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Targeting epigenetic mechanisms in amyloid-β-mediated Alzheimer’s pathophysiology:unveiling therapeutic potential

Neural Regeneration Research 2025年第1期20卷 54-66页

作者： Jennie z.li Nagendran Ramalingam Shaomin li Ann Romney Center for Neurologic Diseases Brigham and Women’s Hospital and Harvard Medical SchoolBostonMAUSA

Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to *** evidence suggests that Alzheimer’s disease is associated with accumulating various amyloid-βoligomers in the brain,influenced by complex genetic and environmental *** memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer’s disease are believed to primarily result from synaptic *** life,environmental factors can lead to enduring changes in gene expression and the emergence of brain *** changes,known as epigenetic modifications,also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal *** this context,we highlight recent advances in understanding the roles played by key components of the epigenetic machinery,specifically DNA methylation,histone modification,and microRNAs,in the development of Alzheimer’s disease,synaptic function,and activity-dependent synaptic ***,we explore various strategies,including enriched environments,exposure to non-invasive brain stimulation,and the use of pharmacological agents,aimed at improving synaptic function and enhancing long-term potentiation,a process integral to epigenetic ***,we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer’s *** suggest that addressing Alzheimer’s disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.

关键词： Alzheimer’s disease DNA methylation enriched environments histone modification microRNAs non-invasive brain stimulation synaptic plasticity

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Optical redox imaging of ANT1-de-cient muscles

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Journal of Innovative Optical Health Sciences 2024年第1期17卷 135-140页

作者： He N.Xu Ryan M.Morrow Min Feng Huaqing zhao Douglas Wallace lin z.li Britton Chance Laboratory of Redox Imaging Department of Radiology Perelman School of Medicine University of Pennsylvania PhiladelphiaPA 19104USA Center for Mitochondrial and Epigenomic Medicine Children's Hospital of Philadelphia Research Institute Philadelphia PA 19104USA Center for Biostatistics and Epidemiology Lewis Katz School of Medicine at Temple University Philadelphia PA 19140USA

Adenine nucleotide translocator(ANT)is a mitochondrial protein involved in the exchange of ADP and ATP across the mitochondrial inner *** plays a crucial role in cellular energy metabolism by facilitating the transport of ATP synthesized within the mitochondria to the *** isoform ANT1 predominately expresses in cardiac and skeletal *** or dysregulation in ANT1 have been implicated in various mitochondrial disorders and neuromuscular *** aimed to examine whether ANT1 deletion may affect mitochondrial redox state in our established ANT1-de-cient *** and quadriceps resected from age-matched wild type(WT)and ANT1-de-cient mice were snap-frozen in liquid *** Chance redox scanner was utilized to perform 3D optical redox *** sample underwent scanning across 3–5 *** averaging analysis showed no signi-cant differences in the redox indices(NADH,flavin adenine dinucleotide containing-flavoproteins Fp,and the redox ratio Fp/(NADH+Fp)between WT and ANT1-de-cient ***,quadriceps had higher Fp than hearts in both groups(p¼0:0004 and 0.01,respectively).Furthermore,the quadriceps were also more oxidized(a higher redox ratio)than hearts in WT group(p¼0:004).NADH levels were similar in all *** data suggest that under non-stressful physical condition,the ANT1-de-cient muscle cells were in the same mitochondrial state as WT ones and that the signi-cant difference in the mitochondrial redox state between quadriceps and hearts found in WT might be diminished in ANT1-de-cient *** imaging of muscles under physical stress can be conducted in future.

关键词： ANT1 redox ratio flavoproteins

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Diverse strategic approaches en route to Taxol total synthesis

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Chinese Chemical Letters 2022年第12期33卷 4957-4968页

作者： zexian li Jianfeng zheng Wei-Dong z.li Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China

Taxol is one of the most famous diterpenoid natural products used in clinical cancer *** and its analogues are popular synthetic targets and have attracted worldwide attention over the past *** research efforts have already been made and ten groups have achieved the total synthesis of Taxol since *** mini-review summarized the recent highlights of divergent strategic approaches towards the chemical synthesis of Taxol's carbocyclic framework bearing a bridged eight-membered ring.

关键词： Taxol Total synthesis Biomimetic synthesis linear strategy Convergent strategy

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Preface: machine-learning approaches for computational mechanics

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Applied Mathematics and Mechanics(English Edition) 2023年第7期44卷 1035-1038页

作者： z.li Guohui HU zhiliang WANG G.E.KARNIADAKIS Department of Mechanical Engineering Clemson UniversityClemsonSouth Carolina 29634U.S.A. Shanghai Institute of Applied Mathematics and Mechanics School of Mechanics and Engineering ScienceShanghai UniversityShanghai 200072China Division of Applied Mathematics Brown UniversityProvidenceRhode Island 02912U.S.A.

Machine-learning(ML) approaches have gained significant attention in recent years for their potential to revolutionize various scientific research fields,including computational mechanics,materials science,and biomedical *** the field of computational mechanics,various neural network models such as feedforward neural networks,convolutional neural networks.

关键词： neural networks engineering

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cardiGAN:A generative adversarial network model for design and discovery of multi principal element alloys

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Journal of Materials Science & Technology 2022年第30期125卷 81-96页

作者： z.li W.T.Nash S.P.O’Brien Y.Qiu R.K.Gupta N.Birbilis College of Engineering and Computer Science The Australian National UniversityA.C.T.Acton 2601Australia Department of Materials Science and Engineering Monash UniversityClaytonVictoria 3800Australia Department of Materials Science and Engineering North Carolina State UniversityRaleighNC 27695USA

Multi-principal element alloys(MPEAs),inclusive of high entropy alloys(HEAs),continue to attract significant research attention owing to their potentially desirable *** MPEAs remain under extensive research,traditional(***)alloy production and testing are both costly and timeconsuming,partly due to the inefficiency of the early discovery process which involves experiments on a large number of alloy *** is intuitive to apply machine learning in the discovery of this novel class of materials,of which only a small number of potential alloys have been probed to *** this work,a proof-of-concept is proposed,combining generative adversarial networks(GANs)with discriminative neural networks(NNs),to accelerate the exploration of novel *** applying the GAN model herein,it was possible to directly generate novel compositions for MPEAs,and to predict their *** verify the predictability of the model,alloys designed by the model are presented and a candidate produced-as *** suggests that the model herein offers an approach that can significantly enhance the capacity and efficiency of development of novel MPEAs.

关键词： Alloy design Machine learning Generative adversarial network Neural network Multi-principal element alloy High entropy alloys

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WORKING WITH AND LEARNING FROM BRIT

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Journal of Innovative Optical Health Sciences 2011年第4期4卷 479-482页

作者： liN z.li Molecular Imaging Lab Department of Radiology Britton Chance Lab of Redox Imaging Eldridge Reeves Johnson Research Foundation Department of Biochemistry and Biophysics Perelman School of MedicineUniversity of Pennsylvania PhiladelphiaPA 19014USA

I had been closely working with *** Chance from 2005-2010 on imaging mitochondrial redox state in cancer and stem cells.I had also learned much from him in daily work and personal *** I would like to share some of my memories and experiences including(1)Great science is not necessarily done with top-grade expensive instruments;(2)Brit was genuinely interested in and dedicated to science;(3)Brit's attention to detail and timely action;(4)Brit's open-mindedness;and(5)Brit being modest,appreciative,and caring for others.

关键词： Britton Chance mitochondria redox state cancer stem cell

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A data-driven approach to modeling high-density terminal areas：A scenario analysis of the new Beijing,China airspace

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Chinese Journal of Aeronautics 2017年第2期30卷 538-553页

作者： Max z.li Megan S.Ryerson Department of Electrical and Systems Engineering University of Pennsylvania Philadelphia PA 19104 USA Department of City and Regional Planning University of Pennsylvania Philadelphia PA 19104 USA

Airports are being developed and expanded rapidly in China to accommodate and promote a growing aviation *** future Beijing Daxing International Airport（DAX） will serve as the central airport of the JingJinJi megaregion,knitting the Beijing,Tianjin,and Hebei regions *** will be a busy airport from its inception,relieving congestion and accommodating growth from Beijing Capital International Airport（PEK）,currently the second busiest airport in the world in passengers *** aim to model terminal airspace designs and possible conflicts in the future Beijing Multi-Airport System（MAS）.We investigate standard arrival procedures and mathematically model current and future arrival trajectories into PEK and DAX by collecting large quantities of publicly available track data from historical arrivals operating within the Beijing terminal *** find that（1） trajectory models constructed from real data capture aberrations and deviations from standard arrival procedures,validating the need to incorporate data on historical trajectories with standard procedures when evaluating the airspace and（2） given all existing constraints,DAX may be restricted to using north and east arrival flows,constraining the capacity required to handle the increases in air traffic demand to *** results indicate that the terminal airspace above Beijing,and the future JingJinJi region,requires careful consideration if the full capacity benefits of the two major airports are to be realized.

关键词： Air traffic management Beijing airspace Multi-airport system Trajectory modeling Terminal airspace

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An Intelligent Harmonic Synthesis Technique for Air-Gap Eccentricity Fault Diagnosis in Induction Motors

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Chinese Journal of Mechanical Engineering 2017年第6期30卷 1296-1304页

作者： De z.li Wilson Wang Fathy Ismail Department of Mechanical Engineering Lakehead University Department of Mechanical & Mechatronics Engineering University of Waterloo

Induction motors （IMs） are commonly used in various industrial applications. To improve energy con- sumption efficiency, a reliable IM health condition moni- toring system is very useful to detect IM fault at its earliest stage to prevent operation degradation, and malfunction of IMs. An intelligent harmonic synthesis technique is pro- posed in this work to conduct incipient air-gap eccentricity fault detection in IMs. The fault harmonic series are syn- thesized to enhance fault features. Fault related local spectra are processed to derive fault indicators for IM air- gap eccentricity diagnosis. The effectiveness of the pro- posed harmonic synthesis technique is examined experi- mentally by IMs with static air-gap eccentricity and dynamic air-gap eccentricity states under different load conditions. Test results show that the developed harmonic synthesis technique can extract fault features effectively for initial IM air-gap eccentricity fault detection.

关键词： Air-gap eccentricity Current signal Faultdetection Induction motor

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EFFECTS OF TEST TEMPERATURE AND STRAIN RATE ON THE MECHANICAL PROPERTIES IN AN INTERCRITICALLYHEAT-TREATED BAINITE-TRANSFORMED STEEL

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Acta Metallurgica Sinica(English Letters) 2004年第6期17卷 840-848页

作者： z.li D.Wu TheStateKeyLaboratoryofRollingandAutomation NortheasternUniversityShenyang110004China／／InstituteofAeronauticalEngineeringShenyangl10034China TheStateKeyLaboratoryofRollingandAutomation NortheasternUniversityShenyang110004China

Larger amount of austenite could be retained in an intercritically heat-treated bainite- transformed steel. The elongation and the strength-ductility balance of the steel could be enhanced considerably due to strain-induced martensite transformation and transformation- induced plasticity (TRIP) of retained austenite. The effects of test temperature and strain rate on the mechanical properties and strain induced transformation behavior of retained austenite in the steel were investigated. Total elongation and strength-ductility balance of the specimen reached maximum when it strained at a strain rate of 2.8×10-4s-1 and at 350℃. The relation between test temperature and tensile properties showed the same tendency at three kinds of strain rates. Flow stress increased considerably with decreasing the strain rate.

关键词： strain rate mechanical property strain-induced transformation trans- formation-induced plasticity (TRIP)

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Unexpected Grob-type fragmentation of vinylogous β-silyloxy-cyclobutanone into γ-lactone

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Chinese Chemical Letters 2017年第5期28卷 968-970页

作者： Xiang Wu Wei-Dong z.li School of Chemistry and Chemical Engineering Hefei University of Technology Innovative Drug Research Centre Chongqing University

An unusual formal oxy transposition of vinylogous β-silyloxy-cyclobutanone 1（a 1,5-difunctionalized substrate） under mild acidic conditions（aqueous HF in CH3CN at 0℃） to the decalinic y-lactone 2 was described.A... 详细信息

关键词： Grob fragmentation Vinylogous β-silyloxy-cyclobutanone Decalinic γ-lactone Oxy transposition Intramolecular γ-lactonization

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