Deep brain implantable microelectrode arrays for detection and functional localization of the subthalamic nucleus in rats with Parkinson’s disease

The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel microelectrode arrays(MEAs)can rapidly and precisely locate the STN,which is important for precise stimulation.In this paper,16-channel MEAs modified with multiwalled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(MWCNT/PEDOT:PSS)nanocomposites were designed and fabricated,and the accurate and rapid identification of the STN in PD rats was performed using detection sites distributed at different brain depths.These results showed that nuclei in 6-hydroxydopamine hydrobromide(6-OHDA)-lesioned brains discharged more intensely than those in unlesioned brains.In addition,the MEA simultaneously acquired neural signals from both the STN and the upper or lower boundary nuclei of the STN.Moreover,higher values of spike firing rate,spike amplitude,local field potential(LFP)power,and beta oscillations were detected in the STN of the 6-OHDA-lesioned brain,and may therefore be biomarkers of STN localization.Compared with the STNs of unlesioned brains,the power spectral density of spikes and LFPs synchronously decreased in the delta band and increased in the beta band of 6-OHDA-lesioned brains.This may be a cause of sleep and motor disorders associated with PD.Overall,this work describes a new cellular-level localization and detection method and provides a tool for future studies of deep brain nuclei.

Sex modulates the outcome of subthalamic nucleus deep brain stimulation in patients with Parkinson's disease

There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient management.Although subthalamic nucleus deep brain stimulation is an established therapy for Parkinson’s disease,the effects of sex on treatment outcome are still unclear.The aim of this retrospective observational study,was to examine sex differences in motor symptoms,nonmotor symptoms,and quality of life after subthalamic nucleus deep brain stimulation.Outcome measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson’s disease undergoing subthalamic nucleus deep brain stimulation aged 63.00±8.01 years(55 men and 35 women).Outcomes of clinical evaluations were compared between sexes via a Student’s t-test and within sex via a paired-sample t-test,and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each sex.We found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months post-operation.Restless legs syndrome was alleviated to a greater extent in men than in women.Women demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain stimulation.Furthermore,Hoehn-Yahr stage was positively correlated with the treatment response in men,while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in women.In conclusion,women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms,non-motor symptoms,and quality of life.We found sex-specific factors,i.e.,Hoehn-Yahr stage and levodopa equivalent dose,that were related to motor improvements.These findings may help to guide subthalamic nucleus deep brain stimulation patient selection,prognosis,and stimulation programming for optimal therapeutic efficacy in Parkinson’s disease.

Quercetin ameliorates oxidative stress-induced senescence in rat nucleus pulposus-derived mesenchymal stem cells via the miR-34a-5p/SIRT1 axis

BACKGROUND Intervertebral disc degeneration(IDD)is a main contributor to low back pain.Oxidative stress,which is highly associated with the progression of IDD,increases senescence of nucleus pulposus-derived mesenchymal stem cells(NPMSCs)and weakens the differentiation ability of NPMSCs in degenerated intervertebral discs(IVDs).Quercetin(Que)has been demonstrated to reduce oxidative stress in diverse degenerative diseases.AIM To investigate the role of Que in oxidative stress-induced NPMSC damage and to elucidate the underlying mechanism.METHODS In vitro,NPMSCs were isolated from rat tails.Senescence-associatedβ-galactosidase(SA-β-Gal)staining,cell cycle,reactive oxygen species(ROS),realtime quantitative polymerase chain reaction(RT-qPCR),immunofluorescence,and western blot analyses were used to evaluated the protective effects of Que.Meanwhile the relationship between miR-34a-5p and Sirtuins 1(SIRT1)was evaluated by dual-luciferase reporter assay.To explore whether Que modulates tert-butyl hydroperoxide(TBHP)-induced senescence of NPMSCs via the miR-34a-5p/SIRT1 pathway,we used adenovirus vectors to overexpress and downregulate the expression of miR-34a-5p and used SIRT1 siRNA to knockdown SIRT1 expression.In vivo,a puncture-induced rat IDD model was constructed,and X rays and histological analysis were used to assess whether Que could alleviate IDD in vivo.RESULTS We found that TBHP can cause NPMSCs senescence changes,such as reduced cell proliferation ability,increased SA-β-Gal activity,cell cycle arrest,the accumulation of ROS,and increased expression of senescence-related proteins.While abovementioned senescence indicators were significantly alleviated by Que treatment.Que decreased the expression levels of senescence-related proteins(p16,p21,and p53)and senescence-associated secreted phenotype(SASP),including IL-1β,IL-6,and MMP-13,and it increased the expression of SIRT1.In addition,the protective effects of Que on cell senescence were partially reversed by miR-34a-5p overexpression and SIRT1 knockdown.In vivo,X-ray,and histological analyses indicated that Que alleviated IDD in a punctureinduced rat model.CONCLUSION In summary,the present study provides evidence that Que reduces oxidative stress-induced senescence of NPMSCs via the miR-34a/SIRT1 signaling pathway,suggesting that Que may be a potential agent for the treatment of IDD.

Automated apoptosis identification in fluorescence imaging of nucleus based on histogram of oriented gradients of high-frequency wavelet coefficients

The automatic and accurate identification of apoptosis facilitates large-scale cell analysis.Most identification approaches using nucleus fluorescence imaging are based on specific morphological parameters.However,these parameters cannot completely describe nuclear morphology,thus limiting the identification accuracy of models.This paper proposes a new feature extraction method to improve the performance of the model for apoptosis identification.The proposed method uses a histogram of oriented gradient(HOG)of high-frequency wavelet coefficients to extract internal and edge texture information.The HOG vectors are classified using support vector machine.The experimental results demonstrate that the proposed feature extraction method well performs apoptosis identification,attaining 95:7% accuracy with low cost in terms of time.We confirmed that our method has potential applications to cell biology research.

Magnetic resonance imaging assessment of the lateral geniculate nucleus volume and height in patients with glaucoma:a Meta-analysis

AIM:To evaluate the lateral geniculate nucleus(LGN)volume and height using magnetic resonance imaging(MRI)in glaucoma patients.METHODS:Literatures retrieval was carried out through Pub Med,Web of Science,Embase,and Cochrane Library.Studies that compared the volume and height of LGN in glaucoma patients with that in control subjects were included.The volume and height of LGN were extracted from the included studies.The Review Manager 5.4.1 software was used for the Meta-analysis.RESULTS:This Meta-analysis included 10 crosssectional studies,including the eyes of 223 glaucoma patients and 185 healthy controls.Compared with the control subjects,the volume and height of LGN in glaucoma patients measured by MRI were significantly reduced{-29.13 mm3,95%[confidence interval(CI):-44.82 to-13.43,P=0.0003;-0.61 mm,95%CI:-0.78 to-0.44,P<0.00001,respectively]}.Subgroup analysis demonstrated that the differences of LGN volume and height between glaucoma patients and control subjects in the older group were smaller than that in the younger group,and LGN volume decreased with the increase of glaucoma severity.CONCLUSION:The results demonstrate that the volume and height of LGN are decreased in glaucoma patients,and LGN volume can be considered a parameter of glaucoma severity.

Acute isolated vertigo with vertical up-beating nystagmus: A rare case of nucleus intercalatus of Staderini ischemia

The role of intercalatus nucleus of Staderini(INS),the most caudal of the perihypoglossal nuclei,is much debated.Last research seems to suggest that this nucleus plays a role as a vertical eyes movements integrator.The few clinical reports present in the literature that describe isolated lesions of the INS have described patients presenting in acute with up-beating vertical spontaneous nystagmus.Isolated acute lesion of INS is,in fact,much rare,and,without other neurological signs,is exceptional.We present a case of acute isolated vertigo with no other neurological signs or symptoms,due to INS ischemia provoked by vertebral artery stenosis.The patient presented with spontaneous vertical up-beating nystagmus that showed at videonystagmographic recording,a clear exponential decay of angular slow-phase velocity,that is considered a typical sign of neural integrator impairment.This case seems to represent a further confirm that INS is part,as a vertical-to-position neural integrator,of the neural circuit controlling the vertical eyes movements.

Bayesian Inference of Nucleus Resonance and Neutron Skin

In this proceeding,some highlight results on the constraints of the nuclear matter equation of state(EOS)from the data of nucleus resonance and neutron-skin thickness using the Bayesian approach based on the Skyrme-Hartree-Fock model and its extension have been presented.Typically,the anti-correlation and positive correlations between the slope parameter and the value of the symmetry energy at the saturation density under the constraint of the neutron-skin thickness and the isovector giant dipole resonance have been discussed respectively.It’s shown that the Bayesian analysis can help to find a compromise for the“PREXII puzzle”and the“soft Tin puzzle”.The possible modifications on the constraints of lower-order EOS parameters as well as the relevant correlation when higher-order EOS parameters are incorporated as independent variables have been further illustrated.For a given model and parameter space,the Bayesian approach serves as a good analysis tool suitable for multi-messengers versus multi-variables,and is helpful for constraining quantitatively the model parameters as well as their correlations.

Nucleus Pulposus Cells from Calcified Discs Promote the Degradation of the Extracellular Matrix through Upregulation of the GATA3 Expression

Objective Disc calcification is strongly associated with disc degeneration;however,the underlying mechanisms driving its pathogenesis are poorly understood.This study aimed to provide a gene expression profile of nucleus pulposus cells(NPCs)from calcified discs,and clarify the potential mechanism in disc degeneration.Methods Primary NPCs were isolated from calcified and control discs(CAL-NPC and CON-NPC),respectively.The proliferation and extracellular matrix(ECM)metabolism capacities of the cells were evaluated using MTT and Western blotting,respectively.RNA sequencing was used to identify differentially expressed genes(DEGs)in the CAL-NPCs.The biological functions of the DEGs were analyzed using the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.The transcription factor database and Cytoscape software were used to construct the transcription factor-DEGs regulatory network.The role of the verified transcription factor in NPC proliferation and ECM metabolism was also investigated.Results The CAL-NPCs exhibited a lower proliferation rate and higher ECM degradation capacity than the CON-NPCs.In total,375 DEGs were identified in the CAL-NPCs.The GO and KEGG analyses showed that the DEGs were primarily involved in the regulation of ribonuclease activity and NF-kappa B and p53 signaling pathways.GATA-binding protein 3(GATA3)with the highest verified levels was selected for further studies.Overexpression of GATA3 in the CON-NPCs significantly inhibited their proliferation and promoted their ECM degradation function,while the knockdown of GATA3 in the CAL-NPCs resulted in the opposite phenotypes.Conclusion This study provided a comprehensive gene expression profile of the NPCs from the calcified discs and supported that GATA3 could be a potential target for reversing calcification-associated disc degeneration.

Effect of CSH Crystal Nucleus on Steam-Free Cured Fly Ash Precast Concrete Components

The measures of steam curing and early-strengthening agents to promote the precast components to reach the target strength quickly can bring different degrees of damage to the concrete.Based on this,the new nanomaterial CSH-the hydration product of cement effectively solves these measures’disadvantages,such as excessive energy consumption,thermal stress damage,and the introduction of external ions.In this paper,the effect of CSH on the early strength of precast fly ash concrete components was investigated in terms of setting time,workability,and mechanical properties and analyzed at the microscopic level using hydration temperature,XRD,and SEM.The results showed that under the same workability,CSH could significantly reduce the amount of admixture,shorten the final setting time,almost not affect the initial setting time,and accelerate the hydration of cement.At the optimum dose of 5%,the mechanical properties of the specimens were improved by more than 98%within 12 h of hydration,resulting in an earlier release time of 12 h and no risk of strength inversion later.The results of this paper give theoretical support to the behavior of precast components under steam-free curing.

Effect of exogenous hydrogen sulfide in the nucleus tractus solitarius on gastric motility in rats

BACKGROUND Hydrogen sulfide(H2S)is a recently discovered gaseous neurotransmitter in the nervous and gastrointestinal systems.It exerts its effects through multiple signaling pathways,impacting various physiological activities.The nucleus tractus solitarius(NTS),a vital nucleus involved in visceral sensation,was investigated in this study to understand the role of H2S in regulating gastric function in rats.AIM To examine whether H2S affects the nuclear factor kappa-B(NF-κB)and transient receptor potential vanilloid 1 pathways and the neurokinin 1(NK1)receptor in the NTS.METHODS Immunohistochemical and fluorescent double-labeling techniques were employed to identify cystathionine beta-synthase(CBS)and c-Fos co-expressed positive neurons in the NTS during rat stress.Gastric motility curves were recorded by inserting a pressure-sensing balloon into the pylorus through the stomach fundus.Changes in gastric motility were observed before and after injecting different doses of NaHS(4 nmol and 8 nmol),physiological saline,Capsazepine(4 nmol)+NaHS(4 nmol),pyrrolidine dithiocarbamate(PDTC,4 nmol)+NaHS(4 nmol),and L703606(4 nmol)+NaHS(4 nmol).RESULTS We identified a significant increase in the co-expression of c-Fos and CBS positive neurons in the NTS after 1 h and 3 h of restraint water-immersion stress compared to the expressions observed in the control group.Intra-NTS injection of NaHS at different doses significantly inhibited gastric motility in rats(P<0.01).However,injection of saline,first injection NF-κB inhibitor PDTC or transient receptor potential vanilloid 1(TRPV1)antagonist Capsazepine or NK1 receptor blockers L703606 and then injection NaHS did not produce significant changes(P>0.05).CONCLUSION NTS contains neurons co-expressing CBS and c-Fos,and the injection of NaHS into the NTS can suppress gastric motility in rats.This effect may be mediated by activating TRPV1 and NK1 receptors via the NF-κB channel.

Nucleus直电极人工耳蜗植入对不同频率残余听力的影响

目的:评估Nucleus直电极人工耳蜗植入对各频率残余听力的影响,探讨耳蜗直电极植入的听力学安全性及其创伤特点。方法:分析23例手术前后能够良好配合纯音听力检查、中耳内耳无明显异常、尚未接受人工耳蜗电刺激的单侧Nucleus直电极人工耳蜗植入者的残余听力变化情况。结果:术前植入侧残余听力在术后有所保留者占60%。将最大输出无反应时的听阈值计为最大输出加上5dBHL,经非参数检验:植入侧1kHz以下各频率的残余听力较术前平均损失约6dBHL,差别有极显著性的意义(P值均<0.01);植入侧2kHz以上各频率及非植入侧各频率较术前平均损失<1dBHL,差别无显著性的意义(P值均>0.05)。结论:Nucleus直电极人工耳蜗植入术后,植入耳多数仍可保留部分残余听力,但其损失在1kHz以下频率重于2kHz以上频率。

Effects of ginkgolide B on neuronal discharges in paraventricular nucleus of rat hypothalamic slices

Objective To study the central role of ginkgolide B （BN52021） in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus （PVN） neurons in hypothalamic slice preparation and to elucidate the mechanism involved. Methods Extracellular single-unit discharge recording technique. Results （1） In response to the application of ginkgolide t3 （0.1, 1, 10 μmol/L; n = 27） into the perfusate for 2 rain, the spontaneous discharge rates （SDR） of 26 （26/27, 96.30%） neurons were significantly decreased in a dose-dependent manner. （2） Pretreatment with L-glutamate （L-Glu, 0.2 mmol/L） led to a marked increase in the SDR of all 8 （100%） neurons in an epileptiform pattern. The increased discharges were suppressed significantly after ginkgolide B （1 μmol/L） was applied into the perfusate for 2 min. （3） In 8 neurons, perfusion of the selective L-type calcium channel agonist, Bay K 8644 （0.1 μmol/L）, induced a significant increase in the discharge rates of 8 （8/8, 100%） neurons, while ginkgolide B （1μmol/L） applied into the perfusate, could inhibit the discharges of 8 （100%） neurons. （4） In 8 neurons, the broad potassium channels blocker, tetraethylammonium （TEA, 1 mmol/L） completely blocked the inhibitory effect of ginkgolide B （1 μmol/L）. Conclusion These results suggest that ginkgolide B can inhibit the electrical activity of paraventricular neurons. The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and potentially concerned with delayed rectifier potassium channel （KDR）.

Analysis on the Relationship between Selective Pressure and Nucleotide Substitution Rate in Nucleus and Organelle Genes of Sorghum and Maize

[Objective]The aim was to research the relationship between nucleotide substitutions rate and selective pressure.[Method]Synonymous and nonsynonymous substitutions and their ratios for some sorghum and maize genes in nucleus and organelle genomes were analyzed by statistical method,and comparative analysis of related functional genes were carried out.[Result]The pure selective pressures of the related functional genes were similar between nucleus and chloroplast genomes,but was lower in mitochondrial genome.The significant differences of nucleotide substitution rate between sorghum and maize orthologous genes in nucleus genome,and among different functional genes in nucleus genome were mainly due to the nonsynonymous substitution difference.[Conclusion]The molecular evolutional rate of different functional genes and different lineages were influenced by selective pressure.The differences of molecular evolutional rate among nucleus,chloroplast and mitochondria genomes had no direct relationship with selective pressure.

Ultrastructural Features of Nucleus Degradation During Programmed Cell Death of Starchy Endosperm Cells in Rice

Ultrastructural features of nucleus degradation during programmed cell death (PCD) of starchy endosperm cells in rice ( Oryza sativa L.) were observed using transmission electron microscopy. Several distinct morphological features of PCD have been found in the developing starchy endosperm cells, e.g. nucleus deformation, chromatin condensation, nuclear envelope disruption, and nuclear matrix leakage. DNA ladder displayed a smear of large DNA fragments from nucleus and evident bands of small DNA fragments (140-180 bp) from both nucleus and cytoplasm. In contrast with the rapid nucleus degradation, cell organelles in cytoplasm, such as rough endoplasmic reticulum, amyloplast, and mitochondrion, maintained their metabolic functions for a longer time. Seed reserves were continually synthesized and accumulated in the starchy endosperm cells despite the nucleus degradation during the PCD process. These results suggest that starchy endosperm cells remain active during reserve material synthesis and accumulation in the PCD process. The specific relationships between nucleus and cytoplasm in the developing endosperm cells and the morphological changes of nucleus in the endosperm PCD process were also discussed.

Functional dissection of parabrachial substrates in processing nociceptive information

Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of suffering.The lateral parabrachial nucleus(lPBN),composed of external-(elPBN),dorsal-(dlPBN),and central/superior-subnuclei(jointly referred to as slPBN),receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption.However,the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear.In this study,we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor(NK1R)(lPBNNK1R)are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle,while elPBN neurons are dispensable for driving such reactions.Notably,lPBNNK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats.Lastly,both lPBNNK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions.Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.

基于Nucleus PLUS的嵌入式系统的软件设计

本文介绍了离子迁移谱仪的工作机理、软件系统设计以及嵌入式实时多任务操作系统 (RTOS)NucleusPLUS ,重点介绍后者在离子迁移谱仪中的具体实现。

基于Nucleus的IC卡设备驱动

首先对IC卡接口设备的工作原理和IC卡接口芯片TDA8007进行了研究,然后分析了嵌入式操作系统Nucleus的设备驱动设计的两大关键技术——中断机制和设备管理机制,最后,结合IC卡接口设备的工作原理以及Nucleus驱动设计的特点,实现了一个结构清晰的IC卡接口芯片的设备驱动程序。

Nucleus24型人工耳蜗植入后的电极有效性

目的 :随访耳蜗植入后出现蜗外电极或坏损电极的情况 ,评价人工耳蜗植入后电极的有效性。方法 :1998年 6月至 2 0 0 2年 8月 5 3例NucleusCI2 4M型耳蜗植入者 ,在术中及术后映射调图时进行电极阻抗测试 ,确定有无电极坏损及其坏损时间。开机时拍摄耳蜗位X线平片 ,确定电极是否完全植入。分析手术过程和术者经验对电极有效性的影响。结果 :电极出现坏损的比例为 13 2 % ,电极在术中插拔两次以上而造成电极坏损的危险度为 0 4 6 5 6。 4年累积生存率达 96 2 %。不完全植入的比例为 15 1% ,其中又以耳蜗形态异常者居多 (7/11)。结论 :NucleusCI2 4M型植入体在开机 1～ 4年内的可靠性较高。电极序列在术中插拔两次以上 ,是导致电极坏损的主要原因。患者耳蜗的纤维化。

Effect of nitric oxide on the expression of apelin receptor mRNA in rat caudate nucleus

Objective To investigate the effect of nitric oxide （NO） on the expression of apelin receptor mRNA, as well as their correlation, in the caudate nucleus of rat. Methods L-Arginine （L-Arg）, N^G-nitro-L-arginine methyl ester （L-NAME） and normal saline （NS） was separately microinjected into rat caudate nucleus. Expressions of neuronal NO synthase （nNOS） mRNA and apelin receptor mRNA were detected by RT-PCR at 4, 8, 12, 24 and 48 h after microinjection, and their correlation was determined. Results The expressions of nNOS mRNA and apelin receptor mRNA were both significantly increased after microinjection of L-Arg, but significantly decreased after microinjection of L-NAME compared with the NS control group. The nNOS mRNA had a positive correlation with the expression of apelin receptor mRNA after microinjection of L-Arg and L-NAME. Conclusion The activity of NOS in the central nervous system, especially in the caudate nucleus, is one of the key factors for NO to exert many kinds of biological actions, such as modulation of central pain, as a neurotransmitter. The neurobiological action of NO in rat caudate nucleus may be associated with apelin receptors.

Nucleus操作系统在ARM11上的移植研究与实现

基于对ARM11架构的启动模式与内存分配的技术研究,通过对Nucleus内核的分析,在ARM11架构的芯片上实现Nucleus操作系统的移植。以S3C6410为例,详细介绍了从板级初始化到任务循环调度过程中的启动模块、中断设计、定时器设计、任务调度流程与触发方式。目前成功移植于TD-LTE系统中,实现操作系统基本功能的同时满足了实验项目中TD-LTE对系统实时性与任务资源管理的需求。