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Senktide blocks aberrant RTN3 interactome to retard memory decline and tau pathology in social isolated Alzheimer’s disease mice

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Protein & Cell 2024年第4期15卷 261-284页

作者： He-Zhou Huang Wen-Qing Ai Na Wei Ling-Shuang Zhu Zhi-Qiang liu Chao-Wen Zhou Man-Fei Deng Wen-Tao Zhang Jia-Chen Zhang Chun-Qing Yang Ya-Zhuo Hu Zhi-Tao Han Hong-Hong Zhang Jian-Jun Jia Jing Wang fang-fang liu Ke Li Qi Xu Mei Yuan Hengye Man Ziyuan Guo Youming Lu Kai Shu Ling-Qiang Zhu Dan liu Department of Pathophysiology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Medical Genetics School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Pathology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450002China Department of Pathology School of Basic MedicineZhengzhou UniversityZhengzhou 450002China The Second Affiliated Hospital Department of NeurologyHengyang Medical SchoolUniversity of South ChinaHengyang 421001China Beijing Key Laboratory of Aging and Geriatrics National Clinical Research Center for Geriatric DiseaseInstitute of GeriatricsChinese PLA General Hospital and Chinese PLA Medical AcademyBeijing 100853China Department of Neurosurgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Neurology Union HospitalHuazhong University of Science and TechnologyWuhan 430022China Department of Biology Boston UniversityBostonMA 02215USA Center for Stem Cell and Organoid Medicine(CuSTOM) Division of Developmental BiologyCincinnati Children’s Hospital Medical CenterCincinnatiOH 45229USA

Sporadic or late-onset Alzheimer’s disease(LOAD)accounts for more than 95%of Alzheimer’s disease(AD)cases without any family history.Although genome-wide association studies have identified associated risk genes and loci for LOAD,numerous studies suggest that many adverse environmental factors,such as social isolation,are associated with an increased risk of dementia.However,the underlying mechanisms of social isolation in AD progression remain elusive.In the current study,we found that 7 days of social isolation could trigger pattern separation impairments and presynaptic abnormalities of the mossy fibre-CA3 circuit in AD mice.We also revealed that social isolation disrupted histone acetylation and resulted in the downregulation of 2 dentate gyrus(DG)-enriched miRNAs,which simultaneously target reticulon 3(RTN3),an endoplasmic reticulum protein that aggregates in presynaptic regions to disturb the formation of functional mossy fibre boutons(MFBs)by recruiting multiple mitochondrial and vesicle-related proteins.Interestingly,the aggregation of RTN3 also recruits the PP2A B subunits to suppress PP2A activity and induce tau hyperphosphorylation,which,in turn,further elevates RTN3 and forms a vicious cycle.Finally,using an artificial intelligence-assisted molecular docking approach,we determined that senktide,a selective agonist of neurokinin3 receptors(NK3R),could reduce the binding of RTN3 with its partners.Moreover,application of senktide in vivo effectively restored DG circuit disorders in socially isolated AD mice.Taken together,our findings not only demonstrate the epigenetic regulatory mechanism underlying mossy fibre synaptic disorders orchestrated by social isolation and tau pathology but also reveal a novel potential therapeutic strategy for AD.

关键词： Alzheimer’s disease memory impairment synaptic disorder tau pathology

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Removal of Cr(Ⅵ)by glutaraldehyde-crosslinked chitosan encapsulating microscale zero-valent iron:Synthesis,mechanism,and longevity

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Journal of Environmental Sciences 2024年第8期142卷 115-128页

作者： Yijun Duan fang liu Xiang liu Miao Li School of Environment Tsinghua UniversityBeijing 100084China Transportation Institute of Inner Mongolia University Hohhot 010070China

Microscale zero-valent iron(mZVI)has shown great potential for groundwater Cr(Ⅵ)remediation.However,low Cr(Ⅵ)removal capacity caused by passivation restricted the wide use of mZVI.We prepared mZVI/GCS by encapsulating mZVI in a porous glutaraldehydecrosslinked chitosan matrix,and the formation of the passivation layer was alleviated by reducing the contact between zero-valent iron particles.The average pore diameter of mZVI/GCS was 8.775 nm,which confirmed the mesoporous characteristic of this material.Results of batch experiments demonstrated that mZVI/GCS exhibited high Cr(Ⅵ)removal efficiency in a wide range of pH(2-10)and temperature(5-35℃).Common groundwater coexisting ions slightly affected m ZVI/GCS.The material showed great reusability,and the average Cr(Ⅵ)removal efficiency was 90.41%during eight cycles.In this study,we also conducted kinetics and isotherms analysis.Pseudo-second-order model was the most matched kinetics model.The Cr(Ⅵ)adsorption process was fitted by both Langmuir and Freundlich isotherms models,and the maximum Langmuir adsorption capacity of m ZVI/GCS reached243.63 mg/g,which is higher than the adsorption capacities of materials reported in most of the previous studies.Notably,the column capacity for Cr(Ⅵ)removal of a mZVI/GCS-packed column was 6.4 times higher than that of a mZVI-packed column in a 50-day experiment.Therefore,mZVI/GCS with a porous structure effectively relieved passivation problems of mZVI and showed practical application prospects as groundwater Cr(Ⅵ)remediation material with practical application prospects.

关键词： Chitosan Glutaraldehyde mZVI Cr(Ⅵ) Groundwater

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Chronic administration of triclosan leads to liver fibrosis through hepcidin-ferroportin axis-mediated iron overload

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Journal of Environmental Sciences 2024年第3期137卷 144-154页

作者： Jing liu Lecong Zhang fang Xu Ping Zhang Yang Song College of Eco-Environmental Engineering Guizhou Minzu UniversityGuiyang 550025China The Institute of Karst Wetland Ecology Guizhou Minzu UniversityGuiyang 550025China State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China

Triclosan(TCS)has been manufactured as an antibacterial compound for half a century.Currently,it is widely used in various personal care products;however,its potential adverse effects raise a lot of attention.Here,we create a long-term oral administration mouse model and identify the corresponding hepatotoxicity of TCS.We discover that daily intragastric administration of 10 mg/kg TCS to mice for 12 weeks results in severe hepatic fibrosis.Further study displays that hepatic iron increased 18%,23%and 29%upon oral TCS treatment for4,8 and 12 weeks,respectively.Accompanied by hepatic iron variation,splenic and duodenal iron are increased,which indicates systemic iron disorder.Not only excessive iron accumulated in the liver,abnormal hepatic malondialdehyde,prostaglandin synthase 2 and glutathione peroxidase 4 are pointed to ferroptosis.Additional study uncovers that hepcidin expression increases 7%,10%,4%in serum and 2.4-,4.8-,and 2.3-fold on transcriptional levels upon TCS exposure for 4,8 and 12 weeks,individually.Taken together,the mice in the TCS-treated group show disordered systemic iron homeostasis via the upregulated hepatic hepcidin-ferroportin axis.Meanwhile,both hepatic iron overload(systemic level)and hepatocyte ferroptosis(cellular level)are accused of TCS-induced liver fibrosis.Ferriprox■,an iron scavenger,significantly ameliorates TCS-induced liver fibrosis.In summary,this study confirms the impact of TCS on liver fibrosis;a critical signal pathway is also displayed.The significance of the current study is to prompt us to reevaluate the“pros and cons”of TCS applications.

关键词： Triclosan Iron metabolism Hepcidin Hepatotoxicity Liver fibrosis

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Exploring battery material failure mechanisms through synchrotron X-ray characterization techniques

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Journal of Energy Chemistry 2024年第7期94卷 128-135页

作者： Lingzhe fang Xiaozhao liu Tao Li Department of Chemistry and Biochemistry Northern Ilinois UniversityDeKalbIL 60115USA X-ray Science Division and Joint Center forEnergy Storage Research Argonne National LaboratoryLemontIL6439UA

Rechargeable battery cycling performance and related safety have been persistent concerns.It is crucial to decipher the capacity fading induced by electrode material failure via a range of techniques.Among these,synchrotron-based X-ray techniques with high flux and brightness play a key role in understanding degradation mechanisms.In this comprehensive review,we summarize recent advancements in degra-dation modes and mechanisms that were revealed by synchrotron X-ray methodologies.Subsequently,an overview of X-ray absorption spectroscopy and X-ray scattering techniques is introduced for charac-terizing failure phenomena at local coordination atomic environment and long-range order crystal struc-ture scale,respectively.At last,we envision the future of exploring material failure mechanism.

关键词： Battery failure Synchrotron-based techniques X-ray scattering X-ray absorption spectroscopy

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Thermo-hydro-mechanical (THM) coupled simulation of the land subsidence due to aquifer thermal energy storage (ATES) system in soft soils

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第6期16卷 1952-1966页

作者： Yang Wang Fengshou Zhang fang liu Department of Geotechnical Engineering College of Civil EngineeringTongji UniversityShanghai200092China Key Laboratory of Geotechnical and Underground Engineering of Ministry of Education Tongji UniversityShanghai200092China Shanghai Engineering and Technology Research Center of Shallow Geothermal Energy Shanghai200072China

Aquifer thermal energy storage(ATES)system has received attention for heating or cooling buildings.However,it is well known that land subsidence becomes a major environmental concern for ATES projects.Yet,the effect of temperature on land subsidence has received practically no attention in the past.This paper presents a thermo-hydro-mechanical(THM)coupled numerical study on an ATES system in Shanghai,China.Four water wells were installed for seasonal heating and cooling of an agriculture greenhouse.The target aquifer at a depth of 74e104.5 m consisted of alternating layers of sand and silty sand and was covered with clay.Groundwater level,temperature,and land subsidence data from 2015 to 2017 were collected using field monitoring instruments.Constrained by data,we constructed a field scale three-dimensional(3D)model using TOUGH(Transport of Unsaturated Groundwater and Heat)and FLAC3D(Fast Lagrangian Analysis of Continua)equipped with a thermo-elastoplastic constitutive model.The effectiveness of the numerical model was validated by field data.The model was used to reproduce groundwater flow,heat transfer,and mechanical responses in porous media over three years and capture the thermo-and pressure-induced land subsidence.The results show that the maximum thermoinduced land subsidence accounts for about 60%of the total subsidence.The thermo-induced subsidence is slightly greater in winter than that in summer,and more pronounced near the cold well area than the hot well area.This study provides some valuable guidelines for controlling land subsidence caused by ATES systems installed in soft soils.

关键词： Aquifer thermal energy storage(ATES) Land subsidence TOUGH-FLAC3D Thermo-elastoplastic constitutive model

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Capturability-based Fuzzy Footstep Planner for a Biped Robot with Centroidal Compliance

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Journal of Bionic Engineering 2024年第1期21卷 84-100页

作者： Zihan Xu Qin fang Yong Ren Chengju liu Robot and Artificial Intelligence Lab(RAIL) College of Electronic and Information EngineeringTongji UniversityShanghai 201804China Applied Technology College Soochow UniversitySuzhou 215000China

Compliance motion and footstep adjustment are active balance control strategies from learning human subconscious behaviors.The force estimation without direct end-actuator force measurement and the optimal footsteps based on complex analytical calculation are still challenging tasks for elementary and kid-size position-controlled robots.In this paper,an online compliant controller with Gravity Projection Observer(GPO),which can express the external force condition of perturbations by the estimated Projection of Gravity(PoG)with estimation covariance,is proposed for the realization of disturbance absorption,with which the robustness of the humanoid contact with environments can be maintained.The fuzzy footstep planner based on capturability analysis is proposed,and the Model Predictive Control(MPC)is applied to generate the desired steps.The fuzzification rules are well-designed and give the corresponding control output responding to complex and changeable external disturbances.To validate the presented methods,a series of experiments on a real humanoid robot are conducted.The results verify the effectiveness of the proposed balance control framework.

关键词： Biped walking Centroidal compliance Gravity projection observer Fuzzy footstep planner

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Constitutive modelling of concrete material subjected to low-velocity projectile impact:insights into damage mechanism and target resistance

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2024年第2期25卷 161-182页

作者： Shen liu Xieping HUANG Xiangzhen KONG Qin fang Center for Hypergravity Experiment and Interdisciplinary Research Zhejiang UniversityHangzhou310058China Institute of Geotechnical Engineering Zhejiang UniversityHangzhou310058China State Key Laboratory of Disaster Prevention&Mitigation of Explosion&Impact Army Engineering University of PLANanjing210007China

This paper presents a numerical study to improve the understanding of the complex subject of penetration and perforation of concrete targets impacted by low-velocity projectiles.The main focus is on the damage mechanisms and the major factors that account for the target resistance of the concrete.An improved continuous surface cap model recently proposed was employed.The model was first equipped with element erosion criteria and was adequately validated by comparisons with ballistic experiments.Comprehensive numerical simulations were carried out where the individual influence of tensile,shear,and volumetric behaviors(pore collapse)of a concrete target on its ballistic performance was investigated.Results demonstrated that cratering on the front face and scabbing on the rear face of the concrete target were mainly dominated by its tensile behavior.The major target resistance came from the second tunneling stage which was primarily governed by the shear and volumetric behaviors of the concrete.Particularly,this study captured the pore collapse-induced damage phenomenon during the high-pressure tunneling stage,which has been extensively reported in experiments but has usually been neglected in previous numerical investigations.

关键词： Penetration Perforation Damage mechanism Target resistance Projectile impact Pore collapse

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Modelling analysis embodies drastic transition among global potential natural vegetations in face of changing climate

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Forest Ecosystems 2024年第2期11卷 184-192页

作者： Zhengchao Ren Lei liu fang Yin Xiaoni liu School of Earth Science and Resources Chang’an UniversityXi’an710054China Research Center of Ecological Construction and Environmental Conservation in Gansu Province Gansu Agricultural UniversityLanzhou730070China State Key Laboratory of Tibetan Plateau Earth System Environment and Resources(TPESER)Institute of Tibetan Plateau ResearchChinese Academy of SciencesBeijing100101China School of Land Engineering Chang’an UniversityXi’an710054China College of Pratacultural Science Gansu Agricultural UniversityLanzhou730070China

Potential natural vegetation(PNV)is a valuable reference for ecosystem renovation and has garnered increasing attention worldwide.However,there is limited knowledge on the spatio-temporal distributions,transitional processes,and underlying mechanisms of global natural vegetation,particularly in the case of ongoing climate warming.In this study,we visualize the spatio-temporal pattern and inter-transition procedure of global PNV,analyse the shifting distances and directions of global PNV under the influence of climatic disturbance,and explore the mechanisms of global PNV in response to temperature and precipitation fluctuations.To achieve this,we utilize meteorological data,mainly temperature and precipitation,from six phases:the Last Inter-Glacial(LIG),the Last Glacial Maximum(LGM),the Mid Holocene(MH),the Present Day(PD),2030(20212040)and 2090(2081–2100),and employ a widely-accepted comprehensive and sequential classification sy–stem(CSCS)for global PNV classification.We find that the spatial patterns of five PNV groups(forest,shrubland,savanna,grassland and tundra)generally align with their respective ecotopes,although their distributions have shifted due to fluctuating temperature and precipitation.Notably,we observe an unexpected transition between tundra and savanna despite their geographical distance.The shifts in distance and direction of five PNV groups are mainly driven by temperature and precipitation,although there is heterogeneity among these shifts for each group.Indeed,the heterogeneity observed among different global PNV groups suggests that they may possess varying capacities to adjust to and withstand the impacts of changing climate.The spatio-temporal distributions,mutual transitions and shift tendencies of global PNV and its underlying mechanism in face of changing climate,as revealed in this study,can significantly contribute to the development of strategies for mitigating warming and promoting re-vegetation in degraded regions worldwide.

关键词： Potential natural vegetation Global warming Vegetation classification Predicted model CSCS

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Optoelectronic Synapses Based on MXene/Violet Phosphorus van der Waals Heterojunctions for Visual‑Olfactory Crossmodal Perception

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Nano-Micro Letters 2024年第6期16卷 38-52页

作者： Hailong Ma Huajing fang Xinxing Xie Yanming liu He Tian Yang Chai Center for Advancing Materials Performance From the Nanoscale(CAMP‑Nano) State Key Laboratory for Mechanical Behavior of MaterialsXi’an Jiaotong UniversityXi’an 710049People’s Republic of China Institute of Microelectronics and Beijing National Research Center for Information Science and Technology(BNRist) Tsinghua UniversityBeijing 100084People’s Republic of China Department of Applied Physics The Hong Kong Polytechnic UniversityHong KongPeople’s Republic of China

The crossmodal interaction of different senses,which is an important basis for learning and memory in the human brain,is highly desired to be mimicked at the device level for developing neuromorphic crossmodal perception,but related researches are scarce.Here,we demonstrate an optoelectronic synapse for vision-olfactory crossmodal perception based on MXene/violet phosphorus(VP)van der Waals heterojunctions.Benefiting from the efficient separation and transport of photogenerated carriers facilitated by conductive MXene,the photoelectric responsivity of VP is dramatically enhanced by 7 orders of magnitude,reaching up to 7.7 A W^(−1).Excited by ultraviolet light,multiple synaptic functions,including excitatory postsynaptic currents,pairedpulse facilitation,short/long-term plasticity and“learning-experience”behavior,were demonstrated with a low power consumption.Furthermore,the proposed optoelectronic synapse exhibits distinct synaptic behaviors in different gas environments,enabling it to simulate the interaction of visual and olfactory information for crossmodal perception.This work demonstrates the great potential of VP in optoelectronics and provides a promising platform for applications such as virtual reality and neurorobotics.

关键词： Violet phosphorus MXene Van der Waals heterojunctions Optoelectronic synapses Crossmodal perception

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Plant gene co-expression defines the biosynthetic pathway of neuroactive alkaloids

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Molecular Plant 2024年第3期17卷 372-374页

作者： fang liu' Alisdair R.Fernie Youjun Zhang Key Laboratory of Seed Innovation Institute of Genetics and Developmental BiologyChinese Academy of Sciences100101 BeijingChina Max Planck Institute of Molecular Plant Physiology Am Muhlenberg 114476 Potsdam-GolmGermany Center for Plant Systems Biology and Biotechnology 4000 PlovdivBulgaria University of Chinese Academy of Sciences 100049 BeijingChina

Transcriptomes comprise gene co-expression clustersor modules,showcasing distinct patterns of coordinated expression among groups of genes across independent biological samples(Serin et al.,2016).The"guilt-by-association"hypothesis suggests the functional importance of these clusters;for example,co-expressed genes associated with metabolism typically contain genes encoding several enzymes associated with the same pathways.

关键词： metabolism alkaloids

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