Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a...Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a stroke.Their dynamic activation and polarization states are key factors that influence the disease process and treatment outcomes.This review article investigates the role of microglia in ischemic stroke and explores potential intervention strategies.Microglia exhibit a dynamic functional state,transitioning between pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.This duality is crucial in ischemic stroke,as it maintains a balance between neuroinflammation and tissue repair.Activated microglia contribute to neuroinflammation through cytokine release and disruption of the blood-brain barrier,while simultaneously promoting tissue repair through anti-inflammatory responses and regeneration.Key pathways influencing microglial activation include Toll-like receptor 4/nuclear factor kappa B,mitogen-activated protein kinases,Janus kinase/signal transducer and activator of transcription,and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways.These pathways are targets for various experimental therapies aimed at promoting M2 polarization and mitigating damage.Potential therapeutic agents include natural compounds found in drugs such as minocycline,as well as traditional Chinese medicines.Drugs that target these regulatory mechanisms,such as small molecule inhibitors and components of traditional Chinese medicines,along with emerging technologies such as single-cell RNA sequencing and spatial transcriptomics,offer new therapeutic strategies and clinical translational potential for ischemic stroke.展开更多
Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications wit...Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications with metabolic reprogramming.Nonetheless,the specific mechanisms and roles of this connection in astrocytes remain unclear.Therefore,this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system.The close relationship between epigenetic modifications and metabolic reprogramming was discussed.Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases.In the nervous system,lactate plays an essential role.However,its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation.The involvement of lactate in epigenetic modifications is currently a hot research topic,especially in lactylation modification,a key determinant in this process.Lactate also indirectly regulates various epigenetic modifications,such as N6-methyladenosine,acetylation,ubiquitination,and phosphorylation modifications,which are closely linked to several neurological disorders.In addition,exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.展开更多
Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival a...Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.展开更多
Stroke remains a leading cause of death and disability worldwide,and electroacupuncture has a long history of use in stroke treatment.This meta-analysis and systematic review aimed to evaluate the efficacy of electroa...Stroke remains a leading cause of death and disability worldwide,and electroacupuncture has a long history of use in stroke treatment.This meta-analysis and systematic review aimed to evaluate the efficacy of electroacupuncture and explore its potential mechanisms in animal models of ischemic stroke.The PubMed,EMBASE,Web of Science,CENTRAL,and CINAHL databases were comprehensively searched up to May 1,2024.This review included articles on preclinical investigations of the efficacy and mechanisms of electroacupuncture in treating ischemic stroke.Data from 70 eligible studies were analyzed in Stata 18.0,using a random-effects model to calculate the standardized mean difference(Hedge’s g).The risk of bias was assessed using RevMan 5.4 software,and the quality of evidence was rated according to the Grading of Recommendations,Assessment,Development,and Evaluation(GRADE)system.Subgroup analyses were conducted to test the consistency of the results and sensitivity analyses were used to assess their robustness.The quality assessment revealed that most studies adequately handled incomplete data and selective reporting.However,several methodological limitations were identified:only 4 studies demonstrated a low risk of allocation concealment,26 achieved a low risk of outcome assessment bias,and 9 had a high risk of randomization bias.Additionally,there was an unclear risk regarding participant blinding and other methodological aspects.The GRADE assessment rated 12 outcomes as moderate quality and 6 as low quality.The mechanisms of electroacupuncture treatment for ischemic stroke can be categorized as five primary pathways:(1)Electroacupuncture significantly reduced infarct volume and apoptotic cell death(P<0.01)in ischemic stroke models;(2)electroacupuncture significantly decreased the levels of pro-inflammatory factors(P<0.01)while increasing the levels of anti-inflammatory factors(P=0.02);(3)electroacupuncture reduced the levels of oxidative stress indicators(P<0.01)and enhanced the expression of antioxidant enzymes(P<0.01);(4)electroacupuncture significantly promoted nerve regeneration(P<0.01);and(5)electroacupuncture influenced blood flow remodeling(P<0.01)and angiogenesis(P<0.01).Subgroup analyses indicated that electroacupuncture was most effective in the transient middle cerebral artery occlusion model(P<0.01)and in post-middle cerebral artery occlusion intervention(P<0.01).Dispersive waves were found to outperform continuous waves with respect to neuroprotection and anti-inflammatory effects(P<0.01),while scalp acupoints demonstrated greater efficacy than body acupoints(P<0.01).The heterogeneity among the included studies was minimal,and sensitivity analyses indicated stable results.Their methodological quality was generally satisfactory.In conclusion,electroacupuncture is effective in treating cerebral ischemia by modulating cell apoptosis,oxidative stress,inflammation,stroke-induced nerve regeneration,blood flow remodeling,and angiogenesis.The efficacy of electroacupuncture may be influenced by factors such as the middle cerebral artery occlusion model,the timing of intervention onset,waveform,and acupoint selection.Despite the moderate to low quality of evidence,these findings suggest that electroacupuncture has clinical potential for improving outcomes in ischemic stroke.展开更多
Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted t...Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.展开更多
Neurodegenerative diseases,which are characterized by progressive neuronal loss and the lack of disease-modifying therapies,are becoming a major global health challenge.The existing neuromodulation techniques,such as ...Neurodegenerative diseases,which are characterized by progressive neuronal loss and the lack of disease-modifying therapies,are becoming a major global health challenge.The existing neuromodulation techniques,such as deep brain stimulation and transcranial magnetic stimulation,show limitations such as invasiveness,restricted cortical targeting,and irreversible tissue effects.In this context,low-intensity transcranial ultrasound has emerged as a promising noninvasive alternative that can penetrate deep into the brain and modulate neuroplasticity.This review comprehensively assesses the therapeutic mechanisms,efficacy,and translational potential of low-intensity transcranial ultrasound in treating neurodegenerative diseases,with emphasis on its role in promoting neuronal regeneration,modulating neuroinflammation,and enhancing functional recovery.We summarize the findings of previous studies and systematically illustrate the potential of low-intensity transcranial ultrasound in regulating cell death mechanisms,enhancing neural repair and regeneration,and alleviating symptoms associated with neurodegenerative diseases.Preclinical findings indicate that low-intensity transcranial ultrasound can enhance the release of neurotrophic factors(e.g.,brain-derived neurotrophic factor),promote autophagy to clear protein aggregates,modulate microglial activation,and temporarily open the blood-brain barrier to facilitate targeted drug delivery.Existing clinical trial data show that low-intensity transcranial ultrasound can reduce amyloid-βplaques,improve motor and cognitive deficits,and promote remyelination in various disease models.Early clinical trials suggest that low-intensity transcranial ultrasound may enhance cognitive scores in Alzheimer’s disease and alleviate motor symptoms in Parkinson’s disease,all while demonstrating a favorable safety profile.Past studies support the notion that by integrating safety,precision,and reversibility,low-intensity transcranial ultrasound can transform the treatment landscape for neurodegenerative disease.However,more advancements are necessary for future clinical application of low-intensity transcranial ultrasound,including optimizing parameters such as frequency,intensity,and duty cycle;considering individual anatomical differences;and confirming long-term efficacy.We believe establishing standardized protocols,conducting larger trials,and investigating the underlying mechanisms to clarify dose-response relationships and refine personalized application strategies are essential in this regard.Future research should focus on translating preclinical findings into clinical practice,addressing technical challenges,and exploring combination therapies with pharmacological or gene interventions.展开更多
The adsorptive denitrification performance of MIL-101(Cr)-0.5 toward pyridine,aniline or quinoline in simulated fuels with basic nitrogen content of 1732μg/g was evaluated separately.Furthermore,the effects of adsorp...The adsorptive denitrification performance of MIL-101(Cr)-0.5 toward pyridine,aniline or quinoline in simulated fuels with basic nitrogen content of 1732μg/g was evaluated separately.Furthermore,the effects of adsorption temperature,adsorption time and adsorbent dosage on their adsorptive denitrification performance were systematically investigated.The experimental results demonstrated that under a fixed adsorbent dosage of 0.05 g and a simulated fuel volume of 10 mL,the optimal removal efficiency for aniline was achieved at 30℃ within 30 min,whereas higher temperatures and longer times(40℃and 40 min)were required for effective removal of pyridine and quinoline.Density Functional Theory(DFT)calculations were conducted via Materials Studio(MS)software to study the adsorptive denitrification mechanism of MIL-101(Cr)toward these three basic nitrogen-containing compounds.The simulation calculation results revealed that the interaction between pyridine and MIL-101(Cr)primarily involved coordination adsorption.In contrast,the interaction between aniline or quinoline and MIL-101(Cr)proceeded mainly through coordination,with additional contributions fromπ-complexation and hydrogen bonding.The overall adsorption strength order is pyridine>aniline>quinoline.During the adsorption process,pyridine and quinoline transfer electrons to the MIL-101(Cr)surface through the H→C→N→Cr^(3+)pathway,while aniline transfers electrons to the MIL-101(Cr)surface through various pathways,including N→Cr^(3+),N→C→Cr^(3+)and N→H→O.Furthermore,adsorption kinetics studies indicated that the adsorption processes for all three basic nitrogen-containing compounds followed the quasi second order kinetic models.The experimental results on the effect of benzene on the adsorptive denitrification performance of MIL-101(Cr)-0.5 demonstrated that benzene exerted a more significant impact on the adsorption of aniline and quinoline.Finally,the adsorbent was regenerated using ethanol washing.It was found that MIL-101(Cr)-0.5 retained stable denitrification performance after two regeneration cycles.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
Voltage-gated sodium channels are essential ionic-conductance pathways in the nervous system,which play an irreplaceable role in modulating neuronal excitability and signal transduction.This review comprehensively ana...Voltage-gated sodium channels are essential ionic-conductance pathways in the nervous system,which play an irreplaceable role in modulating neuronal excitability and signal transduction.This review comprehensively analyzes the molecular mechanisms and pathophysiological significance of voltage-gated sodium channels,with particular emphasis on elucidating the molecular-action mechanisms of the distinct subtypes of these channels,including Nav1.1,Nav1.2,and Nav1.6,across various neurological disorders such as familial hemiplegic migraine,epilepsy,autism spectrum disorder,and retinal dysfunction.This review also provides a comprehensive overview of the pathogenic mechanisms associated with voltage-gated sodium channels,and systematically clarifies the evolutionary pathway of treatment strategies from conventional to innovative approaches.It analyzes two major categories of conventional sodium channel blockers and their applications:antiepileptic drugs(such as carbamazepine,lamotrigine,and phenytoin)and antiarrhythmic drugs(such as lidocaine,flecainide,and quinidine).However,these conventional blockers show limitations because of the lack of selectivity,driving research toward more precise therapeutic directions.Additionally,this review evaluates gabapentin,cannabidiol,and calcium channel blockers with different mechanisms of action.These drugs modulate neuronal excitability from multiple perspectives,providing diverse options for symptom relief.This review also highlights advances in gene therapy for specific diseases,such as STK-001,which promotes effective splicing of the sodium channel voltage-gated type 1 alpha subunit(SCN1A)gene,and ETX101,which utilizes adeno-associated virus 9 vectors to deliver engineered transcription factors.These two agents provide targeted therapeutic solutions for Dravet syndrome.Furthermore,this review summarizes some innovative therapeutic agents in clinical trials,including PRAX-222(for SCN2A gain-offunction mutation-related epilepsy),which has received Food and Drug Administration orphan drug designation,and the selective Nav1.6 inhibitor NBI-921352(for SCN8A-related epilepsy).Collectively,this review comprehensively compares the advantages and disadvantages of conventional drugs and gene therapy and envisions future treatment strategies that integrate the strengths of both approaches,facilitating personalized precision medicine to provide more accurate and effective treatment options for patients with ion channel diseases.展开更多
Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability...Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability. Even without apparent inflammation, injury sites are associated with increased inflammatory markers. This review focuses on how it might be possible to reduce neuropathic pain by reducing inflammation. Physiologically, pain is resolved by a combination of the out-migration of pro-inflammatory cells from the injury site, the down-regulation of the genes underlying the inflammation, up-regulating genes for anti-inflammatory mediators, and reducing nociceptive neuron hyperexcitability. While various techniques reduce chronic neuropathic pain, the best are effective on < 50% of patients, no technique reliably or permanently eliminates neuropathic pain. This is because most techniques are predominantly aimed at reducing pain, not inflammation. In addition, while single factors reduce pain, increasing evidence indicates significant and longer-lasting pain relief requires multiple factors acting simultaneously. Therefore, it is not surprising that extensive data indicate that the application of platelet-rich plasma provides more significant and longer-lasting pain suppression than other techniques, although its analgesia is neither complete nor permanent. However, several case reports indicate that platelet-rich plasma can induce permanent neuropathic pain elimination when the platelet concentration is significantly increased and is applied to longer nerve lengths. This review examines the primary triggers of the development and maintenance of neuropathic pain and techniques that reduce chronic neuropathic pain. The application of plateletrich plasma holds great promise for providing complete and permanent chronic neuropathic pain elimination.展开更多
Recent studies have found that the suppression of phosphatase and tensin homolog is one of the most effective single-gene approaches for promoting optic nerve regeneration.This effect is primarily mediated through the...Recent studies have found that the suppression of phosphatase and tensin homolog is one of the most effective single-gene approaches for promoting optic nerve regeneration.This effect is primarily mediated through the activation of the protein kinase B/phosphoinositide 3-kinase/mammalian target of rapamycin signaling pathway.The purpose of this article is to elucidate how the downregulation of phosphatase and tensin homolog is involved in each key phase of optic nerve regeneration and to summarize the potential targets for therapeutic interventions in this process.Optic nerve regeneration progresses through five phases:stress response,growth navigation,nerve regeneration,synaptic reconstruction,and remyelination.During the stress response phase,the suppression of phosphatase and tensin homolog enhances the survival of retinal ganglion cells and promotes the proliferation of microglia.In the nerve regeneration phase,reduced levels of phosphatase and tensin homolog facilitate mitochondrial transport,while inhibition of the phosphatase and tensin homolog-L isoform specifically promotes mitophagy.During the synaptic reconstruction phase,the deletion of phosphatase and tensin homolog modulates the synthesis of axon extension-related proteins and stabilizes microglial microtubules,thereby accele rating the clearance of damaged synapses and the fo rmation of new ones.During the remyelination phase,the knockout of phosphatase and tensin homolog promotes the proliferation of oligodendrocyte progenitor cells and the diffe rentiation of oligodendrocytes,relieving myelination obstruction.This paper also discusses current strategies and translational challenges for neuron-specific inhibition of phosphatase and tensin homolog,including off-ta rget effects,delive ry precisio n,and long-term safety.By integrating molecular insights with emerging bioengineering approaches,this paper provides a framework for develo ping targeted therapies for optic nerve regeneration and broader applications in the field of central nervous system regeneration.展开更多
Recovering LiFePO_(4) extraction slag(LES)-the FePO_(4)-rich residue formed after Li leaching from spent LiFePO_(4)-has become pivotal to minimizing resource losses,mitigating environmental risks,and advancing circula...Recovering LiFePO_(4) extraction slag(LES)-the FePO_(4)-rich residue formed after Li leaching from spent LiFePO_(4)-has become pivotal to minimizing resource losses,mitigating environmental risks,and advancing circularity in lithium-ion battery value chains.However,integrative frameworks that link closed-loop routes(returning to battery precursors/cathodes)with non-closed-loop upcycling are still limited,constraining process optimization and scale-up.This review synthesizes current progress in LES recycling with emphasis on maximizing recovery efficiency and product value.In closed-loop pathways,hydrometallurgical purification removes impurities to yield battery-grade FePO_(4) as an LiFePO_(4) precursor,while direct relithiation(e.g.,solid-state sintering aided by Li sources and reductants)restores Li and reduces Fe^(3+)to Fe^(2+),thereby regenerating LiFePO_(4) cathodes from LES.In non-closed-loop pathways,compositionally guided upcycling converts LES into advanced materials(e.g.,high-performance electrodes,highcapacity adsorbents),thereby broadening the techno-economic value propositions.We also distill lessons from early industrial practice,identifying constraints arising from feedstock variability,energy-cost coupling(thermal/chemical utilities),and product-quality assurance(battery-grade specifications).Finally,we map research directions-including data-driven feed characterization and process control,defecthealing relithiation strategies and interfacial engineering,quality grading and market pathways,and multi-scenario deployment-to enhance the technical and economic sustainability of LES recycling and accelerate its contribution to a circular battery economy.展开更多
Economical and sustainable wastewater treatment techniques are highly demanded to alleviate the issues of clearwater scarcity globally.In this work,the acetic acid/H_(2)O_(2) (AHP) was leveraged to enrich oxygenated f...Economical and sustainable wastewater treatment techniques are highly demanded to alleviate the issues of clearwater scarcity globally.In this work,the acetic acid/H_(2)O_(2) (AHP) was leveraged to enrich oxygenated functional groups on the biochar surface for efficient ciprofloxacin (CIP) adsorption and biochar regeneration (In situ degradation of CIP in the spent AHP solution).The AHP-modified biochar exhibited significantly enhanced CIP adsorption capacity,about 22 times that of the pristine biochar.The optimized modification condition (acetic acid/H_(2)O_(2):2.11,temperature:45 ℃,and time:12 h) was screened by the response surface method,reaching the highest CIP adsorption capacity of 86.26 mg·g^(−1).Characterization results revealed that the content of carboxyl —C=O—O was enhanced in AHP-modified biochar,which contributed to efficient CIP adsorption by the electrostatic interaction,hydrogen bonding,and hydrophobic interaction.The adsorption of modified biochar to CIP molecules was a spontaneous endothermic process,and in line with the pseudo-second-order model and the Langmuir isotherm model.Moreover,the biochar modification process enabled the spent AHP solution with a strong oxidizing agent of peracetic acid (PAA),which can be employed to degrade adsorbed CIP for biochar in-situ generation.This work tailored a closed-loop strategy for biochar oxidation,contaminant adsorption,and biochar regeneration,highlighting a viable route for sustainable wastewater treatment.展开更多
A novel faujasite(FAU) type zeolitized ceramsite(FZC) was prepared via a novel three dimensional(3D) in-pore growth method.FZC is a centimeter sized spherical particle with a 3-dimensional radial morphology inside,wit...A novel faujasite(FAU) type zeolitized ceramsite(FZC) was prepared via a novel three dimensional(3D) in-pore growth method.FZC is a centimeter sized spherical particle with a 3-dimensional radial morphology inside,with a specific surface area and pore volume 6 and 30 times that of the original ceramsite,respectively.The unique structure was constructed through electrostatic and polymerization interactions between hexadecyl trimethyl ammonium bromide(CTAB) micelles,ceramic pore walls and silicate aluminate ions,which could simultaneously improve adsorption capacity and mass transfer,endowing FZC with excellent heavy metal adsorption properties.FZC-50 could remove the majority of Cu and Zn from solution within shorter periods(73.3 % and 80.0 %of original ceramsite,respectively) with larger adsorption capacities(340 % and 370 % of original ceramsite,respectively).Theoretical analysis and regeneration experiments both indicate that the adsorption of Cu(Ⅱ) and Zn(Ⅱ) on FZC-50 is dominated by ion exchange.And the spent sorbent can be effectively regenerated by NaCl,and the cycle number is expected to be 33 and 26 times for Cu(Ⅱ) and Zn(Ⅱ) adsorption,respectively.This work proposed a novel synthesis route to construct a 3D multi-stage porous zeolite inside ceramsite,and opened up new ideas for the further development of zeolitized ceramsite.展开更多
Design concept Design Theme Color is not only a visual grammar but also a symbolic language of the spirit.This series,“In the Name of Color,”explores three states of the female inner world:awakening in chaos,order i...Design concept Design Theme Color is not only a visual grammar but also a symbolic language of the spirit.This series,“In the Name of Color,”explores three states of the female inner world:awakening in chaos,order in return,and regeneration in flow.The works—Eye of the Storm,Back to the Seed,and Source—form a stream-of-consciousness journey from within to without.Based on the COLORO color system,the series is constructed through hue,chroma,lightness,and domain ratio,treating color as both emotional force and symbolic medium.展开更多
Wound management continues to present major clinical challenges,often necessitating therapeutic strategies that extend beyond conventional dressings,which provide only passive protection.Magnesium(Mg),a biologically i...Wound management continues to present major clinical challenges,often necessitating therapeutic strategies that extend beyond conventional dressings,which provide only passive protection.Magnesium(Mg),a biologically indispensable element,has attracted considerable attention for its multifaceted role in wound repair,including modulation of inflammatory responses,stimulation of fibroblast and keratinocyte proliferation,promotion of angiogenesis,and enhancement of collagen synthesis.However,the direct application of Mg formulations is limited by uncontrolled Mg ion(Mg^(2+))release,localized cytotoxicity at elevated concentrations,and inadequate mechanical stability at the wound site.To address these challenges,Mg-incorporated polymeric scaffolds have been developed as advanced delivery platforms.These systems integrate the regenerative capacity of Mg with the tunable properties of polymers,enabling controlled degradation,mechanical reinforcement,and sustained Mg^(2+)release to establish a favorable microenvironment for tissue repair.This review critically examines the role of Mg in wound healing and the effectiveness of polymeric matrices for controlled Mg^(2+)delivery.It further provides a comprehensive evaluation of recent advances in Mg-incorporated polymeric scaffolds,including nanofibers,hydrogels,and sponges,with emphasis on fabrication strategies,structural characteristics,and therapeutic efficacy.Key challenges,such as optimizing ion release kinetics,enhancing scaffold stability,and facilitating clinical translation,are also discussed.Collectively,this work underscores the potential of Mg-polymeric scaffolds as a next-generation platform for advanced wound care and highlights perspectives for future research and development.展开更多
Bone Research is an open access,fully peer-reviewed journal publishing the foremost progress and novel understanding of all aspects of bone science.The journal highlights the breakthrough discoveries in basic and clin...Bone Research is an open access,fully peer-reviewed journal publishing the foremost progress and novel understanding of all aspects of bone science.The journal highlights the breakthrough discoveries in basic and clinical aspects of bone biology,pathophysiology and regeneration,as well as other significant findings related to bone.展开更多
Materials from natural sources have been studied to replace the conventional synthetic or animal-derived products as a safer alternative to be used in the healthcare field.In dentistry,guided bone regeneration(GBR)rel...Materials from natural sources have been studied to replace the conventional synthetic or animal-derived products as a safer alternative to be used in the healthcare field.In dentistry,guided bone regeneration(GBR)relies on barrier membranes,predominantly from animals or synthetic materials,to improve osteogenesis by avoiding undesired soft tissue cells from defect sites.In this study,membranes were prepared from zein,a corn-derived protein,using a simple extraction and casting method,followed by optional formaldehyde cross-linking to evaluate their behavior for application in GBR.The membranes were characterised by FTIR,DSC,TGA,tensile strength analysis,and in vitro biological assays.Cross-linked membranes exhibited improved mechanical strength(~5 MPa)and slower degradation(~43%mass loss over 30 days),while non-cross-linked membranes disintegrated more rapidly.Cytotoxicity assays using GM07492 fibroblasts confirmed biocompatibility,and cell migration studies demonstrated effective barrier function.These results indicated that zein membranes,particularly in their cross-linked form,combine biodegradability,mechanical integrity,and cellular safety,suggesting significant potential as sustainable GBR materials.This work introduces,for the first time,zein membranes prepared from corn crude extract for GBR in dentistry,paving the way for eco-friendly alternatives to animal-derived products.展开更多
Spinal cord injury is a severe neurological condition characterized by the permanent loss of nerve cell function and a failure in neural circuit reconstruction-key factors contributing to disability.Therefore,explorin...Spinal cord injury is a severe neurological condition characterized by the permanent loss of nerve cell function and a failure in neural circuit reconstruction-key factors contributing to disability.Therefore,exploring effective strategies to promote the repair and regeneration of nerve cells after spinal cord injury is crucial for optimizing patient prognosis.The purpose of this paper is to conduct an in-depth review of the pathological changes in nerve cells after spinal cord injury and to present the state of research on the role of exercise training in promoting the repair and regeneration of nerve cells after spinal cord injury.In terms of the intrinsic growth capacity of neurons,disruptions in the dynamic balance between growth cones and the cytoskeleton,the dysregulation of transcription factors,abnormal protein signaling transduction,and altered epigenetic modifications collectively hinder axonal regeneration.Additionally,the microenvironment of neurons undergoes a series of complex changes,initially manifesting as edema,which may be exacerbated by spinal cord ischemia-reperfusion injury,further increasing the extent of nerve cell damage.The abnormal proliferation of astrocytes leads to the formation of glial scars,creating a physical barrier to nerve regeneration.The inflammatory response triggered by the excessive activation of microglia negatively impacts the process of nerve repair.Non-invasive interventions involving exercise training have shown significant potential in promoting nerve repair as part of a comprehensive treatment strategy for spinal cord injury.Specifically,exercise training can reshape the growth cone and cytoskeletal structures of neurons,regulate transcription factor activity,modulate protein signaling pathways,and influence epigenetic modifications,thereby activating the intrinsic repair mechanisms of neurons.Moreover,exercise training can regulate the activation state of astrocytes,optimize the inflammatory response and metabolic processes,promote astrocyte polarization,enhance angiogenesis,reduce glial scar formation,and modulate the expression levels of nerve growth factors.It also effectively helps regulate microglial activation,promotes axonal regeneration,and improves phagocytic function,thereby optimizing the microenvironment for nerve repair.In terms of clinical translation,we summarize the preliminary results of new drug research and development efforts,the development of innovative devices,and the use of exercise training in promoting clinical advancements in nerve repair following spinal cord injury,while considering their limitations and future application prospects.In summary,this review systematically analyzes findings relating to the pathological changes occurring in nerve cells after spinal cord injury and emphasizes the critical role of exercise training in facilitating the repair and regeneration of nerve cells.This work is expected to provide new ideas and methods for the rehabilitation of patients with spinal cord injury.展开更多
The growing volume of end-of-life lithium-ion batteries(LIBs)represents both an urgent environmental challenge and a critical resource opportunity,especially for cathode materials.Among commercial cathodes,LiFePO4(LFP...The growing volume of end-of-life lithium-ion batteries(LIBs)represents both an urgent environmental challenge and a critical resource opportunity,especially for cathode materials.Among commercial cathodes,LiFePO4(LFP)dominates the market due to its favorable properties;thus,a substantial amount of LFP cathode materials is expected to retire in the near future.The conventional hydrometallurgical method suffers from high costs and serious pollution.Direct regeneration technologies,especially solid-state sintering,provide a more efficient and environmentally benign alternative by repairing cathode structures through high-temperature solid-phase reactions without extra chemical reagents.Traditional solid-state sintering faces challenges in processing spent LFP from diverse sources,struggling to achieve the homogenization of physical–chemical properties and electrochemical performance.To address the limitations above,phase homogenization with a lattice reconstruction strategy has been investigated,which can enable effective lattice reconstruction and microstructural homogenization,demonstrating robust adaptability to spent samples from variable sources.This review systematically summarizes the mechanisms,detailed steps,characterization techniques,and advances in pre-oxidation optimization(including ion-doping and coated carbon layer modification),as well as future research directions for sustainable LFP recycling.Given this,this review is expected to offer theoretical guidance for achieving homogeneous regeneration of LFP cathode.展开更多
基金supported by the National Natural Science Foundation of China,82471345(to LC)the Key Research and Development Program for Social Development by the Jiangsu Provincial Department of Science and Technology.No.BE2022668(to LC).
文摘Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a stroke.Their dynamic activation and polarization states are key factors that influence the disease process and treatment outcomes.This review article investigates the role of microglia in ischemic stroke and explores potential intervention strategies.Microglia exhibit a dynamic functional state,transitioning between pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.This duality is crucial in ischemic stroke,as it maintains a balance between neuroinflammation and tissue repair.Activated microglia contribute to neuroinflammation through cytokine release and disruption of the blood-brain barrier,while simultaneously promoting tissue repair through anti-inflammatory responses and regeneration.Key pathways influencing microglial activation include Toll-like receptor 4/nuclear factor kappa B,mitogen-activated protein kinases,Janus kinase/signal transducer and activator of transcription,and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways.These pathways are targets for various experimental therapies aimed at promoting M2 polarization and mitigating damage.Potential therapeutic agents include natural compounds found in drugs such as minocycline,as well as traditional Chinese medicines.Drugs that target these regulatory mechanisms,such as small molecule inhibitors and components of traditional Chinese medicines,along with emerging technologies such as single-cell RNA sequencing and spatial transcriptomics,offer new therapeutic strategies and clinical translational potential for ischemic stroke.
基金supported by the National Natural Science Foundation of China,Nos.82071383,82371392(to BN)the Natural Science Foundation of Shandong Province of China(Key Project),No.ZR2020KH007(to BN)+1 种基金“Taishan Scholar Distinguished Expert Program”of Shandong Province,No.tstp20231257(to BN)Health Commission Science and Technology Plan Project of Jinan,No.2023-1-8(to YZ).
文摘Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications with metabolic reprogramming.Nonetheless,the specific mechanisms and roles of this connection in astrocytes remain unclear.Therefore,this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system.The close relationship between epigenetic modifications and metabolic reprogramming was discussed.Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases.In the nervous system,lactate plays an essential role.However,its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation.The involvement of lactate in epigenetic modifications is currently a hot research topic,especially in lactylation modification,a key determinant in this process.Lactate also indirectly regulates various epigenetic modifications,such as N6-methyladenosine,acetylation,ubiquitination,and phosphorylation modifications,which are closely linked to several neurological disorders.In addition,exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.
基金supported by the National Research Foundation of Korea,Nos.2021R1A2C2006110,2021M3E5D9021364,2019R1A5A2026045(to BGK)the Korea Initiative for Fostering University of Research and Innovation(KIURI)Program of the NRF funded by the MSIT(to HK),No.NRF2021M3H1A104892211(to HSK)。
文摘Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.
基金supported by the National Natural Science Foundation of China,Nos.82174496(to NW),82374574(to NW),82302865(to LL)Shanghai Science and Technology Committee Sailing Program,Nos.23YF1403800(to LL),23YF1405200(to YX)Shanghai Hospital Development Center Foundation-Shanghai Municipal Hospital Rehabilitation Medicine Specialty Alliance,No.SHDC22023304(to YW).
文摘Stroke remains a leading cause of death and disability worldwide,and electroacupuncture has a long history of use in stroke treatment.This meta-analysis and systematic review aimed to evaluate the efficacy of electroacupuncture and explore its potential mechanisms in animal models of ischemic stroke.The PubMed,EMBASE,Web of Science,CENTRAL,and CINAHL databases were comprehensively searched up to May 1,2024.This review included articles on preclinical investigations of the efficacy and mechanisms of electroacupuncture in treating ischemic stroke.Data from 70 eligible studies were analyzed in Stata 18.0,using a random-effects model to calculate the standardized mean difference(Hedge’s g).The risk of bias was assessed using RevMan 5.4 software,and the quality of evidence was rated according to the Grading of Recommendations,Assessment,Development,and Evaluation(GRADE)system.Subgroup analyses were conducted to test the consistency of the results and sensitivity analyses were used to assess their robustness.The quality assessment revealed that most studies adequately handled incomplete data and selective reporting.However,several methodological limitations were identified:only 4 studies demonstrated a low risk of allocation concealment,26 achieved a low risk of outcome assessment bias,and 9 had a high risk of randomization bias.Additionally,there was an unclear risk regarding participant blinding and other methodological aspects.The GRADE assessment rated 12 outcomes as moderate quality and 6 as low quality.The mechanisms of electroacupuncture treatment for ischemic stroke can be categorized as five primary pathways:(1)Electroacupuncture significantly reduced infarct volume and apoptotic cell death(P<0.01)in ischemic stroke models;(2)electroacupuncture significantly decreased the levels of pro-inflammatory factors(P<0.01)while increasing the levels of anti-inflammatory factors(P=0.02);(3)electroacupuncture reduced the levels of oxidative stress indicators(P<0.01)and enhanced the expression of antioxidant enzymes(P<0.01);(4)electroacupuncture significantly promoted nerve regeneration(P<0.01);and(5)electroacupuncture influenced blood flow remodeling(P<0.01)and angiogenesis(P<0.01).Subgroup analyses indicated that electroacupuncture was most effective in the transient middle cerebral artery occlusion model(P<0.01)and in post-middle cerebral artery occlusion intervention(P<0.01).Dispersive waves were found to outperform continuous waves with respect to neuroprotection and anti-inflammatory effects(P<0.01),while scalp acupoints demonstrated greater efficacy than body acupoints(P<0.01).The heterogeneity among the included studies was minimal,and sensitivity analyses indicated stable results.Their methodological quality was generally satisfactory.In conclusion,electroacupuncture is effective in treating cerebral ischemia by modulating cell apoptosis,oxidative stress,inflammation,stroke-induced nerve regeneration,blood flow remodeling,and angiogenesis.The efficacy of electroacupuncture may be influenced by factors such as the middle cerebral artery occlusion model,the timing of intervention onset,waveform,and acupoint selection.Despite the moderate to low quality of evidence,these findings suggest that electroacupuncture has clinical potential for improving outcomes in ischemic stroke.
基金supported by the National Natural Science Foundation of China,Nos.32271389,31900987(both to PY)the Natural Science Foundation of Jiangsu Province,No.BK20230608(to JJ)。
文摘Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.
基金supported by STI2030-Major Project,No,2021ZD0204200(to LX).
文摘Neurodegenerative diseases,which are characterized by progressive neuronal loss and the lack of disease-modifying therapies,are becoming a major global health challenge.The existing neuromodulation techniques,such as deep brain stimulation and transcranial magnetic stimulation,show limitations such as invasiveness,restricted cortical targeting,and irreversible tissue effects.In this context,low-intensity transcranial ultrasound has emerged as a promising noninvasive alternative that can penetrate deep into the brain and modulate neuroplasticity.This review comprehensively assesses the therapeutic mechanisms,efficacy,and translational potential of low-intensity transcranial ultrasound in treating neurodegenerative diseases,with emphasis on its role in promoting neuronal regeneration,modulating neuroinflammation,and enhancing functional recovery.We summarize the findings of previous studies and systematically illustrate the potential of low-intensity transcranial ultrasound in regulating cell death mechanisms,enhancing neural repair and regeneration,and alleviating symptoms associated with neurodegenerative diseases.Preclinical findings indicate that low-intensity transcranial ultrasound can enhance the release of neurotrophic factors(e.g.,brain-derived neurotrophic factor),promote autophagy to clear protein aggregates,modulate microglial activation,and temporarily open the blood-brain barrier to facilitate targeted drug delivery.Existing clinical trial data show that low-intensity transcranial ultrasound can reduce amyloid-βplaques,improve motor and cognitive deficits,and promote remyelination in various disease models.Early clinical trials suggest that low-intensity transcranial ultrasound may enhance cognitive scores in Alzheimer’s disease and alleviate motor symptoms in Parkinson’s disease,all while demonstrating a favorable safety profile.Past studies support the notion that by integrating safety,precision,and reversibility,low-intensity transcranial ultrasound can transform the treatment landscape for neurodegenerative disease.However,more advancements are necessary for future clinical application of low-intensity transcranial ultrasound,including optimizing parameters such as frequency,intensity,and duty cycle;considering individual anatomical differences;and confirming long-term efficacy.We believe establishing standardized protocols,conducting larger trials,and investigating the underlying mechanisms to clarify dose-response relationships and refine personalized application strategies are essential in this regard.Future research should focus on translating preclinical findings into clinical practice,addressing technical challenges,and exploring combination therapies with pharmacological or gene interventions.
基金Supported by Basic Scientific Research Project of the Liaoning Provincial Department of Education Has Been Unveiled to Facilitate Local Project Funding (JYTMS20230835)Enhanced Scientific Research Project Funded by the Departmentof Higher Education in Liaoning Province (General program)(JYTMS20230852)。
文摘The adsorptive denitrification performance of MIL-101(Cr)-0.5 toward pyridine,aniline or quinoline in simulated fuels with basic nitrogen content of 1732μg/g was evaluated separately.Furthermore,the effects of adsorption temperature,adsorption time and adsorbent dosage on their adsorptive denitrification performance were systematically investigated.The experimental results demonstrated that under a fixed adsorbent dosage of 0.05 g and a simulated fuel volume of 10 mL,the optimal removal efficiency for aniline was achieved at 30℃ within 30 min,whereas higher temperatures and longer times(40℃and 40 min)were required for effective removal of pyridine and quinoline.Density Functional Theory(DFT)calculations were conducted via Materials Studio(MS)software to study the adsorptive denitrification mechanism of MIL-101(Cr)toward these three basic nitrogen-containing compounds.The simulation calculation results revealed that the interaction between pyridine and MIL-101(Cr)primarily involved coordination adsorption.In contrast,the interaction between aniline or quinoline and MIL-101(Cr)proceeded mainly through coordination,with additional contributions fromπ-complexation and hydrogen bonding.The overall adsorption strength order is pyridine>aniline>quinoline.During the adsorption process,pyridine and quinoline transfer electrons to the MIL-101(Cr)surface through the H→C→N→Cr^(3+)pathway,while aniline transfers electrons to the MIL-101(Cr)surface through various pathways,including N→Cr^(3+),N→C→Cr^(3+)and N→H→O.Furthermore,adsorption kinetics studies indicated that the adsorption processes for all three basic nitrogen-containing compounds followed the quasi second order kinetic models.The experimental results on the effect of benzene on the adsorptive denitrification performance of MIL-101(Cr)-0.5 demonstrated that benzene exerted a more significant impact on the adsorption of aniline and quinoline.Finally,the adsorbent was regenerated using ethanol washing.It was found that MIL-101(Cr)-0.5 retained stable denitrification performance after two regeneration cycles.
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supported by the National Natural Science Foundation of China,Nos.82471107,31970930(both to KY)the National Key Research and Development Program of China,No.2024YFA1108701(to KY)+1 种基金the Natural Science Foundation of Hubei Province,Nos.2020CFA069(to KY),2018CFB434(to KY),2025AFB042(to HQ)the Neuroscience Team Development Project of Wuhan University of Science and Technology,Nos.1180002,1180030(both to KY)。
文摘Voltage-gated sodium channels are essential ionic-conductance pathways in the nervous system,which play an irreplaceable role in modulating neuronal excitability and signal transduction.This review comprehensively analyzes the molecular mechanisms and pathophysiological significance of voltage-gated sodium channels,with particular emphasis on elucidating the molecular-action mechanisms of the distinct subtypes of these channels,including Nav1.1,Nav1.2,and Nav1.6,across various neurological disorders such as familial hemiplegic migraine,epilepsy,autism spectrum disorder,and retinal dysfunction.This review also provides a comprehensive overview of the pathogenic mechanisms associated with voltage-gated sodium channels,and systematically clarifies the evolutionary pathway of treatment strategies from conventional to innovative approaches.It analyzes two major categories of conventional sodium channel blockers and their applications:antiepileptic drugs(such as carbamazepine,lamotrigine,and phenytoin)and antiarrhythmic drugs(such as lidocaine,flecainide,and quinidine).However,these conventional blockers show limitations because of the lack of selectivity,driving research toward more precise therapeutic directions.Additionally,this review evaluates gabapentin,cannabidiol,and calcium channel blockers with different mechanisms of action.These drugs modulate neuronal excitability from multiple perspectives,providing diverse options for symptom relief.This review also highlights advances in gene therapy for specific diseases,such as STK-001,which promotes effective splicing of the sodium channel voltage-gated type 1 alpha subunit(SCN1A)gene,and ETX101,which utilizes adeno-associated virus 9 vectors to deliver engineered transcription factors.These two agents provide targeted therapeutic solutions for Dravet syndrome.Furthermore,this review summarizes some innovative therapeutic agents in clinical trials,including PRAX-222(for SCN2A gain-offunction mutation-related epilepsy),which has received Food and Drug Administration orphan drug designation,and the selective Nav1.6 inhibitor NBI-921352(for SCN8A-related epilepsy).Collectively,this review comprehensively compares the advantages and disadvantages of conventional drugs and gene therapy and envisions future treatment strategies that integrate the strengths of both approaches,facilitating personalized precision medicine to provide more accurate and effective treatment options for patients with ion channel diseases.
文摘Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability. Even without apparent inflammation, injury sites are associated with increased inflammatory markers. This review focuses on how it might be possible to reduce neuropathic pain by reducing inflammation. Physiologically, pain is resolved by a combination of the out-migration of pro-inflammatory cells from the injury site, the down-regulation of the genes underlying the inflammation, up-regulating genes for anti-inflammatory mediators, and reducing nociceptive neuron hyperexcitability. While various techniques reduce chronic neuropathic pain, the best are effective on < 50% of patients, no technique reliably or permanently eliminates neuropathic pain. This is because most techniques are predominantly aimed at reducing pain, not inflammation. In addition, while single factors reduce pain, increasing evidence indicates significant and longer-lasting pain relief requires multiple factors acting simultaneously. Therefore, it is not surprising that extensive data indicate that the application of platelet-rich plasma provides more significant and longer-lasting pain suppression than other techniques, although its analgesia is neither complete nor permanent. However, several case reports indicate that platelet-rich plasma can induce permanent neuropathic pain elimination when the platelet concentration is significantly increased and is applied to longer nerve lengths. This review examines the primary triggers of the development and maintenance of neuropathic pain and techniques that reduce chronic neuropathic pain. The application of plateletrich plasma holds great promise for providing complete and permanent chronic neuropathic pain elimination.
基金National Natural Science Foundation of China,Nos.82260279,31960169the Natural Science Foundation of Jiangxi Province,Nos.20202ACB206002,20213BCJ22057a grant from School of Basic Medical Sciences,Nanchang University。
文摘Recent studies have found that the suppression of phosphatase and tensin homolog is one of the most effective single-gene approaches for promoting optic nerve regeneration.This effect is primarily mediated through the activation of the protein kinase B/phosphoinositide 3-kinase/mammalian target of rapamycin signaling pathway.The purpose of this article is to elucidate how the downregulation of phosphatase and tensin homolog is involved in each key phase of optic nerve regeneration and to summarize the potential targets for therapeutic interventions in this process.Optic nerve regeneration progresses through five phases:stress response,growth navigation,nerve regeneration,synaptic reconstruction,and remyelination.During the stress response phase,the suppression of phosphatase and tensin homolog enhances the survival of retinal ganglion cells and promotes the proliferation of microglia.In the nerve regeneration phase,reduced levels of phosphatase and tensin homolog facilitate mitochondrial transport,while inhibition of the phosphatase and tensin homolog-L isoform specifically promotes mitophagy.During the synaptic reconstruction phase,the deletion of phosphatase and tensin homolog modulates the synthesis of axon extension-related proteins and stabilizes microglial microtubules,thereby accele rating the clearance of damaged synapses and the fo rmation of new ones.During the remyelination phase,the knockout of phosphatase and tensin homolog promotes the proliferation of oligodendrocyte progenitor cells and the diffe rentiation of oligodendrocytes,relieving myelination obstruction.This paper also discusses current strategies and translational challenges for neuron-specific inhibition of phosphatase and tensin homolog,including off-ta rget effects,delive ry precisio n,and long-term safety.By integrating molecular insights with emerging bioengineering approaches,this paper provides a framework for develo ping targeted therapies for optic nerve regeneration and broader applications in the field of central nervous system regeneration.
基金financially supported by the National Key Research and Development Program of China(Nos.2023YFC3904800)the National Outstanding Young Scientists Fund(No.52125002)+6 种基金the National Science Foundation of China(No.22476073 and U24A20194)the Key Project of Jiangxi Provincial Research and Development Program(Nos.20223BBG74006and 20243BBI91001)the Jiangsu Special Fund on Technology Innovation of Carbon Dioxide Peaking and Carbon Neutrality(No.BT2024011)the China Postdoctoral Science Foundation(Nos.2024M751282 and 2025T180353)the“Thousand Talents Program”of Jiangxi Province(S2021GDQN2161)the Key Project of Ganzhou City Research and Development Program(No.2023PGX17350)the Key Laboratory of Jiangxi Province for Functional Biology and Pollution Control in Red Soil Regions(No.2023SSY02051)。
文摘Recovering LiFePO_(4) extraction slag(LES)-the FePO_(4)-rich residue formed after Li leaching from spent LiFePO_(4)-has become pivotal to minimizing resource losses,mitigating environmental risks,and advancing circularity in lithium-ion battery value chains.However,integrative frameworks that link closed-loop routes(returning to battery precursors/cathodes)with non-closed-loop upcycling are still limited,constraining process optimization and scale-up.This review synthesizes current progress in LES recycling with emphasis on maximizing recovery efficiency and product value.In closed-loop pathways,hydrometallurgical purification removes impurities to yield battery-grade FePO_(4) as an LiFePO_(4) precursor,while direct relithiation(e.g.,solid-state sintering aided by Li sources and reductants)restores Li and reduces Fe^(3+)to Fe^(2+),thereby regenerating LiFePO_(4) cathodes from LES.In non-closed-loop pathways,compositionally guided upcycling converts LES into advanced materials(e.g.,high-performance electrodes,highcapacity adsorbents),thereby broadening the techno-economic value propositions.We also distill lessons from early industrial practice,identifying constraints arising from feedstock variability,energy-cost coupling(thermal/chemical utilities),and product-quality assurance(battery-grade specifications).Finally,we map research directions-including data-driven feed characterization and process control,defecthealing relithiation strategies and interfacial engineering,quality grading and market pathways,and multi-scenario deployment-to enhance the technical and economic sustainability of LES recycling and accelerate its contribution to a circular battery economy.
基金supported by the National Natural Science Foundation of China(22478266 and 32472027)the National Key Research&Development Program of China(2022YFE0207100)the Department of Science and Technology of Sichuan Province(2024ZYD0080 and 2022YFN0027).
文摘Economical and sustainable wastewater treatment techniques are highly demanded to alleviate the issues of clearwater scarcity globally.In this work,the acetic acid/H_(2)O_(2) (AHP) was leveraged to enrich oxygenated functional groups on the biochar surface for efficient ciprofloxacin (CIP) adsorption and biochar regeneration (In situ degradation of CIP in the spent AHP solution).The AHP-modified biochar exhibited significantly enhanced CIP adsorption capacity,about 22 times that of the pristine biochar.The optimized modification condition (acetic acid/H_(2)O_(2):2.11,temperature:45 ℃,and time:12 h) was screened by the response surface method,reaching the highest CIP adsorption capacity of 86.26 mg·g^(−1).Characterization results revealed that the content of carboxyl —C=O—O was enhanced in AHP-modified biochar,which contributed to efficient CIP adsorption by the electrostatic interaction,hydrogen bonding,and hydrophobic interaction.The adsorption of modified biochar to CIP molecules was a spontaneous endothermic process,and in line with the pseudo-second-order model and the Langmuir isotherm model.Moreover,the biochar modification process enabled the spent AHP solution with a strong oxidizing agent of peracetic acid (PAA),which can be employed to degrade adsorbed CIP for biochar in-situ generation.This work tailored a closed-loop strategy for biochar oxidation,contaminant adsorption,and biochar regeneration,highlighting a viable route for sustainable wastewater treatment.
基金supported by Yunnan Fundamental Research Projects(No.202301BE070001-056)Yunnan Major Scientific and Technological Projects(No.202202AG050019)+2 种基金the National Key Research and Development Program of China(No.2023YFC3906003)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(No.2021044)Beijing Nova Program(No.2024072).
文摘A novel faujasite(FAU) type zeolitized ceramsite(FZC) was prepared via a novel three dimensional(3D) in-pore growth method.FZC is a centimeter sized spherical particle with a 3-dimensional radial morphology inside,with a specific surface area and pore volume 6 and 30 times that of the original ceramsite,respectively.The unique structure was constructed through electrostatic and polymerization interactions between hexadecyl trimethyl ammonium bromide(CTAB) micelles,ceramic pore walls and silicate aluminate ions,which could simultaneously improve adsorption capacity and mass transfer,endowing FZC with excellent heavy metal adsorption properties.FZC-50 could remove the majority of Cu and Zn from solution within shorter periods(73.3 % and 80.0 %of original ceramsite,respectively) with larger adsorption capacities(340 % and 370 % of original ceramsite,respectively).Theoretical analysis and regeneration experiments both indicate that the adsorption of Cu(Ⅱ) and Zn(Ⅱ) on FZC-50 is dominated by ion exchange.And the spent sorbent can be effectively regenerated by NaCl,and the cycle number is expected to be 33 and 26 times for Cu(Ⅱ) and Zn(Ⅱ) adsorption,respectively.This work proposed a novel synthesis route to construct a 3D multi-stage porous zeolite inside ceramsite,and opened up new ideas for the further development of zeolitized ceramsite.
文摘Design concept Design Theme Color is not only a visual grammar but also a symbolic language of the spirit.This series,“In the Name of Color,”explores three states of the female inner world:awakening in chaos,order in return,and regeneration in flow.The works—Eye of the Storm,Back to the Seed,and Source—form a stream-of-consciousness journey from within to without.Based on the COLORO color system,the series is constructed through hue,chroma,lightness,and domain ratio,treating color as both emotional force and symbolic medium.
文摘Wound management continues to present major clinical challenges,often necessitating therapeutic strategies that extend beyond conventional dressings,which provide only passive protection.Magnesium(Mg),a biologically indispensable element,has attracted considerable attention for its multifaceted role in wound repair,including modulation of inflammatory responses,stimulation of fibroblast and keratinocyte proliferation,promotion of angiogenesis,and enhancement of collagen synthesis.However,the direct application of Mg formulations is limited by uncontrolled Mg ion(Mg^(2+))release,localized cytotoxicity at elevated concentrations,and inadequate mechanical stability at the wound site.To address these challenges,Mg-incorporated polymeric scaffolds have been developed as advanced delivery platforms.These systems integrate the regenerative capacity of Mg with the tunable properties of polymers,enabling controlled degradation,mechanical reinforcement,and sustained Mg^(2+)release to establish a favorable microenvironment for tissue repair.This review critically examines the role of Mg in wound healing and the effectiveness of polymeric matrices for controlled Mg^(2+)delivery.It further provides a comprehensive evaluation of recent advances in Mg-incorporated polymeric scaffolds,including nanofibers,hydrogels,and sponges,with emphasis on fabrication strategies,structural characteristics,and therapeutic efficacy.Key challenges,such as optimizing ion release kinetics,enhancing scaffold stability,and facilitating clinical translation,are also discussed.Collectively,this work underscores the potential of Mg-polymeric scaffolds as a next-generation platform for advanced wound care and highlights perspectives for future research and development.
文摘Bone Research is an open access,fully peer-reviewed journal publishing the foremost progress and novel understanding of all aspects of bone science.The journal highlights the breakthrough discoveries in basic and clinical aspects of bone biology,pathophysiology and regeneration,as well as other significant findings related to bone.
基金funded by São Paulo Research Foundation,FAPESP[research project funding 2019-25318-0 and 2017-18782-6]Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq,grant number 305518/2023-2.
文摘Materials from natural sources have been studied to replace the conventional synthetic or animal-derived products as a safer alternative to be used in the healthcare field.In dentistry,guided bone regeneration(GBR)relies on barrier membranes,predominantly from animals or synthetic materials,to improve osteogenesis by avoiding undesired soft tissue cells from defect sites.In this study,membranes were prepared from zein,a corn-derived protein,using a simple extraction and casting method,followed by optional formaldehyde cross-linking to evaluate their behavior for application in GBR.The membranes were characterised by FTIR,DSC,TGA,tensile strength analysis,and in vitro biological assays.Cross-linked membranes exhibited improved mechanical strength(~5 MPa)and slower degradation(~43%mass loss over 30 days),while non-cross-linked membranes disintegrated more rapidly.Cytotoxicity assays using GM07492 fibroblasts confirmed biocompatibility,and cell migration studies demonstrated effective barrier function.These results indicated that zein membranes,particularly in their cross-linked form,combine biodegradability,mechanical integrity,and cellular safety,suggesting significant potential as sustainable GBR materials.This work introduces,for the first time,zein membranes prepared from corn crude extract for GBR in dentistry,paving the way for eco-friendly alternatives to animal-derived products.
基金supported by the National Natural Science Foundation of China,No.81641048Research Project of Yan’an University,No.2023JBZR-011(both to LZ).
文摘Spinal cord injury is a severe neurological condition characterized by the permanent loss of nerve cell function and a failure in neural circuit reconstruction-key factors contributing to disability.Therefore,exploring effective strategies to promote the repair and regeneration of nerve cells after spinal cord injury is crucial for optimizing patient prognosis.The purpose of this paper is to conduct an in-depth review of the pathological changes in nerve cells after spinal cord injury and to present the state of research on the role of exercise training in promoting the repair and regeneration of nerve cells after spinal cord injury.In terms of the intrinsic growth capacity of neurons,disruptions in the dynamic balance between growth cones and the cytoskeleton,the dysregulation of transcription factors,abnormal protein signaling transduction,and altered epigenetic modifications collectively hinder axonal regeneration.Additionally,the microenvironment of neurons undergoes a series of complex changes,initially manifesting as edema,which may be exacerbated by spinal cord ischemia-reperfusion injury,further increasing the extent of nerve cell damage.The abnormal proliferation of astrocytes leads to the formation of glial scars,creating a physical barrier to nerve regeneration.The inflammatory response triggered by the excessive activation of microglia negatively impacts the process of nerve repair.Non-invasive interventions involving exercise training have shown significant potential in promoting nerve repair as part of a comprehensive treatment strategy for spinal cord injury.Specifically,exercise training can reshape the growth cone and cytoskeletal structures of neurons,regulate transcription factor activity,modulate protein signaling pathways,and influence epigenetic modifications,thereby activating the intrinsic repair mechanisms of neurons.Moreover,exercise training can regulate the activation state of astrocytes,optimize the inflammatory response and metabolic processes,promote astrocyte polarization,enhance angiogenesis,reduce glial scar formation,and modulate the expression levels of nerve growth factors.It also effectively helps regulate microglial activation,promotes axonal regeneration,and improves phagocytic function,thereby optimizing the microenvironment for nerve repair.In terms of clinical translation,we summarize the preliminary results of new drug research and development efforts,the development of innovative devices,and the use of exercise training in promoting clinical advancements in nerve repair following spinal cord injury,while considering their limitations and future application prospects.In summary,this review systematically analyzes findings relating to the pathological changes occurring in nerve cells after spinal cord injury and emphasizes the critical role of exercise training in facilitating the repair and regeneration of nerve cells.This work is expected to provide new ideas and methods for the rehabilitation of patients with spinal cord injury.
基金financially supported by National Natural Science Key Foundation of China(52534010)National Natural Science Foundation of China(52374288,52204298)+2 种基金Young Elite Scientists Sponsorship Program by China Association for Science and Technology(2022QNRC001)National Key Research and Development Program of China(2022YFC3900805-4/7)Collaborative Innovation Centre for Clean and Efficient Utilization of Strategic Metal Mineral Resources,Found of State Key Laboratory of Mineral Processing(BGRIMM-KJSKL-2017-13).
文摘The growing volume of end-of-life lithium-ion batteries(LIBs)represents both an urgent environmental challenge and a critical resource opportunity,especially for cathode materials.Among commercial cathodes,LiFePO4(LFP)dominates the market due to its favorable properties;thus,a substantial amount of LFP cathode materials is expected to retire in the near future.The conventional hydrometallurgical method suffers from high costs and serious pollution.Direct regeneration technologies,especially solid-state sintering,provide a more efficient and environmentally benign alternative by repairing cathode structures through high-temperature solid-phase reactions without extra chemical reagents.Traditional solid-state sintering faces challenges in processing spent LFP from diverse sources,struggling to achieve the homogenization of physical–chemical properties and electrochemical performance.To address the limitations above,phase homogenization with a lattice reconstruction strategy has been investigated,which can enable effective lattice reconstruction and microstructural homogenization,demonstrating robust adaptability to spent samples from variable sources.This review systematically summarizes the mechanisms,detailed steps,characterization techniques,and advances in pre-oxidation optimization(including ion-doping and coated carbon layer modification),as well as future research directions for sustainable LFP recycling.Given this,this review is expected to offer theoretical guidance for achieving homogeneous regeneration of LFP cathode.
