recycling methods that are complex,have low efficiency,and fail in performance restoration.Herein,we propose a fast,efficient,and“intelligent”strategy to regenerate and upcycle spent graphite based on defect‐driven targeted remediation.Using Sn as a nanoscale healant,we used rapid heating(~50 ms)to enable dynamic Sn droplets to automatically nucleate around the surface defects on the graphite upon cooling owing to strong binding to the defects(~5.84 eV/atom),thus simultaneously achieving Sn dispersion and graphite remediation.As a result,the regenerated graphite showed enhanced capacity and cycle stability(458.9 mAh g^(−1) at 0.2 A g^(−1) after 100 cycles),superior to those of commercial graphite.Benefiting from the self‐adaption of Sn dispersion,spent graphite with different degrees of defects can be regenerated to similar structures and performance.EverBatt analysis indicates that targeted regeneration and upcycling have significantly lower energy consumption(~99%reduction)and near‐zero CO2 emission,and yield much higher profit than hydrometallurgy,which opens a new avenue for direct upcycling of spend graphite in an efficient,green,and profitable manner for sustainable battery manufacture.
基金the Innovative Team Project of Nanjing Institute of Environmental Sciences MEE(ZX2023QT022)Sino-German Environmental Partnership PhaseⅢ:Strengthening Chinese environmental and nature conservation policy through dialogue+2 种基金The Central Public Welfare Scientific Institution Basal Research Fund,MEE(GYZX210302)Biodiversity Survey,Observation and Assessment Program of Ministry of Ecology and Environment of ChinaThe National Environmental Protection Public Welfare Industry Targeted Research Fund:Research and demonstration of key technologies for dynamic supervision of nature reserves(201509042)。
文摘The structure of plant communities at local scales depends on both the spatial heterogeneity of abiotic environmental factors and the biotic interactions within the community.However,although environmental filtering due to microtopographic heterogeneity and resource competition among plants caused by spatial variation in tree density and size are considered to be very important in explaining the mechanisms of community assembly,their effects on the processes of individual mortality and recruitment in natural forest regeneration,as well as their relative contributions,are still poorly understood.To address this,we established a 12-ha permanent plot in a subtropical evergreen broad-leaved forest area and measured microtopographic variables such as elevation,slope,aspect,and terrain position index(TPI)using a total station.We monitored the individual mortality and recruitment in forest natural regeneration through repeated surveys at 5-year intervals.We fitted spatial covariance models to jointly use multiple factors from three groups of variables(microtopographic effect,neighborhood density effects,neighborhood size effects)as explanatory variables to analyze their roles in driving the mortality and recruitment of all individual and 12 dominant species in forest natural regeneration at the neighborhood scale.Our results show that:(1)In the crucial early stages of secondary forest restoration,natural regeneration is influenced by a synergy of environmental filtering,due to microtopographic heterogeneity,and resource competition among plants.(2)For distinct species responses,evergreen dominant species'mortality is largely explained by neighborhood effects,while deciduous species are more affected by topographic factors.Furthermore,the adverse effects of larger conspecific trees on younger trees indicate a pattern of competitive pressure leading to mortality among regenerating trees,such pattern emphasis the influence of parent trees on natural regeneration.(3)As trees grow,their interaction with these stressors evolves,suggesting a shift in their resource acquisition strategies and response to neighborhood effects and environmental factors.Despite these changes,the relative importance of topographic factors in determining survival and recruitment success remains constant.This research highlights the importance of considering both environmental and neighborhood effects in forest management,particularly in early secondary forest restoration.
基金supported in part by the National Natural Science Foundation of China(51977127)Shanghai Municipal Science and Technology Commission(19020500800)“Shuguang Program”(20SG52)Shanghai Education Development Foundation and Shanghai Municipal Education Commission.
文摘From the perspective of a community energy operator,a two-stage optimal scheduling model of a community integrated energy system is proposed by integrating information on controllable loads.The day-ahead scheduling analyzes whether various controllable loads participate in the optimization and investigates the impact of their responses on the operating economy of the community integrated energy system(IES)before and after;the intra-day scheduling proposes a two-stage rolling optimization model based on the day-ahead scheduling scheme,taking into account the fluctuation of wind turbine output and load within a short period of time and according to the different response rates of heat and cooling power,and solves the adjusted output of each controllable device.The simulation results show that the optimal scheduling of controllable loads effectively reduces the comprehensive operating costs of community IES;the two-stage optimal scheduling model can meet the energy demand of customers while effectively and timely suppressing the random fluctuations on both sides of the source and load during the intra-day stage,realizing the economic and smooth operation of IES.
基金the financial support from the Strategic Priority Research Program of Chinese Academy of Sciences(XDA21010100)。
文摘Light olefins is the incredibly important materials in chemical industry.Methanol to olefins(MTO),which provides a non-oil route for light olefins production,received considerable attention in the past decades.However,the catalyst deactivation is an inevitable feature in MTO processes,and regeneration,therefore,is one of the key steps in industrial MTO processes.Traditionally the MTO catalyst is regenerated by removing the deposited coke via air combustion,which unavoidably transforms coke into carbon dioxide and reduces the carbon utilization efficiency.Recent study shows that the coke species over MTO catalyst can be regenerated via steam,which can promote the light olefins yield as the deactivated coke species can be essentially transferred to industrially useful synthesis gas,is a promising pathway for further MTO processes development.In this work,we modelled and analyzed these two MTO regeneration methods in terms of carbon utilization efficiency and technology economics.As shown,the steam regeneration could achieve a carbon utilization efficiency of 84.31%,compared to 74.74%for air combustion regeneration.The MTO processes using steam regeneration can essentially achieve the near-zero carbon emission.In addition,light olefins production of the MTO processes using steam regeneration is 12.81%higher than that using air combustion regeneration.In this regard,steam regeneration could be considered as a potential yet promising regeneration method for further MTO processes,showing not only great environmental benefits but also competitive economic performance.
基金supported by the National Natural Science Foundation of China,No.82104795 (to RH)。
文摘Runx2 is a major regulator of osteoblast differentiation and function;however,the role of Runx2 in peripheral nerve repair is unclea r.Here,we analyzed Runx2expression following injury and found that it was specifically up-regulated in Schwann cells.Furthermore,using Schwann cell-specific Runx2 knocko ut mice,we studied peripheral nerve development and regeneration and found that multiple steps in the regeneration process following sciatic nerve injury were Runx2-dependent.Changes observed in Runx2 knoc kout mice include increased prolife ration of Schwann cells,impaired Schwann cell migration and axonal regrowth,reduced re-myelination of axo ns,and a block in macrophage clearance in the late stage of regeneration.Taken together,our findings indicate that Runx2 is a key regulator of Schwann cell plasticity,and therefore peripheral nerve repair.Thus,our study shows that Runx2 plays a major role in Schwann cell migration,re-myelination,and peripheral nerve functional recovery following injury.
基金funded by the Scientific Research Project of Tianjin Education Commission(Grant No.2019KJ026).
文摘Stem cell regeneration is an essential biological process in the maintenance of tissue homeostasis;dysregulation of stem cell regeneration may result in dynamic diseases that show oscillations in cell numbers.Cell heterogeneity and plasticity are necessary for the dynamic equilibrium of tissue homeostasis;however,how these features may affect the oscillatory dynamics of the stem cell regeneration process remains poorly understood.Here,based on a mathematical model of heterogeneous stem cell regeneration that includes cell heterogeneity and random transition of epigenetic states,we study the conditions to have oscillation solutions through bifurcation analysis and numerical simulations.Our results show various model system dynamics with changes in different parameters associated with kinetic rates,cellular heterogeneity,and plasticity.We show that introducing heterogeneity and plasticity to cells can result in oscillation dynamics,as we have seen in the homogeneous stem cell regeneration system.However,increasing the cell heterogeneity and plasticity intends to maintain tissue homeostasis under certain conditions.The current study is an initiatory investigation of how cell heterogeneity and plasticity may affect stem cell regeneration dynamics,and many questions remain to be further studied both biologically and mathematically.
基金supported by the German Research Foundation(DA 2255/1-1to SCD)+4 种基金a SickKids Research Training Competition(RESTRACOMP)Graduate Scholarship(to KJWS)an Ontario Graduate Scholarship(to KJWS)a grant from Natural Sciences and Engineering Research Council of Canada(NSERC)(to KJWS)a Kickstarter grant from the Institute of Biomedical Engineering(BME)at the University of Toronto(to KJWS)the Abe Frank Fund from the Riley’s Children Foundation(GHB)。
文摘Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong disability.Currently,there are no FDA-approved therapies available to promote nerve regeneration.Tacrolimus accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve surgery.The authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug exposure.Tacrolimus is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 days.Size and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible byproducts.Tacrolimus released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic delivery.Given its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.
基金supported by the Sichuan Science and Technology Program,No.2023YFS0164 (to JC)。
文摘Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the introduction of applications based on biochemistry and cell molecules, and discuss the emerging role of biomaterials in promoting neural regeneration. Further, we summarize the adaptive biomaterials infused with exosomes produced from stem cells and stem cells themselves for the treatment of traumatic brain injury. Finally, we present the main limitations of biomaterials for the treatment of traumatic brain injury and offer insights into their future potential.
基金supported by grants from the National Key R&D Program of China,Nos.2021YFA1101300,2021YFA1101803,2020YFA0112503the National Natural Science Foundation of China,Nos.82030029,81970882,92149304Science and Technology Department of Sichuan Province,No.2021YFS0371(all to RC)。
文摘Transition metal carbides and nitrides(MXenes)are crystal nanomaterials with a number of surface functional groups such as fluorine,hydroxyl,and oxygen,which can be used as carriers for proteins and drugs.MXenes have excellent biocompatibility,electrical conductivity,surface hydrophilicity,mechanical properties and easy surface modification.However,at present,the stability of most MXenes needs to be improved,and more synthesis methods need to be explored.MXenes are good substrates for nerve cell regeneration and nerve reconstruction,which have broad application prospects in the repair of nervous system injury.Regarding the application of MXenes in neuroscience,mainly at the cellular level,the long-term in vivo biosafety and effects also need to be further explored.This review focuses on the progress of using MXenes in nerve regeneration over the last few years;discussing preparation of MXenes and their biocompatibility with different cells as well as the regulation by MXenes of nerve cell regeneration in two-dimensional and three-dimensional environments in vitro.MXenes have great potential in regulating the proliferation,differentiation,and maturation of nerve cells and in promoting regeneration and recovery after nerve injury.In addition,this review also presents the main challenges during optimization processes,such as the preparation of stable MXenes and long-term in vivo biosafety,and further discusses future directions in neural tissue engineering.
基金supported by Fondo para la Investigación Cientifica y Tecnológica(FONCy T),Argentina,grant#PICT 2015-2473(to PHHL)supported by grants from National Institute of Health/National Institute of Neurological Disorders and Stroke(NIH/NINDS,USA)(NS121621)+2 种基金Department of Defense,USA(Do D-CL1)(PR200530)partially financed with a fellowship for Research in Medicine from Fundación Florencio Fiorinisupported with a PhD fellowship from CONICET。
文摘Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration.These effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so far.The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers.Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632.Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity.In contrast,the same dose showed toxic effects on the regeneration of myelinated fibers.Interestingly,scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632.Overall,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody.Our findings open the possibility of therapeutic pharmacological intervention targeting Rho A/Rock pathway in immune neuropathies associated with the presence of anti-ganglioside antibodies and delayed or incomplete clinical recovery after injury in the peripheral nervous system.
文摘The technique of Farmer Managed Natural Regeneration (FMNR) is being promoted as a cost-effective approach for restoring degraded arable dry lands. Its effectiveness has been observed in many countries across the globe, where it is a traditional practice, and is now being encouraged across the African continent. This study aimed to evaluate the impact of FMNR on floristic Composition, Vegetation Structure, and Regeneration Status of woody Plant Species in the severely degraded Central Rift, Kenya. The study systematically assessed how FMNR influenced species composition, vegetation structure and regeneration status from two sample plots involved in FMNR practices. Transect lines and quadrats methods were utilized to collect data, specifically regarding the floristic composition, vegetation structure, and regeneration status of woody plant species. Quadrats and sub-quadrats of varying sizes (10 m by 10 m, 5 m by 5 m, and 1 m by 1 m) were nested along the transect lines for data collection. Furthermore, measurements of tree growth and development, including root collar diameter, diameter at breast height (D<sub>130</sub>) and heights within the study blocks, were taken. The data was then analyzed using R-software. Results showed a marked progressive increase in numbers of trees, saplings, seedlings, shrubs and herbs in all FMNR sites and reductions in all non-FMNR sites. The study advocates for widespread promotion of the FMNR practice both as an environmental conservation and restoration strategy.