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SIL1 improves cognitive impairment in APP23/PS45 mice by regulating amyloid precursor protein processing and Aβ generation

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Zoological Research 2024年第4期45卷 845-856页

作者： Qunxian Wang Yanshuang Jiang Zijun Meng Xiangjun Dong Dongjie Hu Liangye Ji Weihui Zhou Weihong Song Chongqing key laboratory of Child Neurodevelopment and cognitive Disorders Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400000China Second Affiliated Hospital and Yuying Children’s Hospital Institute of AgingKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceWenzhou Medical UniversityWenzhouZhejiang 325000China Oujiang laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)WenzhouZhejiang 325001China

SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains *** this study,the role of SIL1 in APP processing was explored both in vitro and in *** the in vitro experiment,SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant *** the in vivo experiment,AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type *** blotting(WB),immunohistochemistry,RNA sequencing(RNA-seq),and behavioral experiments were performed to evaluate the relevant *** indicated that SIL1 expression decreased in APP23/PS45 *** of SIL1 significantly decreased the protein levels of APP,presenilin-1(PS1),and C-terminal fragments(CTFs)of APP in vivo and in ***,knockdown of SIL1 increased the protein levels of APP,β-site APP cleavage enzyme 1(BACE1),PS1,and CTFs,as well as APP mRNA expression in 2EB2 ***,SIL1 overexpression reduced the number of senile plaques in APP23/PS45 ***,Y-maze and Morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 *** findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.

关键词： Alzheimer’s disease SIL1 APP processing cognitive impairment

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Hexafluoropropylene oxide trimer acid,a perfluorooctanoic acid alternative,induces cardiovascular toxicity in zebrafish embryos

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Journal of Environmental sciences 2024年第5期139卷 460-472页

作者： Sujie Sun Li Zhang Xue Li Lu Zang Ling Huang Junquan Zeng Zigang Cao Xinjun Liao Zilin Zhong Huiqiang Lu Jianjun Chen Jiangxi Engineering laboratory of Zebrafish Modeling and Drug Screening for Human Diseases Jiangxi Key Laboratory of Developmental Biology of OrgansCenter for Clinical Research Center of the Affiliated Hospital of Jinggangshan UniversityJi’an 343009China Translational Research Institute of brain and brain-like Intelligence Shanghai Key Laboratory of Anesthesiology and Brain Functional ModulationDepartment of PediatricsShanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghai 200434China state Environmental Protection key laboratory of Environmental Health Impact Assessment of Emerging Contaminants School of Environmental Sciences and EngineeringShanghai Jiao Tong UniversityShanghai 200240China Department of Interventional and Vascular Surgery Affiliated Hospital of Jinggangshan UniversityJi’an 343009China Department of Internal Medicine and Hematology Affiliated Hospital of Jinggangshan UniversityJi’an 343009China

As an increasingly used alternative to perfluorooctanoic acid(PFOA),hexafluoropropylene oxide trimer acid(HFPO-TA)has been widely detected in global water ***,little is known regarding its toxic effects on cardiovascular ***,zebrafish embryos were treated with egg water containing 0,60,120,or 240 mg/L *** showed that HFPO-TA treatment led to a significant reduction in both larval survival percentage and heart ***,HFPO-TA exposure caused severe pericardial edema and elongation of the sinus venous to bulbus arteriosus distance(SV-BA)in Tg(myl7:GFP)transgenic larvae,disrupting the expression of genes involved in heart development and thus causing abnormal heart *** sprouting angiogenesis was observed in the 120 and 240 mg/L exposed Tg(fli:GFP)transgenic ***-TA treatment also impacted the mRNA levels of genes involved in the vascular endothelial growth factor(VEGF)pathway and embryonic vascular ***-TA exposure significantly decreased erythrocyte number in Tg(gata1:DsRed)transgenic embryos and influenced gene expression associated with the heme metabolism ***-TA also induced oxidative stress and altered the transcriptional levels of genes related to cell cycle and apoptosis,inhibiting cell proliferation while promoting ***,HFPO-TA exposure may induce abnormal development of the cardiovascular and hematopoietic systems in zebrafish embryos,suggesting it may not be a suitable or safe alternative for PFOA.

关键词： Hexafluoropropylene oxide trimer acid Heart development Vascular development Hemopoiesis Zebrafish embryos

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enOsCas12f1-mediated exon skipping for Duchenne muscular dystrophy therapy in humanized mouse model

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Journal of Genetics and Genomics 2024年第2期51卷 256-259页

作者： Ming Jin Jiajia Lin Yu Zhang Qingquan Xiao Xiangfeng Kong Xiumei Zhang Zhurui Shao Yin Wang Yuyang Yu Jinjing Li Wan-Jin Chen Guoling Li Hui Yang Ning Wang Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of NeuroscienceFujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian 350004China HUIDAGENE Therapeutics Co. Ltd.Shanghai 200131China Institute of Neuroscience State Key Laboratory of NeuroscienceKey Laboratory of Primate NeurobiologyCAS Center for Excellence in Brain Science and Intelligence TechnologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China

Duchenne muscular dystrophy(DMD)is a severe neuromuscular disorder caused by mutations in the dystrophin gene,which encodes the essential protein *** genetic condition,affecting approximately 1 in 5000 male births worldwide(Birnkrant et al.,2018),is characterized by progressive muscle weakness and wasting,leading to premature death in the second or third decade of life(Farini et al.,2016).The absence of dystrophin protein causes instability in the sarcolemma,which predisposes individuals to myonecrosis and activation of inflammatory signaling ***,there is currently no effective cure for DMD,and glucocorticoid steroids are commonly used in clinical settings to delay symptom development(Merlini et al.,2003).

关键词： dystrophy Duchenne

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A mix & act liposomes of phospholipase A2-phosphatidylserine for acute brain detoxification by blood‒brain barrier selective-opening

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1827-1844页

作者： Zinan Zhang Wenbin Cao Huanchun Xing Shuai Guo Lijuan Huang Lin Wang Xin Sui Kui Lu Yuan Luo Yongan Wang Jun Yang state key laboratory of Toxicology and Medical Countermeasures Beijing Institutes of Pharmacology and ToxicologyBeijing 100850China Tianjin University of science and Technology Tianjin 300222China Hebei University of science and Technology Shijiazhuang 050018China

In the treatment of central nervous system disease,the blood-brain barrier(BBB)is a major obstruction to drug delivery that must be *** this study,we propose a brain-targeted delivery strat-egy based on selective opening of the *** strategy allows some simple bare nanoparticles to enter the brain when mixed with special opening material;however,the BBB still maintains the ability to completely block molecules from passing *** on the screening of BBB opening and matrix delivery mate-rials,we determined that phospholipase A2-catalyzed 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine li-posomes can efficiently carry drugs into the brain *** an effective dose,this delivery system is safe,especially with its effect on the BBB being *** mix&act delivery system has a simple structure and rapid preparation,making it a strong potential candidate for drug delivery across the BBB.

关键词： Liposomes Phospholipase A2 Phosphoserine Blood-brainbarrier Selectively open Mix&act

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Role of the globus pallidus in motor and non-motor symptoms of Parkinson's disease

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Neural Regeneration Research 2025年第6期20卷 1628-1643页

作者： Yimiao Jiang Zengxin Qi Huixian Zhu Kangli Shen Ruiqi Liu Chenxin Fang Weiwei Lou Yifan Jiang Wangrui Yuan Xin Cao Liang Chen Qianxing Zhuang Department of Physiology School of MedicineNantong UniversityNantongJiangsu ProvinceChina Department of Neurosurgery Huashan HospitalShanghai Medical CollegeFudan UniversityShanghaiChina National Center for Neurological Disorders ShanghaiChina Shanghai key laboratory of brain Function Restoration and Neural Regeneration ShanghaiChina state key laboratory of Medical Neurobiology and MOE Frontiers Center for brain science Institute of Brain ScienceFudan UniversityShanghaiChina

The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the comp

关键词： anxiety basal ganglia bradykinesia deep brain stimulation depression globus pallidus externus globus pallidus internus lateral globus pallidus medial globus pallidus neural circuit Parkinson's disease

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Dissipative soliton resonance within different dispersion regimes in a single mode-locked laser

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Chinese Physics B 2024年第7期33卷 368-372页

作者：赵哲韬舒沁珂解梓怡任俞宣张颖袁博赵春勃彭俊松曾和平 state key laboratory of Precision Spectroscopy East China Normal UniversityShanghai 200062China China Academy of Space Technology Xi'an 710100China Collaborative Innovation Center of Extreme Optics Shanxi UniversityTaiyuan 030006China Chongqing key laboratory of Precision Optics Chongqing Institute of East China Normal UniversityChongqing 401120China Chongqing Institute for brain and Intelligence Guangyang Bay LaboratoryChongqing 400064China

Dissipative soliton resonance(DSR) was previously studied in separated mode-locked fiber lasers within different dispersion regimes including anomalous, near-zero and normal dispersion. Here we propose a method to study DSR in a single mode-locked laser in these different dispersion regimes. This is achieved by virtue of a waveshaper which can control the laser dispersion readily using software, avoiding the usual tedious cutback method. We find that dispersion has a negligible effect on DSR since the pulse duration keeps constant while dispersion is varied. Moreover, we examine the dynamics of DSR on the parameters of the SA including modulation depth and saturation power, and find that the pulse duration can be changed in a large range when the saturation power is decreased. Our numerical simulations could be important to guide relative experimental studies.

关键词： mode locking laser fiber pulse

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key role of electron accessibility at the noble metal-free catalytic interface in hydrogen evolution reaction

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Nano Research 2024年第4期17卷 2538-2545页

作者： Dongchen Han Nanxing Gao Yuyi Chu Zhaoping Shi Ying Wang Junjie Ge Meiling Xiao Changpeng Liu Wei Xing state key laboratory of Electroanalytical Chemistry Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China School of Applied Chemistry and Engineering University of Science and Technology of ChinaHefei 230026China laboratory of Advanced Power Sources Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Jilin Province key laboratory of Low Carbon Chemical Power Sources Changchun 130022China state key laboratory of Rare Earth Resource Utilization Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China

The reactant concentration at the catalytic interface holds the key to the activity of electrocatalytic hydrogen evolution reaction(HER),mainly referring to the capacity of adsorbing hydrogen and electron *** hydrogen adsorption free energy(ΔGH)as a reactivity descriptor,the volcano curve based on Sabatier principle is established to evaluate the hydrogen evolution activity of ***,the role of electron as reactant received insufficient attention,especially for noble metal-free compound catalysts with poor conductivity,leading to cognitive gap between electronic conductivity and apparent catalytic *** we successfully construct a series of catalyst models with gradient conductivities by regulating molybdenum disulfide(MoS_(2))electronic bandgap via a simple solvothermal *** demonstrate that the conductivity of catalysts greatly affects the overall catalytic *** further elucidate the key role of intrinsic conductivity of catalyst towards water electrolysis,mainly concentrating on the electron transport from electrode to catalyst,the electron accumulation process at the catalyst layer,and the charge transfer progress from catalyst to *** and experimental evidence demonstrates that,with the enhancement in electron accessibility at the catalytic interface,the dominant parameter governing overall HER activity gradually converts from electron accessibility to combination of electron accessibility and hydrogen adsorbing *** results provide the insight from various perspective for developing noble metal-free catalysts in electrocatalysis beyond HER.

关键词： conductivity molybdenum disulfide catalytic interface electron accessibility hydrogen evolution charge transfer.

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Improving iconic memory through contrast detection training with HOA-corrected vision

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Fundamental Research 2024年第1期4卷 95-102页

作者： Ling Gong Junlei Zhao Yun Dai Zili Wang Fang Hou Yudong Zhang Zhong-Lin Lu Jiawei Zhou state key laboratory of Ophthalmology Optometry and Vision ScienceEye HospitalSchool of Ophthalmology and OptometryWenzhou Medical UniversityWenzhou 325027China Institute of Optics and Electronics Chinese Academy of SciencesChengdu 610209China The key laboratory of Adaptive Optics Chinese Academy of SciencesChengdu 610209China Chengdu University of Traditional Chinese Medicine Chengdu 610075China Division of Arts and sciences New York University ShanghaiShanghai 200126China Center for Neural science Department of PsychologyNew York UniversityNew York 10003United States NYU-ECNU Institute of brain and cognitive science at NYU Shanghai Shanghai 200062China

Iconic memory and short-term memory are not only crucial for perception and cognition,but also of great importance to mental ***,we first showed that both types of memory could be improved by improving limiting processes in visual processing through perceptual *** adults were trained in a contrast detection task for ten days,with their higher-order aberrations(HOA)corrected in *** found that the training improved not only their contrast sensitivity function(CSF),but also their iconic memory and baseline information maintenance for short-term memory,and the relationship between memory and CSF improvements could be well-predicted by an observer *** results suggest that training the limiting component of a cognitive task with visual perceptual learning could improve visual *** may also provide an empirical foundation for new therapies to treat people with poor sensory memory.

关键词： Perceptual learning Iconic memory Higher-order aberrations Contrast sensitivity Short-term memory

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SpikingMiniLM: energy-efficient spiking transformer for natural language understanding

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science China(Information sciences) 2024年

作者： Jiayu ZHANG Jiangrong SHEN Zeke WANG Qinghai GUO Rui YAN Gang PAN Huajin TANG College of Computer science and Technology Zhejiang University The state key Lab of brain-Machine Intelligence Zhejiang University Collaborative Innovation Center of Artificial Intelligence Zhejiang University Advanced Computing and Storage laboratory Huawei Technologies Co. Ltd. College of Computer science and Technology Zhejiang University of Technology MOE Frontier science Center for brain science and brain-Machine Integration Zhejiang University

In the era of large-scale pretrained models, artificial neural networks (ANNs) have excelled in natural language understanding (NLU) tasks. However, their success often necessitates substantial computational resources and energy consumption. To address this, we explore the potential of spiking neural networks (SNNs) in NLU—a promising avenue with demonstrated advantages, including reduced power consumption and improved efficiency due to their event-driven characteristics. We propose the SpikingMiniLM,a novel spiking Transformer model tailored for natural language understanding. We first introduce a multistep encoding method to convert text embeddings into spike trains. Subsequently, we redesign the attention mechanism and residual connections to make our model operate on the pure spike-based paradigm without any normalization technique. To facilitate stable and fast convergence, we propose a general parameter initialization method grounded in the stable firing rate principle. Furthermore, we apply an ANN-to-SNN knowledge distillation to overcome the challenges of pretraining SNNs. Our approach achieves a macroaverage score of 75.5 on the dev sets of the GLUE benchmark, retaining 98%of the performance exhibited by the teacher model MiniLMv2. Our smaller model also achieves similar performance to BERTMINIwith fewer parameters and much lower energy consumption, underscoring its competitiveness and resource efficiency in NLU tasks.

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Digital CEOs in Digital Enterprises:Automating,Augmenting,and Parallel in Metaverse/CPSS/TAOs

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IEEE/CAA Journal of Automatica Sinica 2024年第4期11卷 820-823页

作者： Juanjuan Li Rui Qin Sangtian Guan Xiao Xue Peng Zhu Fei-Yue Wang with state key laboratory of Multimodal Artificial Intelligence Systems Institute of AutomationChinese Academy of SciencesBeijing 100190China the College of Intelligence and Computing Tianjin UniversityTianjin 300072China School of Economics and Management Nanjing University of Science and TechnologyNanjing 210094China the state key laboratory for Management and Control of Complex Systems Chinese Academy of SciencesBeijing 100190 Faculty of Innovation Engineering Macao University of Science and TechnologyMacao 999078China

BIG models or foundation models are rapidly emerging as a key force in advancing intelligent societies[1]–[3]Their significance stems not only from their exceptional ability to process complex data and simulate advan... 详细信息

关键词： exceptional Auto advancing

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