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Targeting GPR65 alleviates hepatic inflammation and fibrosis by suppressing the JNK and NF-κB pathways

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Military Medical Research 2024年第4期11卷 500-520页

作者： Kun zhang Meng-Xia zhang Xiao-Xiang Meng Jing Zhu Jia-Jun Wang Yi-Fan He Ye-hua Li Si-Cong Zhao Zhe-Min Shi Li-Na Zheng Tao Han Wei hong Department of Histology and Embryology School of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China Department of Hepatology and Gastroenterology Tianjin Union Medical CenterTianjin Medical UniversityTianjin Union Medical Center Affiliated to Nankai UniversityTianjin 300000China

Background:G-protein coupled receptors(GPCRs)are recognized as attractive targets for drug ***,it remains poorly understood how GPCRs,except for a few chemokine receptors,regulate the progression of liver ***,we aimed to reveal the role of GPR65,a proton-sensing receptor,in liver fibrosis and to elucidate the underlying ***:The expression level of GPR65 was evaluated in both human and mouse fibrotic ***,Gpr65-deficient mice were treated with either bile duct ligation(BDL)for 21 d or carbon tetrachloride(CCl4)for 8 weeks to investigate the role of GPR65 in liver fibrosis.A combination of experimental approaches,including Western blotting,quantitative real-time reverse transcription-polymerase chain reaction(qRT-PCR),and enzyme-linked immunosorbent assay(ELISA),confocal microscopy and rescue studies,were used to explore the underlying mechanisms of GPR65’s action in liver ***,the therapeutic potential of GPR65 inhibitor in the development of liver fibrosis was ***:We found that hepatic macrophage(HM)-enriched GPR65 was upregulated in both human and mouse fibrotic ***,knockout of Gpr65 significantly alleviated BDL-and CCl4-induced liver inflammation,injury and fibrosis in vivo,and mouse bone marrow transplantation(BMT)experiments further demonstrated that the protective effect of Gpr65knockout is primarily mediated by bone marrow-derived macrophages(BMMs).Additionally,in vitro data demonstrated that Gpr65 silencing and GPR65 antagonist inhibited,while GPR65 overexpression and application of GPR65 endogenous and exogenous agonists enhanced the expression and release of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and transforming growth factor-β(TGF-β),all of which subsequently promoted the activation of hepatic stellate cells(HSCs)and the damage of hepatocytes(HCs).Mechanistically,GPR65 overexpression,the acidic pH and GPR65 exogenous agonist induced up-regulation of

关键词： GPR65 Hepatic fibrosis Hepatic macrophages Inflammation c-Jun N-terminal kinase Nuclear factorκB

Effect of Microstructural Characteristics on Fracture Toughness in Direct Energy Deposited Novel Ti-6Al-4V-1Mo Alloy

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Acta Metallurgica Sinica(English Letters) 2024年第1期37卷 119-131页

作者： Chao Xia Kexin Zhao Xin Zhou Yuqi He Panpan Gao Hengxin zhang Guangrui Gao Fengying zhang hua Tan School of Material Science and Engineering Chang’an UniversityXi’an710064China Science and Technology on Plasma Dynamics Laboratory Air Force Engineering UniversityXi’an710038China State Key Laboratory of Solidification Processing Northwestern Polytechnical UniversityXi’an710072China Surface Material Protection Co. LtdXi’an710018China

Meeting the damage tolerance requirements for engineering-grade titanium alloys pose a significant challenge in achieving high fracture toughness in direct energy deposition(DED)titanium *** work primarily investigated the relationship between the microstructure and the fracture toughness of DED new Ti-6Al-4V-1Mo *** types of microstructures were designed via two process strategies:high-line energy density(HE)and low-line energy density(LE).Relative to LE samples,HE samples possess larger-sized microstructural characteristics(coarser grain boundaryα(α_(GB)),largerαcolonies,and coarserαlaths).Lessα/βphase boundaries were formed by coarserαlaths in the HE samples,increasing the movement of dislocations,resulting in tensile strength decreasing from 1007.1 MPa(LE)to 930.8 MPa(HE)and elongation increasing from 10.8%(LE)to 15.7%(HE).Also,HE samples exhibited an excellent fracture toughness of 114.0 MPa m^(1/2),significantly higher than that of LE samples(76.8 MPa m^(1/2)).An analysis of crack propagation paths was conducted to investigate the factors contributing to *** primary factor enhancing toughness is the frequent obstruction of cracks by coarseαGB and largeαcolonies in HE ***,the pretty large-angle deflections induced by the superposition effect of coarseαGB and largeαcolonies play a vital of significant *** factors induced the long and tortuous high-energy pathways,which resulted in ultimately improved fracture *** discovered microstructural toughening mechanisms can serve as a reference for future studies involving titanium alloys,offering insights on how to enhance fracture toughness by achieving similar characteristics.

关键词： Direct energy deposition Ti-6Al-4V-1Mo Tensile properties Fracture toughness Crack propagation

Molecular Mechanisms of Intracellular Delivery of Nanoparticles Monitored by an Enzyme‑Induced Proximity Labeling

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Nano-Micro Letters 2024年第6期16卷 14-37页

作者： Junji Ren Zibin zhang Shuo Geng Yuxi Cheng Huize Han Zhipu Fan Wenbing Dai hua zhang Xueqing Wang Qiang zhang Bing He Department of Pharmaceutics School of Pharmaceutical Sciences Peking University38 Xueyuan RdHaidian DistrictBeijing 100191People’s Republic of China

Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of *** the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular ***,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to ***,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular ***(lactic-co-glycolic acid)nanoparticles coupled with horseradish peroxidase(HRP)were fabricated as a model(HRP(+)-PNPs)to evaluate the molecular mechanism of nano delivery in *** adding the labeling probe biotin-phenol and the catalytic substrate H_(2)O_(2)at different time points in cellular delivery,nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with ***-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over *** on dynamic clustering analysis of these proteins,we further discovered that different organelles,including endosomes,lysosomes,the endoplasmic reticulum,and the Golgi apparatus,are involved in delivery with distinct participation *** importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery in *** summary,these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.

关键词： Enzyme-induced proximity labeling Intracellular delivery Nano-protein interaction Dynamic molecule profiling Macrophages

Exploring the Cation Regulation Mechanism for Interfacial Water Involved in the Hydrogen Evolution Reaction by In Situ Raman Spectroscopy

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Nano-Micro Letters 2024年第3期16卷 303-312页

作者： Xueqiu You Dongao zhang Xia‑Guang zhang Xiangyu Li Jing‑hua Tian Yao‑Hui Wang Jian‑Feng Li School of Ocean Information Engineering Fujian Provincial Key Laboratory of Oceanic Information Perception and Intelligent ProcessingJimei UniversityXiamen 361021People’s Republic of China State Key Laboratory of Physical Chemistry of Solid Surfaces MOE Key Laboratory of Spectrochemical Analysis and InstrumentationiChEMCollege of Chemistry and Chemical EngineeringCollege of MaterialsCollege of EnergyXiamen UniversityXiamen 361005People’s Republic of China Key Laboratory of Green Chemical Media and Reactions Ministry of EducationCollaborative Innovation Center of Henan Province for Green Manufacturing of Fine ChemicalsCollege of Chemistry and Chemical EngineeringHenan Normal UniversityXinxiang 453007People’s Republic of China Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(IKKEM) Xiamen 361005People’s Republic of China

Interfacial water molecules are the most important participants in the hydrogen evolution reaction(HER).Hence,understanding the behavior and role that interfacial water plays will ultimately reveal the HER ***,investigating interfacial water is extremely challenging owing to the interference caused by bulk water molecules and complexity of the interfacial ***,the behaviors of interfacial water in different cationic electrolytes on Pd surfaces were investigated by the electrochemistry,in situ core-shell nanostructure enhanced Raman spectroscopy and theoretical simulation *** spectral evidence reveals a red shift in the frequency and a decrease in the intensity of interfacial water as the potential is shifted in the positively *** comparing the different cation electrolyte systems at a given potential,the frequency of the interfacial water peak increases in the specified order:Li+

关键词： In situ Raman Interfacial water Hydrogen evolution reaction Cations

Risk factors for renal outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis:a nationwide retrospective study in China

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World Journal of Pediatrics 2024年第5期20卷 506-516页

作者： Li-Wen Tan Jun-Li Wan Chun-hua Zhu hong Xu Zheng-Kun Xia Li-Zhi Chen Xiao-Chuan Wu Fang Wang Xiao-Rong Liu Cheng-Guang Zhao Xiao-Zhong Li Jian-hua Mao Xiao-Wen Wang Wen-Yan huang Yu-hong Li Jian-Jiang zhang Shi-Pin Feng Jun Yang Jiao-Jiao Liu Chun-Lin Gao Li-Ping Rong Lan-Jun Shuai Ke Xu He-Jia zhang Qiu Li Ai-hua zhang Mo Wang Department of Nephrology Children’s Hospital of Chongqing Medical UniversityZhongshan 2nd Rd.136Chongqing400014China Ministry of Education Key Laboratory of Child Development and Disorders National Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChildren’s Hospital of Chongqing Medical UniversityChongqingChina Chongqing Key Laboratory of Pediatrics Children’s Hospital of Chongqing Medical UniversityChongqingChina Department of Nephrology Children’s Hospital of Nanjing Medical University72 Guangzhou RoadNanjing210008China Department of Nephrology Children’s Hospital of Fudan UniversityNational Paediatric Medical Center of ChinaShanghaiChina Department of Pediatrics Jinling HospitalNanjing Medical UniversityNanjingChina Department of Pediatrics Jinling HospitalThe First School of Clinical MedicineSouthern Medical UniversityNanjingChina Department of Pediatrics Jinling HospitalMedical School of Nanjing UniversityNanjingChina Department of Pediatric Nephrology and Rheumatology The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina Department of Pediatrics The Second Xiangya Hospital of Central South UniversityChangshaChina Department of Pediatrics Peking University First HospitalBeijingChina Department of Nephrology Beijing Children’s HospitalCapital Medical UniversityBeijing100045China National Center for Children’s Health BeijingChina Department of Pediatrics Shengjing Hospital of China Medical UniversityShenyangChina Department of Nephrology and Immunology Children’s Hospital of Soochow UniversitySuzhouChina Department of Nephrology Children HospitalZhejiang University School of MedicineHangzhouChina Department of Nephrology Wuhan Children’s Hospital(Wuhan Maternal and Child Healthcare Hospital)Tongji Medical CollegeHuazhong University of Science&TechnologyWuhanChina Department of Nephrology and Rheumatology Shanghai Children’s HospitalSchool

Background Pediatric antineutrophil cytoplasmic antibody-associated vasculitis(AAV)is a life-threatening systemic vasculitis featured by liability to renal ***,there are few studies on the risk factors and predictive models for renal outcomes of AAV in *** Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected *** risk factors and predictive model of end-stage renal disease(ESRD)in AAV were *** Renal involvement was the most typical manifestation(95.5%),and the crescent was the predominant pathological lesion(84.9%).The estimated glomerular filtration rate(eGFR)was evaluated in 114 patients,of whom 59.6%developed ESRD,and the median time to ESRD was 3.20 *** eGFR[P=0.006,odds ratio(OR)=0.955,95%confidence interval(CI)=0.924–0.987]and the percentages of global glomerulosclerosis(pGGS;P=0.018,OR=1.060,95%CI=1.010–1.112)were independent risk factors for ESRD of renal *** on the pGGS and eGFR at renal biopsy,we developed three risk grades of ESRD and one predictive *** Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades(P<0.001).Compared with serum creatinine at baseline,the predictive model had higher accuracy(0.86 versus 0.58,P<0.001)and a lower coefficient of variation(0.07 versus 0.92)in external *** Renal involvement is the most common manifestation of pediatric AAV in China,of which more than half deteriorates into *** predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children.

关键词： Antineutrophil cytoplasmic antibody End-stage renal disease Glomerulonephritis Pediatric nephrology Vasculitis

The RNA-binding domain of DCL3 is required for long-distance RNAi signaling

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aBIOTECH 2024年第1期5卷 17-28页

作者： Jie Li Bo-Sen zhang hua-Wei Wu Cheng-Lan Liu Hui-Shan Guo Jian-hua Zhao State Key Laboratory of Plant Genomics Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China CAS Center for Excellence in Biotic Interactions University of the Chinese Academy of SciencesBeijing 100049China Qilu Zhongke Academy of Modern Microbiology Technology Jinan 250022China

Small RNA(sRNA)-mediated RNA silencing(also known as RNA interference,or RNAi)is a conserved mechanism in eukaryotes that includes RNA degradation,DNA methylation,heterochromatin formation and protein translation *** plants,sRNAs can move either cell-to-cell or systemically,thereby acting as mobile silencing signals to trigger noncell autonomous ***,whether and what proteins are also involved in noncell autonomous silencing have not been *** this study,we utilized a previously reported inducible RNAi plant,PDSi,which can induce systemic silencing of the endogenous PDS gene,and we demonstrated that DCL3 is involved in systemic PDS silencing through its RNA binding *** confirmed that the C-terminus of DCL3,including the predicted RNA-binding domain,is capable of binding short *** affecting RNA binding,but not processing activity,reduced systemic PDS silencing,indicating that DCL3 binding to RNAs is required for the induction of systemic *** mosaic virus infection assays showed that the RNA-binding activity of DCL3 is required for antiviral RNAi in systemically noninoculated *** findings demonstrate that DCL3 acts as a signaling agent involved in noncell autonomous silencing and an antiviral effect in addition to its previously known function in the generation of 24-nucleotide sRNAs.

关键词： RNAi signaling DCL3 RBD RNAs Cucumber mosaic virus

Simulation of fire emergency evacuation in a large-passenger-flow subway station based on the on-site measured data of Shenzhen Metro

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Transportation Safety and Environment 2024年第1期6卷 47-55页

作者： hua Chen Chenyang zhang Jieyu zhang Ya Shu Xinjian Qi Chaozhe Jiang Sichuan FAST Fire Safety Assessment Co. LTD.Chengdu 610036SichuanChina School of Transportation and Logistics Southwest Jiaotong UniversityChengdu 611756SichuanChina Sichuan Fire Research Institute of MEM Chengdu 610036SichuanChina Shenzhen Metro Group Co. LTD.Shenzhen 518026GuangdongChina

Because of its large capacity,high efficiency and energy savings,the subway has gradually become the primary mode of transportation for citizens.A high density of passengers exists within a large-passenger-flow subway station,and the number of casualties and injuries during a fire emergency is *** this paper,Pathfinder software and on-site measured data of Pingzhou station in Shenzhen(China)were utilized to simulate a fire emergency evacuation in a large-passenger-flow subway *** Required Safe Egress Time(RSET),number of passengers and flow rates of stairs and escalators were analysed for three fire evacuation scenarios:train fire,platform fire and hall *** evacuation time of the train fire,which was 1173 s,was the longest,and 3621 occupants needed to evacuate when the train was fully *** could not complete the evacuation within 6 mins in all three fire evacuation scenarios,which does not meet the current standard requirements and *** changing the number of passengers and the number of stairs for evacuation,the flow rate capacity and evacuation time were explored,which have reference values for safety management and emergency evacuation plan optimization during peak hours of subway operation.

关键词： fire emergency evacuation large-passenger-flow subway station on-site measured data Pathfinder

Misdiagnosis of hemangioma of left triangular ligament of the liver as gastric submucosal stromal tumor:Two case reports

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2351-2357页

作者： Jing-Jie Wang Fen-Ming zhang Wei Chen hua-Tuo Zhu Ning-Long Gui Ai-Qing Li hong-Tan Chen Department of Gastroenterology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

BACKGROUND Extragastric lesions are typically not misdiagnosed as gastric submucosal tumor(SMT).However,we encountered two rare cases where extrinsic lesions were misdiagnosed as gastric *** SUMMARY We describe two cases of gastric SMT-like protrusions initially misdiagnosed as gastric SMTs by the abdominal contrast-enhanced computed tomography(CT)and endoscopic ultrasound(EUS).Based on the CT and EUS findings,the patients underwent gastroscopy;however,no tumor was identified after incising the gastric *** surgical exploration revealed no gastric lesions in both patients,but a mass was found in the left triangular ligament of the *** patients underwent laparoscopic tumor resection,and the postoperative diagnosis was hepatic *** During EUS procedures,scanning across different layers and at varying degrees of gastric cavity distension,coupled with meticulous image analysis,has the potential to mitigate the likelihood of such misdiagnoses.

关键词： Submucosal tumor Extragastric compression Endoscopic ultrasonography Computed tomography Hemangioma of the left triangular ligament of the liver Case report

Skeletal phenotypes and molecular mechanisms in aging mice

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Zoological Research 2024年第4期45卷 724-746页

作者： Qiao Guan Yuan zhang Zhi-Kun Wang Xiao-hua Liu Jun Zou Ling-Li zhang School of Exercise and Health Shanghai University of SportShanghai 200438China College of Athletic Performance Shanghai University of SportShanghai 200438China

Aging is an inevitable physiological process,often accompanied by age-related bone loss and subsequent bone-related diseases that pose serious health *** on skeletal diseases caused by aging in humans is challenging due to lengthy study durations,difficulties in sampling,regional variability,and substantial ***,mice are preferred for such studies due to their similar motor system structure and function to humans,ease of handling and care,low cost,and short generation *** this review,we present a comprehensive overview of the characteristics,limitations,applicability,bone phenotypes,and treatment methods in naturally aging mice and prematurely aging mouse models(including SAMP6,POLG mutant,LMNA,SIRT6,ZMPSTE24,TFAM,ERCC1,WERNER,and KL/KL-deficient mice).We also summarize the molecular mechanisms of these aging mouse models,including cellular DNA damage response,senescence-related secretory phenotype,telomere shortening,oxidative stress,bone marrow mesenchymal stem cell(BMSC)abnormalities,and mitochondrial ***,this review aims to enhance our understanding of the pathogenesis of aging-related bone diseases.

关键词： Aging Premature aging Mice Bone Gene knockout