A low-molecular-weight polylactide-poly(butylene succinate)(PLA-PBS)copolymer was synthesized and incorporated into polylactide(PLA)as a novel toughening agent by solvent casting.The copolymer had the same chemical st...A low-molecular-weight polylactide-poly(butylene succinate)(PLA-PBS)copolymer was synthesized and incorporated into polylactide(PLA)as a novel toughening agent by solvent casting.The copolymer had the same chemical structure and function as PLA and it was used as a plasticizer to PLA.The copolymer was blended with PLA at a weight ratio from 2 to 10 wt%.Phase separation between PLA and PLA-PBS was not observed from their scanning electron microscopy(SEM)images and the crystal structure of PLA almost remained unchanged based on the X-ray diffraction(XRD)measurement.The melt flow index(MFI)of the blends was higher as the amount of PLA-PBS increased,indicating that the block copolymer did improve the mobility of the PLA chains.Moreover,tensile tests revealed that PLA with greater PLA-PBS copolymer exhibited higher elongation at break and it reached the maximum at 8 wt%of PLA-PBS in PLA,which was around 6 times higher than that of pure PLA.Furthermore,the glass transition temperature,measured by differential scanning calorimetry(DSC),markedly decreased with an increasing amount of the copolymer as it decreased from 61.2℃ for pure PLA to 41.3℃when it was blended with 10 wt%PLA-PBS copolymer.Therefore,the PLA-PBS copolymer was shown to be a promising plasticizer for fully biobased and toughened PLA.展开更多
In this study,as the plasticizer,Camellia oleifera seed-oil-based cyclohexyl ester(COSOCE)was prepared by the reaction of cyclohexene oxide and refined C.oleifera seed oil(RCOSO)obtained by acidification hydrolysis af...In this study,as the plasticizer,Camellia oleifera seed-oil-based cyclohexyl ester(COSOCE)was prepared by the reaction of cyclohexene oxide and refined C.oleifera seed oil(RCOSO)obtained by acidification hydrolysis after saponification.In addition,the structure of the target product was confirmed by Fourier transform infrared(FTIR)spectroscopy,nuclear magnetic resonance(NMR)spectroscopy,and Raman spectroscopy.COSOCE was used as plasticizer-modified polyvinyl chloride(PVC)membranes.The structure of the COSOCE-modified PVC membranes were characterized by Raman spectroscopy and scanning electron microscopy(SEM).The properties of the COSOCE-modified PVC membrane were characterized by contact angle measurements,universal testing machine,thermogravimetric analysis(TGA),and differential scanning calorimetry(DSC).The results revealed that(1)The COSOCE-modified PVC membranes exhibit a good microscopic morphology.Combined with energy-dispersive X-ray spectroscopy(EDS)and contact angle measurement results,the COSOCE-modified PVC membranes are confirmed to be a hydrophilic material.(2)The modified PVC membrane with 60%COSOCE exhibited the best mechanical properties.The tensile strength reached 23.56±2.94 MPa.(3)COSOCE-modified PVC material exhibited better thermal stability,with a loss rate of less than 75%at the end of the first decomposition stage.Compared with that of the dioctyl-phthalate(DOP)-modified PVC membrane,the initial decomposition temperature of PVC was increased by 1.17°C–8.17°C,and the residual rate was increased by 0.67%–5.75%.The carbon–carbon double bond in the COSOCE molecular structure can remove the free radicals generated during the degradation of PVC material and slow down the decomposition rate of PVC.In addition,the double bond can be cross-linked partially with the PVC molecular chain containing the conjugated polyene structure,thereby increasing the movement resistance of the PVC molecular chain segment.Hence,COSOCE can replace DOP as a PVC plasticizer.展开更多
Plasticizers are essential additives in the processing of polyvinyl chloride(PVC),with phthalate plasticizers being widely used.However,these conventional plasticizers have been shown to be harmful to human health and...Plasticizers are essential additives in the processing of polyvinyl chloride(PVC),with phthalate plasticizers being widely used.However,these conventional plasticizers have been shown to be harmful to human health and environmentally unfriendly,necessitating the exploration of eco-friendly bio-based alternatives.In this study,Camellia oleifera seed oil,a specialty resource in China,was utilized as a raw material and reacted with 4,4′-Methylenebis(N,N-diglycidylaniline)(AG-80)to synthesize Phenyl Camellia seed Oil Ester(PCSOE).PCSOE was employed as a plasticizer to prepare modified PVC films with varying concentrations,with the conventional plasticizer dioctyl phthalate(DOP)serving as a control.Experimental results demonstrate that PSCOE-plasticized PVC films exhibit enhanced hydrophilicity,tensile strength,and thermal stability compared to DOP-modified PVC films.The contact angle of PSCOE-plasticized PVC films ranges from 66.26°to 78.48°,which is generally lower than the contact angle of DOP-modified PVC films at 78.40°,indicating improved hydrophilicity due to the modification with PCSOE.The tensile strength of PSCOE-plasticized PVC films ranges from 17.73 to 20.17 MPa,all surpassing the value of 16.41 MPa for DOP-modified PVC films.Moreover,the temperatures corresponding to 5%,10%,and 50%weight loss for PVC samples modified with PCSOE are higher than those for DOP.Hence,PCSOE presents a viable alternative to DOP as a plasticizer for PVC materials.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
The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage.The latter involves gl...The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage.The latter involves global alterations,making understanding plastic responses triggered by local damage difficult.One key feature of the dentate gyrus is that it contains a well-defined neurogenic niche,the subgranular zone,and beyond neurogenesis,newly born granule cells may maintain a“young”phenotype throughout life,adding to the plastic nature of the structure.Here,we present a novel experimental model of local brain damage in organotypic entorhino-hippocampal cultures that results in the activation of adjacent newly born granule cells.A small piece of filter paper was placed on the surface of the granule cell layer of the dentate gyrus,which evoked a foreign body reaction of astrocytes,along with the activation of local young neurons expressing doublecortin.Forty-eight hours after foreign body placement,the number of doublecortin-immunoreactive cells increased in the subgranular zone in the direct vicinity of the foreign body,whereas overall increased doublecortin immunoreactivity was observed in the granule cell layer and molecular layer of the dentate gyrus.Foreign body placement in the pyramidal layer of the CA1 region evoked a comparable local astroglial reaction but did not lead to an increase in doublecortin-immunoreactive in either the CA1 region or the adjacent dentate gyrus.Seven days after foreign body placement in the dentate gyrus,the increase in doublecortin-immunoreactivity was no longer observed,indicating the transient activation of young cells.However,7 days after foreign body placement,the number of doublecortin-immunoreactive granule cells coimmunoreactive for calbindin was lower than that under the control conditions.As calbindin is a marker for mature granule cells,this result suggests that activated young cells remain at a more immature stage following foreign body placement.Live imaging of retrovirally green fluorescent protein-labeled newly born granule cells revealed the orientation and growth of their dendrites toward the foreign body placement.This novel experimental model of foreign body placement in organotypic entorhino-hippocampal cultures could serve as a valuable tool for studying both glial reactivity and neuronal plasticity,specifically of newly born neurons under controlled in vitro conditions.展开更多
Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinso...Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease,this plasticity is disrupted,leading to cognitive and motor deficits.This review explores the mechanisms of neuronal plasticity and its effect on Alzheimer's disease and Parkinson's disease.Alzheimer's disease features amyloid-beta plaques and tau tangles that impair synaptic function,while Parkinson's disease involves the loss of dopaminergic neurons affecting motor control.Enhancing neuronal plasticity offers therapeutic potential for these diseases.A systematic literature review was conducted using databases such as PubMed,Scopus,and Google Scholar,focusing on studies of neuronal plasticity in Alzheimer's disease and Parkinson's disease.Data synthesis identified key themes such as synaptic mechanisms,neurogenesis,and therapeutic strategies,linking molecular insights to clinical applications.Results highlight that targeting synaptic plasticity mechanisms,such as long-term potentiation and long-term depression,shows promise.Neurotrophic factors,advanced imaging techniques,and molecular tools(e.g.,clustered regularly interspaced short palindromic repeats and optogenetics)are crucial in understanding and enhancing plasticity.Current therapies,including dopamine replacement,deep brain stimulation,and lifestyle interventions,demonstrate the potential to alleviate symptoms and improve outcomes.In conclusion,enhancing neuronal plasticity through targeted therapies holds significant promise for treating neurodegenerative diseases.Future research should integrate multidisciplinary approaches to fully harness the therapeutic potential of neuronal plasticity in Alzheimer's disease and Parkinson's disease.展开更多
The capacity of the central nervous system for structural plasticity and regeneration is commonly believed to show a decreasing progression from“small and simple”brains to the larger,more complex brains of mammals.H...The capacity of the central nervous system for structural plasticity and regeneration is commonly believed to show a decreasing progression from“small and simple”brains to the larger,more complex brains of mammals.However,recent findings revealed that some forms of neural plasticity can show a reverse trend.Although plasticity is a well-preserved,transversal feature across the animal world,a variety of cell populations and mechanisms seem to have evolved to enable structural modifications to take place in widely different brains,likely as adaptations to selective pressures.Increasing evidence now indicates that a trade-off has occurred between regenerative(mostly stem cell–driven)plasticity and developmental(mostly juvenile)remodeling,with the latter primarily aimed not at brain repair but rather at“sculpting”the neural circuits based on experience.In particular,an evolutionary trade-off has occurred between neurogenic processes intended to support the possibility of recruiting new neurons throughout life and the different ways of obtaining new neurons,and between the different brain locations in which plasticity occurs.This review first briefly surveys the different types of plasticity and the complexity of their possible outcomes and then focuses on recent findings showing that the mammalian brain has a stem cell–independent integration of new neurons into pre-existing(mature)neural circuits.This process is still largely unknown but involves neuronal cells that have been blocked in arrested maturation since their embryonic origin(also termed“immature”or“dormant”neurons).These cells can then restart maturation throughout the animal's lifespan to become functional neurons in brain regions,such as the cerebral cortex and amygdala,that are relevant to high-order cognition and emotions.Unlike stem cell–driven postnatal/adult neurogenesis,which significantly decreases from small-brained,short-living species to large-brained ones,immature neurons are particularly abundant in large-brained,long-living mammals,including humans.The immature neural cell populations hosted in these complex brains are an interesting example of an“enlarged road”in the phylogenetic trend of plastic potential decreases commonly observed in the animal world.The topic of dormant neurons that covary with brain size and gyrencephaly represents a prospective turning point in the field of neuroplasticity,with important translational outcomes.These cells can represent a reservoir of undifferentiated neurons,potentially granting plasticity within the high-order circuits subserving the most sophisticated cognitive skills that are important in the growing brains of young,healthy individuals and are frequently affected by debilitating neurodevelopmental and degenerative disorders.展开更多
Regenerative capacity of the central nervous system(CNS)is unevenly distributed among vertebrates.While most mammalian species including humans elicit limited repair following CNS injury or disease,highly regenerative...Regenerative capacity of the central nervous system(CNS)is unevenly distributed among vertebrates.While most mammalian species including humans elicit limited repair following CNS injury or disease,highly regenerative vertebrates including urodele amphibians and teleost fish spontaneously reverse CNS damage.Teletost zebrafish(danio rerio)are tropical freshwater fish that proved to be an excellent vertebrate model of successful CNS regeneration.Differential neuronal,glial,and immune injury responses underlie disparate injury outcomes between highly regenerative zebrafish and poorly regenerative mammals.This article describes complications associated with neuronal repair following spinal cord injury(SCI)in poorly regenerative mammals and highlights intersecting modes of plasticity and regeneration in highly regenerative zebrafish(Figures 1 and 2).Comparative approaches evaluating immunoglial SCI responses were recently reviewed elsewhere(Reyes and Mokalled,2024).展开更多
Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglio...Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglion cells and their axons,leading to axonal transport dysfuntion,subsequently causing secondary damage to anterior or posterior ends of the visual system.Accordingly,recent evidence indicates that glaucoma is a degenerative disease of the central nervous system that causes damage throughout the visual pathway.However,the effects of glaucoma on synaptic plasticity in the primary visual cortex remain unclear.In this study,we established a mouse model of unilateral chronic ocular hypertension by injecting magnetic microbeads into the anterior chamber of one eye.We found that,after 4 weeks of chronic ocular hypertension,the neuronal somas were smaller in the superior colliculus and lateral geniculate body regions of the brain contralateral to the affected eye.This was accompanied by glial cell activation and increased expression of inflammatory factors.After 8 weeks of ocular hypertension,we observed a reduction in the number of excitatory and inhibitory synapses,dendritic spines,and activation of glial cells in the primary visual cortex contralateral to the affected eye.These findings suggest that glaucoma not only directly damages the retina but also induces alterations in synapses and dendritic spines in the primary visual cortex,providing new insights into the pathogenesis of glaucoma.展开更多
Immunotherapy has brought unprecedented breakthroughs to advanced malignant tumors,yet the immune microenvironment shaped by the tumor stroma has often been underestimated in the traditional focus on the“immune check...Immunotherapy has brought unprecedented breakthroughs to advanced malignant tumors,yet the immune microenvironment shaped by the tumor stroma has often been underestimated in the traditional focus on the“immune checkpoint-T cell”axis.Collagen not only constitutes a mechanical barrier that distinguishes between the periphery and core of solid tumors but also systematically remodels the orientation of metabolism,vasculature,and immune cell phenotypic plasticity through its spatial density,fiber arrangement,and crosslinking patterns(F igure 1)[1,2].Abundant evidence suggests that over-accumulated types I and III collagen drive CD8+T cell exhaustion,NK cell functional inhibition,and tumor-associated macrophage polarization through ligand-receptor networks involving LAIR-1,DDR2,andβ1/β3 integrins[3-6].Mechanistically,collagen engagement of LAIR-1 delivers inhibitory signals in effector lymphocytes,promoting dysfunctional or exhausted states[7-9].In parallel,collagen-β1/β3 integrin signaling activates mechanotransduction pathways(e.g.,FAK/SRC),reducing T-cell motility and immune-tumor contact,while DDR2 activation supports matrix-remodeling programs that limit lymphocyte trafficking.展开更多
The remodeling of axonal connections following injury is an important feature driving functional recovery.The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory ...The remodeling of axonal connections following injury is an important feature driving functional recovery.The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory fibers.While the reticulospinal tract has been shown to be particularly prone to axonal growth and plasticity following injuries of the spinal cord,the differential capacities of excitatory and inhibitory fibers for plasticity remain unclear.As adaptive axonal plasticity involves a sophisticated interplay between excitatory and inhibitory input,we investigated in this study the plastic potential of glutamatergic(vGlut2)and GABAergic(vGat)fibers originating from the gigantocellular nucleus and the lateral paragigantocellular nucleus,two nuclei important for locomotor function.Using a combination of viral tracing,chemogenetic silencing,and AI-based kinematic analysis,we investigated plasticity and its impact on functional recovery within the first 3 weeks following injury,a period prone to neuronal remodeling.We demonstrate that,in this time frame,while vGlut2-positive fibers within the gigantocellular and lateral paragigantocellular nuclei rewire significantly following cervical spinal cord injury,vGat-positive fibers are rather unresponsive to injury.We also show that the acute silencing of excitatory axonal fibers which rewire in response to lesions of the spinal cord triggers a worsening of the functional recovery.Using kinematic analysis,we also pinpoint the locomotion features associated with the gigantocellular nucleus or lateral paragigantocellular nucleus during functional recovery.Overall,our study increases the understanding of the role of the gigantocellular and lateral paragigantocellular nuclei during functional recovery following spinal cord injury.展开更多
The synergistic effect of low Gd+Mn additions on the evolution of microstructure and mechanical properties of Mg−xGd−0.8Mn alloy was investigated.Gd addition shows a strong grain refinement effect on the extruded Mg−x...The synergistic effect of low Gd+Mn additions on the evolution of microstructure and mechanical properties of Mg−xGd−0.8Mn alloy was investigated.Gd addition shows a strong grain refinement effect on the extruded Mg−xGd−0.8Mn alloy,and leads to a continuous decrease in the area fraction of basal texture grains and the corresponding maximum density of texture components.However,the maximum density of the basal texture components grows abruptly as Gd content increases to 6 wt.%.When the Gd content is below 6 wt.%,the asymmetry of the tensile and compressive yield of the alloy is negatively correlated to the Gd content due to grain refinement and texture weakening effects.Besides,the contribution of grain refinement to higher alloy yield strength is more significant than that of grain orientation.Compared with the extruded Mg−xGd alloy,the extruded Mg−xGd−0.8Mn alloy shows a lower limit composition point that corresponds to solid solution strengthening and plasticizing effect(2 wt.%and 4 wt.%).Finally,the trend of basal slip and prismatic slip resistance variations of the extruded Mg−xGd−0.8Mn alloys was predicted.展开更多
Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery ...Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.展开更多
The microstructural evolution of a cold-rolled and intercritical annealed medium-Mn steel(Fe-0.10C-5Mn)was investigated during uniaxial tensile testing.In-situ observations under scanning electron microscopy,transmiss...The microstructural evolution of a cold-rolled and intercritical annealed medium-Mn steel(Fe-0.10C-5Mn)was investigated during uniaxial tensile testing.In-situ observations under scanning electron microscopy,transmission electron microscopy,and X-ray diffraction analysis were conducted to characterize the progressive transformation-induced plasticity process and associated fracture initiation mechanisms.These findings were discussed with the local strain measurements via digital image correlation.The results indicated that Lüders band formation in the steel was limited to 1.5%strain,which was mainly due to the early-stage martensitic phase transformation of a very small amount of the less stable large-sized retained austenite(RA),which led to localized stress concentrations and strain hardening and further retardation of yielding.The small-sized RA exhibited high stability and progressively transformed into martensite and contributed to a stably extended Portevin-Le Chatelier effect.The volume fraction of RA gradually decreased from 26.8%to 8.2%prior to fracture.In the late deformation stage,fracture initiation primarily occurred at the austenite/martensite and ferrite/martensite interfaces and the ferrite phase.展开更多
Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at...Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.展开更多
Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically poor.We used a plasmalemmal fusogen,polyethylene g...Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically poor.We used a plasmalemmal fusogen,polyethylene glycol(PEG),to immediately fuse closely apposed open ends of severed proximal and distal axons in rat sciatic nerves.We have previously reported that sciatic nerve axons repaired by PEG-fusion do not undergo Wallerian degeneration,and PEG-fused animals exhibit rapid(within 2–6 weeks)and extensive locomotor recovery.Furthermore,our previous report showed that PEG-fusion of severed sciatic motor axons was non-specific,i.e.,spinal motoneurons in PEG-fused animals were found to project to appropriate as well as inappropriate target muscles.In this study,we examined the consequences of PEG-fusion for sensory axons of the sciatic nerve.Young adult male and female rats(Sprague–Dawley)received either a unilateral single cut or ablation injury to the sciatic nerve and subsequent repair with or without(Negative Control)the application of PEG.Compound action potentials recorded immediately after PEG-fusion repair confirmed conduction across the injury site.The success of PEG-fusion was confirmed through Sciatic Functional Index testing with PEG-fused animals showing improvement in locomotor function beginning at 35 days postoperatively.At 2–42 days postoperatively,we anterogradely labeled sensory afferents from the dorsal aspect of the hindpaw following bilateral intradermal injection of wheat germ agglutinin conjugated horseradish peroxidase.PEG-fusion repair reestablished axonal continuity.Compared to unoperated animals,labeled sensory afferents ipsilateral to the injury in PEG-fused animals were found in the appropriate area of the dorsal horn,as well as inappropriate mediolateral and rostrocaudal areas.Unexpectedly,despite having intact peripheral nerves,similar reorganizations of labeled sensory afferents were also observed contralateral to the injury and repair.This central reorganization may contribute to the improved behavioral recovery seen after PEG-fusion repair,supporting the use of this novel repair methodology over currently available treatments.展开更多
To better understand the migration behavior of plastic fragments in the environment,development of rapid non-destructive methods for in-situ identification and characterization of plastic fragments is necessary.Howeve...To better understand the migration behavior of plastic fragments in the environment,development of rapid non-destructive methods for in-situ identification and characterization of plastic fragments is necessary.However,most of the studies had focused only on colored plastic fragments,ignoring colorless plastic fragments and the effects of different environmental media(backgrounds),thus underestimating their abundance.To address this issue,the present study used near-infrared spectroscopy to compare the identification of colored and colorless plastic fragments based on partial least squares-discriminant analysis(PLS-DA),extreme gradient boost,support vector machine and random forest classifier.The effects of polymer color,type,thickness,and background on the plastic fragments classification were evaluated.PLS-DA presented the best and most stable outcome,with higher robustness and lower misclassification rate.All models frequently misinterpreted colorless plastic fragments and its background when the fragment thickness was less than 0.1mm.A two-stage modeling method,which first distinguishes the plastic types and then identifies colorless plastic fragments that had been misclassified as background,was proposed.The method presented an accuracy higher than 99%in different backgrounds.In summary,this study developed a novel method for rapid and synchronous identification of colored and colorless plastic fragments under complex environmental backgrounds.展开更多
The visual cortex is an essential part of the brain for processing visual information.It exhibits structural and functional plasticity,which is crucial for adapting to complex visual environments.The quintessential ma...The visual cortex is an essential part of the brain for processing visual information.It exhibits structural and functional plasticity,which is crucial for adapting to complex visual environments.The quintessential manifestation of visual cortical plasticity is ocular dominance plasticity during the critical period,which involves numerous cellular and molecular events.While previous studies have emphasized the role of visual cortical neurons and their associated functional molecules in visual plasticity,recent findings have revealed that structural factors such as the extracellular matrix and glia are also involved.Investigating how these molecules interact to form a complex network that facilitates plasticity in the visual cortex is crucial to our understanding of the development of the visual system and the advancement of therapeutic strategies for visual disorders like amblyopia.展开更多
Poly(butylene adipate-terephthalate)(PBAT),as one of the most common and promising biodegradable plastics,has been widely used in agriculture,packaging,and other industries due to its strong biodegradability propertie...Poly(butylene adipate-terephthalate)(PBAT),as one of the most common and promising biodegradable plastics,has been widely used in agriculture,packaging,and other industries due to its strong biodegradability properties.It is well known that PBAT suffers a series of natural weathering,mechanical wear,hydrolysis,photochemical transformation,and other abiotic degradation processes before being biodegraded.Therefore,it is particularly important to understand the role of abiotic degradation in the life cycle of PBAT.Since the abiotic degradation of PBAT has not been systematically summarized,this review aims to summarize the mechanisms and main factors of the three major abiotic degradation pathways(hydrolysis,photochemical transformation,and thermochemical degradation)of PBAT.It was found that all of them preferentially destroy the chemical bonds with higher energy(especially C-O and C=O)of PBAT,which eventually leads to the shortening of the polymer chain and then leads to reduction in molecular weight.The main factors affecting these abiotic degradations are closely related to the energy or PBAT structure.These findings provide important theoretical and practical guidance for identifying effective methods for PBAT waste management and proposing advanced schemes to regulate the degradation rate of PBAT.展开更多
文摘A low-molecular-weight polylactide-poly(butylene succinate)(PLA-PBS)copolymer was synthesized and incorporated into polylactide(PLA)as a novel toughening agent by solvent casting.The copolymer had the same chemical structure and function as PLA and it was used as a plasticizer to PLA.The copolymer was blended with PLA at a weight ratio from 2 to 10 wt%.Phase separation between PLA and PLA-PBS was not observed from their scanning electron microscopy(SEM)images and the crystal structure of PLA almost remained unchanged based on the X-ray diffraction(XRD)measurement.The melt flow index(MFI)of the blends was higher as the amount of PLA-PBS increased,indicating that the block copolymer did improve the mobility of the PLA chains.Moreover,tensile tests revealed that PLA with greater PLA-PBS copolymer exhibited higher elongation at break and it reached the maximum at 8 wt%of PLA-PBS in PLA,which was around 6 times higher than that of pure PLA.Furthermore,the glass transition temperature,measured by differential scanning calorimetry(DSC),markedly decreased with an increasing amount of the copolymer as it decreased from 61.2℃ for pure PLA to 41.3℃when it was blended with 10 wt%PLA-PBS copolymer.Therefore,the PLA-PBS copolymer was shown to be a promising plasticizer for fully biobased and toughened PLA.
基金Funding Statement:The authors express their gratitude for the financial support from the National Natural Science Foundation of China(32101475)the Yuemu Technology Plan Project(YMKJ202201).
文摘In this study,as the plasticizer,Camellia oleifera seed-oil-based cyclohexyl ester(COSOCE)was prepared by the reaction of cyclohexene oxide and refined C.oleifera seed oil(RCOSO)obtained by acidification hydrolysis after saponification.In addition,the structure of the target product was confirmed by Fourier transform infrared(FTIR)spectroscopy,nuclear magnetic resonance(NMR)spectroscopy,and Raman spectroscopy.COSOCE was used as plasticizer-modified polyvinyl chloride(PVC)membranes.The structure of the COSOCE-modified PVC membranes were characterized by Raman spectroscopy and scanning electron microscopy(SEM).The properties of the COSOCE-modified PVC membrane were characterized by contact angle measurements,universal testing machine,thermogravimetric analysis(TGA),and differential scanning calorimetry(DSC).The results revealed that(1)The COSOCE-modified PVC membranes exhibit a good microscopic morphology.Combined with energy-dispersive X-ray spectroscopy(EDS)and contact angle measurement results,the COSOCE-modified PVC membranes are confirmed to be a hydrophilic material.(2)The modified PVC membrane with 60%COSOCE exhibited the best mechanical properties.The tensile strength reached 23.56±2.94 MPa.(3)COSOCE-modified PVC material exhibited better thermal stability,with a loss rate of less than 75%at the end of the first decomposition stage.Compared with that of the dioctyl-phthalate(DOP)-modified PVC membrane,the initial decomposition temperature of PVC was increased by 1.17°C–8.17°C,and the residual rate was increased by 0.67%–5.75%.The carbon–carbon double bond in the COSOCE molecular structure can remove the free radicals generated during the degradation of PVC material and slow down the decomposition rate of PVC.In addition,the double bond can be cross-linked partially with the PVC molecular chain containing the conjugated polyene structure,thereby increasing the movement resistance of the PVC molecular chain segment.Hence,COSOCE can replace DOP as a PVC plasticizer.
基金funded by the Scarce and Quality Economic Forest Engineering Technology Research Center(2022GCZX002)the Key Lab.of Biomass Energy and Material,Jiangsu Province(Grant No.JSBEM-S-202305).
文摘Plasticizers are essential additives in the processing of polyvinyl chloride(PVC),with phthalate plasticizers being widely used.However,these conventional plasticizers have been shown to be harmful to human health and environmentally unfriendly,necessitating the exploration of eco-friendly bio-based alternatives.In this study,Camellia oleifera seed oil,a specialty resource in China,was utilized as a raw material and reacted with 4,4′-Methylenebis(N,N-diglycidylaniline)(AG-80)to synthesize Phenyl Camellia seed Oil Ester(PCSOE).PCSOE was employed as a plasticizer to prepare modified PVC films with varying concentrations,with the conventional plasticizer dioctyl phthalate(DOP)serving as a control.Experimental results demonstrate that PSCOE-plasticized PVC films exhibit enhanced hydrophilicity,tensile strength,and thermal stability compared to DOP-modified PVC films.The contact angle of PSCOE-plasticized PVC films ranges from 66.26°to 78.48°,which is generally lower than the contact angle of DOP-modified PVC films at 78.40°,indicating improved hydrophilicity due to the modification with PCSOE.The tensile strength of PSCOE-plasticized PVC films ranges from 17.73 to 20.17 MPa,all surpassing the value of 16.41 MPa for DOP-modified PVC films.Moreover,the temperatures corresponding to 5%,10%,and 50%weight loss for PVC samples modified with PCSOE are higher than those for DOP.Hence,PCSOE presents a viable alternative to DOP as a plasticizer for PVC materials.
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funded by the Alexander von Humboldt Stiftungsupported by DFG (SCH W534/6-1 to SWS)
文摘The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage.The latter involves global alterations,making understanding plastic responses triggered by local damage difficult.One key feature of the dentate gyrus is that it contains a well-defined neurogenic niche,the subgranular zone,and beyond neurogenesis,newly born granule cells may maintain a“young”phenotype throughout life,adding to the plastic nature of the structure.Here,we present a novel experimental model of local brain damage in organotypic entorhino-hippocampal cultures that results in the activation of adjacent newly born granule cells.A small piece of filter paper was placed on the surface of the granule cell layer of the dentate gyrus,which evoked a foreign body reaction of astrocytes,along with the activation of local young neurons expressing doublecortin.Forty-eight hours after foreign body placement,the number of doublecortin-immunoreactive cells increased in the subgranular zone in the direct vicinity of the foreign body,whereas overall increased doublecortin immunoreactivity was observed in the granule cell layer and molecular layer of the dentate gyrus.Foreign body placement in the pyramidal layer of the CA1 region evoked a comparable local astroglial reaction but did not lead to an increase in doublecortin-immunoreactive in either the CA1 region or the adjacent dentate gyrus.Seven days after foreign body placement in the dentate gyrus,the increase in doublecortin-immunoreactivity was no longer observed,indicating the transient activation of young cells.However,7 days after foreign body placement,the number of doublecortin-immunoreactive granule cells coimmunoreactive for calbindin was lower than that under the control conditions.As calbindin is a marker for mature granule cells,this result suggests that activated young cells remain at a more immature stage following foreign body placement.Live imaging of retrovirally green fluorescent protein-labeled newly born granule cells revealed the orientation and growth of their dendrites toward the foreign body placement.This novel experimental model of foreign body placement in organotypic entorhino-hippocampal cultures could serve as a valuable tool for studying both glial reactivity and neuronal plasticity,specifically of newly born neurons under controlled in vitro conditions.
基金financially supported by King Abdulaziz University,Deanship of Scientific Research(DSR)。
文摘Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease,this plasticity is disrupted,leading to cognitive and motor deficits.This review explores the mechanisms of neuronal plasticity and its effect on Alzheimer's disease and Parkinson's disease.Alzheimer's disease features amyloid-beta plaques and tau tangles that impair synaptic function,while Parkinson's disease involves the loss of dopaminergic neurons affecting motor control.Enhancing neuronal plasticity offers therapeutic potential for these diseases.A systematic literature review was conducted using databases such as PubMed,Scopus,and Google Scholar,focusing on studies of neuronal plasticity in Alzheimer's disease and Parkinson's disease.Data synthesis identified key themes such as synaptic mechanisms,neurogenesis,and therapeutic strategies,linking molecular insights to clinical applications.Results highlight that targeting synaptic plasticity mechanisms,such as long-term potentiation and long-term depression,shows promise.Neurotrophic factors,advanced imaging techniques,and molecular tools(e.g.,clustered regularly interspaced short palindromic repeats and optogenetics)are crucial in understanding and enhancing plasticity.Current therapies,including dopamine replacement,deep brain stimulation,and lifestyle interventions,demonstrate the potential to alleviate symptoms and improve outcomes.In conclusion,enhancing neuronal plasticity through targeted therapies holds significant promise for treating neurodegenerative diseases.Future research should integrate multidisciplinary approaches to fully harness the therapeutic potential of neuronal plasticity in Alzheimer's disease and Parkinson's disease.
基金supported by Progetto Trapezio,Compagnia di San Paolo(67935-2021.2174),to LBFondazione CRT(Cassa di Risparmio di Torino,RF=2022.0618),to LBPRIN2022(grant 2022LB4X3N),to LB。
文摘The capacity of the central nervous system for structural plasticity and regeneration is commonly believed to show a decreasing progression from“small and simple”brains to the larger,more complex brains of mammals.However,recent findings revealed that some forms of neural plasticity can show a reverse trend.Although plasticity is a well-preserved,transversal feature across the animal world,a variety of cell populations and mechanisms seem to have evolved to enable structural modifications to take place in widely different brains,likely as adaptations to selective pressures.Increasing evidence now indicates that a trade-off has occurred between regenerative(mostly stem cell–driven)plasticity and developmental(mostly juvenile)remodeling,with the latter primarily aimed not at brain repair but rather at“sculpting”the neural circuits based on experience.In particular,an evolutionary trade-off has occurred between neurogenic processes intended to support the possibility of recruiting new neurons throughout life and the different ways of obtaining new neurons,and between the different brain locations in which plasticity occurs.This review first briefly surveys the different types of plasticity and the complexity of their possible outcomes and then focuses on recent findings showing that the mammalian brain has a stem cell–independent integration of new neurons into pre-existing(mature)neural circuits.This process is still largely unknown but involves neuronal cells that have been blocked in arrested maturation since their embryonic origin(also termed“immature”or“dormant”neurons).These cells can then restart maturation throughout the animal's lifespan to become functional neurons in brain regions,such as the cerebral cortex and amygdala,that are relevant to high-order cognition and emotions.Unlike stem cell–driven postnatal/adult neurogenesis,which significantly decreases from small-brained,short-living species to large-brained ones,immature neurons are particularly abundant in large-brained,long-living mammals,including humans.The immature neural cell populations hosted in these complex brains are an interesting example of an“enlarged road”in the phylogenetic trend of plastic potential decreases commonly observed in the animal world.The topic of dormant neurons that covary with brain size and gyrencephaly represents a prospective turning point in the field of neuroplasticity,with important translational outcomes.These cells can represent a reservoir of undifferentiated neurons,potentially granting plasticity within the high-order circuits subserving the most sophisticated cognitive skills that are important in the growing brains of young,healthy individuals and are frequently affected by debilitating neurodevelopmental and degenerative disorders.
文摘Regenerative capacity of the central nervous system(CNS)is unevenly distributed among vertebrates.While most mammalian species including humans elicit limited repair following CNS injury or disease,highly regenerative vertebrates including urodele amphibians and teleost fish spontaneously reverse CNS damage.Teletost zebrafish(danio rerio)are tropical freshwater fish that proved to be an excellent vertebrate model of successful CNS regeneration.Differential neuronal,glial,and immune injury responses underlie disparate injury outcomes between highly regenerative zebrafish and poorly regenerative mammals.This article describes complications associated with neuronal repair following spinal cord injury(SCI)in poorly regenerative mammals and highlights intersecting modes of plasticity and regeneration in highly regenerative zebrafish(Figures 1 and 2).Comparative approaches evaluating immunoglial SCI responses were recently reviewed elsewhere(Reyes and Mokalled,2024).
基金supported by the National Natural Science Foundation of China,No.82271115(to MY).
文摘Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglion cells and their axons,leading to axonal transport dysfuntion,subsequently causing secondary damage to anterior or posterior ends of the visual system.Accordingly,recent evidence indicates that glaucoma is a degenerative disease of the central nervous system that causes damage throughout the visual pathway.However,the effects of glaucoma on synaptic plasticity in the primary visual cortex remain unclear.In this study,we established a mouse model of unilateral chronic ocular hypertension by injecting magnetic microbeads into the anterior chamber of one eye.We found that,after 4 weeks of chronic ocular hypertension,the neuronal somas were smaller in the superior colliculus and lateral geniculate body regions of the brain contralateral to the affected eye.This was accompanied by glial cell activation and increased expression of inflammatory factors.After 8 weeks of ocular hypertension,we observed a reduction in the number of excitatory and inhibitory synapses,dendritic spines,and activation of glial cells in the primary visual cortex contralateral to the affected eye.These findings suggest that glaucoma not only directly damages the retina but also induces alterations in synapses and dendritic spines in the primary visual cortex,providing new insights into the pathogenesis of glaucoma.
文摘Immunotherapy has brought unprecedented breakthroughs to advanced malignant tumors,yet the immune microenvironment shaped by the tumor stroma has often been underestimated in the traditional focus on the“immune checkpoint-T cell”axis.Collagen not only constitutes a mechanical barrier that distinguishes between the periphery and core of solid tumors but also systematically remodels the orientation of metabolism,vasculature,and immune cell phenotypic plasticity through its spatial density,fiber arrangement,and crosslinking patterns(F igure 1)[1,2].Abundant evidence suggests that over-accumulated types I and III collagen drive CD8+T cell exhaustion,NK cell functional inhibition,and tumor-associated macrophage polarization through ligand-receptor networks involving LAIR-1,DDR2,andβ1/β3 integrins[3-6].Mechanistically,collagen engagement of LAIR-1 delivers inhibitory signals in effector lymphocytes,promoting dysfunctional or exhausted states[7-9].In parallel,collagen-β1/β3 integrin signaling activates mechanotransduction pathways(e.g.,FAK/SRC),reducing T-cell motility and immune-tumor contact,while DDR2 activation supports matrix-remodeling programs that limit lymphocyte trafficking.
基金supported by the Deutsche Forschungsgemeinschaft(DFG),TRR274(Project ID 408885537,Sy Nergy,EXC 2145/ID 390857198,to FMB)。
文摘The remodeling of axonal connections following injury is an important feature driving functional recovery.The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory fibers.While the reticulospinal tract has been shown to be particularly prone to axonal growth and plasticity following injuries of the spinal cord,the differential capacities of excitatory and inhibitory fibers for plasticity remain unclear.As adaptive axonal plasticity involves a sophisticated interplay between excitatory and inhibitory input,we investigated in this study the plastic potential of glutamatergic(vGlut2)and GABAergic(vGat)fibers originating from the gigantocellular nucleus and the lateral paragigantocellular nucleus,two nuclei important for locomotor function.Using a combination of viral tracing,chemogenetic silencing,and AI-based kinematic analysis,we investigated plasticity and its impact on functional recovery within the first 3 weeks following injury,a period prone to neuronal remodeling.We demonstrate that,in this time frame,while vGlut2-positive fibers within the gigantocellular and lateral paragigantocellular nuclei rewire significantly following cervical spinal cord injury,vGat-positive fibers are rather unresponsive to injury.We also show that the acute silencing of excitatory axonal fibers which rewire in response to lesions of the spinal cord triggers a worsening of the functional recovery.Using kinematic analysis,we also pinpoint the locomotion features associated with the gigantocellular nucleus or lateral paragigantocellular nucleus during functional recovery.Overall,our study increases the understanding of the role of the gigantocellular and lateral paragigantocellular nuclei during functional recovery following spinal cord injury.
基金National Natural Science Foundation of China(No.U2241231)National Key Research and Development Program of China(No.2021YFB3701100)+1 种基金Scientific Research Project of Jiangxi Provincial Department of Education,China(No.GJJ211038)Doctoral Research Project of Jinggangshan University,China(No.JZB2110)。
文摘The synergistic effect of low Gd+Mn additions on the evolution of microstructure and mechanical properties of Mg−xGd−0.8Mn alloy was investigated.Gd addition shows a strong grain refinement effect on the extruded Mg−xGd−0.8Mn alloy,and leads to a continuous decrease in the area fraction of basal texture grains and the corresponding maximum density of texture components.However,the maximum density of the basal texture components grows abruptly as Gd content increases to 6 wt.%.When the Gd content is below 6 wt.%,the asymmetry of the tensile and compressive yield of the alloy is negatively correlated to the Gd content due to grain refinement and texture weakening effects.Besides,the contribution of grain refinement to higher alloy yield strength is more significant than that of grain orientation.Compared with the extruded Mg−xGd alloy,the extruded Mg−xGd−0.8Mn alloy shows a lower limit composition point that corresponds to solid solution strengthening and plasticizing effect(2 wt.%and 4 wt.%).Finally,the trend of basal slip and prismatic slip resistance variations of the extruded Mg−xGd−0.8Mn alloys was predicted.
基金supported by the NIH (R01NS103481, R01NS111776, and R01NS131489)Indiana Department of Health (ISDH58180)(all to WW)。
文摘Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.
基金supported by the National Key R&D Program of China(No.2017YFB0304402)。
文摘The microstructural evolution of a cold-rolled and intercritical annealed medium-Mn steel(Fe-0.10C-5Mn)was investigated during uniaxial tensile testing.In-situ observations under scanning electron microscopy,transmission electron microscopy,and X-ray diffraction analysis were conducted to characterize the progressive transformation-induced plasticity process and associated fracture initiation mechanisms.These findings were discussed with the local strain measurements via digital image correlation.The results indicated that Lüders band formation in the steel was limited to 1.5%strain,which was mainly due to the early-stage martensitic phase transformation of a very small amount of the less stable large-sized retained austenite(RA),which led to localized stress concentrations and strain hardening and further retardation of yielding.The small-sized RA exhibited high stability and progressively transformed into martensite and contributed to a stably extended Portevin-Le Chatelier effect.The volume fraction of RA gradually decreased from 26.8%to 8.2%prior to fracture.In the late deformation stage,fracture initiation primarily occurred at the austenite/martensite and ferrite/martensite interfaces and the ferrite phase.
基金supported by Postdoc Fellowship from the Foundation for Angelman Syndrome Therapeutics(FT2022-005 to JM,PD2023-001 to XY,and FT2024-001 to YAH)STTR R41 MH118747(to JM)。
文摘Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.
基金supported by the Department of Defense AFIRMⅢW81XWH-20-2-0029 grant subcontractLone Star Paralysis gift,UT POC19-1774-13 grant+1 种基金Neuraptive Therapeutics Inc.26-7724-56 grantNational Institutes of Health R01-NS128086(all to GDB)。
文摘Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically poor.We used a plasmalemmal fusogen,polyethylene glycol(PEG),to immediately fuse closely apposed open ends of severed proximal and distal axons in rat sciatic nerves.We have previously reported that sciatic nerve axons repaired by PEG-fusion do not undergo Wallerian degeneration,and PEG-fused animals exhibit rapid(within 2–6 weeks)and extensive locomotor recovery.Furthermore,our previous report showed that PEG-fusion of severed sciatic motor axons was non-specific,i.e.,spinal motoneurons in PEG-fused animals were found to project to appropriate as well as inappropriate target muscles.In this study,we examined the consequences of PEG-fusion for sensory axons of the sciatic nerve.Young adult male and female rats(Sprague–Dawley)received either a unilateral single cut or ablation injury to the sciatic nerve and subsequent repair with or without(Negative Control)the application of PEG.Compound action potentials recorded immediately after PEG-fusion repair confirmed conduction across the injury site.The success of PEG-fusion was confirmed through Sciatic Functional Index testing with PEG-fused animals showing improvement in locomotor function beginning at 35 days postoperatively.At 2–42 days postoperatively,we anterogradely labeled sensory afferents from the dorsal aspect of the hindpaw following bilateral intradermal injection of wheat germ agglutinin conjugated horseradish peroxidase.PEG-fusion repair reestablished axonal continuity.Compared to unoperated animals,labeled sensory afferents ipsilateral to the injury in PEG-fused animals were found in the appropriate area of the dorsal horn,as well as inappropriate mediolateral and rostrocaudal areas.Unexpectedly,despite having intact peripheral nerves,similar reorganizations of labeled sensory afferents were also observed contralateral to the injury and repair.This central reorganization may contribute to the improved behavioral recovery seen after PEG-fusion repair,supporting the use of this novel repair methodology over currently available treatments.
基金supported by the National Natural Science Foundation of China(No.22276139)the Shanghai’s Municipal State-owned Assets Supervision and Administration Commission(No.2022028).
文摘To better understand the migration behavior of plastic fragments in the environment,development of rapid non-destructive methods for in-situ identification and characterization of plastic fragments is necessary.However,most of the studies had focused only on colored plastic fragments,ignoring colorless plastic fragments and the effects of different environmental media(backgrounds),thus underestimating their abundance.To address this issue,the present study used near-infrared spectroscopy to compare the identification of colored and colorless plastic fragments based on partial least squares-discriminant analysis(PLS-DA),extreme gradient boost,support vector machine and random forest classifier.The effects of polymer color,type,thickness,and background on the plastic fragments classification were evaluated.PLS-DA presented the best and most stable outcome,with higher robustness and lower misclassification rate.All models frequently misinterpreted colorless plastic fragments and its background when the fragment thickness was less than 0.1mm.A two-stage modeling method,which first distinguishes the plastic types and then identifies colorless plastic fragments that had been misclassified as background,was proposed.The method presented an accuracy higher than 99%in different backgrounds.In summary,this study developed a novel method for rapid and synchronous identification of colored and colorless plastic fragments under complex environmental backgrounds.
基金supported by the National Natural Science Foundation of China(81770956,81371049,32471055 and 82171090)Project of Tianjin 131 Innovative Talent Team(201936)+4 种基金the Science and Technology Planning Project of Tianjin(21JCYBJC00780)the Science and Technology Fund for Health of Tianjin(TJWJ2023ZD008)Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJLab,Shanghai Center for Brain Science and Brain-Inspired Technology,the Lingang Laboratory(LG-QS-202203-12)Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK‑016A).
文摘The visual cortex is an essential part of the brain for processing visual information.It exhibits structural and functional plasticity,which is crucial for adapting to complex visual environments.The quintessential manifestation of visual cortical plasticity is ocular dominance plasticity during the critical period,which involves numerous cellular and molecular events.While previous studies have emphasized the role of visual cortical neurons and their associated functional molecules in visual plasticity,recent findings have revealed that structural factors such as the extracellular matrix and glia are also involved.Investigating how these molecules interact to form a complex network that facilitates plasticity in the visual cortex is crucial to our understanding of the development of the visual system and the advancement of therapeutic strategies for visual disorders like amblyopia.
基金supported by the National Key R&D Program of China(No.2022YFC3901800)the National Natural Science Foundation of China(No.22176041)Guangzhou Science and Technology Planning Project(No.2023A04J0918)。
文摘Poly(butylene adipate-terephthalate)(PBAT),as one of the most common and promising biodegradable plastics,has been widely used in agriculture,packaging,and other industries due to its strong biodegradability properties.It is well known that PBAT suffers a series of natural weathering,mechanical wear,hydrolysis,photochemical transformation,and other abiotic degradation processes before being biodegraded.Therefore,it is particularly important to understand the role of abiotic degradation in the life cycle of PBAT.Since the abiotic degradation of PBAT has not been systematically summarized,this review aims to summarize the mechanisms and main factors of the three major abiotic degradation pathways(hydrolysis,photochemical transformation,and thermochemical degradation)of PBAT.It was found that all of them preferentially destroy the chemical bonds with higher energy(especially C-O and C=O)of PBAT,which eventually leads to the shortening of the polymer chain and then leads to reduction in molecular weight.The main factors affecting these abiotic degradations are closely related to the energy or PBAT structure.These findings provide important theoretical and practical guidance for identifying effective methods for PBAT waste management and proposing advanced schemes to regulate the degradation rate of PBAT.