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KAT7/HMGN1 signaling epigenetically induces tyrosine phosphorylation-regulated kinase 1A expression to ameliorate insulin resistance in Alzheimer’s disease

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World Journal of Psychiatry 2024年第3期14卷 445-455页

作者： Qun-Shan lu Lin Ma Wen-Jing Jiang Xing-Bang Wang mei lu Department of Geriatric Medicine Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Key Laboratory of Cardiovascular Proteomics of Shandong Province Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina

BACKGROUND Epidemiological studies have revealed a correlation between Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2D).Insulin resistance in the brain is a common feature in patients with T2D and AD.KAT7 is a histone acetyltransferase that participates in the modulation of various genes.AIM To determine the effects of KAT7 on insulin patients with AD.METHODS APPswe/PS1-dE9 double-transgenic and db/db mice were used to mimic AD and diabetes,respectively.An in vitro model of AD was established by Aβstimulation.Insulin resistance was induced by chronic stimulation with high insulin levels.The expression of microtubule-associated protein 2(MAP2)was assessed using immunofluorescence.The protein levels of MAP2,Aβ,dual-specificity tyrosine phosphorylation-regulated kinase-1A(DYRK1A),IRS-1,p-AKT,total AKT,p-GSK3β,total GSK3β,DYRK1A,and KAT7 were measured via western blotting.Accumulation of reactive oxygen species(ROS),malondialdehyde(MDA),and SOD activity was measured to determine cellular oxidative stress.Flow cytometry and CCK-8 assay were performed to evaluate neuronal cell death and proliferation,respectively.Relative RNA levels of KAT7 and DYRK1A were examined using quantitative PCR.A chromatin immunoprecipitation assay was conducted to detect H3K14ac in DYRK1A.RESULTS KAT7 expression was suppressed in the AD mice.Overexpression of KAT7 decreased Aβaccumulation and MAP2 expression in AD brains.KAT7 overexpression decreased ROS and MDA levels,elevated SOD activity in brain tissues and neurons,and simultaneously suppressed neuronal apoptosis.KAT7 upregulated levels of p-AKT and p-GSK3βto alleviate insulin resistance,along with elevated expression of DYRK1A.KAT7 depletion suppressed DYRK1A expression and impaired H3K14ac of DYRK1A.HMGN1 overexpression recovered DYRK1A levels and reversed insulin resistance caused by KAT7 depletion.CONCluSION We determined that KAT7 overexpression recovered insulin sensitivity in AD by recruiting HMGN1 to enhance DYRK1A acetylation.Our findings suggest that KAT7 is a novel and

关键词： Alzheimer's disease Diabetes Insulin resistance KAT7 Dual-specificity tyrosine phosphorylation-regulated kinase-1A HMGN1

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The P5-saturation Game

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Acta Mathematicae Applicatae Sinica 2024年

作者： Zhen HE mei lu School of Mathematics and Statistics Beijing Jiaotong University Department of Mathematical Sciences Tsinghua University

Let F,G and H be three graphs with G ■ H.We call G an F-saturated graph relative to H,if there is no copy of F in G but there is a copy of F in G+e for any e ∈ E（H）\ E（G）.The F-saturation game on host graph H consists of two players,named Max and Min,who alternately add edges of H to G such that each chosen edge avoids creating a copy of F in G,and the players continue to choose edges until G becomes F-saturated relative to H.Max wishes to maximize the length of the game,while Min wishes to minimize the process.Let satg（F,H）(resp.satg'（F,H）) denote the number of edges chosen when Max（resp.when Min） starts the game and both players play optimally.In this article,we show that satg（P5,K_n）=satg'（P5,K_n）=n+2 for n≥ 15,and satg(P5,Km,n),satg'(P5,Km,n) lie in {m+n-[m+2/4」,m+n-[m-3/4]} if n≥5/2 m and m≥ 4,respectively.

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The Game of Cops and Robbers on Directed Graphs with Forbidden Subgraphs

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Acta Mathematicae Applicatae Sinica 2022年第3期38卷 684-689页

作者： Ming-rui LIU mei lu Department of Mathematical Sciences Tsinghua UniversityBeijing 100084China

The traditional game of cops and robbers is played on undirected graph. Recently, the same game played on directed graph is getting attention by more and more people. We knew that if we forbid some subgraph we can bound the cop number of the corresponding class of graphs. In this paper, we analyze the game of cops and robbers on H^(-)-free digraphs. However, it is not the same as the case of undirected graph. So we give a new concept(H^(-)^(*)-free digraph) to get a similar conclusion about the case of undirected graph.

关键词： cops and robbers directed graph induced subgraphs

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Effect of applied electric fields on supralinear dendritic integration of interneuron

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Chinese Physics B 2024年第2期33卷 84-95页

作者：樊亚琴魏熙乐卢梅丽伊国胜 Tianjin Key Laboratory of Process Measurement and Control School of Electrical and Information EngineeringTianjin UniversityTianjin 300072China School of Information Technology Engineering Tianjin University of Technology and EducationTianjin 300222China

Evidences show that electric fields(EFs)induced by the magnetic stimulation could modulates brain activities by regulating the excitability of GABAergic interneuron.However,it is still unclear how and why the EF-induced polarization affects the interneuron response as the interneuron receives NMDA synaptic inputs.Considering the key role of NMDA receptor-mediated supralinear dendritic integration in neuronal computations,we suppose that the applied EFs could functionally modulate interneurons’response via regulating dendritic integration.At first,we build a simplified multi-dendritic circuit model with inhomogeneous extracellular potentials,which characterizes the relationship among EF-induced spatial polarizations,dendritic integration,and somatic output.By performing model-based singular perturbation analysis,it is found that the equilibrium point of fast subsystem can be used to asymptotically depict the subthreshold input–output(sI/O)relationship of dendritic integration.It predicted that EF-induced strong depolarizations on the distal dendrites reduce the dendritic saturation output by reducing driving force of synaptic input,and it shifts the steep change of sI/O curve left by reducing stimulation threshold of triggering NMDA spike.Also,the EF modulation prefers the global dendritic integration with asymmetric scatter distribution of NMDA synapses.Furthermore,we identify the respective contribution of EF-regulated dendritic integration and EF-induced somatic polarization to an action potential generation and find that they have an antagonistic effect on AP generation due to the varied NMDA spike threshold under EF stimulation.

关键词： GABAergic interneuron electrical field supralinear dendritic integration action potential generation

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Graphene from microwave-initiated upcycling of waste polyethylene for electrocatalytic reduction of chloramphenicol

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Chinese Chemical Letters 2024年第4期35卷 187-192页

作者： Qiang Cao Xue-Feng Cheng Jia Wang Chang Zhou Liu-Jun Yang Guan Wang Dong-Yun Chen Jing-Hui He Jian-mei lu College of Chemistry Chemical Engineering and Materials ScienceCollaborative Innovation Center of Suzhou Nano Science and TechnologySoochow UniversitySuzhou 215123China

Waste polyolefin plastics, accounting for 50% of all plastic waste, represent a tremendously unexploited carbon source. Efficiently upcycling polyolefin waste into value-added carbon materials for waste water treatment avoiding using noble metals is challenging but economically and environmentally sustainable. In this work, MAX-Ti_(3)AlC_(2) supported Fe selectively catalyzes polyolefin into few-layered graphene in 5 min under microwave treatment. Graphene and MAX supported Fe(Fe@MLC) can completely(99.9%)degrade chloramphenicol(CAP) within 60 min, retain robust after 10 cycles and work efficiently at a wide p H range(3.87–13.03), avoiding the usage of noble metal. Moreover, the electrochemical active surface area(ECSA) of Fe@MLC is 2.7 times higher than that of commercial Pt/C. This work provides a cheap and efficient catalyst that promotes deconstruction of plastic wastes and indirectly degrades antibiotics thereby realizes the treatment of waste water with waste plastic.

关键词： Microwave Ti_(3)AlC_(2) Electrochemistry Dechlorination Chloramphenicol

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Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles

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药学学报:英文版 2023年第9期13卷 3945-3955页

作者： mei lu Haonan Xing Wanxuan Shao Pengfei Wu Yuchuan Fan Huining He Stefan Barth Aiping Zheng Xing-Jie Liang Yuanyu Huang Advanced Research Institute of Multidisciplinary Science School of Life ScienceSchool of Medical TechnologyKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China Chinese Academy of Sciences(CAS)Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaBeijing 100190China State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijing 100850China Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of PharmacyTianjin Medical UniversityTianjin 300070China South African Research Chair in Cancer Biotechnology Institute of Infectious Disease and Molecular Medicine(IDM)Department of Integrative Biomedical SciencesFaculty of Health SciencesUniversity of Cape TownCape Town 7925South Africa

Immunotherapy has revolutionized the landscape of cancer treatment.However,single immunotherapy only works well in a small subset of patients.Combined immunotherapy with antitumor synergism holds considerable potential to boost the therapeutic outcome.Nevertheless,the synergistic,additive or antagonistic antitumor effects of combined immunotherapies have been rarely explored.Herein,we established a novel combined cancer treatment modality by synergizing p21-activated kinase 4(PAK4)silencing with immunogenic phototherapy in engineered extracellular vesicles(EVs)that were fabricated by coating M1 macrophage-derived EVs on the surface of the nano-complex cores assembled with si RNA against PAK4 and a photoactivatable polyethyleneimine.The engineered EVs induced potent PAK4 silencing and robust immunogenic phototherapy,thus contributing to effective antitumor effects in vitro and in vivo.Moreover,the antitumor synergism of the combined treatment was quantitatively determined by the Compu Syn method.The combination index(CI)and isobologram results confirmed that there was an antitumor synergism for the combined treatment.Furthermore,the dose reduction index(DRI)showed favorable dose reduction,revealing lower toxicity and higher biocompatibility of the engineered EVs.Collectively,the study presents a synergistically potentiated cancer treatment modality by combining PAK4 silencing with immunogenic phototherapy in engineered EVs,which is promising for boosting the therapeutic outcome of cancer immunotherapy.

关键词： Antitumor synergism Combined cancer immunotherapy p21-activated kinase 4 RNA interference Immunogenic phototherapy Extracellular vesicles Immune infiltration CompuSyn

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A rice XANTHINE DEHYDROGENASE gene regulates leaf senescence and response to abiotic stresses

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The Crop Journal 2022年第2期10卷 310-322页

作者： Jiangmin Xu Chenyang Pan Han Lin Hanfei Ye Sheng Wang Tao lu Qianyu Chen Kairu Yang mei lu Qian Qian Deyong Ren Yuchun Rao College of Chemistry and Life Sciences Zhejiang Normal UniversityJinhua 321004ZhejiangChina State Key Lab for Rice Biology China National Rice Research InstituteHangzhou 310006ZhejiangChina

Xanthine dehydrogenase, a member of the molybdenum enzyme family, participates in purine metabolism and catalyzes the generation of ureides from xanthine and hypoxanthine. However, the mechanisms by which xanthine dehydrogenase affects rice growth and development are poorly understood. In the present study, we identified a mutant with early leaf senescence and reduced tillering that we named early senescence and less-tillering 1(esl1). Map-based cloning revealed that ESL1 encodes a xanthine dehydrogenase, and it was expressed in all tissues. Chlorophyll content was reduced and chloroplast maldevelopment was severe in the esl1 mutant. Mutation of ESL1 led to decreases in allantoin, allantoate, and ABA contents. Further analysis revealed that the accumulation of reactive oxygen species in esl1 resulted in decreased photosynthesis and impaired chloroplast development, along with increased sensitivity to abscisic acid and abiotic stresses. Ttranscriptome analysis showed that the ESL1 mutation altered the expression of genes involved in the photosynthesis process and reactive oxygen species metabolism.Our results suggest that ESL1 is involved in purine metabolism and the induction of leaf senescence.These findings reveal novel molecular mechanisms of ESL1 gene-mediated plant growth and leaf senescence.

关键词： Xanthine dehydrogenase Leaf senescence Abiotic stresses Purine metabolism

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Survey on Lie Group Machine Learning

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Big Data Mining and Analytics 2020年第4期3卷 235-258页

作者： mei lu Fanzhang Li the School of Software Engineering Jinling Institute of TechnologyNanjing 211169China the School of Computer Science and Technology Jiangsu Normal UniversityXuzhou 221000China the School of Computer Science and Technology Soochow UniversitySuzhou 215006China

Lie group machine learning is recognized as the theoretical basis of brain intelligence,brain learning,higher machine learning,and higher artificial intelligence.Sample sets of Lie group matrices are widely available in practical applications.Lie group learning is a vibrant field of increasing importance and extraordinary potential and thus needs to be developed further.This study aims to provide a comprehensive survey on recent advances in Lie group machine learning.We introduce Lie group machine learning techniques in three major categories:supervised Lie group machine learning,semisupervised Lie group machine learning,and unsupervised Lie group machine learning.In addition,we introduce the special application of Lie group machine learning in image processing.This work covers the following techniques:Lie group machine learning model,Lie group subspace orbit generation learning,symplectic group learning,quantum group learning,Lie group fiber bundle learning,Lie group cover learning,Lie group deep structure learning,Lie group semisupervised learning,Lie group kernel learning,tensor learning,frame bundle connection learning,spectral estimation learning,Finsler geometric learning,homology boundary learning,category representation learning,and neuromorphic synergy learning.Overall,this survey aims to provide an insightful overview of state-of-the-art development in the field of Lie group machine learning.It will enable researchers to comprehensively understand the state of the field,identify the most appropriate tools for particular applications,and identify directions for future research.

关键词： Lie group machine learning Lie group subspace orbit generation learning quantum group learning symplectic group learning Lie group fiber bundle learning

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Some Ore-type Results for Matching and Perfect Matching in k-uniform Hypergraphs

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Acta Mathematica Sinica,English Series 2018年第12期34卷 1795-1803页

作者： Yi ZHANG mei lu Department of Mathematical Sciences Tsinghua University

Let SI and S2 be two （k- 1）-subsets in a k-uniform hypergraph H. We call S1 and S2 strongly or middle or weakly independent if H does not contain an edge e ∈ E（H） such that S1 ∩ e≠ 0 and S2 ∩ e ≠0 or e S1 ∪ S2 or e S1 ∪ S2, respectively. In this paper, we obtain the following results concerning these three independence. （1） For any n ≥ 2k2 - k and k ≥ 3, there exists an n-vertex k-uniform hypergraph, which has degree sum of any two strongly independent （k - 1）-sets equal to 2n - 4（k - 1）, contains no perfect matching; （2） Let d ≥ 1 be an integer and H be a k-uniform hypergraph of order n ≥ kd＋（k- 2）k. If the degree sum of any two middle independent （k- 1）-subsets is larger than 2（d- 1）, then H contains a d-matching; （3） For all k ≥ 3 and sufficiently large n divisible by k, we completely determine the minimum degree sum of two weakly independent （k - 1）-subsets that ensures a perfect matching in a k-uniform hypergraph H of order n.

关键词： Ore-type condition matching perfect matching hypergraph

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Lower Bounds on the(Laplacian) Spectral Radius of Weighted Graphs

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Chinese Annals of Mathematics,Series B 2014年第4期35卷 669-678页

作者： Aimei YU mei lu Department of Mathematics Beijing Jiaotong University Department of Mathematical Sciences Tsinghua University

The weighted graphs, where the edge weights are positive numbers, are considered. The authors obtain some lower bounds on the spectral radius and the Laplacian spectral radius of weighted graphs, and characterize the graphs for which the bounds are attained. Moreover, some known lower bounds on the spectral radius and the Laplacian spectral radius of unweighted graphs can be deduced from the bounds.

关键词：拉普拉斯谱半径加权图下界曲线图正数权重

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