Neuropathic pain is frequently comorbidity with cognitive deficits.Neuralized1(Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory.However,the role of Neurl1 in the cognitive...Neuropathic pain is frequently comorbidity with cognitive deficits.Neuralized1(Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory.However,the role of Neurl1 in the cognitive impairment in neuropathic pain remains elusive.Herein,we found that lumbar 5 spinal nerve ligation(SNL)in male rat-induced neuropathic pain was followed by learning and memory deficits and LTP impairment in the hippocampus.The Neurl1 expression in the hippocampal CA1 was decreased after SNL.And this decrease paralleled the reduction of ubiquitinated-CPEB3 level and reduced production of GluA1 and GluA2.Overexpression of Neurl1 in the CA1 rescued cognitive deficits and LTP impairment,and reversed the reduction of ubiquitinated-CPEB3 level and the decrease of GluA1 and GluA2 production following SNL.Specific knockdown of Neurl1 or CPEB3 in bilateral hippocampal CA1 in naïve rats resulted in cognitive deficits and impairment of synaptic plasticity.The rescued cognitive function and synaptic plasticity by the treatment of overexpression of Neurl1 before SNL were counteracted by the knockdown of CPEB3 in the CA1.Collectively,the above results suggest that the downregulation of Neurl1 through reducing CPEB3 ubiquitination and,in turn,repressing GluA1 and GluA2 production and mediating synaptic plasticity impairment in hippocampal CA1 leads to the genesis of cognitive deficits in neuropathic pain.展开更多
Deep learning(DL)models have demonstrated significant value in computational perception,superresolution imaging,ultra-precision measurement,and photonic device design.In optical communication signal recognition,DL mod...Deep learning(DL)models have demonstrated significant value in computational perception,superresolution imaging,ultra-precision measurement,and photonic device design.In optical communication signal recognition,DL models can achieve fast and accurate identification.However,in high-capacity optical communication systems represented by orbital angular momentum(OAM)beams,neural networks often suffer from excessive parameter sizes and demand large training datasets.To address these challenges,we report a lightweight MobileNetV1 model optimized with efficient channel attention to perform OAM mode recognition after transmission through free space and underwater tank environments.Experimental results show that in simulated small-sample classification tasks with five samples per class,the proposed model achieves an accuracy of 99.67%even under moderate turbulence conditions,outperforming four other DL models.In addition,for experimental datasets collected from both atmospheric turbulence and underwater environments,the model consistently achieves recognition accuracies exceeding 90%,demonstrating strong generalization ability and a 77%reduction in parameter count compared to traditional convolutional neural network(CNN)-based DL models.We provide a new approach for deploying lightweight DL algorithms on resource-constrained embedded optical signal detection devices.展开更多
We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies wer...We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies were performed with whole blood,4 with blood plasma,5 with blood serum,1 with serum neural cell adhesion molecule L1-captured extracellular vesicles,1 with blood cells,and 2 with peripheral blood mononuclear cells.Most of the studies involved children and the study cohorts were largely males.Many of the studies had performed microRNA sequencing or quantitative polymerase chain reaction assays to measure microRNA expression.Only five studies had used real-time polymerase chain reaction assay to validate microRNA expression in autism spectrum disorder subjects compared to controls.The microRNAs that were validated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p,-197-5p,-424-5p,-664a-3p,-365a-3p,-619-5p,-664a-3p,-3135a,-328-3p,and-500a-5p in blood plasma and miR-151a-3p,-181b-5p,-320a,-328,-433,-489,-572,-663a,-101-3p,-106b-5p,-19b-3p,-195-5p,and-130a-3p in blood serum of children,and miR-15b-5p and-6126 in whole blood of adults.Several important limitations were identified in the studies reviewed,and need to be taken into account in future studies.Further studies are warranted with children and adults having different levels of autism spectrum disorder severity and consideration should be given to using animal models of autism spectrum disorder to investigate the effects of suppressing or overexpressing specific microRNAs as a novel therapy.展开更多
In order to directly construct the mapping between multiple state parameters and remaining useful life(RUL),and reduce the interference of random error on prediction accuracy,a RUL prediction model of aeroengine based...In order to directly construct the mapping between multiple state parameters and remaining useful life(RUL),and reduce the interference of random error on prediction accuracy,a RUL prediction model of aeroengine based on principal component analysis(PCA)and one-dimensional convolution neural network(1D-CNN)is proposed in this paper.Firstly,multiple state parameters corresponding to massive cycles of aeroengine are collected and brought into PCA for dimensionality reduction,and principal components are extracted for further time series prediction.Secondly,the 1D-CNN model is constructed to directly study the mapping between principal components and RUL.Multiple convolution and pooling operations are applied for deep feature extraction,and the end-to-end RUL prediction of aeroengine can be realized.Experimental results show that the most effective principal component from the multiple state parameters can be obtained by PCA,and the long time series of multiple state parameters can be directly mapped to RUL by 1D-CNN,so as to improve the efficiency and accuracy of RUL prediction.Compared with other traditional models,the proposed method also has lower prediction error and better robustness.展开更多
The formation of nerve bundles,which is partially regulated by neural cell adhesion molecule 1(NCAM1),is important for neural network organization during peripheral nerve regeneration.However,little is known about how...The formation of nerve bundles,which is partially regulated by neural cell adhesion molecule 1(NCAM1),is important for neural network organization during peripheral nerve regeneration.However,little is known about how the extracellular matrix(ECM)microenvironment affects this process.Here,we seeded dorsal root ganglion tissue blocks on different ECM substrates of peripheral nerve ECM-derived matrixgel,Matrigel,laminin 521,collagen I,and collagen IV,and observed well-aligned axon bundles growing in the peripheral nerve ECM-derived environment.We confirmed that NCAM1 is necessary but not sufficient to trigger this phenomenon.A protein interaction assay identified collagen VI as an extracellular partner of NCAM1 in the regulation of axonal fasciculation.Collagen VI interacted with NCAM1 by directly binding to the FNIII domain,thereby increasing the stability of NCAM1 at the axolemma.Our in vivo experiments on a rat sciatic nerve defect model also demonstrated orderly nerve bundle regeneration with improved projection accuracy and functional recovery after treatment with 10 mg/m L Matrigel and 20μg/m L collagen VI.These findings suggest that the collagen VI-NCAM1 pathway plays a regulatory role in nerve bundle formation.This study was approved by the Animal Ethics Committee of Guangzhou Medical University(approval No.GY2019048)on April 30,2019.展开更多
When the physiopathology of membranous nephropathy was first described,almost 30%of cases were recognized to be secondary to well-known diseases such as autoimmune diseases,tumors or infections.The remaining 70%cases ...When the physiopathology of membranous nephropathy was first described,almost 30%of cases were recognized to be secondary to well-known diseases such as autoimmune diseases,tumors or infections.The remaining 70%cases were called primary membranous nephropathy as the exact mechanism or pathogenic factor involved was unknown.The discovery of the M type phospholipase A2 receptor and thrombospondin type 1 domain containing 7A as causative antigens in these“so called”primary membranous nephropathies provided new insights into the effective causes of a large proportion of these cases.Novel techniques such as laser microdissection and tandem mass spectrometry as well as immunochemistry with antibodies directed against novel proteins allowed the confirmation of new involved antigens.Finally,using confocal microscopy to localize these new antigens and immunoglobulin G and Western blot analysis of serum samples,these new antigens were detected on the glomerular membrane,and the related antibodies were detected in serum samples.The same antigens have been recognized in some cases of secondary membranous disease due to autoimmune diseases,tumors and infections.This has allowed examination of the relationship between antigens in primary membranous nephropathy and their presence in some secondary nephropathies.The aim of this study is to describe the characteristics of the new antigens discovered and their association with other diseases.展开更多
Glucagon-like peptide 1（GLP-1）is secreted from enteroendocrine L cells in response to nutrient ingestion and exhibits insulinotropic properties by stimulating specific G protein-linked receptors（GLP-1Rs）on pancrea...Glucagon-like peptide 1（GLP-1）is secreted from enteroendocrine L cells in response to nutrient ingestion and exhibits insulinotropic properties by stimulating specific G protein-linked receptors（GLP-1Rs）on pancreaticβcells.Several GLP-1 mimetics,such as exenatide（exendin-4（Ex-4））,liraglutide,and lixisenatide,have been developed and approved as treatments for patients with type 2 diabetes.These peptides show bioactiv-ities almost identical to those of GLP- 1 and have a substantially longer plasma half-life than GLP-1 because of their resistance to dipeptidyl peptidase-4, a GLP-1 degrading enzyme.展开更多
Amyotrophic lateral sclerosis is a motoneuron degenerative disease that is challenging to diagnose and presents with considerable variability in survival.Early identification and enhanced understanding of symptomatic ...Amyotrophic lateral sclerosis is a motoneuron degenerative disease that is challenging to diagnose and presents with considerable variability in survival.Early identification and enhanced understanding of symptomatic patterns could aid in diagnosis and provide an avenue for monitoring disease progression.Use of the m SOD1 G93 A mouse model provides control of the confounding environmental factors and genetic heterogeneity seen in amyotrophic lateral sclerosis patients,while investigating underlying disease-induced changes.In the present study,we performed a longitudinal behavioral assessment paradigm and identified an early hindlimb symptom,resembling the common gait abnormality foot drop,along with an accompanying forelimb compensatory mechanism in the m SOD1 G93 A mouse.Following these initial changes,m SOD1 mice displayed a temporary hindlimb compensatory mechanism resembling an exaggerated steppage gait.As the disease progressed,these compensatory mechanisms were not sufficient to sustain fundamental locomotor parameters and more severe deficits appeared.We next applied these initial findings to investigate the inherent variability in B6 SJL m SOD1 G93 A survival.We identified four behavioral variables that,when combined in a cluster analysis,identified two subpopulations with different disease progression rates：a fast progression group and a slow progression group.This behavioral assessment paradigm,with its analytical approaches,provides a method for monitoring disease progression and detecting m SOD1 subgroups with different disease severities.This affords researchers an opportunity to search for genetic modifiers or other factors that likely enhance or slow disease progression.Such factors are possible therapeutic targets with the potential to slow disease progression and provide insight into the underlying pathology and disease mechanisms.展开更多
The regulatory mechanisms of cytoplasmic Ca2+after myocardial infarction-induced Ca2+overload involve secretory pathway Ca2+-ATPase 1 and the Golgi apparatus and are well understood.However,the effect of Golgi apparat...The regulatory mechanisms of cytoplasmic Ca2+after myocardial infarction-induced Ca2+overload involve secretory pathway Ca2+-ATPase 1 and the Golgi apparatus and are well understood.However,the effect of Golgi apparatus on Ca2+overload after cerebral ischemia and reperfusion remains unclear.Four-vessel occlusion rats were used as animal models of cerebral ischemia.The expression of secretory pathway Ca2+-ATPase 1 in the cortex and hippocampus was detected by immunoblotting,and Ca2+concentrations in the cytoplasm and Golgi vesicles were determined.Results showed an overload of cytoplasmic Ca2+during ischemia and reperfusion that reached a peak after reperfusion.Levels of Golgi Ca2+showed an opposite effect.The expression of Golgi-specific secretory pathway Ca2+-ATPase 1 in the cortex and hippocampus decreased before ischemia and reperfusion,and increased after reperfusion for 6 hours.This variation was similar to the alteration of calcium in separated Golgi vesicles.These results indicate that the Golgi apparatus participates in the formation and alleviation of calcium overload,and that secretory pathway Ca2+-ATPase 1 tightly responds to ischemia and reperfusion in nerve cells.Thus,we concluded that secretory pathway Ca2+-ATPase 1 plays an essential role in cytosolic calcium regulation and its expression can be used as a marker of Golgi stress,responding to cerebral ischemia and reperfusion.The secretory pathway Ca2+-ATPase 1 can be an important neuroprotective target of ischemic stroke.展开更多
Expression of genes in the Notch signaling pathway is altered in the injured spinal cord, which indicates that Notch participates in repair after spinal cord injury. Buyang Huanwu decoction, a traditional Chinese herb...Expression of genes in the Notch signaling pathway is altered in the injured spinal cord, which indicates that Notch participates in repair after spinal cord injury. Buyang Huanwu decoction, a traditional Chinese herbal preparation, can promote the growth of nerve cells and nerve fibers; however, it is unclear whether Buyang Huanwu decoction affects the Notch signaling pathway in injured spinal cord. In this study, a rat model was established by injuring the T10 spinal cord. At 2 days after injury, rats were intragastrically administered 2 m L of 0.8 g/m L Buyang Huanwu decoction daily until sacrifice. Real-time reverse transcription polymerase chain reaction analysis demonstrated that at 7, 14 and 28 days after injury, the expression of Notch1 was increased in the Buyang Huanwu decoction group compared with controls. These findings confirm that Buyang Huanwu decoction can promote the expression of Notch1 in rats with incomplete spinal cord injury, and may indicate a mechanism to promote the repair of spinal cord injury.展开更多
The bistratified lobula giant type 1(BLG1) neuron is an identified looming-sensitive neuron in crab's visual brain that demonstrates special sensitivity to diving targets, or descending approaching motions. In thi...The bistratified lobula giant type 1(BLG1) neuron is an identified looming-sensitive neuron in crab's visual brain that demonstrates special sensitivity to diving targets, or descending approaching motions. In this paper, a novel neural model is proposed to shape such unique selectivity through incorporating a bio-plausible feedforward contrast inhibition synapse and a radially extending spatial enhancement distribution. Herein the synaptic connections and neuronal functions of this model are placed within a framework for matching and describing underlying biological findings. The systematic and comparative experiments have validated the proposed computational model that reconciles with the characteristics of BLG1 neurons in crab.展开更多
BACKGROUND： Interstitial stem cell is charactenzed by multiple differentiations, and retinoic acid （RA） can induce differentiation of stromal cells into nerve tissue cells in fetal liver of mice, so, its signal tra...BACKGROUND： Interstitial stem cell is charactenzed by multiple differentiations, and retinoic acid （RA） can induce differentiation of stromal cells into nerve tissue cells in fetal liver of mice, so, its signal transduction pathway should be discussed to trigger differentiation. OBJECTIVE ： To study the effect of RA on expression of neural specific gene and its signal transduction in fetal liver of mice.DESIGN ： Paired controlled study on the basis of cell.SETTING ： Institute of Hematology, Medical College of Jinan University.MATERIALS： The experiment was completed in the Institute of Hematology, Medical College of Jinan University from April to December 2005. C57BL/6 mice, of clean grade, aged 8-10 weeks, weighting 20-35 g, 10 females and 4 males, were selected in this study.METHODS： Sca-1^＋ cells in fetal liver were prepared with MACS kit and cultured with DMEM ＋ 10% fetal bovine serum （FBS）. On the fourth day, it was added with or without protein kinase C （PKC） inhibitor chelerythrine chloride （3μmol/L） and 5×10^-7 mol/L RA for 24 hours, and then incubated in serum-free medium for 5 days. Expressions of genes were assayed by Westem blotting and semi-quantitative RT-PCR.MAIN OUTCOME MEASURES ： Expression of neural specific gene NF-L, NF-H, BF-1 and TH.RESULTS： Expression of neural specific gene NF-L, NF-H, BF-1 and TH was significantly increased after treatment with RA and they were increased 5.06, 5.15, 4.63 and 3.33 times, respectively. However, chelerythrine chloride could inhibit expression of neural specific gene NF-L, NF-H, BF-1 and TH induced by RA.CONCLUSION ： RA can promote the expression of neural specific genes in Sca-1^＋ cells of fetal liver, and its pathway may be related to PKC.展开更多
Baicalin is a flavonoid compound extracted from Scutellaria baicalensis root.Recent evidence indicates that baicalin is neuroprotective in models of ischemic stroke.Here,we investigate the neuroprotective effect of ba...Baicalin is a flavonoid compound extracted from Scutellaria baicalensis root.Recent evidence indicates that baicalin is neuroprotective in models of ischemic stroke.Here,we investigate the neuroprotective effect of baicalin in a neonatal rat model of hypoxic-ischemic encephalopathy.Seven-day-old pups underwent left common carotid artery ligation followed by hypoxia（8% oxygen at 37°C） for 2 hours,before being injected with baicalin（120 mg/kg intraperitoneally） and examined 24 hours later.Baicalin effectively reduced cerebral infarct volume and neuronal loss,inhibited apoptosis,and upregulated the expression of p-Akt and glutamate transporter 1.Intracerebroventricular injection of the phosphoinositide 3-kinase/protein kinase B（PI3 K/Akt） inhibitor LY294002 30 minutes before injury blocked the effect of baicalin on p-Akt and glutamate transporter 1,and weakened the associated neuroprotective effect.Our findings provide the first evidence,to our knowledge that baicalin can protect neonatal rat brains against hypoxic-ischemic injury by upregulating glutamate transporter 1 via the PI3 K/Akt signaling pathway.展开更多
Purpose:With more and more digital collections of various information resources becoming available,also increasing is the challenge of assigning subject index terms and classes from quality knowledge organization syst...Purpose:With more and more digital collections of various information resources becoming available,also increasing is the challenge of assigning subject index terms and classes from quality knowledge organization systems.While the ultimate purpose is to understand the value of automatically produced Dewey Decimal Classification(DDC)classes for Swedish digital collections,the paper aims to evaluate the performance of six machine learning algorithms as well as a string-matching algorithm based on characteristics of DDC.Design/methodology/approach:State-of-the-art machine learning algorithms require at least 1,000 training examples per class.The complete data set at the time of research involved 143,838 records which had to be reduced to top three hierarchical levels of DDC in order to provide sufficient training data(totaling 802 classes in the training and testing sample,out of 14,413 classes at all levels).Findings:Evaluation shows that Support Vector Machine with linear kernel outperforms other machine learning algorithms as well as the string-matching algorithm on average;the string-matching algorithm outperforms machine learning for specific classes when characteristics of DDC are most suitable for the task.Word embeddings combined with different types of neural networks(simple linear network,standard neural network,1 D convolutional neural network,and recurrent neural network)produced worse results than Support Vector Machine,but reach close results,with the benefit of a smaller representation size.Impact of features in machine learning shows that using keywords or combining titles and keywords gives better results than using only titles as input.Stemming only marginally improves the results.Removed stop-words reduced accuracy in most cases,while removing less frequent words increased it marginally.The greatest impact is produced by the number of training examples:81.90%accuracy on the training set is achieved when at least 1,000 records per class are available in the training set,and 66.13%when too few records(often less than A Comparison of Approaches100 per class)on which to train are available—and these hold only for top 3 hierarchical levels(803 instead of 14,413 classes).Research limitations:Having to reduce the number of hierarchical levels to top three levels of DDC because of the lack of training data for all classes,skews the results so that they work in experimental conditions but barely for end users in operational retrieval systems.Practical implications:In conclusion,for operative information retrieval systems applying purely automatic DDC does not work,either using machine learning(because of the lack of training data for the large number of DDC classes)or using string-matching algorithm(because DDC characteristics perform well for automatic classification only in a small number of classes).Over time,more training examples may become available,and DDC may be enriched with synonyms in order to enhance accuracy of automatic classification which may also benefit information retrieval performance based on DDC.In order for quality information services to reach the objective of highest possible precision and recall,automatic classification should never be implemented on its own;instead,machine-aided indexing that combines the efficiency of automatic suggestions with quality of human decisions at the final stage should be the way for the future.Originality/value:The study explored machine learning on a large classification system of over 14,000 classes which is used in operational information retrieval systems.Due to lack of sufficient training data across the entire set of classes,an approach complementing machine learning,that of string matching,was applied.This combination should be explored further since it provides the potential for real-life applications with large target classification systems.展开更多
Human cytomegalovirus(HCMV) infection is a leading cause of birth defects, primarily affecting the central nervous system and causing its maldevelopment. As the essential downstream effector of Notch signaling pathway...Human cytomegalovirus(HCMV) infection is a leading cause of birth defects, primarily affecting the central nervous system and causing its maldevelopment. As the essential downstream effector of Notch signaling pathway, Hes1, and its dynamic expression, plays an essential role on maintaining neural progenitor/stem cells(NPCs) cell fate and fetal brain development. In the present study, we reported the first observation of Hes1 oscillatory expression in human NPCs, with an approximately1.5 hour periodicity and a Hes1 protein half-life of about 17(17.6 ± 0.2) minutes. HCMV infection disrupts the Hes1 rhythm and down-regulates its expression. Furthermore, we discovered that depleting Hes1 protein disturbed NPCs cell fate by suppressing NPCs proliferation and neurosphere formation, and driving NPCs abnormal differentiation. These results suggested a novel mechanism linking disruption of Hes1 rhythm and down-regulation of Hes1 expression to neurodevelopmental disorders caused by congenital HCMV infection.展开更多
＇Core＇ neuropathology of degenerative central nervous system （CNS） disorders The common human neurodegenerative disorders （Alzheimer＇s disease （AD）, Parkinson＇s disease （PD）, amyotrophic lateral sclerosis, ...＇Core＇ neuropathology of degenerative central nervous system （CNS） disorders The common human neurodegenerative disorders （Alzheimer＇s disease （AD）, Parkinson＇s disease （PD）, amyotrophic lateral sclerosis, etc.） vary with respect to risk factors, ages of onset, sex predilections, neuraxial regions affected, hallmark cellular inclusions, behavioral and neurological symptoms, and responses to treatment. Despite these differences, there appears to be a set of ＇core＇ neuropathological features shared among these and related entities. Common to these conditions are 1） pathological deposition of non-transferrin bound iron, 2） oxidative stress and associated protein, lipid and nucleic acid modifications, 3） mitochondrial membrane damage and bioenergetic failure, and 4） macroautophagy in the affected neural tissues.展开更多
The expression of nerve cell adhesion molecule L1 in the neuronal growth cone of the central nervous system is strongly associated with the direction of growth of the axon, but its role in the regeneration of the peri...The expression of nerve cell adhesion molecule L1 in the neuronal growth cone of the central nervous system is strongly associated with the direction of growth of the axon, but its role in the regeneration of the peripheral nerve is still unknown. This study explored the problem in a femoral nerve section model in rats. L1 and semaphorin 3A m RNA and protein expressions were measured over the 4-week recovery period. Quantitative polymerase chain reaction showed that nerve cell adhesion molecule L1 expression was higher in the sensory nerves than in motor nerves at 2 weeks after injury, but vice versa for the expression of semaphorin 3A. Western blot assay results demonstrated that nerve cell adhesion molecule L1 expression was higher in motor nerves than in the sensory nerves at the proximal end after injury, but its expression was greater in the sensory nerves at 2 weeks. Semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 3 days and 1 week after injury. Nerve cell adhesion molecule L1 and semaphorin 3A expressions at the distal end were higher in the motor nerves than in the sensory nerves at 3 days, 1 and 2 weeks. Immunohistochemical staining results showed that nerve cell adhesion molecule L1 expression at the proximal end was greater in the sensory nerves than in the motor nerves; semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 2 weeks after injury. Taken together, these results indicated that nerve cell adhesion molecules L1 and semaphorin 3A exhibited different expression patterns at the proximal and distal ends of sensory and motor nerves, and play a coordinating role in neural chemotaxis regeneration.展开更多
Tetrandrine is one of the major active ingredients in Menispermaceae Stephania tetrandra S.Moore,and has specific therapeutic effects in ischemic cerebrovascular disease.Its use in vascular dementia has not been studi...Tetrandrine is one of the major active ingredients in Menispermaceae Stephania tetrandra S.Moore,and has specific therapeutic effects in ischemic cerebrovascular disease.Its use in vascular dementia has not been studied fully.Here,we investigated whether tetrandrine would improve behavioral and cellular impairments in a two-vessel occlusion rat model of chronic vascular dementia.Eight weeks after model establishment,rats were injected intraperitoneally with 10 or 30 mg/kg tetrandrine every other day for 4 weeks.Behavioral assessment in the Morris water maze showed that model rats had longer escape latencies in training trials,and spent less time swimming in the target quadrant in probe trials,than sham-operated rats.However,rats that had received tetrandrine showed shorter escape latencies and longer target quadrant swimming time than untreated model rats.Hematoxylin-eosin and Nissl staining revealed less neuronal necrosis and pathological damage,and more living cells,in the hippocampus of rats treated with tetrandrine than in untreated model rats.Western blot assay showed that interleukin-1β expression,and phosphorylation of the N-methyl-D-aspartate 2B receptor at tyrosine 1472,were lower in model rats that received tetrandrine than in those that did not.The present findings suggest that tetrandrine may be neuroprotective in chronic vascular dementia by reducing interleukin-1β expression,N-methyl-D-aspartate receptor 2B phosphorylation at tyrosine 1472,and neuronal necrosis.展开更多
For the treatment of brain ischemia using acupuncture, the needle is predominantly inserted into muscular layers and deep tissue. However, few studies have investigated the outcomes of shallow needling. The present st...For the treatment of brain ischemia using acupuncture, the needle is predominantly inserted into muscular layers and deep tissue. However, few studies have investigated the outcomes of shallow needling. The present study established middle cerebral artery occlusion models in rats using the thrombosis method. Shallow needling and conventional needling at the bilateral Neiguan （PC 6） and Gongsun （SP 4） acupoints improved neurological function of middle cerebral artery occlusion rats, increased the expression of the anti-apoptotic Bcl-2, inhibited the expression of the pro-apoptotic Bax, and reduced the expression of the vasoactive substances nitric oxide synthase and endothelin-1. However, these changes were more pronounced in the shallow needling group, indicating that shallow needling is more effective in inhibiting brain ischemic injury.展开更多
Because of a lack of sensitive biomarkers,the diagnosis of Alzheimer＇s disease（AD） cannot be made prior to symptom manifestation.Therefore,it is crucial to identify novel biomarkers for the presymptomatic diagnosis...Because of a lack of sensitive biomarkers,the diagnosis of Alzheimer＇s disease（AD） cannot be made prior to symptom manifestation.Therefore,it is crucial to identify novel biomarkers for the presymptomatic diagnosis of AD.While brain lesions are a major feature of AD,retinal pathological changes also occur in patients.In this study,we investigated the temporal changes in β-site APP-cleaving enzyme 1（BACE1） expression in the retina and brain to determine whether it could serve as a suitable biomarker for early monitoring of AD.APP/PS-1 transgenic mice,3,6 and 8 months of age,were used as an experimental group,and age-matched C57/BL6 wild-type mice served as the control group.In the Morris water maze test,there were no significant differences in escape latency or in the number of crossings in the target area among mice of different ages.Compared with wild-type mice,no changes in learning or memory abilities were detected in transgenic mice at 3 months of age.However,compared with wild-type mice,the escape latency was significantly increased in transgenic mice at 6 months,starting on day 3,and at 8 months,starting on day 2,during Morris water maze training.In addition,the number of crossings of the target area was significantly decreased in transgenic mice.The learning and memory abilities of transgenic mice were further worsened at 8 months of age.Immunohistochemical staining revealed no BACE1 plaques in wild-type mice at 3,6 or 8 months or in transgenic mice at 3 months,but they were clearly found in the entorhinal cortex,hippocampus and prefrontal cortex of transgenic mice at 6 and 8 months.BACE1 expression was not detected in the retina of wild-type mice at 3 months,but weak BACE1 expression was detected in the ganglion cell layer,inner plexiform layer and outer plexiform layer at 6 and 8 months.In transgenic mice,BACE1 expression in the ganglion cell layer was increased at 3 months,and BACE1 expression in the ganglion cell layer,inner plexiform layer and outer plexiform layer was significantly increased at 6 and 8 months,compared with age-matched wild-type mice.Taken together,these results indicate that changes in BACE1 expression appear earlier in the retina than in the brain and precede behavioral deficits.Our findings suggest that abnormal expression of BACE1 in the retina is an early pathological change in APP/PS-1 transgenic mice,and that BACE1 might have potential as a biomarker for the early diagnosis of AD in humans.展开更多
基金supported by the National Natural Science Foundation of China(82171237,82471246,and 82401462)the Natural Science Foundation of Henan Province,China(242300420381).
文摘Neuropathic pain is frequently comorbidity with cognitive deficits.Neuralized1(Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory.However,the role of Neurl1 in the cognitive impairment in neuropathic pain remains elusive.Herein,we found that lumbar 5 spinal nerve ligation(SNL)in male rat-induced neuropathic pain was followed by learning and memory deficits and LTP impairment in the hippocampus.The Neurl1 expression in the hippocampal CA1 was decreased after SNL.And this decrease paralleled the reduction of ubiquitinated-CPEB3 level and reduced production of GluA1 and GluA2.Overexpression of Neurl1 in the CA1 rescued cognitive deficits and LTP impairment,and reversed the reduction of ubiquitinated-CPEB3 level and the decrease of GluA1 and GluA2 production following SNL.Specific knockdown of Neurl1 or CPEB3 in bilateral hippocampal CA1 in naïve rats resulted in cognitive deficits and impairment of synaptic plasticity.The rescued cognitive function and synaptic plasticity by the treatment of overexpression of Neurl1 before SNL were counteracted by the knockdown of CPEB3 in the CA1.Collectively,the above results suggest that the downregulation of Neurl1 through reducing CPEB3 ubiquitination and,in turn,repressing GluA1 and GluA2 production and mediating synaptic plasticity impairment in hippocampal CA1 leads to the genesis of cognitive deficits in neuropathic pain.
基金supported by the China Postdoctoral Science Foundation(Grant No.2024M760415)the Natural Science Foundation of Guangdong Province(Grant No.2022A1515140118).
文摘Deep learning(DL)models have demonstrated significant value in computational perception,superresolution imaging,ultra-precision measurement,and photonic device design.In optical communication signal recognition,DL models can achieve fast and accurate identification.However,in high-capacity optical communication systems represented by orbital angular momentum(OAM)beams,neural networks often suffer from excessive parameter sizes and demand large training datasets.To address these challenges,we report a lightweight MobileNetV1 model optimized with efficient channel attention to perform OAM mode recognition after transmission through free space and underwater tank environments.Experimental results show that in simulated small-sample classification tasks with five samples per class,the proposed model achieves an accuracy of 99.67%even under moderate turbulence conditions,outperforming four other DL models.In addition,for experimental datasets collected from both atmospheric turbulence and underwater environments,the model consistently achieves recognition accuracies exceeding 90%,demonstrating strong generalization ability and a 77%reduction in parameter count compared to traditional convolutional neural network(CNN)-based DL models.We provide a new approach for deploying lightweight DL algorithms on resource-constrained embedded optical signal detection devices.
文摘We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies were performed with whole blood,4 with blood plasma,5 with blood serum,1 with serum neural cell adhesion molecule L1-captured extracellular vesicles,1 with blood cells,and 2 with peripheral blood mononuclear cells.Most of the studies involved children and the study cohorts were largely males.Many of the studies had performed microRNA sequencing or quantitative polymerase chain reaction assays to measure microRNA expression.Only five studies had used real-time polymerase chain reaction assay to validate microRNA expression in autism spectrum disorder subjects compared to controls.The microRNAs that were validated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p,-197-5p,-424-5p,-664a-3p,-365a-3p,-619-5p,-664a-3p,-3135a,-328-3p,and-500a-5p in blood plasma and miR-151a-3p,-181b-5p,-320a,-328,-433,-489,-572,-663a,-101-3p,-106b-5p,-19b-3p,-195-5p,and-130a-3p in blood serum of children,and miR-15b-5p and-6126 in whole blood of adults.Several important limitations were identified in the studies reviewed,and need to be taken into account in future studies.Further studies are warranted with children and adults having different levels of autism spectrum disorder severity and consideration should be given to using animal models of autism spectrum disorder to investigate the effects of suppressing or overexpressing specific microRNAs as a novel therapy.
基金supported by Jiangsu Social Science Foundation(No.20GLD008)Science,Technology Projects of Jiangsu Provincial Department of Communications(No.2020Y14)Joint Fund for Civil Aviation Research(No.U1933202)。
文摘In order to directly construct the mapping between multiple state parameters and remaining useful life(RUL),and reduce the interference of random error on prediction accuracy,a RUL prediction model of aeroengine based on principal component analysis(PCA)and one-dimensional convolution neural network(1D-CNN)is proposed in this paper.Firstly,multiple state parameters corresponding to massive cycles of aeroengine are collected and brought into PCA for dimensionality reduction,and principal components are extracted for further time series prediction.Secondly,the 1D-CNN model is constructed to directly study the mapping between principal components and RUL.Multiple convolution and pooling operations are applied for deep feature extraction,and the end-to-end RUL prediction of aeroengine can be realized.Experimental results show that the most effective principal component from the multiple state parameters can be obtained by PCA,and the long time series of multiple state parameters can be directly mapped to RUL by 1D-CNN,so as to improve the efficiency and accuracy of RUL prediction.Compared with other traditional models,the proposed method also has lower prediction error and better robustness.
基金supported by the National Natural Science Foundation of China,No.31800892(to JLZ)the Natural Science Foundation of Guangdong Province of China,No.2018A030310254(to YY)a grant from Guangzhou Medical University Start-up Project of China,No.B195002002048(to JLZ)。
文摘The formation of nerve bundles,which is partially regulated by neural cell adhesion molecule 1(NCAM1),is important for neural network organization during peripheral nerve regeneration.However,little is known about how the extracellular matrix(ECM)microenvironment affects this process.Here,we seeded dorsal root ganglion tissue blocks on different ECM substrates of peripheral nerve ECM-derived matrixgel,Matrigel,laminin 521,collagen I,and collagen IV,and observed well-aligned axon bundles growing in the peripheral nerve ECM-derived environment.We confirmed that NCAM1 is necessary but not sufficient to trigger this phenomenon.A protein interaction assay identified collagen VI as an extracellular partner of NCAM1 in the regulation of axonal fasciculation.Collagen VI interacted with NCAM1 by directly binding to the FNIII domain,thereby increasing the stability of NCAM1 at the axolemma.Our in vivo experiments on a rat sciatic nerve defect model also demonstrated orderly nerve bundle regeneration with improved projection accuracy and functional recovery after treatment with 10 mg/m L Matrigel and 20μg/m L collagen VI.These findings suggest that the collagen VI-NCAM1 pathway plays a regulatory role in nerve bundle formation.This study was approved by the Animal Ethics Committee of Guangzhou Medical University(approval No.GY2019048)on April 30,2019.
文摘When the physiopathology of membranous nephropathy was first described,almost 30%of cases were recognized to be secondary to well-known diseases such as autoimmune diseases,tumors or infections.The remaining 70%cases were called primary membranous nephropathy as the exact mechanism or pathogenic factor involved was unknown.The discovery of the M type phospholipase A2 receptor and thrombospondin type 1 domain containing 7A as causative antigens in these“so called”primary membranous nephropathies provided new insights into the effective causes of a large proportion of these cases.Novel techniques such as laser microdissection and tandem mass spectrometry as well as immunochemistry with antibodies directed against novel proteins allowed the confirmation of new involved antigens.Finally,using confocal microscopy to localize these new antigens and immunoglobulin G and Western blot analysis of serum samples,these new antigens were detected on the glomerular membrane,and the related antibodies were detected in serum samples.The same antigens have been recognized in some cases of secondary membranous disease due to autoimmune diseases,tumors and infections.This has allowed examination of the relationship between antigens in primary membranous nephropathy and their presence in some secondary nephropathies.The aim of this study is to describe the characteristics of the new antigens discovered and their association with other diseases.
基金supported by a Grant-in-aid for Scientific Research from the Ministry of EducationScience+3 种基金Sports and Culture of Japan(grant number:25430056)the fund from Nukada Institute for Medical and Biological ResearchChibaJapan
文摘Glucagon-like peptide 1（GLP-1）is secreted from enteroendocrine L cells in response to nutrient ingestion and exhibits insulinotropic properties by stimulating specific G protein-linked receptors（GLP-1Rs）on pancreaticβcells.Several GLP-1 mimetics,such as exenatide（exendin-4（Ex-4））,liraglutide,and lixisenatide,have been developed and approved as treatments for patients with type 2 diabetes.These peptides show bioactiv-ities almost identical to those of GLP- 1 and have a substantially longer plasma half-life than GLP-1 because of their resistance to dipeptidyl peptidase-4, a GLP-1 degrading enzyme.
基金supported by a grant from National Institute of Health(NIH)Grant No.NS040433
文摘Amyotrophic lateral sclerosis is a motoneuron degenerative disease that is challenging to diagnose and presents with considerable variability in survival.Early identification and enhanced understanding of symptomatic patterns could aid in diagnosis and provide an avenue for monitoring disease progression.Use of the m SOD1 G93 A mouse model provides control of the confounding environmental factors and genetic heterogeneity seen in amyotrophic lateral sclerosis patients,while investigating underlying disease-induced changes.In the present study,we performed a longitudinal behavioral assessment paradigm and identified an early hindlimb symptom,resembling the common gait abnormality foot drop,along with an accompanying forelimb compensatory mechanism in the m SOD1 G93 A mouse.Following these initial changes,m SOD1 mice displayed a temporary hindlimb compensatory mechanism resembling an exaggerated steppage gait.As the disease progressed,these compensatory mechanisms were not sufficient to sustain fundamental locomotor parameters and more severe deficits appeared.We next applied these initial findings to investigate the inherent variability in B6 SJL m SOD1 G93 A survival.We identified four behavioral variables that,when combined in a cluster analysis,identified two subpopulations with different disease progression rates：a fast progression group and a slow progression group.This behavioral assessment paradigm,with its analytical approaches,provides a method for monitoring disease progression and detecting m SOD1 subgroups with different disease severities.This affords researchers an opportunity to search for genetic modifiers or other factors that likely enhance or slow disease progression.Such factors are possible therapeutic targets with the potential to slow disease progression and provide insight into the underlying pathology and disease mechanisms.
基金supported by the National Natural Science Foundation of China,No.81171239
文摘The regulatory mechanisms of cytoplasmic Ca2+after myocardial infarction-induced Ca2+overload involve secretory pathway Ca2+-ATPase 1 and the Golgi apparatus and are well understood.However,the effect of Golgi apparatus on Ca2+overload after cerebral ischemia and reperfusion remains unclear.Four-vessel occlusion rats were used as animal models of cerebral ischemia.The expression of secretory pathway Ca2+-ATPase 1 in the cortex and hippocampus was detected by immunoblotting,and Ca2+concentrations in the cytoplasm and Golgi vesicles were determined.Results showed an overload of cytoplasmic Ca2+during ischemia and reperfusion that reached a peak after reperfusion.Levels of Golgi Ca2+showed an opposite effect.The expression of Golgi-specific secretory pathway Ca2+-ATPase 1 in the cortex and hippocampus decreased before ischemia and reperfusion,and increased after reperfusion for 6 hours.This variation was similar to the alteration of calcium in separated Golgi vesicles.These results indicate that the Golgi apparatus participates in the formation and alleviation of calcium overload,and that secretory pathway Ca2+-ATPase 1 tightly responds to ischemia and reperfusion in nerve cells.Thus,we concluded that secretory pathway Ca2+-ATPase 1 plays an essential role in cytosolic calcium regulation and its expression can be used as a marker of Golgi stress,responding to cerebral ischemia and reperfusion.The secretory pathway Ca2+-ATPase 1 can be an important neuroprotective target of ischemic stroke.
基金supported by a grant from the University Students’Innovation and Entrepreneurship Training Program in Liaoning Province of China,No.201310160016
文摘Expression of genes in the Notch signaling pathway is altered in the injured spinal cord, which indicates that Notch participates in repair after spinal cord injury. Buyang Huanwu decoction, a traditional Chinese herbal preparation, can promote the growth of nerve cells and nerve fibers; however, it is unclear whether Buyang Huanwu decoction affects the Notch signaling pathway in injured spinal cord. In this study, a rat model was established by injuring the T10 spinal cord. At 2 days after injury, rats were intragastrically administered 2 m L of 0.8 g/m L Buyang Huanwu decoction daily until sacrifice. Real-time reverse transcription polymerase chain reaction analysis demonstrated that at 7, 14 and 28 days after injury, the expression of Notch1 was increased in the Buyang Huanwu decoction group compared with controls. These findings confirm that Buyang Huanwu decoction can promote the expression of Notch1 in rats with incomplete spinal cord injury, and may indicate a mechanism to promote the repair of spinal cord injury.
基金supported by the National Natural Science Foundation of China (No.12031003)the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant Agreement (No.778062 ULTRACEPT)。
文摘The bistratified lobula giant type 1(BLG1) neuron is an identified looming-sensitive neuron in crab's visual brain that demonstrates special sensitivity to diving targets, or descending approaching motions. In this paper, a novel neural model is proposed to shape such unique selectivity through incorporating a bio-plausible feedforward contrast inhibition synapse and a radially extending spatial enhancement distribution. Herein the synaptic connections and neuronal functions of this model are placed within a framework for matching and describing underlying biological findings. The systematic and comparative experiments have validated the proposed computational model that reconciles with the characteristics of BLG1 neurons in crab.
文摘BACKGROUND： Interstitial stem cell is charactenzed by multiple differentiations, and retinoic acid （RA） can induce differentiation of stromal cells into nerve tissue cells in fetal liver of mice, so, its signal transduction pathway should be discussed to trigger differentiation. OBJECTIVE ： To study the effect of RA on expression of neural specific gene and its signal transduction in fetal liver of mice.DESIGN ： Paired controlled study on the basis of cell.SETTING ： Institute of Hematology, Medical College of Jinan University.MATERIALS： The experiment was completed in the Institute of Hematology, Medical College of Jinan University from April to December 2005. C57BL/6 mice, of clean grade, aged 8-10 weeks, weighting 20-35 g, 10 females and 4 males, were selected in this study.METHODS： Sca-1^＋ cells in fetal liver were prepared with MACS kit and cultured with DMEM ＋ 10% fetal bovine serum （FBS）. On the fourth day, it was added with or without protein kinase C （PKC） inhibitor chelerythrine chloride （3μmol/L） and 5×10^-7 mol/L RA for 24 hours, and then incubated in serum-free medium for 5 days. Expressions of genes were assayed by Westem blotting and semi-quantitative RT-PCR.MAIN OUTCOME MEASURES ： Expression of neural specific gene NF-L, NF-H, BF-1 and TH.RESULTS： Expression of neural specific gene NF-L, NF-H, BF-1 and TH was significantly increased after treatment with RA and they were increased 5.06, 5.15, 4.63 and 3.33 times, respectively. However, chelerythrine chloride could inhibit expression of neural specific gene NF-L, NF-H, BF-1 and TH induced by RA.CONCLUSION ： RA can promote the expression of neural specific genes in Sca-1^＋ cells of fetal liver, and its pathway may be related to PKC.
基金supported by the Chinese Medicine Research Foundation of Jiangxi Provincial Health Department of China,No.2013A040the Science and Technology Program of Jiangxi Provincial Health Department of China,No.20123023the Science and Technology Support Program of Jiangxi Province of China,No.2009BSB11209
文摘Baicalin is a flavonoid compound extracted from Scutellaria baicalensis root.Recent evidence indicates that baicalin is neuroprotective in models of ischemic stroke.Here,we investigate the neuroprotective effect of baicalin in a neonatal rat model of hypoxic-ischemic encephalopathy.Seven-day-old pups underwent left common carotid artery ligation followed by hypoxia（8% oxygen at 37°C） for 2 hours,before being injected with baicalin（120 mg/kg intraperitoneally） and examined 24 hours later.Baicalin effectively reduced cerebral infarct volume and neuronal loss,inhibited apoptosis,and upregulated the expression of p-Akt and glutamate transporter 1.Intracerebroventricular injection of the phosphoinositide 3-kinase/protein kinase B（PI3 K/Akt） inhibitor LY294002 30 minutes before injury blocked the effect of baicalin on p-Akt and glutamate transporter 1,and weakened the associated neuroprotective effect.Our findings provide the first evidence,to our knowledge that baicalin can protect neonatal rat brains against hypoxic-ischemic injury by upregulating glutamate transporter 1 via the PI3 K/Akt signaling pathway.
文摘Purpose:With more and more digital collections of various information resources becoming available,also increasing is the challenge of assigning subject index terms and classes from quality knowledge organization systems.While the ultimate purpose is to understand the value of automatically produced Dewey Decimal Classification(DDC)classes for Swedish digital collections,the paper aims to evaluate the performance of six machine learning algorithms as well as a string-matching algorithm based on characteristics of DDC.Design/methodology/approach:State-of-the-art machine learning algorithms require at least 1,000 training examples per class.The complete data set at the time of research involved 143,838 records which had to be reduced to top three hierarchical levels of DDC in order to provide sufficient training data(totaling 802 classes in the training and testing sample,out of 14,413 classes at all levels).Findings:Evaluation shows that Support Vector Machine with linear kernel outperforms other machine learning algorithms as well as the string-matching algorithm on average;the string-matching algorithm outperforms machine learning for specific classes when characteristics of DDC are most suitable for the task.Word embeddings combined with different types of neural networks(simple linear network,standard neural network,1 D convolutional neural network,and recurrent neural network)produced worse results than Support Vector Machine,but reach close results,with the benefit of a smaller representation size.Impact of features in machine learning shows that using keywords or combining titles and keywords gives better results than using only titles as input.Stemming only marginally improves the results.Removed stop-words reduced accuracy in most cases,while removing less frequent words increased it marginally.The greatest impact is produced by the number of training examples:81.90%accuracy on the training set is achieved when at least 1,000 records per class are available in the training set,and 66.13%when too few records(often less than A Comparison of Approaches100 per class)on which to train are available—and these hold only for top 3 hierarchical levels(803 instead of 14,413 classes).Research limitations:Having to reduce the number of hierarchical levels to top three levels of DDC because of the lack of training data for all classes,skews the results so that they work in experimental conditions but barely for end users in operational retrieval systems.Practical implications:In conclusion,for operative information retrieval systems applying purely automatic DDC does not work,either using machine learning(because of the lack of training data for the large number of DDC classes)or using string-matching algorithm(because DDC characteristics perform well for automatic classification only in a small number of classes).Over time,more training examples may become available,and DDC may be enriched with synonyms in order to enhance accuracy of automatic classification which may also benefit information retrieval performance based on DDC.In order for quality information services to reach the objective of highest possible precision and recall,automatic classification should never be implemented on its own;instead,machine-aided indexing that combines the efficiency of automatic suggestions with quality of human decisions at the final stage should be the way for the future.Originality/value:The study explored machine learning on a large classification system of over 14,000 classes which is used in operational information retrieval systems.Due to lack of sufficient training data across the entire set of classes,an approach complementing machine learning,that of string matching,was applied.This combination should be explored further since it provides the potential for real-life applications with large target classification systems.
基金supported by the National Natural Science Foundation of China(31600145)
文摘Human cytomegalovirus(HCMV) infection is a leading cause of birth defects, primarily affecting the central nervous system and causing its maldevelopment. As the essential downstream effector of Notch signaling pathway, Hes1, and its dynamic expression, plays an essential role on maintaining neural progenitor/stem cells(NPCs) cell fate and fetal brain development. In the present study, we reported the first observation of Hes1 oscillatory expression in human NPCs, with an approximately1.5 hour periodicity and a Hes1 protein half-life of about 17(17.6 ± 0.2) minutes. HCMV infection disrupts the Hes1 rhythm and down-regulates its expression. Furthermore, we discovered that depleting Hes1 protein disturbed NPCs cell fate by suppressing NPCs proliferation and neurosphere formation, and driving NPCs abnormal differentiation. These results suggested a novel mechanism linking disruption of Hes1 rhythm and down-regulation of Hes1 expression to neurodevelopmental disorders caused by congenital HCMV infection.
基金supported by grants from the Canadian Institutes of Health Researchthe Mary Katz Claman Foundationthe Oberfeld Family Fund for Alzheimer Research
文摘＇Core＇ neuropathology of degenerative central nervous system （CNS） disorders The common human neurodegenerative disorders （Alzheimer＇s disease （AD）, Parkinson＇s disease （PD）, amyotrophic lateral sclerosis, etc.） vary with respect to risk factors, ages of onset, sex predilections, neuraxial regions affected, hallmark cellular inclusions, behavioral and neurological symptoms, and responses to treatment. Despite these differences, there appears to be a set of ＇core＇ neuropathological features shared among these and related entities. Common to these conditions are 1） pathological deposition of non-transferrin bound iron, 2） oxidative stress and associated protein, lipid and nucleic acid modifications, 3） mitochondrial membrane damage and bioenergetic failure, and 4） macroautophagy in the affected neural tissues.
基金supported by the National Natural Science Foundation of China,No.81371389,31500927,31300942,81201017the Collegiate Natural Science Foundation of Jiangsu Province of China,No.13KJB180018the Natural Science Foundation of Nantong University of China,No.14ZY013
文摘The expression of nerve cell adhesion molecule L1 in the neuronal growth cone of the central nervous system is strongly associated with the direction of growth of the axon, but its role in the regeneration of the peripheral nerve is still unknown. This study explored the problem in a femoral nerve section model in rats. L1 and semaphorin 3A m RNA and protein expressions were measured over the 4-week recovery period. Quantitative polymerase chain reaction showed that nerve cell adhesion molecule L1 expression was higher in the sensory nerves than in motor nerves at 2 weeks after injury, but vice versa for the expression of semaphorin 3A. Western blot assay results demonstrated that nerve cell adhesion molecule L1 expression was higher in motor nerves than in the sensory nerves at the proximal end after injury, but its expression was greater in the sensory nerves at 2 weeks. Semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 3 days and 1 week after injury. Nerve cell adhesion molecule L1 and semaphorin 3A expressions at the distal end were higher in the motor nerves than in the sensory nerves at 3 days, 1 and 2 weeks. Immunohistochemical staining results showed that nerve cell adhesion molecule L1 expression at the proximal end was greater in the sensory nerves than in the motor nerves; semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 2 weeks after injury. Taken together, these results indicated that nerve cell adhesion molecules L1 and semaphorin 3A exhibited different expression patterns at the proximal and distal ends of sensory and motor nerves, and play a coordinating role in neural chemotaxis regeneration.
基金supported by the National Natural Science Foundation of China,No.81070886
文摘Tetrandrine is one of the major active ingredients in Menispermaceae Stephania tetrandra S.Moore,and has specific therapeutic effects in ischemic cerebrovascular disease.Its use in vascular dementia has not been studied fully.Here,we investigated whether tetrandrine would improve behavioral and cellular impairments in a two-vessel occlusion rat model of chronic vascular dementia.Eight weeks after model establishment,rats were injected intraperitoneally with 10 or 30 mg/kg tetrandrine every other day for 4 weeks.Behavioral assessment in the Morris water maze showed that model rats had longer escape latencies in training trials,and spent less time swimming in the target quadrant in probe trials,than sham-operated rats.However,rats that had received tetrandrine showed shorter escape latencies and longer target quadrant swimming time than untreated model rats.Hematoxylin-eosin and Nissl staining revealed less neuronal necrosis and pathological damage,and more living cells,in the hippocampus of rats treated with tetrandrine than in untreated model rats.Western blot assay showed that interleukin-1β expression,and phosphorylation of the N-methyl-D-aspartate 2B receptor at tyrosine 1472,were lower in model rats that received tetrandrine than in those that did not.The present findings suggest that tetrandrine may be neuroprotective in chronic vascular dementia by reducing interleukin-1β expression,N-methyl-D-aspartate receptor 2B phosphorylation at tyrosine 1472,and neuronal necrosis.
基金the National Natural Science Foundation of China, No. 3076031918
文摘For the treatment of brain ischemia using acupuncture, the needle is predominantly inserted into muscular layers and deep tissue. However, few studies have investigated the outcomes of shallow needling. The present study established middle cerebral artery occlusion models in rats using the thrombosis method. Shallow needling and conventional needling at the bilateral Neiguan （PC 6） and Gongsun （SP 4） acupoints improved neurological function of middle cerebral artery occlusion rats, increased the expression of the anti-apoptotic Bcl-2, inhibited the expression of the pro-apoptotic Bax, and reduced the expression of the vasoactive substances nitric oxide synthase and endothelin-1. However, these changes were more pronounced in the shallow needling group, indicating that shallow needling is more effective in inhibiting brain ischemic injury.
基金supported by the National Natural Science Foundation of China(to JFH,DC,JBT),No.81371011,81400399,81471107a grant from the Project of Innovation-driven Plan of Central South University(to DC),No.2015CXS022+2 种基金a grant from the National Key Technologies Research and Development Program of China(to JFH),No.2012BAK14B03Fundamental Research Funds of Central South University of China(to HW),No.2010QZZD022Graduate Thesis Innovation Foundation of Central South University of China(to LL),No.2011ssxt106
文摘Because of a lack of sensitive biomarkers,the diagnosis of Alzheimer＇s disease（AD） cannot be made prior to symptom manifestation.Therefore,it is crucial to identify novel biomarkers for the presymptomatic diagnosis of AD.While brain lesions are a major feature of AD,retinal pathological changes also occur in patients.In this study,we investigated the temporal changes in β-site APP-cleaving enzyme 1（BACE1） expression in the retina and brain to determine whether it could serve as a suitable biomarker for early monitoring of AD.APP/PS-1 transgenic mice,3,6 and 8 months of age,were used as an experimental group,and age-matched C57/BL6 wild-type mice served as the control group.In the Morris water maze test,there were no significant differences in escape latency or in the number of crossings in the target area among mice of different ages.Compared with wild-type mice,no changes in learning or memory abilities were detected in transgenic mice at 3 months of age.However,compared with wild-type mice,the escape latency was significantly increased in transgenic mice at 6 months,starting on day 3,and at 8 months,starting on day 2,during Morris water maze training.In addition,the number of crossings of the target area was significantly decreased in transgenic mice.The learning and memory abilities of transgenic mice were further worsened at 8 months of age.Immunohistochemical staining revealed no BACE1 plaques in wild-type mice at 3,6 or 8 months or in transgenic mice at 3 months,but they were clearly found in the entorhinal cortex,hippocampus and prefrontal cortex of transgenic mice at 6 and 8 months.BACE1 expression was not detected in the retina of wild-type mice at 3 months,but weak BACE1 expression was detected in the ganglion cell layer,inner plexiform layer and outer plexiform layer at 6 and 8 months.In transgenic mice,BACE1 expression in the ganglion cell layer was increased at 3 months,and BACE1 expression in the ganglion cell layer,inner plexiform layer and outer plexiform layer was significantly increased at 6 and 8 months,compared with age-matched wild-type mice.Taken together,these results indicate that changes in BACE1 expression appear earlier in the retina than in the brain and precede behavioral deficits.Our findings suggest that abnormal expression of BACE1 in the retina is an early pathological change in APP/PS-1 transgenic mice,and that BACE1 might have potential as a biomarker for the early diagnosis of AD in humans.
