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The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions:insights from a single-arm,phase II trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2202-2214页

作者： Bo Cheng Caichen Li Jianfu Li Longlong Gong Peng Liang Ying Chen Shuting Zhan Shan Xiong Ran Zhong Hengrui Liang Yi Feng Runchen Wang Haixuan Wang Hongbo Zheng Jun Liu Chengzhi Zhou Wenlong Shao Yuan Qiu Jiancong Sun Zhanhong Xie Zhu Liang Chenglin Yang Xiuyu Cai Chunxia Su Wei Wang Jianxing He Wenhua Liang Department of Thoracic Surgery and Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Medical Department Genecast Biotechnology Co.LtdWuxiChina Department of Radiation Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Department of Respiratory Medicine the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Department of Cardiothoracic Surgery Affiliated Hospital of Guangdong Medical UniversityZhanjiangChina Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenChina Department of VIP Inpatient Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaSun Yat-sen UniversityGuangzhouChina Department of Medical Oncology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina

Immune checkpoint inhibitors targeting the programmed cell death-1(PD-1)protein significantly improve survival in patients with advanced non-small-cell lung cancer(NSCLC),but its impact on early-stage ground-glass opacity(GGO)lesions remains unclear.This is a single-arm,phase II trial(NCT04026841)using Simon’s optimal two-stage design,of which 4 doses of sintilimab(200 mg per 3 weeks)were administrated in 36 enrolled multiple primary lung cancer(MPLC)patients with persistent high-risk(Lung-RADS category 4 or had progressed within 6 months)GGOs.The primary endpoint was objective response rate(ORR).T/B/NK-cell subpopulations,TCR-seq,cytokines,exosomal RNA,and multiplexed immunohistochemistry(mIHC)were monitored and compared between responders and non-responders.Finally,two intent-to-treat(ITT)lesions(pure-GGO or GGO-predominant)showed responses(ORR:5.6%,2/36),and no patients had progressive disease(PD).No grade 3-5 TRAEs occurred.The total response rate considering two ITT lesions and three non-intent-to-treat(NITT)lesions(pure-solid or solid-predominant)was 13.9%(5/36).The proportion of CD8^(+)T cells,the ratio of CD8^(+)/CD4^(+),and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over time.Correspondingly,the mIHC analysis showed more CD8^(+)T cells infiltrated in responders.Besides,responders’cytokine concentrations of EGF and CTLA-4 increased during treatment.The exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among responders.Collectively,PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety concerns.Such effects were associated with specific T-cell re-distribution,EGF/CTLA-4 cytokine compensation,and regulation of metabolism pathways.

关键词： lesions metabolism doses

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Hypomethylation of glycine dehydrogenase promoter in peripheral blood mononuclear cells is a new diagnostic marker of hepatitis B virus-associated hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 35-42页

作者： Li-Li Miao Jing-Wen Wang Hui-Hui Liu Shuai Gao Yu-Chen Fan Kai Wang Department of Hepatology Qilu Hospital of Shandong UniversityJinan 250012China Experimental Center Shandong University of Traditional Chinese MedicineJinan 250355China Institute of Hepatology Shandong UniversityJinan 250012China

Background: Glycine dehydrogenase(GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnostic value for hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC). Methods: We enrolled 197 patients, 111 with HBV-HCC, 51 with chronic hepatitis B(CHB), and 35 healthy controls(HCs). The methylation status of GLDC promoter in peripheral mononuclear cells(PBMCs) was identified by methylation specific polymerase chain reaction(MSP). The mRNA expression was examined using real-time quantitative polymerase chain reaction(q PCR). Results: The methylation frequency of the GLDC promoter was significantly lower in HBV-HCC patients(27.0%) compared to that in CHB patients(68.6%) and HCs(74.3%)( P < 0.001). The methylated group had lower alanine aminotransferase level( P = 0.035) and lower rates of tumor node metastasis(TNM) Ⅲ/Ⅳ( P = 0.043) and T3/T4( P = 0.026). TNM stage was identified to be an independent factor for GLDC promoter methylation. GLDC mRNA levels in CHB patients and HCs were significantly lower than those in HBV-HCC patients( P = 0.022 and P < 0.001, respectively). GLDC mRNA levels were significantly higher in HBV-HCC patients with unmethylated GLDC promoters than those with methylated GLDC promoters( P = 0.003). The diagnostic accuracy of alpha-fetoprotein(AFP) combined with GLDC promoter methylation for HBV-HCC was improved compared with that of AFP alone(AUC: 0.782 vs. 0.630, P < 0.001). In addition, GLDC promoter methylation was an independent predictor for overall survival of HBV-HCC patients( P = 0.038). Conclusions: The methylation frequency of GLDC promoter was lower in PBMCs from HBV-HCC patients than that from patients with CHB and HCs. The combination of AFP and GLDC promoter hypomethylation significantly improved the diagnostic accuracy of HBV-HCC.

关键词： Hepatocellular carcinoma Glycine dehydrogenase DNA methylation Peripheral blood mononuclear cells

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Performance and Application of Double-layered Microcapsule Corrosion Inhibitors

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Journal of Wuhan University of technology(Materials science) 2024年第4期39卷 845-853页

作者：余海燕 WANG Yingxiang WANG Ruizhi HU Lintong WANG Tianlei School of Materials science and Engineering Tianjin Chengjian UniversityTianjin 300384China Tianjin key Laboratory of Building Green Functional Materials Tianjin Chengjian UniversityTianjin 300384China

Double-layered microcapsule corrosion inhibitors were developed by sodium monofluorophosphate as the core material,polymethyl methacrylate as the inner wall material,and polyvinyl alcohol as the outer wall material combining the solvent evaporation method and spray drying method.The protection by the outer capsule wall was used to prolong the service life of the corrosion inhibitor.The dispersion,encapsulation,thermal stability of microcapsules,and the degradation rate of capsule wall in concrete pore solution were analyzed by ultra-deep field microscopy,scanning electron microscopy,thermal analyzer,and sodium ion release rate analysis.The microcapsules were incorporated into mortar samples containing steel reinforcement,and the effects of double-layered microcapsule corrosion inhibitors on the performance of the cement matrix and the actual corrosion-inhibiting effect were analyzed.The experimental results show that the double-layered microcapsules have a moderate particle size and uniform distribution,and the capsules were completely wrapped.The microcapsules as a whole have good thermal stability below 230 ℃.The monolayer membrane structure microcapsules completely broke within 1 day in the simulated concrete pore solution,and the double-layer membrane structure prolonged the service life of the microcapsules to 80 days in the simulated concrete pore solution before the core material was completely released.The mortar samples containing steel reinforcement incorporated with the double-layered microcapsule corrosion inhibitors still maintained a higher corrosion potential than the monolayer microcapsule corrosion inhibitors control group at 60 days.The incorporation of double-layered microcapsules into the cement matrix has no significant adverse effect on the setting time and early strength.

关键词： corrosion inhibitors microcapsule double-layer structure potentiodynamic polarization curve

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The genesis and resource potential of gold deposits in the Liaodong Peninsula

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science China Earth sciences 2024年第3期67卷 657-672页

作者： Rixiang ZHU Jin-Hui YANG Gongwen WANG Qingdong ZENG Guoqiang XUE Tao XU Xinghui LI Peng ZHANG Da LEI Guang ZHU State key Laboratory of Lithospheric Evolution Institute of Geology and GeophysicsChinese Academy of SciencesBeijing 100029China School of Earth sciences and Resources China University of GeosciencesBeijing 100083China Shenyang Center China Geological SurveyShenyang 110034China School of Resources and Environmental Engineering Hefei University of TechnologyHefei 230009China

Plenty of gold deposits related to Late Mesozoic craton destruction are widely distributed in eastern North China Craton. However, significant differences in research degrees, ore-forming characteristics, and proven reserves exist among different regions in the North China Craton. The Liaodong Peninsula has similar regional geological characteristics to those of the Jiaodong Peninsula, with both experiencing craton destruction during Late Mesozoic, but the two areas have substantial differences in terms of gold mineralization and the proven gold resources. Based on regional geology, Mesozoic magmatictectonic evolution and ore geology, combined with integrated geophysical exploration and big data AI resource prediction, in this paper, we propose that the ore-forming materials of Late Mesozoic gold deposits in Liaodong were mainly originated from mantle-derived melts and/or fluids induced by craton destruction. The gold deposits were primarily controlled by NE-NNEtrending faults, mainly classified as fracture-controlled altered rock-type and sulfide-bearing quartz vein-type. Moreover, our study predicts that the Yalu River fault zone and its related secondary faults, as well as the periphery and deeper parts of known goldfields, are the important regions for future gold resource exploration. The Yalu River metallogenic belt has an enormous potential for gold resources, and the Liaodong Peninsula has a potential to add thousands of tons of gold resources.

关键词： Liaodong Peninsula Gold deposit Integrated geophysical exploration Prospecting potential Direction for prospecting breakthroughs

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Pulses in ground motions identified through surface partial matching and their impact on seismic rocking consequence

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Earthquake Engineering and Engineering Vibration 2024年第1期23卷 35-50页

作者： Tang Yuchuan Wang Jiankang Wu Gang School of Civil Engineering Southeast UniversityKey Laboratory of Concrete and Prestressed Concrete Structures of the Ministry of EducationNanjing 211102China national and Local Joint Engineering research Center for Intelligent Construction and Maintenance Nanjing 211102China

In seismology and earthquake engineering,it is fundamental to identify and characterize the pulse-like features in pulse-type ground motions.To capture the pulses that dominate structural responses,this study establishes congruence and shift relationships between response spectrum surfaces.A similarity search between spectrum surfaces,supplemented with a similarity search in time series,has been applied to characterize the pulse-like features in pulse-type ground motions.The identified pulses are tested in predicting the rocking consequences of slender rectangular blocks under the original ground motions.Generally,the prediction is promising for the majority of the ground motions where the dominant pulse is correctly identified.

关键词： velocity pulse ground motion surface similarity rocking overturning

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Exploring Antarctic subglacial lakes with RECoverable Autonomous Sonde(RECAS):Design and first field tests

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science China(Technological sciences) 2024年第6期67卷 1866-1878页

作者： SUN YouHong PAVEL Talalay LI YuanSheng YU HaiBin WANG DongLiang LI GuoPing XU LiPing GONG Da WANG JiXin WANG JianHua WANG Ting ZHANG Nan WANG ZhiGang CHEN YanJi LIU YunChen LI YaZhou PENG ShiLin SHI JianGuang AN ChunLei GE Qun XU Jing NI XiaoKang CUI QiFeng JIANG Qiang MIKHAIL Sysoev Yang Yang WANG RuSheng WEI XianZhe WANG Yu ZHU TianXin DENG ZhiPeng ALEXEY Markov LI Bing FAN XiaoPeng Polar research Center Jilin UniversityChangchun130000China School of Engineering and technology China University of GeosciencesBeijing100083China Polar research Institute of China Shanghai200120China College of Electronics and Information Hangzhou Dianzi UniversityHangzhou310018China Aerospace System Engineering Shanghai Shanghai201109China Nanjing Institute of Astronomical Optics&technology National Astronomical ObservatoriesChinese Academy of SciencesNanjing210000China national Ocean technology Center Tianjin300000China

Conducting scientific drilling on subglacial lakes and obtaining samples of subglacial lake water holds great significance in unraveling the formation and evolution of Antarctic subglacial lakes and early Earth's life forms.Despite various approaches to access and directly sample subglacial water and sediments,clean access and exploration of subglacial lakes remain challenging.To address this concern,Jilin University has developed the RECoverable Autonomous Sonde(RECAS)prototype.This technology enables sampling and in-situ detection of subglacial lake water while being isolated from the surface,thus minimizing the risk of pollution.Laboratory tests,including downward and upward drilling,long-running,remote-control,and cold-environment assessments,were conducted to validate the sonde's principle and functionality.During the 38th Chinese national Antarctic research Expedition,CHINARE(2021–2022 season),the RECAS prototype underwent testing on the flank region of D?lk glacier,10 km from Zhongshan Station in Antarctica.Three boreholes with depths of 200.3,183.2,and 133.5 m were successfully drilled,with the refrozen meltwater sealing the boreholes during the process.Approximately 600 mL of melted water samples were collected from each hole.Throughout the drilling tests,all systems of the RECAS prototype performed within the expected ranges.

关键词： subglacial lake thermal drilling water sampling Antarctic autonomous sonde

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Molecule aging induced by electron attacking

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Journal of Energy Chemistry 2024年第6期93卷 519-525,I0013页

作者： Ping Song Yining Dong Xue Gong Mingbo Ruan Baoxin Ni Xuanhao Mei Kun Jiang Weilin Xu State key Laboratory of Electroanalytical Chemistry and Jilin Province key Laboratory of Low Carbon Chemical Power Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022JilinChina School of Applied Chemistry and Engineering University of Science and Technology of Chin1Hefei 230026AnhuiChina Shanghai key Laboratory of Molecular Catalysis and Innovative Materials Collaborative Innovation Center of Chemistry for Energy MaterialsDepartment of ChemistryFudan UniversityShanghai 200438China

Here we propose a new concept of"molecule aging":with some special treatment,a molecule could be"aged"by losing some unknown tiny particles or pieces from atoms in the molecule,Such"aging"or loss of unknown tiny particles does not change apparently its molecular structure or chemical composition,but some physicochemical properties could be changed irreversibly.We further confirm such"molecule aging"via a long-term electron attacking to age water(H_(2)O)molecules.The IR spectra show no structural difference between the fresh water and the aged one,while the NMR spectra show that the electron attacking can decrease the size of water clusters.Such facts indicate that the electron attacking indeed can"affect"the structure of water molecule slightly but without damaging to its basic molecule frame.Further exploration reveals that the hydrogen evolution reaction(HER)activity of the aged water molecule is lower than the fresh water on the same Pt/C electrocatalyst.The density functional theory calculations indicate that the shortened O-H bond in H_(2)O indeed can present lower HER activity,so the observed size decrease of water clusters from NMR probably could be attributed to the shortening of O-H bond in water molecules.Such results indicate significantly that the molecule aging can produce materials with new functions for new possible applications.

关键词： Aging of molecules Electron attacking Full width at half maxima Hydrogen evolution reaction

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Microstructures and mechanical properties of laser-directed energy deposited CrCoNi medium-entropy alloy

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Rare Metals 2024年第7期43卷 3286-3300页

作者： Wen-Jie Zhao Chang-Yu Liu Peng-Cheng Che Zhi-Liang Ning Hong-Bo Fan Jian-Fei Sun Yong-Jiang Huang Alfonso H.W.Ngan national key Laboratory for Precision Hot Processing of Metals Harbin Institute of Technology Space Environment Simulation research Infrastructure Harbin Institute of Technology Department of Mechanical Engineering The University of Hong Kong

The distinctive intrinsic heat treatment(IHT)originating from cyclic reheating in the laser-directed energy deposition(LDED) has attracted growing attention in recent years.In this investigation,simulations and experimental characterizations were performed to examine the impact of IHT on the micros true ture and mechanical properties of LDED-fabricated CrCoNi medium-entropy alloy(MEA).The results show that the intensity of the IHT is proportional to the utilized laser energy density(LED).As the LED increased,significant dynamic recrystallization and grain refinement occurred within the alloy due to the enhanced intensity of IHT.However,the high LED leads to severe hot cracking within the as-built MEA,resulting in inferior ductility.By decreasing LED,the hot cracking was effectively eliminated.Meanwhile,low LED weakened the intensity of IHT and consequently inhibited kinetic conditions of dynamic recrystallization,resulting in a heterogeneous grain structure characterized by multi-scale-sized grains.This structure provides significant hetero-deformation-induced hardening during plastic deformation,enabling the alloy to have a sustainable work-hardening capacity.We expect that this work will have implications in taking full advantage of the unique IHT of the LDED process to fabricate ME As with excellent metallurgical quality and mechanical performance.

关键词： Intrinsic heat treatment Laser-directed energy deposition CrCoNi MEA Dynamic recrystallization Heterogeneous grain structure

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Transcriptome analysis reveals immune-related genes in tissues of Vibrio anguillarum-infected turbot Scophthalmus maximus

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Journal of Oceanology and Limnology 2024年第1期42卷 332-344页

作者： Yuting SONG Maqsood Ahmed SOOMRO Xianzhi DONG Guobin HU College of Marine Life sciences Ocean University of ChinaQingdao 266003China Institute of Evolution&Marine Biodiversity Ocean University of ChinaQingdao 266003China Institute of Biophysis Chinese Academy of SciencesBeijing 100101China

Turbot Scophthalmus maximus is an important mariculture fish species with high economic value.However,the bacterial diseases caused by Vibrio anguillarum infection bring huge economic losses to the turbot aquaculture industry.To understand the immune response of the turbot against V.anguillarum infection and to explore novel immune-related genes,the transcriptome analysis of turbot spleen and gills were conducted after V.anguillarum infection.Differentially expressed genes(DEGs)were identified in spleen and gill of the turbot amounted to 17261 and 16436,respectively.A large number of immunerelated DEGs were enriched in cytokine-cytokine receptor interaction signaling pathway,and the others by the kyoto encyclopedia of genes and genomes(KEGG)enrichment.The gene ontology(GO)classification analysis revealed that V.anguillarum infection had the greatest effect on biological processes and cellular components.Twelve immune-related DEGs were identified in the spleen(cstl.1,egfl6,lamb21,v2rx4,calcr,and gpr78a)and gills(ghra,sh3gl2a,cst12,inhbaa,cxcl8,and il-1b)by heat map.The proteinprotein interaction(PPI)networks were constructed to analyze the immune mechanism.The results demonstrate that the maturation and antigen processing of major histocompatibility complex(MHC)class II molecule,and calcitonin-or adrenomedullin-regulated physiological activity were important events in the immunity of turbot against V.anguillarum infection.In the gills,the protein interactions in TGF-βsignaling pathway,production of inflammatory factors,and endocytosis regulation were most significant.Our research laid a foundation for discovering novel immune-related genes and enriching the knowledge of immune mechanisms of turbot against V.anguillarum infection.

关键词： Scophthalmus maximus Vibrio anguillarum transcriptome differentially expressed genes immune mechanism

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Heterostructured Pt-Ni_(3)Mo_(3)N formed via ammonia-containing polyoxometalates for highly efficient electrocatalytic hydrogen evolution in acid medium

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Journal of Energy Chemistry 2024年第5期92卷 698-704页

作者： Bianqing Ren Xue Gong Jing Cao Dezheng Zhang Zizhun Wang Ping Song Ce Han Weilin Xu State key Laboratory of Electroanalytical Chemistry Jilin Province Key Laboratory of Low Carbon Chemical PowerChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022JilinChina School of Applied Chemistry and Engineering University of Science and Technology of ChinaHefei 230026AnhuiChina key Laboratory of Automobile Materials MOE School of Materials Science&EngineeringJilin Provincial International Cooperation Key Laboratory of High-Efficiency Clean Energy MaterialsElectron Microscopy Centerand International Center of Future ScienceJilin UniversityChangchun 130012JilinChina

Constructing heterostructured nanohybrid is considered as a prominent route to fabricate alternative electrocatalysts to commercial Pt/C for hydrogen evolution reaction(HER).In this work,(NH_(4))_(4)[NiH_(6)Mo_(6)O_(4)]·5H_(2)O polyoxometalates(NiMo_(6))are adopted as the cluster precursors for simple fabrication of heterostructured Pt-Ni_(3)Mo_(3)N nanohybrids supported by carbon black(Pt-Ni_(3)Mo_(3)N/C)without using additional N sources.The improved porosity and enhanced electronic interaction of Pt-Ni_(3)Mo_(3)N/C should be attributed to the integration of Pt with NiMo_(6),which favors the mass transport,promotes the formation of exposed catalytic sites,and benefits the regulation of intrinsic activity.Thus,the as-obtained Pt-Ni_(3)Mo_(3)N/C exhibits impressive and durable HER performance as indicated by the low overpotential of 13.7 mV at the current density of 10 mA cm^(-2) and the stable overpotential during continuous working at 100 mA cm^(-2) for 100 h.This work provides significant insights for the synthesis of new highly active heterostructured electrocatalysts for renewable energy devices.

关键词： Polyoxometalates Cluster precursors Heterostructured nanohybrids Hydrogen evolution reaction Electrocatalysis

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