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SARS-CoV-2 envelope protein impairs airway epithelial barrier function and exacerbates airway inflammation via increased intracellular Cl^(-)concentration

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1745-1759页

作者： Jian-Bang Xu Wei-jie Guan Yi-Lin Zhang Zhuo-Er Qiu Lei Chen Xiao-Chun Hou Junqing Yue Yu-Yun Zhou jie sheng Lei Zhao Yun-Xin Zhu Jing Sun Jincun Zhao Wen-Liang Zhou Nan-Shan Zhong State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseNational Center for Respiratory MedicineDepartment of Respiratory and Critical Care MedicineGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China Department of Thoracic Surgery Guangzhou Institute for Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China Guangzhou National Laboratory GuangzhouP.R.China School of Life Sciences Sun Yat-sen UniversityGuangzhouP.R.China Guangdong Provincial Key Laboratory of Pharmaceutical Functional Genes School of Life SciencesSun Yat-sen UniversityGuangzhouP.R.China Department of Physiology School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhouP.R.China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection disrupts the epithelial barrier and triggers airway inflammation.The envelope(E)protein,a core virulence structural component of coronaviruses,may play a role in this process.Pathogens could interfere with transepithelial Cl^(-)transport via impairment of the cystic fibrosis transmembrane conductance regulator(CFTR),which modulates nuclear factor kB(NF-kB)signaling.However,the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function,Cl^(-)transport and the robust inflammatory response remain to be elucidated.Here,we have demonstrated that E protein down-regulated the expression of tight junctional proteins,leading to the disruption of the airway epithelial barrier.In addition,E protein triggered the activation of Toll-like receptor(TLR)2/4 and downstream c-Jun N-terminal kinase(JNK)signaling,resulting in an increased intracellular Cl^(-)concentration([Cl^(-)]_(i))via up-regulating phosphodiesterase 4D(PDE4D)expression in airway epithelial cells.This elevated[Cl^(-)]_(i);contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1(SGK1).Moreover,blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E protein.Overall,these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection.

关键词： airway inflammation elevated

Melatonin decreases GSDME mediated mesothelial cell pyroptosis and prevents peritoneal fibrosis and ultrafiltration failure

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Science China(Life Sciences) 2024年第2期67卷 360-378页

作者： Hongxia Ruan Xuejuan Li Lina Zhou Zihan Zheng Rulin Hua Xu Wang Yuan Wang Yujie Fan Shuwen Guo Lihua Wang Shafiq ur Rahman Ziwei Wang Yuyuan Wei Shuangyan Yu Rongzhi Zhang Qian Cheng jie sheng Xue Li Xiaoyan Liu Ruqiang Yuan Xiaoyan Zhang Lihong Chen Guowang Xu Youfei Guan Jing Nie Hongqiang Qin Feng Zheng Advanced Institute for Medical Sciences Dalian Medical UniversityDalian 116044China Department of Nephrology Second HospitalDalian Medical UniversityDalian 116023China CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China Chongqing International Institute for Immunology Chongqing 401320China Department of Nephrology Shenzhen HospitalSouthern Medical UniversityShenzhen 518101China Wuhu Hospital and Health Science Center East China Normal UniversityShanghai 200241China Peking University First Hospital Peking UniversityBeijing 100034China

Peritoneal fibrosis together with increased capillaries is the primary cause of peritoneal dialysis failure.Mesothelial cell loss is an initiating event for peritoneal fibrosis.We find that the elevated glucose concentrations in peritoneal dialysate drive mesothelial cell pyroptosis in a manner dependent on caspase-3 and Gasdermin E,driving downstream inflammatory responses,including the activation of macrophages.Moreover,pyroptosis is associated with elevated vascular endothelial growth factor A and C,two key factors in vascular angiogenesis and lymphatic vessel formation.GSDME deficiency mice are protected from high glucose induced peritoneal fibrosis and ultrafiltration failure.Application of melatonin abrogates mesothelial cell pyroptosis through a MT1R-mediated action,and successfully reduces peritoneal fibrosis and angiogenesis in an animal model while preserving dialysis efficacy.Mechanistically,melatonin treatment maintains mitochondrial integrity in mesothelial cells,meanwhile activating m TOR signaling through an increase in the glycolysis product dihydroxyacetone phosphate.These effects together with quenching free radicals by melatonin help mesothelial cells maintain a relatively stable internal environment in the face of high-glucose stress.Thus,Melatonin treatment holds some promise in preserving mesothelium integrity and in decreasing angiogenesis to protect peritoneum function in patients undergoing peritoneal dialysis.

关键词： melatonin mitochondria pyroptosis GSDME peritoneal fibrosis mTOR

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Bipolar hip arthroplasty using conjoined tendon preserving posterior lateral approach in treatment of displaced femoral neck fractures

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World Journal of Clinical Cases 2024年第6期12卷 1076-1083页

作者： Ting-Xin Yan sheng-jie Dong Bo Ning Yu-Chi Zhao Department of Joint Surgery Yantaishan HospitalYantai 264003Shandong ProvinceChina Department of Joint Surgery Dongying People's HospitalDongying 257091Shandong ProvinceChina

BACKGROUND Hip fractures account for 23.8%of all fractures in patients over the age of 75 years.More than half of these patients are older than 80 years.Bipolar hemiarthroplasty(BHA)was established as an effective management option for these patients.Various approaches can be used for the BHA procedure.However,there is a high risk of postoperative dislocation.The conjoined tendon-preserving posterior(CPP)lateral approach was introduced to reduce postoperative dislocation rates.AIM To evaluate the effectiveness and safety of the CPP lateral approach for BHA in elderly patients.METHODS We retrospectively analyzed medical data from 80 patients with displaced femoral neck fractures who underwent BHA.The patients were followed up for at least 1 year.Among the 80 patients,57(71.3%)were female.The time to operation averaged 2.3 d(range:1-5 d).The mean age was 80.5 years(range:67-90 years),and the mean body mass index was 24.9 kg/m^(2)(range:17-36 kg/m^(2)).According to the Garden classification,42.5%of patients were typeⅢand 57.5%of patients were typeⅣ.Uncemented bipolar hip prostheses were used for all patients.Torn conjoined tendons,dislocations,and adverse complications during and after surgery were recorded.RESULTS The mean postoperative follow-up time was 15.3 months(range:12-18 months).The average surgery time was 52 min(range:40-70 min)with an average blood loss of 120 mL(range:80-320 mL).The transfusion rate was 10%(8 of 80 patients).The gemellus inferior was torn in 4 patients(5%),while it was difficult to identify in 2 patients(2.5%)during surgery.The posterior capsule was punctured by the fractured femoral neck in 3 patients,but the conjoined tendon and the piriformis tendon remained intact.No patients had stem varus greater than 3 degrees or femoral fracture.There were no patients with stem subsidence more than 5 mm at the last follow-up.No postoperative dislocations were observed throughout the follow-up period.No significance was found between preoperative and postoperative mean Health Service System score

关键词： Conjoined tendon preserving Bipolar hip arthroplasty Femoral neck fractures Postoperative dislocation Posterolateral approach

Clinicopathological characteristics and typing of multilocular cystic renal neoplasm of low malignant potential

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World Journal of Clinical Cases 2024年第14期12卷 2332-2341页

作者： Wen-Long Gao Gang Li Dong-sheng Zhu Yuan-jie Niu Department of Urology The Second Hospital of Tianjin Medical UniversityTianjin 300211China Department of Pediatric Surgery The First People’s Hospital of LianyungangLianyungang 222000Jiangsu ProvinceChina

BACKGROUND Up until now,no research has been reported on the association between the cli-nical growth rate of multilocular cystic renal neoplasm of low malignant potential(MCRNLMP)and computed tomography(CT)imaging characteristics.Our study sought to examine the correlation between them,with the objective of distin-guishing unique features of MCRNLMP from renal cysts and exploring effective management strategies.AIM To investigate optimal management strategies of MCRNLMP.METHODS We retrospectively collected and analyzed data from 1520 patients,comprising 1444 with renal cysts and 76 with MCRNLMP,who underwent renal cyst decom-pression,radical nephrectomy,or nephron-sparing surgery for renal cystic disease between January 2013 and December 2021 at our institution.Detection of MC-RNLMP utilized the Bosniak classification for imaging and the 2016 World Health Organization criteria for clinical pathology.RESULTS Our meticulous exploration has revealed compelling findings on the occurrence of MCRNLMP.Precisely,it comprises 1.48%of all cases involving simple renal cysts,5.26%of those with complex renal cysts,and a noteworthy 12.11%of renal tumors coexisting with renal cysts,indicating a statistically significant difference(P=0.001).Moreover,MCRNLMP constituted a significant 22.37%of the patient po-pulation whose cysts demonstrated a rapid growth rate of≥2.0 cm/year,whereas it only represented 0.66%among those with a growth rate below 2.0 cm/year.Of the 76 MCRNLMP cases studied,none of the nine patients who underwent subsequent nephron-sparing surgery or radical nephrectomy following renal cyst decompression experienced recurrence or metastasis.In the remaining 67 patients,who were actively monitored over a 3-year postoperative period,only one showed suspicious recurrence on CT scans.CONCLUSION MCRNLMP can be tentatively identified and categorized into three types based on CT scanning and growth rate indicators.In treating MCRNLMP,partial nephrectomy is preferred,while radical nephrectomy should be minimi-zed.After surg

关键词： Renal cysts Multilocular cystic renal neoplasm of low malignant potential Computed tomography Diagnosis Treatment

Slicing capacity-centered mode selection and resource optimization for network-assisted full-duplex cell-free distributed massive MIMO systems

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Science China(Information Sciences) 2024年第1期67卷 203-220页

作者： jie WANG Jiamin LI Pengcheng ZHU Dongming WANG Hongbiao ZHANG Yue HAO Bin sheng National Mobile Communications Research Laboratory Southeast University 2. Purple Mountain Laboratories China Mobile Research Institute

Network-assisted full-duplex(NAFD) cell-free distributed massive multiple-input multipleoutput(MIMO) systems enable uplink(UL) and downlink(DL) communications within the same timefrequency resources,which potentially reduce latency by avoiding the overhead of switching UL/DL modes.However,how to choose UL/DL modes remains an important factor affecting system performance.With the dramatic increase in the number of users and access points(APs),massive access brings significant overhead in the mode selection.Additionally,the different quality of service(QoS) among users also makes the effective utilization of resources difficult.As one of the most promising technologies in sixth-generation(6G),network slicing enables the adaptive configuration of limited UL/DL resources through the resource isolation assisted NAFD technique.Therefore,we propose a slicing capacity-centered scheme.Under this scheme,APs are motivated by slicing requirements and associated slices to form different subsystems.Collaborative mode selection and resource allocation are performed within each subsystem to reduce overhead and improve resource utilization.To implement this scheme efficiently,a double-layer deep reinforcement learning(DRL)mechanism is used to realize the joint optimization of mode selection and resource allocation.Simulation results show that the slicing capacity-centered scheme can effectively improve resource utilization and reduce overhead.

关键词： network-assisted full-duplex network slicing mode selection resource optimization deep reinforcement learning

Lymph node-biomimetic scaffold boosts CAR-T therapy against solid tumor

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National Science Review 2024年第4期11卷 206-215页

作者： Ziyan Liao jie Jiang Wei Wu Jiaqi Shi Yanfang Wang Yuejun Yao Tao sheng Feng Liu Wei Liu Peng Zhao Feifei Lv jie Sun Hongjun Li Zhen Gu Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang University Liangzhu Laboratory Zhejiang University Bone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology Zhejiang University School of Medicine Department of Medical Oncology The First Affiliated Hospital School of Medicine Zhejiang University Department of Laboratory Medicine The First Affiliated Hospital Zhejiang University School of Medicine Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated HospitalSchool of MedicineZhejiang University Jinhua Institute of Zhejiang University MOE Key Laboratory of Macromolecular Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang University

The limited infiltration and persistence of chimeric antigen receptor(CAR)-T cells is primarily responsible for their treatment deficits in solid tumors. Here, we present a three-dimensional scaffold, inspired by the physiological process of T-cell proliferation in lymph nodes. This scaffold gathers the function of loading,delivery, activation and expansion for CAR-T cells to enhance their therapeutic effects on solid tumors. This porous device is made from poly(lactic-co-glycolic acid) by a microfluidic technique with the modification of T-cell stimulatory signals, including anti-CD3, anti-CD28 antibodies, as well as cytokines. This scaffold fosters a 50-fold CAR-T cell expansion in vitro and a 15-fold cell expansion in vivo. Particularly, it maintains long-lasting expansion of CAR-T cells for up to 30 days in a cervical tumor model and significantly inhibits the tumor growth. This biomimetic delivery strategy provides a versatile platform of cell delivery and activation for CAR-T cells in treating solid tumors.

关键词： drug delivery cell therapy bioinspired biomaterials cancer immunotherapy

Mitochondrial dysfunction affects hepatic immune and metabolic remodeling in patients with hepatitis B virus-related acute-onchronic liver failure

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World Journal of Gastroenterology 2024年第8期30卷 881-900页

作者： Yu Zhang Xiao-Ling Tian jie-Qun Li Dong-sheng Wu Qiang Li Bin Chen Department of Hepatology Institute of HepatologyThe First Affiliated Hospital of Hunan University of Chinese MedicineChangsha 410021Hunan ProvinceChina Department of Liver Transplant Transplant Medical Research CenterThe Second Xiangya Hospital of Central South UniversityChangsha 410011Hunan ProvinceChina Department of Surgery The First Affiliated Hospital of Hunan University of Chinese MedicineChangsha 410021Hunan ProvinceChina

BACKGROUND Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).However,the mechanisms underlying immune and metabolic derangement in patients with advanced HBV-ACLF are unclear.AIM To identify the bioenergetic alterations in the liver of patients with HBV-ACLF causing hepatic immune dysregulation and metabolic disorders.METHODS Liver samples were collected from 16 healthy donors(HDs)and 17 advanced HBV-ACLF patients who were eligible for liver transplantation.The mitochondrial ultrastructure,metabolic characteristics,and immune microenvironment of the liver were assessed.More focus was given to organic acid metabolism as well as the function and subpopulations of macrophages in patients with HBV-ACLF.RESULTS Compared with HDs,there was extensive hepatocyte necrosis,immune cell infiltration,and ductular reaction in patients with ACLF.In patients,the liver suffered severe hypoxia,as evidenced by increased expression of hypoxia-inducible factor-1α.Swollen mitochondria and cristae were observed in the liver of patients.The number,length,width,and area of mitochondria were adaptively increased in hepatocytes.Targeted metabolomics analysis revealed that mitochondrial oxidative phosphorylation decreased,while anaerobic glycolysis was enhanced in patients with HBV-ACLF.These findings suggested that,to a greater extent,hepa-tocytes used the extra-mitochondrial glycolytic pathway as an energy source.Patients with HBV-ACLF had elevated levels of chemokine C-C motif ligand 2 in the liver homogenate,which stimulates peripheral monocyte infiltration into the liver.Characterization and functional analysis of macrophage subsets revealed that patients with ACLF had a high abundance of CD68^(+)HLA-DR^(+)macrophages and elevated levels of both interleukin-1βand transforming growth factor-β1 in their livers.The abundance of CD206^(+)CD163^(+)macrophages and expression of interleukin-10 decreased.Th

关键词： Acute-on-chronic liver failure Hypoxia-inducible factor-1α Mitochondria Metabolic phenotype Immune cells

Effect of Artificial Electric Field Surface by Wave-Driven Triboelectricity on Anti-Bioadhesion for Riser Protection

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China Ocean Engineering 2024年第3期38卷 483-490页

作者： YI Peng QIU Hong-yuan LI Yong CAI Bao-ping Javad MOSTAGHIMI ZHANGWen-jie XIAO Wen-sheng College of Mechanical and Electrical Engineering China University of PetroleumQingdao 266580China CNOOC EnerTech Equipment Technology Co. Ltd.Tianjin 300450China Department of Mechanical&Industrial Engineering University of TorontoToronto ONM5S3G8Canada

Biofouling has been a persistent problem in marine riser system, resulting in energy waste and equipment damage. Inthis study, a kind of water wave-driven contact-mode flexible triboelectric nanogeneration has been prepared byusing graphene-doped PDMS as dielectric friction material. When the graphene content is 2%, the average outputvoltage can reach 46 V under the contact frequency 10 Hz. The flexible triboelectric nanogeneration encapsulationmodule is impinged by water waves to generate alternating microelectric field on the riser surface and destroy theadhesion conditions of microorganisms during the biofilm stage. In the biofouling experiments at different stages, thebiofouling area of the platymonas subcordiformis has been reduced by 53%, 62% and 61%. It provides a new ideafor effective treatment of biofouling of mussels, oysters and barnacles attached to risers.

关键词： wave-drive triboelectric nanogeneration alternating microelectric field anti-biofouling

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An Efficient Optimization Design Framework for Low-Resistance Shape of Bionic Amphibious Robot

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China Ocean Engineering 2024年第1期38卷 117-128页

作者： ZHANG Dai-yu ZHANG Man-yu WANG Zhi-dong ZHENG Wen-sheng LING Hong-jie HU Jun-ming School of Naval Architecture and Ocean Engineering Jiangsu University of Science and TechnologyZhenjiang 212003China

To realize the low-resistance shape optimization design of amphibious robots,an efficient optimization design framework is proposed to improve the geometric deformation flexibility and optimization efficiency.In the proposed framework,the free-form deformation parametric model of the flat slender body is established and an analytical calculation method for the height constraints is derived.CFD method is introduced to carry out the high-precision resistance calculation and a constrained Kriging-based optimization method is built to improve the optimization efficiency by circularly infilling the new sample points which satisfying the constraints.Finally,the shape of an amphibious robot example is optimized to get the low-resistance shape and the results demonstrate that the presented optimization design framework has the advantages of simplicity,flexibility and high efficiency.

关键词： amphibious robot optimization method free-form deformation CFD-based hydrodynamic calculation

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