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LONP1 ameliorates liver injury and improves gluconeogenesis dysfunction in acute-on-chronic liver failure

Chinese Medical Journal 2024年第2期137卷 190-199页

作者： muchen wu Jing wu Kai Liu Minjie Jiang Fang Xie Xuehong Yin Jushan wu Qinghua Meng Department of Liver Disease Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Beijing Institute of Hepatology Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Department of General Surgery Beijing You-An HospitalCapital Medical UniversityBeijing 100069China

Background:Acute-on-chronic liver failure(ACLF)is a severe liver disease with complex *** hypoglycemia is common in patients with ACLF and often predicts a worse *** evidence suggests that glucose metabolic disturbance,especially gluconeogenesis dysfunction,plays a critical role in the disease progression of *** protease-1(LONP1)is a novel mediator of energy and glucose ***,whether gluconeogenesis is a potential mechanism through which LONP1 modulates ACLF remains ***:In this study,we collected liver tissues from ACLF patients,established an ACLF mouse model with carbon tetrachloride(CCl 4),lipopolysaccharide(LPS),and D-galactose(D-gal),and constructed an in vitro hypoxia and hyperammonemia-triggered hepatocyte injury ***1 overexpression and knockdown adenovirus were used to assess the protective effect of LONP1 on liver injury and gluconeogenesis *** histopathology,biochemical index,mitochondrial morphology,cell viability and apoptosis,and the expression and activity of key gluconeogenic enzymes were detected to explore the underlying protective mechanisms of LONP1 in ***:We found that LONP1 and the expressions of gluconeogenic enzymes were downregulated in clinical ACLF liver ***,LONP1 overexpression remarkably attenuated liver injury,which was characterized by improved liver histopathological lesions and decreased serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in ACLF ***,mitochondrial morphology was improved upon overexpression of ***,the expression and activity of the key gluconeogenic enzymes were restored by LONP1 ***,the hepatoprotective effect was also observed in the hepatocyte injury model,as evidenced by improved cell viability,reduced cell apoptosis,and improved gluconeogenesis level and activity,while LONP1 knockdown worsened liver injury and gluconeogenesis ***

关键词： Acute-on-chronic liver failure Lon protease-1 Gluconeogenesis disturbance Mitochondrial dysfunction Metabolism

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Application of Global Leadership Initiative on Malnutrition criteria in patients with liver cirrhosis

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Chinese Medical Journal 2024年第1期137卷 97-104页

作者： Minjie Jiang Juan Chen muchen wu Jing wu Xiaotong Xu Juan Li Can Liu Yaping Zhao Xin Hua Qinghua Meng Department of Hepatology Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Beijing Institute of Hepatology Beijing 100069China Department of Medical Oncology Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Department of Nutrition Beijing You-An HospitalCapital Medical UniversityBeijing 100069China

Background:The Global Leadership Initiative on Malnutrition(GLIM)criteria were published to build a global consensus on nutritional *** muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus ***,there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical *** study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIM-defined malnutrition,as well as the prevalence of GLIM-defined malnutrition in hospitalized cirrhotic ***:This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1,2018,and February 28,2022,at Beijing You-An Hospital,Capital Medical *** patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography(CT)examination during hospitalization were included in the *** patients were randomly divided into a modeling group(cohort 1,667 patients)and a validation group(cohort 2,335 patients).In cohort 1,optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index(L3-SMI)were determined using receiver operating characteristic analyses against in-hospital mortality in different gender ***,patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002(NRS-2002),and malnutrition was diagnosed by GLIM ***,the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort *** logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical ***:The optimal cut-off values of L3-SMI were 39.50 cm 2/m 2 for male patients and 33.06 cm 2/m 2 for female *** on the cut-off values,31.63%(68/215)of the male patients and 23.3%(28/120)of the female patients had CT-determ

关键词： Malnutrition Liver cirrhosis Sarcopenia Clinical outcomes GLIM criteria

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非参数化概率盒下随机与认知不确定性的分离式灵敏度分析

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航空学报 2023年第1期44卷 187-202页

作者：吴沐宸陈江涛夏侯唐凡赵炜刘宇电子科技大学机械与电气工程学院成都611731 中国空气动力研究与发展中心计算空气动力研究所绵阳621000 电子科技大学系统可靠性与安全性研究中心成都611731

灵敏度分析(SA)能辨识影响复杂系统响应的关键参数,为系统的稳健设计提供决策依据。非参数化概率盒作为一种典型的不精确概率模型,可以同时量化随机和认知2类不确定性,且在实际工程中应用广泛。由于非参数化概率盒耦合了随机和认知不确... 详细信息

灵敏度分析(SA)能辨识影响复杂系统响应的关键参数,为系统的稳健设计提供决策依据。非参数化概率盒作为一种典型的不精确概率模型,可以同时量化随机和认知2类不确定性,且在实际工程中应用广泛。由于非参数化概率盒耦合了随机和认知不确定性,非参数化概率盒下灵敏度分析方法能阐明输入概率盒的随机和认知不确定性对系统响应不确定性的影响程度。从随机与认知不确定性分离式角度出发,提出了一种非参数化概率盒下分离式灵敏度分析(SSA)方法。构建了格点法和期望值法分离非参数化概率盒的随机和认知不确定性,采用双层嵌套不确定性传播算法建立输出响应的概率盒,提出了最大方差和面积度量指标分别衡量系统输入的随机、认知不确定性对输出的随机、认知不确定性的影响。以NACA0012翼型升阻比预测为例,分析了来流参数和湍流模型参数的随机、认知不确定性对升阻比的随机、认知不确定性的影响。

关键词：分离式灵敏度分析非参数化概率盒格点法最大方差指标面积指标

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应对可转移多黏菌素耐药性--饲料添加剂来源的白屈菜红碱具有双重效应

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Engineering 2024年第1期32卷 163-173页

作者： Huangwei Song Xueyang Wang muchen Zhang Zhiyu Zou Siyuan Yang Tian Yi Jianfeng Wang Dejun Liu Yingbo Shen Chongshan Dai Zhihai Liu Timothy R.Walsh Jianzhong Shen Congming wu Yang Wang National Key Laboratory of Veterinary Public Health and Safety College ofVeterinary MedicineChina Agricultural UniversityBeijing 100193China Guangdong Laboratory for Lingnan Modern Agriculture Guangzhou 510642China State Key Laboratory for Zoonotic Diseases Key Laboratory of Zoonosis ResearchMinistry of EducationInstitute of ZoonosisCollege of Veterinary MedicineJilin UniversityChangchun 130015China College of Chemistry and Pharmaceutical Sciences Qingdao Agricultural University.Qingdao 266109China Ineos-Oxford Institute of Antimicrobial Research Department of BiologyUniversity of OxfordOxford OX13SZUK

The emergence and spread of the mobile colistin-resistance gene,mcr-1,and its variants pose achallenge to the use of colistin,a last-resort antibiotic used to treat severe infections caused by extensively drug-resistant(XDR)Gram-negative *** adjuvants are a promising strategy to enhance the efficacy of colistin against colistin-resistant pathogens;however,few studies have considered the effects of adjuvants on limiting resistance-gene *** found that chelerythrine(4 mg·L^(-1))derived from Macleaya cordata extract,which is used as an animal feed additive,reduced the minimal inhibitory concentration(MIC)of colistin against an mcr-1 positive Escherichia coli(***)strain by 16-fold(from 2.000 to 0.125 mg·L^(-1)).eliminated approximately 10^(4) colony-forming units(CFUs)of an mcr-1-carrying strain in a murine intestinal infection model,and inhibited the conjugation of an mcr-1-bearing plasmid in vitro(by>100-fold)and in a mouse model(by up to 5-fold).A detailed analysis revealed that chelery-thrine binds to phospholipids on bacterial membranes and increases cytoplasmic membrane fluidity,thereby impairing respiration,disrupting proton motive force(PMF),generating reactive oxygen species(ROS),and decreasing intracellular adenosine triphosphate(ATP)levels,which subsequently downregu-lates mcr-1 and conjugation-associated *** dual effects of chelerythrine can expand the use of antibiotic adjuvants and may provide a new strategy for circumventing mobile colistin resistance.

关键词： Chelerythrine Antibiotic adjuvant Conjugation inhibitor Colistin mcr-1 Dual effects

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Ballistic performances of the hourglass lattice sandwich structures under high-velocity fragments

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Defence Technology（防务技术） 2024年第1期31卷 312-325页

作者： He-xiang wu Jia Qu Lin-zhi wu Key Laboratory of Advanced Ship Materials and Mechanics College of Aerospace and Civil EngineeringHarbin Engineering UniversityHarbin150001China School of Civil Engineering Northeast Forestry UniversityHarbin150040China

In this paper,the numerical simulation method is used to study the ballistic performances of hourglass lattice sandwich structures with the same mass under the vertical incidence of *** is paid to elucidating the influences of rod cross-section dimensions,structure height,structure layer,and rod inclination angle on the deformation mode,ballistic performances,and ability to change the ballistic direction of *** results show that the ballistic performances of hourglass lattice sandwich structures are mainly affected by their structural *** this respect,structural parameters optimization of the hourglass lattice sandwich structures enable one to effectively improve their ballistic limit velocity and,consequently,ballistic performances.

关键词： Hourglass lattice sandwich structures Ballistic performances high-velocity Finite element analysis

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Resilience-incorporated seismic risk assessment of precast concrete frames with“dry”connections

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Earthquake Engineering and Engineering Vibration 2024年第2期23卷 403-425页

作者： wu Chenhao Tang Yuchuan Cao Xuyang wu Gang Key Laboratory of Concrete and Prestressed Concrete Structures of the Ministry of Education Nanjing 211102China Department of Civil and Environmental Engineering University of CaliforniaLos AngelesCA 90095USA School of Civil Engineering Southeast UniversityNanjing 211102China College of Civil and Transportation Engineering Hohai UniversityNanjing 210024China

A resilience-incorporated risk assessment framework is proposed and demonstrated in this study to manifest the advantageous seismic resilience of precast concrete frame(PCF)structures with“dry”connections in terms of their low damage and rapid *** framework integrates various uncertainties in the seismic hazard,fragility,capacity,demand,loss functions,and post-earthquake *** this study,the PCF structures are distinguished from ordinary reinforced concrete frame(RCF)structures by characterizing multiple limit states for the PCF based on its unique damage ***,probabilistic story-wise pushover analyses are performed to yield story-wise capacities for the predefined limit *** the seismic resilience analysis,a step-wise recovery model is proposed to idealize the functionality recovery process,with separate considerations of the repair and non-repair *** recovery model leverages the economic loss and downtime to delineate the stochastic post-earthquake recovery curves for the resilience loss *** such,contingencies in the probabilistic post-earthquake repairs are incorporated and the empirical judgments on the recovery parameters are largely *** proposed framework is demonstrated through a comparative study between two“dry”connected PCFs and one RCF designed as alternative structural systems for a prototype *** results from the risk quantification indicate that the PCFs show reduced loss hazards and lower expected losses relative to the ***,the PCF equipped with energy dissipation devices at the“dry”connections largely reduces the expected economic loss,downtime,and resilience loss by 29%,56%,and 60%,respectively,compared to the RCF.

关键词： precast concrete frame non-emulative precast system seismic resilience seismic risk functional recovery

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New findings on the influence of El Nino events on tropical cyclone formation

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Science China Earth Sciences 2024年第3期67卷 892-893页

作者： Liguang wu Department of Atmospheric and Oceanic Sciences Institute of Atmospheric SciencesFudan UniversityShanghai 200438China

Tropical cyclones typically form over warm tropical and subtropical ocean surfaces, as their formation and intensification rely primarily on the energy provided by the ocean. Pioneering research by Gray (1968) revealed that the formation of tropical cyclones requires the sea surface temperature (SST) to be no less than 26.5℃. Consequently, SST is commonly recognized as a crucial parameter among the environmental factors influencing tropical cyclone formation(Gray, 1979;Emanuel and Nolan, 2004).

关键词： tropical cyclone ocean

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Two-dimensional semiconductor heterostructures for photocatalytic CO_(2)conversion

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Science China Chemistry 2024年第8期67卷 2434-2447页

作者： Yang wu Mingyu wu Yongfu Sun Yi Xie Hefei National Research Center for Physical Sciences at Microscale University of Science and Technology of ChinaHefei 230026China

The CO_(2)reduction into carbon-contained fuel via solar energy offers the powerful tools to realize the zero-emission carbon *** to the intriguing features of the two-dimensional(2D)heterostructures,it is susceptible to modulate the electronic structure as well as the surface geometry for optimizing the photocatalytic CO_(2)*** this perspective,we surveyed the fundamental insights of 2D semiconductor heterostructures,involving the fabrication strategies and classification of the 2D semiconductor ***,we have detailly discussed the overview of 2D semiconductor heterostructure for optimizing CO_(2)photocatalytic influenced factors,including the solar energy utilization,photogenerated carriers separation,and redox reaction ***,we showed the significant advantages of 2D heterostructures in elevating CO_(2)photoreduction performance,focusing on activity,selectivity and *** analyzing the limitations and developments,we ended by putting forward insights into the further researches about the CO_(2)photocatalysts and reactor design,even industrial applications.

关键词： two-dimensional semiconductor heterostructures photocatalysis CO_(2)conversion

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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

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Rational surface charge engineering of haloalkane dehalogenase for boosting the enzymatic performance in organic solvent solutions

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Chinese Journal of Chemical Engineering 2024年第1期65卷 276-285页

作者： Yin wu Yan Sun Department of Biochemical Engineering School of Chemical Engineering and Technology and Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology(Ministry of Education)Tianjin UniversityTianjin 300350China

Biocatalysis in organic solvents(OSs)has numerous important applications,but native enzymes in OSs often exhibit limited catalytic ***,we proposed a computation-aided surface charge engineering strategy to improve the catalytic performance of haloalkane dehalogenase DhaA in OSs based on the energetic analysis of substrate binding to the DhaA *** variants with enhanced OS resistance were obtained by replacing negative charged residues on the surface with positive charged residue(Arg).Particularly,a four-substitution variant E16R/E93R/E121R/E257R exhibited the best catalytic performance(five-fold improvement in OS resistance and seven-fold half-life increase in 40%(vol)dimethylsulfoxide).As a result,the overall catalytic performance of the variant could be at least 26 times higher than the wild-type *** spectroscopy and molecular dynamics simulation studies revealed that the residue substitution mainly enhanced OS resistance from four aspects:(a)improved the overall structural stability,(b)increased the hydrophobicity of the local microenvironment around the catalytic triad,(c)enriched the hydrophobic substrate around the enzyme molecule,and(d)lowered the contact frequency between OS molecules and the catalytic *** findings validate that computationaided surface charge engineering is an effective and ingenious rational strategy for tailoring enzyme performance in OSs.

关键词： Surface charge engineering Organic solvent resistance Molecular dynamics simulation Haloalkane dehalogenase

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