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Targeting tau in Alzheimer's disease:from mechanisms to clinical therapy

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Neural Regeneration Research 2024年第7期19卷 1489-1498页

作者： Jinwang ye Huali Wan Sihua Chen Gong-ping Liu Shenzhen Key Laboratory of Marine Biotechnology and Ecology College of Life Sciences and OceanographyShenzhen UniversityShenzhenGuangdong ProvinceChina Department of Laboratory Medicine Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina Co-innovation Center of Neurodegeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Pathophysiology School of Basic Medicine and the Collaborative Innovation Center for Brain ScienceKey Laboratory of Ministry of Education of China and Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Alzheimer’s disease is the most prevalent neurodegenerative disease affecting older *** features of Alzheimer’s disease include extra cellular aggregation of amyloid-βplaques and the accumulation of neurofibrillary tangles,fo rmed by tau protein,in the *** there are amyloid-β-ta rgeting therapies for the treatment of Alzheimer’s disease,these therapies are costly and exhibit potential negative side *** evidence suggests significant involvement of tau protein in Alzheimer’s disease-related *** an important microtubule-associated protein,tau plays an important role in maintaining the stability of neuronal microtubules and promoting axonal *** fact,clinical studies have shown that abnormal phosphorylation of tau protein occurs before accumulation of amyloid-βin the *** therapeutic strategies targeting tau protein have begun to emerge,and are considered possible methods to prevent and treat Alzheimer’s ***,abnormalities in post-translational modifications of the tau protein,including aberrant phosphorylation,ubiquitination,small ubiquitin-like modifier(SUMO)ylation,acetylation,and truncation,contribute to its microtubule dissociation,misfolding,and subcellular *** causes mitochondrial damage,synaptic impairments,gliosis,and neuroinflammation,eventually leading to neurodegeneration and cognitive *** review summarizes the recent findings on the underlying mechanisms of tau protein in the onset and progression of Alzheimer’s disease and discusses tau-targeted treatment of Alzheimer’s disease.

关键词： acetylation Alzheimer’s disease cognitive deficits gliosis mitochondria damage neuroinflammation phosphorylation synaptic impairments tau tau immunotherapy

Designing Bioorthogonal Reactions for Biomedical Applications

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Research 2024年第3期2023卷 625-650页

作者： Qingfei Zhang Gaizhen Kuang Li Wang ping Duan Weijian Sun Fangfu ye Wenzhou Institute University of Chinese Academy of SciencesWenzhou 325001China Beijing National Laboratory for Condensed Matter Physics Institute of PhysicsChinese Academy of SciencesBeijing 100190China. Department of Obstetrics and Gynecology The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325027China. Department of Gastrointestinal Surgery The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou325027China.

Bioorthogonal reactions are a class of chemical reactions that can be carried out in living organisms without interfering with other reactions, possessing high yield, high selectivity, and high efficiency. Since the first proposal of the conception by Professor Carolyn Bertozzi in 2.03, bioorthogonal chemistry has attracted great attention and has been quickly developed. As an important chemical biology tool, bioorthogonal reactions have been applied broadly in biomedicine, including bio-labeling, nucleic acid functionalization, drug discovery, drug activation, synthesis of antibody–drug conjugates, and proteolysis-targeting chimeras. Given this, we summarized the basic knowledge, development history, research status, and prospects of bioorthogonal reactions and their biomedical applications. The main purpose of this paper is to furnish an overview of the intriguing bioorthogonal reactions in a variety of biomedical applications and to provide guidance for the design of novel reactions to enrich bioorthogonal chemistry toolkits.

关键词： orthogonal summarized chemistry

Optical Transient Source AT2.2.lfa:A Possible“Dirty Fireball”

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Research in Astronomy and Astrophysics 2024年第4期24卷 124-133页

作者： Xue-Mei ye Da-Ming Wei Yi-Ming Zhu Zhi-ping Jin Key Laboratory of Dark Matter and Space Astronomy Purple Mountain ObservatoryChinese Academy of SciencesNanjing 210023China School of Astronomy and Space Science University of Science and Technology of ChinaHefei 230026China National Astronomical Observatories/Nanjing Institute of Astronomical Optics&Technology Chinese Academy of SciencesNanjing 210042China CAS Key Laboratory of Astronomical Optics&Technology Nanjing Institute of Astronomical Optics&TechnologyNanjing 210042China

AT2.2.lfa,also known as ZTF2.aayokph,was detected by the Zwicky Transient Facility on 2.2. May 4,a 05:34:48 ***-up observations were conducted using a range of ground-based optical telescopes,as wel as Swift/XRT and VLA ***2.2.lfa is classified as an“orphan afterglow”candidate due to its rapid flux decline and its reddened color(g-r=0.17±0.14 mag).For an optical transient source without promp gamma-ray detection,one key point is to determine its burst *** we measure the burst time through fitting the initial bump feature of AT2.2.lfa and obtain its burst time as 2.2. May 3,at 2.:09:50 *** afterglowpy,we model the multi-band afterglow of AT2.2.lfa and find that the standard model canno reproduce the late radio observations *** that the microphysical parameters ε_(e),ε_(B)(the energy fraction given to electrons and magnetic field),andξN(the fraction of accelerated electrons)may vary with time we then model the afterglow of AT2.2.lfa taking into account the temporal evolution of the physical parameters ε_(e),ε^(B),and ξ_(N) and find in this case the multi-wavelength observations can be reproduced *** initial Lorentz factor of AT2.2.lfa can be estimated from the peak time of the early afterglow,which yields a value of about 18 suggesting that AT2.2.lfa should be classified as a“dirty fireball.”From the upper limit for the prompt emission energy of AT2.2.lfa,we obtain that the radiation efficiency is less than 0.02.,which is much smaller than that of ordinary gamma-ray bursts(GRBs).It is also interesting that the fitted values of jet angle and viewing angle are very large,θ_(c)~0.66 rad,θ_(v)~0.53 rad,which may lead to the low Lorentz factor and radiation *** compared with GRB afterglow samples,it is evident that the onset bump timescale of AT2.2.lfa satisfies the empirical relationships observed in GRB ***,the luminosity of AT2.2.lfa falls within the range of observations for GRB samples;howeve

关键词： gamma-rays:ISM methods:numerical radiation mechanisms:non-thermal

Double casing warhead with sandwiched charge:The axial distribution of fragments velocities

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Defence Technology（防务技术） 2024年第4期34卷 201-216页

作者： ping ye Yongxiang Dong Qitian Sun Peizhuo Shi Wang Yao Yongnan Li Yujing Li Mingze Li State Key Laboratory of Explosion Science and Technology Beijing Institute of TechnologyBeijing 100081China

The double casing warhead with sandwiched charge is a novel fragmentation warhead that can produce two groups of fragments with different velocity,and the previous work has presented a calculation formula to determine the maximum fragment *** current work builds on the published formula to further develop a formula for calculating the axial distribution characteristics of the fragment *** this type of warhead,the simulation of the dispersion characteristics of the detonation products at different positions shows that the detonation products at the ends have a much larger axial velocity than those in the middle,and the detonation products have a greater axial dispersion velocity when they are closer to the central *** loading process and the fragment velocity vary with the axial position for both casing layers,and the total velocity of the fragments is the vector sum of the radial velocity and the axial *** the same axial position,the acceleration time of the inner casing is greater than that of the outer *** the same casing,the fragments generated at the ends have a longer acceleration time than the fragments from the *** proposed formula is validated with the X-ray radiography results of the four warheads previously tested experimentally and the 3D smoothedparticle hydrodynamics numerical simulation results of several series of new warheads with different *** formula can accurately and reliably calculate the fragment velocity when the lengthto-diameter ratio of the charge is greater than 1.5 and the thickness of the casing is less than 2.%its inner *** work thus provides a key reference for the theoretical analysis and the design of warheads with multiple casings.

关键词： Double casing warhead Sandwiched charge Fragment velocity Rarefaction wave Gurney formula Explosive loading

Clinical study of different prediction models in predicting diabetic nephropathy in patients with type 2.diabetes mellitus

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World Journal of Diabetes 2024年第1期15卷 43-52页

作者： Sha-Sha Cai Teng-ye Zheng Kang-Yao Wang Hui-ping Zhu Department of Nephrology The First People’s Hospital of WenlingWenling 317500Zhejiang ProvinceChina

BACKGROUND Among older adults,type 2.diabetes mellitus(T2.M)is widely recognized as one of the most prevalent *** nephropathy(DN)is a frequent com-plication of DM,mainly characterized by renal microvascular *** detection,aggressive prevention,and cure of DN are key to improving *** a diagnostic and predictive model for DN is crucial in auxiliary *** To investigate the factors that impact T2.M complicated with DN and utilize this information to develop a predictive *** The clinical data of 2.0 patients diagnosed with T2.M and admitted to the First People’s Hospital of Wenling between August 2.19 and August 2.2. were retrospectively *** to whether the patients had DN,they were divided into the DN group(complicated with DN)and the non-DN group(without DN).Multivariate logistic regression analysis was used to explore factors affecting DN in patients with *** data were randomly split into a training set(n=147)and a test set(n=63)in a 7:3 ratio using a random *** training set was used to construct the nomogram,decision tree,and random forest models,and the test set was used to evaluate the prediction performance of the model by comparing the sensitivity,specificity,accuracy,recall,precision,and area under the receiver operating characteristic *** Among the 2.0 patients with T2.M,74(35.34%)had *** validation dataset showed that the accuracies of the nomogram,decision tree,and random forest models in predicting DN in patients with T2.M were 0.746,0.714,and 0.730,*** sensitivities were 0.710,0.710,and 0.806,respectively;the specificities were 0.844,0.875,and 0.844,respectively;the area under the receiver operating characteristic curve(AUC)of the patients were 0.811,0.735,and 0.850,*** Delong test results revealed that the AUC values of the decision tree model were lower than those of the random forest and nomogram models(P<0.05),whereas the differ

关键词： Type 2.diabetes mellitus Diabetic nephropathy Random forest Decision-making tree Nomogram Forecast

Enhanced electrochemical performance of nanoscale single crystal NMC811 modification by coating LiNbO_(3)

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Chinese Chemical Letters 2024年第5期35卷 514-518页

作者： Fengyu Zhang Yali Liang Zhangran ye Lei Deng Yunna Guo ping Qiu Peng Jia Qiaobao Zhang Liqiang Zhang Clean Nano Energy Center State Key Laboratory of Metastable Materials Science and Technology Yanshan UniversityQinhuangdao 066004China School of New Energy and Materials China University of Petroleum BeijingBeijing 102249China Hebei Key Laboratory of Applied Chemistry College of Environmental and Chemical EngineeringYanshan UniversityQinhuangdao 066004China State Key Laboratory of Physical Chemistry of Solid Surfaces College of MaterialsXiamen UniversityXiamen 361005China

Single crystallization is an important strategy to resolve intergranular cracks and unnecessary side reactions with electrolytes in layered transition metal oxide cathodes LiNi_(0.8)Mn_(0.1)Co_(0.1)O_(2.(NMC811).Due to the limitations of high-temperature sintering and multi-step calcination,single crystal NMC811 generally shows irregular particles with a size of 2.3μ***,the prolonged Li-ion diffusion pathway and the stress generated by the uneven de-/intercalation sluggish Li-ion diffusion kinetics,what is more,cause structural damage such as intragranular cracks.A slow Li extraction rate or particle size reduction will ameliorate the structural damage and improve the cycling *** the most promising cathodes for next-generation power batteries,NMC811 required fast charge performance and cycle *** size reduction appears to be the displacement *** is an effective strategy to mitigate intragranular cracks of single crystal ***,the serious aggregation and increased specific surface area become new *** this article,we synthesized monodisperse nanoscale single crystal NMC811 by molten salt method and modified the surface by LiNbO3 *** electrochemical performance shows that nanoscale single crystal NMC811 has faster kinetic and higher capacity retention,so the strategy of combining nanonization and surface coating is an alternative way to prepare high specific capacity and cycle stable single crystal NMC811.

关键词： Ni-rich NMC811 Molten salt method Nanonization Surface coating Micron cracks

High-resolution single-photon LiDAR without range ambiguity using hybrid-mode imaging [Invited]

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Chinese Optics Letters 2024年第6期22卷 33-37页

作者： Xin-Wei Kong Wen-Long ye Wenwen Li Zheng-ping Li Feihu Xu Hefei National Research Center for Physical Sciences at the Microscale and School of Physical Sciences University of Science and Technology of ChinaHefei 230026China Shanghai Research Center for Quantum Science and CAS Center for Excellence in Quantum Information and Quantum Physics University of Science and Technology of ChinaShanghai 201315China School of Mechanical Electrical and Information EngineeringShandong UniversityWeihai 264209China Hefei National Laboratory University of Science and Technology of ChinaHefei 230088China

We proposed a hybrid imaging scheme to estimate a high-resolution absolute depth map from low photon counts. It leverages measurements of photon arrival times from a single-photon LiDAR and an intensity image from a conventional high-resolution camera. Using a tailored fusion algorithm, we jointly processed the raw measurements from both sensors and output a high-resolution absolute depth map. We scaled up the resolution by a factor of 10, achieving 1300 × 2.11 pixels and extending ~4.7 times the unambiguous range. These results demonstrated the superior capability of long-range high-resolution 3D imaging without range ambiguity.

关键词： single-photon LiDAR single-photon imaging hybrid-mode imaging

The First Ground-based White Light Lunar Polarization Imaging:A New Kind of FeO Observation on the Near Side of the Moon

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Research in Astronomy and Astrophysics 2024年第6期24卷 1-6页

作者： Wei-Nan Wang Jin-Song ping Ming-Yuan Wang Wen-Zhao Zhang Han-Lin ye Xing-Wei Han Song-Feng Kou Changchun Observatory National Astronomical ObservatoriesChinese Academy of SciencesChangchun 130117China National Astronomical Observatories Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 101408China Astronomy Department Beijing Normal UniversityBeijing 100875China International Center for Climate and Environment Sciences Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China Nanjing Institute of Astronomical Optics and Technology Chinese Academy of SciencesNanjing 210042China

Lunar optical polarization is a fascinating phenomenon that occurs when sunlight reflects off the surface of the Moon and becomes *** study employs a novel split-focus plane polarimetric camera to conduct the initial white light polarimetric observations on the near side of the *** obtained the linear degree of polarization(DOP)parameters of white light by observation from the eastern and western hemispheres of the *** findings indicate that the white light polarization is lower in the lunar highland than in the lunar maria *** the analysis of lunar soil samples,we noticed and determined that the DOP parameters of white light demonstrate high consistency with iron oxide on the *** study may serve as a new diagnostic tool for the Moon.

关键词： techniques:photometric polarization methods:observational Moon

Impact of volcanism on the formation and hydrocarbon generation of organic-rich shale in the Jiyang Depression, Bohai Bay Basin, China

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Petroleum Science 2024年第3期21卷 1539-1551页

作者： Jia-Hong Gao Xin-ping Liang Zhi-Jun Jin Quan-You Liu Chang-Rong Li Xiao-Wei Huang Ju-ye Shi Peng Li State Key Laboratory of Shale Oil and Gas Enrichment Mechanisms and Efficient Development Institute of EnergyPeking University Petroleum Exploration and Production Research Institute SINOPECBeijing100871 China School of Energy Resources China University of Geosciences Beijing100083 China

Globally,most organic-rich shales are deposited with volcanic ash *** ash,a source for many sedimentary basins,can affect the sedimentary water environment,alter the primary productivity,and preserve the organic matter(OM)through physical,chemical,and biological *** an increasing number of breakthroughs in shale oil exploration in the Bohai Bay Basin in recent years,less attention has been paid to the crucial role of volcanic impact especially its influence on the OM enrichment and hydrocarbon ***,we studied the petrology,mineralogy,and geochemical characteristics of the organic-rich shale in the upper submember of the fourth member(Es_(4)^(1))and the lower submember of the third member(Es_(3)^(3))of the Shahejie Formation,aiming to better understand the volcanic impact on organic-rich shale *** results show that total organic carbon is higher in the upper shale intervals rich in volcanic ash with enriched light rare earth elements and moderate Eu *** indicates that volcanism promoted OM formation before or after the *** positive correlation between Eu/Eu*and Post-Archean Australian Shale indicates hydrothermal activity before the volcanic *** plane graph of the hydrocarbon-generating intensity(S1+S2.suggests that the heat released by volcanism promoted hydrocarbon ***,the nutrients carried by volcanic ash promoted biological blooms during Es_(4)^(1 )and Es_(3)^(3) deposition,yielding a high primary *** blooms consume large amounts of oxygen and form anoxic environments conducive to the burial and preservation of ***,this study helps to further understand the organic-inorganic interactions caused by typical geological events and provides a guide for the next step of shale oil exploration and development in other lacustrine basins in China.

关键词： Volcanic ash Hydrocarbon generation Organic-rich shale Shahejie Formation Jiyang Depression