The organization of biological neuronal networks into functional modules has intrigued scientists and inspired engineers to develop artificial systems.These networks are characterized by two key properties.First,they ...The organization of biological neuronal networks into functional modules has intrigued scientists and inspired engineers to develop artificial systems.These networks are characterized by two key properties.First,they exhibit dense interconnectivity(Braitenburg and Schüz,1998;Campagnola et al.,2022).The strength and probability of connectivity depend on cell type,inter-neuronal distance,and species.Still,every cortical neuron receives input from thousands of other neurons while transmitting output to a similar number of neurons.Second,communication between neurons occurs primarily via chemical or electrical synapses.展开更多
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
Spinal cord injury(SCI) often results in permanent dysfunction of locomotion,sensation,and autonomic regulation,imposing a substantial burden on both individuals and society(Anjum et al.,2020).SCI has a complex pathop...Spinal cord injury(SCI) often results in permanent dysfunction of locomotion,sensation,and autonomic regulation,imposing a substantial burden on both individuals and society(Anjum et al.,2020).SCI has a complex pathophysiology:an initial primary injury(mechanical trauma,axonal disruption,and hemorrhage) is followed by a progressive secondary injury cascade that involves ischemia,neuronal loss,and inflammation.Given the challenges in achieving regeneration of the injured spinal cord,neuroprotection has been at the forefront of clinical research.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
The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzh...The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzheimer's or Parkinson's disease)or traumatic injuries(such as spinal cord lesions).In the last 20 years,the field has made significant progress in unlocking axon regrowth.展开更多
Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological s...Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.展开更多
Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functio...Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functional recovery after brain injury.Neuromodulation technologies represent one of the fastest-growing fields in medicine.These techniques utilize electricity,magnetism,sound,and light to restore or optimize brain functions by promoting reorganization or long-term changes that support functional recovery in patients with brain injury.Therefore,this review aims to provide a comprehensive overview of the effects and underlying mechanisms of neuromodulation technologies in supporting motor function recovery after brain injury.Many of these technologies are widely used in clinical practice and show significant improvements in motor function across various types of brain injury.However,studies report negative findings,potentially due to variations in stimulation protocols,differences in observation periods,and the severity of functional impairments among participants across different clinical trials.Additionally,we observed that different neuromodulation techniques share remarkably similar mechanisms,including promoting neuroplasticity,enhancing neurotrophic factor release,improving cerebral blood flow,suppressing neuroinflammation,and providing neuroprotection.Finally,considering the advantages and disadvantages of various neuromodulation techniques,we propose that future development should focus on closed-loop neural circuit stimulation,personalized treatment,interdisciplinary collaboration,and precision stimulation.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
Analyzing the function of gene sets is a critical step in interpreting the results of high-throughput experiments in systems biology. A variety of enrichment analysis tools have been developed in recent years, but mos...Analyzing the function of gene sets is a critical step in interpreting the results of high-throughput experiments in systems biology. A variety of enrichment analysis tools have been developed in recent years, but most output a long list of significantly enriched terms that are often redundant, making it difficult to extract the most meaningful functions. In this paper, we present GOMA, a novel enrichment analysis method based on the new concept of enriched functional Gene Ontology (GO) modules. With this method, we systematically revealed functional GO modules, i.e., groups of functionally similar GO terms, via an optimization model and then ranked them by enrichment scores. Our new method simplifies enrichment analysis results by reducing redundancy, thereby preventing inconsistent enrichment results among functionally similar terms and providing more biologically meaningful results.展开更多
Modularity is the key to improving the cost-variety trade-off in product development. To achieve the functional independency and structural independency of modules, a method of clustering components to identify module...Modularity is the key to improving the cost-variety trade-off in product development. To achieve the functional independency and structural independency of modules, a method of clustering components to identify modules based on functional and structural analysis was presented. Two stages were included in the method. In the first stage the products’ function was analyzed to determine the primary level of modules. Then the objective function for modules identifying was formulated to achieve functional independency of modules. Finally the genetic algorithm was used to solve the combinatorial optimization problem in modules identifying to form the primary modules of products. In the second stage the cohesion degree of modules and the coupling degree between modules were analyzed. Based on this structural analysis the modular scheme was refined according to the thinking of structural independency. A case study on the gear reducer was conducted to illustrate the validity of the presented method.展开更多
Tin dioxide(SnO_(2))has been demonstrated as one of the promising electron transport layers for high-efficiency perovskite solar cells(PSCs).However,scalable fabrication of SnO_(2) films with uniform coverage,desirabl...Tin dioxide(SnO_(2))has been demonstrated as one of the promising electron transport layers for high-efficiency perovskite solar cells(PSCs).However,scalable fabrication of SnO_(2) films with uniform coverage,desirable thickness and a low defect density in perovskite solar mod-ules(PSMs)is still challenging.Here,we report preparation of high-quality large-area SnO_(2) films by chemical bath depo-sition(CBD)with the addition of KMnO_(4).The strong oxidiz-ing nature of KMnO_(4) promotes the conversion from Sn(II)to Sn(VI),leading to reduced trap defects and a higher carrier mobility of SnO_(2).In addition,K ions diffuse into the per-ovskite film resulting in larger grain sizes,passivated grain boundaries,and reduced hysteresis of PSCs.Furthermore,Mn ion doping improves both the crystallinity and the phase stability of the perovskite film.Such a multifunctional interface engineering strategy enabled us to achieve a power conversion efficiency(PCE)of 21.70% with less hysteresis for lab-scale PSCs.Using this method,we also fabricated 5×5 and 10×10 cm^(2) PSMs,which showed PCEs of 15.62% and 11.80%(active area PCEs are 17.26%and 13.72%),respectively.For the encapsulated 5×5 cm^(2) PSM,we obtained a T80 operation lifetime(the lifespan during which the solar module PCE drops to 80%of its initial value)exceeding 1000 h in ambient condition.展开更多
In this editorial preface, I briefly r eview cancer bioinformatics and introduce the four articles in this special issue highlighting important applications of the field: detection of chromatin states; detection of SN...In this editorial preface, I briefly r eview cancer bioinformatics and introduce the four articles in this special issue highlighting important applications of the field: detection of chromatin states; detection of SNP- containing motifs and association with transcription factor-binding sites; improvements in functional enrichment modules; and gene association studies on aging and cancer. We expect this issue to provide bioinformatics scientists, cancer biologists, and clinical doctors with a better understanding of how cancer bioinformatics can be used to identify candidate biomarkers and targets and to conduct functional analysis.展开更多
Wind is one kind of clean and free renewable energy sources. Wind speed plays a pivotal role in the wind power output. However, due to the random and unstable nature of the wind, accurate prediction of wind speed is a...Wind is one kind of clean and free renewable energy sources. Wind speed plays a pivotal role in the wind power output. However, due to the random and unstable nature of the wind, accurate prediction of wind speed is a particularly challenging task. This paper presents a novel neural fuzzy method for the hourly wind speed prediction. Firstly, a neural structure is proposed for the functional-type single-input-rule-modules(FSIRMs) connected fuzzy inference system(FIS) to combine the merits of both the FSIRMs connected FIS and the neural network. Then, in order to achieve both the smallest training errors and the smallest parameters, a least square method based parameter learning algorithm is presented for the proposed FSIRMs connected neural fuzzy system(FSIRMNFS). Further,the proposed FSIRMNFS and its parameter learning algorithm are applied to the hourly wind speed prediction. Experiments and comparisons are also made to show the effectiveness and advantages of the proposed approach. Experimental results verified that our study has presented an effective approach for the hourly wind speed prediction. The proposed approach can also be used for the prediction of wind direction, wind power and some other prediction applications in the research field of renewable energy.展开更多
MicroRNAs(miRNAs)are non-coding RNAs that interact with target genes and are involved in many physiological processes in plants.miR172-AP2 mainly plays a role in the regulation of f lowering time and floral organ diff...MicroRNAs(miRNAs)are non-coding RNAs that interact with target genes and are involved in many physiological processes in plants.miR172-AP2 mainly plays a role in the regulation of f lowering time and floral organ differentiation.Bud dormancy release is necessary for forcing culture of tree peony in winter,but the mechanism of dormancy regulation is unclear.In this study,we found that a miR172 family member,PsmiR172b,was downregulated during chilling-induced bud dormancy release in tree peony,exhibiting a trend opposite to that of PsTOE3.RNA ligase-mediated(RLM)5-RACE(rapid amplification of cDNA ends)confirmed that miR172b targeted PsTOE3,and the cleavage site was between bases 12(T)and 13(C)within the complementary site to miR172b.The functions of miR172b and PsTOE3 were detected by virus-induced gene silencing(VIGS)and their overexpression in tree peony buds.PsmiR172b negatively regulated bud dormancy release,but PsTOE3 promoted bud dormancy release,and the genes associated with bud dormancy release,including PsEBB1,PsEBB3,PsCYCD,and PsBG6,were upregulated.Further analysis indicated that PsTOE3 directly regulated PsEBB1 by binding to its promoter,and the specific binding site was a C-repeat(ACCGAC).Ectopic expression in Arabidopsis revealed that the PsmiR172b-PsTOE3 module displayed conservative function in regulating f lowering.In conclusion,our results provided a novel insight into the functions of PsmiR172-PsTOE3 and possible molecular mechanism underlying bud dormancy release in tree peony.展开更多
In this paper, we firstly identify the functional modules enriched with differentially expressed genes （DEGs） and characterized by biological processes in specific cellular locations, based on gene ontology （GO） a...In this paper, we firstly identify the functional modules enriched with differentially expressed genes （DEGs） and characterized by biological processes in specific cellular locations, based on gene ontology （GO） and microarray data. Then, we further define and filter disease relevant signature modules according to the ranking of the disease discriminating abilities of the pre-selected functional modules. At last, we analyze the potential way by which they cooperate towards human disease. Application of the proposed method to the analysis of a liver cancer dataset shows that, using the same false discovery rate （ FDR ） threshold, we can find more biologically meaningful and detailed processes by using the cellular localization information. Some biological evidences support the relevancy of our biological modules to the disease mechanism.展开更多
Electric vehicles(EVs)have garnered significant attention as a vital driver of economic growth and environmental sustainability.Nevertheless,ensuring the safety of high-energy batteries is now a top priority that cann...Electric vehicles(EVs)have garnered significant attention as a vital driver of economic growth and environmental sustainability.Nevertheless,ensuring the safety of high-energy batteries is now a top priority that cannot be overlooked during large-scale applications.This paper proposes an innovative active protection and cooling integrated battery module using smart materials,magneto-sensitive shear thickening fluid(MSTF),which is specifically designed to address safety threats posed by lithium-ion batteries(LIBs)exposed to harsh mechanical and environmental conditions.The theoretical framework introduces a novel approach for harnessing the smoothed-particle hydrodynamics(SPH)methodology that incorporates the intricate interplay of non-Newtonian fluid behavior,capturing the fluid-structure coupling inherent to the MSTF.This approach is further advanced by adopting an enhanced Herschel-Bulkley(H-B)model to encapsulate the intricate rheology of the MSTF under the influence of the magnetorheological effect(MRE)and shear thickening(ST)behavior.Numerical simulation results show that in the case of cooling,the MSTF is an effective cooling medium for rapidly reducing the temperature.In terms of mechanical abuse,the MSTF solidifies through actively applying the magnetic field during mechanical compression and impact within the battery module,resulting in 66%and 61.7%reductions in the maximum stress within the battery jellyroll,and 31.1%and 23%reductions in the reaction force,respectively.This mechanism effectively lowers the risk of short-circuit failure.The groundbreaking concepts unveiled in this paper for active protection battery modules are anticipated to be a valuable technological breakthrough in the areas of EV safety and lightweight/integrated design.展开更多
基金supported in part by the Rosetrees Trust(#CF-2023-I-2_113)by the Israel Ministry of Innovation,Science,and Technology(#7393)(to ES).
文摘The organization of biological neuronal networks into functional modules has intrigued scientists and inspired engineers to develop artificial systems.These networks are characterized by two key properties.First,they exhibit dense interconnectivity(Braitenburg and Schüz,1998;Campagnola et al.,2022).The strength and probability of connectivity depend on cell type,inter-neuronal distance,and species.Still,every cortical neuron receives input from thousands of other neurons while transmitting output to a similar number of neurons.Second,communication between neurons occurs primarily via chemical or electrical synapses.
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Spinal cord injury(SCI) often results in permanent dysfunction of locomotion,sensation,and autonomic regulation,imposing a substantial burden on both individuals and society(Anjum et al.,2020).SCI has a complex pathophysiology:an initial primary injury(mechanical trauma,axonal disruption,and hemorrhage) is followed by a progressive secondary injury cascade that involves ischemia,neuronal loss,and inflammation.Given the challenges in achieving regeneration of the injured spinal cord,neuroprotection has been at the forefront of clinical research.
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 ANR(ANR-21CE16-0008-01)ANR(ANR-21-CE16-0008-02 and ANR-23CE52-0007)+1 种基金UNADEV(A22018CS)(to HN)UNADEV(A22020CS)(to SB)。
文摘The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzheimer's or Parkinson's disease)or traumatic injuries(such as spinal cord lesions).In the last 20 years,the field has made significant progress in unlocking axon regrowth.
基金supported by Deutsche Forschungsgemeinschaft,German Research Foundation grant GA 654/13-2 to OG.
文摘Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.
基金supported by the National Natural Science Foundation of China,No.82371399(to YY)the Natural Science Foundation of Jiangsu Province,No.BK20221206(to YY)+1 种基金the Young Elite Scientists Sponsorship Program of Jiangsu Province,No.TJ-2022-028(to YY)the Scientific Research Program of Wuxi Health Commission,No.Z202302(to LY)。
文摘Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functional recovery after brain injury.Neuromodulation technologies represent one of the fastest-growing fields in medicine.These techniques utilize electricity,magnetism,sound,and light to restore or optimize brain functions by promoting reorganization or long-term changes that support functional recovery in patients with brain injury.Therefore,this review aims to provide a comprehensive overview of the effects and underlying mechanisms of neuromodulation technologies in supporting motor function recovery after brain injury.Many of these technologies are widely used in clinical practice and show significant improvements in motor function across various types of brain injury.However,studies report negative findings,potentially due to variations in stimulation protocols,differences in observation periods,and the severity of functional impairments among participants across different clinical trials.Additionally,we observed that different neuromodulation techniques share remarkably similar mechanisms,including promoting neuroplasticity,enhancing neurotrophic factor release,improving cerebral blood flow,suppressing neuroinflammation,and providing neuroprotection.Finally,considering the advantages and disadvantages of various neuromodulation techniques,we propose that future development should focus on closed-loop neural circuit stimulation,personalized treatment,interdisciplinary collaboration,and precision stimulation.
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 grants from the National Natural Science Foundation of China(No.60970091, 61171007, 11131009)
文摘Analyzing the function of gene sets is a critical step in interpreting the results of high-throughput experiments in systems biology. A variety of enrichment analysis tools have been developed in recent years, but most output a long list of significantly enriched terms that are often redundant, making it difficult to extract the most meaningful functions. In this paper, we present GOMA, a novel enrichment analysis method based on the new concept of enriched functional Gene Ontology (GO) modules. With this method, we systematically revealed functional GO modules, i.e., groups of functionally similar GO terms, via an optimization model and then ranked them by enrichment scores. Our new method simplifies enrichment analysis results by reducing redundancy, thereby preventing inconsistent enrichment results among functionally similar terms and providing more biologically meaningful results.
基金National Basic Research Programme of China (973 Program) (No. 2003CB317005)Key Project of Chinese Ministry of Educa-tion (No. 105065)
文摘Modularity is the key to improving the cost-variety trade-off in product development. To achieve the functional independency and structural independency of modules, a method of clustering components to identify modules based on functional and structural analysis was presented. Two stages were included in the method. In the first stage the products’ function was analyzed to determine the primary level of modules. Then the objective function for modules identifying was formulated to achieve functional independency of modules. Finally the genetic algorithm was used to solve the combinatorial optimization problem in modules identifying to form the primary modules of products. In the second stage the cohesion degree of modules and the coupling degree between modules were analyzed. Based on this structural analysis the modular scheme was refined according to the thinking of structural independency. A case study on the gear reducer was conducted to illustrate the validity of the presented method.
基金supported by funding from the Energy Materials and Surface Sciences Unit of the Okinawa Institute of Science and Technology Graduate Universitythe OIST R&D Cluster Research Program,the OIST Proof of Concept(POC)ProgramJST A-STEP Grant Number JPMJTM20HS,Japan。
文摘Tin dioxide(SnO_(2))has been demonstrated as one of the promising electron transport layers for high-efficiency perovskite solar cells(PSCs).However,scalable fabrication of SnO_(2) films with uniform coverage,desirable thickness and a low defect density in perovskite solar mod-ules(PSMs)is still challenging.Here,we report preparation of high-quality large-area SnO_(2) films by chemical bath depo-sition(CBD)with the addition of KMnO_(4).The strong oxidiz-ing nature of KMnO_(4) promotes the conversion from Sn(II)to Sn(VI),leading to reduced trap defects and a higher carrier mobility of SnO_(2).In addition,K ions diffuse into the per-ovskite film resulting in larger grain sizes,passivated grain boundaries,and reduced hysteresis of PSCs.Furthermore,Mn ion doping improves both the crystallinity and the phase stability of the perovskite film.Such a multifunctional interface engineering strategy enabled us to achieve a power conversion efficiency(PCE)of 21.70% with less hysteresis for lab-scale PSCs.Using this method,we also fabricated 5×5 and 10×10 cm^(2) PSMs,which showed PCEs of 15.62% and 11.80%(active area PCEs are 17.26%and 13.72%),respectively.For the encapsulated 5×5 cm^(2) PSM,we obtained a T80 operation lifetime(the lifespan during which the solar module PCE drops to 80%of its initial value)exceeding 1000 h in ambient condition.
文摘In this editorial preface, I briefly r eview cancer bioinformatics and introduce the four articles in this special issue highlighting important applications of the field: detection of chromatin states; detection of SNP- containing motifs and association with transcription factor-binding sites; improvements in functional enrichment modules; and gene association studies on aging and cancer. We expect this issue to provide bioinformatics scientists, cancer biologists, and clinical doctors with a better understanding of how cancer bioinformatics can be used to identify candidate biomarkers and targets and to conduct functional analysis.
基金supported by the National Natural Science Foundation of China(61473176,61402260,61573225)the Natural Science Foundation of Shandong Province for Outstanding Young Talents in Provincial Universities(ZR2015JL021,ZR2015JL003)the Open Program from the State Key Laboratory of Management and Control for Complex Systems(20140102)
文摘Wind is one kind of clean and free renewable energy sources. Wind speed plays a pivotal role in the wind power output. However, due to the random and unstable nature of the wind, accurate prediction of wind speed is a particularly challenging task. This paper presents a novel neural fuzzy method for the hourly wind speed prediction. Firstly, a neural structure is proposed for the functional-type single-input-rule-modules(FSIRMs) connected fuzzy inference system(FIS) to combine the merits of both the FSIRMs connected FIS and the neural network. Then, in order to achieve both the smallest training errors and the smallest parameters, a least square method based parameter learning algorithm is presented for the proposed FSIRMs connected neural fuzzy system(FSIRMNFS). Further,the proposed FSIRMNFS and its parameter learning algorithm are applied to the hourly wind speed prediction. Experiments and comparisons are also made to show the effectiveness and advantages of the proposed approach. Experimental results verified that our study has presented an effective approach for the hourly wind speed prediction. The proposed approach can also be used for the prediction of wind direction, wind power and some other prediction applications in the research field of renewable energy.
基金supported by grants fromNational Natural Science Foundation of China(31872145 and 31972452)the National Key R&D Programof China(2018YFD1000403).
文摘MicroRNAs(miRNAs)are non-coding RNAs that interact with target genes and are involved in many physiological processes in plants.miR172-AP2 mainly plays a role in the regulation of f lowering time and floral organ differentiation.Bud dormancy release is necessary for forcing culture of tree peony in winter,but the mechanism of dormancy regulation is unclear.In this study,we found that a miR172 family member,PsmiR172b,was downregulated during chilling-induced bud dormancy release in tree peony,exhibiting a trend opposite to that of PsTOE3.RNA ligase-mediated(RLM)5-RACE(rapid amplification of cDNA ends)confirmed that miR172b targeted PsTOE3,and the cleavage site was between bases 12(T)and 13(C)within the complementary site to miR172b.The functions of miR172b and PsTOE3 were detected by virus-induced gene silencing(VIGS)and their overexpression in tree peony buds.PsmiR172b negatively regulated bud dormancy release,but PsTOE3 promoted bud dormancy release,and the genes associated with bud dormancy release,including PsEBB1,PsEBB3,PsCYCD,and PsBG6,were upregulated.Further analysis indicated that PsTOE3 directly regulated PsEBB1 by binding to its promoter,and the specific binding site was a C-repeat(ACCGAC).Ectopic expression in Arabidopsis revealed that the PsmiR172b-PsTOE3 module displayed conservative function in regulating f lowering.In conclusion,our results provided a novel insight into the functions of PsmiR172-PsTOE3 and possible molecular mechanism underlying bud dormancy release in tree peony.
基金the National High Technology Research and Development Programme of China(No.2003AA2Z20512002AA2Z2052)+1 种基金the National Natural Science Foundation of China(No.3017051530370388)
文摘In this paper, we firstly identify the functional modules enriched with differentially expressed genes （DEGs） and characterized by biological processes in specific cellular locations, based on gene ontology （GO） and microarray data. Then, we further define and filter disease relevant signature modules according to the ranking of the disease discriminating abilities of the pre-selected functional modules. At last, we analyze the potential way by which they cooperate towards human disease. Application of the proposed method to the analysis of a liver cancer dataset shows that, using the same false discovery rate （ FDR ） threshold, we can find more biologically meaningful and detailed processes by using the cellular localization information. Some biological evidences support the relevancy of our biological modules to the disease mechanism.
基金Project supported by the National Natural Science Foundation of China(Nos.12072183 and11872236)the Key Research Project of Zhejiang Laboratory(No.2021PE0AC02)。
文摘Electric vehicles(EVs)have garnered significant attention as a vital driver of economic growth and environmental sustainability.Nevertheless,ensuring the safety of high-energy batteries is now a top priority that cannot be overlooked during large-scale applications.This paper proposes an innovative active protection and cooling integrated battery module using smart materials,magneto-sensitive shear thickening fluid(MSTF),which is specifically designed to address safety threats posed by lithium-ion batteries(LIBs)exposed to harsh mechanical and environmental conditions.The theoretical framework introduces a novel approach for harnessing the smoothed-particle hydrodynamics(SPH)methodology that incorporates the intricate interplay of non-Newtonian fluid behavior,capturing the fluid-structure coupling inherent to the MSTF.This approach is further advanced by adopting an enhanced Herschel-Bulkley(H-B)model to encapsulate the intricate rheology of the MSTF under the influence of the magnetorheological effect(MRE)and shear thickening(ST)behavior.Numerical simulation results show that in the case of cooling,the MSTF is an effective cooling medium for rapidly reducing the temperature.In terms of mechanical abuse,the MSTF solidifies through actively applying the magnetic field during mechanical compression and impact within the battery module,resulting in 66%and 61.7%reductions in the maximum stress within the battery jellyroll,and 31.1%and 23%reductions in the reaction force,respectively.This mechanism effectively lowers the risk of short-circuit failure.The groundbreaking concepts unveiled in this paper for active protection battery modules are anticipated to be a valuable technological breakthrough in the areas of EV safety and lightweight/integrated design.
