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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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Identification and validation of novel prognostic fatty acid metabolic gene signatures in colon adenocarcinoma through systematic approaches

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Oncology Research 2024年第2期32卷 297-308页

作者： HENG ZHANG WENJING CHENG HAIBO zhao WEIDONG CHEN QIUJIE ZHANG qing-qing yu Department of Laboratory Shandong Daizhuang HospitalJining272051China Jining No.1 People’s Hospital Shandong First Medical UniversityJining272000China

Colorectal cancer(CRC)belongs to the class of significantly malignant tumors found in humans.Recently,dysregulated fatty acid metabolism(FAM)has been a topic of attention due to its modulation in cancer,specifically CRC.However,the regulatory FAM pathways in CRC require comprehensive elucidation.Methods:The clinical and gene expression data of 175 fatty acid metabolic genes(FAMGs)linked with colon adenocarcinoma(COAD)and normal cornerstone genes were gathered through The Cancer Genome Atlas(TCGA)-COAD corroborating with the Molecular Signature Database v7.2(MSigDB).Initially,crucial prognostic genes were selected by uni-and multi-variate Cox proportional regression analyses;then,depending upon these identified signature genes and clinical variables,a nomogram was generated.Lastly,to assess tumor immune characteristics,concomitant evaluation of tumor immune evasion/risk scoring were elucidated.Results:A 8-gene signature,including ACBD4,ACOX1,CD36,CPT2,ELOVL3,ELOVL6,ENO3,and SUCLG2,was generated,and depending upon this,CRC patients were categorized within high-risk(H-R)and low-risk(L-R)cohorts.Furthermore,risk and age-based nomograms indicated moderate discrimination and good calibration.The data confirmed that the 8-gene model efficiently predicted CRC patients’prognosis.Moreover,according to the conjoint analysis of tumor immune evasion and the risk scorings,the H-R cohort had an immunosuppressive tumor microenvironment,which caused a substandard prognosis.Conclusion:This investigation established a FAMGs-based prognostic model with substantially high predictive value,providing the possibility for improved individualized treatment for CRC individuals.

关键词： Fatty acid metabolism Colorectal cancer Gene signatures Machine learning

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Identifying the origin of porous evolution of microsized bismuth in potassium-ion batteries

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Science China Chemistry 2024年第7期67卷 2234-2239页

作者： Shenxu Chu Kaixiang Lei Qian Yang Jiaxin Li yuqing zhao Mengjia Gu Lin Li Xing Hu yu Zhang Zhuo Chen Shuo Shi Shulei Chou Shijian Zheng Tianjin Key Laboratory of Materials Laminating Fabrication and Interface Control Technology School of Materials Science and EngineeringHebei University of TechnologyTianjin 300401China Institute for Carbon Neutralization Technology College of Chemistry and Materials EngineeringWenzhou UniversityWenzhou 325035China

Microsized bismuth(Bi)with in-situ constructed three-dimensional(3D)porous network has been considered as a promising anode for high-performance potassium-ion batteries(PIBs).However,the mechanism of the in-situ porous evolution of microsized Bi during the charge/discharge process is still mysterious.Herein,various electrolytes are employed to disclose the origin of porous evolution of microsized Bi in PIBs.Experimentally and theoretically,the 3D porous network originates from the uniform interfacial charge distribution on the Bi surface in the linear ether-based electrolyte.In addition,the universality of the interfacial charge distribution mechanism was verified by microsized Sn and Sb.The in-situ constructed 3D porous network of Bi enables a superior potassium storage performance in a wide temperature range from-40 to 40°C.More importantly,the K_(0.9)Mn_(0.7)Ni_(0.3)O_(2)||Bi full cell delivers excellent cycling stability(a high capacity retention of 88.44%even after 2,000 cycles)and good temperature tolerance.This work gives a distinct clarification of the origin of the porous evolution of microsized Bi during cycling,which is critical for developing high-performance PIBs.

关键词： potassium-ion batteries microsized Bi porous evolution linear ether-based electrolyte interfacial charge distribution

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Properties of collective flow and pion production in intermediate-energy heavy-ion collisions with a relativistic quantum molecular dynamics model

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Nuclear Science and Techniques 2024年第1期35卷 155-169页

作者： Si-Na Wei zhao-qing Feng School of Physics and Optoelectronics South China University of TechnologyGuangzhou 510640China

The relativistic mean-field approach was implemented in the Lanzhou quantum molecular dynamics transport model(LQMD.RMF). Using the LQMD.RMF, the properties of collective flow and pion production were investigated systematically for nuclear reactions with various isospin asymmetries. The directed and elliptic flows of the LQMD.RMF are able to describe the experimental data of STAR Collaboration. The directed flow difference between free neutrons and protons was associated with the stiffness of the symmetry energy, that is, a softer symmetry energy led to a larger flow difference. For various collision energies, the ratio between the π^(-) and π^(+) yields increased with a decrease in the slope parameter of the symmetry energy. When the collision energy was 270 MeV/nucleon, the single ratio of the pion transverse momentum spectra also increased with decreasing slope parameter of the symmetry energy in both nearly symmetric and neutron-rich systems.However, it is difficult to constrain the stiffness of the symmetry energy with the double ratio because of the lack of threshold energy correction on the pion production.

关键词： Heavy-ion collision Collective flow Pion production Symmetry energy Relativistic mean field

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Prospects in the application of ultrasensitive chromosomal aneuploidy detection in precancerous lesions of gastric cancer

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World Journal of Gastrointestinal Surgery 2024年第1期16卷 6-12页

作者： Su-Ting Qian Fei-Fei Xie Hao-yu zhao qing-Sheng Liu Dan-Li Cai Department of Digestive Hangzhou Hospital of Traditional Chinese MedicineHangzhou 310007Zhejiang ProvinceChina Science and Education Section Hangzhou Hospital of Traditional Chinese MedicineHangzhou 310007Zhejiang ProvinceChina Intensive Care Unit The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 311122Zhejiang ProvinceChina

Gastric cancer(GC)is a prevalent malignant tumor within the digestive system,with over 40%of new cases and deaths related to GC globally occurring in China.Despite advancements in treatment modalities,such as surgery supplemented by adjuvant radiotherapy or chemotherapeutic agents,the prognosis for GC remains poor.New targeted therapies and immunotherapies are currently under invest-igation,but no significant breakthroughs have been achieved.Studies have indicated that GC is a heterogeneous disease,encompassing multiple subtypes with distinct biological characteristics and roles.Consequently,personalized treatment based on clinical features,pathologic typing,and molecular typing is crucial for the diagnosis and management of precancerous lesions of gastric cancer(PLGC).Current research has categorized GC into four subtypes:Epstein-Barr virus-positive,microsatellite instability,genome stability,and chromosome instability(CIN).Technologies such as multi-omics analysis and gene sequencing are being employed to identify more suitable novel testing methods in these areas.Among these,ultrasensitive chromosomal aneuploidy detection(UCAD)can detect CIN at a genome-wide level in subjects using low-depth whole genome sequencing technology,in conjunction with bioinformatics analysis,to achieve qualitative and quantitative detection of chromosomal stability.This editorial reviews recent research advancements in UCAD technology for the diagnosis and management of PLGC.

关键词： Gastric cancer Precancerous lesions of gastric cancer Molecular typing Ultrasensitive chromosomal aneuploidy detection Adjuvant therapy Application prospects

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Data driven analysis reveals prognostic genes and immunological targets in human sepsis-associated acute kidney injury

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World Journal of Emergency Medicine 2024年第2期15卷 91-97页

作者： qing zhao Jinfu Ma Jianguo Xiao Zhe Feng Hui Liu Department of Diagnosis and Treatment of Cadres the First Medical CenterChinese PLA General HospitalBeijing 100853China Intensive Care Unit the 305th Hospital of Chinese PLABeijing 100032China Department of Critical Care Medicine the First Medical CenterChinese PLA General HospitalBeijing 100853China Nephrology Department the First Medical CenterChinese PLA General HospitalBeijing 100853China

BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-AKI.METHODS:The microarray datasets GSE65682,GSE30718,and GSE174220 were downloaded from the Gene Expression Omnibus(GEO)database.We identified the co-DEGs and constructed a gene co-expression network to screen the hub genes.We analyzed immune correlations and disease correlations and performed functional annotation of the hub genes.We also performed single-cell and microenvironment analyses and investigated the enrichment pathways and the main transcription factors.Finally,we conducted a correlation analysis to evaluate the role of the hub genes.RESULTS:Interleukin 32(IL32)was identified as the hub gene in SA-AKI,and the main enriched signaling pathways were associated with hemopoiesis,cellular response to cytokine stimulus,inflammatory response,and regulation of kidney development.Additionally,IL32 was significantly associated with mortality in SA-AKI patients.Monocytes,macrophages,T cells,and NK cells were closely related to IL32 and were involved in the immune microenvironment in SA-AKI patients.IL32 expression increased significantly in the kidney of septic mouse.Toll-like receptor 2(TLR2)was significantly and negatively correlated with IL32.CONCLUSION:IL32 is the key gene involved in SA-AKI and is significantly associated with prognosis.TLR2 and relevant immune cells are closely related to key genes.

关键词： Sepsis Acute kidney injury Interleukin 32 Toll-like receptor 2 Bioinformatics analysis

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Physics of cavitation near particles

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Journal of Hydrodynamics 2024年第1期36卷 102-118页

作者： Jia-xin yu Xiao-yu Wang Jun-wei Shen Jin-sen Hu Xiang-qing Zhang Da-qing He yu-ning Zhang Key Laboratory of Power Station Energy Transfer Conversion and System(Ministry of Education) School of Energy Power and Mechanical EngineeringNorth China Electric Power UniversityBeijing102206China

The combined effect of cavitation and silt abrasion presents a great challenge and threat to secure the operation and the efficiency of hydraulic machineries working in sediment-laden fluid.The present paper critically reviews the current research progress on the interaction mechanisms of the bubbles and the particles.Firstly,the analytical models including boundary treatment methods for predicting the jet dynamics of the bubble collapse near particles are demonstrated.Secondly,the bubble collapsing dynamics,jet dynamics and shock wave characteristics near particles are revealed both experimentally and numerically.Finally,the bubble-particle-wall system is investigated with a focus on microjets.

关键词： Cavitation bubble particle jet shock wave

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Formation of free-surface vortex and vortex suppression by rotating stopper-rod at end of tundish casting

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Journal of Iron and Steel Research(International) 2024年第5期31卷 1104-1116页

作者： qing Fang Peng zhao Hua Zhang Wen-hao Zhou Gang yu Jia-hui Wang Hong-wei Ni The State Key Laboratory of Refractories and Metallurgy Wuhan University of Science and TechnologyWuhan430081HubeiChina Hunan Valin Xiangtan Iron and Steel Co. Ltd.Xiangtan411101HunanChina Hubei Provincial Key Laboratory for New Processes of Ironmaking and Steelmaking Wuhan University of Science and TechnologyWuhan430081HubeiChina

A rotating stopper-rod technique was proposed to suppress the formation of free-surface vortex in the tundish.The large eddy simulation model coupled with volume of fluid model was developed to study the steel–slag–gas three-phase flow behavior.The critical slag entrapment height of the free-surface vortex and mass of residual steel were predicted at different rotating speeds(30,60,90 and 120 r/min)of the rotating stopper-rod.The numerical model was verified by water model experiment.The results showed that by rotating the stopper-rod in the opposite direction of the vortex above the submerged entry nozzle,the formation of vortex can be effectively disturbed and the critical height of the free-surface vortex can be reduced.Particularly for the 2nd strand,when the rotating speeds are 30,60,90 and 120 r/min,the critical height of the free-surface vortex above the 2nd strand is 7.3,4.7,6.3 and 7.4 cm,respectively.A reasonable rotating speed should be 60 r/min,which can reduce about 2 tons of residual steel.Other rotating speeds just can reduce about 1.6 tons of residual steel.

关键词： Tundish Free-surface vortex Stopper-rod Numerical simulation Multiphase flow

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Bifurcation Analysis Reveals Solution Structures of Phase Field Models

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Communications on Applied Mathematics and Computation 2024年第1期6卷 64-89页

作者： Xinyue Evelyn zhao Long-qing Chen Wenrui Hao Yanxiang zhao Department of Mathematics Vanderbilt UniversityNashvilleTN37212USA Department of Materials Science and Engineering Pennsylvania State UniversityUniversity ParkPA16802USA Department of Mathematics Pennsylvania State UniversityUniversity ParkPA16802USA Department of Mathematics The George Washington UniversityWashingtonDC20052US

The phase field method is playing an increasingly important role in understanding and predicting morphological evolution in materials and biological systems.Here,we develop a new analytical approach based on the bifurcation analysis to explore the mathematical solution structure of phase field models.Revealing such solution structures not only is of great mathematical interest but also may provide guidance to experimentally or computationally uncover new morphological evolution phenomena in materials undergoing electronic and structural phase transitions.To elucidate the idea,we apply this analytical approach to three representative phase field equations:the Allen-Cahn equation,the Cahn-Hilliard equation,and the Allen-Cahn-Ohta-Kawasaki system.The solution structures of these three phase field equations are also verified numerically by the homotopy continuation method.

关键词： Phase field modeling Bifurcations Multiple solutions

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To explore the mechanism of Yigong San anti-gastric cancer and immune regulation

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1965-1994页

作者： Dou-Dou Lu Ling yuan zhao-zhao Wang Jian-Jun zhao yu-Hua Du Na Ning Guo-qing Chen Shi-Cong Huang Yi Yang Zhe Zhang Yi Nan School of Clinical Medicine Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina College of Pharmacy Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina Traditional Chinese Medicine College Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina Department of Chinese Medical Gastrointestinal China-Japan Friendship HospitalBeijing 100029China Key Laboratory of Ningxia Minority Medicine Modernization Ministry of Education Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina

BACKGROUND Yigong San(YGS)is a representative prescription for the treatment of digestive disorders,which has been used in clinic for more than 1000 years.However,the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear.AIM To explore the mechanism of YGS anti-gastric cancer and immune regulation.METHODS Firstly,collect the active ingredients and targets of YGS,and the differentially expressed genes of gastric cancer.Secondly,constructed a protein-protein interaction network between the targets of drugs and diseases,and screened hub genes.Then the clinical relevance,mutation and repair,tumor microenvironment and drug sensitivity of the hub gene were analyzed.Finally,molecular docking was used to verify the binding ability of YGS active ingredient and hub genes.RESULTS Firstly,obtained 55 common targets of gastric cancer and YGS.The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6,EGFR,MMP2,MMP9 and TGFB1 as the hub genes.The 5 hub genes were involved in gastric carcinogenesis,staging,typing and prognosis,and their mutations promote gastric cancer progression.Finally,molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets.CONCLUSION YGS has the effect of anti-gastric cancer and immune regulation.

关键词： Gastric cancer Yigong San Mechanism Immune

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