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Perilipin 5 regulates hepatic stellate cell activation and high-fat diet-induced non-alcoholic fatty liver disease

Animal Models and Experimental Medicine 2024年第2期7卷 166-178页

作者： Xuecui Yin Lin Dong xiaohan Wang Zhenzhen Qin Yuying ma xiaofei Ke Ya Li Qingde Wang Yang Mi Quanjun Lyu xia Xu Pengyuan Zheng Youcai Tang Department of Internal Medicine the Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Department of Pediatrics the Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Department of Clinical Nutrition the First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Key Laboratory of Advanced Drug Preparation Technologies Ministry of Education of ChinaCo-innovation Center of Henan Province for New drug R&D and Preclinical SafetySchool of Pharmaceutical SciencesZhengzhou UniversityZhengzhouChina Department of Pediatrics GastroenterologyHenan Key Laboratory of Rehabilitation MedicineHenan Joint International Research Laboratory of Chronic Liver Injury and Henan Provincial Outstanding Overseas Scientists Chronic Liver Injury Studiothe Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhouChina

Background:Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases *** stellate cells(HSCs)are the major effector cells of liver *** contain abundant lipid droplets(LDs)in their cytoplasm during *** 5(PLIN 5)is a LD surface-associated protein that plays a crucial role in lipid ***,little is known about the role of PLIN 5 in HSC ***:PLIN 5 was overexpressed in HSCs of Sprague–Dawley rats by lentivirus *** the same time,PLIN 5 gene knockout mice were constructed and fed with a high-fat diet(HFD)for 20 weeks to study the role of PLIN 5 in *** corresponding reagent kits were used to measure TG,GSH,Caspase 3 activity,ATP level,and mitochondrial DNA copy *** analysis of mice liver tissue metabolism was performed based on UPLC-MS/***,mitochondrial function,cell proliferation,and apoptosis-related genes and proteins were detected by western blotting and ***:Overexpression of PLIN 5 in activated HSCs led to a decrease in ATP levels in mitochondria,inhibition of cell proliferation,and a significant increase in cell apoptosis through AMPK *** addition,compared with the HFD-fed C57BL/6J mice,PLIN 5 knockout mice fed with HFD showed reduced liver fat deposition,decreased LD abundance and size,and reduced liver ***:These findings highlight the unique regulatory role of PLIN 5 in HSCs and the role of PLIN 5 in the fibrosis process of NAFLD.

关键词： AMPK apoptosis hepatic stellate cell liver fibrosis perilipin 5

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Diagnostic performance of a multiplexed gastrointestinal PCR panel for identifying diarrheal pathogens in children undergoing hematopoietic stem cell transplant

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World Journal of Pediatrics 2024年第9期20卷 966-975页

作者： Yue Tao Cheng-Juan Luo Bing-Hua Zhang Xin-Yan Shen Rui-Ke Zhao Bei-Ying ma Nan Shen Chang-Ying Luo Jian-Min Wang Yi-Jun xia Li Xie Jing Chen Xi Mo Pediatric Translational Medicine Institute Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong University1678 Dongfang Rd.Shanghai200127China Department of Hematology and Oncology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong University1678 Dongfang Rd.Shanghai200127China Department of Infectious Diseases Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Medical Affairs BioMérieux(Shanghai)CompanyLimitedShanghaiChina Clinical Research Institute School of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background Diarrhea is a common complication of hematopoietic stem cell transplantation(HSCT)and is associated with substantial morbidity,but its etiology is often *** of diarrhea in this population include infectious causes,chemotherapy-or medication-induced mucosal injury and graft-versus-host disease(GVHD).Distinguishing these potential causes of diarrhea is challenging since diarrheal symptoms are often multifactorial,and the etiologies often overlap in transplant *** objectives of this study were to evaluate whether the Filmarray gastrointestinal(GI)panel would increase diagnostic yield and the degree to which pre-transplantation colonization predicts post-transplantation *** From November 2019 to February 2021,a total of 158 patients undergoing HSCT were prospectively included in the *** specimens were obtained from all HSCT recipients prior to conditioning therapy,28±7 days after transplantation and at any new episode of *** stool samples were tested by the Filmarray GI panel and other clinical microbiological *** The primary cause of post-transplantation diarrhea was infection(57/84,67.86%),followed by medication(38/84,45.24%)and GVHD(21/84,25.00%).Ninety-five of 158 patients were colonized with at least one gastrointestinal pathogen before conditioning therapy,and the incidence of infectious diarrhea was significantly higher in colonized patients(47/95,49.47%)than in non-colonized patients(10/63,15.87%)(Pmarray GI panel testing improved the diagnostic yield by almost twofold in our study(55/92,59.78%vs.30/92,32.61%).Conclusions Our data show that more than half of pediatric patients who were admitted for HSCT were colonized

关键词： Children Diarrhea Hematopoietic stem cell transplantation Multiplexed polymerase chain reaction

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Structure-based design of pan-coronavirus inhibitors targeting host cathepsin L and calpain-1

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1651-1664页

作者： Xiong Xie Qiaoshuai Lan Jinyi Zhao Sulin Zhang Lu Liu Yumin Zhang Wei Xu maolin shao Jingjing Peng Shuai xia Yan Zhu Keke Zhang xianglei Zhang Ruxue Zhang jian Li Wenhao Dai Zhen Ge Shulei Hu Changyue Yu Jiang Wang Dakota ma Mingyue Zheng Haitao Yang Gengfu xiao Zihe Rao Lu Lu Leike Zhang Fang Bai Yao Zhao Shibo Jiang Hong Liu Drug Discovery and Design Center State Key Laboratory of Drug ResearchCAS Key Laboratory of Receptor ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) School of Basic Medical SciencesShanghai Institute of Infectious Disease and BiosecurityFudan UniversityShanghai 200032China Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China State Key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China School of Chinese materia Medica Nanjing University of Chinese Medicine138 Xian Lin RoadJiangsu 210023 NanjingChina School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyUCASHangzhou 310024China National Clinical Research Center for Infectious Disease Shenzhen Third People's HospitalShenzhen 518112China

Respiratory disease caused by coronavirus infection remains a global health *** several SARS-CoV-2-specific vaccines and direct-acting antivirals are available,their effcacy on emerging coronaviruses in the future,including SARS-CoV-2 variants,might be ***-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging *** L(CTSL)and calpain-1(CAPN1)are host cysteine proteases which play crucial roles in coronaviral entrance into cells and infection-related immune ***,two peptidomimetic a-ketoamide compounds,14a and 14b,were identified as potent dual target inhibitors against CTSL and *** X-ray crystal structures of human CTSL and CAPN1 in complex with 14a and 14b revealed the covalent binding of a-ketoamide groups of 14a and 14b to C25 of CTSL and C115 of *** showed potent and broad-spectrum anticoronaviral activities in vitro,and it is worth noting that they exhibited low nanomolar potency against SARS-CoV-2 and its variants of concern(VOCs)with ECso values ranging from 0.80 to 161.7 nM in various *** mechanistic exploration indicated that they exhibited anticoronaviral activity through blocking viral ***,14a and 14b exhibited good oral pharmacokinetic properties in mice,rats and dogs,and favorable safety in *** addition,both 14a and 14b treatments demonstrated potent antiviral potency against SARS-CoV-2 XBB 1.16 variant infection in a K18-hACE2 transgenic mouse *** 14b also showed effective antiviral activity against HCoV-OC43 infection in a mouse model with a final survival rate of 60%.Further evaluation showed that 14a and 14b exhibited excellent antiinflammatory effects in Raw 264.7 mouse macrophages and in mice with acute *** together,these results suggested that 14a and 14b are promising drug candidates,providing novel insight into developing pan-coronavirus inhibitors with anti

关键词： calpain overcome entrance

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蒿本内酯对葡聚糖硫酸钠诱导的溃疡性结肠炎小鼠的改善作用

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食品工业科技 2024年第4期45卷 321-327页

作者：马广礼夏晓培马金亮许昌职业技术学医疗卫生学院河南许昌461000 河南科技大学食品与生物工程学院河南洛阳471000

目的:探究蒿本内酯(ligustilide,Lig)对葡聚糖硫酸钠(dextran sodium sulfate,DSS)诱导溃疡性结肠炎(ulcerative colitis,UC)小鼠的改善作用及机制。方法:将60只雄性SPF级C57BL/6小鼠随机分成6组,分别为空白组、DSS组、阳性药柳氮磺吡啶... 详细信息

目的:探究蒿本内酯(ligustilide,Lig)对葡聚糖硫酸钠(dextran sodium sulfate,DSS)诱导溃疡性结肠炎(ulcerative colitis,UC)小鼠的改善作用及机制。方法:将60只雄性SPF级C57BL/6小鼠随机分成6组,分别为空白组、DSS组、阳性药柳氮磺吡啶(sulfasalazine,SASP)组、Lig低、中、高剂量组。DSS组小鼠自由饮用3%DSS水溶液7 d复制UC模型,同时对Lig低、中、高剂量组小鼠灌胃给予药物干预治疗。通过记录小鼠每日体重和结肠长度,检测疾病活动指数(disease activity index,DAI)评分,采用酶联免疫吸附测定试剂盒定量检测血清中TNF-α、IL-6和IL-1β的表达水平,检测结肠中TLR4/NF-κB蛋白表达水平,并结合苏木素-伊红染色实验,探究Lig对小鼠UC的作用及机制。结果:与空白组比较,DSS组小鼠体重显著减轻(P<0.05),结肠长度显著缩短(P<0.05),DAI评分显著升高(P<0.05),肠道出现大量炎症性浸润现象,且结肠组织中TNF-α、IL-6和IL-1β表达水平显著升高(P<0.05);与DSS组比较,Lig中剂量组和高剂量组小鼠的肠道组织中TNF-α、IL-6和IL-1β的表达以及TLR4/NF-κB信号均被显著抑制(P<0.05),表明Lig中剂量组和高剂量组小鼠肠道损伤得到显著改善。结论:Lig能有效改善DSS诱导的小鼠UC,其机制可能是抑制NF-κB信号通路的激活。

关键词：蒿本内酯溃疡性结肠炎葡聚糖硫酸钠炎症因子

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High-throughput screening of novel TFEB agonists in protecting against acetaminopheninduced liver injury in mice

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Acta Pharmaceutica Sinica B 2024年第1期14卷 190-206页

作者： xiaojuan Chao Mengwei Niu shaogui Wang xiaowen ma xiao Yang Hua Sun Xujia Hu Hua Wang Li Zhang Ruili Huang Menghang xia Andrea Ballabio Hartmut Jaeschke Hong-Min Ni Wen-Xing Ding Department of Pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKS 66160USA NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Oncology the First Affiliated Hospital of Anhui Medical UniversityAnhui Medical UniversityHefei 230032China National Center for Advancing Translational Sciences National Institutes of HealthBethesdaMD 20892USA Telethon Institute of Genetics and Medicine TIGEMPozzuoliNaples 80131Italy Medical Genetics Department of Translational MedicineFederico II UniversityNaples 80131Italy Department of Molecular and Human Genetics Baylor College of MedicineHoustonTX 77030USA Department of Internal Medicine Division of GastroenterologyHepatology&MotilityUniversity of Kansas Medical CenterKansas CityKS 66160USA

macroautophagy(referred to as autophagy hereafter)is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and *** studies showed that autophagy protects against acetaminophen(APAP)-induced injury(AILI)via selective removal of damaged mitochondria and APAP protein *** lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with *** the present study,we showed that transcription factor EB(TFEB),a master transcription factor for lysosomal biogenesis,was impaired by APAP resulting in decreased lysosomal biogenesis in mouse *** loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI,***,overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2(NRF2)activation to protect against *** also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB *** these agonists,salinomycin,an anticoccidial and antibacterial agent,activated TFEB and protected against AILI in *** conclusion,genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

关键词： Autophagy DILI Drug screening Hepatotoxicity Lysosome Mitochondria Mitophagy NRF2

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Hyphae-mediated bioassembly of carbon fibers derivatives for advanced battery energy storage

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Carbon Energy 2024年第6期6卷 140-150页

作者： Lei Huang Zhong Qiu Ping Liu Xinhui xia Feng Cao Xinping He Chen Wang Wangjun Wan Yongqi Zhang Yang xia Wenkui Zhang Minghua Chen Jiancang Zhou Department of Critical Care Medicine Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouChina State Key Laboratory of Silicon materials Key Laboratory of Advanced Materials and Applications for Batteries of Zhejiang ProvinceSchool of Materials Science&EngineeringZhejiang UniversityHangzhouChina College of materials Science&Engineering Zhejiang University of TechnologyHangzhouChina State Key Laboratory of Photocatalysis on Energy and Environment Fuzhou UniversityFuzhouChina Department of Engineering Technology Huzhou CollegeHuzhouChina Zhejiang Academy of Science and Technology for Inspection&Quarantine HangzhouZhejiangChina Institute of Fundamental and Frontier Science University of Electronic Science and Technology of ChinaChengduChina Key Laboratory of Engineering Dielectric and Applications(Ministry of Education) School of Electrical and Electronic EngineeringHarbin University of Science and TechnologyHarbinChina

Ingenious design and fabrication of advanced carbon-based sulfur cathodes are extremely important to the development of high-energy lithium-sulfur batteries,which hold promise as the next-generation power ***,for the first time,we report a novel versatile hyphae-mediated biological assembly technology to achieve scale production of hyphae carbon fibers(HCFs)derivatives,in which different components including carbon,metal compounds,and semiconductors can be homogeneously assembled with HCFs to form composite *** mechanism of biological adsorption assembly is also *** a representative,reduced graphene oxides(rGOs)decorated with hollow carbon spheres(HCSs)successfully co-assemble with HCFs to form HCSs@rGOs/HCFs hosts for sulfur *** this unique architecture,not only large accommodation space for sulfur but also restrained volume expansion and fast charge transport paths are ***,multiscale physical barriers plus chemisorption sites are simultaneously established to anchor soluble lithium ***,the designed HCSs@rGOs/HCFs-S cathodes deliver a high capacity(1189 ma h g^(-1)at 0.1 C)and good high-rate capability(686 ma h g^(-1)at 5 C).Our work provides a new approach for the preparation of high-performance carbon-based electrodes for energy storage devices.

关键词： bioassembly carbon fibers energy storage graphene lithium-sulfur batteries

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Effect of BaO and MgO on structure and properties of aluminate slag with various CaO/Al_(2)0_(3)ratios

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Journal of Iron and Steel Research International 2024年第1期31卷 204-214页

作者： Yu-qi Kong Ting Wu Wen-zhi xia Wen Yang Hai-chuan Wang School of Metallurgical Engineering Anhui University of TechnologyMa’anshan243032AnhuiChina Key Laboratory of Metallurgical Emission Reduction and Resource Recycling(Ministry of Education) Anhui University of TechnologyMa’anshan243002AnhuiChina

To provide theoretical guidance for performance stability control of low-reactive mold fluxes,the effects of BaO and MgO on the structure and properties of aluminate slag with various CaO/Al_(2)0_(3)(C/A)ratios were investigated using the Fourier transform infrared spectrometer,Raman spectroscope,hemispherical melting point instrument,rotational viscometer and X-ray *** results indicated that with BaO and MgO addition,the structure polymerization was first weakened and then enhanced at C/A of 1.1,and the transition contents corresponded to 8 wt.%BaO and 2 wt.%MgO,respectively,while the structure polymerization decreased continuously at C/A of *** the viscosity change was well consistent with the structure evolution,the polymerization degree played a more prominent role in the slag viscosity than superheat degree when the melting temperature difference was within 40℃.The break temperature decreased initially and then increased with augment of BaO and MgO at C/A of 1.1,while it manifested a decrease trend with BaO addition,and it decreased obviously but then turned to increase with MgO increment at C/A of *** crystallization phase and crystallization ratio kept stable with BaO increment,while the crystallization ratio rose greatly with MgO promoting LiAlO_(2)precipitation at C/A of *** crystal types of all experimental slags were mainly Ca_(12)Al_(14)O_(33)and CaF_(2)at C/A of 1.3,and the precipitation of crystalline phase BaAl2O4 demonstrated a rising trend,while that of Ca_(12)Al_(14)O_(33)gradually declined with BaO augment.

关键词： Aluminate slag Structure MgO BaO Viscosity Property

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Predictive value of thrombocytopenia for bloodstream infection in patients with sepsis and septic shock

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World Journal of Critical Care Medicine 2024年第1期13卷 49-57页

作者： xia Li Sheng Wang Jun ma Su-Ge Bai Su-Zhen Fu Department of Critical Care Medicine Xingtai People HospitalXingtai 054001Hebei ProvinceChina Department of Physiology Hebei Collaborative Innovation Center for Cardiocerebrovascular DiseaseHebei Medical UniversityShijiazhuang 050000Hebei ProvinceChina

BACKGROUND Thrombocytopenia is common in patients with sepsis and septic *** To analyse the decrease in the number of platelets for predicting bloodstream infection in patients with sepsis and septic shock in the intensive care *** A retrospective analysis of patients admitted with sepsis and septic shock in Xingtai People Hospital was *** population characteristics and laboratory data were collected for *** The study group consisted of 85(39%)inpatients with bloodstream infection,and the control group consisted of 133(61%)with negative results or *** percentage decline in platelet counts(PPCs)in patients positive for pathogens[57.1(41.3-74.6)]was distinctly higher than that in the control group[18.2(5.1–43.1)](P<0.001),whereas the PPCs were not significantly different among those with gram-positive bacteraemia,gram-negative bacteraemia,and fungal *** receiver operating characteristic curves,the area under the curve of the platelet drop rate was 0.839(95%CI:0.783-0.895).CONCLUSION The percentage decline in platelet counts is sensitive in predicting bloodstream infection in patients with sepsis and septic ***,it cannot identify gram-positive bacteraemia,gram-negative bacteraemia,and fungal infection.

关键词： Platelet counts Thrombocytopenia Bloodstream infection Sepsis Shock

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Application Analysis of Doctor-Nurse Cooperation Follow-up Model Based on the Internet Platform in Continuation Care of Patients after Urooncology Surgery

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Journal of Clinical and Nursing Research 2024年第7期8卷 310-321页

作者： Yan Guo Hanjing Zhu Sijie You Yeli Cao Liya ma xia Yuan Nursing Department Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China

Objective:To explore the application effect of a doctor-nurse cooperation follow-up model based on an Internet platform in the continuation of care for patients after uro-oncology ***:A convenient sampling method was used to select patients with urinary system tumors who underwent surgery in the Department of Urology in Grade III A general hospital in Shanghai from may to August *** who underwent surgery from may to June 2022 were assigned to the control group,and those who underwent surgery from July to August 2022 were assigned to the experimental *** control group received routine post-discharge nursing health education and telephone *** the basis of routine discharge guidance,the experimental group implemented the intervention method based on the Internet platform in continuation *** levels of self-management efficacy,satisfaction,and incidence of unplanned readmission were compared one month after discharge between the two ***:One month after discharge,the self-management efficacy of the experimental group(90.15±7.92)was significantly higher than that of the control group(79.10±7.84),and the patient satisfaction score(97.83±2.32)was significantly higher than that of the control group(90.23±2.58),with statistical significance(Pmanagement efficiency of patients after discharge and enhance patient satisfaction,providing a new approach for discharge follow-up of urological tumor patients after surgery.

关键词： Urologic neoplasms Internet platform Doctor-nurse cooperation Continuation care

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Viscoelastic plastic interaction of tunnel support and strain-softening rock mass considering longitudinal effect

Rock Mechanics Bulletin

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Rock Mechanics Bulletin 2024年第4期3卷 70-82页

作者： Chen Xu Sheng Wang Caichu xia Lei Liu Zhifu ma Jun Yang Institute of Rock Mechanics Ningbo UniversityNingbo315211China Ningbo Key Laboratory of Energy Geostructure Ningbo315211China Shenzhen Shenshui Water Resources Consulting Co. LtdShenzhen518000China POWERCHINA Chengdu Engineering Co. LtdUrban and Rural Development Engineering BranchChengdu610031China

A simplified two-stage method was employed to provide an explicit solution for the time-dependent tunnel-rock interaction,considering the generalized Zhang-Zhu strength ***,a simplified mechanical model of the yielding support structure was *** tunnel excavation is simplified to a two-stage process:the first stage is affected by the longitudinal effect,while the second stage is affected by rheological *** cases are considered:one is that the rigid support is constructed during the first stage,and the other is that constructed at the second *** by the support timing at the seconde stage,different kinds of the“yield-resist combination”support method are divided into three categories:“yield before resist”support,“yield-resist”support,and“control-yield-resist”*** show that the support reaction of“control-yield-resist”is much higher than that of“yield before resist”if the initial geostress is not very high,but the effect is not obvious on controlling the surrounding rock ***,the“yield before resist”support is much more economical and practical when the ground stress is not very ***,under high geostress condition,through applying relatively high support reaction actively to surrounding rock at the first stage,the“control-yield-resist”support is superior in controlling the deformation rate of surrounding ***,in the high geostress environment,it is recommended to construct prestressed yielding anchor immediately after excavation,and then construct rigid support after the surrounding rock deformation reaches the predetermined deformation.

关键词： Tunnel excavation Strain-softening Generalized Zhang-Zhu strength criterion Time-dependent behavior Longitudinal effect

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