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Blockade of CD300A enhances the ability of human NK cells to lyse hematologic malignancies

Cancer Biology & Medicine 2024年第4期21卷 331-346页

作者： Shuangcheng Li Tianci Wang Xinghui Xiao Xiaodong Zheng Haoyu sun Rui sun Hongdi Ma Zhigang Tian Xiaohu Zheng Hefei National Research Center for Physical Sciences at Microscale The CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesCenter for Advanced Interdisciplinary Science and Biomedicine of IHMDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China Institute of Immunology University of Science and Technology of ChinaHefei 230027China Hefei TG ImmunoPharma Corporation Limited Hefei 230601China Research Unit of NK Cell Study Chinese Academy of Medical SciencesBeijing 100864China Key Laboratory of Quantitative Synthetic Biology Shenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(NK) cells targeting hematologic malignancies(HMs).Methods: We implemented a stimulation system involving the CD300A ligand, phosphatidylserine(PS), exposed to the outer surface of malignant cells. Additionally, we utilized CD300A overexpression, a CD300A blocking system, and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings. Furthermore, we explored the association between CD300A and HM progression in patients.Results: Our findings indicated that PS hampers the function of NK cells. Increased CD300A expression inhibited HM lysis by NK cells. CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells. Blocking PS–CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells, thereby augmenting the ability to lyse HMs. Clinically, heightened CD300A expression correlated with shorter survival and an “exhausted” phenotype of intratumoral NK cells in patients with HMs or solid tumors.Conclusions: These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.

关键词： NK cell CD300A phosphatidylserine immune checkpoint hematologic malignancy

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Experimental and simulation research on hollow AZ31 magnesium alloy three-channel joint by hot extrusion forming with sand mandrel

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Journal of Magnesium and Alloys 2024年第1期12卷 98-109页

作者： Shi Shengnan Wang Hongyu Teng Fei Jiang Lei sun Juncai sun Jie Zhang Shunhu Transportation Engineering College Dalian Maritime UniversityDalianLiaoning 106026China State Key Laboratory of Rolling and Automation Northeastern UniversityShenyangLiaoning 110819China Shagang School of Iron and Steel Soochow UniversitySuzhouJiangsu 215021China

Magnesium alloy is one of the lightest metal structural materials.The weight is further reduced through the hollow structure.However,the hollow structure is easily damaged during processing.In order to maintain the hollow structure and to transfer the stresses during the high temperature deformation,the sand mandrel is proposed.In this paper,the hollow AZ31 magnesium alloy three-channel joint is studied by hot extrusion forming.Sand as one of solid granule medium is used to fill the hollow magnesium alloy.The extrusion temperatures are 230℃ and 300℃,respectively.The process parameters(die angle,temperature,bottom thickness,sidewall thickness,edge-to-middle ratio in bottom,bottom shape)of the hollow magnesium alloy are analyzed based on the results of experiments and the finite element method.The results are shown that the formability of the hollow magnesium alloy will be much better when the ratio of sidewall thickness to the bottom thickness is 1:1.5.Also when edge-to-middle ratio in bottom is about 1:1.5,a better forming product can be received.The best bottom shape in these experiments will be convex based on the forming results.The grain will be refined obviously after the extrusion.Also the microstructures will be shown as streamlines.And these lines will be well agreement with the mold in the corner.

关键词： AZ31 magnesium alloy Three-channel joint Sand Experiments and the finite element Die angle

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Pylorus-preserving gastrectomy for early gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 653-658页

作者： Ke-Kang sun Yong-You Wu Department of Gastrointestinal Surgery The Affiliated Kunshan Hospital to Jiangsu UniversitySuzhou 215300Jiangsu ProvinceChina Department of Gastrointestinal Surgery The Second Affiliated Hospital of Soochow UniversitySuzhou 215008Jiangsu ProvinceChina

Pylorus-preserving gastrectomy(PPG)has been widely accepted as a function-preserving gastrectomy for middle-third early gastric cancer(EGC)with a distal tumor border at least 4 cm proximal to the pylorus.The procedure essentially preserves the function of the pyloric sphincter,which requires to preserve the upper third of the stomach and a pyloric cuff at least 2.5 cm.The suprapyloric and infrapyloric vessels are usually preserved,as are the hepatic and pyloric branches of the vagus nerve.Compared with distal gastrectomy,PPG has significant advantages in preventing dumping syndrome,body weight loss and bile reflux gastritis.The postoperative complications after PPG have reached an acceptable level.PPG can be considered a safe,effective,and superior choice in EGC,and is expected to be extensively performed in the future.

关键词： Gastric cancer Pylorus-preserving gastrectomy Oncological safety Gastric stasis

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Exploring changes of precipitation extremes under climate change through global variable-resolution modeling

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Science Bulletin 2024年第2期69卷 237-247页

作者： Wei sun Jian Li Rucong Yu Nina Li Yi Zhang State Key Laboratory of Severe Weather Chinese Academy of Meteorological SciencesBeijing 100081China Institute of Tibetan Plateau Meteorology China Meteorological AdministrationChengdu 610072China Department of Atmospheric Science Yunnan UniversityKunming 650091China National Meteorological Center China Meteorological AdministrationBeijing 100081China 2035 Future Laboratory PIESAT Information Technology Co.Ltd.Beijing 100105China

Understanding the responses of precipitation extremes to global climate change remains limited owing to their poor representations in models and complicated interactions with multi-scale systems.Here we take the record-breaking precipitation over China in 2021 as an example,and study its changes under three different climate scenarios through a developed pseudo-global-warming(PGW)experimental framework with 60-3 km variable-resolution global ensemble modeling.Compared to the present climate,the precipitation extreme under a warmer(cooler)climate increased(decreased)in intensity,coverage,and total amount at a range of 24.3%-37.8%(18.7%-56.1%).With the help of the proposed PGW experimental framework,we further reveal the impacts of the multi-scale system interactions in climate change on the precipitation extreme.Under the warmer climate,large-scale water vapor transport converged from double typhoons and the subtropical high marched into central China,enhancing the convective energy and instability on the leading edge of the transport belt.As a result,the mesoscale convective system(Mcs)that directly contributed to the precipitation extreme became stronger than that in the present climate.On the contrary,the cooler climate displayed opposite changing characteristics relative to the warmer climate,ranging from the large-scale systems to local environments and to the Mcs.In summary,our study provides a promising approach to scientifically assess the response of precipitation extremes to climate change,making it feasible to perform ensemble simulations while investigating the multi-scale system interactions over the globe.

关键词： Precipitation extreme Climate change Pseudo-global-warming experiment Variable-resolution modeling Multi-scale system interaction

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Towards Data-Driving Multi-View Evaluation Framework for Scratch

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Tsinghua Science and Technology 2024年第2期29卷 517-528页

作者： Xiaolin Chai Yan sun Yan Gao Department of Computer Science Beijing University of Posts and TelecommunicationBeijing 100876China Intellectual Property Institute Shandong Polytechnic CollegeJining 272067China

As one of the most popular visual programming languages,Scratch has a lot of evaluation around it.Reasonable evaluation can help programmers understand their projects better.At the same time,it can also provide a reference for them to browse other projects in the online community.Most of the existing evaluations on Scratch are carried from three perspectives:Computational Thinking(CT)ability,visual presentation aesthetics,and code quality.Among them,the assessment of CT and code quality is mainly carried out from the program script,while the evaluation of visual aesthetics is analyzed from the perspective of image sequences generated by project execution.The single-view evaluation focuses on the performance of a program in a certain aspect and is one-sided.In this paper,we propose a multi-view evaluation framework to integrate various evaluations using different policies.We quantitatively analyze the assessment of different views driven by data.Combined with overall evaluations that represent human opinions,we analyze their differences and connections.Through experiments,we determine the weights of different integration policies,the proposed multi-view evaluation method can generate evaluation results similar to human opinions.

关键词： Scratch Computational Thinking(CT) visual aesthetic static analysis integration policy machine learning

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A combined evaluation of the characteristics and antibiotic resistance induction potential of antibiotic wastewater during the treatment process

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Journal of Environmental Sciences 2024年第4期138卷 626-636页

作者： sun Miao Yanyan Zhang Cong Men Yiou Mao Jiane Zuo State Key Joint Laboratory of Environment Simulation and Pollution Control School of EnvironmentTsinghua UniversityBeijing 100084China School of Energy and Environmental Engineering Beijing Key Laboratory of Resource-Oriented Treatment of Industrial PollutantsUniversity of Science and Technology BeijingBeijing 100083China High School Affiliated to Renmin University of China Beijing 100080China Tsinghua Shenzhen International Graduate School Shenzhen 518055China

Antibiotic wastewater contains a variety of pollutant stressors that can induce and promote antibiotic resistance(AR)when released into the environment.Although these substances are mostly in concentrations lower than those known to induce AR individually,it is possible that antibiotic wastewater discharge might still promote the AR transmission risk via additive or synergistic effects.However,the comprehensive effect of antibiotic wastewater on AR development has rarely been evaluated,and its treatment efficiency remains unknown.Here,samples were collected from different stages of a cephalosporin production wastewater treatment plant,and the potential AR induction effect of their chemical mixtures was explored through the exposure of the antibiotic-sensitive Escherichia coli K12 strain.Incubation with raw cephalosporin production wastewater significantly promoted mutation rates(3.6×10^(3)-9.3×10^(3)-fold)and minimum inhibition concentrations(6.0-6.7-fold)of E.coli against ampicillin and chloramphenicol.This may be attributed to the inhibition effect and oxidative stress of cephalosporin wastewater on E.coli.The AR induction effect of cephalosporin wastewater decreased after the coagulation sedimentation treatment and was completely removed after the full treatment process.A Pearson correlation analysis revealed that the reduction in the AR induction effect had a strong positive correlation with the removal of organics and biological toxicity.This indicates that the antibiotic wastewater treatment had a collaborative processing effect of conventional pollutants,toxicity,and the AR induction effect.This study illustrates the potential AR transmission risk of antibiotic wastewater and highlights the need for its adequate treatment.

关键词： Antibiotic wastewater treatment plant Antibiotic resistance Antibiotic resistance induction effect Correlation analysis Biological toxicity

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Stem cell-based ischemic stroke therapy:Novel modifications and clinical challenges

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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 18-34页

作者： Yuankai sun Xinchi Jiang Jianqing Gao Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Hangzhou Institute of Innovative Medicine College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Dr.Li Dak Sum&Yip Yio Chin Center for Stem Cell and Regenerative Medicine Zhejiang UniversityHangzhou 310058China Department of Pharmacy The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China

Ischemic stroke(IS)causes severe disability and high mortality worldwide.Stem cell(SC)therapy exhibits unique therapeutic potential for IS that differs from current treatments.SC’s cell homing,differentiation and paracrine abilities give hope for neuroprotection.Recent studies on SC modification have enhanced therapeutic effects for IS,including gene transfection,nanoparticle modification,biomaterial modification and pretreatment.Thesemethods improve survival rate,homing,neural differentiation,and paracrine abilities in ischemic areas.However,many problems must be resolved before SC therapy can be clinically applied.These issues include production quality and quantity,stability during transportation and storage,as well as usage regulations.Herein,we reviewed the brief pathogenesis of IS,the“multi-mechanism”advantages of SCs for treating IS,various SC modification methods,and SC therapy challenges.We aim to uncover the potential and overcome the challenges of using SCs for treating IS and convey innovative ideas for modifying SCs.

关键词： Ischemic stroke Stem cell therapy Stem cell modification Cell therapy challenge

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Changes in extreme high temperature warning indicators over China under different global warming levels

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Science China Earth Sciences 2024年第6期67卷 1895-1909页

作者： Yuxia ZHANG Ying sun Ting HU Chinese Academy of Meteorological Sciences Beijing 100081China National Climate Center Laboratory for Climate StudiesChina Meteorological AdministrationBeijing 100081China

High temperature warning indicators play a pivotal role in meteorological departments,serving as crucial criteria for issuing warnings that guide both social production and daily life.Despite their importance,limited studies have explored the relationship between different global warming levels and changes in high temperature warning indicators.In this study,we analyze data from 2,419 meteorological stations over China and utilize the Coupled Model Intercomparison Project Phase 6(CMIP6)models to examine historical changes in high temperature warning indicators used by the China Meteorological Administration.We evaluate model performance and estimate future changes in these indicators using an annual cycle bias correction method.The results indicate that since 1961,the number of high temperature days(TX35d and TX40d)and length of season(TX40d and TX40l)with daily maximum temperature reaching or exceeding 35℃ and 40℃ have increased over China.The intensity of high temperatures(TXx)has strengthened and the geographical extent affected by high temperatures has expanded.In 2022,the occurrence of 40℃ high temperatures surges,with Eastern China experiencing a two-day increase in TX40d and an extended seasonal length in TX40l by over five days.While CMIP6 models have underestimated the high temperature indictors associated with 35℃ during historical periods,notable difference is not observed between the models and observations for TX40d and TX40l,given their rare occurrence.However,future projections,after bias correction,indicate that the increasing trends for 35℃ and 40℃ high temperature days and length of season become more pronounced than the raw projection,suggesting a more severe increase than that anticipated originally.As global warming intensifies,the high temperature days and length of season are projected to increase non-linearly,while the intensity of high temperatures is expected to increase linearly.For every 1℃ increase in global temperature,the intensity is projected to rise by approximately 1.4℃.The impa

关键词： Extreme high temperatures Meteorological warning CMIP6 Global warming levels Future projection

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Feeding prehistoric coastal community:A study of marine faunal remains at the Jingtoushan site

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Science China Earth Sciences 2024年第5期67卷 1574-1590页

作者： Endong WU Guoping sun Ying ZHANG School of Culture History and LanguageAustralian National UniversityCanberra 2600Australia Zhejiang Provincial Institute of Cultural Relics and Archaeology Hangzhou 310012China National Centre for Archaeology Beijing 100013China

This article examines the abundant marine mollusc,and fish remains at the Jingtoushan shell midden(8,300 to7,800 cal a BP)in Zhejiang Province,China,to investigate the fishing economy,community development,the palaeoenvironment,and their interactions among the prehistoric populations in the lower Yangtze River Basin and southeastern coastal China.It also attempts to explore the prosperity and decline of coastal settlements in China during the Neolithic Age and the potential reasons for their rise and fall,respectively.Based on the ecological and biological principles of marine animals,standard zooarchaeological methods and radiocarbon dating analysis are used for sampling,identification,measurement,and quantification.Results show that at least 11 mollusc taxa and 14 fish taxa can be identified from the Jingtoushan faunal assemblage.The ancient Jingtoushan residents possibly lived in a settlement close to the coast and engaged in inshore and offshore fishing,hunting,and gathering as their primary subsistence strategies,with low-level rice cultivation as a supplementary means of sustenance.Eventually,the changes in the coastal environment could be one of the reasons why the Jingtoushan residents abandoned their settlement.The research contributes to Chinese Neolithic archaeology with new evidence of the exploitation of marine resources around 8000 a BP in the eastern coastal areas and the relationship between Neolithic community development and environmental changes.

关键词： Neolithic Age Marine faunal remains Fishing economy Palaeoenvironment Community development

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Influence of nitrogen status on fermentation performances of non-Saccharomyces yeasts:a review

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Food Science and Human Wellness 2024年第2期13卷 556-567页

作者： Jinchen Li Mengmeng Yuan Nan Meng Hehe Li Jinyuan sun Baoguo sun Key Laboratory of Brewing Molecular Engineering of China Light Industry Beijing Key Laboratory of Flavor ChemistryBeijing Technology&Business UniversityBeijing 100048China

Nitrogen,one of the most crucial nutrients present in grapes and musts,plays a key role in yeast activities during alcoholic fermentation.Such influences are imposed on yeast growth and fermentation performances including the formation of secondary metabolites.Saccharomyces cerevisiae,the main yeast responsible for fermentation,has been studied extensively regarding nitrogen impacts.On the other hand,a similar study for non-Saccharomyces yeasts,whose contributions to winemaking have gradually been acknowledged,remains to be fully explored,with a few studies being reported.This review starts by discussing nitrogen impacts on non-Saccharomyces yeast growth and fermentation kinetics in different case scenarios,then proceeds to summarize the nitrogen preferences of individual yeast strains with regulation mechanisms elucidated by recent studies.Detailed discussions on the influences on the production of volatile compounds and proposed pathways therein are made,followed by future work suggested as the final section.In summarizing the nitrogen impacts on non-Saccharomyces yeasts throughout alcoholic fermentation,this review will be helpful in obtaining a more comprehensive view on these non-conventional wine yeasts in terms of nutrient requirements and corresponding volatile production.Research gaps will therefore be elucidated for future research.

关键词： Non-Saccharomyces yeasts Nitrogen Fermentation kinetics Nitrogen preference Wine aroma

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