Exercise fatigue is a complex physiological and psychological phenomenon that includes peripheral fatigue in the muscles and central fatigue in the brain. Peripheral fatigue refers to the loss of force caused at the distal end of the neuromuscular junction, whereas central fatigue involves decreased motor output from the primary motor cortex, which is associated with modulations at anatomical sites proximal to nerves that innervate skeletal muscle. The central regulatory failure reflects a progressive decline in the central nervous system’s capacity to recruit motor units during sustained physical activity. Emerging evidence highlights the critical involvement of central neurochemical regulation in fatigue development, particularly through neurotransmitter-mediated modulation. Alterations in neurotransmitter release and receptor activity could influence excitatory and inhibitory signal pathways, thus modulating the perception of fatigue and exercise performance. Increased serotonin (5-HT) could increase perception of effort and lethargy, reduce motor drive to continue exercising, and contribute to exercise fatigue. Decreased dopamine (DA) and noradrenaline (NE) neurotransmission can negatively impact arousal, mood, motivation, and reward mechanisms and impair exercise performance. Furthermore, the serotonergic and dopaminergic systems interact with each other; a low 5-HT/DA ratio enhances motor motivation and improves performance, and a high 5-HT/DA ratio heightens fatigue perception and leads to decreased performance. The expression and activity of neurotransmitter receptors would be changed during prolonged exercise to fatigue, affecting the transmission of nerve signals. Prolonged high-intensity exercise causes excess 5-HT to overflow from the synaptic cleft to the axonal initial segment and activates the 5-HT1A receptor, thereby inhibiting the action potential of motor neurons and affecting the recruitment of motor units. During exercise to fatigue, the DA secretion is decreased, which blocks the binding of DA to D1 receptor in the caudate putamen and inhibits the activation of the direct pathway of the basal ganglia to suppress movement, meanwhile the binding of DA to D2 receptor is restrained in the caudate putamen, which activates the indirect pathway of the basal ganglia to influence motivation. Furthermore, other neurotransmitters and their receptors, such as adenosine (ADO), glutamic acid (Glu), and γ‑aminobutyric acid (GABA) also play important roles in regulating neurotransmitter balance and fatigue. The occurrence of central fatigue is not the result of the action of a single neurotransmitter system, but a comprehensive manifestation of the interaction between multiple neurotransmitters. This review explores the important role of neurotransmitters and their receptors in central motor fatigue, reveals the dynamic changes of different neurotransmitters such as 5-HT, DA, NE, and ADO during exercise, and summarizes the mechanisms by which these neurotransmitters and their receptors regulate fatigue perception and exercise performance through complex interactions. Besides, this study presents pharmacological evidence that drugs such as agonists, antagonists, and reuptake inhibitors could affect exercise performance by regulating the metabolic changes of neurotransmitters. Recently, emerging interventions such as dietary bioactive components intake and transcranial electrical stimulation may provide new ideas and strategies for the prevention and alleviation of exercise fatigue by regulating neurotransmitter levels and receptor activity. Overall, this work offers new theoretical insights into the understanding of exercise central fatigue, and future research should further investigate the relationship between neurotransmitters and their receptors and exercise fatigue.

ObjectiveTo investigate the effects of jujuboside A （JuA） on the learning and memory abilities and histopathological changes in the rat model of vascular cognitive impairment （VCI） and explore the potential mechanisms by which JuA treats VCI. MethodsA total of 50 male SPF-grade SD rats were randomized into a sham operation group （n=10）， a blank control group （n=10）， and a modeling group （n=30）. The rats in the modeling group underwent bilateral carotid artery ligation （2-VO） for the modeling of VCI. After stabilization， the VCI rats were randomized into model， JuA （20 mg·kg^-¹）， and donepezil （0.45 mg·kg^-¹） groups. After 4 weeks of gavage， the novel object recognition and Morris water maze tests were conducted to evaluate the learning and memory abilities of rats. Nissl staining was employed to evaluate the morphology and number of hippocampal neurons. Real-time PCR was employed to measure the mRNA levels of glycogen synthase kinase-3β （GSK-3β）， cAMP response element-binding protein （CREB）， B cell lymphoma-2 （Bcl-2）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） in the hippocampal tissue. Western blot was employed to quantify the protein levels of GSK-3β， p-GSK-3β， p-CREB， Bcl-2， PI3K， p-PI3K， Akt， and p-Akt in the hippocampal tissue. ResultCompared with the sham operation group， the model group exhibited declines in the learning and memory abilities （P<0.01）， neuronal damage and decreased neurons in the hippocampal CA1 region （P<0.01）， up-regulation in the mRNA level of GSK-3β （P<0.01）， and down-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2， as well as the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.01）. In comparison to the model group， both the JuA and donepezil groups demonstrated improvements in the learning and memory abilities （P<0.05， P<0.01）， with reduced neuronal damage and increased neurons （P<0.05， P<0.01）. In addition， the two groups showed down-regulation in the mRNA level of GSK-3β （P<0.01） and up-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2 and the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.05， P<0.01）. There were no statistically significant differences between the blank control and sham operation groups in terms of the learning and memory abilities， neuron count， and mRNA and protein levels of PI3K/Akt/GSK-3β pathway-related factors. ConclusionJuA can ameliorate the cognitive impairment in the rat model of VCI by activating the PI3K/Akt signaling pathway， reducing the apoptosis of hippocampal neurons， and alleviating the hippocampal neuronal damage.

ObjectiveTo investigate the mechanism by which Huanglian Jiedutang （HLJDT） inhibits pyroptosis and neuroinflammation in Alzheimer's disease （AD） mice via the NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific protease-1 （Caspase）-1/gasdermin D （GSDMD） pathway. MethodsThirty APP/PS1 double transgenic mice were randomly and evenly divided into the model group （model group）， the positive control group （Donepezil group， 0.65 mg·kg^-1）， and the HLJDT treatment group （HLJDT group， 5.2 g·kg^-1）. Ten C57BL/6 mice were assigned to the blank control group （control group）. The Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Nissl staining was employed to observe the morphology， quantity， and distribution of neurons in the hippocampal region. Golgi staining was used to examine the morphology and density of neuronal dendritic spines in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was performed to detect the mRNA expression of neuroinflammation-related factors and genes in the NLRP3/Caspase-1/GSDMD pyroptosis pathway in the hippocampus. Western blot was used to detect the expression of postsynaptic density protein 95 （PSD95）， amyloid precursor protein （APP）， inflammatory factors including nuclear factor-κB （NF-κB）， phosphorylated NF-κB （p-NF-κB）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， as well as pyroptosis pathway-related proteins including NLRP3， Caspase-1， GSDMD， and GSDMD-N. ResultsCompared with the control group， the model group exhibited significantly decreased learning and memory abilities （P<0.01）， reduced numbers of neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly increased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.01）. Protein levels of PSD95 were markedly decreased， while the expression levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly elevated （P<0.01）. Compared with the model group， both the Donepezil and HLJDT groups showed significantly improved learning and memory abilities （P<0.05， P<0.01）， increased numbers of hippocampal neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly decreased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.05， P<0.01）. Protein levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly downregulated， while PSD95 expression was significantly upregulated （P<0.05， P<0.01）. There was no statistically significant difference in GSDMD-N levels in the Donepezil group， while GSDMD-N expression was significantly decreased in the HLJDT group （P<0.05）. ConclusionThis study confirms that HLJDT can improve learning and memory abilities in APP/PS1 double transgenic mice， and attenuate neuronal loss and synaptic damage， possibly through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD pathway.

ObjectiveTo investigate the mechanism by which Huanglian Jiedutang （HLJDT） inhibits pyroptosis and neuroinflammation in Alzheimer's disease （AD） mice via the NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific protease-1 （Caspase）-1/gasdermin D （GSDMD） pathway. MethodsThirty APP/PS1 double transgenic mice were randomly and evenly divided into the model group （model group）， the positive control group （Donepezil group， 0.65 mg·kg^-1）， and the HLJDT treatment group （HLJDT group， 5.2 g·kg^-1）. Ten C57BL/6 mice were assigned to the blank control group （control group）. The Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Nissl staining was employed to observe the morphology， quantity， and distribution of neurons in the hippocampal region. Golgi staining was used to examine the morphology and density of neuronal dendritic spines in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was performed to detect the mRNA expression of neuroinflammation-related factors and genes in the NLRP3/Caspase-1/GSDMD pyroptosis pathway in the hippocampus. Western blot was used to detect the expression of postsynaptic density protein 95 （PSD95）， amyloid precursor protein （APP）， inflammatory factors including nuclear factor-κB （NF-κB）， phosphorylated NF-κB （p-NF-κB）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， as well as pyroptosis pathway-related proteins including NLRP3， Caspase-1， GSDMD， and GSDMD-N. ResultsCompared with the control group， the model group exhibited significantly decreased learning and memory abilities （P<0.01）， reduced numbers of neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly increased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.01）. Protein levels of PSD95 were markedly decreased， while the expression levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly elevated （P<0.01）. Compared with the model group， both the Donepezil and HLJDT groups showed significantly improved learning and memory abilities （P<0.05， P<0.01）， increased numbers of hippocampal neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly decreased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.05， P<0.01）. Protein levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly downregulated， while PSD95 expression was significantly upregulated （P<0.05， P<0.01）. There was no statistically significant difference in GSDMD-N levels in the Donepezil group， while GSDMD-N expression was significantly decreased in the HLJDT group （P<0.05）. ConclusionThis study confirms that HLJDT can improve learning and memory abilities in APP/PS1 double transgenic mice， and attenuate neuronal loss and synaptic damage， possibly through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD pathway.

Objectives:To explore the relationship between insomnia symptoms and neuroticism in patients with COVID-19,and to explore the role of anxiety and psychological capital in the relationship.Methods:Totally 687 patients with COVID-19 were recruited from Shanghai Fangcang Hospital.The Athens Insomnia Scale(AIS),Eysenck Personality Questionnaire-Revised Short Scale for Chinese Neuroticism Subscale(EPQ-RSC-N),Self-Rat-ing Anxiety Scale(SAS)and Psychological Capital Questionnaire(PCQ)were used to measure insomnia symp-toms,neuroticism personality trait,anxiety symptoms and psychological capital levels.The deviation-corrected per-centile Bootstrap method was used to test the mediating effect,and the PROCESS program was used to test the moderated effect.Results:The detection rate of insomnia symptoms was 49.93％.The AIS scores were lower in male patients than in female patients(P＜0.01).The SAS scores partly mediated the relationship between neuroti-cism scores and AIS scores,with an effect size of 0.03,accounting for 18.29％of the total effect.With the im-provement of PCQ scores,the predictive effect of SAS scores on AIS scores gradually decreased(β=-0.01,t=-4.41,P＜0.001).Conclusions:Anxiety symptoms in patients with COVID-19 play a partial mediating role in the positive relationship between insomnia symptoms and neuroticism.The psychological capital moderates the relation-ship between insomnia and anxiety symptoms.

Objective To explore the improving effect and mechanism of saikosaponin A on insomnia rats based on cAMP/PKA/CREB pathway.Methods Seventy-five SD rats were randomly divided into blank group,model group,low-dose saikosaponin A group(0.625 mg·kg-1),high-dose saikosaponin A group(2.500 mg·kg-1)and Estazolam group(0.1 mg·kg-1),with 15 rats in each group.Insomnia rat model was established by intraperitoneal injection of Phenylalanine(PCPA,0.1 mg·kg-1).The general condition and circadian rhythm of rats were observed;the sleep latency and sleep duration of rats were measured by pentobarbital sodium righting experiment.The sleep phase of rats was observed,and the duration of slow wave sleep phase 1(SWS1),slow wave sleep phase 2(SWS2),rapid eye movement sleep phase(REMS)and total sleep time(TST)were recorded.The mRNA expression levels of hypothalamic circadian genes Clock,Bmal1 and clock-controlled genes Rev-erbα and Rorα were determined by qRT-PCR.The expression level of NeuN in hippocampus was determined by immunofluorescence.The level of cAMP in brain tissue was determined by ELISA.The expression levels of Clock,Bmal1,Rev-erbα,Rorα and cAMP/PKA/CREB pathway-related proteins in brain tissue were determined by Western Blot.Results Compared with the blank group,the rats in the model group had disordered circadian rhythms,extreme excitement,irritability,and reduced sleep;the sleep latency was significantly prolonged(P＜0.05),and the sleep duration and SWS1,SWS2,REMS and TST were significantly shortened(P＜0.05).The arrangement of neurons was disordered,and the IOD value of NeuN positive neurons was significantly decreased(P＜0.05).The mRNA and protein expression levels of Clock,Bmal1,Rev-erbα and Rorα in brain tissue were significantly decreased(P＜0.05).The expression levels of cAMP,p-PKA/PKA and p-CREB/CREB in brain tissue were significantly decreased(P＜0.05).Compared with the model group,the aggressiveness of the rats in the administration group was significantly weakened,the circadian rhythm was rhythmic,the activity was reduced,and the sleep was increased.The sleep latency was significantly shortened(P＜0.05),and the sleep duration and SWS1,SWS2,REMS and TST were significantly prolonged(P＜0.05).The disorder of neuronal arrangement was restored,and the IOD value of NeuN positive neurons was significantly increased(P＜0.05).The mRNA and protein expression levels of Clock,Bmal1,Rev-erbα and Rorα in brain tissue were significantly increased(P＜0.05).The protein expression levels of cAMP,p-PKA/PKA and p-CREB/CREB in brain tissue were significantly increased(P＜0.05).Conclusion Saikosaponin A may improve the circadian rhythm of insomnia rats by activating cAMP/PKA/CREB pathway.

An increasing number of studies have been focused on the field of immune system in the central nervous system(CNS),as the viewpoint of CNS immune privilege being challenged.Among them,CNS boarder-associated macrophages(BAMs)play a prominent role in the regulation of brain homeostasis and related diseases.Unlike microglia located in the brain parenchyma,BAMs are a type of specialized macrophages located in the meninges(including dura,arachnoid,and leptomeninges),perivascular spaces,and choroid plexus.They are crucial for immune surveillance,cerebrospinal fluid drainage,antigen clearance,material exchange,and etc.Here,we reviewed a series of relevant studies on the origin and roles of BAMs in CNS,so as to broaden the understanding of the mechanisms of by which BAMs maintain the brain homeostasis,as well as provide novel insights into the treatment of CNS diseases including Alzheimer's disease.

Objective:To explore the mechanism of anti anxiety (AD) effect of Shenqi Schisandra chinensis using network pharmacology and molecular docking technology.Methods:The main active ingredients of S-Q-W-W-Z (Shenqi Schisandra chinensis) were screened through the TCMSP database. The corresponding targets of the active ingredients were obtained through the TCMSP database and SymMap database. The drug active ingredient target relationship network was visualized using Cytoscape. Utilize TTD, OMIM, NCBI, Drugbank, and GeneCards databases to directly identify potential targets for anxiety. We constructed interaction diagrams of potential targets based on the String database, and used Cytoscape tool to obtain key target proteins. Gene ontology (GO) enrichment analysis and Tokyo Encyclopedia of Genomes (KEGG) signaling pathway analysis were used to identify key targets and signaling pathways for anti anxiety effects of Schisandra chinensis. AutodockTools software was used to perform molecular docking on key active ingredients and key target proteins, and their binding energies were calculated. The molecular docking results were visualized using PyMol software.Results:The 63 effective ingredients in Shen-Qi-Wu-Wei-Zi (Shenqi Schisandra chinensis) can act on anxiety disorder through 69 targets. Among them, quercetin, luteolin, and stigmasterol are the main active ingredients, and serine threonine protein kinase 1 (AKT1) protein and interleukin-6 (IL-6) protein are key target proteins. Molecular docking technology has verified the good binding ability between these key active ingredients and key target proteins. Shenqi Schisandra mainly exerted therapeutic effects on anxiety disorders by regulating Toll like receptor signaling pathways, tumor necrosis factor (TNF) signaling pathways, cancer pathways, and other pathways.Conclusions:The Shenqi Schisandra may exert anti anxiety effects by regulating related targets such as AKT1 and IL-6, regulating inflammatory reactions, cell apoptosis, and other processes.

Objective To study whether there is a difference in the percentage consonants correct(PCC)of children with functional speech sound disorders(SSD)at different ages,and to explore the distribution in types of consonant errors at different ages.Methods A total of 172 children with ages from 4 to 7 years who were diagnosed with functional speech sound disorders and admitted to the Department of Rehabilitation of the Third Xiangya hospi-tal of Central South University participated in the study.The children were divided into three groups according to their ages:Groups 1 to 3.Groups 1,2,and 3 consisted of 97,45,and 30 children,respectively(Group 1:63 boys and 34 girls,aged 4 to＜5 years;Group 2:36 boys and 9 girls,aged 5 to＜6 years;and Group 3:36 boys and 9 girls,aged 6 to＜7 years).Picture-naming task was used to assess children's phonology.The types of consonant error were recorded and the percentage consonants correct(PCC)and the incidence of consonant errors in different places of articulation(stopping,affrication,frication,nasalization,and lateralization)was calculated.Results ①There was no significant difference in the PCC results among the three groups(P＞0.05).②There was a significant difference in omission errors(Z=6.531,P=0.038＜0.05),but not for substitution and distortion errors among the three groups(P＞0.05).③The omission of the lateral/l/was major among the three groups of children.④There were more stopping,affrication and frication in all three groups of children,yet no significant difference in the results of incidence of consonant errors in different places of articulation(stopping,nasalization,affrication,frica-tion and lateralization)among the three groups(P＞0.05).Conclusion There was no significant difference in the PCC among children with functional speech sound disorders at different ages.There were obvious differences in the distribution of omission errors in different age groups,suggesting idiosyncrasy.Children with SSD demonstrated similar characteristics of consonant phonetic errors at different age stages,included mainly the omission of the lateral/1/and more stopping,affrication and frication.

OBJECTIVE: Invent a simulator which provides a simulation of heart rate and respiratory rate to the intelligent sleep monitoring devices based on precision pressure sensors. METHODS: The simulator was composed of control part and simulated silicone doll. The simulated silicone doll contains heartbeat simulator and breathing simulation airbag. Heartbeat and breathing combination pressure signal can be produced according to frequency set values. Frequencies of pressure signal of the simulator were compared with the monitoring results of intelligent sleep monitoring devices with known accuracy to verify the frequency accuracy of pressure signal of the simulator. Verified the repeatability and stability of the simulator with a stopwatch. RESULTS: The heart rate of the simulator was with in ±2 beats per minute of the monitoring results of intelligent sleep monitoring devices and the respiratory rate of the simulator was with in ±2 times per minute of the monitoring results. The repeatability and stability of the simulator was better than ±5% according to results with a stopwatch. CONCLUSIONS It's practicable to use the simulator which provides a simulation of heart rate and respiratory rate to the accuracy test of the intelligent sleep monitoring devices based on precision pressure sensor.