With an increase in internet-connected devices and a dependency on online services,the threat of Distributed Denial of Service(DDoS)attacks has become a significant concern in cybersecurity.The proposed system follows...With an increase in internet-connected devices and a dependency on online services,the threat of Distributed Denial of Service(DDoS)attacks has become a significant concern in cybersecurity.The proposed system follows a multi-step process,beginning with the collection of datasets from different edge devices and network nodes.To verify its effectiveness,experiments were conducted using the CICDoS2017,NSL-KDD,and CICIDS benchmark datasets alongside other existing models.Recursive feature elimination(RFE)with random forest is used to select features from the CICDDoS2019 dataset,on which a BiLSTM model is trained on local nodes.Local models are trained until convergence or stability criteria are met while simultaneously sharing the updates globally for collaborative learning.A centralised server evaluates real-time traffic using the global BiLSTM model,which triggers alerts for potential DDoS attacks.Furthermore,blockchain technology is employed to secure model updates and to provide an immutable audit trail,thereby ensuring trust and accountability among network nodes.This research introduces a novel decentralized method called Federated Random Forest Bidirectional Long Short-Term Memory(FRF-BiLSTM)for detecting DDoS attacks,utilizing the advanced Bidirectional Long Short-Term Memory Networks(BiLSTMs)to analyze sequences in both forward and backward directions.The outcome shows the proposed model achieves a mean accuracy of 97.1%with an average training delay of 88.7 s and testing delay of 21.4 s.The model demonstrates scalability and the best detection performance in large-scale attack scenarios.展开更多
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 rode...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.展开更多
Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life ...Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.展开更多
Alzheimer's disease(AD),a neurodegenera-tive disorder with complex etiologies,manifests through a cascade of pathological changes before clinical symptoms become apparent.Among these early changes,alterations in t...Alzheimer's disease(AD),a neurodegenera-tive disorder with complex etiologies,manifests through a cascade of pathological changes before clinical symptoms become apparent.Among these early changes,alterations in the expression of non-coding RNAs(ncRNAs)have emerged as pivotal events.In this study,we focused on the aber-rant expression of ncRNAs and revealed that Lamrl-ps1,a pseudogene of the laminin receptor,significantly exac-erbates early spatial learning and memory deficits in APP/PS1 mice.Through a combination of bioinformatics pre-diction and experimental validation,we identified the miR-29c/Bacel pathway as a potential regulatory mechanism by which Lamrl-ps1 influences AD pathology.Importantly,augmenting the miR-29c-3p levels in mice ameliorated memory deficits,underscoring the therapeutic potential of targeting miR-29c-3p in early AD intervention.This study not only provides new insights into the role of pseudogenes in AD but also consolidates a foundational basis for consid-ering miR-29c as a viable therapeutic target,offering a novel avenue for AD research and treatment strategies.展开更多
Recent genome studies indicate that tree shrew is in the order or a closest sister of primates,and thus may be one of the best animals to model human diseases.In this paper,we report on a social defeat model of depres...Recent genome studies indicate that tree shrew is in the order or a closest sister of primates,and thus may be one of the best animals to model human diseases.In this paper,we report on a social defeat model of depression in tree shrew（Tupaia belangeri chinensis）.Two male tree shrews were housed in a pair-cage consisting of two independent cages separated by a wire mesh partition with a door connecting the two cages.After one week adaptation,the connecting door was opened and a brief fighting occurs between the two male tree shrews and this social conflict session consisted of 1 h direct conflict（fighting） and 23 h indirect influence（e.g.smell,visual cues） per day for 21 days.The defeated tree shrew was considered the subordinate.Compared with na？ve animals,subordinate tree shrews at the final week of social conflict session showed alterations in body weight,locomotion,avoidance behavior and urinary cortisol levels.Remarkably,these alterations persisted for over two weeks.We also report on a novel captive conditioning model of learning and memory in tree shrew.An automatic trapping cage was placed in a small closed room with a freely-moving tree shrew.For the first four trials,the tree shrew was not trapped when it entered the cage and ate the bait apple,but it was trapped and kept in the cage for 1 h on the fifth trial.Latency was defined as the time between release of the tree shrew and when it entered the captive cage.Latencies during the five trials indicated adaptation.A test trial 24 h later was used to measure whether the one-trial trapping during the fifth trial could form captive memory.Tree shrews showed much longer trapping latencies in the test trial than the adaptation trials.The N-methyl-d-aspartate（NMDA） receptor antagonist MK-801（0.2 mg/kg,i.p.）,known to prevent the formation of memory,did not affect latencies in the adaptation trails,but did block captive memory as it led to much shorter trapping latencies compared to saline treatment in the test trial.These results demonstrate a chronic social defeat model of depression and a novel one-trial captive conditioning model for learning and memory in tree shrews,which are important for mechanism studies of depression,learning,memory,and preclinical evaluation for new antidepressants.展开更多
Objective To investigate whether estrogen modulates learning and memory and long-term potentiation （LTP） in the hippocampus of rats with Alzheimer＇s disease （AD）. Methods The rats were divided into ovariectomy （...Objective To investigate whether estrogen modulates learning and memory and long-term potentiation （LTP） in the hippocampus of rats with Alzheimer＇s disease （AD）. Methods The rats were divided into ovariectomy （OVX） and estrogen replacement therapy （ERT） groups. Rats in the ERT group received OVX, followed by ERT, while rats in the OVX group received only OVX. The rat model of AD was established by injection of 1 μL （10 μg/μL） amyloid-beta peptide 1-40（Aβ1-40） into the hippocampus. The learning and memory ability and LTP were determined by Morris water maze and electrophysiological method, respectively. Results The escape latency in Morris water maze significantly decreased in ERT group compared with that in OVX group （P 〈 0.05）. Besides, rats in ERT group exhibited a significant enhancement of the magnitude of LTP at 30 min after high-frequency stimulation （HFS）, compared with that in OVX group （P 〈 0.01）. Conclusion ERT can attenuate the cognitive deficits in the rat model of AD, and estrogen can regulate LTP and synaptic remodeling in AD rats.展开更多
Objective NMDA receptor channel plays an important role in the pathophysiological process of traumatic brain injury （TBI）. The present study aims to study the pathological mechanism of TBI and the impairment of lear...Objective NMDA receptor channel plays an important role in the pathophysiological process of traumatic brain injury （TBI）. The present study aims to study the pathological mechanism of TBI and the impairment of learning and memory after TBI, and to investigate the mechanism of the protective effect of NMDA receptor antagonist MK-801 on learning and memory disorder after TBI. Methods Forty Sprague-Dawley rats （weighing approximately 200 g） were randomized into 5 groups （n = 8 in each group）： control group, model group, low-dose group （MK-801 0.5 mg/kg）, middle-dose group （MK-801 2 mg/kg）, and high-dose group （MK-801 10 mg/kg）. TBI model was established using a weight-drop head injury mode. After 2-month drug treatment, learning and memory ability was evaluated by using Morris water maze test. Then the animals were sacrificed, and brain tissues were taken out for morphological and immunohistochemical assays. Results The ability of learning and memory was significantly impaired in the TBI model animals. Besides, the neuronal caspase-3 expression, neuronal nitric oxide synthase （nNOS）-positive neurons and OX-42-positive microglia were all increased in TBI animals. Meanwhile, the number of neuron synapses was decreased, and vacuoles degeneration could be observed in mitochondria. After MK-801 treatment at 3 different dosages, the ability of learning and memory was markedly improved, as compared to that of the TBI model animals. Moreover, neuronal caspase-3 expression, OX-42-positive microglia and nNOS-positive neurons were all significantly decreased. Meanwhile, the mitochondria degeneration was greatly inhibited. Conclusion MK-801 could significantly inhibit the degeneration and apoptosis of neurons in damaged brain areas. It could also inhibit TBI-induced increase in nNOS-positive neurons and OX-42-positive microglia. Impairment in learning and memory in TBI animals could be repaired by treatment with MK-801.展开更多
The highly dynamic nature,strong uncertainty,and coupled multiple safety constraints inherent in carrier aircraft recovery operations pose severe challenges for real-time decision-making.Addressing bolter scenarios,th...The highly dynamic nature,strong uncertainty,and coupled multiple safety constraints inherent in carrier aircraft recovery operations pose severe challenges for real-time decision-making.Addressing bolter scenarios,this study proposes an intelligent decision-making framework based on a deep long short-term memory Q-network.This framework transforms the real-time sequencing for bolter recovery problem into a partially observable Markov decision process.It employs a stacked long shortterm memory network to accurately capture the long-range temporal dependencies of bolter event chains and fuel consumption.Furthermore,it integrates a prioritized experience replay training mechanism to construct a safe and adaptive scheduling system capable of millisecond-level real-time decision-making.Experimental demonstrates that,within large-scale mass recovery scenarios,the framework achieves zero safety violations in static environments and maintains a fuel safety violation rate below 10%in dynamic scenarios,with single-step decision times at the millisecond level.The model exhibits strong generalization capability,effectively responding to unforeseen emergent situations—such as multiple bolters and fuel emergencies—without requiring retraining.This provides robust support for efficient carrier-based aircraft recovery operations.展开更多
The distributed permutation flow shop scheduling problem(DPFSP)has received increasing attention in recent years.The iterated greedy algorithm(IGA)serves as a powerful optimizer for addressing such a problem because o...The distributed permutation flow shop scheduling problem(DPFSP)has received increasing attention in recent years.The iterated greedy algorithm(IGA)serves as a powerful optimizer for addressing such a problem because of its straightforward,single-solution evolution framework.However,a potential draw-back of IGA is the lack of utilization of historical information,which could lead to an imbalance between exploration and exploitation,especially in large-scale DPFSPs.As a consequence,this paper develops an IGA with memory and learning mechanisms(MLIGA)to efficiently solve the DPFSP targeted at the mini-malmakespan.InMLIGA,we incorporate a memory mechanism to make a more informed selection of the initial solution at each stage of the search,by extending,reconstructing,and reinforcing the information from previous solutions.In addition,we design a twolayer cooperative reinforcement learning approach to intelligently determine the key parameters of IGA and the operations of the memory mechanism.Meanwhile,to ensure that the experience generated by each perturbation operator is fully learned and to reduce the prior parameters of MLIGA,a probability curve-based acceptance criterion is proposed by combining a cube root function with custom rules.At last,a discrete adaptive learning rate is employed to enhance the stability of the memory and learningmechanisms.Complete ablation experiments are utilized to verify the effectiveness of the memory mechanism,and the results show that this mechanism is capable of improving the performance of IGA to a large extent.Furthermore,through comparative experiments involving MLIGA and five state-of-the-art algorithms on 720 benchmarks,we have discovered that MLI-GA demonstrates significant potential for solving large-scale DPFSPs.This indicates that MLIGA is well-suited for real-world distributed flow shop scheduling.展开更多
OBJECTIVE: To investigate the effects of electroacupuncture(EA) at the Guanyuan(CV 4) or Sanyinjiao(SP 6) acupoints on the hypothalamus-pituitary-ovary(HPO) axis and spatial learning and memory in female mice.METHODS:...OBJECTIVE: To investigate the effects of electroacupuncture(EA) at the Guanyuan(CV 4) or Sanyinjiao(SP 6) acupoints on the hypothalamus-pituitary-ovary(HPO) axis and spatial learning and memory in female mice.METHODS: Nine-month-old female mice with senescence-accelerated mouse prone 8(SAMP8)were divided into three groups: the disease model,EA-Guanyuan and EA-Sanyinjiao groups. Concurrently, 9-month old female mice with senescence-accelerated mouse resistance 1(SAMR1)were set as the control model group. The two treatment groups were given the same pattern of EA stimulation. Gonadotropin-releasing hormone, luteinizing hormone, follicle-stimulating hormone(FSH) and Serum estradiol levels in the Hypothalamus-pituitary-ovary axis were assessed by enzyme-linked immunosorbent assay to determinethe HPO axis function level. Spatial learning and memory were assessed by the Morris Water Maze(MWM) test.RESULTS:(a) HPO axis: compared with the control model group, the disease model group displayed a decrease in E2 levels(P < 0.01), and an increase in Gn RH, LH and FSH levels(P < 0.01). E2 levels were increased in EA treatment groups compared with the disease model group(P < 0.05). In contrast,Gn RH and LH and FSH levels were reduced(P <0.05). EA-Sanyinjiao group was superior than EA-Guanyuan group on increasing E2 and declining Gn RH levels(P < 0.01).(b) The MWM test demonstrated that the response latency in the EA-Sanyinjiao treatment group declined from day 2 to day5 compared with the disease model group(P <0.05), whereas the EA-Guanyuan treatment group showed no significant difference.CONCLUSION: EA can regulate hormone(E2, FSH,LH, Gn RH) levels in the HPO axis and the spatial learning and memory ability in female SAMP8 mice. Moreover, this effect may have been more pronounced in the EA-Sanyinjiao group than the EA-Guanyuan group. The underlying mechanism of the EA-induced changes may be related to gonadal hormone shifts in the HPO axis, followed by an improvement in spatial learning and memory.展开更多
BACKGROUND： The pharmacological actions of Panax notoginseng saponins （PNS） lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheime...BACKGROUND： The pharmacological actions of Panax notoginseng saponins （PNS） lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheimer＇s disease. OBJECTIVE： Using the Morris water maze, immunohistochemistry, real-time PCR and RT-PCR, this study aimed to measure improvement in spatial learning, memory, expression of amyloid precursor protein （App） and β -amyloid （A β ）, to investigate the mechanism of action of PNS in the treatment of AD in the senescence accelerated mouse-prone 8 （SAMP8） and compare the effects with huperzine A. DESIGN, TIME AND SETTING： A completely randomized grouping design, controlled animal experiment was performed in the Center for Research ＆ Development of New Drugs, Guangxi Traditional Chinese Medical University from July 2005 to April 2007. MATERIALS： Sixty male SAMP8 mice, aged 3 months, purchased from Tianjin Chinese Traditional Medical University of China, were divided into four groups： PNS high-dosage group, PNS low-dosage group, huperzine A group and control group. PNS was provided by Weihe Pharmaceutical Co., Ltd. （batch No.： Z53021485, Yuxi, Yunan Province, China）. Huperzine A was provided by Zhenyuan Pharmaceutical Co., Ltd. （batch No.： 20040801, Zhejiang, China）. METHODS： The high-dosage group and low-dosage group were treated with 93.50 and 23.38 mg/kg PNS respectively per day and the huperzine A group was treated with 0.038 6 mg/kg huperzine A per day, all by intragastric administration, for 8 consecutive weeks. The same volume of double distilled water was given to the control group. MAIN OUTCOME MEASURES： After drug administration, learning and memory abilities were assessed by place navigation and spatial probe tests. The recording indices consisted of escape latency （time-to-platform）, and the percentage of swimming time spent in each quadrant. The number of A β 1-40, A β 1-42 and App immunopositive neurons in the brains of SAMP8 mice was analyzed by immunohistochemistry. The mRNA content ofApp, tau, acetylcholinesterase, and synaptophysin （Syp） was tested by real time PCR and RT-PCR. RESULTS： The PCR results show that PNS can downregulate the expression of the App gene and upregulate the expression of the Syp gene in the parietal cortex and hippocampus of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than those of the PNS low-dosage group and the huperzine A group （P 〈 0.05）. The results of the Morris water maze and immunohistochemistry indicated that PNS can improve the capacity for spatial learning and memory in SAMP8 mice, and reduce the content of A β 1-40, A β 1-42 and expression of App in the brains of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than that of the PNS low-dosage group and the huperzine A group （P 〈 0.05）. CONCLUSION： These results support the hypothesis that PNS plays a therapeutic and protective role on the pathological lesions and learning dysfunction of Alzheimer＇s disease. The therapeutic effects of PNS for Alzheimer＇s disease are possibly achieved through downregulating the expression of the App gene and upregulating the expression of the Syp gene. The therapeutic effects of PNS are dose-dependent and are greater than the effect of huperzine A.展开更多
The present study was aimed at determining the effects of Tongqiao Huoxue Decoction （TQHXD） on the Ca2＋-CaMKII-CREB pathway and the memory and learning capacities of rats with vascular dementia （VD）. The rat VD m...The present study was aimed at determining the effects of Tongqiao Huoxue Decoction （TQHXD） on the Ca2＋-CaMKII-CREB pathway and the memory and learning capacities of rats with vascular dementia （VD）. The rat VD model was established by using an improved bilateral carotid artery ligation method. The Morris water maze experiment was used to evaluate the ethology of the VD rats following treatments with TQHXD at 3.01, 6.02, and 12.04 g.kg-1 per day for 31 days. At the end of experiment, the hippocampus were harvested and analyzed. Western blotting and RT-PCR were used to measure the expression levels of calmodulin-binding protein kinase II（CaMKII）, protein kinase A（PKA）, cAMP-response element binding protein（CREB）, and three N-methyl-D-aspart^c acid receptor subunits （NR1, NR2A, and NR2B）. Our results revealed that TQHXD could alleviate the loss of learning abilities and increase the memory capacity （P 〈 0.05 and P 〈 0.01 vs the model group, respectively）. The treatment with 6.02 and 12.04 g.kg-1 of TQHXD significantly up-regulated the Ca2＋-CaMKII-CREB pathway in the hippocampus. In conclusion, TQHXD showed therapeutic effects on a bilateral carotid artery ligation-induced vascular dementia model, through the up-regulation of calcium signalling oathwavs.展开更多
Nitric oxide （NO） is a novel type of neurotransmitter that is closely associated with synaptic plasticity, learning and memory. In the present study, we assessed the effects of Larginine and NnitroL arginine methyle...Nitric oxide （NO） is a novel type of neurotransmitter that is closely associated with synaptic plasticity, learning and memory. In the present study, we assessed the effects of Larginine and NnitroL arginine methylester （LNAME, a nitric oxide synthase inhibitor） on learning and memory. Rats were assigned to three groups receiving intracerebroventricular injections of LArg （the NO precursor）, LNAME, or 0.9% NaCI （control）, once daily for seven con secutive days. Twelve hours after the last injection, they underwent an electric shockpaired Y maze test. Twentyfour hours later, the rats＇ memory of the safe illuminated arm was tested. After that, the levels of NO and a7 nicotinic acetylcholine receptor （a7 nAChR） in the prefrontal cortex and hippocampus were assessed using an NO assay kit, and immunohistochemistry and Western blots, respectively. We found that, compared to controls, LArgtreated rats received fewer foot shocks and made fewer errors to reach the learning criterion, and made fewer errors during the memorytesting session. In contrast, LNAMEtreated rats received more foot shocks and made more errors than controls to reach the learning criterion, and made more errors during the memorytesting session. In parallel, NO content in the prefrontal cortex and hippocampus was higher in LArgtreated rats and lower inLNAME rats, compared to controls. Similarly, （]7 nAChR immunoreactivity and protein expression in the prefrontal cortex and hippocampus were higher in LArgtreated rats and lower in LNAME rats, compared to controls. These results suggest that the modulation of NO content in the brain correlates with a7 nAChR distribution and expression in the prefrontal cortex and hippocampus, as well as with learning and memory performance in the Ymaze.展开更多
OBJECTIVE: To investigate the role of Eclipta prostrata (E. prostrata) extract in improving spatial learning and memory deficits in D-galactose-induced aging in rats. METHODS: Rats were divided into five groups, with ...OBJECTIVE: To investigate the role of Eclipta prostrata (E. prostrata) extract in improving spatial learning and memory deficits in D-galactose-induced aging in rats. METHODS: Rats were divided into five groups, with 10 animals in each group. Aging rats were produced by treatment with 100 mg·kg-1·d-1 of D-galactose for 6 weeks. Rats in the E. prostrata treatment groups received an aqueous extract of E. prostrata orally at a concentration of 50, 100, or 200 mg·kg-1· d-1 for 3 weeks. Animals in both the normal and model groups were treated with similar volumes of saline. Spatial memory performance was measured using the Morris water maze. The mRNA levels and enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were analyzed using real- time quantitative PCR and spectrophotometry,respectively. The levels of induced nitric oxide synthase (iNOS), nitric oxide (NO), dopamine (DA), norepinephrine (NE), and serotonin (5-HT) were determined using enzyme-linked immunosorbent assay and spectrophotometry. RESULTS: Compared with the normal group, rats in the D-galactose-treated model group exhibited significant memory loss. There was severe damage to the hippocampal CA1 area, and expression levels of SOD, CAT, GPx, and GR were significantly decreased in the model group compared with the normal group. In the model group, levels of iNOS and NO were significantly increased compared with the normal group. However, treatment with E. prostrata extract reversed the conditions caused by D-galactose- induced aging, especially in the groups with higher treatment concentrations. Compared with the normal group, the levels of DA, NE, and 5-HT were significantly lower in the D-galactose-treated model group. In the E. prostrata extract-treated groups, however, there was a dose-dependent upregulation of DA, NE, and 5-HT expression. CONCLUSION: Our results suggest that administration of E. prostrata extract can result in an improvement in the learning and memory impairments that are induced by D-galactose treatment in rats. This improvement may be the result of enhanced antioxidative ability, decreased iNOS and NO levels, and the induction of DA, NE, and 5-HT expression in the brain.展开更多
Accurate forecasting of blast furnace gas(BFG)production is an essential prerequisite for reasonable energy scheduling and management to reduce carbon emissions.Coupling forecasting between BFG generation and consumpt...Accurate forecasting of blast furnace gas(BFG)production is an essential prerequisite for reasonable energy scheduling and management to reduce carbon emissions.Coupling forecasting between BFG generation and consumption dynamics was taken as the research object.A multi-task learning(MTL)method for BFG forecasting was proposed,which integrated a coupling correlation coefficient(CCC)and an inverted transformer structure.The CCC method could enhance key information extraction by establishing relationships between multiple prediction targets and relevant factors,while MTL effectively captured the inherent correlations between BFG generation and consumption.Finally,a real-world case study was conducted to compare the proposed model with four benchmark models.Results indicated significant reductions in average mean absolute percentage error by 33.37%,achieving 1.92%,with a computational time of 76 s.The sensitivity analysis of hyperparameters such as learning rate,batch size,and units of the long short-term memory layer highlights the importance of hyperparameter tuning.展开更多
BACKGROUND： Ginsenoside extracted from the stem and leaf of ginseng （GSL） and choline have both been shown to improve learning and memory functions; however, further studies are needed to understand the synergistic...BACKGROUND： Ginsenoside extracted from the stem and leaf of ginseng （GSL） and choline have both been shown to improve learning and memory functions; however, further studies are needed to understand the synergistic effects of a combination of both. OBJECTIVE： To verify the combined improved synergistic effects of GSL and choline on learning and memory disorders in rats. DESIGN： Control observation. SETTING： Taishan Medical College. MATERIALS： A total of 150 male Kunming mice weighing （204-2） g and 40 healthy male Wistar rats weighing （2204-20） g were provided by the Experimental Animal Department of Jilin University. Animal experimentation received confirmed consent from the local ethic committee. GSL was provided by the Department of Chemistry, Norman Bethune Medical University, and choline was provided by the Third Experiment Factory, Shanghai. METHODS： This study was performed at the Life Science Institute, Taishan Medical College from October 2006 to February 2007. ① Scopolamine-induced learning and memory disorders in rats： Forty rats were randomly divided into control group, model group, combination group （400 mg/kg GSL ＋ 200 mg/kg choline）, GSL （400 mg/kg） group, and choline （200 mg/kg） group, 8 rats/group. Rats were perfused and administrated in the morning, once a day for 14 successive days. Rats in the control group and model group were perfused with 20 mL/kg distilled water and underwent Morris water maze spatial resolution test 1 hour after perfusion on the 10m, 11m, and 12m days after administration. Rats also underwent passive step-down avoidance test 1 hour after reperfusion on the 13m and 14m days after administration. Thirty minutes prior to experimentation, rats in the remaining three groups were intraperitoneally （i.p） injected with 2 mg/kg scopolamine, and rats in the control group were i.p. injected with 2 mL/kg saline. ② Scopolamine-induced learning disorder and memory acquired disorder in mice： Fifty mice were randomly divided into control group, model group, combination group （400 mg/kg GSL ＋200 mg/kg choline）, GSL （400 mg/kg） group, and choline （200 mg/kg） group, with 10 mice/group. Mice were perfused and administrated in the morning, once a day for 9 successive days. Mice in the control group and model group were perfused with 20 mL/kg distilled water and underwent passive step down avoidance test 1 hour after reperfusion on the 8th and 9th day after administration. Twenty minutes prior to training, mice in the remaining three groups were i.p. injected with 2 mg/kg scopolamine, and mice in the control group were i.p. injected with 10 mL/kg saline. ③ Sodium nitrite-induced memory consolidation disorder in mice： Grouping, administration, and testing were the same as mentioned above. After training, mice in the remaining three groups were immediately subcutaneously injected with 120 mg/kg sodium nitrite, and mice in the control group were subcutaneously injected with 20 mL/kg saline. ④ Ethanol-induced memory reconsolidation disorder in mice： Grouping, administration, and testing were the same as mentioned above. At 24 hours after training and 20 minutes before retraining, mice in the remaining four groups were perfused with 10 mL/kg ethanol （0.3 volume fraction）, and mice in the control group were perfused with 10 mL/kg saline. MAIN OUTCOME MEASURES： Synergistic effects of GSL and choline on learning and memory deficits induced by scopolamine, sodium nitrite, and ethanol in experimental animals. RESULTS： All 40 rats and 150 mice were included in the final analysis. ① Synergistic effects of GSL and choline on learning and memory disorders induced by scopolamine in rats： During passive step-down avoidance and Morris water maze spatial resolution tests, the number of error responses and length of maze training in the model group were significantly greater than in the control group （P 〈 0.01）; while the number of error responses and length of maze training in the combination group were significantly less than in the model group, GSL group, and choline group （P 〈 0.05-0.01）. The Q value was 〉 1 after combining administration, which suggests that the combination of GSL and choline had synergistic effects. ② Synergistic effects of GSL and choline on learning disorder and memory-acquired disorder induced by scopolamine in mice： During passive step-down avoidance test, the number of error responses in the model group were significantly greater than in the control group （P 〈 0.01 ）; while the number of error responses in the combination group were significantly less than in the model group, GSL group, and choline group （P 〈 0.05-0.01）. The Q value was 〉 1 after combining administration, which suggests GSL and choline had synergistic effects. ③ Synergistic effects of GSL and choline on memory sodium nitrate-induced consolidation disorder in mice： During passive step down avoidance test, the number of error responses in the model group were significantly less than in the control group （P 〈 0.01 ）; while the number of error responses in the combination group were significantly less than in the model group, GSL group, and choline group （P 〈 0.05-0.01）. The Q value was 〉 1 after combined administration, which suggests GSL and choline had synergistic effects. ④ Synergistic effects of GSL and choline on ethanol-induced memory reconsolidation disorder in mice： During passive step down avoidance test, the number of error responses in the model group were significantly greater than in the control group （P 〈 0.01）; while the number of error responses in the combination group were significantly less than in the model group, GSL group, and choline group （P 〈 0.05-0.01）. The Q value was 〉 1 after combined administration, which suggests GSL and choline had synergistic effects. CONCLUSION： GSL and choline have synergistic effects on learning and memory functions.展开更多
OBJECTIVE:To investiage the effect of electroacupuncture(EA)at a single acupoint of Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6)and at combined acupoints of Shenmen(HT7)and Baihui(GV20)and Sanyinjiao(SP6)on the PKA/CREB ...OBJECTIVE:To investiage the effect of electroacupuncture(EA)at a single acupoint of Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6)and at combined acupoints of Shenmen(HT7)and Baihui(GV20)and Sanyinjiao(SP6)on the PKA/CREB and BDNF/TrkB signaling,as well as neuroapoptosis and neurogenesis in hippocampus and elucidate the underlying mechanism of single and combined acupoints on ameliorating spatial learning and memory deficits in a rat model of primary insomnia.METHODS:Primary insomnia was modeled by intraperitoneal injection of para-chlorophenylalanine(PCPA)once daily for 2 d.EA was applied at Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6),or Shenmen(HT7)+Baihui(GV20)+Sanyinjiao(SP6)(combined)for 30 min daily for 4 d.Spatial learning and memory function was evaluated by the Morris water maze(MWM)test.Protein expressions of hippocampal cAMP-dependent protein kinase(PKA)-Cβ,phosphorylated cAMP-responsive element-binding protein(p-CREB),brainderived neurotrophic factor(BDNF),and tyrosine kinase receptor B(TrkB)were evaluated by Western blotting.Neuronal apoptosis in the hippocampus was detected with the transferase-mediated dUTP-X nick end labeling assay.Endogenous neurogenesis was examined with bromodeoxyuridine staining.The MWM test and hippocampal p-CREB,BDNF,and TrkB protein levels in the combined acupoints group were evaluated after the administration of a PKA-selective inhibitor(H89).RESULTS:Spatial learning and memory were significantly impaired in rats with insomnia.The spatial learning deficits were ameliorated in the Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6),and combined groups;this improvement was significantly greater in the combined group than the single acupoint groups.The spatial memory impairment was improved in the combined,Baihui(GV20),and Shenmen(HT7)groups,but not the Sanyinjiao(SP6)group.The expressions of PKA-Cβ,p-CREB,BDNF,and TrkB were decreased in rats with insomnia.All these proteins were significantly upregulated in the combined group.PKA/p-CREB protein levels were elevated in the Baihui(GV20)and Shenmen(HT7)groups,whereas BDNF/TrkB expression was upregulated in the Sanyinjiao(SP6)group.The staining results showed significant attenuation of hippocampal cell apoptosis and increased numbers of proliferating cells in the combined group,whereas the single acupoint groups only showed decreased numbers of apoptotic cells.In the combined group,the PKA inhibitor reversed the improvement of spatial memory and upregulation of pCREB expression caused by EA,but did not affect its activation of BDNF/TrkB signaling.CONCLUSIONS:EA at the single acupoints Baihui(GV20),Shenmen(HT7),or Sanyinjiao(SP6)had an ameliorating effect on the spatial learning and memory deficits induced by insomnia.EA at combined acupoints exerted a synergistic effect on the improvements in spatial learning and memory impairment in rats with insomnia by upregulating the hippocampal PKA/CREB and BDNF/TrkB signaling,facilitating neurogenesis,and inhibiting neuronal apoptosis.These findings indicate that EA at combined acupoints[(Baihui(GV20),Shenmen(HT7),and Sanyinjiao(SP6)]achieves a more pronounced regulation of hippocampal neuroplasticity than EA at single acupoints,which may partly explain the underlying mechanisms by which EA at combined acupoints exerts a better ameliorative effect on the cognitive dysfunction caused by insomnia.展开更多
Objective To gain a better understanding of gene expression changes in the brain following microwave exposure in mice. This study hopes to reveal mechanisms contributing to microwave-induced learning and memory dysfun...Objective To gain a better understanding of gene expression changes in the brain following microwave exposure in mice. This study hopes to reveal mechanisms contributing to microwave-induced learning and memory dysfunction. Methods Mice were exposed to whole body 2100 MHz microwaves with specific absorption rates (SARs) of 0.45 W/kg, 1.8 W/kg, and 3.6 W/kg for 1 hour daily for 8 weeks. Differentially expressing genes in the brains were screened using high-density oligonucleotide arrays, with genes showing more significant differences further confirmed by RT-PCR. Results The gene chip results demonstrated that 41 genes (0.45 W/kg group), 29 genes (1.8 W/kg group), and 219 genes (3.6 W/kg group) were differentially expressed. GO analysis revealed that these differentially expressed genes were primarily involved in metabolic processes, cellular metabolic processes, regulation of biological processes, macromolecular metabolic processes, biosynthetic processes, cellular protein metabolic processes, transport, developmental processes, cellular component organization, etc. KEGG pathway analysis showed that these genes are mainly involved in pathways related to ribosome, Alzheimer's disease, Parkinson's disease, long-term potentiation, Huntington's disease, and Neurotrophin signaling. Construction of a protein interaction network identified several important regulatory genes including synbindin (sbdn), Crystallin (CryaB), PPP1CA, Ywhaq, Psap, Psmb1, Pcbp2, etc., which play important roles in the processes of learning and memory. Conclusion Long-term, low-level microwave exposure may inhibit learning and memory by affecting protein and energy metabolic processes and signaling pathways relating to neurological functions or diseases.展开更多
Deep learning enables neural networks to improve prediction performance through data supplementation.In financial time series forecasting,however,such data-driven approaches can encounter limitations where additional ...Deep learning enables neural networks to improve prediction performance through data supplementation.In financial time series forecasting,however,such data-driven approaches can encounter limitations where additional data degrade performance,contrary to common expectations.While more data can still be beneficial,it may introduce systemic concept drift due to the complex nonstationarities of stock price index time series,thereby exacerbating overfitting.One such drift is memory inconsistency:locally measured long memories fluctuate over time,alternately approaching and deviating from the random walk condition.We address this problem by typifying memory inconsistencies into two simplified forms:long-term dependentto-independent(D2I)and long-term independent-to-dependent(I2D)inconsistencies.The first experiment,which uses U.S.stock price indices,suggests that additional training examples may lead to performance deterioration of long short-term memory(LSTM)networks,especially when memory inconsistencies are prominent.Since stock markets are influenced by numerous unknown dynamics,the second experiment,which uses simulated mean-reverting time series derived from the fractional Ornstein–Uhlenbeck(fOU)process,is conducted to focus solely on challenges arising from memory inconsistencies.The experimental results demonstrate that memory inconsistencies disrupt the performance of LSTM networks.Theoretically,additional errors from D2I and I2D inconsistencies increase as the time lag increases.Since LSTM networks are inherently recurrent,causing information from distant steps to attenuate,they fail to effectively capture memory inconsistencies in practical offline learning schemes.Nonetheless,transplanting pretrained memory-consistent gate parameters into the LSTM model partially mitigates the performance deterioration caused by memory inconsistencies,suggesting that memory augmentation strategies have the potential to overcome this problem.As such a memory augmentation method,we propose the Gate-of-Gates(GoG)model,which extends the capacity of LSTM gates and demonstrates that it can mitigate additional errors arising from memory inconsistencies.展开更多
An ischemic-hypoxic animal model was established using right common carotid artery occlusions and inhalation of low concentrations of oxygen in mice. At 10 days after the ischemic-hypoxic injuries, saline-treated mice...An ischemic-hypoxic animal model was established using right common carotid artery occlusions and inhalation of low concentrations of oxygen in mice. At 10 days after the ischemic-hypoxic injuries, saline-treated mice exhibited significantly prolonged escape latencies in water-maze tests and significantly shorter memory latencies and more mistakes in step-down tests. In contrast, mice treated with 5 mg/kg minocycline exhibited significant reversals of each of these effects compared with the saline-treated control mice. Moreover, we found that minocycline can relieve brain water content and morphological changes in mice following ischemic-hypoxic cerebral injuries. Accordingly, our findings indicate that minocycline provides some protections against the deleterious effects of these injuries in mice.展开更多
基金supported by the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea(NRF-2025S1A5A2A01005171)by the BK21 programat Chungbuk National University(2025).
文摘With an increase in internet-connected devices and a dependency on online services,the threat of Distributed Denial of Service(DDoS)attacks has become a significant concern in cybersecurity.The proposed system follows a multi-step process,beginning with the collection of datasets from different edge devices and network nodes.To verify its effectiveness,experiments were conducted using the CICDoS2017,NSL-KDD,and CICIDS benchmark datasets alongside other existing models.Recursive feature elimination(RFE)with random forest is used to select features from the CICDDoS2019 dataset,on which a BiLSTM model is trained on local nodes.Local models are trained until convergence or stability criteria are met while simultaneously sharing the updates globally for collaborative learning.A centralised server evaluates real-time traffic using the global BiLSTM model,which triggers alerts for potential DDoS attacks.Furthermore,blockchain technology is employed to secure model updates and to provide an immutable audit trail,thereby ensuring trust and accountability among network nodes.This research introduces a novel decentralized method called Federated Random Forest Bidirectional Long Short-Term Memory(FRF-BiLSTM)for detecting DDoS attacks,utilizing the advanced Bidirectional Long Short-Term Memory Networks(BiLSTMs)to analyze sequences in both forward and backward directions.The outcome shows the proposed model achieves a mean accuracy of 97.1%with an average training delay of 88.7 s and testing delay of 21.4 s.The model demonstrates scalability and the best detection performance in large-scale attack scenarios.
基金supported by the National Institutes of Health,Nos.AA025919,AA025919-03S1,and AA025919-05S1(all to RAF).
文摘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.
基金supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG)the Key Talent Project for Strengthening Health during the 13^(th)Five-Year Plan Period,No.ZDRCA2016069(to XG)+1 种基金the National Key R&D Program of China,No.2018YFC2001901(to XG)Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。
文摘Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.
基金supported by a Cooperation Project of Nanchong Science and Technology(22SXZRKX0016)the Research Development Fund of North Sichuan Medical College(CBY21-QD24)+2 种基金the Sichuan Science and Technology Program(2022NSFSC1472)the National Natural Science Foundation of China(32200795)the Natural Science Foundation of Hubei Province(2022CFB608).
文摘Alzheimer's disease(AD),a neurodegenera-tive disorder with complex etiologies,manifests through a cascade of pathological changes before clinical symptoms become apparent.Among these early changes,alterations in the expression of non-coding RNAs(ncRNAs)have emerged as pivotal events.In this study,we focused on the aber-rant expression of ncRNAs and revealed that Lamrl-ps1,a pseudogene of the laminin receptor,significantly exac-erbates early spatial learning and memory deficits in APP/PS1 mice.Through a combination of bioinformatics pre-diction and experimental validation,we identified the miR-29c/Bacel pathway as a potential regulatory mechanism by which Lamrl-ps1 influences AD pathology.Importantly,augmenting the miR-29c-3p levels in mice ameliorated memory deficits,underscoring the therapeutic potential of targeting miR-29c-3p in early AD intervention.This study not only provides new insights into the role of pseudogenes in AD but also consolidates a foundational basis for consid-ering miR-29c as a viable therapeutic target,offering a novel avenue for AD research and treatment strategies.
基金supported by grants KSCX2-EW-R-12 and KSCX2-EW-J-23 from the Chinese Academy of Sciences
文摘Recent genome studies indicate that tree shrew is in the order or a closest sister of primates,and thus may be one of the best animals to model human diseases.In this paper,we report on a social defeat model of depression in tree shrew（Tupaia belangeri chinensis）.Two male tree shrews were housed in a pair-cage consisting of two independent cages separated by a wire mesh partition with a door connecting the two cages.After one week adaptation,the connecting door was opened and a brief fighting occurs between the two male tree shrews and this social conflict session consisted of 1 h direct conflict（fighting） and 23 h indirect influence（e.g.smell,visual cues） per day for 21 days.The defeated tree shrew was considered the subordinate.Compared with na？ve animals,subordinate tree shrews at the final week of social conflict session showed alterations in body weight,locomotion,avoidance behavior and urinary cortisol levels.Remarkably,these alterations persisted for over two weeks.We also report on a novel captive conditioning model of learning and memory in tree shrew.An automatic trapping cage was placed in a small closed room with a freely-moving tree shrew.For the first four trials,the tree shrew was not trapped when it entered the cage and ate the bait apple,but it was trapped and kept in the cage for 1 h on the fifth trial.Latency was defined as the time between release of the tree shrew and when it entered the captive cage.Latencies during the five trials indicated adaptation.A test trial 24 h later was used to measure whether the one-trial trapping during the fifth trial could form captive memory.Tree shrews showed much longer trapping latencies in the test trial than the adaptation trials.The N-methyl-d-aspartate（NMDA） receptor antagonist MK-801（0.2 mg/kg,i.p.）,known to prevent the formation of memory,did not affect latencies in the adaptation trails,but did block captive memory as it led to much shorter trapping latencies compared to saline treatment in the test trial.These results demonstrate a chronic social defeat model of depression and a novel one-trial captive conditioning model for learning and memory in tree shrews,which are important for mechanism studies of depression,learning,memory,and preclinical evaluation for new antidepressants.
基金supported by the National Natural Science Foundation of China (No. 30700938,30872656, 30700861, 30800451) the Natural Science Foundation of Liaoning Province, China (No. 20082078)
文摘Objective To investigate whether estrogen modulates learning and memory and long-term potentiation （LTP） in the hippocampus of rats with Alzheimer＇s disease （AD）. Methods The rats were divided into ovariectomy （OVX） and estrogen replacement therapy （ERT） groups. Rats in the ERT group received OVX, followed by ERT, while rats in the OVX group received only OVX. The rat model of AD was established by injection of 1 μL （10 μg/μL） amyloid-beta peptide 1-40（Aβ1-40） into the hippocampus. The learning and memory ability and LTP were determined by Morris water maze and electrophysiological method, respectively. Results The escape latency in Morris water maze significantly decreased in ERT group compared with that in OVX group （P 〈 0.05）. Besides, rats in ERT group exhibited a significant enhancement of the magnitude of LTP at 30 min after high-frequency stimulation （HFS）, compared with that in OVX group （P 〈 0.01）. Conclusion ERT can attenuate the cognitive deficits in the rat model of AD, and estrogen can regulate LTP and synaptic remodeling in AD rats.
基金supported by the grants from Nanjing Military Medical Science and Technology Innovation Project (No. 08MA007)
文摘Objective NMDA receptor channel plays an important role in the pathophysiological process of traumatic brain injury （TBI）. The present study aims to study the pathological mechanism of TBI and the impairment of learning and memory after TBI, and to investigate the mechanism of the protective effect of NMDA receptor antagonist MK-801 on learning and memory disorder after TBI. Methods Forty Sprague-Dawley rats （weighing approximately 200 g） were randomized into 5 groups （n = 8 in each group）： control group, model group, low-dose group （MK-801 0.5 mg/kg）, middle-dose group （MK-801 2 mg/kg）, and high-dose group （MK-801 10 mg/kg）. TBI model was established using a weight-drop head injury mode. After 2-month drug treatment, learning and memory ability was evaluated by using Morris water maze test. Then the animals were sacrificed, and brain tissues were taken out for morphological and immunohistochemical assays. Results The ability of learning and memory was significantly impaired in the TBI model animals. Besides, the neuronal caspase-3 expression, neuronal nitric oxide synthase （nNOS）-positive neurons and OX-42-positive microglia were all increased in TBI animals. Meanwhile, the number of neuron synapses was decreased, and vacuoles degeneration could be observed in mitochondria. After MK-801 treatment at 3 different dosages, the ability of learning and memory was markedly improved, as compared to that of the TBI model animals. Moreover, neuronal caspase-3 expression, OX-42-positive microglia and nNOS-positive neurons were all significantly decreased. Meanwhile, the mitochondria degeneration was greatly inhibited. Conclusion MK-801 could significantly inhibit the degeneration and apoptosis of neurons in damaged brain areas. It could also inhibit TBI-induced increase in nNOS-positive neurons and OX-42-positive microglia. Impairment in learning and memory in TBI animals could be repaired by treatment with MK-801.
基金supported by the National Natural Science Foundation of China(Grant No.62403486)。
文摘The highly dynamic nature,strong uncertainty,and coupled multiple safety constraints inherent in carrier aircraft recovery operations pose severe challenges for real-time decision-making.Addressing bolter scenarios,this study proposes an intelligent decision-making framework based on a deep long short-term memory Q-network.This framework transforms the real-time sequencing for bolter recovery problem into a partially observable Markov decision process.It employs a stacked long shortterm memory network to accurately capture the long-range temporal dependencies of bolter event chains and fuel consumption.Furthermore,it integrates a prioritized experience replay training mechanism to construct a safe and adaptive scheduling system capable of millisecond-level real-time decision-making.Experimental demonstrates that,within large-scale mass recovery scenarios,the framework achieves zero safety violations in static environments and maintains a fuel safety violation rate below 10%in dynamic scenarios,with single-step decision times at the millisecond level.The model exhibits strong generalization capability,effectively responding to unforeseen emergent situations—such as multiple bolters and fuel emergencies—without requiring retraining.This provides robust support for efficient carrier-based aircraft recovery operations.
基金supported in part by the National Key Research and Development Program of China under Grant No.2021YFF0901300in part by the National Natural Science Foundation of China under Grant Nos.62173076 and 72271048.
文摘The distributed permutation flow shop scheduling problem(DPFSP)has received increasing attention in recent years.The iterated greedy algorithm(IGA)serves as a powerful optimizer for addressing such a problem because of its straightforward,single-solution evolution framework.However,a potential draw-back of IGA is the lack of utilization of historical information,which could lead to an imbalance between exploration and exploitation,especially in large-scale DPFSPs.As a consequence,this paper develops an IGA with memory and learning mechanisms(MLIGA)to efficiently solve the DPFSP targeted at the mini-malmakespan.InMLIGA,we incorporate a memory mechanism to make a more informed selection of the initial solution at each stage of the search,by extending,reconstructing,and reinforcing the information from previous solutions.In addition,we design a twolayer cooperative reinforcement learning approach to intelligently determine the key parameters of IGA and the operations of the memory mechanism.Meanwhile,to ensure that the experience generated by each perturbation operator is fully learned and to reduce the prior parameters of MLIGA,a probability curve-based acceptance criterion is proposed by combining a cube root function with custom rules.At last,a discrete adaptive learning rate is employed to enhance the stability of the memory and learningmechanisms.Complete ablation experiments are utilized to verify the effectiveness of the memory mechanism,and the results show that this mechanism is capable of improving the performance of IGA to a large extent.Furthermore,through comparative experiments involving MLIGA and five state-of-the-art algorithms on 720 benchmarks,we have discovered that MLI-GA demonstrates significant potential for solving large-scale DPFSPs.This indicates that MLIGA is well-suited for real-world distributed flow shop scheduling.
基金the National Science Foundation of China(the Experimental Research on Acupuncture for Prevention and Treatment Alzheimer's Disease Based on the Adjustment Imbalances of NIM,No.81072768)
文摘OBJECTIVE: To investigate the effects of electroacupuncture(EA) at the Guanyuan(CV 4) or Sanyinjiao(SP 6) acupoints on the hypothalamus-pituitary-ovary(HPO) axis and spatial learning and memory in female mice.METHODS: Nine-month-old female mice with senescence-accelerated mouse prone 8(SAMP8)were divided into three groups: the disease model,EA-Guanyuan and EA-Sanyinjiao groups. Concurrently, 9-month old female mice with senescence-accelerated mouse resistance 1(SAMR1)were set as the control model group. The two treatment groups were given the same pattern of EA stimulation. Gonadotropin-releasing hormone, luteinizing hormone, follicle-stimulating hormone(FSH) and Serum estradiol levels in the Hypothalamus-pituitary-ovary axis were assessed by enzyme-linked immunosorbent assay to determinethe HPO axis function level. Spatial learning and memory were assessed by the Morris Water Maze(MWM) test.RESULTS:(a) HPO axis: compared with the control model group, the disease model group displayed a decrease in E2 levels(P < 0.01), and an increase in Gn RH, LH and FSH levels(P < 0.01). E2 levels were increased in EA treatment groups compared with the disease model group(P < 0.05). In contrast,Gn RH and LH and FSH levels were reduced(P <0.05). EA-Sanyinjiao group was superior than EA-Guanyuan group on increasing E2 and declining Gn RH levels(P < 0.01).(b) The MWM test demonstrated that the response latency in the EA-Sanyinjiao treatment group declined from day 2 to day5 compared with the disease model group(P <0.05), whereas the EA-Guanyuan treatment group showed no significant difference.CONCLUSION: EA can regulate hormone(E2, FSH,LH, Gn RH) levels in the HPO axis and the spatial learning and memory ability in female SAMP8 mice. Moreover, this effect may have been more pronounced in the EA-Sanyinjiao group than the EA-Guanyuan group. The underlying mechanism of the EA-induced changes may be related to gonadal hormone shifts in the HPO axis, followed by an improvement in spatial learning and memory.
基金the National Natural Science Foundation of China, No: 30560189
文摘BACKGROUND： The pharmacological actions of Panax notoginseng saponins （PNS） lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheimer＇s disease. OBJECTIVE： Using the Morris water maze, immunohistochemistry, real-time PCR and RT-PCR, this study aimed to measure improvement in spatial learning, memory, expression of amyloid precursor protein （App） and β -amyloid （A β ）, to investigate the mechanism of action of PNS in the treatment of AD in the senescence accelerated mouse-prone 8 （SAMP8） and compare the effects with huperzine A. DESIGN, TIME AND SETTING： A completely randomized grouping design, controlled animal experiment was performed in the Center for Research ＆ Development of New Drugs, Guangxi Traditional Chinese Medical University from July 2005 to April 2007. MATERIALS： Sixty male SAMP8 mice, aged 3 months, purchased from Tianjin Chinese Traditional Medical University of China, were divided into four groups： PNS high-dosage group, PNS low-dosage group, huperzine A group and control group. PNS was provided by Weihe Pharmaceutical Co., Ltd. （batch No.： Z53021485, Yuxi, Yunan Province, China）. Huperzine A was provided by Zhenyuan Pharmaceutical Co., Ltd. （batch No.： 20040801, Zhejiang, China）. METHODS： The high-dosage group and low-dosage group were treated with 93.50 and 23.38 mg/kg PNS respectively per day and the huperzine A group was treated with 0.038 6 mg/kg huperzine A per day, all by intragastric administration, for 8 consecutive weeks. The same volume of double distilled water was given to the control group. MAIN OUTCOME MEASURES： After drug administration, learning and memory abilities were assessed by place navigation and spatial probe tests. The recording indices consisted of escape latency （time-to-platform）, and the percentage of swimming time spent in each quadrant. The number of A β 1-40, A β 1-42 and App immunopositive neurons in the brains of SAMP8 mice was analyzed by immunohistochemistry. The mRNA content ofApp, tau, acetylcholinesterase, and synaptophysin （Syp） was tested by real time PCR and RT-PCR. RESULTS： The PCR results show that PNS can downregulate the expression of the App gene and upregulate the expression of the Syp gene in the parietal cortex and hippocampus of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than those of the PNS low-dosage group and the huperzine A group （P 〈 0.05）. The results of the Morris water maze and immunohistochemistry indicated that PNS can improve the capacity for spatial learning and memory in SAMP8 mice, and reduce the content of A β 1-40, A β 1-42 and expression of App in the brains of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than that of the PNS low-dosage group and the huperzine A group （P 〈 0.05）. CONCLUSION： These results support the hypothesis that PNS plays a therapeutic and protective role on the pathological lesions and learning dysfunction of Alzheimer＇s disease. The therapeutic effects of PNS for Alzheimer＇s disease are possibly achieved through downregulating the expression of the App gene and upregulating the expression of the Syp gene. The therapeutic effects of PNS are dose-dependent and are greater than the effect of huperzine A.
基金supported by the Annual Key Research Project of Anhui Province(1301043047)
文摘The present study was aimed at determining the effects of Tongqiao Huoxue Decoction （TQHXD） on the Ca2＋-CaMKII-CREB pathway and the memory and learning capacities of rats with vascular dementia （VD）. The rat VD model was established by using an improved bilateral carotid artery ligation method. The Morris water maze experiment was used to evaluate the ethology of the VD rats following treatments with TQHXD at 3.01, 6.02, and 12.04 g.kg-1 per day for 31 days. At the end of experiment, the hippocampus were harvested and analyzed. Western blotting and RT-PCR were used to measure the expression levels of calmodulin-binding protein kinase II（CaMKII）, protein kinase A（PKA）, cAMP-response element binding protein（CREB）, and three N-methyl-D-aspart^c acid receptor subunits （NR1, NR2A, and NR2B）. Our results revealed that TQHXD could alleviate the loss of learning abilities and increase the memory capacity （P 〈 0.05 and P 〈 0.01 vs the model group, respectively）. The treatment with 6.02 and 12.04 g.kg-1 of TQHXD significantly up-regulated the Ca2＋-CaMKII-CREB pathway in the hippocampus. In conclusion, TQHXD showed therapeutic effects on a bilateral carotid artery ligation-induced vascular dementia model, through the up-regulation of calcium signalling oathwavs.
基金supported by Undergraduate Innovational Experimentation Program of Shanxi Province, China (2009103)
文摘Nitric oxide （NO） is a novel type of neurotransmitter that is closely associated with synaptic plasticity, learning and memory. In the present study, we assessed the effects of Larginine and NnitroL arginine methylester （LNAME, a nitric oxide synthase inhibitor） on learning and memory. Rats were assigned to three groups receiving intracerebroventricular injections of LArg （the NO precursor）, LNAME, or 0.9% NaCI （control）, once daily for seven con secutive days. Twelve hours after the last injection, they underwent an electric shockpaired Y maze test. Twentyfour hours later, the rats＇ memory of the safe illuminated arm was tested. After that, the levels of NO and a7 nicotinic acetylcholine receptor （a7 nAChR） in the prefrontal cortex and hippocampus were assessed using an NO assay kit, and immunohistochemistry and Western blots, respectively. We found that, compared to controls, LArgtreated rats received fewer foot shocks and made fewer errors to reach the learning criterion, and made fewer errors during the memorytesting session. In contrast, LNAMEtreated rats received more foot shocks and made more errors than controls to reach the learning criterion, and made more errors during the memorytesting session. In parallel, NO content in the prefrontal cortex and hippocampus was higher in LArgtreated rats and lower inLNAME rats, compared to controls. Similarly, （]7 nAChR immunoreactivity and protein expression in the prefrontal cortex and hippocampus were higher in LArgtreated rats and lower in LNAME rats, compared to controls. These results suggest that the modulation of NO content in the brain correlates with a7 nAChR distribution and expression in the prefrontal cortex and hippocampus, as well as with learning and memory performance in the Ymaze.
基金Supported by the by the Natural Science Foundation of Henan:Study of Eclipta Prostrata Extract in Aging(2020-ZZJH-339,17A180010)
文摘OBJECTIVE: To investigate the role of Eclipta prostrata (E. prostrata) extract in improving spatial learning and memory deficits in D-galactose-induced aging in rats. METHODS: Rats were divided into five groups, with 10 animals in each group. Aging rats were produced by treatment with 100 mg·kg-1·d-1 of D-galactose for 6 weeks. Rats in the E. prostrata treatment groups received an aqueous extract of E. prostrata orally at a concentration of 50, 100, or 200 mg·kg-1· d-1 for 3 weeks. Animals in both the normal and model groups were treated with similar volumes of saline. Spatial memory performance was measured using the Morris water maze. The mRNA levels and enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were analyzed using real- time quantitative PCR and spectrophotometry,respectively. The levels of induced nitric oxide synthase (iNOS), nitric oxide (NO), dopamine (DA), norepinephrine (NE), and serotonin (5-HT) were determined using enzyme-linked immunosorbent assay and spectrophotometry. RESULTS: Compared with the normal group, rats in the D-galactose-treated model group exhibited significant memory loss. There was severe damage to the hippocampal CA1 area, and expression levels of SOD, CAT, GPx, and GR were significantly decreased in the model group compared with the normal group. In the model group, levels of iNOS and NO were significantly increased compared with the normal group. However, treatment with E. prostrata extract reversed the conditions caused by D-galactose- induced aging, especially in the groups with higher treatment concentrations. Compared with the normal group, the levels of DA, NE, and 5-HT were significantly lower in the D-galactose-treated model group. In the E. prostrata extract-treated groups, however, there was a dose-dependent upregulation of DA, NE, and 5-HT expression. CONCLUSION: Our results suggest that administration of E. prostrata extract can result in an improvement in the learning and memory impairments that are induced by D-galactose treatment in rats. This improvement may be the result of enhanced antioxidative ability, decreased iNOS and NO levels, and the induction of DA, NE, and 5-HT expression in the brain.
基金supported by the National Natural Science Foundation of China(No.52474435)China Baowu Low Carbon Metallurgy Innovation Foundation(BWLCF202307).
文摘Accurate forecasting of blast furnace gas(BFG)production is an essential prerequisite for reasonable energy scheduling and management to reduce carbon emissions.Coupling forecasting between BFG generation and consumption dynamics was taken as the research object.A multi-task learning(MTL)method for BFG forecasting was proposed,which integrated a coupling correlation coefficient(CCC)and an inverted transformer structure.The CCC method could enhance key information extraction by establishing relationships between multiple prediction targets and relevant factors,while MTL effectively captured the inherent correlations between BFG generation and consumption.Finally,a real-world case study was conducted to compare the proposed model with four benchmark models.Results indicated significant reductions in average mean absolute percentage error by 33.37%,achieving 1.92%,with a computational time of 76 s.The sensitivity analysis of hyperparameters such as learning rate,batch size,and units of the long short-term memory layer highlights the importance of hyperparameter tuning.
文摘BACKGROUND： Ginsenoside extracted from the stem and leaf of ginseng （GSL） and choline have both been shown to improve learning and memory functions; however, further studies are needed to understand the synergistic effects of a combination of both. OBJECTIVE： To verify the combined improved synergistic effects of GSL and choline on learning and memory disorders in rats. DESIGN： Control observation. SETTING： Taishan Medical College. MATERIALS： A total of 150 male Kunming mice weighing （204-2） g and 40 healthy male Wistar rats weighing （2204-20） g were provided by the Experimental Animal Department of Jilin University. Animal experimentation received confirmed consent from the local ethic committee. GSL was provided by the Department of Chemistry, Norman Bethune Medical University, and choline was provided by the Third Experiment Factory, Shanghai. METHODS： This study was performed at the Life Science Institute, Taishan Medical College from October 2006 to February 2007. ① Scopolamine-induced learning and memory disorders in rats： Forty rats were randomly divided into control group, model group, combination group （400 mg/kg GSL ＋ 200 mg/kg choline）, GSL （400 mg/kg） group, and choline （200 mg/kg） group, 8 rats/group. Rats were perfused and administrated in the morning, once a day for 14 successive days. Rats in the control group and model group were perfused with 20 mL/kg distilled water and underwent Morris water maze spatial resolution test 1 hour after perfusion on the 10m, 11m, and 12m days after administration. Rats also underwent passive step-down avoidance test 1 hour after reperfusion on the 13m and 14m days after administration. Thirty minutes prior to experimentation, rats in the remaining three groups were intraperitoneally （i.p） injected with 2 mg/kg scopolamine, and rats in the control group were i.p. injected with 2 mL/kg saline. ② Scopolamine-induced learning disorder and memory acquired disorder in mice： Fifty mice were randomly divided into control group, model group, combination group （400 mg/kg GSL ＋200 mg/kg choline）, GSL （400 mg/kg） group, and choline （200 mg/kg） group, with 10 mice/group. Mice were perfused and administrated in the morning, once a day for 9 successive days. Mice in the control group and model group were perfused with 20 mL/kg distilled water and underwent passive step down avoidance test 1 hour after reperfusion on the 8th and 9th day after administration. Twenty minutes prior to training, mice in the remaining three groups were i.p. injected with 2 mg/kg scopolamine, and mice in the control group were i.p. injected with 10 mL/kg saline. ③ Sodium nitrite-induced memory consolidation disorder in mice： Grouping, administration, and testing were the same as mentioned above. After training, mice in the remaining three groups were immediately subcutaneously injected with 120 mg/kg sodium nitrite, and mice in the control group were subcutaneously injected with 20 mL/kg saline. ④ Ethanol-induced memory reconsolidation disorder in mice： Grouping, administration, and testing were the same as mentioned above. At 24 hours after training and 20 minutes before retraining, mice in the remaining four groups were perfused with 10 mL/kg ethanol （0.3 volume fraction）, and mice in the control group were perfused with 10 mL/kg saline. MAIN OUTCOME MEASURES： Synergistic effects of GSL and choline on learning and memory deficits induced by scopolamine, sodium nitrite, and ethanol in experimental animals. RESULTS： All 40 rats and 150 mice were included in the final analysis. ① Synergistic effects of GSL and choline on learning and memory disorders induced by scopolamine in rats： During passive step-down avoidance and Morris water maze spatial resolution tests, the number of error responses and length of maze training in the model group were significantly greater than in the control group （P 〈 0.01）; while the number of error responses and length of maze training in the combination group were significantly less than in the model group, GSL group, and choline group （P 〈 0.05-0.01）. The Q value was 〉 1 after combining administration, which suggests that the combination of GSL and choline had synergistic effects. ② Synergistic effects of GSL and choline on learning disorder and memory-acquired disorder induced by scopolamine in mice： During passive step-down avoidance test, the number of error responses in the model group were significantly greater than in the control group （P 〈 0.01 ）; while the number of error responses in the combination group were significantly less than in the model group, GSL group, and choline group （P 〈 0.05-0.01）. The Q value was 〉 1 after combining administration, which suggests GSL and choline had synergistic effects. ③ Synergistic effects of GSL and choline on memory sodium nitrate-induced consolidation disorder in mice： During passive step down avoidance test, the number of error responses in the model group were significantly less than in the control group （P 〈 0.01 ）; while the number of error responses in the combination group were significantly less than in the model group, GSL group, and choline group （P 〈 0.05-0.01）. The Q value was 〉 1 after combined administration, which suggests GSL and choline had synergistic effects. ④ Synergistic effects of GSL and choline on ethanol-induced memory reconsolidation disorder in mice： During passive step down avoidance test, the number of error responses in the model group were significantly greater than in the control group （P 〈 0.01）; while the number of error responses in the combination group were significantly less than in the model group, GSL group, and choline group （P 〈 0.05-0.01）. The Q value was 〉 1 after combined administration, which suggests GSL and choline had synergistic effects. CONCLUSION： GSL and choline have synergistic effects on learning and memory functions.
基金“973”Program of the Ministry of Science and Technology of China:Research on Acupoint Optimization,Combination and Evaluation Methods(No.2014CB543103)the SelfSelected Research Program from of China Academy of Chinese Medical Sciences:Study on the Mechanism of Central Amygdala Nucleus Mediated Electroacupuncture on Relieving Chronic Pain and Related Aversive Mood(No.ZZ13-YQ-063)。
文摘OBJECTIVE:To investiage the effect of electroacupuncture(EA)at a single acupoint of Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6)and at combined acupoints of Shenmen(HT7)and Baihui(GV20)and Sanyinjiao(SP6)on the PKA/CREB and BDNF/TrkB signaling,as well as neuroapoptosis and neurogenesis in hippocampus and elucidate the underlying mechanism of single and combined acupoints on ameliorating spatial learning and memory deficits in a rat model of primary insomnia.METHODS:Primary insomnia was modeled by intraperitoneal injection of para-chlorophenylalanine(PCPA)once daily for 2 d.EA was applied at Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6),or Shenmen(HT7)+Baihui(GV20)+Sanyinjiao(SP6)(combined)for 30 min daily for 4 d.Spatial learning and memory function was evaluated by the Morris water maze(MWM)test.Protein expressions of hippocampal cAMP-dependent protein kinase(PKA)-Cβ,phosphorylated cAMP-responsive element-binding protein(p-CREB),brainderived neurotrophic factor(BDNF),and tyrosine kinase receptor B(TrkB)were evaluated by Western blotting.Neuronal apoptosis in the hippocampus was detected with the transferase-mediated dUTP-X nick end labeling assay.Endogenous neurogenesis was examined with bromodeoxyuridine staining.The MWM test and hippocampal p-CREB,BDNF,and TrkB protein levels in the combined acupoints group were evaluated after the administration of a PKA-selective inhibitor(H89).RESULTS:Spatial learning and memory were significantly impaired in rats with insomnia.The spatial learning deficits were ameliorated in the Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6),and combined groups;this improvement was significantly greater in the combined group than the single acupoint groups.The spatial memory impairment was improved in the combined,Baihui(GV20),and Shenmen(HT7)groups,but not the Sanyinjiao(SP6)group.The expressions of PKA-Cβ,p-CREB,BDNF,and TrkB were decreased in rats with insomnia.All these proteins were significantly upregulated in the combined group.PKA/p-CREB protein levels were elevated in the Baihui(GV20)and Shenmen(HT7)groups,whereas BDNF/TrkB expression was upregulated in the Sanyinjiao(SP6)group.The staining results showed significant attenuation of hippocampal cell apoptosis and increased numbers of proliferating cells in the combined group,whereas the single acupoint groups only showed decreased numbers of apoptotic cells.In the combined group,the PKA inhibitor reversed the improvement of spatial memory and upregulation of pCREB expression caused by EA,but did not affect its activation of BDNF/TrkB signaling.CONCLUSIONS:EA at the single acupoints Baihui(GV20),Shenmen(HT7),or Sanyinjiao(SP6)had an ameliorating effect on the spatial learning and memory deficits induced by insomnia.EA at combined acupoints exerted a synergistic effect on the improvements in spatial learning and memory impairment in rats with insomnia by upregulating the hippocampal PKA/CREB and BDNF/TrkB signaling,facilitating neurogenesis,and inhibiting neuronal apoptosis.These findings indicate that EA at combined acupoints[(Baihui(GV20),Shenmen(HT7),and Sanyinjiao(SP6)]achieves a more pronounced regulation of hippocampal neuroplasticity than EA at single acupoints,which may partly explain the underlying mechanisms by which EA at combined acupoints exerts a better ameliorative effect on the cognitive dysfunction caused by insomnia.
基金supported by the Foundation of Astronaut Research and Training Center of China(No.SN 02-3)
文摘Objective To gain a better understanding of gene expression changes in the brain following microwave exposure in mice. This study hopes to reveal mechanisms contributing to microwave-induced learning and memory dysfunction. Methods Mice were exposed to whole body 2100 MHz microwaves with specific absorption rates (SARs) of 0.45 W/kg, 1.8 W/kg, and 3.6 W/kg for 1 hour daily for 8 weeks. Differentially expressing genes in the brains were screened using high-density oligonucleotide arrays, with genes showing more significant differences further confirmed by RT-PCR. Results The gene chip results demonstrated that 41 genes (0.45 W/kg group), 29 genes (1.8 W/kg group), and 219 genes (3.6 W/kg group) were differentially expressed. GO analysis revealed that these differentially expressed genes were primarily involved in metabolic processes, cellular metabolic processes, regulation of biological processes, macromolecular metabolic processes, biosynthetic processes, cellular protein metabolic processes, transport, developmental processes, cellular component organization, etc. KEGG pathway analysis showed that these genes are mainly involved in pathways related to ribosome, Alzheimer's disease, Parkinson's disease, long-term potentiation, Huntington's disease, and Neurotrophin signaling. Construction of a protein interaction network identified several important regulatory genes including synbindin (sbdn), Crystallin (CryaB), PPP1CA, Ywhaq, Psap, Psmb1, Pcbp2, etc., which play important roles in the processes of learning and memory. Conclusion Long-term, low-level microwave exposure may inhibit learning and memory by affecting protein and energy metabolic processes and signaling pathways relating to neurological functions or diseases.
基金supported by the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea(NRF-2023S1A5A8077102).
文摘Deep learning enables neural networks to improve prediction performance through data supplementation.In financial time series forecasting,however,such data-driven approaches can encounter limitations where additional data degrade performance,contrary to common expectations.While more data can still be beneficial,it may introduce systemic concept drift due to the complex nonstationarities of stock price index time series,thereby exacerbating overfitting.One such drift is memory inconsistency:locally measured long memories fluctuate over time,alternately approaching and deviating from the random walk condition.We address this problem by typifying memory inconsistencies into two simplified forms:long-term dependentto-independent(D2I)and long-term independent-to-dependent(I2D)inconsistencies.The first experiment,which uses U.S.stock price indices,suggests that additional training examples may lead to performance deterioration of long short-term memory(LSTM)networks,especially when memory inconsistencies are prominent.Since stock markets are influenced by numerous unknown dynamics,the second experiment,which uses simulated mean-reverting time series derived from the fractional Ornstein–Uhlenbeck(fOU)process,is conducted to focus solely on challenges arising from memory inconsistencies.The experimental results demonstrate that memory inconsistencies disrupt the performance of LSTM networks.Theoretically,additional errors from D2I and I2D inconsistencies increase as the time lag increases.Since LSTM networks are inherently recurrent,causing information from distant steps to attenuate,they fail to effectively capture memory inconsistencies in practical offline learning schemes.Nonetheless,transplanting pretrained memory-consistent gate parameters into the LSTM model partially mitigates the performance deterioration caused by memory inconsistencies,suggesting that memory augmentation strategies have the potential to overcome this problem.As such a memory augmentation method,we propose the Gate-of-Gates(GoG)model,which extends the capacity of LSTM gates and demonstrates that it can mitigate additional errors arising from memory inconsistencies.
基金supported by the National Natural Science Foundation of China, No. 81160157Key Program of the Science and Technology Department of Guizhou Province, No. SY20093075
文摘An ischemic-hypoxic animal model was established using right common carotid artery occlusions and inhalation of low concentrations of oxygen in mice. At 10 days after the ischemic-hypoxic injuries, saline-treated mice exhibited significantly prolonged escape latencies in water-maze tests and significantly shorter memory latencies and more mistakes in step-down tests. In contrast, mice treated with 5 mg/kg minocycline exhibited significant reversals of each of these effects compared with the saline-treated control mice. Moreover, we found that minocycline can relieve brain water content and morphological changes in mice following ischemic-hypoxic cerebral injuries. Accordingly, our findings indicate that minocycline provides some protections against the deleterious effects of these injuries in mice.
