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E674Q(Shanghai APP mutant),a novel amyloid precursor protein mutation,in familial late-onset Alzheimer's disease

Genes & Diseases 2024年第2期11卷 1022-1034页

作者： Yongfang Zhang Xinyi xie Boyu Chen Lina Pan Jianping Li Wanbing Wang Jintao Wang Ran Tang qiang Huang Xiaofen Chen Rujing Ren Zhentao Zhang Wei Fu Gang Wang Department of Neurology Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of Pharmacology and Chemical Biology Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of Medicinal Chemistry School of PharmacyFudan UniversityShanghai 201203China Department of Neurology Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research Institute of NeuroscienceSchool of MedicineXiamen UniversityXiamenFujian 361102China Shenzhen Research Institute of Xiamen University ShenzhenGuangdong 518063China

Identified as the pathogenic genes of Alzheimer's disease(AD),APP,PSEN1,and PSEN2 mainly lead to early-onset AD,whose course is more aggressive,and atypical symptoms are more common than sporadic ***,a novel missense mutation,APP E674Q(also named“Shanghai APP”),was detected in a Chinese index patient with typical late-onset AD(LOAD)who developed memory decline in his *** results from neuroimaging were consistent with AD,where widespread amyloidβdeposition was demonstrated in 18 F-florbetapir Positron Emission Tomography(PET).APP E674Q is close to theβ-secretase cleavage site and the well-studied Swedish APP mutation(KM670/671NL),which was predicted to be pathogenic in *** dynamics simulation indicated that the E674Q mutation resulted in a rearrangement of the interaction mode between APP and BACE1 and that the E674Q mutation was more prone to cleavage by *** in vitro results suggested that the E674Q mutation was pathogenic by facilitating the BACE1-mediated processing of APP and the production of Aβ.Furthermore,we applied an adeno-associated virus(AAV)-mediated transfer of the human E674Q mutant APP gene to the hippocampi of two-month-old C57Bl/6 J ***-E674Q-injected mice exhibited impaired learning behavior and increased pathological burden in the brain,implying that the E674Q mutation had a pathogenicity that bore a comparison with the classical Swedish ***,we report a strong amyloidogenic effect of the E674Q substitution in *** our knowledge,E674Q is the only pathogenic mutation within the amyloid processing sequence causing LOAD.

关键词： Alzheimer's disease Amyloid beta APP mutation E674Q Late onset

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Heterophase junction engineering-induced Co spin-state modulation of CoSe_(2) for large-current hydrogen evolution reaction

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Rare Metals 2024年第6期43卷 2660-2670页

作者： Bao-Chai Xu ya-Ping Miao Min-Qin Mao Dong-Lian Li Song xie Wei-Hong Jin Shu Xiao Jing Wen Zaenab Abd-Allah Zhi-Tian Liu Xiang Peng Paul K.Chu Hubei Key Laboratory of Plasma Chemistry and Advanced Materials School of Materials Science and EngineeringWuhan Institute of TechnologyWuhan 430205China School of Textile Science and Engineering Xi'an Polytechnic UniversityXi'an 710048China Institute of Advanced Wear and Corrosion Resistant and Functional Materials Jinan UniversityGuangzhou 510632China Institute of Safety Science and Engineering South China University of TechnologyGuangzhou 510641China Department of Engineering Manchester Metropolitan UniversityManchester M156BHUK Department of Physics Department of Materials Science and Engineeringand Department of Biomedical EngineeringCity University of Hong KongHong Kong 999077China

Efficient electrocatalysts are vital to large-current hydrogen production in commercial water splitting for green energy ***,a novel heterophase engineering strategy is described to produce polymorphic CoSe_(2)*** composition of the electrocatalysts consisting of both cubic CoSe_(2)(c-CoSe_(2))and orthorhombic CoSe_(2)(o-CoSe_(2))phases can be controlled *** results demonstrate that junction-induced spin-state modulation of Co atoms enhances the adsorption of intermediates and accelerates charge transfer resulting in superior large-current hydrogen evolution reaction(HER)***,the CoSe_(2)based heterophase catalyst with the optimal c-CoSe_(2)content requires an overpotential of merely 240 mV to achieve 1,000 mA·cm^(-2)as well as a Tafel slope of 50.4 mV·dec^(-1).Furthermore,the electrocatalyst can maintain a large current density of 1,500 mA·cm^(-2)for over 320 h without *** results reveal the advantages and potential of heterophase junction engineering pertaining to design and fabrication of low-cost transition metal catalysts for large-current water splitting.

关键词： Heterophase junction Spin-state Hydrogen evolution reaction Large current electrochemical hydrogen production Water splitting

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Accurate diagnosis of severe coronary stenosis based on resting magnetocardiography: a prospective, single-center, cross-sectional analysis

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Journal of Geriatric Cardiology 2024年第4期21卷 407-420页

作者： Jian-Guo CUI Feng TIAN Yu-Hao MIAO Qin-Hua JIN ya-Jun SHI Li LI Meng-Jun SHEN Xiao-Ming xie Shu-Lin ZHANG Yun-Dai CHEN School of Medicine Nankai UniversityTianjinChina Senior Department of Cardiology the Sixth Medical CenterChinese PLA General HospitalBeijingChina Joint Laboratory of Bioimaging Technology and Applications SAS-SIM-IT&MEDIShanghaiChina Shanghai Institute of Microsystem and Information Technology Chinese Academy of SciencesShanghaiChina

OBJECTIVE To evalu ate the role of resting magnetocardiography in identifying seve re coronary artery stenosis in patients with suspected coronary artery *** A total of 513 patients with angina symptoms were included and divided into two groups based on the extent of coronary artery disease determined by angiography:the non-severe coronary stenusis group(<70% stenosis) and the severe coronary stenosis group(≥70% stenosis).The diagnostic model was constructed using magnetic field map(MFM) parameters,either individually or in combination with clinical *** performance of the models was evaluated using receiver operating characteristic curves,accuracy,sensitivity,specificity,positive predictive value(PPV) and ne gative predictive value(NPV).Calibration plots and decision curve analysis were performed to investigate the clinical utility and performance of the models,*** In the severe coronary stenosis group,QR_MCTDd,S_MDp,and TT_(MA)C_(50) were significantly higher than those in the non-severe coronary stenosis group(10,46±10.66 vs,5.11±6.07,P <0.001;7.2±8.64 vs.4.68±6.95,P=0.003;0.32±57.29 vs.0.26±57.29,P <0.001).While,QR_MV_(amp),R_(MA),and T_(MA) in the severe coronary stenosis group were lower(0.23±0.16 vs.0.28±0.16,P<0.001;55.06±48.68 vs.59.24±53.01,P<0.001;51.67±39.32 vs. 60.45±51.33,P <0.001).Seven MFM parameters were integrated into the model,resulting in an area under the curve of 0.810(95% CI:0.765-0.855).The sensitivity,specificity,PPV,NPV,and accurecy were 71.7%,80.4%,93.3%,42.8 %,and 73.5%;*** combined model exhibited an area under the curve of 0.845(95% CI:0.798-0.892).The sensitivity,specificity,PPV,NPV,and accuracy were 84.3%,73.8%,92.6%,54.6%,and 82.1%;*** curves demonstrate d excellent agreement between the nomogram prediction and actual *** decision curve analysis showed that the c ombine d model provided greater net benefit compared to the magnetocardingraphy model.C

关键词： coronary stenosis specificity

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FDX1 as a novel biomarker and treatment target for stomach adenocarcinoma

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1803-1824页

作者： Xian-Ze xie Lei Zuo Wei Huang Qiao-Mei Fan ya-Yun Weng Wen-Dong yao Jia-Li Jiang Jia-Qi Jin Department of Pharmacy The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine)Hangzhou 310018Zhejiang ProvinceChina Anhui Province Huainan City Shou County Agricultural Machinery Affairs Management Center Huainan 232200Anhui ProvinceChina

BACKGROUND Stomach adenocarcinoma(STAD)is one of the main reasons for cancer-related deaths *** investigation aimed to define the connection between STAD and Cuproptosis-related genes(CRGs).Cuproptosis is a newly identified form of mitochondrial cell death triggered by *** To explore the identification of potential biomarkers for STAD disease based on *** A predictive model using Gene Ontology(GO),Least Absolute Shrinkage and Selection Operator(LASSO),Kyoto Encyclopedia of Genes and Genomes(KEGG),Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis analyzed gene interconnections,focusing on 3 copper-related genes and their expression in The Cancer Genome *** for mRNA-miRNA and mRNA-transcription factor interactions were *** prognostic significance of CRG scores was evaluated using time-receiver operating characteristic,Kaplan-Meier curves,and COX regression *** was conducted with datasets GSE26942,GSE54129,and *** of copper-related differ-entially expressed genes was also analyzed in various human tissues and gastric cancer subpopulations using the human protein *** Three significant genes(FDX1,LIAS,MTF1)were identified and selected via LASSO analysis to predict and classify individuals with STAD into high and low CRG score *** genes were down-regulated in both risk *** and KEGG analyses highlighted their involvement mainly in the electron transport *** validating their differential expression,FDX1 emerged as the most accurate diagnostic marker for gastric ***,the RCircos package localized FDX1 on chromosome *** Our study revealed that FDX1 could be a potential biomarker and treatment target for gastric malignancy,providing new ideas for further scientific research.

关键词： Stomach adenocarcinoma disease Copper death FDX1 prognostic biomarkers Cuproptosis-related genes

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Mitigated reaction kinetics between lithium metal anodes and electrolytes by alloying lithium metal with low-content magnesium

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Journal of Energy Chemistry 2024年第8期95卷 644-650,I0014页

作者： yang-yang Wang ya-Nan Wang Nan yao Shu-Yu Sun Xiao-Qing Ding Chen-Xi Bi Qian-Kui Zhang Zhao Zheng Cheng-Bin Jin Bo-Quan Li Xue-qiang Zhang Jia-Qi Huang School of Materials Science and Engineering Beijing Institute of TechnologyBeijing 100081China Advanced Research Institute of Multidisciplinary Science Beijing Institute of TechnologyBeijing 100081China Beijing Key Laboratory of Green Chemical Reaction Engineering and Technology Department of Chemical EngineeringTsinghua UniversityBeijing 100084China College of Materials and Chemistry China Jiliang UniversityHangzhou 310018ZhejiangChina

Lithium(Li)metal is regarded as a promising anode candidate for high-energy-density rechargeable ***,Li metal is highly reactive against electrolytes,leading to rapid decay of active Li metal ***,alloying Li metal with low-content magnesium(Mg)is proposed to mitigate the reaction kinetics between Li metal anodes and *** atoms enter the lattice of Li atoms,forming solid solution due to the low amount(5 wt%)of *** atoms mainly concentrate near the surface of Mg-alloyed Li metal *** reactivity of Mg-alloyed Li metal is mitigated kinetically,which results from the electron transfer from Li to Mg atoms due to the electronegativity *** on quantitative experimental analysis,the consumption rate of active Li and electrolytes is decreased by using Mgalloyed Li metal anodes,which increases the cycle life of Li metal batteries under demanding ***,a pouch cell(1.25 Ah)with Mg-alloyed Li metal anodes delivers an energy density of 340 Wh kg^(-1)and a cycle life of 100 *** work inspires the strategy of modifying Li metal anodes to kinetically mitigate the side reactions with electrolytes.

关键词： Lithium metal anodes Alloying Anode/electrolyte interface Reaction kinetics Pouch cell

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Molecular mechanism of hypoxia and alpha-ketoglutaric acid on collagen expression in scleral fibroblasts

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International Journal of Ophthalmology(English edition) 2024年第10期17卷 1780-1790页

作者： Yun Sun Zhuo-Zheng Li Jing yang ya-Ru Sha Xin-Yu Hou Hong Fu Jia-Yin Li Shu-Chang Bai Yong-Fang xie Guo-Hui Wang School of Life Science and Technology Shandong Second Medical UniversityWeifang 261053Shandong ProvinceChina

AIM:To investigate the molecular mechanisms underlying the influence of hypoxia and alpha-ketoglutaric acid(α-KG)on scleral collagen ***:Meta-analysis and clinical statistics were used to prove the changes in choroidal thickness(ChT)during *** establishment of a hypoxic myopia model(HYP)for rabbit scleral fibroblasts through hypoxic culture and the effects of hypoxia andα-KG on collagen expression were demonstrated by Sirius red *** analysis was used to verify the genes and pathways that hypoxia andα-KG affect collagen ***,real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)was used for reverse ***:Meta-analysis results aligned with clinical statistics,revealing a thinning of ChT,leading to scleral *** red staining indicated lower collagen expression in the HYP group and higher collagen expression in the HYP+α-KG group,showed that hypoxia reduced collagen expression in scleral fibroblasts,whileα-KG can elevated collagen expression under HYP *** analysis unveiled the related genes and signaling pathways of hypoxia andα-KG affect scleral collagen expression and the results were verified by ***:The potential molecular mechanisms through which hypoxia andα-KG influencing myopia is unraveled and three novel genes TLCD4,TBC1D4,and EPHX3 are *** findings provide a new perspective on the prevention and treatment of myopia via regulating collagen expression.

关键词： sclera scleral collagen expression hypoxia alpha-ketoglutaric acid myopia

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基于深度学习的图像中无人机与飞鸟检测研究综述

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计算机工程与应用 2024年第8期60卷 46-55页

作者：谢威宇张强中国民用航空飞行学院空中交通管理学院四川广汉618307

随着民用无人机产业的发展,无人机已经成为一项影响公共安全的重要问题。目前针对低空无人机的监视手段主要是采用雷达探测结合图像识别的方法,然而在图像检测识别中易受到与无人机同属“低、慢、小”目标的飞鸟的干扰。为了能够在基于... 详细信息

随着民用无人机产业的发展,无人机已经成为一项影响公共安全的重要问题。目前针对低空无人机的监视手段主要是采用雷达探测结合图像识别的方法,然而在图像检测识别中易受到与无人机同属“低、慢、小”目标的飞鸟的干扰。为了能够在基于可见光图像的无人机检测中排除飞鸟目标的干扰,利用深度神经网络对可见光图像中无人机与飞鸟进行精确的检测与分类,有效地排除飞鸟对无人机检测的干扰。系统阐释了目标检测技术的发展历程,讨论了各类基于深度学习网络目标检测算法的差异,对比了各类算法的优缺点。对可用于无人机与飞鸟检测的图像数据集进行了梳理与介绍,对相关研究的已有成果进行分析;再从实际应用出发,对无人机与飞鸟检测当中可能会存在的问题进行梳理,阐述与分析了能解决相应检测问题的卷积神经网络的相关研究。最后,针对该研究后续可能的发展方向进行展望。

关键词：深度学习卷积神经网络目标检测无人机飞鸟检测

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Cross-sectional network analysis of plasma proteins/metabolites correlated with pathogenesis and therapeutic response in acute promyelocytic leukemia

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Frontiers of Medicine 2024年第2期18卷 327-343页

作者： Niu Qiao Yizhu Lyu Feng Liu Yuliang Zhang Xiaolin Ma Xiaojing Lin Junyu Wang Yinyin xie Ruihong Zhang Jing Qiao Hongming Zhu Li Chen Hai Fang Tong Yin Zhu Chen qiang Tian Saijuan Chen Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Hematology Second Hospital of Dalian Medical UniversityDalian116021China

The treatment of PML/RARA+acute promyelocytic leukemia(APL)with all-trans-retinoic acid and arsenic trioxide(ATRA/ATO)has been recognized as a model for translational medicine *** an altered microenvironment is a general cancer hallmark,how APL blasts shape their plasma composition is poorly ***,we reported a cross-sectional correlation network to interpret multilayered datasets on clinical parameters,proteomes,and metabolomes of paired plasma samples from patients with APL before or after ATRA/ATO induction *** study revealed the two prominent features of the APL plasma,suggesting a possible involvement of APL blasts in modulating plasma *** was characterized by altered secretory protein and metabolite profiles correlating with heightened proliferation and energy consumption in APL blasts,and the other featured APL plasma-enriched proteins or enzymes catalyzing plasma-altered metabolites that were potential trans-regulatory targets of PML/***,results indicated heightened interferon-gamma signaling characterizing a tumor-suppressing function of the immune system at the first hematological complete remission stage,which likely resulted from therapy-induced cell death or senescence and ensuing supraphysiological levels of intracellular ***,our work sheds new light on the pathophysiology and treatment of APL and provides an information-rich reference data cohort for the exploratory and translational study of leukemia microenvironment.

关键词： acute promyelocytic leukemia plasma proteomics plasma metabolomics cross-sectional correlation network pathogenesis treatment

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Role of targeting ferroptosis as a component of combination therapy in combating drug resistance in colorectal cancer

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World Journal of Clinical Oncology 2024年第3期15卷 375-377页

作者： Xiao-Ting xie qiang-Hu Pang Lian-Xiang Luo The First Clinical College Guangdong Medical UniversityZhanjiang 524023Guangdong ProvinceChina The Marine Biomedical Research Institute Guangdong Medical UniversityZhanjiang 524023Guangdong ProvinceChina

Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor ***,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of *** have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon *** has emerged as a promising candidate for CRC treatment by diminishing stemness and ***,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism *** into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.

关键词： Colorectal cancer Ferroptosis Immunotherapy Drug resistance Chemotherapy Nanodrug delivery systems

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基于车轮-桥面相干激励的大跨连续梁桥振动响应

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吉林大学学报（工学版） 2024年第2期54卷 436-444页

作者：韩智强谢刚卓亚娟骆佐龙李华腾太原科技大学车辆与交通工程学院太原030024 太原科技大学先进控制与装备智能化山西省重点实验室太原030024 山西大学电力与建筑学院太原030024

为获取桥面相干激励下大跨连续梁桥动力响应规律,基于虚功原理,建立五轴重载车辆动力学模型,采用模态叠加法建立桥梁动力方程,通过谐波叠加法建立桥面相干激励模型,根据轮-桥间几何和力学耦合关系,组建车轮-桥面相干激励模型,采用Matla... 详细信息

为获取桥面相干激励下大跨连续梁桥动力响应规律,基于虚功原理,建立五轴重载车辆动力学模型,采用模态叠加法建立桥梁动力方程,通过谐波叠加法建立桥面相干激励模型,根据轮-桥间几何和力学耦合关系,组建车轮-桥面相干激励模型,采用Matlab软件编译大跨连续梁桥车桥耦合振动分析系统,并开展不同等级的相干桥面激励模型对大跨连续梁桥动力响应影响研究。结果表明:当未考虑桥面不平顺影响时,桥梁冲击系数均小于规范取值,但随着桥面状况的恶化,结构典型截面的动力响应增长较快,且完全相干模型对桥梁动力响应的影响均大于部分相干激励模型,均超过规范值,其中挠度幅值最大偏差约为7.7%,弯矩幅值最大偏差约为20%,挠度冲击系数相对误差为4%~34%,弯矩冲击系数相对误差为2%~43%;随着车速的增大,桥梁冲击系数呈先增大后减小变化。最后,给出了大跨连续梁桥挠度和弯矩冲击系数包络图。相关研究成果可为连续梁桥的结构动力响应的分析与研究提供参考。

关键词：桥梁工程桥面相干激励模型车桥耦合动力响应冲击系数

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