Glucocorticoid receptor signaling in the brain and its involvement in cognitive function

The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental challenges.In the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and neuroplasticity.The glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic mechanisms.Protein interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive functions.An appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive impairment.Patients with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor expression.This review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive activities.It emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive impairment.This provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders.

Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway:a potential therapeutic approach for neurodegenerative diseases

The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain axis.The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine systems.Conversely,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host interactions.This reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological diseases.The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological diseases.This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological diseases.Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders.This can be achieved through various methods such as dietary modifications,probiotic supplements,Chinese herbal extracts,combinations of Chinese herbs,and innovative dosage forms.These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.

Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease

Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.

Netrin-1 signaling pathway mechanisms in neurodegenerative diseases

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.

Prolonged intermittent theta burst stimulation restores the balance between A_(2A)R-and A_(1)R-mediated adenosine signaling in the 6-hydroxidopamine model of Parkinson's disease

An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.

Open World Recognition of Communication Jamming Signals

To improve the recognition ability of communication jamming signals,Siamese Neural Network-based Open World Recognition(SNNOWR)is proposed.The algorithm can recognize known jamming classes,detect new(unknown)jamming classes,and unsupervised cluseter new classes.The network of SNN-OWR is trained supervised with paired input data consisting of two samples from a known dataset.On the one hand,the network is required to have the ability to distinguish whether two samples are from the same class.On the other hand,the latent distribution of known class is forced to approach their own unique Gaussian distribution,which is prepared for the subsequent open set testing.During the test,the unknown class detection process based on Gaussian probability density function threshold is designed,and an unsupervised clustering algorithm of the unknown jamming is realized by using the prior knowledge of known classes.The simulation results show that when the jamming-to-noise ratio is more than 0d B,the accuracy of SNN-OWR algorithm for known jamming classes recognition,unknown jamming detection and unsupervised clustering of unknown jamming is about 95%.This indicates that the SNN-OWR algorithm can make the effect of the recognition of unknown jamming be almost the same as that of known jamming.

Fuzzy Jamming Pattern Recognition Based on Statistic Parameters of Signal’s PSD

In order to recognize the jamming pattern in anti-jamming, a novel fuzzy jamming recognition method based on statistic parameters of received signal’s power spectral density (PSD) is proposed. It exploits PSD’s shape factor and skewness of received signal as classified characters of jamming pattern. After the mean center and variance of each jamming pattern are calculated by using some jamming samples, an exponential fuzzy membership function is used to calculate the membership value of the recognized sample. Finally, the jamming pattern of received signal is recognized by the maximum membership principle. The simulation results show that the proposed algorithm can recognize common eight jamming patterns accurately.

Noise amplitude modulation jamming signal suppression based on weighted-matching pursuit

To suppress noise amplitude modulation jamming in a single-antenna radar system, a new method based on weighted-matching pursuit （WMP） algorithm is proposed, which can achieve underdetermined blind sources separation of the jamming and the target echo from the jammed mixture in the single channel of the receiver. Firstly, the presented method utilizes a prior information about the differences between the jamming component and the radar transmitted signal to construct two signal-adapted sub-dictionaries and to determine the weights. Then the WMP algorithm is applied to remove the jamming component from the mixture. Experimental results verify the validity of the presented method. By comparison of the pulse compression performance, the simulation results shows that the presented method is superior to the method of frequency domain cancellation （FDC） when the jamming-to-signal ratio （JSR） is lower than 15 dB.

Traffic jam in signalized road network

Traffic jam in large signalized road network presents a complex nature.In order to reveal the jam characteristics,two indexes,SVS(speed of virtual signal) and VOS(velocity of spillover),were proposed respectively.SVS described the propagation of queue within a link while VOS reflected the spillover velocity of vehicle queue.Based on the two indexes,network jam simulation was carried out on a regular signalized road network.The simulation results show that:1) The propagation of traffic congestion on a signalized road network can be classified into two stages:virtual split driven stage and flow rate driven stage.The former stage is characterized by decreasing virtual split while the latter only depends on flow rate; 2) The jam propagation rate and direction are dependent on traffic demand distribution and other network parameters.The direction with higher demand gets more chance to be jammed.Our findings can serve as the basis of the prevention of the formation and propagation of network traffic jam.

Navigation jamming signal recognition based on long short-term memory neural networks

This paper introduces the time-frequency analyzed long short-term memory(TF-LSTM) neural network method for jamming signal recognition over the Global Navigation Satellite System(GNSS) receiver. The method introduces the long shortterm memory(LSTM) neural network into the recognition algorithm and combines the time-frequency(TF) analysis for signal preprocessing. Five kinds of navigation jamming signals including white Gaussian noise(WGN), pulse jamming, sweep jamming, audio jamming, and spread spectrum jamming are used as input for training and recognition. Since the signal parameters and quantity are unknown in the actual scenario, this work builds a data set containing multiple kinds and parameters jamming to train the TF-LSTM. The performance of this method is evaluated by simulations and experiments. The method has higher recognition accuracy and better robustness than the existing methods, such as LSTM and the convolutional neural network(CNN).

基于Jamming转变理论的沥青路面车辙演化机制

沥青路面宏观车辙其实质是混合料细观结构演变的结果,为了深入理解路面车辙流变行为的发展过程,基于颗粒物质Jamming理论开展了沥青混合料车辙演化机制研究。采用图像处理技术构建了沥青混合料细观结构模型,基于时-温等效原理开展了车辙仿真测试,分析了车辙变形过程中混合料宏细观结构的变化特征,探究了沥青路面Unjamming转变行为的影响规律与车辙演化机制。结果表明:Jamming理论可以很好地解释沥青路面的车辙演变全过程,车辙深度与沥青混合料颗粒的堵塞程度密切相关;随着加载时间和作用荷载的增加,混合料Jamming堵塞程度增大,车辙深度和面积分数也逐渐增加,并最终趋于稳定,颗粒体系Jammed态的转变受到了沥青砂浆和集料骨架共同作用的影响;随着测试温度升高,试件内部颗粒位移和位移差增大,混合料Jamming堵塞程度降低。沥青路面颗粒体系由稳定的Jammed态转变为不稳定的Unjammed态,是诱导路面车辙和泛油病害发生的内因,研究结果实现了Jamming理论在非晶体系中的应用,为深入理解沥青混合料的车辙演变行为提供了一种新的研究思路。

Optimal Periodic Pulse Jamming Signal Design for QPSK Systems

The problem of optimal periodic pulse jamming design for a quadrature phase shift keying（QPSK）communication system is investigated.First a closed-form bit-error-rate（BER）of QPSK system under the jamming of pulse signal is derived.Then the asymptotic performance of the derived BER is analyzed as the signal-to-noise ratio（SNR）grows to infinity.In order to maximize the BER of the QPSK system,the optimal parameters of periodic pulse jamming signal,including the duty cycle and signal-tojamming power ratio（SJR）,are found out.Numerical results are presented to verify our analytical results and the optimality of our design.

Research on Blanket Jamming to Beidou Navigation Signals Based on BOC Modulation

Aiming at the issue of influence of blanket jamming on performances of Beidou navigation signals, through studying Beidou signals based on the BOC modulation technology, establishing a blanket jamming mathematical model, and performing modeling and simulation on multiple jamming technologies, to attain the jamming curves of time domains and frequency domains of Beidou signals, and the correlation curve of the signal-to-jamming rate and the bit error rate under blanket jamming, and thus realizing evaluation on the jamming performance.

Digital signal acquisition system for complex nuclear reaction experiments

A digital data-acquisition system based on XIA LLC products was used in a complex nuclear reaction experiment using radioactive ion beams.A flexible trigger system based on a field-programmable gate array(FPGA)parametrization was developed to adapt to different experimental sizes.A user-friendly interface was implemented,which allows converting script language expressions into FPGA internal control parameters.The proposed digital system can be combined with a conventional analog data acquisition system to provide more flexibility.The performance of the combined system was veri-fied using experimental data.

Timosaponin AⅢ induces drug-metabolizing enzymes by activating constitutive androstane receptor (CAR) via dephosphorylation of the EGFR signaling pathway

The current study aimed to assess the effect of timosaponin AⅢ(T-AⅢ)on drug-metabolizing enzymes during anticancer therapy.The in vivo experiments were conducted on nude and ICR mice.Following a 24-day administration of T-AⅢ,the nude mice exhibited an induction of CYP2B10,MDR1,and CYP3A11 expression in the liver tissues.In the ICR mice,the expression levels of CYP2B10 and MDR1 increased after a three-day T-AⅢ administration.The in vitro assessments with HepG2 cells revealed that T-AⅢ induced the expression of CYP2B6,MDR1,and CYP3A4,along with constitutive androstane receptor(CAR)activation.Treatment with CAR siRNA reversed the T-AⅢ-induced increases in CYP2B6 and CYP3A4 expression.Furthermore,other CAR target genes also showed a significant increase in the expression.The up-regulation of murine CAR was observed in the liver tissues of both nude and ICR mice.Subsequent findings demonstrated that T-AⅢ activated CAR by inhibiting ERK1/2 phosphorylation,with this effect being partially reversed by the ERK activator t-BHQ.Inhibition of the ERK1/2 signaling pathway was also observed in vivo.Additionally,T-AⅢ inhibited the phosphorylation of EGFR at Tyr1173 and Tyr845,and suppressed EGF-induced phosphorylation of EGFR,ERK,and CAR.In the nude mice,T-AⅢ also inhibited EGFR phosphorylation.These results collectively indicate that T-AⅢ is a novel CAR activator through inhibition of the EGFR pathway.

PHD17 acts as a target of miR1320 to negatively control cold tolerance via JA-activated signaling in rice

Plant Homeo Domain(PHD)proteins are involved in diverse biological processes during plant growth.However,the regulation of PHD genes on rice cold stress response remains largely unknown.Here,we reported that PHD17 negatively regulated cold tolerance in rice seedlings as a cleavage target of miR1320.PHD17 expression was greatly induced by cold stress,and was down-regulated by miR1320 overexpression and up-regulated by miR1320 knockdown.Through 5'RACE and dual luciferase assays,we found that miR1320 targeted and cleaved the 3'UTR region of PHD17.PHD17 was a nuclearlocalized protein and acted as a transcriptional activator in yeast.PHD17 overexpression reduced cold tolerance of rice seedlings,while knockout of PHD17 increased cold tolerance,partially via the CBF cold signaling.By combining transcriptomic and physiological analyses,we demonstrated that PHD17 modulated ROS homeostasis and flavonoid accumulation under cold stress.K-means clustering analysis revealed that differentially expressed genes in PHD17 transgenic lines were significantly enriched in the jasmonic acid(JA)biosynthesis pathway,and expression of JA biosynthesis and signaling genes was verified to be affected by PHD17.Cold stress tests applied with MeJA or IBU(JA synthesis inhibitor)further suggested the involvement of PHD17 in JA-mediated cold signaling.Taken together,our results suggest that PHD17 acts downstream of miR1320 and negatively regulates cold tolerance of rice seedlings through JA-mediated signaling pathway.

Calmodulins and calmodulin-like proteins-mediated plant organellar calcium signaling networks under abiotic stress

Plant calmodulins(CaMs)and calmodulin-like proteins(CMLs)mediate Ca~(2+)signaling in response to abiotic stresses.Manipulation of this signaling in crops could increase stress tolerance.We review methods for detecting Ca~(2+)signals,regulatory roles of Ca Ms and CMLs,binding targets,and Ca~(2+)networks under abiotic stress in organelles.

Localizing Jammer in an Indoor Environment by Estimating Signal Strength and Kalman Filter

Localizing a jammer in an indoor environment in wireless sensor networks becomes a significant research problem due to the ease of blocking the communication between legitimate nodes. An adversary may emit radio frequency to prevent the transmission between nodes. In this paper, we propose detecting the position of the jammer indoor by using the received signal strength and Kalman filter (KF) to reduce the noise due to the multipath signal caused by obstacles in the indoor environment. We compare our work to the Linear Prediction Algorithm (LP) and Centroid Localization Algorithm (CL). We observed that the Kalman filter has better results when estimating the distance compared to other algorithms.

Gut microbiota dysbiosis contributes toα-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson’s disease

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.

Melatonin improves synapse development by PI3K/Akt signaling in a mouse model of autism spectrum disorder

Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic spines.The role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea r.In the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal cortex.Our findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout mice.Furthermore,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this region.The pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of GABAergic synaptic function.These findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.