An exploratory multinuclear magnetic resonance(MR)and magnetic resonance imaging(MRI)study was performed on lithium-ion battery cells with ^(7)Li,^(19)F,and ^(1)H measurements.A variable field superconducting magnet w...An exploratory multinuclear magnetic resonance(MR)and magnetic resonance imaging(MRI)study was performed on lithium-ion battery cells with ^(7)Li,^(19)F,and ^(1)H measurements.A variable field superconducting magnet with a fixed frequency parallel-plate radiofrequency(RF)probe was employed in the study.The magnetic field was changed to set the resonance frequency of each nucleus to the fixed RF probe frequency of 33.7 MHz.Two cartridge-like lithium-ion cells,with graphite anodes and LiNi_(0.5)Mn_(0.3)Co_(0.2)O_(2)(NMC)cathodes,were interrogated.One cell was pristine,and one was charged to a cell voltage of 4.2 V.The results presented demonstrate the great potential of the variable field magnet approach in multinuclear measurement of lithium-ion batteries.These methods open the door for developing faster and simpler methods for detecting,quantifying,and interpreting MR and MRI data from lithium-ion and other batteries.展开更多
Blast pressure of C-H-O solvents on failed lithium-ion cells at the voltage range between 3.8 V and 4.18 V may be calculated by means of the simple semi-empirical equation, y = (Ia + Jb)/(Ka + Lb + Me), p is th...Blast pressure of C-H-O solvents on failed lithium-ion cells at the voltage range between 3.8 V and 4.18 V may be calculated by means of the simple semi-empirical equation, y = (Ia + Jb)/(Ka + Lb + Me), p is the initial density of solvent, Q is the chemical energy of explosion, v is the voltage. The values of a, b, c depend on C-H-O composition. Value of I, J, K, L, Mmay be estimated from the H20-CO2 arbitrary decomposition assumption. Blast pressure derived in this manner can provide preliminary protective estimation and it is compared with experiment results by adiabatic calorimeter.展开更多
In this paper,overcharge behaviors and thermal runaway(TR)features of large format lithium-ion(Liion)cells with different cathode materials(LiFePO4(LFP),Li[Ni_(1/3)Co_(1/3)Mn_(1/3)]O_(2)(NCM111),Li[Ni_(0.6)Co_(0.2)Mn_...In this paper,overcharge behaviors and thermal runaway(TR)features of large format lithium-ion(Liion)cells with different cathode materials(LiFePO4(LFP),Li[Ni_(1/3)Co_(1/3)Mn_(1/3)]O_(2)(NCM111),Li[Ni_(0.6)Co_(0.2)Mn_(0.2)]O_(2)(NCM622)and Li[Ni_(0.8)Co_(0.1)Mn_(0.1)]O_(2)(NCM811))were investigated.The results showed that,under the same overcharge condition,the TR of LFP Li-ion cell occurred earlier compared with the NCM Li-ion cells,indicating its poor overcharge tolerance and high TR risk.However,when TR occurred,LFP Li-ion cell exhibited lower maximum temperature and mild TR response.All NCM Liion cells caught fire or exploded during TR,while the LFP Li-ion cell only released a large amount of smoke without fire.According to the overcharge behaviors and TR features,a safety assessment score system was proposed to evaluate the safety of the cells.In short,NCM Li-ion cells have better performance in energy density and overcharge tolerance(or low TR risk),while LFP Li-ion cell showed less severe response to overcharging(or less TR hazards).For NCM Li-ion cells,as the ratio of nickel in cathode material increases,the thermal stability of the cathode materials becomes poorer,and the TR hazards increase.Such a comparison study on large format Li-ion cells with different cathode materials can provide deeper insights into the overcharge behaviors and TR features,and provide guidance for engineers to reasonably choose battery materials in automotive applications.展开更多
Thermal runaway(TR)of lithium-ion(Li-ion)batteries(LIBs)involves multiple forms of hazards,such as gas venting/jetting,fire,or even explosion.Explosion,as the most extreme case,is caused by the generated flammable gas...Thermal runaway(TR)of lithium-ion(Li-ion)batteries(LIBs)involves multiple forms of hazards,such as gas venting/jetting,fire,or even explosion.Explosion,as the most extreme case,is caused by the generated flammable gases,and a deflagration to detonation transition(DDT)may occur in this process.Here,overheat-to-TR tests and the corresponding outgas-induced explosion tests were conducted on 42 Ah Li-ion cells with Li[Ni_(1/3)Co_(1/3)Mn_(1/3)]O2cathode.The sum of CO_(2),H_(2),C_(2)H_(4),CO,and CH4accounted for more than 90%of the gases.Lower/upper explosion limits(LEL/UEL),laminar flame speed,and ideal stable detonation pressure were calculated to interpret the explosion characteristics and boundary.It turned out that shockwave was easily to be compressed and accelerated under higher state of charge(SOC)conditions.Thus,Li-ion cells explosion may evolve into unstable detonation in encapsulated battery pack and its evolution mechanism was explained,which provides a new idea for explosion-proof design of LIBs system.Additionally,a comprehensive assessment method was developed to intuitively characterize TR hazards.Severity of explosion presented an upward trend with the increase of SOC while the sensitivity was not the same.This study provides a further anatomy of TR,which is instructive to the safety of power battery systems.展开更多
Given the importance of lithium-ion cell safety,a comprehensive review on the thermal stability of lithium-ion cells investigated by accelerating rate calorimetry(ARC),is provided in the present work.The operating mec...Given the importance of lithium-ion cell safety,a comprehensive review on the thermal stability of lithium-ion cells investigated by accelerating rate calorimetry(ARC),is provided in the present work.The operating mechanism of ARC is discussed first,including the usage and the reaction kinetics.Besides that,the thermal stability of the cathode/anode materials at elevated temperatures is revealed by examining the impacts of some significant factors,i.e.,the lithium content,particle size,material density,lithium salt,solvent,additive,binder and initial heating temperature.A comparison of the common cathode materials indicates that the presence of Mn and polyanion could significantly enhance the thermal stability of cathode materials,while the doping of Al also helps to restrain the reactivity.Except for their high capacity,some alloy materials demonstrate more competitive safety than traditional carbon anode materials.Furthermore,the thermal behaviors of full cells under abusive conditions are reviewed here.Due to the sensitivity of ARC to the kinetic parameters,a reaction kinetic modeling can be built on the basis of ARC profiles,to predict the thermal behaviors of cell components and cells.Herein,a shortcircuit modeling is exampled.展开更多
Lithium-ion thermoelectrochemical cell(LTEC), featuring simultaneous energy conversion and storage, has emerged as promising candidate for low-grade heat harvesting. However, relatively poor thermosensitivity and heat...Lithium-ion thermoelectrochemical cell(LTEC), featuring simultaneous energy conversion and storage, has emerged as promising candidate for low-grade heat harvesting. However, relatively poor thermosensitivity and heat-to-current behavior limit the application of LTECs using LiPF_6 electrolyte. Introducing additives into bulk electrolyte is a reasonable strategy to solve such problem by modifying the solvation structure of electrolyte ions. In this work, we develop a dual-salt electrolyte with fluorosurfactant(FS) additive to achieve high thermopower and durability of LTECs during the conversion of low-grade heat into electricity. The addition of FS induces a unique Li~+ solvation with the aggregated double anions through a crowded electrolyte environment,resulting in an enhanced mobility kinetics of Li~+ as well as boosted thermoelectrochemical performances. By coupling optimized electrolyte with graphite electrode, a high thermopower of 13.8 mV K^(-1) and a normalized output power density of 3.99 mW m^(–2) K^(–2) as well as an outstanding output energy density of 607.96 J m^(-2) can be obtained.These results demonstrate that the optimization of electrolyte by regulating solvation structure will inject new vitality into the construction of thermoelectrochemical devices with attractive properties.展开更多
As a prevailing cathode material of lithium-ion batteries(LIBs),LiCoO_(2)(LCO)still encounters the tricky problems of structural collapse,whose morphological engineering and cation doping are crucial for surmounting t...As a prevailing cathode material of lithium-ion batteries(LIBs),LiCoO_(2)(LCO)still encounters the tricky problems of structural collapse,whose morphological engineering and cation doping are crucial for surmounting the mechanical strains and alleviating phase degradation upon cycling.Hereinafter,we propose a strategy using a zeolitic imidazolate framework(ZIF)as the self-sacrificing template to directionally prepare a series of LiNi_(0.1)Co_(0.9)O_(2)(LNCO)with tailorable electrochemical properties.The rational selection of sintering temperature imparts the superiority of the resultant products in lithium storage,during which the sample prepared at 700℃(LNCO-700)outperforms its counterparts in cyclability(156.8 mA h g^(-1)at 1 C for 200 cycles in half cells,1 C=275 mA g^(-1))and rate capability due to the expedited ion/electron transport and the strengthen mechanical robustness.The feasibility of proper Ni doping is also divulged by half/full cell tests and theoretical study,during which LNCO-700(167 mA h g^(-1)at 1 C for 100 cycles in full cells)surpasses LCO-700 in battery performance due to the mitigated phase deterioration,stabilized layered structu re,ameliorated electro nic co nductivity,a nd exalted lithium sto rage activity.This work systematically unveils tailorable electrochemical behaviors of LNCO to better direct their practical application.展开更多
Small coin cell batteries are predominantly used for testing lithium-ion batteries(LIBs)in academia because they require small amounts of material and are easy to assemble.However,insufficient attention is given to di...Small coin cell batteries are predominantly used for testing lithium-ion batteries(LIBs)in academia because they require small amounts of material and are easy to assemble.However,insufficient attention is given to difference in cell performance that arises from the differences in format between coin cells used by academic researchers and pouch or cylindrical cells which are used in industry.In this article,we compare coin cells and pouch cells of different size with exactly the same electrode materials,electrolyte,and electrochemical conditions.We show the battery impedance changes substantially depending on the cell format using techniques including Electrochemical Impedance Spectroscopy(EIS)and Galvanostatic Intermittent Titration Technique(GITT).Using full cell NCA-graphite LIBs,we demonstrate that this difference in impedance has important knock-on effects on the battery rate performance due to ohmic polarization and the battery life time due to Li metal plating on the anode.We hope this work will help researchers getting a better idea of how small coin cell formats impact the cell performance and help predicting improvements that can be achieved by implementing larger cell formats.展开更多
The demand for electronic devices that utilize lithium is steadily increasing in this rapidly advancing technological world.Obtaining high-purity lithium in an environmentally friendly way is challenging by using comm...The demand for electronic devices that utilize lithium is steadily increasing in this rapidly advancing technological world.Obtaining high-purity lithium in an environmentally friendly way is challenging by using commercialized methods.Herein,we propose the first fuel cell system for continuous lithium-ion extraction using a lithium superionic conductor membrane and advanced electrode.The fuel cell system for extracting lithium-ion has demonstrated a twofold increase in the selectivity of Li^(+)/Na^(+)while producing electricity.Our data show that the fuel cell with a titania-coated electrode achieves 95%lithium-ion purity while generating 10.23 Wh of energy per gram of lithium.Our investigation revealed that using atomic layer deposition improved the electrode's uniformity,stability,and electrocatalytic activity.After 2000 cycles determined by cyclic voltammetry,the electrode preserved its stability.展开更多
Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflamm...Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.展开更多
Separators play a critical role in the safety and performance of lithium-ion batteries.However,commercial polyolefin separators are limited by their poor affinity with electrolytes and low melting points.In this work,...Separators play a critical role in the safety and performance of lithium-ion batteries.However,commercial polyolefin separators are limited by their poor affinity with electrolytes and low melting points.In this work,we constructed a reinforced-concrete-like structure by homogeneously dispersing nano-Al_(2)O_(3) and cellulose on the separators to improve their stability and performance.In this reinforcedconcrete-like structure,the cellulose is a reinforcing mesh,and the nano-Al_(2)O_(3) acts as concrete to support the separator.After constructing the reinforced-concrete-like structure,the separators exhibit good stability even at 200℃(thermal shrinkage of 0.3%),enhanced tensile strain(tensile stress of 133.4 MPa and tensile strains of 62%),and better electrolyte wettability(a contact angle of 6.5°).Combining these advantages,the cells with nano-Al_(2)O_(3)@cellulose-coated separators exhibit stable cycling performance and good rate performance.Therefore,the construction of the reinforced-concretelike structure is a promising technology to promote the application of lithium-ion batteries in extreme environments.展开更多
Cell-to-cell variations(CtCV) compromise the electrochemical performance of battery packs, yet the evolutional mechanism and quantitative impacts of CtCV on the pack's fast-charging performance remain unexplored. ...Cell-to-cell variations(CtCV) compromise the electrochemical performance of battery packs, yet the evolutional mechanism and quantitative impacts of CtCV on the pack's fast-charging performance remain unexplored. This knowledge gap is vital for the proliferation of electric vehicles. This study underlies the relationship between CtCV and charging performance by assessing the pack's charge speed, final electric quantity, and temperature consistency. Cell variations and pack status are depicted using 2D parameter diagrams, and an m PnS configured pack model is built upon a decomposed electrode cell model.Variations in three single electric parameters, i.e., capacity(Q), electric quantity(E), and internal resistance(R), and their dual interactions, i.e., E-Q and R-Q, are analyzed carefully. The results indicate that Q variations predominantly affect the final electric quantity of the pack, while R variations impact the charge speed most. With incremental variances in cell parameters, the pack's fast-charging capability first declines linearly and then deteriorates sharply as variations intensify. This research elucidates the correlations between pack charging capabilities and cell variations, providing essential insights for optimizing cell sorting and assembly, battery management design, and charging protocol development for battery packs.展开更多
The state-of-the-art lithium-ion capacitors (LICs),consisting of high-capacity battery-type anode and high-rate capacitor-type cathode,can deliver high energy density and large power density when comparing with tradit...The state-of-the-art lithium-ion capacitors (LICs),consisting of high-capacity battery-type anode and high-rate capacitor-type cathode,can deliver high energy density and large power density when comparing with traditional supercapacitors and lithium-ion batteries,respectively.However,the ion kinetics mismatch between cathode and anode leads to unsatisfied cycling lifetime and anode degradation.Tremendous efforts have been devoted to solving the abovementioned issue.One promising strategy is altering high conductive hard carbon anode with excellent structural stability to match with activated carbon cathode,assembling dual-carbon LIC.In this contribution,one-pot in-situ expansion and heteroatom doping strategy was adopted to prepare sheet-like hard carbon,while activated carbon was obtained involving activation.Ammonium persulfate was used as expanding and doping agent simultaneously.While furfural residues (FR) were served as carbon precursor.The resulting hard carbon (FRNS-HC) and activated carbon (FRNS-AC)show excellent electrochemical performance as negative and positive electrodes in a lithium-ion battery (LIB).To be specific,374.2 m Ah g^(-1)and 123.1 m Ah g^(-1)can be achieved at 0.1 A g^(-1)and 5 A g^(-1)when FRNS-HC was tested as anode.When combined with a highly porous carbon cathode (S_(BET)=2961 m^(2)g^(-1)) synthesized from the same precursor,the LIC showed high specific energy of147.67 Wh kg^(-1)at approximately 199.93 W kg^(-1),and outstanding cycling life with negligible capacitance fading over 1000 cycles.This study could lead the way for the development of heteroatom-doped porous carbon nanomaterials applied to Li-based energy storage applications.展开更多
Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve rep...Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication.Nevertheless,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear.To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation.The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells.We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells.Subsequently,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded miR-21-5p.Finally,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously restored.These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p.miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome.This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves,and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.展开更多
Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain met...Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.展开更多
Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied fo...Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.展开更多
The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative disease.Although the detailed patho...The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative disease.Although the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear,the advancement of stem cell approaches has shown promise for Parkinson's disease research and therapy.The induced pluripotent stem cells have been commonly used to generate dopaminergic neurons,which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease therapies.The current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem cells.The benefits of induced pluripotent stem cell-based research are highlighted.Various dopaminergic neuron differentiation protocols from induced pluripotent stem cells are compared.The emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are evaluated.Finally,limitations,challenges,and future directions of induced pluripotent stem cell–based approaches are analyzed and proposed,which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.展开更多
Neuronal cell death and the loss of connectivity are two of the primary pathological mechanisms underlying Alzheimer's disease.The accumulation of amyloid-βpeptides,a key hallmark of Alzheimer's disease,is be...Neuronal cell death and the loss of connectivity are two of the primary pathological mechanisms underlying Alzheimer's disease.The accumulation of amyloid-βpeptides,a key hallmark of Alzheimer's disease,is believed to induce neuritic abnormalities,including reduced growth,extension,and abnormal growth cone morphology,all of which contribute to decreased connectivity.However,the precise cellular and molecular mechanisms governing this response remain unknown.In this study,we used an innovative approach to demonstrate the effect of amyloid-βon neurite dynamics in both two-dimensional and three-dimensional cultu re systems,in order to provide more physiologically relevant culture geometry.We utilized various methodologies,including the addition of exogenous amyloid-βpeptides to the culture medium,growth substrate coating,and the utilization of human-induced pluripotent stem cell technology,to investigate the effect of endogenous amyloid-βsecretion on neurite outgrowth,thus paving the way for potential future applications in personalized medicine.Additionally,we also explore the involvement of the Nogo signaling cascade in amyloid-β-induced neurite inhibition.We demonstrate that inhibition of downstream ROCK and RhoA components of the Nogo signaling pathway,achieved through modulation with Y-27632(a ROCK inhibitor)and Ibuprofen(a Rho A inhibitor),respectively,can restore and even enhance neuronal connectivity in the presence of amyloid-β.In summary,this study not only presents a novel culture approach that offers insights into the biological process of neurite growth and inhibition,but also proposes a specific mechanism for reduced neural connectivity in the presence of amyloid-βpeptides,along with potential intervention points to restore neurite growth.Thereby,we aim to establish a culture system that has the potential to serve as an assay for measuring preclinical,predictive outcomes of drugs and their ability to promote neurite outgrowth,both generally and in a patient-specific manner.展开更多
Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limit...Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.展开更多
Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory enshea...Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.展开更多
基金BJB thanks the Canada Chairs program for a Research Chair in MRI of Materials[950e230894]an NSERC Discovery Grant[2015-6122]GRG thanks NSERC for a Discovery Grant[RGPIN-2017-06095].
文摘An exploratory multinuclear magnetic resonance(MR)and magnetic resonance imaging(MRI)study was performed on lithium-ion battery cells with ^(7)Li,^(19)F,and ^(1)H measurements.A variable field superconducting magnet with a fixed frequency parallel-plate radiofrequency(RF)probe was employed in the study.The magnetic field was changed to set the resonance frequency of each nucleus to the fixed RF probe frequency of 33.7 MHz.Two cartridge-like lithium-ion cells,with graphite anodes and LiNi_(0.5)Mn_(0.3)Co_(0.2)O_(2)(NMC)cathodes,were interrogated.One cell was pristine,and one was charged to a cell voltage of 4.2 V.The results presented demonstrate the great potential of the variable field magnet approach in multinuclear measurement of lithium-ion batteries.These methods open the door for developing faster and simpler methods for detecting,quantifying,and interpreting MR and MRI data from lithium-ion and other batteries.
文摘Blast pressure of C-H-O solvents on failed lithium-ion cells at the voltage range between 3.8 V and 4.18 V may be calculated by means of the simple semi-empirical equation, y = (Ia + Jb)/(Ka + Lb + Me), p is the initial density of solvent, Q is the chemical energy of explosion, v is the voltage. The values of a, b, c depend on C-H-O composition. Value of I, J, K, L, Mmay be estimated from the H20-CO2 arbitrary decomposition assumption. Blast pressure derived in this manner can provide preliminary protective estimation and it is compared with experiment results by adiabatic calorimeter.
基金supported by the National Natural Science Foundation of China(Nos.U1564206,U1764258)the National Key R&D Program of China(No.2018YFB0105700)+1 种基金the support from China Scholarship Council(No.201806030115)supported by the Department of Energy(DOE),Office of Electricity(OE)at Oak Ridge National Laboratory managed by UL-Battelle LLC under contract DE-AC05-00OR22725。
文摘In this paper,overcharge behaviors and thermal runaway(TR)features of large format lithium-ion(Liion)cells with different cathode materials(LiFePO4(LFP),Li[Ni_(1/3)Co_(1/3)Mn_(1/3)]O_(2)(NCM111),Li[Ni_(0.6)Co_(0.2)Mn_(0.2)]O_(2)(NCM622)and Li[Ni_(0.8)Co_(0.1)Mn_(0.1)]O_(2)(NCM811))were investigated.The results showed that,under the same overcharge condition,the TR of LFP Li-ion cell occurred earlier compared with the NCM Li-ion cells,indicating its poor overcharge tolerance and high TR risk.However,when TR occurred,LFP Li-ion cell exhibited lower maximum temperature and mild TR response.All NCM Liion cells caught fire or exploded during TR,while the LFP Li-ion cell only released a large amount of smoke without fire.According to the overcharge behaviors and TR features,a safety assessment score system was proposed to evaluate the safety of the cells.In short,NCM Li-ion cells have better performance in energy density and overcharge tolerance(or low TR risk),while LFP Li-ion cell showed less severe response to overcharging(or less TR hazards).For NCM Li-ion cells,as the ratio of nickel in cathode material increases,the thermal stability of the cathode materials becomes poorer,and the TR hazards increase.Such a comparison study on large format Li-ion cells with different cathode materials can provide deeper insights into the overcharge behaviors and TR features,and provide guidance for engineers to reasonably choose battery materials in automotive applications.
基金sponsored by the China Postdoctoral Science Foundation(China National Postdoctoral Program for Innovative Talents,BX20210362022M710383)the National Natural Science Foundation of China(52072040,U21A20170)。
文摘Thermal runaway(TR)of lithium-ion(Li-ion)batteries(LIBs)involves multiple forms of hazards,such as gas venting/jetting,fire,or even explosion.Explosion,as the most extreme case,is caused by the generated flammable gases,and a deflagration to detonation transition(DDT)may occur in this process.Here,overheat-to-TR tests and the corresponding outgas-induced explosion tests were conducted on 42 Ah Li-ion cells with Li[Ni_(1/3)Co_(1/3)Mn_(1/3)]O2cathode.The sum of CO_(2),H_(2),C_(2)H_(4),CO,and CH4accounted for more than 90%of the gases.Lower/upper explosion limits(LEL/UEL),laminar flame speed,and ideal stable detonation pressure were calculated to interpret the explosion characteristics and boundary.It turned out that shockwave was easily to be compressed and accelerated under higher state of charge(SOC)conditions.Thus,Li-ion cells explosion may evolve into unstable detonation in encapsulated battery pack and its evolution mechanism was explained,which provides a new idea for explosion-proof design of LIBs system.Additionally,a comprehensive assessment method was developed to intuitively characterize TR hazards.Severity of explosion presented an upward trend with the increase of SOC while the sensitivity was not the same.This study provides a further anatomy of TR,which is instructive to the safety of power battery systems.
基金supported by NSERC,Tesla Motors,the National Natural Science Foundation of China (No.52204213,52272396)the China Postdoctoral Science Foundation (No.2022M711602)+2 种基金the Opening Fund of State Key Laboratory of Fire Science (SKLFS) (No.HZ2022-KF07)the Jiangsu Project Plan for Outstanding Talents Team in Six Research Fields (No.TD-XNYQC-002)the support of the China Scholarship Council。
文摘Given the importance of lithium-ion cell safety,a comprehensive review on the thermal stability of lithium-ion cells investigated by accelerating rate calorimetry(ARC),is provided in the present work.The operating mechanism of ARC is discussed first,including the usage and the reaction kinetics.Besides that,the thermal stability of the cathode/anode materials at elevated temperatures is revealed by examining the impacts of some significant factors,i.e.,the lithium content,particle size,material density,lithium salt,solvent,additive,binder and initial heating temperature.A comparison of the common cathode materials indicates that the presence of Mn and polyanion could significantly enhance the thermal stability of cathode materials,while the doping of Al also helps to restrain the reactivity.Except for their high capacity,some alloy materials demonstrate more competitive safety than traditional carbon anode materials.Furthermore,the thermal behaviors of full cells under abusive conditions are reviewed here.Due to the sensitivity of ARC to the kinetic parameters,a reaction kinetic modeling can be built on the basis of ARC profiles,to predict the thermal behaviors of cell components and cells.Herein,a shortcircuit modeling is exampled.
基金supported by the Leading Edge Technology of Jiangsu Province (BK20220009, BK20202008)Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)。
文摘Lithium-ion thermoelectrochemical cell(LTEC), featuring simultaneous energy conversion and storage, has emerged as promising candidate for low-grade heat harvesting. However, relatively poor thermosensitivity and heat-to-current behavior limit the application of LTECs using LiPF_6 electrolyte. Introducing additives into bulk electrolyte is a reasonable strategy to solve such problem by modifying the solvation structure of electrolyte ions. In this work, we develop a dual-salt electrolyte with fluorosurfactant(FS) additive to achieve high thermopower and durability of LTECs during the conversion of low-grade heat into electricity. The addition of FS induces a unique Li~+ solvation with the aggregated double anions through a crowded electrolyte environment,resulting in an enhanced mobility kinetics of Li~+ as well as boosted thermoelectrochemical performances. By coupling optimized electrolyte with graphite electrode, a high thermopower of 13.8 mV K^(-1) and a normalized output power density of 3.99 mW m^(–2) K^(–2) as well as an outstanding output energy density of 607.96 J m^(-2) can be obtained.These results demonstrate that the optimization of electrolyte by regulating solvation structure will inject new vitality into the construction of thermoelectrochemical devices with attractive properties.
基金the financial support from the Special Funds for the Cultivation of Guangdong College Students’Scientific and Technological Innovation(“Climbing Program”Special Funds,pdjh2023b0145)Guangdong Provincial International Joint Research Center for Energy Storage Materials(2023A0505090009)。
文摘As a prevailing cathode material of lithium-ion batteries(LIBs),LiCoO_(2)(LCO)still encounters the tricky problems of structural collapse,whose morphological engineering and cation doping are crucial for surmounting the mechanical strains and alleviating phase degradation upon cycling.Hereinafter,we propose a strategy using a zeolitic imidazolate framework(ZIF)as the self-sacrificing template to directionally prepare a series of LiNi_(0.1)Co_(0.9)O_(2)(LNCO)with tailorable electrochemical properties.The rational selection of sintering temperature imparts the superiority of the resultant products in lithium storage,during which the sample prepared at 700℃(LNCO-700)outperforms its counterparts in cyclability(156.8 mA h g^(-1)at 1 C for 200 cycles in half cells,1 C=275 mA g^(-1))and rate capability due to the expedited ion/electron transport and the strengthen mechanical robustness.The feasibility of proper Ni doping is also divulged by half/full cell tests and theoretical study,during which LNCO-700(167 mA h g^(-1)at 1 C for 100 cycles in full cells)surpasses LCO-700 in battery performance due to the mitigated phase deterioration,stabilized layered structu re,ameliorated electro nic co nductivity,a nd exalted lithium sto rage activity.This work systematically unveils tailorable electrochemical behaviors of LNCO to better direct their practical application.
基金funding from the ERC(Consolidator Grant MIGHTY,866005)the Innovate UK(UKRI:104174)Faraday Institution-Future CAT(FIRG017)and Degradation(FIRG001)
文摘Small coin cell batteries are predominantly used for testing lithium-ion batteries(LIBs)in academia because they require small amounts of material and are easy to assemble.However,insufficient attention is given to difference in cell performance that arises from the differences in format between coin cells used by academic researchers and pouch or cylindrical cells which are used in industry.In this article,we compare coin cells and pouch cells of different size with exactly the same electrode materials,electrolyte,and electrochemical conditions.We show the battery impedance changes substantially depending on the cell format using techniques including Electrochemical Impedance Spectroscopy(EIS)and Galvanostatic Intermittent Titration Technique(GITT).Using full cell NCA-graphite LIBs,we demonstrate that this difference in impedance has important knock-on effects on the battery rate performance due to ohmic polarization and the battery life time due to Li metal plating on the anode.We hope this work will help researchers getting a better idea of how small coin cell formats impact the cell performance and help predicting improvements that can be achieved by implementing larger cell formats.
文摘The demand for electronic devices that utilize lithium is steadily increasing in this rapidly advancing technological world.Obtaining high-purity lithium in an environmentally friendly way is challenging by using commercialized methods.Herein,we propose the first fuel cell system for continuous lithium-ion extraction using a lithium superionic conductor membrane and advanced electrode.The fuel cell system for extracting lithium-ion has demonstrated a twofold increase in the selectivity of Li^(+)/Na^(+)while producing electricity.Our data show that the fuel cell with a titania-coated electrode achieves 95%lithium-ion purity while generating 10.23 Wh of energy per gram of lithium.Our investigation revealed that using atomic layer deposition improved the electrode's uniformity,stability,and electrocatalytic activity.After 2000 cycles determined by cyclic voltammetry,the electrode preserved its stability.
基金supported by grants from the Major Program of National Key Research and Development Project,Nos.2020YFA0112600(to ZH)the National Natural Science Foundation of China,No.82171270(to ZL)+5 种基金Public Service Platform for Artificial Intelligence Screening and Auxiliary Diagnosis for the Medical and Health Industry,Ministry of Industry and Information Technology of the People’s Republic of China,No.2020-0103-3-1(to ZL)the Natural Science Foundation of Beijing,No.Z200016(to ZL)Beijing Talents Project,No.2018000021223ZK03(to ZL)Beijing Municipal Committee of Science and Technology,No.Z201100005620010(to ZL)CAMS Innovation Fund for Medical Sciences,No.2019-I2M-5-029(to YW)Shanghai Engineering Research Center of Stem Cells Translational Medicine,No.20DZ2255100(to ZH).
文摘Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.
基金funding from the Natural Science Foundation of China(22278150,22075086,22138005,and 22141001)the Guangdong Basic and Applied Basic Research Foundation(2022A1515010980,2023A1515010046)the Fundamental Research Funds for the Central Universities(2022ZYGXZR101).
文摘Separators play a critical role in the safety and performance of lithium-ion batteries.However,commercial polyolefin separators are limited by their poor affinity with electrolytes and low melting points.In this work,we constructed a reinforced-concrete-like structure by homogeneously dispersing nano-Al_(2)O_(3) and cellulose on the separators to improve their stability and performance.In this reinforcedconcrete-like structure,the cellulose is a reinforcing mesh,and the nano-Al_(2)O_(3) acts as concrete to support the separator.After constructing the reinforced-concrete-like structure,the separators exhibit good stability even at 200℃(thermal shrinkage of 0.3%),enhanced tensile strain(tensile stress of 133.4 MPa and tensile strains of 62%),and better electrolyte wettability(a contact angle of 6.5°).Combining these advantages,the cells with nano-Al_(2)O_(3)@cellulose-coated separators exhibit stable cycling performance and good rate performance.Therefore,the construction of the reinforced-concretelike structure is a promising technology to promote the application of lithium-ion batteries in extreme environments.
基金supported by the National Natural Science Foundation of China under No. 52177217the Postdoctoral Innovative Talents Support Program under No. BX20240232。
文摘Cell-to-cell variations(CtCV) compromise the electrochemical performance of battery packs, yet the evolutional mechanism and quantitative impacts of CtCV on the pack's fast-charging performance remain unexplored. This knowledge gap is vital for the proliferation of electric vehicles. This study underlies the relationship between CtCV and charging performance by assessing the pack's charge speed, final electric quantity, and temperature consistency. Cell variations and pack status are depicted using 2D parameter diagrams, and an m PnS configured pack model is built upon a decomposed electrode cell model.Variations in three single electric parameters, i.e., capacity(Q), electric quantity(E), and internal resistance(R), and their dual interactions, i.e., E-Q and R-Q, are analyzed carefully. The results indicate that Q variations predominantly affect the final electric quantity of the pack, while R variations impact the charge speed most. With incremental variances in cell parameters, the pack's fast-charging capability first declines linearly and then deteriorates sharply as variations intensify. This research elucidates the correlations between pack charging capabilities and cell variations, providing essential insights for optimizing cell sorting and assembly, battery management design, and charging protocol development for battery packs.
基金financially supported by the National Natural Science Foundation of China (22075308, 22209197)Natural Science Foundation of Shanxi Province (20210302 1224439, 202203021211002)Shanxi Province Science Foundation for Youths (No: SQ2019001)。
文摘The state-of-the-art lithium-ion capacitors (LICs),consisting of high-capacity battery-type anode and high-rate capacitor-type cathode,can deliver high energy density and large power density when comparing with traditional supercapacitors and lithium-ion batteries,respectively.However,the ion kinetics mismatch between cathode and anode leads to unsatisfied cycling lifetime and anode degradation.Tremendous efforts have been devoted to solving the abovementioned issue.One promising strategy is altering high conductive hard carbon anode with excellent structural stability to match with activated carbon cathode,assembling dual-carbon LIC.In this contribution,one-pot in-situ expansion and heteroatom doping strategy was adopted to prepare sheet-like hard carbon,while activated carbon was obtained involving activation.Ammonium persulfate was used as expanding and doping agent simultaneously.While furfural residues (FR) were served as carbon precursor.The resulting hard carbon (FRNS-HC) and activated carbon (FRNS-AC)show excellent electrochemical performance as negative and positive electrodes in a lithium-ion battery (LIB).To be specific,374.2 m Ah g^(-1)and 123.1 m Ah g^(-1)can be achieved at 0.1 A g^(-1)and 5 A g^(-1)when FRNS-HC was tested as anode.When combined with a highly porous carbon cathode (S_(BET)=2961 m^(2)g^(-1)) synthesized from the same precursor,the LIC showed high specific energy of147.67 Wh kg^(-1)at approximately 199.93 W kg^(-1),and outstanding cycling life with negligible capacitance fading over 1000 cycles.This study could lead the way for the development of heteroatom-doped porous carbon nanomaterials applied to Li-based energy storage applications.
基金supported by the National Natural Science Foundation of China,No.31870977(to HYS)the National Key Technologies Research and Development Program of China,No.2017YFA0104700(to FD)+2 种基金2022 Jiangsu Funding Program for Excellent Postdoctoral Talent(to MC)Priority Academic Program Development of Jiangsu Higher Education Institutions[PAPD]the Major Project of Basic Science(Natural Science)Research in Higher Education Institutions of Jiangsu Province,No.22KJA180001(to QRH)。
文摘Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication.Nevertheless,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear.To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation.The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells.We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells.Subsequently,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded miR-21-5p.Finally,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously restored.These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p.miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome.This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves,and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.
基金supported by the National Natural Science Foundation of China, No.82274616the Key Laboratory Project for General Universities in Guangdong Province, No.2019KSYS005Guangdong Province Science and Technology Plan International Cooperation Project, No.2020A0505100052 (all to QW)。
文摘Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.
文摘Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.
基金supported by Singapore National Medical Research Council(NMRC)grants,including CS-IRG,HLCA2022(to ZDZ),STaR,OF LCG 000207(to EKT)a Clinical Translational Research Programme in Parkinson's DiseaseDuke-Duke-NUS collaboration pilot grant(to ZDZ)。
文摘The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative disease.Although the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear,the advancement of stem cell approaches has shown promise for Parkinson's disease research and therapy.The induced pluripotent stem cells have been commonly used to generate dopaminergic neurons,which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease therapies.The current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem cells.The benefits of induced pluripotent stem cell-based research are highlighted.Various dopaminergic neuron differentiation protocols from induced pluripotent stem cells are compared.The emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are evaluated.Finally,limitations,challenges,and future directions of induced pluripotent stem cell–based approaches are analyzed and proposed,which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.
基金supported by a BBSRC CASE training studentship,No.BB/K011413/1(to KG)。
文摘Neuronal cell death and the loss of connectivity are two of the primary pathological mechanisms underlying Alzheimer's disease.The accumulation of amyloid-βpeptides,a key hallmark of Alzheimer's disease,is believed to induce neuritic abnormalities,including reduced growth,extension,and abnormal growth cone morphology,all of which contribute to decreased connectivity.However,the precise cellular and molecular mechanisms governing this response remain unknown.In this study,we used an innovative approach to demonstrate the effect of amyloid-βon neurite dynamics in both two-dimensional and three-dimensional cultu re systems,in order to provide more physiologically relevant culture geometry.We utilized various methodologies,including the addition of exogenous amyloid-βpeptides to the culture medium,growth substrate coating,and the utilization of human-induced pluripotent stem cell technology,to investigate the effect of endogenous amyloid-βsecretion on neurite outgrowth,thus paving the way for potential future applications in personalized medicine.Additionally,we also explore the involvement of the Nogo signaling cascade in amyloid-β-induced neurite inhibition.We demonstrate that inhibition of downstream ROCK and RhoA components of the Nogo signaling pathway,achieved through modulation with Y-27632(a ROCK inhibitor)and Ibuprofen(a Rho A inhibitor),respectively,can restore and even enhance neuronal connectivity in the presence of amyloid-β.In summary,this study not only presents a novel culture approach that offers insights into the biological process of neurite growth and inhibition,but also proposes a specific mechanism for reduced neural connectivity in the presence of amyloid-βpeptides,along with potential intervention points to restore neurite growth.Thereby,we aim to establish a culture system that has the potential to serve as an assay for measuring preclinical,predictive outcomes of drugs and their ability to promote neurite outgrowth,both generally and in a patient-specific manner.
基金supported by the National Natural Science Foundation of China,No.82271114the Natural Science Foundation of Zhejiang Province of China,No.LZ22H120001(both to ZLC).
文摘Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.
基金supported by the Spanish Ministry of Economy and Competitiveness,No.PID2019-106498GB-I00(to MVS)the Instituto de Salud CarlosⅢ,Fondo Europeo de Desarrollo Regional“Una manera de hacer Europa”,No.PI19/00071(to MAB)+1 种基金Ministerio de Ciencia e Innovación Project,No.SAF2017-82736-C2-1-R(to MTMF)in Universidad Autónoma de MadridFundación Universidad Francisco de Vitoria(to JS)。
文摘Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.