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The Functional Redundancy of Neddylation E2s and E3s in Modulating the Fitness of Regulatory T Cells

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Research 2024年第2期2023卷 373-387页

作者： Di Wu yi sun 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 Zhejang Provincial Clinical Research Center for Cancer Zhejang ProvinceChina Key Laboratory of Molecular Biology in Medical Sciences Zhejang ProvinceChina Research Center for Life Science and Human Health Binjiang Institute of Zhejiang UniversityHangzhou 310053China

Neddylation is necessary for activation of Cullin-RING ligases(CRLs),which degrade various immune regulatory *** recent study showed that while depletion of neddylation E2-E3 pair Ube2f-Sag in regulatory T(T_(reg))cells had no obvious phenotype,the same depletion of either Ube2m or Rbx1 caused inflammation disorders with different *** these E2s or E3s compensate each other in functional regulations of T_(reg)cells is,however,previously *** this report,we generated Foxp3^(Cre);Ube2m^(fl/fl);Ube2f^(fl/fl)or Foxp3^(Cre);Rbx1^(fl/fl);Sag^(fl/fl)double-null mice by simultaneous deletion of both neddylation E2s or E3s in T_(reg)cells,***,Ube2m&Ube2f double-null mice developed much severe autoimmune phenotypes than did Ube2m-null mice,indicating that Ube2m markedly compensates Ube2f in T_(reg)*** minor worsened autoimmune phenotypes seen at the very early stage in Rbx1&Sag double-null than Rbx1-null mice is likely due to already severe phenotypes of the later,indicating a minor compensation of Rbx1 for *** RNA profiling-based analyses revealed that up-and down-regulations of few signaling pathways in T_(reg)cells are associated with the severity of autoimmune ***,severer inflammation phenotypes seen in mice with double E3-null than with double E2-null T_(reg)cells indicate a neddylation-independent mechanism of 2 E3s,also known to serve as the RING component of CRLs in regulation of T_(reg)cell fitness.

关键词： Foxp3 inflammation markedly

Improved Twin Support Vector Machine Algorithm and Applications in Classification Problems

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China Communications 2024年第5期21卷 261-279页

作者： sun yi Wang Zhouyang Beijing University of Posts and Telecommunications School of Computer Science(National Pilot Software Engineering School) Beijing University of Posts and Telecommunications International School

The distribution of data has a significant impact on the results of *** the distribution of one class is insignificant compared to the distribution of another class,data imbalance *** will result in rising outlier values and ***,the speed and performance of classification could be greatly *** the above problems,this paper starts with the motivation and mathematical representing of classification,puts forward a new classification method based on the relationship between different classification *** with the vector characteristics of the actual problem and the choice of matrix characteristics,we firstly analyze the orderly regression to introduce slack variables to solve the constraint problem of the lone *** we introduce the fuzzy factors to solve the problem of the gap between the isolated points on the basis of the support vector *** introduce the cost control to solve the problem of sample ***,based on the bi-boundary support vector machine,a twostep weight setting twin classifier is *** can help to identify multitasks with feature-selected patterns without the need for additional optimizers,which solves the problem of large-scale classification that can’t deal effectively with the very low category distribution gap.

关键词： fuzzy ordered regression(OR) relaxing variables twin support vector machine

Neddylation Regulation of Immune Responses

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Research 2024年第3期2023卷 545-559页

作者： Hongmei Mao Xin Lin yi sun 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 Institute for Immunology School of MedicineTsinghua UniversityBeijing 100084China Changping Laboratory Beijing 102206China Cancer Center of Zhejiang University Hangzhou 310029China Zhejiang Provincial Clinical Research Center for Cancer HangzhouZhejiang ProvinceChina Key Laboratory of Molecular Biology in Medical Sciences HangzhouZhejiang ProvinceChina Research Center for Life Science and Human Health Binjiang Institute of Zhejiang UniversityHangzhou 310053China.

Neddylation plays a vital role in post-translational modification, intricately shaping the regulation of diverse biological processes, including those related to cellular immune responses. In fact, neddylation exerts control over both innate and adaptive immune systems via various mechanisms. Specifically, neddylation influences the function and survival of innate immune cells, activation of pattern recognition receptors and GMP-AMP synthase–stimulator of interferon genes pathways, as well as the release of various cytokines in innate immune reactions. Moreover, neddylation also governs the function and survival of antigen-presenting cells, which are crucial for initiating adaptive immune reactions. In addition, neddylation regulates T cell activation, proliferation, differentiation, survival, and their effector functions, thereby ensuring an appropriate adaptive immune response. In this review, we summarize the most recent findings in these aspects and delve into the connection between dysregulated neddylation events and immunological disorders, especially inflammatory diseases. Lastly, we propose future directions and potential treatments for these diseases by targeting neddylation.

关键词： activation thereby initiating

NADPH oxidase 4(NOX4)as a biomarker and therapeutic target in neurodegenerative diseases

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Neural Regeneration Research 2024年第9期19卷 1961-1966页

作者： Napissara Boonpraman sun Shin yi BK21 four Program Department of Medical SciencesSoonchunhyang UniversityAsanSouth Korea Department of Biomedical Laboratory Science Soonchunhyang UniversityAsanSouth Korea iConnectome Co.Ltd.CheonanSouth Korea

Diseases like Alzheimer’s and Parkinson’s diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NADPH oxidase 4, is viewed as a potential therapeutic touchstone and indicative marker for these ailments. This in-depth review brings to light distinct features of NADPH oxidase 4, responsible for generating superoxide and hydrogen peroxide, emphasizing its pivotal role in activating glial cells, inciting inflammation, and disturbing neuronal functions. Significantly, malfunctioning astrocytes, forming the majority in the central nervous system, play a part in advancing neurodegenerative diseases, due to their reactive oxygen species and inflammatory factor secretion. Our study reveals that aiming at NADPH oxidase 4 within astrocytes could be a viable treatment pathway to reduce oxidative damage and halt neurodegenerative processes. Adjusting NADPH oxidase 4 activity might influence the neuroinflammatory cytokine levels, including myeloperoxidase and osteopontin, offering better prospects for conditions like Alzheimer’s disease and Parkinson’s disease. This review sheds light on the role of NADPH oxidase 4 in neural degeneration, emphasizing its drug target potential, and paving the path for novel treatment approaches to combat these severe conditions.

关键词： Alzheimer’s disease astrocytes mitochondrial dysfunction myeloperoxidase NADPH oxidase 4 NADPH oxidase 4 inhibitors neurodegenerative diseases osteopontin Parkinson’s disease reactive oxygen species

Evaluation of water management on arsenic methylation and volatilization in arsenic-contaminated soils strengthened by bioaugmentation and biostimulation

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Journal of Environmental Sciences 2024年第3期137卷 515-526页

作者： Peng Chen yi Liu Guo-Xin sun State Key Laboratory of Urban and Regional Ecology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China Key Laboratory of Aquatic Botany and Watershed Ecology Wuhan Botanical GardenChinese Academy of SciencesWuhan 430074China University of Chinese Academy of Sciences Beijing 100049China

Arsenic(As) fate in paddy fields has been one of the most significant current issues due to the strong As accumulation potential of rice plants under fooded conditions. However,no attempt was done to explore As methylation and volatilization under non-fooded conditions. Herein, we investigated the effects of water management on As methylation and volatilization in three arsenic-contaminated soils enhanced by biostimulation with strawderived organic matter and bioaugmentation with genetic engineered Pseudomonas putida KT2440(GE P. putida). Under fooded conditions, the application of biochar(BC), rice straw(RS)and their combination(BC+RS) increased total As in porewater. However, these effects were greatly attenuated under non-fooded conditions. Compared with RS amendment alone, the combination of GE P. putida and RS further promoted the As methylation and volatilization,and the promotion percentage under non-fooded conditions were significantly higher than that under fooded conditions. The combined GE P. putida and RS showed the highest efficiency in As methylation(88 μg/L) and volatilization(415.4 μg/(kg·year)) in the non-fooded soil with moderate As contamination. Finally, stepwise multiple linear regression analysis presented that methylated As, DOC and p H in porewater were the most important factors contributing to As volatilization. Overall, our findings suggest that combination of bioaugmentation with GE P. putida and biostimulation with RS/BC+RS is a potential strategy for bioremediation of arsenic-contaminated soils by enhancing As methylation and volatilization under non-fooded conditions.

关键词： Arsenic methylation Arsenic volatilization Water management Straw incorporation Bioaugmentation

Shape optimisation of basin insulator for DC gas insulated switchgear/gas insulated transmission lines based on artificial bee colony algorithm

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High Voltage 2024年第2期9卷 275-286页

作者： yi Luo Shiyi Mao ju Tang Zijun Pan Cheng Pan State Key Laboratory of Power Grid Environmental Protection School of Electrical Engineering and AutomationWuhan UniversityWuhanChina

The surface charge accumulation on the basin insulator is a particular problem in high-voltage direct current(HVDC)gas insulated switchgears(GIS)and gas insulated trans-mission lines(GIL),which restricts the development and application of extra/ultra high-voltage(EHV/UHV)*** surface charge distribution and anti-flashover performance are closely related to the insulator *** obtain the optimal basin insulator,a shape optimisation model based on artificial bee colony algorithm was established,and the minimisation objective functions based on capacitive(initial)electric field distribution and resistive(steady-state)electric field distribution were respectively *** optimisation results of the two objective functions were calculated,and the electric field and charge distribution on the surface of the insulator before and after optimisation were evaluated and compared using the simulation *** results indicated that the optimisation based on the capacitive electric field can significantly inhibit the surface charge accumulation,and the optimised insulator can significantly reduce the surface normal electric field and make the distribution of the tangential electric field more uniform,and the maximum tangential electric field can be reduced by 10%;the optimisation based on resistive electric field can achieve similar results,but requires more computational *** on the results,the‘anti-charge’basin insulator structure suitable for the DC field was given.

关键词： insulator artificial charge

Navigating the safe operation of high-voltage cathodes:Challenges and strategies

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Nano Research 2024年第10期17卷 8694-8705页

作者： Yue sun Changjian Zuo yi-Chun Lu Electrochemical Energy and Interfaces Laboratory Department of Mechanical and Automation EngineeringThe Chinese University of Hong KongHong Kong 999077China

Lithium-ion batteries play a crucial role in storing energy for renewable sources and electric vehicles,yet face challenges related to insufficient energy *** the working-voltage of cathodes is promising to boost the energy density of batteries by increasing both the output voltage and capacity of cathode,which however could compromise life cycle and *** review provides a comprehensive summary of essential factors governing pathways of cathode-induced thermal runaway,including electrolyte decomposition,phase transitions,and crosstalk-induced *** and electrolyte modifications aimed at mitigating parasitic reactions and preventing crosstalk were also *** review concludes with insights into the future application of these strategies,providing a comprehensive perspective on the realization of high-energy and safe batteries.

关键词： battery safety high-voltage cathode lithium-ion battery thermal runaway

The KDM4B–CCAR1–MED1 axis is a critical regulator of osteoclast differentiation and bone homeostasis

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Bone Research 2021年第3期9卷 323-335页

作者： sun-ju yi You-Jee Jang Hye-jung Kim Kyubin Lee Hyerim Lee Yeojin Kim junil Kim Seon Young Hwang Jin Sook Song Hitoshi Okada Jae-Il Park Kyuho Kang Kyunghwan Kim Department of Biological Sciences and Biotechnology Chungbuk National UniversityCheongjuChungbukRepublic of Korea Korea Basic Science Institute Gwangju Center at Chonnam National UniversityGwangjuRepublic of Korea New Drug Development Center KBIO Osong Medical Innovation FoundationCheongjuChungbukRepublic of Korea Data Convergence Drug Research Center Therapeutics&Biotechnology DivisionKorea Research Institute of Chemical TechnologyDaejeonRepublic of Korea Department of Biochemistry Kindai University Faculty of MedicineOsakasayamaOsakaJapan

Bone undergoes a constant and continuous remodeling process that is tightly regulated by the coordinated and sequential actions of bone-resorbing osteoclasts and bone-forming *** studies have shown that histone demethylases are implicated in osteoblastogenesis;however,little is known about the role of histone demethylases in osteoclast ***,we identified KDM4B as an epigenetic regulator of osteoclast *** of KDM4B significantly blocked the formation of tartrate-resistant acid phosphatase-positive multinucleated *** with myeloid-specific conditional knockout of KDM4B showed an osteopetrotic phenotype due to osteoclast *** analysis revealed that KDM4B physically and functionally associates with CCAR1 and MED1 in a *** genome-wide chromatin immunoprecipitation(ChIP)-sequencing,we revealed that the KDM4B–CCAR1–MED1 complex is localized to the promoters of several osteoclast-related genes upon receptor activator of NF-κB ligand *** demonstrated that the KDM4B–CCAR1–MED1 signaling axis induces changes in chromatin structure(euchromatinization)near the promoters of osteoclast-related genes through H3K9 demethylation,leading to NF-κB p65 recruitment via a direct interaction between KDM4B and ***,small molecule inhibition of KDM4B activity impeded bone loss in an ovariectomized mouse *** together,our findings establish KDM4B as a critical regulator of osteoclastogenesis,providing a potential therapeutic target for osteoporosis.

关键词： formation. critical MED1

Ytterbium modified birnessite MnO_(2) for improving deep oxidation of toluene

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Journal of Rare Earths 2024年第4期42卷 668-675页

作者： Linjiang sun Yan Cheng Yujie Liu Can yi Faculty of Geosciences and Environmental Engineering Southwest Jiaotong UniversityChengdu611756China

A series of rare earth metals modified birnessite manganese dioxides(RE-Mn)was synthesized by hydrothermal method and their catalytic degradation of toluene was ***-Mn shows the best toluene oxidation activity with the conversion of T50%and T99%at 196 and 226℃,*** physiochemical characterizations identified that the high catalytic performance and excellent stability of Yb-Mn are mainly associated with its higher molar ratios of Mn^(4+)/Mn^(3+),more lattice oxygen(Olatt),and better mobility of surface adsorbed oxygen(O_(ads)).Moreover,it is confirmed that introduction of Yb into birnessite MnO_(2) facilitates the production of acetic acid at lower *** results can aid the design of high-efficiency manganese oxide catalysts for the catalytic combustion of VOCs.

关键词： Manganese oxide Rare earth metal doping Toluene Catalytic combustion