Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after inju...Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.展开更多
Invasive as well as non-invasive neurotechnologies conceptualized to interface the central and peripheral nervous system have been probed for the past decades,which refer to electroencephalography,electrocorticography...Invasive as well as non-invasive neurotechnologies conceptualized to interface the central and peripheral nervous system have been probed for the past decades,which refer to electroencephalography,electrocorticography and microelectrode arrays.The challenges of these mentioned approaches are characterized by the bandwidth of the spatiotemporal resolution,which in turn is essential for large-area neuron recordings(Abiri et al.,2019).展开更多
In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tum...In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.展开更多
Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission ...Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.展开更多
Freezing of gait is a significant and debilitating motor symptom often observed in individuals with Parkinson's disease.Resting-state functional magnetic resonance imaging,along with its multi-level feature indice...Freezing of gait is a significant and debilitating motor symptom often observed in individuals with Parkinson's disease.Resting-state functional magnetic resonance imaging,along with its multi-level feature indices,has provided a fresh perspective and valuable insight into the study of freezing of gait in Parkinson's disease.It has been revealed that Parkinson's disease is accompanied by widespread irregularities in inherent brain network activity.However,the effective integration of the multi-level indices of resting-state functional magnetic resonance imaging into clinical settings for the diagnosis of freezing of gait in Parkinson's disease remains a challenge.Although previous studies have demonstrated that radiomics can extract optimal features as biomarkers to identify or predict diseases,a knowledge gap still exists in the field of freezing of gait in Parkinson's disease.This cross-sectional study aimed to evaluate the ability of radiomics features based on multi-level indices of resting-state functional magnetic resonance imaging,along with clinical features,to distinguish between Parkinson's disease patients with and without freezing of gait.We recruited 28 patients with Parkinson's disease who had freezing of gait(15 men and 13 women,average age 63 years)and 30 patients with Parkinson's disease who had no freezing of gait(16 men and 14 women,average age 64 years).Magnetic resonance imaging scans were obtained using a 3.0T scanner to extract the mean amplitude of low-frequency fluctuations,mean regional homogeneity,and degree centrality.Neurological and clinical characteristics were also evaluated.We used the least absolute shrinkage and selection operator algorithm to extract features and established feedforward neural network models based solely on resting-state functional magnetic resonance imaging indicators.We then performed predictive analysis of three distinct groups based on resting-state functional magnetic resonance imaging indicators indicators combined with clinical features.Subsequently,we conducted 100 additional five-fold cross-validations to determine the most effective model for each classification task and evaluated the performance of the model using the area under the receiver operating characteristic curve.The results showed that when differentiating patients with Parkinson's disease who had freezing of gait from those who did not have freezing of gait,or from healthy controls,the models using only the mean regional homogeneity values achieved the highest area under the receiver operating characteristic curve values of 0.750(with an accuracy of 70.9%)and 0.759(with an accuracy of 65.3%),respectively.When classifying patients with Parkinson's disease who had freezing of gait from those who had no freezing of gait,the model using the mean amplitude of low-frequency fluctuation values combined with two clinical features achieved the highest area under the receiver operating characteristic curve of 0.847(with an accuracy of 74.3%).The most significant features for patients with Parkinson's disease who had freezing of gait were amplitude of low-frequency fluctuation alterations in the left parahippocampal gyrus and two clinical characteristics:Montreal Cognitive Assessment and Hamilton Depression Scale scores.Our findings suggest that radiomics features derived from resting-state functional magnetic resonance imaging indices and clinical information can serve as valuable indices for the identification of freezing of gait in Parkinson's disease.展开更多
Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0...Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.展开更多
Protonic solid oxide electrolysis cells(P-SOECs)are a promising technology for water electrolysis to produce green hydrogen.However,there are still challenges related key materials and anode/electrolyte interface.P-SO...Protonic solid oxide electrolysis cells(P-SOECs)are a promising technology for water electrolysis to produce green hydrogen.However,there are still challenges related key materials and anode/electrolyte interface.P-SOECs with Zr-rich electrolyte,called Zr-rich side P-SOECs,possess high thermodynamically stability under high steam concentrations but the large reaction resistances and the current leakage,thus the inferior performances.In this study,an efficient functional interlayer Ba_(0.95)La_(0.05)Fe_(0.8)Zn_(0.2)O_(3-δ)(BLFZ)in-between the anode and the electrolyte is developed.The electrochemical performances of P-SOECs are greatly enhanced because the BLFZ can greatly increase the interface contact,boost anode reaction kinetics,and increase proton injection into electrolyte.As a result,the P-SOEC yields high current density of 0.83 A cm^(-2) at 600℃ in 1.3 Vamong all the reported Zr-rich side cells.This work not only offers an efficient functional interlayer for P-SOECs but also holds the potential to achieve P-SOECs with high performances and long-term stability.展开更多
The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia ...The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be crucial.Tryptanthrin possesses an anti-inflammatory biological function.However,its roles and the underlying molecular mechanisms in spinal cord injury remain unknown.In this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro.Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway.Additionally,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord injury.Finally,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis.Taken together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.展开更多
Mutations in the protocadherin-19(PCDH19)gene(Xq22.1)cause the X-linked syndrome known as developmental and epileptic encephalopathy 9(DEE9,OMIM#300088)(Dibbens et al.,2008).DEE9 is characterized by early-onset cluste...Mutations in the protocadherin-19(PCDH19)gene(Xq22.1)cause the X-linked syndrome known as developmental and epileptic encephalopathy 9(DEE9,OMIM#300088)(Dibbens et al.,2008).DEE9 is characterized by early-onset clustering epilepsy associated with intellectual disability ranging from mild to profound,autism spectrum disorder,and other neuropsychiatric features including schizophrenia,anxiety,attentiondeficit/hyperactivity,and obsessive or aggressive behaviors.While seizures may become less frequent in adolescence,psychiatric comorbidities persist and often worsen with age(Dibbens et al.,2008;Kolc et al.,2020).展开更多
There is an error in the name of the cell line in the abstract of the published paper“MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons”published on pages 2698-2707,Issue 12,Volume 19 of Ne...There is an error in the name of the cell line in the abstract of the published paper“MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons”published on pages 2698-2707,Issue 12,Volume 19 of Neural Regeneration Research(Sharma et al.,2024),because of oversight during final proof checking.The correct description should be“human-GABA receptor A-α1/β2/γ2L human embryonic kidney(HEK)recombinant cell line.”The authors apologize for any inconvenience this correction may cause for readers and editors of Neural Regeneration Research.展开更多
Five-valued Boolean functions play an important role in the design of symmetric cryptography.While the design and properties of single-output almost optimal five-valued spectra Boolean functions have been extensively ...Five-valued Boolean functions play an important role in the design of symmetric cryptography.While the design and properties of single-output almost optimal five-valued spectra Boolean functions have been extensively studied over the past few decades,there has been limited research on the construction of almost optimal five-valued spectra vectorial Boolean functions.In this paper,we present a construction method for even-variable 2-output almost optimal five-valued spectra balanced Boolean functions,whose Walsh spectra values belong to the set{0,±2^(n/2),±2^(n/2+1)},at the same time,we discuss the existence of sufficient conditions in the construction.Additionally,this paper presents a novel construction method for balanced single-output Boolean functions with even variables featuring a special five-valued spectral structure,whose Walsh spectra values are constrained to the set{0,±2^(n/2),±3·2^(n/2)}.These functions provide new canonical examples for the study of Boolean function spectral theory.展开更多
There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons...There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).展开更多
The Red Sea-Gulf of Suez-Cairo-Alexandria Clysmic-Trend in northern Egypt is the main earthquake zone in the country,with a moderate-to-high seismic hazard and a history of significant earthquakes caused by rifting an...The Red Sea-Gulf of Suez-Cairo-Alexandria Clysmic-Trend in northern Egypt is the main earthquake zone in the country,with a moderate-to-high seismic hazard and a history of significant earthquakes caused by rifting and active faulting.To improve our understanding of the tectonic and seismic processes in this area,more comprehensive imaging of the crustal structure is required.This can be achieved by increasing the number of receiver functions(RFs)recorded by the seismic stations in northern Egypt and the southeastern Mediterranean.Data handling and processing should also be automated to increase process efficiency.In this study,we developed a capsule neural network for automated selection of RFs.The model was trained on a dataset containing RFs(both selected and unselected)from five broadband stations in northern Egypt.Stations SLM,SIWA,KOT,NBNS,and NKL are located in the unstable shelf region of Egypt,where limited knowledge of the deep crustal structure is available.The proposed capsule neural network achieved an average precision of 80%on the test set.The automated selection of RFs using a capsule neural network has the potential to significantly improve the efficiency and accuracy of RF analysis,as demonstrated by the stacking test.This could lead to a better understanding of crustal structure and tectonic processes in northern Egypt and the southeastern Mediterranean.展开更多
Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network lev...Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network level have not been elucidated.This study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve transfer.Sprague–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper trunk.Resting-state brain functional magnetic resonance imaging was obtained 7 months after surgery.The independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the component.Alterations in intra-network resting-state functional connectivity were compared among the groups.Target muscle reinnervation was assessed by behavioral observation(elbow flexion)and electromyography.The results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural pathway.Nerve repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor representation.The thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve transfer.Brain areas related to cognition and emotion were enhanced after end-to-side nerve transfer.Our study revealed important brain networks related to different nerve reconstructions.These networks may be potential targets for enhancing motor recovery.展开更多
Cp_(2)TiCl_(2) as a Lewis acid precursor and nicotinic acid as a ligand have been used synergistically for the one-pot synthesis of 2-(N-substituted amino)-1,4-naphthoquinones.This method establishes a general strateg...Cp_(2)TiCl_(2) as a Lewis acid precursor and nicotinic acid as a ligand have been used synergistically for the one-pot synthesis of 2-(N-substituted amino)-1,4-naphthoquinones.This method establishes a general strategy for the functionalization and conversion of C-H bonds of 1,4-naphthoquinones into C-N bonds,providing an effective route to synthesize 2-(N-substituted amino)-1,4-naphthoquinone with high yield under mild conditions.Additionally,the synergistic catalytic mechanism was investigated by 1H NMR titration experiments and LC-MS analysis,with experimental results sufficiently and consistently supporting the proposed mechanism of the catalytic cycle.展开更多
During the initial impoundment period of a canyon-shaped reservoir,the water body fluctuated violently regarding water level,hydrological condition,and thermal stratification.These variations may alter the structure o...During the initial impoundment period of a canyon-shaped reservoir,the water body fluctuated violently regarding water level,hydrological condition,and thermal stratification.These variations may alter the structure of phytoplankton community,resulting in algal blooms and seriously threatening the ecological security of the reservoir.It is of great significance to understand the continuous changes of phytoplankton in the initial impoundment period for the protection of reservoir water quality.Therefore,a two-year in-situ monitoring study was conducted on water quality and phytoplankton in a representative canyonshaped reservoir named Sanhekou and the interannual changes of phytoplankton community and its response to environmental changes during the initial impoundment period were discussed at taxonomic versus functional classification levels.The results showed that the total nitrogen and permanganate index levels were relatively high in the first year due to rapid water storage and heavy rainfall input,and the more stable hydrological conditions in the second year promoted the increase of algae density and the transformation of community,and the proportion of cyanobacteria increased significantly.The succession order of phytoplankton in the first year of the initial impoundment periodwas Chlorophyta-Bacillariophyta-Chlorophyta,or J/F/X1-P/MP/W1-A/X1/MP,respectively.And the succession order in the second year was Cyanobacteria/Chlorophyta-Bacillariophyta-Chlorophyta,or L_(M)/G/P-P/A/X1-X1/J/G.Water temperature,relativewater column stability,mixing depth,and pHwere crucial factors affecting phytoplankton community succession.This study revealed the interannual succession law and driving factors of phytoplankton in the initial impoundment period and provided an important reference for the operation management and ecological protection of canyon-shaped reservoirs.展开更多
Zinc-ion batteries(ZIBs)are inexpensive and safe,but side reactions on the Zn anode and Zn dendrite growth hinder their practical applications.In this study,1,3,5-triformylphloroglycerol(Tp)and various diamine monomer...Zinc-ion batteries(ZIBs)are inexpensive and safe,but side reactions on the Zn anode and Zn dendrite growth hinder their practical applications.In this study,1,3,5-triformylphloroglycerol(Tp)and various diamine monomers(p-phenylenediamine(Pa),benzidine(BD),and 4,4"-diamino-p-terphenyl(DATP))were used to synthesize a series of two-dimensional covalent-organic frameworks(COFs).The resulting COFs were named TpPa,TpBD,and TpDATP,respectively,and they showed uniform zincophilic sites,different pore sizes,and high Young's moduli on the Zn anode.Among them,TpPa and TpBD showed lower surface work functions and higher ion transfer numbers,which were conducive to uniform galvanizing/stripping zinc and inhibited dendrite growth.Theoretical calculations showed that TpPa and TpBD had wider negative potential region and greater adsorption capacity for Zn2+than TpDATP,providing more electron donor sites to coordinate with Zn^(2+).Symmetric cells protected by TpPa and TpBD stably cycled for more than 2300 h,whereas TpDATP@Zn and the bare zinc symmetric cells failed after around 150 and200 h.The full cells containing TpPa and TpBD modification layers also showed excellent cycling capacity at 1 A/g.This study provides comprehensive insights into the construction of highly reversible Zn anodes via COF modification layers for advanced rechargeable ZIBs.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
文摘Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.
文摘Invasive as well as non-invasive neurotechnologies conceptualized to interface the central and peripheral nervous system have been probed for the past decades,which refer to electroencephalography,electrocorticography and microelectrode arrays.The challenges of these mentioned approaches are characterized by the bandwidth of the spatiotemporal resolution,which in turn is essential for large-area neuron recordings(Abiri et al.,2019).
文摘In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.
基金supported by the National Natural Science Foundation of China,Nos.32070989(to YMZ),31872766(to YMZ),81790640(to XLY),and 82070993(to SJW)the grant from Sanming Project of Medicine in Shenzhen,No.SZSM202011015(to XLY)。
文摘Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.
基金supported by the National Natural Science Foundation of China,No.82071909(to GF)the Natural Science Foundation of Liaoning Province,No.2023-MS-07(to HL)。
文摘Freezing of gait is a significant and debilitating motor symptom often observed in individuals with Parkinson's disease.Resting-state functional magnetic resonance imaging,along with its multi-level feature indices,has provided a fresh perspective and valuable insight into the study of freezing of gait in Parkinson's disease.It has been revealed that Parkinson's disease is accompanied by widespread irregularities in inherent brain network activity.However,the effective integration of the multi-level indices of resting-state functional magnetic resonance imaging into clinical settings for the diagnosis of freezing of gait in Parkinson's disease remains a challenge.Although previous studies have demonstrated that radiomics can extract optimal features as biomarkers to identify or predict diseases,a knowledge gap still exists in the field of freezing of gait in Parkinson's disease.This cross-sectional study aimed to evaluate the ability of radiomics features based on multi-level indices of resting-state functional magnetic resonance imaging,along with clinical features,to distinguish between Parkinson's disease patients with and without freezing of gait.We recruited 28 patients with Parkinson's disease who had freezing of gait(15 men and 13 women,average age 63 years)and 30 patients with Parkinson's disease who had no freezing of gait(16 men and 14 women,average age 64 years).Magnetic resonance imaging scans were obtained using a 3.0T scanner to extract the mean amplitude of low-frequency fluctuations,mean regional homogeneity,and degree centrality.Neurological and clinical characteristics were also evaluated.We used the least absolute shrinkage and selection operator algorithm to extract features and established feedforward neural network models based solely on resting-state functional magnetic resonance imaging indicators.We then performed predictive analysis of three distinct groups based on resting-state functional magnetic resonance imaging indicators indicators combined with clinical features.Subsequently,we conducted 100 additional five-fold cross-validations to determine the most effective model for each classification task and evaluated the performance of the model using the area under the receiver operating characteristic curve.The results showed that when differentiating patients with Parkinson's disease who had freezing of gait from those who did not have freezing of gait,or from healthy controls,the models using only the mean regional homogeneity values achieved the highest area under the receiver operating characteristic curve values of 0.750(with an accuracy of 70.9%)and 0.759(with an accuracy of 65.3%),respectively.When classifying patients with Parkinson's disease who had freezing of gait from those who had no freezing of gait,the model using the mean amplitude of low-frequency fluctuation values combined with two clinical features achieved the highest area under the receiver operating characteristic curve of 0.847(with an accuracy of 74.3%).The most significant features for patients with Parkinson's disease who had freezing of gait were amplitude of low-frequency fluctuation alterations in the left parahippocampal gyrus and two clinical characteristics:Montreal Cognitive Assessment and Hamilton Depression Scale scores.Our findings suggest that radiomics features derived from resting-state functional magnetic resonance imaging indices and clinical information can serve as valuable indices for the identification of freezing of gait in Parkinson's disease.
基金supported by the National Natural Science Foundation of China,Nos.82204360(to HM)and 82270411(to GW)National Science and Technology Innovation 2030 Major Program,No.2021ZD0200900(to YL)。
文摘Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.
基金financial support from the JSPS KAKENHI Grant-in-Aid for Scientific Research(B),No.21H02035KAKENHI Grant-in-Aid for Challenging Research(Exploratory),No.21K19017+2 种基金KAKENHI Grant-in-Aid for Transformative Research Areas(B),No.21H05100National Natural Science Foundation of China,No.22409033 and No.22409035Basic and Applied Basic Research Foundation of Guangdong Province,No.2022A1515110470.
文摘Protonic solid oxide electrolysis cells(P-SOECs)are a promising technology for water electrolysis to produce green hydrogen.However,there are still challenges related key materials and anode/electrolyte interface.P-SOECs with Zr-rich electrolyte,called Zr-rich side P-SOECs,possess high thermodynamically stability under high steam concentrations but the large reaction resistances and the current leakage,thus the inferior performances.In this study,an efficient functional interlayer Ba_(0.95)La_(0.05)Fe_(0.8)Zn_(0.2)O_(3-δ)(BLFZ)in-between the anode and the electrolyte is developed.The electrochemical performances of P-SOECs are greatly enhanced because the BLFZ can greatly increase the interface contact,boost anode reaction kinetics,and increase proton injection into electrolyte.As a result,the P-SOEC yields high current density of 0.83 A cm^(-2) at 600℃ in 1.3 Vamong all the reported Zr-rich side cells.This work not only offers an efficient functional interlayer for P-SOECs but also holds the potential to achieve P-SOECs with high performances and long-term stability.
基金supported by the National Natural Science Foundation of China,Nos.82071387(to HT),81971172(to YW)the Natural Science Foundation of Zhejiang Province,China,No.LY22H090012(to HT)the Basic Research Project of Wenzhou City,China,No.Y20220923(to MZ)。
文摘The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be crucial.Tryptanthrin possesses an anti-inflammatory biological function.However,its roles and the underlying molecular mechanisms in spinal cord injury remain unknown.In this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro.Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway.Additionally,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord injury.Finally,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis.Taken together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.
基金supported by a grant from Telethon Foundation(grant No.GGP20056 to SB)The generation of Pcdh19 floxed mouse model was funded by Cariplo Foundation(grant No.2014-0972 to SB)。
文摘Mutations in the protocadherin-19(PCDH19)gene(Xq22.1)cause the X-linked syndrome known as developmental and epileptic encephalopathy 9(DEE9,OMIM#300088)(Dibbens et al.,2008).DEE9 is characterized by early-onset clustering epilepsy associated with intellectual disability ranging from mild to profound,autism spectrum disorder,and other neuropsychiatric features including schizophrenia,anxiety,attentiondeficit/hyperactivity,and obsessive or aggressive behaviors.While seizures may become less frequent in adolescence,psychiatric comorbidities persist and often worsen with age(Dibbens et al.,2008;Kolc et al.,2020).
文摘There is an error in the name of the cell line in the abstract of the published paper“MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons”published on pages 2698-2707,Issue 12,Volume 19 of Neural Regeneration Research(Sharma et al.,2024),because of oversight during final proof checking.The correct description should be“human-GABA receptor A-α1/β2/γ2L human embryonic kidney(HEK)recombinant cell line.”The authors apologize for any inconvenience this correction may cause for readers and editors of Neural Regeneration Research.
基金National Natural Science Foundation of China(62272360)。
文摘Five-valued Boolean functions play an important role in the design of symmetric cryptography.While the design and properties of single-output almost optimal five-valued spectra Boolean functions have been extensively studied over the past few decades,there has been limited research on the construction of almost optimal five-valued spectra vectorial Boolean functions.In this paper,we present a construction method for even-variable 2-output almost optimal five-valued spectra balanced Boolean functions,whose Walsh spectra values belong to the set{0,±2^(n/2),±2^(n/2+1)},at the same time,we discuss the existence of sufficient conditions in the construction.Additionally,this paper presents a novel construction method for balanced single-output Boolean functions with even variables featuring a special five-valued spectral structure,whose Walsh spectra values are constrained to the set{0,±2^(n/2),±3·2^(n/2)}.These functions provide new canonical examples for the study of Boolean function spectral theory.
基金supported by the National Institute of Mental Health (NIH/NIMH)the National Institute of Neurological Disorders and Stroke(NIH/NINDS):Grants#R21 MH132136 to FSN and R01 MH123700 and R01 NS040701 to MLD
文摘There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).
文摘The Red Sea-Gulf of Suez-Cairo-Alexandria Clysmic-Trend in northern Egypt is the main earthquake zone in the country,with a moderate-to-high seismic hazard and a history of significant earthquakes caused by rifting and active faulting.To improve our understanding of the tectonic and seismic processes in this area,more comprehensive imaging of the crustal structure is required.This can be achieved by increasing the number of receiver functions(RFs)recorded by the seismic stations in northern Egypt and the southeastern Mediterranean.Data handling and processing should also be automated to increase process efficiency.In this study,we developed a capsule neural network for automated selection of RFs.The model was trained on a dataset containing RFs(both selected and unselected)from five broadband stations in northern Egypt.Stations SLM,SIWA,KOT,NBNS,and NKL are located in the unstable shelf region of Egypt,where limited knowledge of the deep crustal structure is available.The proposed capsule neural network achieved an average precision of 80%on the test set.The automated selection of RFs using a capsule neural network has the potential to significantly improve the efficiency and accuracy of RF analysis,as demonstrated by the stacking test.This could lead to a better understanding of crustal structure and tectonic processes in northern Egypt and the southeastern Mediterranean.
基金supported by the National Natural Science Foundation of China,Nos.81871836(to MZ),82172554(to XH),and 81802249(to XH),81902301(to JW)the National Key R&D Program of China,Nos.2018YFC2001600(to JX)and 2018YFC2001604(to JX)+3 种基金Shanghai Rising Star Program,No.19QA1409000(to MZ)Shanghai Municipal Commission of Health and Family Planning,No.2018YQ02(to MZ)Shanghai Youth Top Talent Development PlanShanghai“Rising Stars of Medical Talent”Youth Development Program,No.RY411.19.01.10(to XH)。
文摘Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network level have not been elucidated.This study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve transfer.Sprague–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper trunk.Resting-state brain functional magnetic resonance imaging was obtained 7 months after surgery.The independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the component.Alterations in intra-network resting-state functional connectivity were compared among the groups.Target muscle reinnervation was assessed by behavioral observation(elbow flexion)and electromyography.The results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural pathway.Nerve repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor representation.The thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve transfer.Brain areas related to cognition and emotion were enhanced after end-to-side nerve transfer.Our study revealed important brain networks related to different nerve reconstructions.These networks may be potential targets for enhancing motor recovery.
基金2024 Special Talent Introduction Projects of Key R&D Program of Ningxia Hui Autonomous Region(2024BEH04049)the 2024 Guyuan City Innovation-Driven Achievement Transformation Project(2024BGTYF01-47)2025 Ningxia Natural Science Foundation Program(2025AAC030624).
文摘Cp_(2)TiCl_(2) as a Lewis acid precursor and nicotinic acid as a ligand have been used synergistically for the one-pot synthesis of 2-(N-substituted amino)-1,4-naphthoquinones.This method establishes a general strategy for the functionalization and conversion of C-H bonds of 1,4-naphthoquinones into C-N bonds,providing an effective route to synthesize 2-(N-substituted amino)-1,4-naphthoquinone with high yield under mild conditions.Additionally,the synergistic catalytic mechanism was investigated by 1H NMR titration experiments and LC-MS analysis,with experimental results sufficiently and consistently supporting the proposed mechanism of the catalytic cycle.
基金supported by the National Key R&D Program of China(No.2022YFC3203602)the Natural Science Foundation of China(No.52370018)+1 种基金Shaanxi Provincial Youth Innovation Team Project(No.22JP040)Shaanxi Provincial Key Scientific and Technological Innovation Team(No.2023-CX-TD-32).
文摘During the initial impoundment period of a canyon-shaped reservoir,the water body fluctuated violently regarding water level,hydrological condition,and thermal stratification.These variations may alter the structure of phytoplankton community,resulting in algal blooms and seriously threatening the ecological security of the reservoir.It is of great significance to understand the continuous changes of phytoplankton in the initial impoundment period for the protection of reservoir water quality.Therefore,a two-year in-situ monitoring study was conducted on water quality and phytoplankton in a representative canyonshaped reservoir named Sanhekou and the interannual changes of phytoplankton community and its response to environmental changes during the initial impoundment period were discussed at taxonomic versus functional classification levels.The results showed that the total nitrogen and permanganate index levels were relatively high in the first year due to rapid water storage and heavy rainfall input,and the more stable hydrological conditions in the second year promoted the increase of algae density and the transformation of community,and the proportion of cyanobacteria increased significantly.The succession order of phytoplankton in the first year of the initial impoundment periodwas Chlorophyta-Bacillariophyta-Chlorophyta,or J/F/X1-P/MP/W1-A/X1/MP,respectively.And the succession order in the second year was Cyanobacteria/Chlorophyta-Bacillariophyta-Chlorophyta,or L_(M)/G/P-P/A/X1-X1/J/G.Water temperature,relativewater column stability,mixing depth,and pHwere crucial factors affecting phytoplankton community succession.This study revealed the interannual succession law and driving factors of phytoplankton in the initial impoundment period and provided an important reference for the operation management and ecological protection of canyon-shaped reservoirs.
基金financially supported by the National Natural Science Foundation of China(62464010)Spring City Plan-Special Program for Young Talents(K202005007)+3 种基金Yunnan Talents Support Plan for Yong Talents(XDYC-QNRC-2022-0482)Yunnan Local Colleges Applied Basic Research Projects(202101BA070001-138)Key Laboratory of Artificial Microstructures in Yunnan Higher EducationFrontier Research Team of Kunming University 2023。
文摘Zinc-ion batteries(ZIBs)are inexpensive and safe,but side reactions on the Zn anode and Zn dendrite growth hinder their practical applications.In this study,1,3,5-triformylphloroglycerol(Tp)and various diamine monomers(p-phenylenediamine(Pa),benzidine(BD),and 4,4"-diamino-p-terphenyl(DATP))were used to synthesize a series of two-dimensional covalent-organic frameworks(COFs).The resulting COFs were named TpPa,TpBD,and TpDATP,respectively,and they showed uniform zincophilic sites,different pore sizes,and high Young's moduli on the Zn anode.Among them,TpPa and TpBD showed lower surface work functions and higher ion transfer numbers,which were conducive to uniform galvanizing/stripping zinc and inhibited dendrite growth.Theoretical calculations showed that TpPa and TpBD had wider negative potential region and greater adsorption capacity for Zn2+than TpDATP,providing more electron donor sites to coordinate with Zn^(2+).Symmetric cells protected by TpPa and TpBD stably cycled for more than 2300 h,whereas TpDATP@Zn and the bare zinc symmetric cells failed after around 150 and200 h.The full cells containing TpPa and TpBD modification layers also showed excellent cycling capacity at 1 A/g.This study provides comprehensive insights into the construction of highly reversible Zn anodes via COF modification layers for advanced rechargeable ZIBs.
