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E674Q(shanghai APP mutant),a novel amyloid precursor protein mutation,in familial late-onset Alzheimer's disease

Genes & Diseases 2024年第2期11卷 1022-1034页

作者： Yongfang Zhang Xinyi Xie Boyu Chen Lina Pan Jianping Li Wanbing Wang Jintao Wang Ran Tang Qiang Huang Xiaofen Chen Rujing Ren Zhentao Zhang Wei Fu Gang Wang Department of Neurology Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of Pharmacology and Chemical Biology Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of Medicinal Chemistry School of PharmacyFudan UniversityShanghai 201203China Department of Neurology Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research Institute of NeuroscienceSchool of MedicineXiamen UniversityXiamenFujian 361102China Shenzhen Research institute of Xiamen University ShenzhenGuangdong 518063China

Identified as the pathogenic genes of Alzheimer's disease(AD),APP,PSEN1,and PSEN2 mainly lead to early-onset AD,whose course is more aggressive,and atypical symptoms are more common than sporadic ***,a novel missense mutation,APP E674Q(also named“shanghai APP”),was detected in a Chinese index patient with typical late-onset AD(LOAD)who developed memory decline in his *** results from neuroimaging were consistent with AD,where widespread amyloidβdeposition was demonstrated in 18 F-florbetapir Positron Emission Tomography(PET).APP E674Q is close to theβ-secretase cleavage site and the well-studied Swedish APP mutation(KM670/671NL),which was predicted to be pathogenic in *** dynamics simulation indicated that the E674Q mutation resulted in a rearrangement of the interaction mode between APP and BACE1 and that the E674Q mutation was more prone to cleavage by *** in vitro results suggested that the E674Q mutation was pathogenic by facilitating the BACE1-mediated processing of APP and the production of Aβ.Furthermore,we applied an adeno-associated virus(AAV)-mediated transfer of the human E674Q mutant APP gene to the hippocampi of two-month-old C57Bl/6 J ***-E674Q-injected mice exhibited impaired learning behavior and increased pathological burden in the brain,implying that the E674Q mutation had a pathogenicity that bore a comparison with the classical Swedish ***,we report a strong amyloidogenic effect of the E674Q substitution in *** our knowledge,E674Q is the only pathogenic mutation within the amyloid processing sequence causing LOAD.

关键词： Alzheimer's disease Amyloid beta APP mutation E674Q Late onset

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Feature-aided pose estimation approach based on variational auto-encoder structure for spacecrafts

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Chinese Journal of Aeronautics 2024年第8期37卷 329-341页

作者： Yanfang LIU Rui ZHOU Desong DU Shuqing CAO Naiming QI Department of Aerospace Engineering Harbin Institute of TechnologyHarbin 150001China Suzhou Research institute of HIT Suzhou 215104China shanghai institute of Spaceflight Control Technology Shanghai 201109China shanghai Key Laboratory of Aerospace Intelligent Control Technology Shanghai 201109China

Real-time 6 Degree-of-Freedom(DoF)pose estimation is of paramount importance for various on-orbit *** from the development of deep learning,Convolutional Neural Networks(CNNs)in feature extraction has yielded impressive achievements for spacecraft pose *** improve the robustness and interpretability of CNNs,this paper proposes a Pose Estimation approach based on Variational Auto-Encoder structure(PE-VAE)and a Feature-Aided pose estimation approach based on Variational Auto-Encoder structure(FA-VAE),which aim to accurately estimate the 6 DoF pose of a target *** methods treat the pose vector as latent variables,employing an encoder-decoder network with a Variational Auto-Encoder(VAE)*** enhance the precision of pose estimation,PE-VAE uses the VAE structure to introduce reconstruction mechanism with the whole ***,FA-VAE enforces feature shape constraints by exclusively reconstructing the segment of the target spacecraft with the desired *** evaluation against leading methods on public datasets reveals similar accuracy with a threefold improvement in processing speed,showcasing the significant contribution of VAE structures to accuracy enhancement,and the additional benefit of incorporating global shape prior features.

关键词： Pose estimation Variational auto-encoder Feature-aided Pose Estimation Approach On-orbit measurement tasks Simulated and experimental dataset

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Oxidative stress-initiated one-carbon metabolism drives the generation of interleukin-10-producing B cells to resolve pneumonia

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Cellular & Molecular immunology 2024年第1期21卷 19-32页

作者： Ying Fu Baichao Yu Qi Wang Zhou Lu Hushan Zhang Dan Zhang Feifei Luo Ronghua Liu Luman Wang Yiwei Chu Department of immunology School of Basic Medical SciencesShanghai Key Laboratory of Medical Epigenetics and MetabolismInstitutes of Biomedical SciencesFudan UniversityShanghaiChina Zhongshan Hospital institute of Clinical Science Zhongshan HospitalShanghaiChina Zhaotong Health Vocational College ZhaotongYunnanChina Department of Digestive Diseases Huashan HospitalFudan UniversityShanghaiChina shanghai Fifth People’s Hospital Fudan UniversityShanghaiChina

The metabolic reprogramming underlying the generation of regulatory B cells during infectious diseases remains *** a Pseudomonas aeruginosa-induced pneumonia model,we reported that IL-10-producing B cells(IL-10+B cells)play a key role in spontaneously resolving infection-mediated *** cytosolic reactive oxygen species(ROS)during inflammation were shown to drive IL-10+B-cell generation by remodeling one-carbon *** of the enzyme serine hydroxymethyltransferase 1(Shmt1)led to inadequate one-carbon metabolism and decreased IL-10+B-cell ***,increased one-carbon flux elevated the levels of the methyl donor S-adenosylmethionine(SAM),altering histone H3 lysine 4 methylation(H3K4me)at the Il10 gene to promote chromatin accessibility and upregulate Il10 expression in B ***,the one-carbon metabolism-associated compound ethacrynic acid(EA)was screened and found to potentially treat infectious pneumonia by boosting IL-10+B-cell ***,these findings reveal that ROS serve as modulators to resolve inflammation by reprogramming one-carbon metabolism pathways in B cells.

关键词： IL-10-producing B cell Reactive oxygen species One-carbon metabolism H3K4me Pneumonia

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Conceptual design of a 714-MHz RFQ for compact proton injectors and development of a new tuning algorithm on its aluminium prototype

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Nuclear Science and Techniques 2024年第1期35卷 45-58页

作者： Yi-Xing Lu Wen-Cheng Fang Yu-Sen Guo Zhen-Tang Zhao shanghai institute of Applied Physics Chinese Academy of Sciences Shanghai 201800China University of Chinese Academy of Sciences Beijing 101408China shanghai Advanced Research institute Chinese Academy of Sciences Shanghai 201204China shanghai Key Laboratory of Cryogenics&Superconducting RF Technology Shanghai 201800China shanghaiTech University Shanghai 201210China

Radio frequency quadrupoles(RFQs),which are crucial components of proton injectors,significantly affect the performance of proton accelerator *** RFQ with a high frequency of 714 MHz dedicated to compact proton injectors for medi-cal applications is designed in this *** RFQ is designed to accelerate proton beams from 50 keV to 4 MeV within a short length of 2 m and can be matched closely with the downstream drift tube linac to capture more particles through a preliminary *** develop an advanced RFQ,challenging techniques,including fabrication and tuning method,must be evaluated and verified using a *** aluminium prototype is derived from the conceptual design of the RFQ and then redesigned to confirm the radio frequency performance,fabrication procedure,and feasibility of the tuning ***,a new tuning algorithm based on the response matrix and least-squares method is developed,which yields favorable results based on the prototype,i.e.,the errors of the dipole and quadrupole components reduced to a low level after several tuning *** from the conceptual design and techniques obtained from the prototype,the formal mechanical design of the 2-m RFQ is ready for the next manufacturing step.

关键词： Compact proton injector RFQ IH-DTL High gradient Tuning

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On-surface photo-induced dechlorination

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Chinese Chemical Letters 2024年第9期35卷 198-201页

作者： Yu He Hao Jiang Shaoxuan Yuan Jiayi Lu Qiang Sun Materials Genome institute Shanghai UniversityShanghai 200444China

On-surface Ullmann-type reaction,or the dehalogenated coupling,is arguably the most pivotal reaction in on-surface synthesis for the fabrications of carbon ***,the vast majority of works rely on activating the C-Br bond of aryl bromide which has a moderate bond dissociation *** C-Cl bond of aryl chloride has a higher dissociation energy and requires much higher thermal energy to break the *** this study,we have explored the on-surface photo-induced dechlorination and achieved the activation of three distinct aryl chlorines on the Au(111)surface with mild *** work enriches our understanding of on-surface photo-induced reactions and highlights the potential of photochemistry in realizing unconventional reactions.

关键词： On-surface synthesis Scanning probe microscopy On-surface photochemistry Dechlorination reaction

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Tuina alleviates neuropathic pain through regulate the activation of microglia and the secretion of inflammatory cytokine in spinal cord

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Journal of Traditional Chinese Medicine 2024年第4期44卷 762-769页

作者： WU Zhiwei ZHU Qingguang KONG Lingjun SONG Pengfei ZHOU Xin GUO Guangxin ZHANG Shuaipan HE Tianxiang CHENG Yanbin FANG Min Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Shanghai University of Traditional Chinese MedicineShanghai 200437China institute of Tuina Shanghai Institute of Traditional Chinese MedicineShanghai 200437China Shuguang Hospital Shanghai University of Traditional Chinese MedicineShanghai 200021China Department of Acupuncture and Tuina Shanghai University of Traditional Chinese MedicineShanghai 201203China

OBJECTIVE:To observe the analgesic effects of Tuina on neuropathic pain(NPP)and the underlying ***:Forty-eight Sprague-Dawley(SD)rats were assigned by random into three treatment groups:sham,chronic constriction injury(CCI),and *** group contained sixteen *** model was generated by ligating the right sciatic *** changes of CCI were assessed by the paw withdrawal threshold(PWT)and paw withdrawal latency(PWL).In addition,biochemical techniques such as immunofluorescence staining,enzyme-linked immunosorbent assay(ELISA)and Western blotting were used to profile levels of microglia activation and inflammatory factors in the spinal dorsal horn(SDH)of ***(clockwise pressing and rubbing)was performed at Chengshan(BL57)to observe the analgesic effects on CCI rats and the underlying ***:Rats with CCI experienced significant reduction in the PWT and PWL of the right hind paw relative to CCI group at day *** treatment rescued this situation significantly on days 10 and ***,Iba-1,microglia M1 receptor CD68,tumor necrosis factor-α(TNF-α),and interleukin-1β(IL-1β)were higher in the right SDH for CCI group compared to the sham group on day *** expected,Tuina partially downregulated the CCI-induced overexpressed Iba-1,CD68,TNF-α,and IL-1βin the SDH of CCI ***:Tuina induces a time-dependent cumulative analgesic effect in CCI rats by inhibiting the activation of microglia and the secretion of IL-1βand TNF-αin SDH.

关键词： Tuina neuralgia microglia inflammatory cytokine spinal cord

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Multi-blade rubbing characteristics of the shaft-disk-blade-casing system with large rotation

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Applied Mathematics and Mechanics(English Edition) 2024年第1期45卷 111-136页

作者： Zhiyuan WU Linchuan ZHAO Han YAN Ge YAN Ao CHEN Wenming ZHANG State Key Laboratory of Mechanical System and Vibration Shanghai Jiao Tong UniversityShanghai 200240China shanghai institute of Aerospace Systems Engineering Shanghai 201108China

Blade rubbing faults cause detrimental impact on the operation of aeroengines. Most of the existing studies on blade rubbing in the shaft-disk-blade-casing(SDBC) system have overlooked the elastic deformation of the blade, while some only consider the whirl of the rotor, neglecting its spin. To address these limitations, this paper proposes a dynamic model with large rotation for the SDBC system. The model incorporates the spin and whirl of the rotor, enabling the realistic reproduction of multiblade rubbing faults. To verify the accuracy of the SDBC model with large rotation and demonstrate its capability to effectively consider the rotational effects such as the centrifugal stiffening and gyroscopic effects, the natural characteristics and dynamic responses of the proposed model are compared with those obtained from reported research and experimental results. Furthermore, the effects of the rotating speed, contact stiffness,and blade number on the dynamic characteristics of the SDBC system with multi-blade rubbing are investigated. The results indicate that the phase angle between the rotor deflection and the unbalance excitation force increases with the increasing rotating speed,which significantly influences the rubbing penetration of each blade. The natural frequency of the SDBC system with rubbing constrain can be observed in the acceleration response of the casing and the torsional response of the shaft, and the frequency is related to the contact stiffness. Moreover, the vibration amplitude increases significantly with the product of the blade number under rubbing, and the rotating frequency approaches the natural frequency of the SDBC system. The proposed model can provide valuable insight for the fault diagnosis of rubbing in bladed rotating machinery.

关键词： shaft-disk-blade-casing(SDBC) large rotation spin and whirl multi-blade rubbing rotational effect

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Space truss construction modeling based on on-orbit assembly motion feature

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Chinese Journal of Aeronautics 2024年第3期37卷 365-379页

作者： Changjie ZHAO Weizhong GUO Meng CHEN Jiaxing HU Youcheng HAN Rongfu LIN State Key Lab of Mechanical System and Vibration Shanghai Jiao Tong UniversityShanghai 200240China institute of Aerospace System Engineering shanghai Shanghai 201109China

More space truss construction has been planned to develop and utilize space *** trusses are designed in the way of large-scale,complex,modular,and on-orbit *** meet the upcoming challenge of large-scale space infrastructure construction,it is necessary to study space truss automation design and robotic *** paper proposes an ordinal finite screw adjacency matrix model(OFSAMM),focusing on the relationship between assembly motions,to express and compute a space truss *** this model,a space truss is abstracted as a set of ordered assembly motions,each of which is recorded as a finite screw as the basic element of the truss and its *** operation of truss transformation is also derived under this ***,the truss configuration,the assembly sequence,the truss sub-assembly,the truss components,and the on-orbit assembly task can be expressed and calculated in a unified model,which is calculated and stores the truss topology and assembly with the minimum storage *** the end of this paper,we introduce how to synthesize and optimize space truss design through two *** study will help to improve design ***,it provides a theoretical basis for the automatic construction of space truss structures,especially in the next stage.

关键词： Adjacency matrix Finite screw On-orbit construction modeling Space applications Space trusses Topology design

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Operational Characteristics of Loop Heat Pipe in Microgravity and Normal Gravity Environments

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Journal of Thermal Science 2024年第4期33卷 1394-1408页

作者： ZHONG Siyuan XIE Rongjian LI Yunfei SUN Xiaojin shanghai Institution of Technology and Physics Shanghai200083China University of Chinese Academy of Sciences Beijing100049China shanghai institute of Satellite Engineering Shanghai200240China

The loop heat pipe(LHP)is an advanced,efficient two-phase heat transfer unit,whose operational performance may be affected by microgravity conditions in contrast to ground-based *** performance of on-orbit temperature data and ground test of a copper-propylene LHP with a condenser temperature range of 243.15 K to 303.15 K were employed to compared and *** LHP has successfully started up for more than 193 times with a good heat transfer performance and a stable start-up stabilization on-orbit under a complex orbital heating environment for more than eight *** a small heat load(10.0W),the average start-up time is 110.0 s while the start-up temperature ranges from 5.71 K-12.78 *** start-up time at large temperature differences in the high temperature zone will be higher than the time required for start-up at smaller temperature differences in the low *** the condenser temperature is 250.0 K,the stable temperature difference on orbit is 3.83 K,which is generally consistent in heat transfer compared to 2.20 K in the ground *** this paper,we can conclude that the on-orbit flight data up to now can provide a reference to the design of subsequent LHP space applications.

关键词： Loop Heat Pipe(LHP) start up microgravity on-orbit experiment

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An active high-static-low-dynamic-stiffness vibration isolator with adjustable buckling beams:theory and experiment

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Applied Mathematics and Mechanics(English Edition) 2024年第3期45卷 425-440页

作者： Kefan XU Muqing NIU Yewei ZHANG Liqun CHEN School of Science Harbin Institute of TechnologyShenzhen 518055Guangdong ProvinceChina College of Aerospace Engineering Shenyang Aerospace UniversityShenyang 110136China shanghai Key Laboratory of Mechanics in Energy Engineering Shanghai Frontier Science Center of MechanoinformaticsShanghai Institute of Applied Mathematics and MechanicsSchool of Mechanics and Engineering ScienceShanghai UniversityShanghai 200444China shanghai institute of Aircraft Mechanics and Control Shanghai 200092China

High-static-low-dynamic-stiffness(HSLDS)vibration isolators with buckling beams have been widely used to isolate external *** active adjustable device composed of proportion integration(PI)active controllers and piezoelectric actuators is proposed for improving the negative stiffness stroke of buckling beams.A nonlinear output frequency response function is used to analyze the effect of the vibration *** prototype of the active HSLDS device is built,and the verification experiment is *** results show that compared with the traditional HSLDS vibration isolator,the active HSLDS device can broaden the isolation frequency bandwidth,and effectively reduce the resonant amplitude by adjusting the active control *** maximum vibration reduction rate of the active HSLDS vibration isolator can attain 89.9%,and the resonant frequency can be reduced from 31.08 Hz to 13.28 ***,this paper devotes to providing a new design scheme for enhanced HSLDS vibration isolators.

关键词： active control high-static-low-dynamic-stiffness(HSLDS) vibration isola-tor dynamic analysis

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