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Neural Regeneration Research 2023年第4期18卷 779-783页

作者： chia-wei huang Nicholas C.Rust Hsueh-Fu Wu Gerald W.Hart Complex Carbohydrate Research Center University of GeorgiaAthensGAUSA Department of Biochemistry and Molecular Biology University of GeorgiaAthensGAUSA Center for Molecular Medicine University of GeorgiaAthensGAUSA

Alzheimer’s disease is a neurodegenerative disease that affected over 6.5 million people in the United States in 2021,with this number expected to double in the next 40 years without any sort of *** to its heterogeneity and complexity,the etiology of Alzheimer’s disease,especially sporadic Alzheimer’s disease,remains largely *** evidence suggests that brain glucose hypometabolism,preceding Alzheimer’s disease hallmarks,is involved in the pathogenesis of Alzheimer’s ***,we discuss the potential causes of reduced glucose uptake and the mechanisms underlying glucose hypometabolism and Alzheimer’s disease ***,decreased O-Glc NAcylation levels by glucose deficiency alter mitochondrial functions and together contribute to Alzheimer’s disease *** major problem with Alzheimer’s disease research is that the disease progresses for several years before the onset of any symptoms,suggesting the critical need for appropriate models to study the molecular changes in the early phase of Alzheimer’s disease ***,this review also discusses current available sporadic Alzheimer’s disease models induced by metabolic abnormalities and provides novel directions for establishing a human neuronal sporadic Alzheimer’s disease model that better represents human sporadic Alzheimer’s disease as a metabolic disease.

关键词： Alzheimer’s disease amyloid beta brain glucose deficiency glucose uptake hypometabolism mitochondrial dysfunction neurodegenerative disease neurons O-GlcNAc Tau

Genome-wide DNA hypermethylation and homocysteine increase a risk for myopia

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International Journal of Ophthalmology(English edition) 2019年第1期12卷 38-45页

作者： Edward Hsi Yung-Song Wang chia-wei huang Ming-Lung Yu Suh-Hang Hank Juo Chung-Ling Liang Centre for Myopia and Eye Disease Department of Medical ResearchChina Medical University(Taiwan) Hospital Department of Genome Medicine Kaohsiung Medical University Institute of Fisheries Science National Taiwan University Department of Biotechnology Kaohsiung Medical University Hepatobiliary Division Department of Internal MedicineKaohsiung Medical University Hospital Faculty of Medicine College of Medicine Kaohsiung Medical University Centre for Myopia and Eye Disease Department of Medical Research China Medical University(Taiwan) Hospital Graduate Institute of Biomedical Sciences China Medical University(Taiwan) Institute of New Drug Development China Medical University(Taiwan) Drug Development Center China Medical University(Taiwan) Department of Ophthalmology Asia University Hospital Department of Optometry College of Medical and Health ScienceAsia University

AIM: To test for the association between genome-wide methylation and myopia in human and mice. METHODS: Long interspersed nucleotide element 1(LINE-1) methylation levels were used to surrogate genome-wide methylation level. We first tested for the association between high myopia(<-6 D) and LINE-1 methylation in leukocytes in 220 cases and 220 control subjects. Secondly, we validated the results of LINE-1 methylation in eyes from the form deprivation myopia(FDM) mice. Furthermore,we calculated the correlation of LINE-1 methylation levels between leukocyte DNA and ocular DNA in the mice. We also tested whether dopamine can alter LINE-1 methylation levels. RESULTS: The LINE-1 methylation level was significantly higher in the myopic human subjects than controls. The upper and middle tertiles of the methylation levels increased an approximately 2-fold(P≤0.002) risk for myopia than the lower tertile. Similarly, FDM mice had high LINE-1 methylation levels in the leukocyte, retina and sclera, and furthermore the methylation levels detected from these three tissues were significantly correlated. Immunohistochemical staining revealed higher levels of homocysteine and methionine in the rodent myopic eyes than normal eyes. Dopamine treatment to the cells reduced both LINE-1 methylation and DNA methyltransferase levels. CONCLUSION: LINE-1 hypermethylation may be associated with high myopia in human and mice. Homocysteine and methionine are accumulated in myopic eyes, which may provide excess methyl group for genome-wide methylation.

关键词： methylation myopia LINE-1 homocysteine dopamine

Photoinduced radical sulfur dioxide insertion with asymmetric cyclization of alkenes: accessing β-chiral sulfones bearing S-stereocentric cyclic sulfinamides

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Science China Chemistry 2025年第1期68卷 257-263页

作者： Jiapian huang Chenxin Wang Xu Wang Xiaoyu Zhou wei Xiao Jie Wu School of Pharmaceutical and Chemical Engineering & Institute for Advanced Studies Taizhou University State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences School of Chemistry and Chemical Engineering Henan Normal University

The generation of various β-chiral sulfones bearing chiral cyclic sulfinamides through photoredox-catalyzed sulfur dioxide insertion with asymmetric radical cyclization is described. This method features a broad substrate scope and excellent stereospecificity. Computational studies reveal that the dispersion interaction between sulfinyl group and CH2SO2Ph group plays a crucial role in the stereoselectivity control.

关键词： β-chiral sulfones chiral cyclic sulfinamides sulfur dioxide insertion asymmetric radical cyclization stereoselectivity

Cobalamin-dependent radical S-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

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Science China Chemistry 2025年第1期68卷 308-316页

作者： Sili Wang Jiancheng huang Yanan Du wei huang Yufeng Xue Xiaokun Xu Guannan Zhong Yuanyuan Shi Bin Hong Xiaoying Bian Wen Liu State Key Laboratory of Chemical Biology Shanghai Institute of Organic Chemistry University of Chinese Academy of SciencesChinese Academy of Sciences State Key Laboratory of Microbial Technology Shandong University National Health Commission (NHC) Key Laboratory of Biotechnology for Microbial Drugs Institute of Medicinal BiotechnologyChinese Academy of Medical Science & Peking Union Medical College

Cobalamin(Cbl)-dependent radical S-adenosyl-L-methionine(SAM) proteins constitute the largest collection of the radical SAM superfamily that has hundreds of thousands of individual members. Many of these proteins are involved in the biosynthesis of pharmaceutically important natural products to catalyze chemically demanding reactions. In the biosynthetic pathway of chuangxinmycin(CXM), a unique indole alkaloid antibiotic with potent anti-infective activity, functionalization of the characteristic thiopyrano[4,3,2-cd]indole scaffold by regio-and stereoselective C3-methylation is believed to rely on a Cbl-dependent radical process, which, however, remained to be reconstituted biochemically. We here report the dissection of this enzymatic process, which requires the incorporation of Cxm8, a Cbl-dependent radical SAM protein, with Cxm9, a DUF5825family protein that shares no homology to any proteins of known functions. Cxm8 and Cxm9 function together by forming an unexpected heterodimeric complex that selectively catalyzes C3-methylation of the tricyclic indole-S-hetero ring system in a successive manner, achieving CXM and a recently identified, C3-dimethylated congener. Detailed biochemical characterization,isotope labeling, structural simulation and bioinformatics analysis rationalized the catalysis of the Cxm8/Cxm9 complex and particularly the necessity of the DUF5825 protein for C3-methylase activity. This is the first example that a Cbl-dependent protein acts with a partner to exhibit radical SAM activity.

关键词： cbl-dependent radical SAM protein biosynthesis chuangxinmycin stereoselective methylation

Small modifications of endo-functionalized cavities lead to large changes in molecular interaction in water

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Science China Chemistry 2025年第1期68卷 369-376页

作者： Song-Meng Wang Hao Nian Yan-Fang Wang Li-Shuo Zheng Yu-Tao Zheng Yi-wei Dong Liping huang Xiaoping Wang wei Jiang Liu-Pan Yang Department of Chemistry Southern University of Science and Technology School of Chemistry and Pharmaceutical Sciences State Key Laboratory for Chemistry and Molecular Engineering of Medicinal ResourcesGuangxi Normal University School of Pharmaceutical Science Hengyang Medical School University of South China

Studying molecular recognition in aqueous environments is crucial for understanding biological processes. Herein, we present a series of N-doped endo-functionalized anthracene-based cavities by introducing inward-directed pyridine units. The subtle modifications can significantly affect the binding properties of these receptors, which is similar to the mutations in biological systems. Combining theoretical calculations and molecular recognition experiments demonstrated that these “mutations” have an impact on the hydrophobicity and charge distribution of the hosts, consequently significantly influencing molecular *** is crucial for understanding the intricate mechanisms of molecular-level interactions in biological receptors.

关键词： host-guest interaction hydrophobic effect endo-functionalized cavity mutation pyridine

Deep learning identification of novel autophagic protein-protein interactions and experimental validation of Beclin 2-Ubiquilin 1 axis in triple-negative breast cancer

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Oncology Research 2025年第1期33卷 67-81页

作者： XIANG LI WENKE JIN LIFENG WU HUAN WANG XIN XIE wei huang BO LIU State Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy and College of Medical TechnologyChengdu University of Traditional Chinese MedicineChengdu611137China Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China

Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional *** is an important process for maintaining cellular homeostasis,and there are currently autophagy biomarkers that play an effective role in the clinical treatment of *** contrast to targeting protein activity,intervention with proteinprotein interaction(PPI)can avoid unrelated crosstalk and regulate the autophagy process with minimal interference ***:Here,we employed Naive Bayes,Decision Tree,and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC,aiming to uncover novel therapeutic ***,the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay,and the interaction relationship was verified by molecular docking and CO-IP experiments after *** formation,cellular immunofluorescence,cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)tests were used to predict the clinical therapeutic effects of manipulating candidate ***:By developing three PPI classification models and analyzing over 13,000 datasets,we identified 3733 previously unknown autophagy-related *** network analysis revealed the central role of Beclin 2 in autophagy regulation,uncovering its interactions with 39 newly identified ***,the CO-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1,which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay ***,in vitro investigations showed that overexpressing Beclin 2 increased Ubiquilin 1,promoted autophagy-dependent cell death,and inhibited proliferation and metastasis in MDA-MB-231 ***:This study not

关键词： Triple-negative breast cancer(TNBC) Autophagy Protein-protein interactions(PPI) Artificial intelligence(AI) Beclin 2 Ubiquilin 1

Effect of Ti Additions on Mechanical and Thermodynamic Properties of W-Ti Alloys: A First-principles Study

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Journal of Wuhan University of Technology(Materials Science) 2025年第1期40卷 246-257页

作者： ZHANG Jian NIE wei huang Jin ZHU Ke LIU Ruxia ZHANG Ruizhi LUO Guoqiang SHEN Qiang State Key Laboratory of Advanced Technology for Materials Synthesis and Processing Wuhan University of TechnologyWuhan 430070China Institute for Carbon Neutrality University of Science and Technology BeijingBeijing 100083China

The mechanical and thermodynamic properties of W-Ti alloys(including W_(15)Ti_(1),W_(14)Ti_(2),W_(12)Ti_(4) and W_(8)Ti_(8) alloys)were investigated by the first-principles approach based on density functional *** results indicate that W-Ti alloys except W_(8)Ti_(8) are thermodynamically *** modulus and hardness of W-Ti alloys are smaller than those of pure tungsten and gradually decrease with increasing Ti ***,their B/G ratios and Poisson's ratios exceed those of pure tungsten,suggesting that the introduction of Ti decreases the mechanical strength while enhancing the ductility of W-Ti *** thermal expansion coefficients for W-Ti alloys all surpass those of pure tungsten,indicating that the introduction of titanium exacerbates the thermal expansion behavior of W-Ti ***,elevated pressure has the capacity to suppress the thermal expansion tendencies in titanium-doped tungsten *** study offers theoretical insights for the design of nuclear materials by exploring the mechanical and thermodynamic properties of W-Ti alloys.

关键词： first-principles mechanical properties thermodynamic properties tungsten-titanium alloys

Microstructure Evolution and Mechanism of Strength Development of Fly Ash Paste

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Journal of Wuhan University of Technology(Materials Science) 2025年第1期40卷 152-163页

作者： MA Shuzhao WU Shunchuan huang Mingqing CHENG Haiyong JIANG Guanzhao NIU Yonghui LIU Zemin SUN wei Faculty of Land Resources Engineering Kunming University of Science and TechnologyKunming 650093China Zijin School of Ge-ology and Mining Fuzhou UniversityFuzhou 350108China

Three types of activators such as sodium hydroxide,calcium oxide and triethanolamine(TEA)are used to establish different activation environments to address the problems associated with the process of activating fly ash *** conducted mechanical tests and numerical simulations to understand the evolution of microstructure,and used environmental scanning electron microscopy(ESEM)and energy dispersive spectroscopy(EDS)techniques to analyze the microenvironments of the *** mechanical properties of fly ash paste under different activation conditions and the changes in the microstructure and composition were *** results revealed that under conditions of low NaOH content(1%-3%),the strength of the sample increased *** the content exceeded 4%,the rate of increase in strength *** on the results,the optimal NaOH content was identified,which was about 4%.A good activation effect,especially for short-term activation(3-7 d),was achieved using TEA under high doping *** activation effect was poor for long-term strength after 28 *** CaO content did not significantly affect the degree of activation *** maximum effect was exerted when the content of CaO was 2%.The virtual cement and concrete testing laboratory(VCCTL)was used to simulate the hydration process,and the results revealed that the use of the three types of activators accelerated the formation of Ca(OH)_(2) in the *** activators also corroded the surface of the fly ash particles,resulting in a pozzolanic *** active substances in fly ash were released efficiently,and hydration was *** pores were filled with hydration products,and the microstructure changed to form a new frame of paste filling that helped improve the strength of fly ash paste.

关键词： paste filling fly ash activator unconfined compressive strength microstructure hydration simulation

A low redox potential and long life organic anode material for sodium-ion batteries

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Journal of Energy Chemistry 2025年第1期100卷 557-564页

作者： Zhi Li Yang wei Kang Zhou Xin huang Xing Zhou Jie Xu Taoyi Kong Junwei Lucas Bao Xiaoli Dong Yonggang Wang Department of Chemistry and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials Institute of New Energy Collaborative Innovation Center of Chemistry for Energy Materials (iChEM) Fudan University Department of Chemistry Boston College School of Materials Science and Engineering Anhui University of Technology

Sodium-ion batteries （SIBs） with organic electrodes are an emerging research direction due to the sustainability of organic materials based on elements like C,H,O,and sodium ***,organic electrode materials for SIBs are mainly used as cathodes because of their relatively high redox potentials（>1 V）.Organic electrodes with low redox potential that can be used as anode are ***,a novel organic anode material （tetrasodium 1,4,5,8-naphthalenetetracarboxylate,Na4TDC） has been developed with low redox potential （<0.7 V） and excellent cyclic *** three-sodium storage mechanism was demonstrated with various in-situ/ex-situ spectroscopy and theoretical calculations,showing a high capacity of 208 mAh/g and an average decay rate of merely 0.022%per ***,the Na4TDC-hard carbon composite can further acquire improved capacity and cycling stability for 1200 cycles even with a high mass loading of up to 20 mg *** pairing with a thick Na3V2（PO4）3cathode (20.6 mg cm-2),the as-fabricated full cell exhibited high operating voltage （2.8 V）,excellent rate performance and cycling stability with a high capacity retention of 88.7% after 200 cycles,well highlighting the Na4TDC anode material for SIBs.

关键词： Organic anode material Low redox potential Composite anode Sodium-ion batteries

Quickly obtaining densely dispersed coherent particles in steel matrix and its related mechanical property

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 111-118页

作者： Xiaoxiao Wang Qingsong huang School of Chemical Engineering Sichuan UniversityChengdu 610065China

Densely distributed coherent nanoparticles(DCN)in steel matrix can enhance the work-hardening ability and ductility of steel *** the routes to this end can be generally classified into the liquid-solid route and the solid-solid ***,the formation of DCN structures in steel requires long processes and complex *** far,obtaining steel with coherent particle enhancement in a short time remains a bottleneck,and some necessary steps remain ***,we show a high-efficiency liquid-phase refining process reinforced by a dynamic magnetic ***-Y-Mn-O particles had an average size of around(3.53±1.21)nm and can be obtained in just around 180 *** small nanoparticles were coherent with the matrix,implying no accumulated dislocations between the particles and the steel *** findings have a potential application for improving material machining capacity,creep resistance,and radiation resistance.

关键词： ferritic steels coherent particles microstructure compression test work hardening