In this paper, a two-dimensional(2D) DOA estimation algorithm of coherent signals with a separated linear acoustic vector-sensor(AVS) array consisting of two sparse AVS arrays is proposed. Firstly,the partitioned spat...In this paper, a two-dimensional(2D) DOA estimation algorithm of coherent signals with a separated linear acoustic vector-sensor(AVS) array consisting of two sparse AVS arrays is proposed. Firstly,the partitioned spatial smoothing(PSS) technique is used to construct a block covariance matrix, so as to decorrelate the coherency of signals. Then a signal subspace can be obtained by singular value decomposition(SVD) of the covariance matrix. Using the signal subspace, two extended signal subspaces are constructed to compensate aperture loss caused by PSS.The elevation angles can be estimated by estimation of signal parameter via rotational invariance techniques(ESPRIT) algorithm. At last, the estimated elevation angles can be used to estimate automatically paired azimuth angles. Compared with some other ESPRIT algorithms, the proposed algorithm shows higher estimation accuracy, which can be proved through the simulation results.展开更多
AIM:To evaluate the alterations of the retinal microvasculature and foveal avascular zone in patients with Parkinson’s disease(PD)using optical coherence tomography angiography(OCT-A).METHODS:A retrospective study of...AIM:To evaluate the alterations of the retinal microvasculature and foveal avascular zone in patients with Parkinson’s disease(PD)using optical coherence tomography angiography(OCT-A).METHODS:A retrospective study of PD patients examined in the Ophthalmology Department of the General Hospital of Athens,“Georgios Gennimatas”from March 2021 to March 2022 was conducted.Totally 44 patients with PD were included and 18 healthy controls were examined,hence a total of 124 eyes were enrolled in the study.The foveal and parafoveal superficial and deep capillary plexus vascular density(fSCP-VD,fDCP-VD,pSCP-VD,pDCP-CD)and foveal avascular zone(FAZ)were quantified with OCTA.Optical coherence tomography(OCT)was used to measure macular thickness.Our statistical analysis was conducted by using a mixed effect linear regression model.RESULTS:After adjustment for age and gender,the mean parafoveal superficial capillary plexus vascular density(pSCP-VD)and mean parafoveal deep capillary plexus vascular density(pDCP-VD)were significantly decreased in individuals with PD(P<0.001 in both)by-2.35(95%CI-3.3,-1.45)and-7.5(95%CI-10.4,-4.6)respectively.fSCP-VD and fDCP-VD didn’t approach statistical significance.The FAZ area and perimeter were significantly decreased(P<0.001 in both)by-0.1 mm^(2)(95%CI-0.13,-0.07)and-0.49 mm^(2)(95%CI-0.66,-0.32)respectively.Circularity didn’t approach statistical significance.Central retinal thickness(CRT)was significantly decreased in individuals with PD(P<0.001)by-23.1μm(95%CI-30.2,-16)and temporal retinal thickness(TRT)was decreased(P=0.025)by-11μm(95%CI-22,-1.5)while nasal retinal thickness(NRT)only approached statistical significance(P=0.066).CONCLUSION:The mean pSCP-VD,pDCP-VD,CRT and TRT are significantly decreased and FAZ is altered in individuals with PD.These findings can be potentially used as biomarkers for the diagnosis and evaluation of early PD.展开更多
Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal sur...Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.展开更多
Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosi...Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.展开更多
Examining the retinal tissue has the potential to provide a unique method and technique to quantify Alzheimer’s disease-related changes in participants at various stages of the disease.In this metaanalysis,we aimed t...Examining the retinal tissue has the potential to provide a unique method and technique to quantify Alzheimer’s disease-related changes in participants at various stages of the disease.In this metaanalysis,we aimed to investigate the association of various optical coherence tomography parameters with Alzheimer’s disease and whether retinal measurements can be used to diffe rentiate between Alzheimer’s disease and control subjects.Scientific databases including Google Schola r,Web of Science,and PubMed were systematically searched for published articles that evaluated retinal nerve fiber layer thickness and retinal microvascular network in Alzheimer’s disease and control subjects.Seventy-three studies(5850 participants,including 2249 Alzheimer’s disease patients and 3601controls) were included in this meta-analysis.Relative to controls,Alzheimer’s disease patients had a significantly lower global retinal nerve fiber layer thickness(standardized mean difference [SMD]=-0.79,95% confidence intervals [CI]:-1.03 to-0.54,P <0.00001) as well as each quadrant being thinner in Alzheimer’s disease versus controls.Regarding macular paramete rs,values measured by optical coherence tomography were significantly lower in Alzheimer’s disease than controls for macular thickness(pooled SMD:-0.44,95% CI:-0.67 to-0.20,P=0.0003),foveal thickness(pooled SMD=-0.39,95% CI:-0.58 to-0.19,P <0.0001),ganglion cell inner plexiform layer(SMD=-1.26,95% CI:-2.24 to-0.27,P=0.01) and macular volume(pooled SMD=-0.41,95% CI-0.76 to-0.07,P=0.02).Analysis using optical coherence tomography angiography parameters revealed mixed results between Alzheimer’s disease and controls.Superficial vessel density(pooled SMD=-0.42,95% CI:-0.68 to-0.17,P=0.0001) and deep vessel density(pooled SMD=-0.46,95% CI:-0.75 to-0.18,P=0.001) were found to be thinner in Alzheimer’s disease patients whereas the foveal avascular zone(SMD=0.84,95% CI:0.17-1.51,P=0.01) was larger in controls.Vascular density and thickness of various retinal laye rs were decreased in Alzheimer’s disease patients compared to controls.Our results provide evidence for optical coherence tomography technology having the potential to detect retinal and microvascular changes in patients diagnosed with Alzheimer’s disease and aid in monito ring and early diagnosis methods.展开更多
A multi-GPU system designed for high-speed,real-time signal processing of optical coherencetomography(OCT)is described herein.For the OCT data sampled in linear wave numbers,themaximum procesing rates reached 2.95 MHz...A multi-GPU system designed for high-speed,real-time signal processing of optical coherencetomography(OCT)is described herein.For the OCT data sampled in linear wave numbers,themaximum procesing rates reached 2.95 MHz for 1024-OCT and 1.96 MHz for 2048-OCT.Data sampled using linear wavelengths were re-sampled using a time-domain interpolation method and zero-padding interpolation method to improve image quality.The maximum processing rates for1024-OCT reached 2.16 MHz for the time-domain method and 1.26 MHz for the zero-paddingmethod.The maximum processing rates for 2048-0CT reached_1.58 MHz,and 0.68 MHz,respectively.This method is capable of high-speed,real-time processing for O CT systems.展开更多
The correlated spectroscopy revamped by asymmetric Z-gradient echo detection (CRAZED) sequence is modified to investigate intermolecular double-quantum coherence nuclear magnetic resonance signal dips in highly pola...The correlated spectroscopy revamped by asymmetric Z-gradient echo detection (CRAZED) sequence is modified to investigate intermolecular double-quantum coherence nuclear magnetic resonance signal dips in highly polarized spin systems. It is found that the occurrence of intermolecular double-quantum coherence signal dips is related to sample geometry, field inhomogeneity and dipolar correlation distance. If the field inhomogeneity is refocused, the signal dip occurs at a fixed position whenever the dipolar correlation distance approaches the sample dimension. However, the position is shifted when the field inhomogeneity exists. Experiments and simulations are performed to validate our theoretic analysis. These signal features may offer a unique way to investigate porous structures and may find applications in biomedicine and material science.展开更多
Icariin,a major prenylated flavonoid found in Epimedium spp.,is a bioactive constituent of Herba Epimedii and has been shown to exert neuroprotective effects in experimental models of Alzheimer’s disease.In this stud...Icariin,a major prenylated flavonoid found in Epimedium spp.,is a bioactive constituent of Herba Epimedii and has been shown to exert neuroprotective effects in experimental models of Alzheimer’s disease.In this study,we investigated the neuroprotective mechanism of icariin in an APP/PS1/Tau triple-transgenic mouse model of Alzheimer’s disease.We performed behavioral tests,pathological examination,and western blot assay,and found that memory deficits of the model mice were obviously improved,neuronal and synaptic damage in the cerebral cortex was substantially mitigated,and amyloid-βaccumulation and tau hyperphosphorylation were considerably reduced after 5 months of intragastric administration of icariin at a dose of 60 mg/kg body weight per day.Furthermore,deficits of proteins in the insulin signaling pathway and their phosphorylation levels were significantly reversed,including the insulin receptor,insulin receptor substrate 1,phosphatidylinositol-3-kinase,protein kinase B,and glycogen synthase kinase 3β,and the levels of glucose transporter 1 and 3 were markedly increased.These findings suggest that icariin can improve learning and memory impairments in the mouse model of Alzheimer’s disease by regulating brain insulin signaling and glucose transporters,which lays the foundation for potential clinical application of icariin in the prevention and treatment of Alzheimer’s disease.展开更多
To estimate the direction-of-arrival (DOA) of wideband coherent signals, a new method by modifying the orthogonality of the projected suhspaces method is proposed. And it can deal with randomly position perturbed ar...To estimate the direction-of-arrival (DOA) of wideband coherent signals, a new method by modifying the orthogonality of the projected suhspaces method is proposed. And it can deal with randomly position perturbed arrays by using the Toeplitz method. This method needn't the primary information of DOA for focusing matrix and the sector dividing of interpolated method, which improving the precision of estimation and reducing the computational complexity. Simulations illustrate the effectiveness of this method.展开更多
In most wireless communication systems, two-dimensional Directions-Of-Arrival (DOA) of multipath signals need to be found for spatial selective transmission. However, it is quite difficult to find their DOAs due to th...In most wireless communication systems, two-dimensional Directions-Of-Arrival (DOA) of multipath signals need to be found for spatial selective transmission. However, it is quite difficult to find their DOAs due to the coherent nature of multipath signals and considerable computations when performing 2-D searches. In this paper, a new algorithm to estimate 2-D DOA of multiple narrow-band signals is proposed. A DOA cyclic matrix is constructed whose eigenvalues and eigenvectors can be simultaneously used to extract 2-D DOA without 2-D searches. By exploiting the temporal property of cyclostationarity, the signal detection capability is significantly improved. Besides, based on the decorrelation model for mobile terminal signals, the algorithm can be effectively extended to the coherent case without spatial smoothing and the loss of array aperture. Simulation results are given to illustrate the performance of the new algorithm.展开更多
Objective Intrauterine growth restriction followed by postnatal catch-up growth(CG-IUGR)increases the risk of insulin resistance-related diseases.Low-density lipoprotein receptor-related protein 6(LRP6)plays a substan...Objective Intrauterine growth restriction followed by postnatal catch-up growth(CG-IUGR)increases the risk of insulin resistance-related diseases.Low-density lipoprotein receptor-related protein 6(LRP6)plays a substantial role in glucose metabolism.However,whether LRP6 is involved in the insulin resistance of CG-IUGR is unclear.This study aimed to explore the role of LRP6 in insulin signaling in response to CG-IUGR.Methods The CG-IUGR rat model was established via a maternal gestational nutritional restriction followed by postnatal litter size reduction.The mRNA and protein expression of the components in the insulin pathway,LRP6/β-catenin and mammalian target of rapamycin(mTOR)/S6 kinase(S6K)signaling,was determined.Liver tissues were immunostained for the expression of LRP6 andβ-catenin.LRP6 was overexpressed or silenced in primary hepatocytes to explore its role in insulin signaling.Results Compared with the control rats,CG-IUGR rats showed higher homeostasis model assessment for insulin resistance(HOMA-IR)index and fasting insulin level,decreased insulin signaling,reduced mTOR/S6K/insulin receptor substrate-1(IRS-1)serine307 activity,and decreased LRP6/β-catenin in the liver tissue.The knockdown of LRP6 in hepatocytes from appropriate-for-gestational-age(AGA)rats led to reductions in insulin receptor(IR)signaling and mTOR/S6K/IRS-1 serine307 activity.In contrast,LRP6 overexpression in hepatocytes of CG-IUGR rats resulted in elevated IR signaling and mTOR/S6K/IRS-1 serine307 activity.Conclusion LRP6 regulated the insulin signaling in the CG-IUGR rats via two distinct pathways,IR and mTOR-S6K signaling.LRP6 may be a potential therapeutic target for insulin resistance in CG-IUGR individuals.展开更多
AIM:To evaluate the changes in fundus parameters in patients with Alzheimer’s type dementia(ATD)using optical coherence tomography angiography(OCTA),to record flash electroretinograms(ERG)using the RETeval system and...AIM:To evaluate the changes in fundus parameters in patients with Alzheimer’s type dementia(ATD)using optical coherence tomography angiography(OCTA),to record flash electroretinograms(ERG)using the RETeval system and to explore changes in retinal function.METHODS:Twenty-nine patients with ATD and 26 age-matched normal subjects were enrolled.All subjects underwent OCTA scans to analyse the superficial retinal vessel parameters in the macular area,including the vessel length density,the vessel perfusion density and the area of foveal avascular zone(FAZ),as well as the choroidal thickness.The differences between the patients with ATD and the normal control group were compared and explored the relevant factors affecting vessel parameters.We also recorded the flash ERGs using the RETeval system and intended to explore changes in retinal function by analysing the ERG image amplitude in patients with ATD.RESULTS:The vessel parameters[Pvessel length density=0.005 and Pvessel perfusion density=0.006]and average choroid thickness(P<0.001)in the macular area of the ATD group was less than the control group.The FAZ area was statistically significantly enlarged in the ATD group(P<0.001).These parameters were correlated with the Mini-Mental State Examination(MMSE)score and the Montreal Cognitive Assessment(MoCA).CONCLUSION:Patients with ATD exhibit decreases in the parameters associated with fundus.In addition,these indicators significantly correlate with the MMSE score and the MoCA score.OCTA may be an adjunct tool with strong potential to track changes in the diagnosis and monitoring the progression of the disease.展开更多
[Objectives] To investigate the effects of ginseng protein on gut microbiota and BDNF/TrkB signaling pathway in Alzheimer s disease (AD) mice. [Methods] D-galactose/AlCl 3 co-induction was used to establish AD model, ...[Objectives] To investigate the effects of ginseng protein on gut microbiota and BDNF/TrkB signaling pathway in Alzheimer s disease (AD) mice. [Methods] D-galactose/AlCl 3 co-induction was used to establish AD model, and mice were randomly divided into normal group 1, normal group 2, model group 1, model group 2, ginseng protein group, and microbiota transplantation group. Morris water maze experiment was used to evaluate learning and memory ability, and Western blot method was used to detect the expression of APP, p-Tau, BDNF, TrkB, p-TrkB proteins in brain tissue, and 16S rDNA was used to detect diversity of fecal microbiota. [Results] Ginseng protein and microbiota transplantation can shorten the escape latency of mice ( P <0.05), increase the number of crossing platforms ( P <0.05), reduce the expression of APP and p-Tau proteins in brain tissue ( P <0.05, P <0.01), increase the expression of BDNF, p-TrkB, p-TrkB/TrkB proteins ( P <0.05, P <0.01), and reduce the abundance of Alloprevotella, Ruminococcaceae _UCG-014, Prevotellaceae _UCG-001, and Ruminococcus _1 ( P <0.05, P <0.01). [Conclusions] The action mechanism of ginseng protein anti AD may be through regulating gut microbiota diversity and activating the BDNF/TrkB signaling pathway.展开更多
The pathology of Alzheimer’s disease involves a long preclinical period,where the characteristic clinical symptoms of the changes in the brain are undetectable.During the preclinical period,homeostatic mechanisms may...The pathology of Alzheimer’s disease involves a long preclinical period,where the characteristic clinical symptoms of the changes in the brain are undetectable.During the preclinical period,homeostatic mechanisms may help prevent widespread cell death.Evidence has pointed towards selective cell death of diseased neurons playing a potentially protective role.As the disease progresses,dysregulation of signaling pathways that govern cell death contributes to neurodegeneration.Aberrant activation of the c-Jun N-terminal kinase pathway has been established in human and animal models of Alzheimer’s disease caused by amyloid-beta 42-or tau-mediated neurodegeneration.Clonal mosaic studies in Drosophila that examine amyloid-beta 42 in a subset of neurons suggest complex interplay between amyloid-beta 42-expressing and wild-type cells.This review examines the role of c-Jun N-terminal kinase signaling in the context of cell competition and short-range signaling interactions between amyloid-beta 42-expressing and wild-type neurons.Cell competition is a conserved phenomenon regulating tissue integrity by assessing the fitness of cells relative to their neighbors and eliminating suboptimal cells.Somatic clones of amyloid-beta 42 that juxtapose genetically distinct neuronal cell populations show promise for studying neurodegeneration.Generating genetic mosaics with labeled clones of amyloid-beta 42-or tau-expressing and wild-type neurons will allow us to understand how short-range signaling alterations trigger cell death in neurons and thereby contribute to the progression of Alzheimer’s disease.These approaches have the potential to uncover biomarkers for early Alzheimer’s disease detection and new therapeutic targets for intervention.展开更多
The approach of estimating the number of signals based on information theoretic criteria has good performance in the assumption of white noise, but it always leads to false estimation of the coherent sources in colore...The approach of estimating the number of signals based on information theoretic criteria has good performance in the assumption of white noise, but it always leads to false estimation of the coherent sources in colored noise. An approach combining the combined information theoretic criteria and eigen- value correction, is presented to determine number of signals. The method uses maximum likelihood (ML) and information theoretic criteria to estimate coherent signals alternately, then eliminate the inequality of the eigenvalues caused by colored noise by correcting the noise eigenvalues. The computer simulation results prove the effective performance of the method.展开更多
A new method is proposed in this paper for simultaneous frequency and direction estimation of coherent signals. The method is based on the rotational invariance techniques and uses an array triplet in motion to estima...A new method is proposed in this paper for simultaneous frequency and direction estimation of coherent signals. The method is based on the rotational invariance techniques and uses an array triplet in motion to estimate the central frequencies and azimuths of coherent signals from narrowband sources. Without searching in the space of frequency-direction, the computational efficiency of the method is improved significantly. Simulation resultsin the typical examples demonstrate the performance of this new method.展开更多
Based on Evans’spatial smoothing preprocessing scheme,a new approach calledtwo-direction spatial smoothing preprocessing method is presented.It is proved that the decorre-lation,the effective aperture and the maximum...Based on Evans’spatial smoothing preprocessing scheme,a new approach calledtwo-direction spatial smoothing preprocessing method is presented.It is proved that the decorre-lation,the effective aperture and the maximum number of distinguishable coherent signals(whenarray size is given)of the new method are better than those of the Evans’method.Simulationresults give a comparison between the eigenvector spectrums produced by the two methods.展开更多
基金supported by the National Natural Science Foundation of China (62261047,62066040)the Foundation of Top-notch Talents by Education Department of Guizhou Province of China (KY[2018]075)+3 种基金the Science and Technology Foundation of Guizhou Province of China (ZK[2022]557,[2020]1Y004)the Science and Technology Research Program of the Chongqing Municipal Education Commission (KJQN202200637)PhD Research Start-up Foundation of Tongren University (trxyDH1710)Tongren Science and Technology Planning Project ((2018)22)。
文摘In this paper, a two-dimensional(2D) DOA estimation algorithm of coherent signals with a separated linear acoustic vector-sensor(AVS) array consisting of two sparse AVS arrays is proposed. Firstly,the partitioned spatial smoothing(PSS) technique is used to construct a block covariance matrix, so as to decorrelate the coherency of signals. Then a signal subspace can be obtained by singular value decomposition(SVD) of the covariance matrix. Using the signal subspace, two extended signal subspaces are constructed to compensate aperture loss caused by PSS.The elevation angles can be estimated by estimation of signal parameter via rotational invariance techniques(ESPRIT) algorithm. At last, the estimated elevation angles can be used to estimate automatically paired azimuth angles. Compared with some other ESPRIT algorithms, the proposed algorithm shows higher estimation accuracy, which can be proved through the simulation results.
文摘AIM:To evaluate the alterations of the retinal microvasculature and foveal avascular zone in patients with Parkinson’s disease(PD)using optical coherence tomography angiography(OCT-A).METHODS:A retrospective study of PD patients examined in the Ophthalmology Department of the General Hospital of Athens,“Georgios Gennimatas”from March 2021 to March 2022 was conducted.Totally 44 patients with PD were included and 18 healthy controls were examined,hence a total of 124 eyes were enrolled in the study.The foveal and parafoveal superficial and deep capillary plexus vascular density(fSCP-VD,fDCP-VD,pSCP-VD,pDCP-CD)and foveal avascular zone(FAZ)were quantified with OCTA.Optical coherence tomography(OCT)was used to measure macular thickness.Our statistical analysis was conducted by using a mixed effect linear regression model.RESULTS:After adjustment for age and gender,the mean parafoveal superficial capillary plexus vascular density(pSCP-VD)and mean parafoveal deep capillary plexus vascular density(pDCP-VD)were significantly decreased in individuals with PD(P<0.001 in both)by-2.35(95%CI-3.3,-1.45)and-7.5(95%CI-10.4,-4.6)respectively.fSCP-VD and fDCP-VD didn’t approach statistical significance.The FAZ area and perimeter were significantly decreased(P<0.001 in both)by-0.1 mm^(2)(95%CI-0.13,-0.07)and-0.49 mm^(2)(95%CI-0.66,-0.32)respectively.Circularity didn’t approach statistical significance.Central retinal thickness(CRT)was significantly decreased in individuals with PD(P<0.001)by-23.1μm(95%CI-30.2,-16)and temporal retinal thickness(TRT)was decreased(P=0.025)by-11μm(95%CI-22,-1.5)while nasal retinal thickness(NRT)only approached statistical significance(P=0.066).CONCLUSION:The mean pSCP-VD,pDCP-VD,CRT and TRT are significantly decreased and FAZ is altered in individuals with PD.These findings can be potentially used as biomarkers for the diagnosis and evaluation of early PD.
基金supported by the National Natural Science Foundation of China(Youth Science Fund Project),No.81901292(to GC)the National Key Research and Development Program of China,No.2021YFC2502100(to GC)the National Natural Science Foundation of China,No.82071183(to ZZ).
文摘Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.
基金supported by Jiangsu Provincial Medical Key Discipline,No.ZDXK202217(to CFL)Jiangsu Planned Projects for Postdoctoral Research Funds,No.1601056C(to SL).
文摘Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.
基金National Health and Medical Research Council (NHMRC) Australia (to VG)。
文摘Examining the retinal tissue has the potential to provide a unique method and technique to quantify Alzheimer’s disease-related changes in participants at various stages of the disease.In this metaanalysis,we aimed to investigate the association of various optical coherence tomography parameters with Alzheimer’s disease and whether retinal measurements can be used to diffe rentiate between Alzheimer’s disease and control subjects.Scientific databases including Google Schola r,Web of Science,and PubMed were systematically searched for published articles that evaluated retinal nerve fiber layer thickness and retinal microvascular network in Alzheimer’s disease and control subjects.Seventy-three studies(5850 participants,including 2249 Alzheimer’s disease patients and 3601controls) were included in this meta-analysis.Relative to controls,Alzheimer’s disease patients had a significantly lower global retinal nerve fiber layer thickness(standardized mean difference [SMD]=-0.79,95% confidence intervals [CI]:-1.03 to-0.54,P <0.00001) as well as each quadrant being thinner in Alzheimer’s disease versus controls.Regarding macular paramete rs,values measured by optical coherence tomography were significantly lower in Alzheimer’s disease than controls for macular thickness(pooled SMD:-0.44,95% CI:-0.67 to-0.20,P=0.0003),foveal thickness(pooled SMD=-0.39,95% CI:-0.58 to-0.19,P <0.0001),ganglion cell inner plexiform layer(SMD=-1.26,95% CI:-2.24 to-0.27,P=0.01) and macular volume(pooled SMD=-0.41,95% CI-0.76 to-0.07,P=0.02).Analysis using optical coherence tomography angiography parameters revealed mixed results between Alzheimer’s disease and controls.Superficial vessel density(pooled SMD=-0.42,95% CI:-0.68 to-0.17,P=0.0001) and deep vessel density(pooled SMD=-0.46,95% CI:-0.75 to-0.18,P=0.001) were found to be thinner in Alzheimer’s disease patients whereas the foveal avascular zone(SMD=0.84,95% CI:0.17-1.51,P=0.01) was larger in controls.Vascular density and thickness of various retinal laye rs were decreased in Alzheimer’s disease patients compared to controls.Our results provide evidence for optical coherence tomography technology having the potential to detect retinal and microvascular changes in patients diagnosed with Alzheimer’s disease and aid in monito ring and early diagnosis methods.
基金the support from the union project of Peking University third hospital&Chinese Academy of Sciences(Grant No.7490-04,Grant No.KJZD-EW-TZ-L03)the Sichuan Youth Science&Technology Foundation(Grant No.13QNJJ0034)+1 种基金the West Light Foundation of the Chinese Academy of Sciences,the National Major Scientific Equipment program(Grant No.2012YQ120080)the National Science Foundation of China(Grant No.6118082).
文摘A multi-GPU system designed for high-speed,real-time signal processing of optical coherencetomography(OCT)is described herein.For the OCT data sampled in linear wave numbers,themaximum procesing rates reached 2.95 MHz for 1024-OCT and 1.96 MHz for 2048-OCT.Data sampled using linear wavelengths were re-sampled using a time-domain interpolation method and zero-padding interpolation method to improve image quality.The maximum processing rates for1024-OCT reached 2.16 MHz for the time-domain method and 1.26 MHz for the zero-paddingmethod.The maximum processing rates for 2048-0CT reached_1.58 MHz,and 0.68 MHz,respectively.This method is capable of high-speed,real-time processing for O CT systems.
基金supported by the National Natural Science Foundation of China (Grant Nos. 10875101 and 11074209)the Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20090121110030)
文摘The correlated spectroscopy revamped by asymmetric Z-gradient echo detection (CRAZED) sequence is modified to investigate intermolecular double-quantum coherence nuclear magnetic resonance signal dips in highly polarized spin systems. It is found that the occurrence of intermolecular double-quantum coherence signal dips is related to sample geometry, field inhomogeneity and dipolar correlation distance. If the field inhomogeneity is refocused, the signal dip occurs at a fixed position whenever the dipolar correlation distance approaches the sample dimension. However, the position is shifted when the field inhomogeneity exists. Experiments and simulations are performed to validate our theoretic analysis. These signal features may offer a unique way to investigate porous structures and may find applications in biomedicine and material science.
基金supported by the National Natural Science Foundation of China, Nos. 82060727 (to FJ), 81660599 (to FJ)the National Innovation Training Project for College Students, No. 201910661009 (to FJ)the Science and Technology Cooperation Project of Zunyi Science and Technology Bureau and Zunyi Medical University, No. (2019) 47 (to XLF)
文摘Icariin,a major prenylated flavonoid found in Epimedium spp.,is a bioactive constituent of Herba Epimedii and has been shown to exert neuroprotective effects in experimental models of Alzheimer’s disease.In this study,we investigated the neuroprotective mechanism of icariin in an APP/PS1/Tau triple-transgenic mouse model of Alzheimer’s disease.We performed behavioral tests,pathological examination,and western blot assay,and found that memory deficits of the model mice were obviously improved,neuronal and synaptic damage in the cerebral cortex was substantially mitigated,and amyloid-βaccumulation and tau hyperphosphorylation were considerably reduced after 5 months of intragastric administration of icariin at a dose of 60 mg/kg body weight per day.Furthermore,deficits of proteins in the insulin signaling pathway and their phosphorylation levels were significantly reversed,including the insulin receptor,insulin receptor substrate 1,phosphatidylinositol-3-kinase,protein kinase B,and glycogen synthase kinase 3β,and the levels of glucose transporter 1 and 3 were markedly increased.These findings suggest that icariin can improve learning and memory impairments in the mouse model of Alzheimer’s disease by regulating brain insulin signaling and glucose transporters,which lays the foundation for potential clinical application of icariin in the prevention and treatment of Alzheimer’s disease.
文摘To estimate the direction-of-arrival (DOA) of wideband coherent signals, a new method by modifying the orthogonality of the projected suhspaces method is proposed. And it can deal with randomly position perturbed arrays by using the Toeplitz method. This method needn't the primary information of DOA for focusing matrix and the sector dividing of interpolated method, which improving the precision of estimation and reducing the computational complexity. Simulations illustrate the effectiveness of this method.
基金Supported in part by National High Technology Research Project under Grant 863-317-9603-07-4Foundation of Radalr Signal Processing Key Laboratory
文摘In most wireless communication systems, two-dimensional Directions-Of-Arrival (DOA) of multipath signals need to be found for spatial selective transmission. However, it is quite difficult to find their DOAs due to the coherent nature of multipath signals and considerable computations when performing 2-D searches. In this paper, a new algorithm to estimate 2-D DOA of multiple narrow-band signals is proposed. A DOA cyclic matrix is constructed whose eigenvalues and eigenvectors can be simultaneously used to extract 2-D DOA without 2-D searches. By exploiting the temporal property of cyclostationarity, the signal detection capability is significantly improved. Besides, based on the decorrelation model for mobile terminal signals, the algorithm can be effectively extended to the coherent case without spatial smoothing and the loss of array aperture. Simulation results are given to illustrate the performance of the new algorithm.
基金supported by the National Natural Science Foundation of China(No.82001651 and No.81660268).
文摘Objective Intrauterine growth restriction followed by postnatal catch-up growth(CG-IUGR)increases the risk of insulin resistance-related diseases.Low-density lipoprotein receptor-related protein 6(LRP6)plays a substantial role in glucose metabolism.However,whether LRP6 is involved in the insulin resistance of CG-IUGR is unclear.This study aimed to explore the role of LRP6 in insulin signaling in response to CG-IUGR.Methods The CG-IUGR rat model was established via a maternal gestational nutritional restriction followed by postnatal litter size reduction.The mRNA and protein expression of the components in the insulin pathway,LRP6/β-catenin and mammalian target of rapamycin(mTOR)/S6 kinase(S6K)signaling,was determined.Liver tissues were immunostained for the expression of LRP6 andβ-catenin.LRP6 was overexpressed or silenced in primary hepatocytes to explore its role in insulin signaling.Results Compared with the control rats,CG-IUGR rats showed higher homeostasis model assessment for insulin resistance(HOMA-IR)index and fasting insulin level,decreased insulin signaling,reduced mTOR/S6K/insulin receptor substrate-1(IRS-1)serine307 activity,and decreased LRP6/β-catenin in the liver tissue.The knockdown of LRP6 in hepatocytes from appropriate-for-gestational-age(AGA)rats led to reductions in insulin receptor(IR)signaling and mTOR/S6K/IRS-1 serine307 activity.In contrast,LRP6 overexpression in hepatocytes of CG-IUGR rats resulted in elevated IR signaling and mTOR/S6K/IRS-1 serine307 activity.Conclusion LRP6 regulated the insulin signaling in the CG-IUGR rats via two distinct pathways,IR and mTOR-S6K signaling.LRP6 may be a potential therapeutic target for insulin resistance in CG-IUGR individuals.
文摘AIM:To evaluate the changes in fundus parameters in patients with Alzheimer’s type dementia(ATD)using optical coherence tomography angiography(OCTA),to record flash electroretinograms(ERG)using the RETeval system and to explore changes in retinal function.METHODS:Twenty-nine patients with ATD and 26 age-matched normal subjects were enrolled.All subjects underwent OCTA scans to analyse the superficial retinal vessel parameters in the macular area,including the vessel length density,the vessel perfusion density and the area of foveal avascular zone(FAZ),as well as the choroidal thickness.The differences between the patients with ATD and the normal control group were compared and explored the relevant factors affecting vessel parameters.We also recorded the flash ERGs using the RETeval system and intended to explore changes in retinal function by analysing the ERG image amplitude in patients with ATD.RESULTS:The vessel parameters[Pvessel length density=0.005 and Pvessel perfusion density=0.006]and average choroid thickness(P<0.001)in the macular area of the ATD group was less than the control group.The FAZ area was statistically significantly enlarged in the ATD group(P<0.001).These parameters were correlated with the Mini-Mental State Examination(MMSE)score and the Montreal Cognitive Assessment(MoCA).CONCLUSION:Patients with ATD exhibit decreases in the parameters associated with fundus.In addition,these indicators significantly correlate with the MMSE score and the MoCA score.OCTA may be an adjunct tool with strong potential to track changes in the diagnosis and monitoring the progression of the disease.
基金Supported by Liaoning Province Science and Technology Department Project(20180530033,2022-MS-281)Liaoning Provincial Department of Education Project(LJKZZ20220105)Liaoning University of Traditional Chinese Medicine Project(2021LZY042).
文摘[Objectives] To investigate the effects of ginseng protein on gut microbiota and BDNF/TrkB signaling pathway in Alzheimer s disease (AD) mice. [Methods] D-galactose/AlCl 3 co-induction was used to establish AD model, and mice were randomly divided into normal group 1, normal group 2, model group 1, model group 2, ginseng protein group, and microbiota transplantation group. Morris water maze experiment was used to evaluate learning and memory ability, and Western blot method was used to detect the expression of APP, p-Tau, BDNF, TrkB, p-TrkB proteins in brain tissue, and 16S rDNA was used to detect diversity of fecal microbiota. [Results] Ginseng protein and microbiota transplantation can shorten the escape latency of mice ( P <0.05), increase the number of crossing platforms ( P <0.05), reduce the expression of APP and p-Tau proteins in brain tissue ( P <0.05, P <0.01), increase the expression of BDNF, p-TrkB, p-TrkB/TrkB proteins ( P <0.05, P <0.01), and reduce the abundance of Alloprevotella, Ruminococcaceae _UCG-014, Prevotellaceae _UCG-001, and Ruminococcus _1 ( P <0.05, P <0.01). [Conclusions] The action mechanism of ginseng protein anti AD may be through regulating gut microbiota diversity and activating the BDNF/TrkB signaling pathway.
基金supported by 1RO1EY032959-01,NIH1R15GM124654-01 from NIHSchuellein Chair Endowment Fund and STEM Catalyst Grant and start-up support from the University of Dayton(to AS,MKS is Co-PI on NIH RO1 and Co-I on NIH R15)。
文摘The pathology of Alzheimer’s disease involves a long preclinical period,where the characteristic clinical symptoms of the changes in the brain are undetectable.During the preclinical period,homeostatic mechanisms may help prevent widespread cell death.Evidence has pointed towards selective cell death of diseased neurons playing a potentially protective role.As the disease progresses,dysregulation of signaling pathways that govern cell death contributes to neurodegeneration.Aberrant activation of the c-Jun N-terminal kinase pathway has been established in human and animal models of Alzheimer’s disease caused by amyloid-beta 42-or tau-mediated neurodegeneration.Clonal mosaic studies in Drosophila that examine amyloid-beta 42 in a subset of neurons suggest complex interplay between amyloid-beta 42-expressing and wild-type cells.This review examines the role of c-Jun N-terminal kinase signaling in the context of cell competition and short-range signaling interactions between amyloid-beta 42-expressing and wild-type neurons.Cell competition is a conserved phenomenon regulating tissue integrity by assessing the fitness of cells relative to their neighbors and eliminating suboptimal cells.Somatic clones of amyloid-beta 42 that juxtapose genetically distinct neuronal cell populations show promise for studying neurodegeneration.Generating genetic mosaics with labeled clones of amyloid-beta 42-or tau-expressing and wild-type neurons will allow us to understand how short-range signaling alterations trigger cell death in neurons and thereby contribute to the progression of Alzheimer’s disease.These approaches have the potential to uncover biomarkers for early Alzheimer’s disease detection and new therapeutic targets for intervention.
文摘The approach of estimating the number of signals based on information theoretic criteria has good performance in the assumption of white noise, but it always leads to false estimation of the coherent sources in colored noise. An approach combining the combined information theoretic criteria and eigen- value correction, is presented to determine number of signals. The method uses maximum likelihood (ML) and information theoretic criteria to estimate coherent signals alternately, then eliminate the inequality of the eigenvalues caused by colored noise by correcting the noise eigenvalues. The computer simulation results prove the effective performance of the method.
基金Supported by the pre-research fund issued by the China Academy of Electronics & Information Technology. Contract No. 28.5.3.3
文摘A new method is proposed in this paper for simultaneous frequency and direction estimation of coherent signals. The method is based on the rotational invariance techniques and uses an array triplet in motion to estimate the central frequencies and azimuths of coherent signals from narrowband sources. Without searching in the space of frequency-direction, the computational efficiency of the method is improved significantly. Simulation resultsin the typical examples demonstrate the performance of this new method.
文摘Based on Evans’spatial smoothing preprocessing scheme,a new approach calledtwo-direction spatial smoothing preprocessing method is presented.It is proved that the decorre-lation,the effective aperture and the maximum number of distinguishable coherent signals(whenarray size is given)of the new method are better than those of the Evans’method.Simulationresults give a comparison between the eigenvector spectrums produced by the two methods.