Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

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.

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

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

Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism

Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.

Machine learning-assisted efficient design of Cu-based shape memory alloy with specific phase transition temperature

The martensitic transformation temperature is the basis for the application of shape memory alloys(SMAs),and the ability to quickly and accurately predict the transformation temperature of SMAs has very important practical significance.In this work,machine learning(ML)methods were utilized to accelerate the search for shape memory alloys with targeted properties(phase transition temperature).A group of component data was selected to design shape memory alloys using reverse design method from numerous unexplored data.Component modeling and feature modeling were used to predict the phase transition temperature of the shape memory alloys.The experimental results of the shape memory alloys were obtained to verify the effectiveness of the support vector regression(SVR)model.The results show that the machine learning model can obtain target materials more efficiently and pertinently,and realize the accurate and rapid design of shape memory alloys with specific target phase transition temperature.On this basis,the relationship between phase transition temperature and material descriptors is analyzed,and it is proved that the key factors affecting the phase transition temperature of shape memory alloys are based on the strength of the bond energy between atoms.This work provides new ideas for the controllable design and performance optimization of Cu-based shape memory alloys.

Early identification of stroke through deep learning with multi-modal human speech and movement data

Early identification and treatment of stroke can greatly improve patient outcomes and quality of life.Although clinical tests such as the Cincinnati Pre-hospital Stroke Scale(CPSS)and the Face Arm Speech Test(FAST)are commonly used for stroke screening,accurate administration is dependent on specialized training.In this study,we proposed a novel multimodal deep learning approach,based on the FAST,for assessing suspected stroke patients exhibiting symptoms such as limb weakness,facial paresis,and speech disorders in acute settings.We collected a dataset comprising videos and audio recordings of emergency room patients performing designated limb movements,facial expressions,and speech tests based on the FAST.We compared the constructed deep learning model,which was designed to process multi-modal datasets,with six prior models that achieved good action classification performance,including the I3D,SlowFast,X3D,TPN,TimeSformer,and MViT.We found that the findings of our deep learning model had a higher clinical value compared with the other approaches.Moreover,the multi-modal model outperformed its single-module variants,highlighting the benefit of utilizing multiple types of patient data,such as action videos and speech audio.These results indicate that a multi-modal deep learning model combined with the FAST could greatly improve the accuracy and sensitivity of early stroke identification of stroke,thus providing a practical and powerful tool for assessing stroke patients in an emergency clinical setting.

Machine learning applications in healthcare clinical practice and research

Machine learning(ML)is a type of artificial intelligence that assists computers in the acquisition of knowledge through data analysis,thus creating machines that can complete tasks otherwise requiring human intelligence.Among its various applications,it has proven groundbreaking in healthcare as well,both in clinical practice and research.In this editorial,we succinctly introduce ML applications and present a study,featured in the latest issue of the World Journal of Clinical Cases.The authors of this study conducted an analysis using both multiple linear regression(MLR)and ML methods to investigate the significant factors that may impact the estimated glomerular filtration rate in healthy women with and without non-alcoholic fatty liver disease(NAFLD).Their results implicated age as the most important determining factor in both groups,followed by lactic dehydrogenase,uric acid,forced expiratory volume in one second,and albumin.In addition,for the NAFLD-group,the 5th and 6th most important impact factors were thyroid-stimulating hormone and systolic blood pressure,as compared to plasma calcium and body fat for the NAFLD+group.However,the study's distinctive contribution lies in its adoption of ML methodologies,showcasing their superiority over traditional statistical approaches(herein MLR),thereby highlighting the potential of ML to represent an invaluable advanced adjunct tool in clinical practice and research.

Efficient Penetration Testing Path Planning Based on Reinforcement Learning with Episodic Memory

Intelligent penetration testing is of great significance for the improvement of the security of information systems,and the critical issue is the planning of penetration test paths.In view of the difficulty for attackers to obtain complete network information in realistic network scenarios,Reinforcement Learning(RL)is a promising solution to discover the optimal penetration path under incomplete information about the target network.Existing RL-based methods are challenged by the sizeable discrete action space,which leads to difficulties in the convergence.Moreover,most methods still rely on experts’knowledge.To address these issues,this paper proposes a penetration path planning method based on reinforcement learning with episodic memory.First,the penetration testing problem is formally described in terms of reinforcement learning.To speed up the training process without specific prior knowledge,the proposed algorithm introduces episodic memory to store experienced advantageous strategies for the first time.Furthermore,the method offers an exploration strategy based on episodic memory to guide the agents in learning.The design makes full use of historical experience to achieve the purpose of reducing blind exploration and improving planning efficiency.Ultimately,comparison experiments are carried out with the existing RL-based methods.The results reveal that the proposed method has better convergence performance.The running time is reduced by more than 20%.

Cognitive Navigation for Intelligent Mobile Robots:A Learning-Based Approach With Topological Memory Configuration

Autonomous navigation for intelligent mobile robots has gained significant attention,with a focus on enabling robots to generate reliable policies based on maintenance of spatial memory.In this paper,we propose a learning-based visual navigation pipeline that uses topological maps as memory configurations.We introduce a unique online topology construction approach that fuses odometry pose estimation and perceptual similarity estimation.This tackles the issues of topological node redundancy and incorrect edge connections,which stem from the distribution gap between the spatial and perceptual domains.Furthermore,we propose a differentiable graph extraction structure,the topology multi-factor transformer(TMFT).This structure utilizes graph neural networks to integrate global memory and incorporates a multi-factor attention mechanism to underscore elements closely related to relevant target cues for policy generation.Results from photorealistic simulations on image-goal navigation tasks highlight the superior navigation performance of our proposed pipeline compared to existing memory structures.Comprehensive validation through behavior visualization,interpretability tests,and real-world deployment further underscore the adapt-ability and efficacy of our method.

Tree shrew models:A chronic social defeat model of depression and a one-trial captive conditioning model of learning and memory

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.

DISCRETE BIDIRECTIONAL ASSOCIATIVE MEMORY WITH LEARNING FUNCTION

In this paper we propose a new discrete bidirectional associative memory (DBAM) which is derived from our previous continuous linear bidirectional associative memory (LBAM). The DBAM performs bidirectionally the optimal associative mapping proposed by Kohonen. Like LBAM and NBAM proposed by one of the present authors,the present BAM ensures the guaranteed recall of all stored patterns,and possesses far higher capacity compared with other existing BAMs,and like NBAM, has the strong ability to suppress the noise occurring in the output patterns and therefore reduce largely the spurious patterns. The derivation of DBAM is given and the stability of DBAM is proved. We also derive a learning algorithm for DBAM,which has iterative form and make the network learn new patterns easily. Compared with NBAM the present BAM can be easily implemented by software.

On the Role of Memorization in ESL/EFL Learning

Memorization has been long viewed as a bad practice or the opposite of meaningful learning.A survey on the role of memorization in ESL/EFL learning is carried out in Vestal Middle School,Binghamton High School and Binghamton University under the guidance of Professor Jennifer Brondell.The result shows that a majority of subjects were found to emphasize the important role of memorization as a strategy in helping students to obtain better accuracy and fluency,use language knowledge reserve,and gain more self-confidence.

基于改进Q-Learning的移动机器人路径规划算法

随着移动机器人在生产生活中的深入应用,其路径规划能力也需要向快速性和环境适应性兼备发展。为解决现有移动机器人使用强化学习方法进行路径规划时存在的探索前期容易陷入局部最优、反复搜索同一区域,探索后期收敛率低、收敛速度慢的问题,本研究提出一种改进的Q-Learning算法。该算法改进Q矩阵赋值方法,使迭代前期探索过程具有指向性,并降低碰撞的情况;改进Q矩阵迭代方法,使Q矩阵更新具有前瞻性,避免在一个小区域中反复探索;改进随机探索策略,在迭代前期全面利用环境信息,后期向目标点靠近。在不同栅格地图仿真验证结果表明,本文算法在Q-Learning算法的基础上,通过上述改进降低探索过程中的路径长度、减少抖动并提高收敛的速度,具有更高的计算效率。

M-learning结合CBL在消化科规培教学中的探讨及应用

目的探究移动学习平台(M-learning,ML)结合案例教学(Case-based Learning,CBL)在消化科住院医师规范化培训(简称规培)教学中的应用效果。方法选取2021年1月—2023年1月于上海市徐汇区中心医院消化科参加规培学习的80名医师作为研究对象,将其按照随机数表法分为研究组和对照组,每组40名。对照组给予传统讲授式教学法,研究组给予M-learning结合CBL教学法,对比两组医师的理论考试成绩、实践技能考试成绩和学习满意度。结果研究组的理论成绩和实践技能考试成绩均高于对照组,差异具有统计学意义(P均<0.05);研究组的学习满意度明显高于对照组,差异具有统计学意义(P<0.05)。结论将Mlearning结合CBL教学法应用于消化科规培教学中,不仅能够提升医师的理论考试成绩和实践技能考试成绩,还能够有效提高医师学习满意度。

基于Q-Learning的航空器滑行路径规划研究

针对传统算法规划航空器滑行路径准确度低、不能根据整体场面运行情况进行路径规划的问题,提出一种基于Q-Learning的路径规划方法。通过对机场飞行区网络结构模型和强化学习的仿真环境分析,设置了状态空间和动作空间,并根据路径的合规性和合理性设定了奖励函数,将路径合理性评价值设置为滑行路径长度与飞行区平均滑行时间乘积的倒数。最后,分析了动作选择策略参数对路径规划模型的影响。结果表明,与A*算法和Floyd算法相比,基于Q-Learning的路径规划在滑行距离最短的同时,避开了相对繁忙的区域,路径合理性评价值高。

Machine learning applications in stroke medicine:advancements,challenges,and future prospectives

Stroke is a leading cause of disability and mortality worldwide,necessitating the development of advanced technologies to improve its diagnosis,treatment,and patient outcomes.In recent years,machine learning techniques have emerged as promising tools in stroke medicine,enabling efficient analysis of large-scale datasets and facilitating personalized and precision medicine approaches.This abstract provides a comprehensive overview of machine learning’s applications,challenges,and future directions in stroke medicine.Recently introduced machine learning algorithms have been extensively employed in all the fields of stroke medicine.Machine learning models have demonstrated remarkable accuracy in imaging analysis,diagnosing stroke subtypes,risk stratifications,guiding medical treatment,and predicting patient prognosis.Despite the tremendous potential of machine learning in stroke medicine,several challenges must be addressed.These include the need for standardized and interoperable data collection,robust model validation and generalization,and the ethical considerations surrounding privacy and bias.In addition,integrating machine learning models into clinical workflows and establishing regulatory frameworks are critical for ensuring their widespread adoption and impact in routine stroke care.Machine learning promises to revolutionize stroke medicine by enabling precise diagnosis,tailored treatment selection,and improved prognostication.Continued research and collaboration among clinicians,researchers,and technologists are essential for overcoming challenges and realizing the full potential of machine learning in stroke care,ultimately leading to enhanced patient outcomes and quality of life.This review aims to summarize all the current implications of machine learning in stroke diagnosis,treatment,and prognostic evaluation.At the same time,another purpose of this paper is to explore all the future perspectives these techniques can provide in combating this disabling disease.

改进Q-Learning的路径规划算法研究

针对Q-Learning算法学习效率低、收敛速度慢且在动态障碍物的环境下路径规划效果不佳的问题,本文提出一种改进Q-Learning的移动机器人路径规划算法.针对该问题,算法根据概率的突变性引入探索因子来平衡探索和利用以加快学习效率;通过在更新函数中设计深度学习因子以保证算法探索概率;融合遗传算法,避免陷入局部路径最优同时按阶段探索最优迭代步长次数,以减少动态地图探索重复率;最后提取输出的最优路径关键节点采用贝塞尔曲线进行平滑处理,进一步保证路径平滑度和可行性.实验通过栅格法构建地图,对比实验结果表明,改进后的算法效率相较于传统算法在迭代次数和路径上均有较大优化,且能够较好的实现动态地图下的路径规划,进一步验证所提方法的有效性和实用性.

基于Q-learning的自适应链路状态路由协议

针对大规模无人机自组网面临的任务需求多样性、电磁环境复杂性、节点高机动性等问题,充分考虑无人机节点高速移动的特点,基于无人机拓扑稳定度和链路通信容量指标设计了一种无人机多点中继(multi-point relay,MPR)选择方法;为了减少网络路由更新时间,增加无人机自组网路由策略的稳定性和可靠性,提出了一种基于Q-learning的自适应链路状态路由协议(Q-learning based adaptive link state routing,QALSR)。仿真结果表明,所提算法性能指标优于现有的主动路由协议。

A spatiotemporal deep learning method for excavation-induced wall deflections

Data-driven approaches such as neural networks are increasingly used for deep excavations due to the growing amount of available monitoring data in practical projects.However,most neural network models only use the data from a single monitoring point and neglect the spatial relationships between multiple monitoring points.Besides,most models lack flexibility in providing predictions for multiple days after monitoring activity.This study proposes a sequence-to-sequence(seq2seq)two-dimensional(2D)convolutional long short-term memory neural network(S2SCL2D)for predicting the spatiotemporal wall deflections induced by deep excavations.The model utilizes the data from all monitoring points on the entire wall and extracts spatiotemporal features from data by combining the 2D convolutional layers and long short-term memory(LSTM)layers.The S2SCL2D model achieves a long-term prediction of wall deflections through a recursive seq2seq structure.The excavation depth,which has a significant impact on wall deflections,is also considered using a feature fusion method.An excavation project in Hangzhou,China,is used to illustrate the proposed model.The results demonstrate that the S2SCL2D model has superior prediction accuracy and robustness than that of the LSTM and S2SCL1D(one-dimensional)models.The prediction model demonstrates a strong generalizability when applied to an adjacent excavation.Based on the long-term prediction results,practitioners can plan and allocate resources in advance to address the potential engineering issues.

Significant risk factors for intensive care unit-acquired weakness:A processing strategy based on repeated machine learning

BACKGROUND Intensive care unit-acquired weakness(ICU-AW)is a common complication that significantly impacts the patient's recovery process,even leading to adverse outcomes.Currently,there is a lack of effective preventive measures.AIM To identify significant risk factors for ICU-AW through iterative machine learning techniques and offer recommendations for its prevention and treatment.METHODS Patients were categorized into ICU-AW and non-ICU-AW groups on the 14th day post-ICU admission.Relevant data from the initial 14 d of ICU stay,such as age,comorbidities,sedative dosage,vasopressor dosage,duration of mechanical ventilation,length of ICU stay,and rehabilitation therapy,were gathered.The relationships between these variables and ICU-AW were examined.Utilizing iterative machine learning techniques,a multilayer perceptron neural network model was developed,and its predictive performance for ICU-AW was assessed using the receiver operating characteristic curve.RESULTS Within the ICU-AW group,age,duration of mechanical ventilation,lorazepam dosage,adrenaline dosage,and length of ICU stay were significantly higher than in the non-ICU-AW group.Additionally,sepsis,multiple organ dysfunction syndrome,hypoalbuminemia,acute heart failure,respiratory failure,acute kidney injury,anemia,stress-related gastrointestinal bleeding,shock,hypertension,coronary artery disease,malignant tumors,and rehabilitation therapy ratios were significantly higher in the ICU-AW group,demonstrating statistical significance.The most influential factors contributing to ICU-AW were identified as the length of ICU stay(100.0%)and the duration of mechanical ventilation(54.9%).The neural network model predicted ICU-AW with an area under the curve of 0.941,sensitivity of 92.2%,and specificity of 82.7%.CONCLUSION The main factors influencing ICU-AW are the length of ICU stay and the duration of mechanical ventilation.A primary preventive strategy,when feasible,involves minimizing both ICU stay and mechanical ventilation duration.

Machine learning for predicting the outcome of terminal ballistics events

Machine learning(ML) is well suited for the prediction of high-complexity,high-dimensional problems such as those encountered in terminal ballistics.We evaluate the performance of four popular ML-based regression models,extreme gradient boosting(XGBoost),artificial neural network(ANN),support vector regression(SVR),and Gaussian process regression(GP),on two common terminal ballistics’ problems:(a)predicting the V50ballistic limit of monolithic metallic armour impacted by small and medium calibre projectiles and fragments,and(b) predicting the depth to which a projectile will penetrate a target of semi-infinite thickness.To achieve this we utilise two datasets,each consisting of approximately 1000samples,collated from public release sources.We demonstrate that all four model types provide similarly excellent agreement when interpolating within the training data and diverge when extrapolating outside this range.Although extrapolation is not advisable for ML-based regression models,for applications such as lethality/survivability analysis,such capability is required.To circumvent this,we implement expert knowledge and physics-based models via enforced monotonicity,as a Gaussian prior mean,and through a modified loss function.The physics-informed models demonstrate improved performance over both classical physics-based models and the basic ML regression models,providing an ability to accurately fit experimental data when it is available and then revert to the physics-based model when not.The resulting models demonstrate high levels of predictive accuracy over a very wide range of projectile types,target materials and thicknesses,and impact conditions significantly more diverse than that achievable from any existing analytical approach.Compared with numerical analysis tools such as finite element solvers the ML models run orders of magnitude faster.We provide some general guidelines throughout for the development,application,and reporting of ML models in terminal ballistics problems.