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Neddylation is a novel therapeutic target for lupus by regulating double negative T cell homeostasis

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Signal Transduction and Targeted Therapy 2024年第2期9卷 738-750页

作者： Yun Zhang Lijun Du Chenxi Wang Zhangsheng Jiang Qingchi Duan Yiping Li Zhijun Xie Zhixing He Yi Sun lin huang Liwei Lu Chengping Wen Key Laboratory of Chinese medicine rheumatology of Zhejiang Province Research Institute of Chinese Medical Clinical Foundation and ImmunologyCollege of Basic Medical ScienceZhejiang Chinese Medical UniversityHangzhou 310053China Department of General Surgery Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China Cancer Center of Zhejiang University Hangzhou 310029China Department of Pathology and Shenzhen Institute of Research and Innovation The University of Hong KongHong KongChina Chongqing International Institute for Immunology Chongqing 400038China

Systemic lupus erythematosus(SLE),a severe autoimmune disorder,is characterized by systemic inflammatory response,autoantibody accumulation and damage to organs.The dysregulation of double-negative(DN)T cells is considered as a crucial commander during SLE.Neddylation,a significant type of protein post-translational modification(PTM),has been well-proved to regulate T cell-mediated immune response.However,the function of neddylation in SLE is still unknown.Here,we reported that neddylation inactivation with MLN4924,a specific inhibitor of NEDD8-activating enzyme E1(NAE1),or genetic abrogation of Ube2m in T cells decreased DN T cell accumulation and attenuated murine lupus development.Further investigations revealed that inactivation of neddylation blocked Bim ubiquitination degradation and maintained Bim level in DN T cells,contributing to the apoptosis of the accumulated DN T cells in lupus mice.Then double knockout(KO)lupus-prone mice(Ube2m-/-Bim-/-lpr)were generated and results showed that loss of Bim reduced Ube2m deficiency-induced apoptosis in DN T cells and reversed the alleviated lupus progression.Our findings identified that neddylation inactivation promoted Bim-mediated DN T cell apoptosis and attenuated lupus progression.Clinically,we also found that in SLE patients,the proportion of DN T cells was raised and their apoptosis was reduced.Moreover,compared to healthy groups,SLE patients exhibited decreased Bim levels and elevated Cullin1 neddylation levels.Meantime,the inhibition of neddylation induced Bim-dependent apoptosis of DN T cells isolated from SLE patients.Altogether,our findings provide the direct evidence about the function of neddylation during lupus,suggesting a promising therapeutic approach for this disease.

关键词： inactivation double finding

Consensus on rapid screening for prodromal Alzheimer's disease in China

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General Psychiatry 2024年第1期37卷 1-16页

作者： lin huang Qinjie Li Yao Lu Fengfeng Pan Liang Cui Ying Wang Ya Miao Tianlu Chen Yatian Li Jingnan Wu Xiaochun Chen Jianping Jia Qihao Guo Department of Gerontology Shanghai Sixth People's Hospital Afiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina shanghai BestCovered ShanghaiChina ADepartment of Neurology Fujan Medical University Union HospitalFuzhouChina Department of Neurology National Clinical Research Center for Geriatric DiseasesBeijingChina

Alzheimer's disease(AD)is a common cause of dementia,characterised by cerebral amyloid-βdeposition,pathological tau and neurodegeneration.The prodromal stage of AD(pAD)refers to patients with mild cognitive impairment(MCl)and evidence of AD's pathology.At this stage,disease-modifying interventions should be used to prevent the progression to dementia.Given the inherent heterogeneity of MCl,more specific biomarkers are needed to elucidate the underlying AD's pathology.Although the uses of cerebrospinal fluid and positron emission tomography are widely accepted methods for detecting AD's pathology,their clinical applications are limited by their high costs and invasiveness,particularly in low-income areas in China.Therefore,to improve the early detection of Alzheimer's disease(AD)pathology through cost-effective screening methods,a panel of 45neurologists,psychiatrists andgerontologistswas invited to establish a formal consensus on the screening of pAD in China.The supportive evidence and grades of recommendations are based on a systematic literature review andfocus group discussion.National meetings were held to allow participants to review,vote and provide their expert opinions to reach a consensus.A majority(two-thirds)decision was used for questions for which consensus could not be reached.Recommended screening methods are presented in this publication,including neuropsychological assessment,peripheral biomarkers and brain imaging.In addition,a general workflow for Screening pAD in China is established,which will help clinicians identify individuals at high risk and determine therapeutic targets.

关键词： Alzheimer income screening

A Review of Terahertz Solid-state Electronic/Optoelectronic Devices and Communication Systems

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Chinese Journal of Electronics 2024年

作者： Wenbo LI Hongxin ZENG lin huang Sen GONG Haoyi CAO Weipeng WANG Zheng WANG Hongji ZHOU Shixiong LIANG Ziqiang YANG Yaxin ZHANG University of Electronic Science and Technology of China Huzhou Key Laboratory of Terahertz Integrated Circuits and Systems Yangtze Delta Region Institute (Huzhou)University of Electronic Science and Technology of China Terahertz Institute Zhangjiang National Laboratory National Key Laboratory of Application Specific Integrated Circuit Hebei Semiconductor Research Institute

With the rapid development of modern communication technology, spectrum resources have become non-renewable and precious resources, and the terahertz frequency band has entered people's vision. Nowadays, terahertz communication technology has become one of the core technologies for future high-capacity and high-rate communication. This paper discusses and analyzes the core technologies related to the field of terahertz communication.We introduce the characteristics, domestic and international comparisons and development trends of the core devices for terahertz communication, and also introduce and discuss the terahertz solid-state frequency mixing communication system, terahertz direct modulation communication system, and terahertz optoelectronic communication system.Finally, we summarize the development of terahertz communication technology and the outlook of future applications.

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Determination of Benzoylaconitine Compounds in the Decoctions of Aconiti Lateralis Radix Praeparata(Heishun Pieces),Trichosanthis Fructus and Their Combination

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Medicinal Plant 2024年第3期15卷 1-3,22页

作者： Luyao XIE Xiaoxia LI Jing FU Jinhua LIU Yaobin huang Xuri WEI Tingting MO Shaomian PAN lin huang Jiabao MA Graduate School of Guangxi University of Chinese Medicine Nanning 530200China The First Affiliated Hospital of Guangxi University of Chinese Medicine Nanning 530023China

[Objectives]This study was conducted to determine the contents of benzoylmesaconine,benzoylaconitine and benzoylhypacoitine in the decoctions of Heishun pieces,Trichosanthis Fructus and their combination.[Methods]Heishun pieces,Trichosanthis Fructus and their combination were extracted for different time periods,and then grouped.HPLC was performed using an Agilent ZORBAX SB-C 18 chromatographic column(4.6 mm×250 mm,5μm)and acetonitrile-0.02 mol/L sodium dihydrogen phosphate as the mobile phase at a flow rate of 1 mL/min and a column temperature of 30℃,and the sample volume was 20μL.The detection wavelength was 230 nm.[Results]The total amounts of benzoylmesaconine,benzoylaconitine and benzoylhypacoitine in the single decoction group of Heishun pieces were all significantly different from those in the combined decoction group at corresponding time.[Conclusions]The total content of the benzoylaconitine type increased significantly after the combined decoction of Heishun pieces and Fructus Trichosanthis,which proves the scientificity of"eighteen incompatible medicaments,19 counteraction"in traditional Chinese medicine to some extent.

关键词： Aconiti Lateralis Radix Praeparata Trichosanthis Fructus Benzoylaconitine compound Content determination

Na^(+)/K^(+)-ATPase:ion pump,signal transducer,or cytoprotective protein,and novel biological functions

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Neural Regeneration Research 2024年第12期19卷 2684-2697页

作者： Songqiang huang Wanting Dong Xiaoqian lin Jinsong Bian Department of Pharmacology Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and DiseasesSchool of MedicineSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina Department of Pharmacology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell membrane.Na^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of cells.Therefo re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological diseases.However,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell function.Our recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's disease.Stabilization of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these diseases.For this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell migration.Thus,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related pathogenesis.The potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.

关键词： antibody biological functions cellular communication electrochemical gradient ion balance ion channels Na^(+)/K^(+)-ATPase neurological diseases neurotransmitter release signal transduction

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A Server Placement Algorithm for Reducing Risk and Improving Power Utilization in Data Centers

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Tsinghua Science and Technology 2024年第1期29卷 158-173页

作者： Rui Chen Huikang huang Xiaoxuan Luo Weiwei lin School of Computer Science and Engineering South China University of TechnologyGuangzhou 510006China Peng Cheng Laboratory Shenzhen 518066China

As the power demand in data centers is increasing,the power capacity of the power supply system has become an essential resource to be optimized.Although many data centers use power oversubscription to make full use of the power capacity,there are unavoidable power supply risks associated with it.Therefore,how to improve the data center power capacity utilization while ensuring power supply security has become an important issue.To solve this problem,we first define it and propose a risk evaluation metric called Weighted Power Supply Risk(WPSRisk).Then,a method,named Hybrid Genetic Algorithm with Ant Colony System(HGAACS),is proposed to improve power capacity utilization and reduce power supply risks by optimizing the server placement in the power supply system.HGAACS uses historical power data of each server to find a better placement solution by population iteration.HGAACS possesses not only the remarkable local search ability of Ant Colony System(ACS),but also enhances the global search capability by incorporating genetic operators from Genetic Algorithm(GA).To verify the performance of HGAACS,we experimentally compare it with five other placement algorithms.The experimental results show that HGAACS can perform better than other algorithms in both improving power utilization and reducing the riskof powersupply system.

关键词： server placement power utilization power supply risk swarm intelligence algorithm

Drug repurposing for cancer therapy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1981-2013页

作者： Ying Xia Ming Sun Hai huang Wei-lin Jin Center for Clinical Laboratories The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004PR China The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine Guiyang 550001PR China School of Clinical Laboratory Science Guizhou Medical UniversityGuiyang 550004PR China Division of Gastroenterology and Hepatology Department of Medicine andDepartment of OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMD 21287USA Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhou 730000PR China

Cancer,a complex and multifactorial disease,presents a significant challenge to global health.Despite significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic strategy.However,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer therapeutics.One promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved drugs.Drug repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety profiles.In light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat cancer.We describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor microenvironment.In addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug delivery.We also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy regimen.To conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.

关键词： drugs integrating spite

Method for triangular fuzzy multiple attribute decision making based on two-dimensional density operator method

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Journal of Systems Engineering and Electronics 2024年第1期35卷 178-185页

作者： lin Youliang LI Wu LIU Gang huang Dong School of Economics and Management Hunan Institute of Science and TechnologyYueyang 414000China Hunan Vocational College for Nationalities Yueyang 414000China School of Information Science and Engineering Hunan Institute of Science and TechnologyYueyang 414000China

Aiming at the triangular fuzzy(TF)multi-attribute decision making(MADM)problem with a preference for the distribution density of attribute(DDA),a decision making method with TF number two-dimensional density(TFTD)operator is proposed based on the density operator theory for the decision maker(DM).Firstly,a simple TF vector clustering method is proposed,which considers the feature of TF number and the geometric distance of vectors.Secondly,the least deviation sum of squares method is used in the program model to obtain the density weight vector.Then,two TFTD operators are defined,and the MADM method based on the TFTD operator is proposed.Finally,a numerical example is given to illustrate the superiority of this method,which can not only solve the TF MADM problem with a preference for the DDA but also help the DM make an overall comparison.

关键词： fuzzy decision making clustering density operator multi-attribute decision making(MADM)

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Exploring the Roles of Single Atom in Hydrogen Peroxide Photosynthesis

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Nano-Micro Letters 2024年第2期16卷 32-67页

作者： Kelin He Zimo huang Chao Chen Chuntian Qiu Yu lin Zhong Qitao Zhang International Collaborative Laboratory of 2D Materials for Optoelectronics Science and Technology of Ministry of Education Institute of Microscale OptoelectronicsShenzhen UniversityShenzhen 518000China Queensland Micro‑and Nanotechnology Centre School of Environment and ScienceGriffith UniversityNathanQLD 4222Australia Institute for Sustainable Transformation School of Chemical Engineering and Light IndustryGuangdong University of TechnologyGuangzhou 51006China ZJU‑Hangzhou Global Scientific and Technological Innovation Center Zhejiang UniversityHangzhou 311215China

This comprehensive review provides a deep exploration of the unique roles of single atom catalysts(SACs)in photocatalytic hydrogen peroxide(H_(2)O_(2))production.SACs offer multiple benefits over traditional catalysts such as improved efficiency,selectivity,and flexibility due to their distinct electronic structure and unique properties.The review discusses the critical elements in the design of SACs,including the choice of metal atom,host material,and coordination environment,and how these elements impact the catalytic activity.The role of single atoms in photocatalytic H_(2)O_(2)production is also analysed,focusing on enhancing light absorption and charge generation,improving the migration and separation of charge carriers,and lowering the energy barrier of adsorption and activation of reactants.Despite these advantages,several challenges,including H_(2)O_(2)decomposition,stability of SACs,unclear mechanism,and low selectivity,need to be overcome.Looking towards the future,the review suggests promising research directions such as direct utilization of H_(2)O_(2),high-throughput synthesis and screening,the creation of dual active sites,and employing density functional theory for investigating the mechanisms of SACs in H_(2)O_(2)photosynthesis.This review provides valuable insights into the potential of single atom catalysts for advancing the field of photocatalytic H_(2)O_(2)production.

关键词： Single atom catalysts H_(2)O_(2)photosynthesis Catalyst design and optimization

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