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Ubiquitin-specific protease 47 regulates intestinal inflammation through deubiquitination of TRAF6 in epithelial cells

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Science China(Life Sciences) 2022年第8期65卷 1624-1635页

作者： Hu Lei Li Yang hanzhang xu Zhengting Wang Xiangyun Li Meng Liu Yingli Wu Hongqiao International Institute of Medicine Shanghai Tongren Hospital/Faculty of Basic MedicineKey Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of EducationShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Gastroenterology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Deubiquitinates(DUBs) alter the stabilities, localizations or activities of substrates by removing their ubiquitin conjugates,which are closely related to the development of inflammatory response. Here, we show that ubiquitin-specific protease 47(USP47) prevents inflammation development in inflammatory bowel disease(IBD). Compared with wild-type mice, Usp47 knockout mice are more susceptible to dextran sodium sulfate(DSS)-induced acute and chronic colitis with higher inflammatory cytokines expression and severe intestinal tissue damage. Chimeric mouse experiments suggest that non-hematopoietic cells mainly contribute to the phenotype. And, DSS-induced colitis of the Usp47 knockout mice depends on commensal ***, down-regulation of USP47 aggravates the activation of NF-κB signaling pathway by increasing the K63-linked poly-ubiquitination of tumor necrosis factor receptor-associated factor 6(TRAF6) in intestinal epithelial cells. Furthermore, the expression of USP47, negatively correlated with the degree of inflammation, is lower at colonic inflammatory lesions than that non-inflammatory sites from the intestine from ulcerative colitis(UC) and Crohn's disease(CD) patients. These data, taken together, indicate that USP47 regulates intestinal inflammation through de-ubiquitination of K63-linked poly-ubiquitination TRAF6 in intestinal epithelial cells.

关键词： ubiquitin-specific protease 47 TRAF6 intestinal epithelial cell inflammation inflammatory bowel disease

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Self-reported diabetes treatment among Chinese middle-aged and older adults with diabetes:Comparison of urban residents,migrants in urban settings,and rural residents

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International Journal of Nursing Sciences 2015年第1期2卷 9-14页

作者： hanzhang xu Jianfeng Luo Bei Wu Duke University School of Nursing DurhamNC 27710USA Department of Health Statistics and Social Medicine School of Public HealthFudan UniversityShanghaiChina Duke University Center for the Study of Aging and Human Development DurhamNC 27710USA Duke Global Health Institute DurhamNC 27710USA

Purpose:To compare self-reported diabetes treatments among Chinese urban residents,rural migrants in urban settings,and rural ***:Data from 993 diabetics at least 45 years of age were collected from the China Health and Retirement Longitudinal Study conducted in *** logistic regressions were performed to examine the associations between individual characteristics and diabetes ***:In total,719/993(72.4%)of the respondents received treatment for diabetes;of which<8% used insulin *** residents were more likely than rural residents to use insulin therapy[odds ratio(OR)=0.44,confidence interval(CI):0.20-0.99;p<0.05],and more likely to use traditional Chinese medicine than migrants(OR=0.30,CI:0.10-0.96;p<0.05).Overall,rural residents showed lower treatment rates than urban and migrant ***:Efforts to improve and enhance diabetes treatments,particularly among rural residents,are urgently needed in China.

关键词： treatment likely among

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YL064 activates proteasomal-dependent degradation of c-Myc and synergistically enhances the anti-tumor activity of ABT-199 in diffuse large B cell lymphoma

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1441-1444页

作者： Huizhuang Shan Yang Cao Xinhua Xiao Meng Liu Yunzhao Wu Qi Zhu hanzhang xu Hu Lei Zhujun Yao Yingli Wu Hongqiao International Institute of Medicine Tongren Hospital/Faculty of Basic MedicineChemical Biology Division of Shanghai Universities E-InstitutesKey Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of EducationShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Hematology The Third Affiliated Hospital of Soochow UniversityChangzhouJiangsu Province 213003PR China State Key Laboratory for Medical Genomics Shanghai Institute of HematologyCollaborative Innovation Center of HematologyNational Research Center for Translational MedicineRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Institute of Oncology Shanghai 9th People’s HospitalShanghai Jiao Tong University School of Medicine639 Zhizaoju RdShanghai 200011China State Key Laboratory of Coordination Chemistry Jiangsu Key Laboratory of Advanced Organic MaterialsSchool of Chemistry and Chemical EngineeringNanjing University163 Xianlin AvenueNanjingJiangsu 210023China

Dear Editor,c-Myc is highly associated with poor prognosis and aggressive progression of diffuse large B cell lymphoma(DLBCL)and is thus a desirable drug ***,studies indicate that 5–15%of DLBCL patients harbor MYC and BCL-2 translocations,while 20–35%DLBCL patients simultaneously overexpress of c-Myc and BCL-2 proteins without gene rearrangements.1 These two types of DLBCL are referred as“double-hit”lymphoma(DHL)and“double-expressor”lymphoma(DEL),*** DHL and DEL lymphomas have inferior clinical outcomes and are refractory to R-CHOP or even hematopoietic stem cell transplant.2 Thus,targeting both c-Myc and BCL-2 is a promising strategy to treat high-risk DLBCLs.3 Although BCL-2 inhibitors are clinically available,c-Myc remains to be“undruggable”owing to its lack of kinase activity and intrinsically disordered structure.4 Thus,developing clinically applicable c-Myc inhibitor remains challenging.

关键词： lymphoma synergistic harbor

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Hsp90/C terminal Hsc70-interacting protein regulates the stability of Ikaros in acute myeloid leukemia cells

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Science China(Life Sciences) 2021年第9期64卷 1481-1490页

作者： Meng Liu Jin Jin Yanjie Ji Huizhuang Shan Zhihui Zou Yang Cao Li Yang Ligen Liu Li Zhou Hu Lei Yunzhao Wu hanzhang xu Yingli Wu Hongqiao International Institute of Medicine Shanghai Tongren Hospital/Faculty of Basic MedicineChemical Biology Division of Shanghai Universities E-InstitutesKey Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of EducationShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Ultrasound Second Affiliated Hospital of Zhejiang UniversityHangzhou 310009China Department of Hematology The Third Affiliated Hospital of Soochow UniversityChangzhou 213003China Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China

The stability of Ikaros family zinc finger protein 1(Ikaros),a critical hematopoietic transcription factor,can be regulated by cereblon(CRBN)ubiquitin ligase stimulated by immunomodulatory drugs in multiple ***,other stabilization mechanisms of Ikaros have yet to be *** this study,we show that the pharmacologic inhibition or knockdown of Hsp90 downregulates Ikaros in acute myeloid leukemia(AML)*** inhibitor MG132 but not autophagy inhibitor chloroquine could suppress the Hsp90 inhibitor STA-9090-induced reduction of Ikaros,which is accompanied with the increased ubiquitination of ***,Ikaros interacts with E3 ubiquitin-ligase C terminal Hsc70 binding protein(CHIP),which mediates the STA-9090-induced ubiquitination of *** addition,the knockdown of Ikaros effectively inhibits the proliferation of leukemia cells,but this phenomenon could be rescued by Ikaros ***,our findings indicate that the interplay between HSP90 and CHIP regulates the stability of Ikaros in AML cells,which provides a novel strategy for AML treatment through targeting the HSP90/Ikaros/CHIP axis.

关键词： Ikaros CHIP Hsp90 AML STA-9090

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低速柴油机启动工况下主轴承瞬态润滑分析

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内燃机学报 2023年第3期41卷 280-287页

作者：徐含章李文达钟宁赵滨刘志刚哈尔滨工程大学动力与能源工程学院黑龙江哈尔滨150001 中船动力研究院有限公司上海201208 重庆跃进机械厂有限公司重庆402160

基于油膜厚度方程、平均雷诺方程、能量方程和动力学方程,综合考虑启动时变工况、热效应、热弹性变形和粗糙度等因素,建立主轴承瞬态混合热弹流润滑分析模型.基于上述模型探究进油温度、半径间隙和启动时长对主轴承润滑特性参数(包括微... 详细信息

基于油膜厚度方程、平均雷诺方程、能量方程和动力学方程,综合考虑启动时变工况、热效应、热弹性变形和粗糙度等因素,建立主轴承瞬态混合热弹流润滑分析模型.基于上述模型探究进油温度、半径间隙和启动时长对主轴承润滑特性参数(包括微凸体接触力、油膜厚度、油膜压力和温升分布)的影响规律,结果表明:针对所研究的低速柴油机主轴承,在启动工况下,适当降低进油温度可以减小微凸体接触力,缩短混合润滑时间;半径间隙在启动过程前期对润滑特性参数的影响几乎可以忽略,而在启动过程后期随着转速增加,其影响开始显现;缩短启动时长可一定程度上减小启动过程中的温升和微凸体接触力.

关键词：低速柴油机主轴承启动工况瞬态混合热弹流润滑

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Riverine sulfate sources and behaviors in arid environment,Northwest China:Constraints from sulfur and oxygen isotopes

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Journal of Environmental Sciences 2024年第3期137卷 716-731页

作者： Yifu xu Wenjing Liu Bing xu Zhifang xu Key Laboratory of Cenozoic Geology and Environment Institute of Geology and GeophysicsChinese Academy of SciencesBeijing 100029China Innovation Academy for Earth Science Chinese Academy of SciencesBeijing 100029China University of Chinese Academy of Sciences Beijing 100049China

The fate of riverine sulfate ion (SO_(4)^(2-)) and its environmental effects in arid environment are difficult to evaluate due to its complicated sources and strongly coupled behaviors with water cycle which is significantly modified by *** understand the sulfur cycle in aquatic systems in arid environment,the chemical and sulfur and oxygen isotopic compositions (δ^(34)S_(SO4)and δ^(18)O_(SO4)) of major rivers around the Badain Jaran Desert,northwestern China,were *** rivers had averaged SO_(4)^(2-)content at 1336μmol/L,over 10times higher than the global *** δ^(34)S_(SO4)and δ^(18)O_(SO4)values ranged from-5.3‰to+11.8‰and+1.6‰to+12.8‰,*** end-member analysis and the inverse model showed that riverine sulfate was mainly derived from evaporites dissolution (0-87%),sulfide oxidation (13%-100%) and precipitation (0-33%),indicating heterogeneity in sulfur sources and behaviors along the river drainage with the lithology variations and climate *** isotopic tools combining with hydro-chemistry compositions could be applied to reveal sulfur cycle in arid *** on the calculation,sulfide oxidation plays the primary role in the headwater and upstream in the Qilian-Mountains area,where sulfide is widely *** the proportion of evaporites dissolution contributing to riverine sulfate is much higher in downstream in a drier ***,less precipitation and higher temperature can lead to more intensive evaporation,affecting the process of sulfide oxidation and enhancing the rates of evaporites dissolution and sulfate precipitation in the basin.

关键词： Sulfur and oxygen isotopes Source apportionment Inverse model Arid environment Inland rivers Northwestern China

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Laboratory evaluation of high-friction thin overlays for pavement preservation

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Frontiers of Structural and Civil Engineering 2024年第6期18卷 936-948页

作者： Ouming xu Rentao xu Lintong JIN School of Highway Chang’an UniversityXi’an 710064China School of Materials Science and Engineering Chang’an UniversityXi’an 710061China

Traditional asphalt concrete(AC)and stone matrix asphalt(SMA),which are used as thin asphalt overlays,are common maintenance strategies to enhancing ride quality,skid resistance,and ***,several studies have used a novel asphalt mixture known as a high-friction thin overlay(HFTO)to improve surface ***,it remains uncertain whether the laboratory properties of HFTO differ significantly from those of conventional *** study aims to evaluate the laboratory properties of HFTO mixtures and compare them with those of AC and *** mixtures with nominal maximum size of 9.5 mm were produced in the laboratory,and performance tests were conducted,including wheel tracking test,low temperature flexural creep test,moisture susceptibility test,Cantabro Abrasion Test,Marshall Test,sand patch test,British pendulum test,and indoor tire-rollingdown *** results showed that the HFTO exhibited a lower tire/pavement noise than the AC and ***,HFTO had superior high-temperature stability,larger macro texture,and higher skid resistance in comparison to those of AC,but lower than those of ***,HFTO mixtures may be considered a suitable replacement for traditional AC mixtures in regions where skid resistance and noise reduction are concerns.

关键词： road engineering pavement maintenance high friction thin overlay performance skid resistance tire/pavement noise

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Emergency medical services use and its association with acute ischaemic stroke evaluation and treatment in Singapore

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Stroke & Vascular Neurology 2020年第2期5卷 121-127页

作者： hanzhang xu Ying Xian Fung Peng Woon Janet Prvu Bettger Daniel T Laskowitz Yih Yng Ng Marcus Eng Hock Ong David Bruce Matchar Deidre Anne De Silva Department of Family Medicine and Community Health Duke University School of MedicineDurhamNorth CarolinaUnited States Duke University School of Nursing DurhamNorth CarolinaUnited States Duke Clinical Research Institute DurhamNorth CarolinaUnited States Department of Neurology Duke University School of MedicineDurhamNorth CarolinaUnited States Department of Neurology National Neuroscience Institute-Singapore General Hospital CampusSingapore Department of Orthopaedic Surgery Duke University School of MedicineDurhamNorth CarolinaUnited States HomeTeam Government of Singapore Ministry of Home AffairsSingapore Department of Emergency Medicine Singapore General HospitalSingapore Program in Health Services and Systems Research Duke-NUS Graduate Medical SchoolSingapore Department of Medicine(General Internal Medicine) Duke University School of MedicineDurhamNorth CarolinaUnited States

Background Emergency medical services(EMS)is a critical link in the chain of stroke *** aimed to assess EMS use for stroke in Singapore,identify characteristics associated with EMS use and the association of EMS use with stroke evaluation and *** The Singapore Stroke Registry combines nationwide EMS and public hospital data for stroke cases in *** regressions with the generalised estimating equations were performed to examine the association between EMS use and timely stroke evaluation and *** Of 3555 acute ischaemic patients with symptom onset within 24 hours admitted to all five public hospitals between 2015 and 2016,68%arrived via *** who used EMS were older,were less likely to be female,had higher stroke severity by National Institute of Health Stroke Scale and had a higher prevalence of atrial fibrillation or peripheral arterial *** transported by EMS were more likely to receive rapid evaluation(door-to imaging time≤25 min 34.3%vs 11.1%,OR=2.74(95%CI 1.40 to 5.38))and were more likely to receive intravenous tissue plasminogen activator(tPA,22.8%vs 4.6%,OR=4.61(95%CI 3.52 to 6.03)).Among patients treated with tPA,patients who arrived via EMS were more likely to receive timely treatment than self-transported patients(door-to needle time≤60 min 52.6%vs 29.4%,OR=2.58(95%CI 1.35 to 4.92)).Conclusions EMS use is associated with timely stroke evaluation and treatment in *** EMS-Hospital stroke pathways and targeted public campaigns to advocate for appropriate EMS use have the potential to improve acute stroke care.

关键词： needle treatment likely

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Aldehyde oxidase mediated enantioselective metabolic health risk of dinotefuran

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Science China Chemistry 2024年第6期67卷 2079-2091页

作者： Liwei xu Xinxin xu Hua Kuang Chuanlai xu Xiaoling Wu State Key Laboratory of Food Science and Resources Jiangnan UniversityWuxi214122China International Joint Research Laboratory for Biointerface and Biodetection and School of Food Science and Technology Jiangnan UniversityWuxi214122China Collaborative Innovation center of Food Safety and Quality Control in Jiangsu Province Jiangnan UniversityWuxi214122China

Chiral pollutants often pose significant differential environmental health *** this study,the biotransformation of chiral dinotefuran(DIN)and its enantioselective metabolic toxicity mechanisms have been systemically ***,reversedphase chromatography-high resolution mass spectrometry was developed to quantify the content of DIN R/S chiral enantiomer with pg level sensitivity,revealing a lower elimination rate constant(K_(e))of S-DIN(0.730 h^(-1))than R-DIN(0.746 h^(-1)).Secondly,the interaction mechanism between DIN metabolism and important endogenous bioactive molecules,such as aldehyde oxidase(AOX)and neurotransmitters,was *** DIN nitro-group was converted into a guanidine group by the reducing site of nearby flavin adenine dinucleotide(FAD)in AOX with the preferred higher affinity of ***,the endogenous tryptophan(Trp)aldehyde metabolic intermediate,5-hydroxyindoleacetaldehyde(5-HIAL),provides a persistent electron donor for DIN reduction via the oxidation-catalyzed site in AOX,resulting in remarkable up-regulation of monoamine neurotransmitters such as serotonin and ***,the higher level of neurotransmitters further mediated dysregulation of oxylipin homeostasis via the serotonergic pathway,where S-DIN exhibited more pronounced liver lipid damage and environmental health risk with the accumulated lipid biomarkers,oxidized triglyceride(OxTG)and oxidized sphingomyelin(OxSM).This study elucidates the AOX-mediated enantioselectivity metabolic pathway of DIN,providing a new analytical method for chiral pollutants and paves the way for their health risk assessments.

关键词： neonicotinoid dinotefuran enantiomer aldehyde oxidase metabolomics health risk

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Skeletal interoception in osteoarthritis

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Bone Research 2024年第2期12卷 241-254页

作者： Dinglong Yang Jiawen xu Ke xu Peng xu Department of Joint Surgery Honghui HospitalXi’an Jiaotong UniversityXi’an 710054China Department of Orthopedic Surgery and Orthopedic Research Institute West China HospitalSichuan UniversityChengdu 610041China

The interoception maintains proper physiological conditions and metabolic homeostasis by releasing regulatory signals after perceving changes in the internal state of the *** its various forms,skeletal interoception specifically regulates the metabolic homeostasis of ***(OA)is a complex joint disorder involving cartilage,subchondral bone,and *** subchondral bone undergoes continuous remodeling to adapt to dynamic joint *** findings highlight that skeletal interoception mediated by aberrant mechanical loads contributes to pathological remodeling of the subchondral bone,resulting in subchondral bone sclerosis in *** skeletal interoception is also a potential mechanism for chronic synovial inflammation in *** this review,we offer a general overview of interoception,specifically skeletal interoception,subchondral bone microenviroment and the aberrant subchondral *** also discuss the role of skeletal interoception in abnormal subchondral bone remodeling and synovial inflammation in OA,as well as the potential prospects and challenges in exploring novel OA therapies that target skeletal interoception.

关键词： homeostasis inflammation releasing

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