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Protein neddylation and its role in health and diseases

Signal Transduction and Targeted Therapy 2024年第5期9卷 1869-1904页

作者： shizhen zhang Qing Yu Zhijian Li Yongchao Zhao Yi Sun Department of Breast Surgery the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310029China Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310029China Institute of Translational Medicine Zhejiang University School of MedicineHangzhou 310029China Department of Thyroid Surgery Zhejiang Cancer HospitalInstitute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhou 310022China Key Laboratory of Head&Neck Cancer Translational Research of Zhejiang Province Hangzhou 310022China Department of Hepatobiliary and Pancreatic Surgery Zhejiang University School of MedicineHangzhou 310029China Zhejiang Provincial Key Laboratory of Pancreatic Disease The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310029China Zhejiang University Cancer Center Hangzhou 310029China Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang Hangzhou 310024China Research Center for Life Science and Human Health Binjiang Institute of Zhejiang UniversityHangzhou 310053China

NEDD8(Neural precursor cell expressed developmentally downregulated protein 8)is an ubiquitin-like protein that is covalently attached to a lysine residue of a protein substrate through a process known as neddylation,catalyzed by the enzyme cascade,namely NEDD8 activating enzyme(E1),NEDD8 conjugating enzyme(E2),and NEDD8 ligase(E3).The substrates of neddylation are categorized into cullins and non-cullin proteins.Neddylation of cullins activates CRLs(cullin RING ligases),the largest family of E3 ligases,whereas neddylation of non-cullin substrates alters their stability and activity,as well as subcellular localization.Significantly,the neddylation pathway and/or many neddylation substrates are abnormally activated or over-expressed in various human diseases,such as metabolic disorders,liver dysfunction,neurodegenerative disorders,and cancers,among others.Thus,targeting neddylation becomes an attractive strategy for the treatment of these diseases.In this review,we first provide a general introduction on the neddylation cascade,its biochemical process and regulation,and the crystal structures of neddylation enzymes in complex with cullin substrates;then discuss how neddylation governs various key biological processes via the modification of cullins and non-cullin substrates.We further review the literature data on dysregulated neddylation in several human diseases,particularly cancer,followed by an outline of current efforts in the discovery of small molecule inhibitors of neddylation as a promising therapeutic approach.Finally,few perspectives were proposed for extensive future investigations.

关键词： NEDD8 attached attractive

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Al-driven analysis establishes the single base substitution signatures as personalized prognostic predictors for five-year survival of gastric cancer

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Genes & Diseases 2024年第4期11卷 73-76页

作者： Zhenzhang Li Lingqing Xu Wen Luo Shaoan zhangg Chunyu Hou Xiaohong Xu ,Xubei Peng E.Shiju Janak L.Pathak shizhen zhang Jiawei Liu Linhai Li Yang Li School of Biomedical Engineering The Sixth Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdong 511436China College of Mathematics and Systems Science Guangdong Polytechnic Normal UniversityGuangzhouGuangdong 510665China The Second Affiliated Hospital Guangzhou Medical UniversityGuangzhouGuangdong 510260China Center for Learning Sciences and Technologies The Chinese University of Hong KongShatinNew Territories 999077China Affiliated Stomatology Hospital of Guangzhou Medical University Guangzhou Medical UniversityGuangzhouGuangdong 510182China International School of Photonics Cochin University of Science and TechnologyKochiKerala 682022India

Al-driven genetic engineering,as a burgeoning diagnostic tool,can offer predictive information on the five-year survival rate(FYSR)in the setup of a prognostic therapeutic schedule.This approach provides the individuality and accuracy of prognosis for FYSR of gastric cancer(GC).Unlike traditional neoplasm staging criteria,our technique ensures accuracy and individuality without relying on statistical data and empirical study.

关键词： cancer gastric prognosis

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Metal-organic framework hybrid materials of ZIF-8/RGO for immobilization of D-amino acid dehydrogenase

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Nano Research 2024年第1期17卷 290-296页

作者： Hangbin Lei Qian zhang Xiaoyan Xiang Liang Jiang Shiyan Wang Lingxuan Duan shizhen Wang Department of Chemical and Biochemical Engineering College of Chemistry and Chemical EngineeringXiamen UniversityXiamen 361005China Xiamen Key Laboratory of Synthetic Biotechnology Xiamen UniversityXiamen 361005China

Immobilization of D-amino acid dehydrogenase(DAADH)by the assembly of peptide linker was studied for the biosynthesis of Dphenylalanine.Hybrid material of zeolitic imidazolate framework-8(ZIF-8)combined with reduced graphene oxide(RGO)was applied for the immobilization of DAADH from Ureibacillus thermosphaericus.The recovery rate of DAADH/ZIF-8/RGO was 165.6%.DAADH/ZIF-8/RGO remained 53.4%of its initial activity at 50°C for 10 h while the free enzyme was inactivated.DAADH/ZIF-8/RGO maintained 70.5%activity in hyperalkaline solution with pH 12.Kinetic parameters indicated that DAADH/ZIF-8/RGO had greater affinity of phenylpyruvate as V_(max)/K_(m)of DAADH/ZIF-8/RGO was 1.27-fold than free enzyme.After seven recycles,the activity of DAADH/ZIF-8/RGO remained 64.3%.Furthermore,one-step separation and in situ immobilization of DAADH by ZIF-8/RGO/Ni was carried out with 1.5-fold activity enhancement.Combining peptide linker and metal-organic framework(MOF)immobilization,thermostability and activity of the immobilized DAADH were significantly improved.

关键词： D-Amino acid dehydrogenase immobilization metal-organic frameworks zeolitic imidazolate framework-8(ZIF-8) reduced graphene oxide

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Design and development of a five-axis machine tool with high accuracy,stiffness and efficiency for aero-engine casing manufacturing

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Chinese Journal of Aeronautics 2022年第4期35卷 485-496页

作者： Yutian WANG Dong WANG shizhen zhang Zihan TANG Liping WANG Yanmin LIU State Key Laboratory of Tribology and Institute of Manufacturing Engineering Department of Mechanical EngineeringTsinghua UniversityBeijing 100084China Beijing Key Lab of Precision Ultraprecision Manufacturing Equipment and Control Beijing 100084China Beijing Precision Machinery&Engineering Research Co.LTD Beijing 101312China Beijing Institute of Control Engineering Beijing 100094China

In order to satisfy the machining requirements of aero-engine casing in modern aviation industry, this paper investigates three main issues during the design and development process of a five-axis machine tool with high accuracy, stiffness and efficiency, including whole structure design,key components design, and supporting stiffness design. First, an appropriate structure of five-axis machine tool is determined considering the processing characteristics of aero-engine casing. Then, a dual drive swing head and a compact motorized spindle are designed with enough drive capability and stiffness, and related structure, assembly method, cooling technology, and performance simulation are given in detail. Next, a design method of supporting stiffness of guide is proposed through the deformation prediction of the spindle end. Based on above work, a prototype of machine tool is developed, and some experiments are carried out, including performance tests of swing head and motorized spindle, and machining of a simulated workpiece of aero-engine casing. All experimental results show that the machine tool has satisfactory accuracy, stiffness and efficiency, which meets the machining requirements of aero-engine casing. The main work can be used as references for engineers and technicians, which are meaningful in practice.

关键词： Aero-engine casing manufacturing Compact motorized spindle Dual drive swing head Five-axis machine tool Supporting stiffness

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Targeting oncogenic SOX2 in human cancer cells: therapeutic application

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Protein & Cell 2020年第2期11卷 82-84页

作者： shizhen zhang Yi Sun Division of Radiation and Cancer Biology Department of Radiation OncologyUniversity of MichiganAnn ArborMl 48109USA The Cancer Institute of the Second Affiliated Hospital and Institute of Translational Medicine Zhejiang University School of MedicineHangzhou 310029China

Sry-related high-mobility box 2(SOX2)is a critical transcription factor that plays an important role in various phases of embryonic development and maintenance of undifferentiated embryonic stem cells(ESCs)(Feng and Wen,2015).SOX2,as one of the Yamanaka factors,is involved in the conversion of mouse embryonic fibroblast cells(MEFs)into induced pluripotent stem cells(iPSCs)(Takahashi and Yamanaka,2006).Recently,SOX2 amplification,usually couples with aberrantly increased expression,were found in various human cancers,including breast,lung,esophagus,colon,prostate,ovarian among the others(Novak et al.,2019).SOX2 overexpression promotes cancer progression by accelerating cell proliferation,colony formation,migration,invasion,and sphere formation.Furthermore,SOX2 is causally related to the development of the resistance of cancer cells to chemotherapy.

关键词： SOX2 cancer invasion

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Functional characterization of SOX2 as an anticancer target

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1304-1320页

作者： shizhen zhang Xiufang Xiong Yi Sun The Cancer Institute of the Second Affiliated Hospital and Institute of Translational Medicine Zhejiang University School of MedicineHangzhou 310029China

SOX2 is a well-characterized pluripotent factor that is essential for stem cell self-renewal,reprogramming,and homeostasis.The cellular levels of SOX2 are precisely regulated by a complicated network at the levels of transcription,post-transcription,and posttranslation.In many types of human cancer,SOX2 is dysregulated due to gene amplification and protein overexpression.SOX2 overexpression is associated with poor survival of cancer patients.Mechanistically,SOX2 promotes proliferation,survival,invasion/metastasis,cancer stemness,and drug resistance.SOX2 is,therefore,an attractive anticancer target.However,little progress has been made in the efforts to discover SOX2 inhibitors,largely due to undruggable nature of SOX2 as a transcription factor.In this review,we first briefly introduced SOX2 as a transcription factor,its domain structure,normal physiological functions,and its involvement in human cancers.We next discussed its role in embryonic development and stem cell-renewal.We then mainly focused on three aspects of SOX2:(a)the regulatory mechanisms of SOX2,including how SOX2 level is regulated,and how SOX2 cross-talks with multiple signaling pathways to control growth and survival;(b)the role of SOX2 in tumorigenesis and drug resistance;and(c)current drug discovery efforts on targeting SOX2,and the future perspectives to discover specific SOX2 inhibitors for effective cancer therapy.

关键词： SOX2 invasion involvement

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Road map for, and technical challenges of, carbon-nanotube integrated circuit technology

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National Science Review 2024年第3期11卷 14-16页

作者： Jia Si Panpan zhang Zhiyong zhang Key Laboratory for the Physics and Chemistry of Nanodevices and Center for Carbon-based Electronics School of Electronics Peking University State Key Laboratory of Information Photonics and Optical Communications Beijing University of Posts and Telecommunications

The past decade has witnessed an explosion of research on carbon-nanotube(CNT) electronics due to their outstanding properties, including an ultrathin body, a high carrier mobility and a high saturation velocity.

关键词： TRANSISTORS

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New structure transistors for advanced technology node CMOS ICs

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National Science Review 2024年第3期11卷 24-41页

作者： Qingzhu zhang Yongkui zhang Yanna Luo Huaxiang Yin Integrated Circuit Advanced Process R&D Center Institute of Microelectronics of Chinese Academy of Sciences(IMECAS) State key Lab of Fabrication Technologies for Integrated Circuits Institute of Microelectronics of Chinese Academy of Sciences School of Integrated Circuits University of Chinese Academy of Sciences

Over recent decades, advancements in complementary metal-oxide-semiconductor integrated circuits(ICs)have mainly relied on structural innovations in transistors. From planar transistors to the fin field-effect transistor(FinFET) and gate-all-around FET(GAAFET), more gate electrodes have been added to three-dimensional(3D) channels with enhanced control and carrier conductance to provide higher electrostatic integrity and higher operating currents within the same device footprint. Beyond the 1-nm node, Moore's law scaling is no longer expected to be applicable to geometrical shrinkage. Vertical transistor stacking, e.g. in complementary FETs(CFET), 3D stack(3DS) FETs and vertical-channel transistors(VFET), for enhanced density and variable circuit or system design represents a revolutionary scaling approach for sustained IC development. Herein, innovative works on specific structures, key process breakthroughs, shrinking cell sizes and design methodologies for transistor structure research and development are reviewed. Perspectives on future innovations in advanced transistors with new channel materials and operating theories are also discussed.

关键词： transistor CMOS GAAFET CFET 3DS FET

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Advances in methane emissions from agricultural sources:Part I.Accounting and mitigation

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Journal of Environmental Sciences 2024年第6期140卷 279-291页

作者： Xiaokun Wu Ying zhang Yinghui Han Yagang zhang Yuhang zhang Xiaodan Cheng Pei Zhong Xue Yuan Yuanxun zhang Zhengqiang Li State Key Laboratory of Alternate Electrical Power System with Renewable Energy Sources North China Electric Power UniversityBeijing 102206China Hebei Key Laboratory of Physics and Energy Technology North China Electric Power UniversityBaoding 071003China College of Resources and Environment University of Chinese Academy of SciencesBeijing 101408China Interdisciplinary Mathematics Institute University of South CarolinaColumbiaSC 29208United States Aerospace Information Research Institute Chinese Academy of SciencesBeijing 100094China

Methane is one of the major greenhouse gases(GHGs)and agriculture is recognized as its primary emitter.Methane accounting is a prerequisite for developing effective agriculture mitigation strategies.In this review,methane accounting methods and research status for various agricultural emission source including rice fields,animal enteric fermentation and livestock and poultry manure management were overview,and the influencing factors of each emission source were analyzed and discussed.At the same time,it analyzes the different research efforts involving agricultural methane accounting and makes recommendations based on the actual situation.Finally,mitigation strategies based on accounting results and actual situation are proposed.This review aims to provide basic data and reference for agriculture-oriented countries and regions to actively participate in climate action and carry out effective methane emission mitigation.

关键词： Methane emission Agricultural sources Accounting methodology Mitigation Emission influencing factors

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Interface Engineering of Titanium Nitride Nanotube Composites for Excellent Microwave Absorption at Elevated Temperature

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Nano-Micro Letters 2024年第9期16卷 147-160页

作者： Cuiping Li Dan Li Shuai zhang Long Ma Lei zhang* Jingwei zhang Chunhong Gong College of Chemistry and Molecular Sciences Henan UniversityKaifeng 475004People’s Republic of China National and Local Joint Engineering Research Center for Applied Technology of Hybrid Nanomaterials Henan UniversityKaifeng 475004People’s Republic of China

Currently,the microwave absorbers usually suffer dreadful electromagnetic wave absorption(EMWA)performance damping at elevated temperature due to impedance mismatching induced by increased conduction loss.Consequently,the development of high-performance EMWA materials with good impedance matching and strong loss ability in wide temperature spectrum has emerged as a top priority.Herein,due to the high melting point,good electrical conductivity,excellent environmental stability,EM coupling effect,and abundant interfaces of titanium nitride(TiN)nanotubes,they were designed based on the controlling kinetic diffusion procedure and Ostwald ripening process.Benefiting from boosted heterogeneous interfaces between TiN nanotubes and polydimethylsiloxane(PDMS),enhanced polarization loss relaxations were created,which could not only improve the depletion efficiency of EMWA,but also contribute to the optimized impedance matching at elevated temperature.Therefore,the TiN nanotubes/PDMS composite showed excellent EMWA performances at varied temperature(298-573 K),while achieved an effective absorption bandwidth(EAB)value of 3.23 GHz and a minimum reflection loss(RLmin)value of−44.15 dB at 423 K.This study not only clarifies the relationship between dielectric loss capacity(conduction loss and polarization loss)and temperature,but also breaks new ground for EM absorbers in wide temperature spectrum based on interface engineering.

关键词： TiN nanotubes Interface engineering Polarization loss Impedance matching Electromagnetic wave absorption performance

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