In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the c...In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.展开更多
Rab5 is a GTPase protein that is involved in intracellular membrane trafficking. It functions by binding to various effector proteins and regulating cellular responses, including the formation of transport vesicles an...Rab5 is a GTPase protein that is involved in intracellular membrane trafficking. It functions by binding to various effector proteins and regulating cellular responses, including the formation of transport vesicles and their fusion with the cellular membrane. Rab5 has been reported to play an important role in the development of the zebrafish embryo;however, its role in axonal regeneration in the central nervous system remains unclear. In this study, we established a zebrafish Mauthner cell model of axonal injury using single-cell electroporation and two-photon axotomy techniques. We found that overexpression of Rab5 in single Mauthner cells promoted marked axonal regeneration and increased the number of intra-axonal transport vesicles. In contrast, treatment of zebrafish larvae with the Rab kinase inhibitor CID-1067700markedly inhibited axonal regeneration in Mauthner cells. We also found that Rab5 activated phosphatidylinositol 3-kinase(PI3K) during axonal repair of Mauthner cells and promoted the recovery of zebrafish locomotor function. Additionally, rapamycin, an inhibitor of the mechanistic target of rapamycin downstream of PI3K, markedly hindered axonal regeneration. These findings suggest that Rab5 promotes the axonal regeneration of injured zebrafish Mauthner cells by activating the PI3K signaling pathway.展开更多
Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kines...Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.展开更多
Objective To observe the effects of moxibustion at Huantiao(GB30)acupoint on nerve repair,regeneration,and function in rats with sciatic nerve injury(SNI),and explore the possible mechanism of SNI improvement via moxi...Objective To observe the effects of moxibustion at Huantiao(GB30)acupoint on nerve repair,regeneration,and function in rats with sciatic nerve injury(SNI),and explore the possible mechanism of SNI improvement via moxibustion.Methods A total of 70 specific pathogen-free(SPF)grade male Sprague-Dawley(SD)rats were randomly assigned to control group(n=10)and model group(n=60).Following replication of SNI to model group rats,60 SNI model rats were randomly allocated to SNI groups of 1 d,3 d,and 7 d and moxibustion groups of 1 d,3 d,and 7 d with 10 rats in each group.Moxibustion groups were given moxibustion at the Huantiao(GB30)acupoint on the affected side with a 5 cm distance from the skin under isoflurane respiratory anesthesia and treated once a day for 20 min for 1 d,3 d,and 7 d,respectively.Control and SNI groups were anesthetized with isoflurane daily for 20 min.Open field tests and thermal pain threshold tests were conducted,and the general condition of rats was observed in each group pre-modeling and on treatment day 1,3,and 7.At the end of the treatment,immunofluorescence was used to detect the axonal growth rate,axonal growth density,and Schwann cells(SCs)proliferation in the middle 1-mm cross-section of the crush injury segment in rats.The gastrocnemius muscles on both sides of the rats were taken and weighed to calculate the wet weight ratio of the gastrocnemius muscles on both sides to observe the muscle atrophy of the rats,and hematoxylin-eosin(HE)staining was used to observe the pathomorphological changes of the gastrocnemius muscles on the affected side.Quantitative real-time polymerase chain reaction(qPCR)was used to detect the expression levels of nerve growth factor(NGF),interferon(IFN),macrophage migration inhibitory factor(MIF),interleukin(IL)-4,and transforming growth factor(TGF)-βin the sciatic nerve tissue of the rats.Results After modeling,rats in both moxibustion and SNI groups showed typical signs of pain behaviors(bending and curling of the hind soles of the affected side,licking claws,and lameness)and decreased activity compared with control group.The main benefits of moxibustion were evident from day 3:compared with SNI group,rats in moxibustion group had marked relief of pain behavior,increased activity levels and movement,and a lower response to thermal pain.At the same time,moxibustion significantly promoted the repair of SNI,as evidenced by the significantly better axonal growth rate,growth density,and SCs proliferation density in the crush injury segment compared with SNI group(P<0.01).Moxibustion also regulated the local microenvironment of the injury,up-regulated the pro-nerve repair factors NGF,IL-4,and TGF-β(P<0.05),and down-regulated the pro-inflammatory factors IFN-γ(P<0.01)and MIF(P<0.05).By day 7,the histomorphology of the gastrocnemius muscle in moxibustion group was improved,as indicated by enlarged muscle fibers,elevated regular myocyte morphology and wet weight ratio of the affected and unaffected sides(P<0.05),as well as a sustained high expression levels of NGF,IL-4,and TGF-β(P<0.05,P<0.05,and P<0.01,respectively),and a maintenance of low level of IFN-γ(P<0.01).Concurrently,the MIF level was not significantly different from SNI group(P>0.05).Conclusion Moxibustion at the Huantiao(GB30)acupoint effectively improves motor function and promotes recovery of sensory function and nerve regeneration in SNI rats,which may be related to the regulation of local inflammatory response,the promotion of nerve growth factor expression,the improvement of regenerative microenvironment,and the acceleration of SCs proliferation and axonal growth rate in damaged nerves.展开更多
Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor site.As an alternative,nerve guidance conduit...Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor site.As an alternative,nerve guidance conduits may be used.The ideal conduit should be flexible,resistant to kinks and lumen collapse,and provide physical cues to guide nerve regeneration.We designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align them.Subsequently,we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber lumen.The presence of aligned fibers on the inner surface can promote the extension of nerve cells along the fibers.The helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide stability.Our novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model,suggesting that it has potential for clinical use in human nerve injuries.展开更多
With the approaching of large-scale retirement of power lithium-ion batteries(LIBs),their urgent handling is required for environmental protection and resource reutilization.However,at present,substantial spent power ...With the approaching of large-scale retirement of power lithium-ion batteries(LIBs),their urgent handling is required for environmental protection and resource reutilization.However,at present,substantial spent power batteries,especially for those high recovery value cathode materials,have not been greenly,sustainably,and efficiently recycled.Compared to the traditional recovery method for cathode materials with high energy consumption and severe secondary pollution,the direct repair regeneration,as a new type of short-process and efficient treatment methods,has attracted widespread attention.However,it still faces challenges in homogenization repair,electrochemical performance decline,and scaling-up production.To promote the direct regeneration technology development of failed NCM materials,herein we deeply discuss the failure mechanism of nickel-cobalt-manganese(NCM)ternary cathode materials,including element loss,Li/Ni mixing,phase transformation,structural defects,oxygen release,and surface degradation and reconstruction.Based on this,the detailed analysis and summary of the direct regeneration method embracing solid-phase sintering,eutectic salt assistance,solvothermal synthesis,sol-gel process,spray drying,and redox mediation are provided.Further,the upcycling strategy for regeneration materials,such as single-crystallization and high-nickelization,structural regulation,ion doping,and surface engineering,are discussed in deep.Finally,the challenges faced by the direct regeneration and corresponding countermeasures are pointed out.Undoubtedly,this review provides valuable guidance for the efficient and high-value recovery of failed cathode materials.展开更多
A tunable oxidization and reduction strategy was proposed to directly regenerate spent LiFePO_(4)/C cathode materials by oxidizing excessive carbon powders with the addition of FePO_(4).Experimental results indicate t...A tunable oxidization and reduction strategy was proposed to directly regenerate spent LiFePO_(4)/C cathode materials by oxidizing excessive carbon powders with the addition of FePO_(4).Experimental results indicate that spent LiFePO_(4)/C cathode materials with good performance can be regenerated by roasting at 650℃ for 11 h with the addition ofLi_(2)CO_(3),FePO_(4),V_(2)O_(5),and glucose.V_(2)O_(5) is added to improve the cycle performance of regenerated cathode materials.Glucose is used to revitalize the carbon layers on the surface of spent LiFePO_(4)/C particles for improving their conductivity.The regenerated V-doped LiFePO_(4)/C shows an excellent electrochemical performance with the discharge specific capacity of 161.36 mA·h/g at 0.2C,under which the capacity retention is 97.85%after 100 cycles.展开更多
For realizing the goals of“carbon peak”and“carbon neutrality”,lithium-ion batteries(LIB)with LiFePO_(4)as the cathode material have been widely applied.However,this has also led to a large number of spent lithium-...For realizing the goals of“carbon peak”and“carbon neutrality”,lithium-ion batteries(LIB)with LiFePO_(4)as the cathode material have been widely applied.However,this has also led to a large number of spent lithium-ion batteries,and the safe disposal of spent lithium-ion batteries is an urgent issue.Currently,the main reason for the capacity decay of LiFePO_(4)materials is the Li deficiency and the formation of the Fe^(3+)phase.In order to address this issue,we performed high-temperature calcination of the discarded lithium iron phosphate cathode material in a carbon dioxide environment to reduce or partially remove the carbon coating on its surface.Subsequently,mechanical grinding was conducted to ensure thorough mixing of the lithium source with the discarded lithium iron phosphate.The reaction between CO_(2)and the carbon coating produced a reducing atmosphere,reducing Fe^(3+)to Fe^(2+)and thereby reducing the content of Fe^(3+).The Fe^(3+)content in the repaired LiFePO_(4)material is reduced.The crystal structure of spent LiFePO_(4)cathode materials was repaired more completely compare with the traditional pretreatment method,and the repaired LiFePO_(4)material shows good electrochemical performance and cycling stability.Under 0.1 C conditions,the initial capacity can reach 149.1 m Ah/g.It can be reintroduced for commercial use.展开更多
Dermal substitutes have provided a template for the regeneration and reconstruction of the dermis.However,the healed skin tissue often exhibits abnormal morphology and functionality,including scarring and inflammation...Dermal substitutes have provided a template for the regeneration and reconstruction of the dermis.However,the healed skin tissue often exhibits abnormal morphology and functionality,including scarring and inflammation.In this study,a composite bioink composed of methacrylated gelatin(GelMA)and chitosan oligosaccharide(COS)was proposed for printing a dermal scaffold using digital light processing(DLP)technology.The GelMA/COS bioink exhibited suitable porosity,swelling,degradation rate,and mechanical properties.The inclusion of COS demonstrated antibacterial effects against both Gram positive and Gram-negative bacteria,while simultaneously fostering the proliferation of human dermal fibroblasts(HDFs).Additionally,the application of COS could effectively reduce the expression levels of fibrosis-related genes,such as collagen I,collagen III,and fibronectin I.The three-dimensionally printed cell-laden dermal scaffold exhibited excellent shape fidelity and high cellular viability,facilitating the extension of HDFs along the scaffold and the simultaneous secretion of extracellular matrix proteins.Furthermore,the HDF-laden dermal scaffold transplanted into full-thickness skin defect sites in nude mice was shown to accelerate wound closure,reduce inflammation,and improve wound healing.Overall,the DLP-printed dermal scaffold provides an appealing approach for effectively treating full-thickness skin defects in clinical settings.展开更多
The intricate hierarchical structure of musculoskeletal tissues,including bone and interface tissues,necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes.T...The intricate hierarchical structure of musculoskeletal tissues,including bone and interface tissues,necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes.This has led to growing interest in the development of gradient bone scaffolds with hierarchical structures mimicking the extracellular matrix of native tissues to achieve improved therapeutic outcomes.Building on the anatomical characteristics of bone and interfacial tissues,this review provides a summary of current strategies used to design and fabricate biomimetic gradient scaffolds for repairing musculoskeletal tissues,specifically focusing on methods used to construct compositional and structural gradients within the scaffolds.The latest applications of gradient scaffolds for the regeneration of bone,osteochondral,and tendon-to-bone interfaces are presented.Furthermore,the current progress of testing gradient scaffolds in physiologically relevant animal models of skeletal repair is discussed,as well as the challenges and prospects of moving these scaffolds into clinical application for treating musculoskeletal injuries.展开更多
FK506(Tacrolimus)is a systemic immunosuppressant approved by the U.S.Food and Drug Administration.FK506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways ...FK506(Tacrolimus)is a systemic immunosuppressant approved by the U.S.Food and Drug Administration.FK506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain unclear.In this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function recovery.These findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.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
Lithium iron phosphate(LiFePO_(4),LFP)batteries have shown extensive adoption in power applications in recent years for their reliable safety,high theoretical capability and low cost.Nevertheless,the finite lifespan o...Lithium iron phosphate(LiFePO_(4),LFP)batteries have shown extensive adoption in power applications in recent years for their reliable safety,high theoretical capability and low cost.Nevertheless,the finite lifespan of these batteries necessitates the future processing of a significant number of spent LFP batteries,underscoring the urgent need for the development of both efficient and eco-friendly recycling methods.This study combines the advantages of wet leaching and direct regeneration methods,leveraging citric acid's multifaceted role to streamline the combined leaching and hydrothermal processes.Results indicate that citric acid efficiently leaches all elements from spent LFP batteries.Furthermore,through its unique structure,it enhances hydrothermal regeneration by stabilizing metal ions and controlling crystal growth,and also acts as a carbon source for the surface carbon coating of regenerated LFP(RLFP).The R-LFP shows outstanding electrochemical stability,achieving a discharge capacity of 155.1 mAh.g^(-1)at 0.1C,with a capacity retention rate of 93.2%after 300 cycles at 1C.Furthermore,economic and environmental analyses demonstrate this method's superior cost-effectiveness and sustainability.Therefore,the method proposed in this study is efficient,simple and avoids the complex process of element separation,innovatively using a single reagent to achieve closed-loop recycling of LFP batteries,providing a novel and effective solution for the resource sustainability application.展开更多
Bioactive molecules have shown great promise for effectively regulating various bone formation processes,rendering them attractive therapeutics for bone regeneration.However,the widespread application of bioactive mol...Bioactive molecules have shown great promise for effectively regulating various bone formation processes,rendering them attractive therapeutics for bone regeneration.However,the widespread application of bioactive molecules is limited by their low accumulation and short half-lives in vivo.Hydrogels have emerged as ideal carriers to address these challenges,offering the potential to prolong retention times at lesion sites,extend half-lives in vivo and mitigate side effects,avoid burst release,and promote adsorption under physiological conditions.This review systematically summarizes the recent advances in the development of bioactive molecule-loaded hydrogels for bone regeneration,encompassing applications in cranial defect repair,femoral defect repair,periodontal bone regeneration,and bone regeneration with underlying diseases.Additionally,this review discusses the current strategies aimed at improving the release profiles of bioactive molecules through stimuli-responsive delivery,carrier-assisted delivery,and sequential delivery.Finally,this review elucidates the existing challenges and future directions of hydrogel encapsulated bioactive molecules in the field of bone regeneration.展开更多
Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and hi...Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical properties.Inspired by Chinese ramen,we propose a universal fabricating method(printing-P,training-T,cross-linking-C,PTC&PCT)for tough hydrogel scaffolds to fill this gap.First,3D printing fabricates a hydrogel scaffold with desired structures(P).Then,the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance(T).Finally,the training results are fixed by photo-cross-linking processing(C).The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66 MPa(622-fold untreated)and have excellent biocompatibility.Furthermore,this scaffold possesses functional surface structures from nanometer to micron to millimeter,which can efficiently induce directional cell growth.Interestingly,this strategy can produce bionic human tissue with mechanical properties of 10 kPa-10 MPa by changing the type of salt,and many hydrogels,such as gelatin and silk,could be improved with PTC or PCT strategies.Animal experiments show that this scaffold can effectively promote the new generation of muscle fibers,blood vessels,and nerves within 4 weeks,prompting the rapid regeneration of large-volume muscle loss injuries.展开更多
High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the ex...High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.展开更多
Severe tissue defects present formidable challenges to human health,persisting as major contributors to mortality rates.The complex pathological microenvironment,particularly the disrupted immune landscape within thes...Severe tissue defects present formidable challenges to human health,persisting as major contributors to mortality rates.The complex pathological microenvironment,particularly the disrupted immune landscape within these defects,poses substantial hurdles to existing tissue regeneration strategies.However,the emergence of nanobiotechnology has opened a new direction in immunomodulatory nanomedicine,providing encouraging prospects for tissue regeneration and restoration.This review aims to gather recent advances in immunomodulatory nanomedicine to foster tissue regeneration.We begin by elucidating the distinctive features of the local immune microenvironment within defective tissues and its crucial role in tissue regeneration.Subsequently,we explore the design and functional properties of immunomodulatory nanosystems.Finally,we address the challenges and prospects of clinical translation in nanomedicine development,aiming to propose a potent approach to enhance tissue regeneration through synergistic immune modulation and nanomedicine integration.展开更多
The visual system of teleost fish grows continuously,which is a useful model for studying regeneration of the central nervous system.Glial cells are key for this process,but their contribution is still not well define...The visual system of teleost fish grows continuously,which is a useful model for studying regeneration of the central nervous system.Glial cells are key for this process,but their contribution is still not well defined.We followed oligodendrocytes in the visual system of adult zebrafish during regeneration of the optic nerve at 6,24,and 72 hours post-lesion and at 7 and 14 days post-lesion via the sox10:tagRFP transgenic line and confocal microscopy.To understand the changes that these oligodendrocytes undergo during regeneration,we used Sox2 immunohistochemistry,a stem cell marker involved in oligodendrocyte differentiation.We also used the Click-iT™ Plus TUNEL assay to study cell death and a BrdU assay to determine cell proliferation.Before optic nerve crush,sox10:tagRFP oligodendrocytes are located in the retina,in the optic nerve head,and through all the entire optic nerve.Sox2-positive cells are present in the peripheral germinal zone,the mature retina,and the optic nerve.After optic nerve crush,sox10:tagRFP cells disappeared from the optic nerve crush zone,suggesting that they died,although they were not TUNEL positive.Concomitantly,the number of Sox2-positive cells increased around the crushed area,the optic nerve head,and the retina.Then,between 24 hours post-lesion and 14 days post-lesion,double sox10:tagRFP/Sox2-positive cells were detected in the retina,optic nerve head,and whole optic nerve,together with a proliferation response at 72 hours post-lesion.Our results confirm that a degenerating process may occur prior to regeneration.First,sox10:tagRFP oligodendrocytes that surround the degenerated axons stop wrapping them,change their“myelinating oligodendrocyte”morphology to a“nonmyelinating oligodendrocyte”morphology,and die.Then,residual oligodendrocyte progenitor cells in the optic nerve and retina proliferate and differentiate for the purpose of remyelination.As new axons arise from the surviving retinal ganglion cells,new sox10:tagRFP oligodendrocytes arise from residual oligodendrocyte progenitor cells to guide,nourish and myelinate them.Thus,oligodendrocytes play an active role in zebrafish axon regeneration and remyelination.展开更多
BACKGROUND Exosome-based therapies represent a promising approach for hair regeneration.Unlike conventional treatments such as minoxidil and finasteride,exosomes deliver bioactive cargo that can stimulate dermal papil...BACKGROUND Exosome-based therapies represent a promising approach for hair regeneration.Unlike conventional treatments such as minoxidil and finasteride,exosomes deliver bioactive cargo that can stimulate dermal papilla cells,enhance angiogenesis,and modulate inflammatory pathways.However,variability in exosome sources,isolation techniques,and dosing protocols limits their clinical translation.AIM To synthesize findings from in vitro,preclinical and clinical studies,and to evaluate the efficacy,mechanisms,and challenges associated with exosome-based hair restoration therapies.METHODS A literature search was conducted using multiple databases(PubMed/Medline,Embase,Scopus,and Web of Science)employing terms for exosomes and hair regeneration for articles published in English to February 2025,following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.RESULTS A total of 27 studies(three in vitro,three pre-clinical,18 with both in vitro and preclinical component and three clinical)met the pre-defined search and inclusion criteria and were included in this review.CONCLUSION Exosome-based therapies hold immense promise for hair regeneration by leveraging their ability to modulate key signaling pathways and enhance hair follicle regeneration.While in vitro and preclinical studies demonstrate consistent efficacy across diverse exosome sources,methodological heterogeneity and a limited number of clinical studies warrant further clinical research to realize their full clinical potential for hair regeneration.展开更多
Inactivation of carbon-based transition metal catalysts,which was caused by electron loss,limited their application in advanced oxidation processes.Therefore,Co and TiO_(2) double-loaded carbon nanofiber material(Co@C...Inactivation of carbon-based transition metal catalysts,which was caused by electron loss,limited their application in advanced oxidation processes.Therefore,Co and TiO_(2) double-loaded carbon nanofiber material(Co@CNFs-TiO_(2))was synthesized in this study.Photocatalytic and chemical catalytic systems were synergized efficiently.Tetracycline was eliminated within 15 min.The degradation rate remained above 90%after five cycles,and the 50%promotion proved the high stability of Co@CNFs-TiO_(2).The main reactive oxygen species in this system were sulfate radicals,whereas Co and TiO_(2) represented the active sites of the catalytic reaction.Electrons generated from TiO_(2) during the photocatalytic process were transferred to Co,which promoted the Co(Ⅲ)/Co(Ⅱ)cycle and maintained Co in a low-valence state,thereby stimulating the generation of sulfate radicals.In this study,the effective regulation of reactive oxygen species in the reaction system was realized.The results provided a guidance for in situ electron replenishment and regeneration of carbon-based transition metal catalysts,which will expand the practical application of advanced oxidation processes.展开更多
基金supported by Ohio State Start Up FundNational Institutes of Health(NIH)+12 种基金Department of Defense(DoD)Wings for Life Spinal Cord Research Foundation,Wings for Life Spinal Cord Research Foundation(Austria)California Institute of Regenerative Medicine(CIRM)International Spinal Research Trust(United Kingdom)Stanford University Bio-X Program Interdisciplinary Initiatives Seed Grant IIP-7Dennis Chan FoundationKlein Family FundLucile Packard Foundation for Children's HealthStanford Institute for Neuro-Innovation and Translational Neurosciences(SINTN)Saunders Family Neuroscience FundJames Doty Neurosurgery FundHearst Neuroscience FundEileen Bond Research Fund(to GP)。
文摘In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.
基金supported by the Research Funds of the Center for Advanced Interdisciplinary Science and Biomedicine of IHM,No.QYZD20220002the National Natural Science Foundation of China,No.82071357a grant from the Ministry of Science and Technology of China,No.2019YFA0405600 (all to BH)。
文摘Rab5 is a GTPase protein that is involved in intracellular membrane trafficking. It functions by binding to various effector proteins and regulating cellular responses, including the formation of transport vesicles and their fusion with the cellular membrane. Rab5 has been reported to play an important role in the development of the zebrafish embryo;however, its role in axonal regeneration in the central nervous system remains unclear. In this study, we established a zebrafish Mauthner cell model of axonal injury using single-cell electroporation and two-photon axotomy techniques. We found that overexpression of Rab5 in single Mauthner cells promoted marked axonal regeneration and increased the number of intra-axonal transport vesicles. In contrast, treatment of zebrafish larvae with the Rab kinase inhibitor CID-1067700markedly inhibited axonal regeneration in Mauthner cells. We also found that Rab5 activated phosphatidylinositol 3-kinase(PI3K) during axonal repair of Mauthner cells and promoted the recovery of zebrafish locomotor function. Additionally, rapamycin, an inhibitor of the mechanistic target of rapamycin downstream of PI3K, markedly hindered axonal regeneration. These findings suggest that Rab5 promotes the axonal regeneration of injured zebrafish Mauthner cells by activating the PI3K signaling pathway.
基金supported by the Portuguese Foundation for Science and Technology(FCT),Centro 2020 and Portugol2020 and the EU FEDER program,via the project GoBack to SIV(PTDC/CVT-CVT/32261/2017,CENTRO-01-0145-FEDER-032261)the doctoral grants of PDC(SFRH/BD/139974/2018)and BMS(2020.06525.BD and DOI 10.54499/2020.06525.BD)+5 种基金the post-doctoral grant to JPF(SFRH/BPD/113359/2015-program-contract described in paragraphs 4,5,6 of art.23 of Law no.100157/2016,of August 29,as amended by Law no.57/2017 of July 2019),the project PTDC/MED-NEU/1677/2021 to JBRthe Institute of Biomedicine iBiMED(UIDB/04501/2020 and DOI 10.54499/UIDB/04501/2020,UIDP/04501/2020 and DOI 10.54499/UIDP/04501/2020)its LiM Bioimaging Facility-a PPBI node(POCI-01-0145-FEDER-022122)supported by the Research Commission of the Medical Faculty of the Heinrich-Heine-University(HHU)Düsseldorf,of the Biologisch-Medizinisches Forschungszentrum(BMFZ)of HHUfinanced by the Spanish"Plan Nacional de Investigacion Cientifica,Desarrollo e Innovacion Tecnologica,Ministerio de Economia y Competitividad(Instituto de Salud CarlosⅢ)",co-financed by the European Union(FEDER program),(grant FIS P/20/00318 and FIS P23/00337 to VC)grant CPP2021-009070 to VC by the"Proyectos de colaboracion publico-privada,Plan de Investigacion Cientifica,Tecnica y de inovacion 2021-2023,Ministerio de Ciencia e Innovacion,Union Europea,Agencia Estatal de Investigacion,Espana"。
文摘Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.
基金Hunan Provincial Natural Science Foundation Youth Fund Project (2023JJ40480)Hunan Province Key Research and Development Program Project (2024JK2130)Outstanding Youth Project of Hunan University of Chinese Medicine (2022XJB003)。
文摘Objective To observe the effects of moxibustion at Huantiao(GB30)acupoint on nerve repair,regeneration,and function in rats with sciatic nerve injury(SNI),and explore the possible mechanism of SNI improvement via moxibustion.Methods A total of 70 specific pathogen-free(SPF)grade male Sprague-Dawley(SD)rats were randomly assigned to control group(n=10)and model group(n=60).Following replication of SNI to model group rats,60 SNI model rats were randomly allocated to SNI groups of 1 d,3 d,and 7 d and moxibustion groups of 1 d,3 d,and 7 d with 10 rats in each group.Moxibustion groups were given moxibustion at the Huantiao(GB30)acupoint on the affected side with a 5 cm distance from the skin under isoflurane respiratory anesthesia and treated once a day for 20 min for 1 d,3 d,and 7 d,respectively.Control and SNI groups were anesthetized with isoflurane daily for 20 min.Open field tests and thermal pain threshold tests were conducted,and the general condition of rats was observed in each group pre-modeling and on treatment day 1,3,and 7.At the end of the treatment,immunofluorescence was used to detect the axonal growth rate,axonal growth density,and Schwann cells(SCs)proliferation in the middle 1-mm cross-section of the crush injury segment in rats.The gastrocnemius muscles on both sides of the rats were taken and weighed to calculate the wet weight ratio of the gastrocnemius muscles on both sides to observe the muscle atrophy of the rats,and hematoxylin-eosin(HE)staining was used to observe the pathomorphological changes of the gastrocnemius muscles on the affected side.Quantitative real-time polymerase chain reaction(qPCR)was used to detect the expression levels of nerve growth factor(NGF),interferon(IFN),macrophage migration inhibitory factor(MIF),interleukin(IL)-4,and transforming growth factor(TGF)-βin the sciatic nerve tissue of the rats.Results After modeling,rats in both moxibustion and SNI groups showed typical signs of pain behaviors(bending and curling of the hind soles of the affected side,licking claws,and lameness)and decreased activity compared with control group.The main benefits of moxibustion were evident from day 3:compared with SNI group,rats in moxibustion group had marked relief of pain behavior,increased activity levels and movement,and a lower response to thermal pain.At the same time,moxibustion significantly promoted the repair of SNI,as evidenced by the significantly better axonal growth rate,growth density,and SCs proliferation density in the crush injury segment compared with SNI group(P<0.01).Moxibustion also regulated the local microenvironment of the injury,up-regulated the pro-nerve repair factors NGF,IL-4,and TGF-β(P<0.05),and down-regulated the pro-inflammatory factors IFN-γ(P<0.01)and MIF(P<0.05).By day 7,the histomorphology of the gastrocnemius muscle in moxibustion group was improved,as indicated by enlarged muscle fibers,elevated regular myocyte morphology and wet weight ratio of the affected and unaffected sides(P<0.05),as well as a sustained high expression levels of NGF,IL-4,and TGF-β(P<0.05,P<0.05,and P<0.01,respectively),and a maintenance of low level of IFN-γ(P<0.01).Concurrently,the MIF level was not significantly different from SNI group(P>0.05).Conclusion Moxibustion at the Huantiao(GB30)acupoint effectively improves motor function and promotes recovery of sensory function and nerve regeneration in SNI rats,which may be related to the regulation of local inflammatory response,the promotion of nerve growth factor expression,the improvement of regenerative microenvironment,and the acceleration of SCs proliferation and axonal growth rate in damaged nerves.
基金supported by the National Natural Science Foundation of China,No.82202718the Natural Science Foundation of Beijing,No.L212050the China Postdoctoral Science Foundation,Nos.2019M664007,2021T140793(all to ZL)。
文摘Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor site.As an alternative,nerve guidance conduits may be used.The ideal conduit should be flexible,resistant to kinks and lumen collapse,and provide physical cues to guide nerve regeneration.We designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align them.Subsequently,we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber lumen.The presence of aligned fibers on the inner surface can promote the extension of nerve cells along the fibers.The helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide stability.Our novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model,suggesting that it has potential for clinical use in human nerve injuries.
基金financially supported by the National Key Research and Development Program of China(2023YFB3809300)。
文摘With the approaching of large-scale retirement of power lithium-ion batteries(LIBs),their urgent handling is required for environmental protection and resource reutilization.However,at present,substantial spent power batteries,especially for those high recovery value cathode materials,have not been greenly,sustainably,and efficiently recycled.Compared to the traditional recovery method for cathode materials with high energy consumption and severe secondary pollution,the direct repair regeneration,as a new type of short-process and efficient treatment methods,has attracted widespread attention.However,it still faces challenges in homogenization repair,electrochemical performance decline,and scaling-up production.To promote the direct regeneration technology development of failed NCM materials,herein we deeply discuss the failure mechanism of nickel-cobalt-manganese(NCM)ternary cathode materials,including element loss,Li/Ni mixing,phase transformation,structural defects,oxygen release,and surface degradation and reconstruction.Based on this,the detailed analysis and summary of the direct regeneration method embracing solid-phase sintering,eutectic salt assistance,solvothermal synthesis,sol-gel process,spray drying,and redox mediation are provided.Further,the upcycling strategy for regeneration materials,such as single-crystallization and high-nickelization,structural regulation,ion doping,and surface engineering,are discussed in deep.Finally,the challenges faced by the direct regeneration and corresponding countermeasures are pointed out.Undoubtedly,this review provides valuable guidance for the efficient and high-value recovery of failed cathode materials.
基金National Natural Science Foundation of China(Nos.52174269,52374293)Science and Technology Innovation Program of Hunan Province,China(Nos.2024CK1009,2022RC1123)。
文摘A tunable oxidization and reduction strategy was proposed to directly regenerate spent LiFePO_(4)/C cathode materials by oxidizing excessive carbon powders with the addition of FePO_(4).Experimental results indicate that spent LiFePO_(4)/C cathode materials with good performance can be regenerated by roasting at 650℃ for 11 h with the addition ofLi_(2)CO_(3),FePO_(4),V_(2)O_(5),and glucose.V_(2)O_(5) is added to improve the cycle performance of regenerated cathode materials.Glucose is used to revitalize the carbon layers on the surface of spent LiFePO_(4)/C particles for improving their conductivity.The regenerated V-doped LiFePO_(4)/C shows an excellent electrochemical performance with the discharge specific capacity of 161.36 mA·h/g at 0.2C,under which the capacity retention is 97.85%after 100 cycles.
基金supported by Heilongjiang Province Key R&D Program(No.GA22A014)。
文摘For realizing the goals of“carbon peak”and“carbon neutrality”,lithium-ion batteries(LIB)with LiFePO_(4)as the cathode material have been widely applied.However,this has also led to a large number of spent lithium-ion batteries,and the safe disposal of spent lithium-ion batteries is an urgent issue.Currently,the main reason for the capacity decay of LiFePO_(4)materials is the Li deficiency and the formation of the Fe^(3+)phase.In order to address this issue,we performed high-temperature calcination of the discarded lithium iron phosphate cathode material in a carbon dioxide environment to reduce or partially remove the carbon coating on its surface.Subsequently,mechanical grinding was conducted to ensure thorough mixing of the lithium source with the discarded lithium iron phosphate.The reaction between CO_(2)and the carbon coating produced a reducing atmosphere,reducing Fe^(3+)to Fe^(2+)and thereby reducing the content of Fe^(3+).The Fe^(3+)content in the repaired LiFePO_(4)material is reduced.The crystal structure of spent LiFePO_(4)cathode materials was repaired more completely compare with the traditional pretreatment method,and the repaired LiFePO_(4)material shows good electrochemical performance and cycling stability.Under 0.1 C conditions,the initial capacity can reach 149.1 m Ah/g.It can be reintroduced for commercial use.
基金supported by the National Natural Science Foundation of China(Nos.51975400 and 62031022)the Shanxi Provincial Key Medical Scientific Research Project(No.2020XM06)+2 种基金the Shanxi Provincial Basic Research Project(Nos.202103021221006,20210302123040,and 202103021223069)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2021L044)the Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering(No.2022SX-TD026).
文摘Dermal substitutes have provided a template for the regeneration and reconstruction of the dermis.However,the healed skin tissue often exhibits abnormal morphology and functionality,including scarring and inflammation.In this study,a composite bioink composed of methacrylated gelatin(GelMA)and chitosan oligosaccharide(COS)was proposed for printing a dermal scaffold using digital light processing(DLP)technology.The GelMA/COS bioink exhibited suitable porosity,swelling,degradation rate,and mechanical properties.The inclusion of COS demonstrated antibacterial effects against both Gram positive and Gram-negative bacteria,while simultaneously fostering the proliferation of human dermal fibroblasts(HDFs).Additionally,the application of COS could effectively reduce the expression levels of fibrosis-related genes,such as collagen I,collagen III,and fibronectin I.The three-dimensionally printed cell-laden dermal scaffold exhibited excellent shape fidelity and high cellular viability,facilitating the extension of HDFs along the scaffold and the simultaneous secretion of extracellular matrix proteins.Furthermore,the HDF-laden dermal scaffold transplanted into full-thickness skin defect sites in nude mice was shown to accelerate wound closure,reduce inflammation,and improve wound healing.Overall,the DLP-printed dermal scaffold provides an appealing approach for effectively treating full-thickness skin defects in clinical settings.
基金supported by the National Natural Science Foundation of China(Grant No.52473121,52403370 and 52221006)Fundamental Research Funds for the Central Universities(buctrc202020,buctrc202312).
文摘The intricate hierarchical structure of musculoskeletal tissues,including bone and interface tissues,necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes.This has led to growing interest in the development of gradient bone scaffolds with hierarchical structures mimicking the extracellular matrix of native tissues to achieve improved therapeutic outcomes.Building on the anatomical characteristics of bone and interfacial tissues,this review provides a summary of current strategies used to design and fabricate biomimetic gradient scaffolds for repairing musculoskeletal tissues,specifically focusing on methods used to construct compositional and structural gradients within the scaffolds.The latest applications of gradient scaffolds for the regeneration of bone,osteochondral,and tendon-to-bone interfaces are presented.Furthermore,the current progress of testing gradient scaffolds in physiologically relevant animal models of skeletal repair is discussed,as well as the challenges and prospects of moving these scaffolds into clinical application for treating musculoskeletal injuries.
基金supported by the National Natural Science Foundation of China,No.81971177(to YK)the Natural Science Foundation of Beijing,No.7222198(to NH)the Peking University People's Hospital Research and Development Fund,No.RDX2021-01(to YK)。
文摘FK506(Tacrolimus)is a systemic immunosuppressant approved by the U.S.Food and Drug Administration.FK506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain unclear.In this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function recovery.These findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.
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financially supported by the Natural Science Foundation of China(No.22162007)the Science and Technology Supporting Project of Guizhou Province(Nos.[2021]480 and[2023]379)+1 种基金Wengfu(Group)Co.,Ltd.Technology Development Project(No.WH-220787(YF))the project from Guizhou Institute of Innovation and development of dual-carbon and new energy technologies(No.DCRE-2023-05)。
文摘Lithium iron phosphate(LiFePO_(4),LFP)batteries have shown extensive adoption in power applications in recent years for their reliable safety,high theoretical capability and low cost.Nevertheless,the finite lifespan of these batteries necessitates the future processing of a significant number of spent LFP batteries,underscoring the urgent need for the development of both efficient and eco-friendly recycling methods.This study combines the advantages of wet leaching and direct regeneration methods,leveraging citric acid's multifaceted role to streamline the combined leaching and hydrothermal processes.Results indicate that citric acid efficiently leaches all elements from spent LFP batteries.Furthermore,through its unique structure,it enhances hydrothermal regeneration by stabilizing metal ions and controlling crystal growth,and also acts as a carbon source for the surface carbon coating of regenerated LFP(RLFP).The R-LFP shows outstanding electrochemical stability,achieving a discharge capacity of 155.1 mAh.g^(-1)at 0.1C,with a capacity retention rate of 93.2%after 300 cycles at 1C.Furthermore,economic and environmental analyses demonstrate this method's superior cost-effectiveness and sustainability.Therefore,the method proposed in this study is efficient,simple and avoids the complex process of element separation,innovatively using a single reagent to achieve closed-loop recycling of LFP batteries,providing a novel and effective solution for the resource sustainability application.
基金supported by the National Natural Science Foundation of China(51925304)Natural Science Foundation of Sichuan Province(2024NSFSC1023)Medical Research Program of Sichuan Province(Q23015).
文摘Bioactive molecules have shown great promise for effectively regulating various bone formation processes,rendering them attractive therapeutics for bone regeneration.However,the widespread application of bioactive molecules is limited by their low accumulation and short half-lives in vivo.Hydrogels have emerged as ideal carriers to address these challenges,offering the potential to prolong retention times at lesion sites,extend half-lives in vivo and mitigate side effects,avoid burst release,and promote adsorption under physiological conditions.This review systematically summarizes the recent advances in the development of bioactive molecule-loaded hydrogels for bone regeneration,encompassing applications in cranial defect repair,femoral defect repair,periodontal bone regeneration,and bone regeneration with underlying diseases.Additionally,this review discusses the current strategies aimed at improving the release profiles of bioactive molecules through stimuli-responsive delivery,carrier-assisted delivery,and sequential delivery.Finally,this review elucidates the existing challenges and future directions of hydrogel encapsulated bioactive molecules in the field of bone regeneration.
基金supported by the Innovative Research Group Project of the National Natural Science Foundation of China(T2121004)Key Programme(52235007)National Outstanding Youth Foundation of China(52325504).
文摘Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical properties.Inspired by Chinese ramen,we propose a universal fabricating method(printing-P,training-T,cross-linking-C,PTC&PCT)for tough hydrogel scaffolds to fill this gap.First,3D printing fabricates a hydrogel scaffold with desired structures(P).Then,the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance(T).Finally,the training results are fixed by photo-cross-linking processing(C).The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66 MPa(622-fold untreated)and have excellent biocompatibility.Furthermore,this scaffold possesses functional surface structures from nanometer to micron to millimeter,which can efficiently induce directional cell growth.Interestingly,this strategy can produce bionic human tissue with mechanical properties of 10 kPa-10 MPa by changing the type of salt,and many hydrogels,such as gelatin and silk,could be improved with PTC or PCT strategies.Animal experiments show that this scaffold can effectively promote the new generation of muscle fibers,blood vessels,and nerves within 4 weeks,prompting the rapid regeneration of large-volume muscle loss injuries.
基金supported by a grant of the M.D.-Ph.D./Medical Scientist Training Program through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(to HK)+3 种基金supported by National Research Foundation of Korea(NRF)grants funded by the Korean government(MSITMinistry of Science and ICT)(NRF2019R1A5A2026045 and NRF-2021R1F1A1061819)a grant from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(HR21C1003)New Faculty Research Fund of Ajou University School of Medicine(to JYC)。
文摘High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.
基金supported by the National Science Foundation of China(82202714).
文摘Severe tissue defects present formidable challenges to human health,persisting as major contributors to mortality rates.The complex pathological microenvironment,particularly the disrupted immune landscape within these defects,poses substantial hurdles to existing tissue regeneration strategies.However,the emergence of nanobiotechnology has opened a new direction in immunomodulatory nanomedicine,providing encouraging prospects for tissue regeneration and restoration.This review aims to gather recent advances in immunomodulatory nanomedicine to foster tissue regeneration.We begin by elucidating the distinctive features of the local immune microenvironment within defective tissues and its crucial role in tissue regeneration.Subsequently,we explore the design and functional properties of immunomodulatory nanosystems.Finally,we address the challenges and prospects of clinical translation in nanomedicine development,aiming to propose a potent approach to enhance tissue regeneration through synergistic immune modulation and nanomedicine integration.
基金supported by the Lanzadera TCUE and C2 program(Universidad de Salamanca)(to ASL)the Spanish National Research Council(CSIC)funded by the Junta de Castilla y León and co-financed by the European Regional Development Fund(ERDF“Europe drives our growth”):Internationalization Project“CL-EI-2021-08-IBFG Unit of Excellence”,Grant(PID2022-138478OA-100)funded by MICIU/AEI/10.13039/501100011033 and,by FEDER,UE(to MGM)+3 种基金Junta de Castilla y León(SA225P23)Gerencia Regional de Salud(2701/A1/2023)(to AV)the Plan Especial Grado Medicina(USAL)(to CPM)a Ramón y Cajal researcher:Grant RYC2021-033684-I funded by MICIU/AEI/10.13039/501100011033 and,by European Union NextGenerationEU/PRTR.
文摘The visual system of teleost fish grows continuously,which is a useful model for studying regeneration of the central nervous system.Glial cells are key for this process,but their contribution is still not well defined.We followed oligodendrocytes in the visual system of adult zebrafish during regeneration of the optic nerve at 6,24,and 72 hours post-lesion and at 7 and 14 days post-lesion via the sox10:tagRFP transgenic line and confocal microscopy.To understand the changes that these oligodendrocytes undergo during regeneration,we used Sox2 immunohistochemistry,a stem cell marker involved in oligodendrocyte differentiation.We also used the Click-iT™ Plus TUNEL assay to study cell death and a BrdU assay to determine cell proliferation.Before optic nerve crush,sox10:tagRFP oligodendrocytes are located in the retina,in the optic nerve head,and through all the entire optic nerve.Sox2-positive cells are present in the peripheral germinal zone,the mature retina,and the optic nerve.After optic nerve crush,sox10:tagRFP cells disappeared from the optic nerve crush zone,suggesting that they died,although they were not TUNEL positive.Concomitantly,the number of Sox2-positive cells increased around the crushed area,the optic nerve head,and the retina.Then,between 24 hours post-lesion and 14 days post-lesion,double sox10:tagRFP/Sox2-positive cells were detected in the retina,optic nerve head,and whole optic nerve,together with a proliferation response at 72 hours post-lesion.Our results confirm that a degenerating process may occur prior to regeneration.First,sox10:tagRFP oligodendrocytes that surround the degenerated axons stop wrapping them,change their“myelinating oligodendrocyte”morphology to a“nonmyelinating oligodendrocyte”morphology,and die.Then,residual oligodendrocyte progenitor cells in the optic nerve and retina proliferate and differentiate for the purpose of remyelination.As new axons arise from the surviving retinal ganglion cells,new sox10:tagRFP oligodendrocytes arise from residual oligodendrocyte progenitor cells to guide,nourish and myelinate them.Thus,oligodendrocytes play an active role in zebrafish axon regeneration and remyelination.
文摘BACKGROUND Exosome-based therapies represent a promising approach for hair regeneration.Unlike conventional treatments such as minoxidil and finasteride,exosomes deliver bioactive cargo that can stimulate dermal papilla cells,enhance angiogenesis,and modulate inflammatory pathways.However,variability in exosome sources,isolation techniques,and dosing protocols limits their clinical translation.AIM To synthesize findings from in vitro,preclinical and clinical studies,and to evaluate the efficacy,mechanisms,and challenges associated with exosome-based hair restoration therapies.METHODS A literature search was conducted using multiple databases(PubMed/Medline,Embase,Scopus,and Web of Science)employing terms for exosomes and hair regeneration for articles published in English to February 2025,following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.RESULTS A total of 27 studies(three in vitro,three pre-clinical,18 with both in vitro and preclinical component and three clinical)met the pre-defined search and inclusion criteria and were included in this review.CONCLUSION Exosome-based therapies hold immense promise for hair regeneration by leveraging their ability to modulate key signaling pathways and enhance hair follicle regeneration.While in vitro and preclinical studies demonstrate consistent efficacy across diverse exosome sources,methodological heterogeneity and a limited number of clinical studies warrant further clinical research to realize their full clinical potential for hair regeneration.
基金the financial support from the National Natural Science Foundation of China(Nos.52074176,52300165,52300056,52300099)Natural Science Foundation of Shandong Province Youth Project(No.ZR2022QB155)Open Project Program of Engineering Research Center of Groundwater Pollution Control and Remediation,Ministry of Education of China(No.GW202203)。
文摘Inactivation of carbon-based transition metal catalysts,which was caused by electron loss,limited their application in advanced oxidation processes.Therefore,Co and TiO_(2) double-loaded carbon nanofiber material(Co@CNFs-TiO_(2))was synthesized in this study.Photocatalytic and chemical catalytic systems were synergized efficiently.Tetracycline was eliminated within 15 min.The degradation rate remained above 90%after five cycles,and the 50%promotion proved the high stability of Co@CNFs-TiO_(2).The main reactive oxygen species in this system were sulfate radicals,whereas Co and TiO_(2) represented the active sites of the catalytic reaction.Electrons generated from TiO_(2) during the photocatalytic process were transferred to Co,which promoted the Co(Ⅲ)/Co(Ⅱ)cycle and maintained Co in a low-valence state,thereby stimulating the generation of sulfate radicals.In this study,the effective regulation of reactive oxygen species in the reaction system was realized.The results provided a guidance for in situ electron replenishment and regeneration of carbon-based transition metal catalysts,which will expand the practical application of advanced oxidation processes.
