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Integrative single-cell multiomics analyses dissect molecular signatures of intratumoral heterogeneities and differentiation states of human gastric cancer

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National Science Review 2023年第6期10卷 96-107页

作者： Shuhui Bian Yicheng Wang Yuan Zhou Wendong Wang Limei Guo Lu Wen Wei Fu Xin Zhou Fuchou Tang Biomedical Pioneering Innovation Center School of Life Sciences Department of General Surgery Third Hospital Peking University State Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical University Beijing Advanced Innovation Center for Genomics (ICG) Ministry of Education Key Laboratory of Cell Proliferation and Differentiation Department of Pathology Peking University Third Hospital School of Basic Medical Science Peking University Health Science Center Peking University Third Hospital Cancer Center Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary Studies Peking University

Human gastric cancer is a highly lethal disease,but the underlying multiomic mole cular signatures remain largely uncle ar.Here,we performed multi-regional sampling,parallel single-cell multiomics sequencing and integrated analyses of human gastric cancer.We identified common transcrip tomic alterations of gastric cancer cells,such as aberrant down-regulation of genes associated with normal stomach function and up-regulation of KRT7,PI3,S100A4,etc.Surprisingly,aberrant and prevalent up-regulation of genes highly expressed in normal colorectal epithelial cells were also identified in cancer cells,which maybe partially regulated by promoter chromatin accessibility and DNA methylation levels.We reve aled the single-cell DNA methylome landscape of gastric cancer,and identified candidate DNA methylation biomarkers,such as hypermethylated promoters of TMEM240 and HAGLROS,and hypomethylated promoters of TRPM2-AS and HRH1.Additionally,the relationships between genetic lineages,D NA methylation and transcriptomic clusters were systematically revealed at single-cell level.We showed that DNA methylation heterogeneities were mainly among different genetic lineages of cancer cells.Moreover,we found that D NA methylation levels of cancer cells with poorer differentiation states tend to be higher than those of cancer cells with better differentiation states in the primary tumor within the same patient,although still lower than in normal gastric epithelial cells.Cancer cells with poorer differentiation states also prevalently down-regulated MUC1 expression and immune-related pathways,and had poor infiltration of CD 8+T cells.Our study dissected the mole cular signatures of intratumoral heterogeneities and differentiation states of human gastric cancer using integrative single-cell multiomics analyses.

关键词： gastric cancer single-cell multiomics analysis intratumoral heterogeneity tumor differentiation

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Proteomic Analysis of the Small Intestine Reveals Adaptive Strategies for Energy Restriction of Phrynocephalus vlangalii at High Altitude

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Asian Herpetological Research 2023年第2期14卷 167-174页

作者： Yangyang ZHAO Cui YANG Yongxing HE Yue QI shuhui CAO Xue bian Wei ZHAO Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution School of Life SciencesLanzhou UniversityLanzhou 730000GansuChina

The environmental characteristics of hypothermia and hypoxia exert great selective pressure on the energy metabolism of high-altitude animals,especially the ectotherms.Current research on energy-limited adaptation of high-altitude ectotherms has focused on energy expenditures.However,the mechanisms of increasing energy intake in high-altitude ectotherms have been studied rarely.In order to investigate the adaptation mechanism of the small intestine,the key part of energy acquisition for animals,to energy limitation at high altitude in ectotherms,the gut proteins of Phrynocephalus vlangalii from high-and low-altitude populations were compared using label free proteomics.GO enrichment and KEGG pathway analysis showed that proteins associated with energy intake,such as those involved in oxidation-reduction processes,glutathione metabolism,oxidoreductase activity,cofactor binding,catalytic activity and metabolic pathways,were significantly up-regulated in high-altitude populations;while proteins associated with energy expenditure,such as immune responses and processes,membrane attack complexes,natural killer pathway and other immune-related processes,were significantly down-regulated in expression.

关键词： energy intake energy limitation high altitude label-free proteomic analysis lipid metabolism Phrynocephalus vlangalii

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Combinatorial metabolic engineering of Saccharomyces cerevisiae for improved production of 7-dehydrocholesterol

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Engineering Microbiology 2023年第4期3卷 29-37页

作者： Yuehao Gu shuhui Chen Xue Jiao Qi bian Lidan Ye Hongwei Yu Key Laboratory of Biomass Chemical Engineering(Education Ministry) College of Chemical and Biological EngineeringZhejiang UniversityHangzhou 310058China Institute of Bioengineering College of Chemical and Biological EngineeringZhejiang UniversityHangzhou 310058China

7-Dehydrocholesterol(7-DHC),a key pharmaceutical intermediate in the production of vitamin D3,has a wide range of applications.To explore fermentative synthesis of 7-DHC,a 7-DHC-producing Saccharomyces cerevisiae strain was constructed by blocking the competitive pathway,eliminating rate-limiting steps,altering global reg-ulation,and pathway compartmentalization.After blocking the competitive pathway by disrupting ERG5 and ERG6 and introducing DHCR24 from Gallus gallus,S.cerevisiae produced 139.72 mg/L(17.04 mg/g dry cell weight,hereafter abbreviated as DCW)7-DHC.Subsequent alteration of global regulation by deleting ROX1 and overexpressing UPC2-1 increased 7-DHC production to 217.68 mg/L(37.56 mg/g DCW).To remove the accu-mulated squalene,the post-squalene pathway was strengthened by co-overexpression of PGAL1-driven ERG11 and PGAL10-driven ERG1,which improved 7-DHC titer and yield to 281.73 mg/L and 46.78 mg/g DCW,respectively,and reduced squalene content by 90.12%.We surmised that the sterol precursors in the plasma membrane and peroxisomes may not be accessible to the pathway enzymes,thus we re-localized DHCR24p and Erg2p-GGGGS-Erg3p to the plasma membrane and peroxisomes,boosting 7-DHC production to 357.53 mg/L(63.12 mg/g DCW).Iron supplementation further increased 7-DHC production to 370.68 mg/L in shake flasks and 1.56 g/L in fed-batch fermentation.This study demonstrates the power of global regulation and subcellular relocalization of key enzymes to improve 7-DHC synthesis in yeast.

关键词： 7-Dehydrocholesterol Saccharomyces cerevisiae Metabolic engineering Global regulation Pathway re-localization

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Multi-factor principle for electrolyte additive molecule design for facilitating the development of electrolyte chemistry

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Green Energy & Environment 2022年第1期7卷 1-2页

作者： shuhui Sun Institut National de la Recherche Scientifique(INRS)-Center for Energy Materials and TelecommunicationsVarennesQuébec J3X 1S2Canada

When I read the paper“Electrolytes enriched by potassium perfluorinated sulfonates for lithium metal batteries”from Prof.Jianmin Ma’s group,which was published in Science Bulletin(***/10.1016/j.scib.2020.09.018),I felt excited as presented a multi-factor principle for applying potassium perfluorinated sulfonates to suppress the dendrite growth and protect the cathode from the viewpoint of electrolyte additives.The effects of these additives are revealed through experimental results,molecular dynamics simulations and first-principle calculations.Specifically,it involves the influence of additives on Li^(+)solvation structure,solid electrolyte interphase(SEI),Li growth and nucleation.Following the guidance of the multi-factor principle,every part of the additive molecule should be utilized to regulate electrolytes.This multifactor principle for electrolyte additive molecule design(EAMD)offers a unique insight on understanding the electrochemical behavior of iontype electrolyte additives on both the Li metal anode and high-voltage cathode.In these regards,I would be delighted to write a highlight for this innovative work and,hopefully,it may raise more interest in the areas of electrolyte additives.

关键词： Lithium metal batteries Multi-factor principle Electrolyte additives Dendrite growth suppression Lithium protection

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Approaching the commercial threshold of solar water splitting toward hydrogen byⅢ-nitrides nanowires

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Frontiers in Energy 2024年第1期18卷 122-124页

作者： Baowen ZHOU shuhui SUN Key Laboratory for Power Machinery and Engineering of the Ministry of Education School of Mechanical EngineeringShanghai Jiao Tong UniveristyShanghai 200240China Institut National de la Recherche Scientifique(INRS)-CenterÉnergie Matériaux Télécommunications VarennesQuebec J3X 1P7Canada

In a recent article in Nature,Mi and coworkers from the University of Michigan reported a solar-to-hydrogen(STH)efficiency of>9%in converting water into hydrogen and oxygen[1],which represents an important breakthrough in this field due to the benchmarking leap in STH efficiency of photocatalytic overall water splitting under natural sunlight.

关键词： breakthrough splitting Michigan

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Material manufacturing from atomic layer

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International Journal of Extreme Manufacturing 2023年第4期5卷 454-460页

作者： Xinwei Wang Rong Chen shuhui Sun School of Advanced Materials Shenzhen Graduate SchoolPeking UniversityShenzhen 518055People’s Republic of China School of Mechanical Science and Engineering Huazhong University of Science and TechnologyWuhan 430070People’s Republic of China Institut National de la Recherche Scientifique(INRS) Centre Energie Matériaux TélécommunicationsVarennesQuébec J3X 1P7Canada

Atomic scale engineering of materials and interfaces has become increasingly important in material manufacturing.Atomic layer deposition(ALD)is a technology that can offer many unique properties to achieve atomic-scale material manufacturing controllability.Herein,we discuss this ALD technology for its applications,attributes,technology status and challenges.We envision that the ALD technology will continue making significant contributions to various industries and technologies in the coming years.

关键词： atomic-scale manufacturing,atomic layer deposition,area selective deposition,applications

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Distributed user pairing and effective computation offloading in aerial edge networks

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Chinese Journal of Aeronautics 2024年第4期37卷 378-390页

作者： Wei LIANG shuhui WEN Lixin LI Jingjing CUI School of Electronics and Information Northwestern Polytechnical UniversityXi’an CN710072China The State Key Laboratory of Integrated Services Networks Xidian UniversityXi’an CN710126China School of Electronics and Computer Science University of SouthamptonSouthampton SO167NSUK

Future Sixth-Generation (6G) mobile communication networks extremely require the global connectivity and the ground Base Stations (BSs) are difficult to develop in some specific areas,such as mountainous areas.Therefore,the aerial networks are the key framework for the future communications,in which the aerial vehicle could act as the access point.Additionally,Mobile Edge Computing (MEC) is also essential to enhance the data processing capabilities of aerial networks.In this paper,we study a comprehensive communication-computation resource management problem for jointly optimizing user pairing,power and time allocation in the MEC aided Cognitive Radio (CR) aerial networks,namely CR-MEC aerial networks.Explicitly,this multilevel optimization problem could be decomposed into the user pairing and power allocation as well as time allocation sub-problems.In the conceived CR-MEC aerial networks,we propose a User Pairing and Computation Offloading Management Algorithm (UPCOMA) based on three-sided matching theory,aiming to minimize the system’s energy consumption.At the first step of UPCOMA,multiple Primary Users (PUs) and Cognitive Users (CUs) on the ground negotiate to each other with the suitable power allocation coefficients and construct the stable user pairs.Moreover,the stable user pairs would match to a high altitude platform who act as the base station,which is for appropriately allocating Transmission Time Slots (TSs) at the second step of UPCOMA.Additionally,a hybrid offloading mode is proposed in our conceived networks in order to support ground users to offload their tasks adaptively according to their individual deadlines.Furthermore,the simulation results reveal that the relative performance of UPCOMA is close to that of the Brute-Force Search Algorithm (BFSA) with low complexity.Meanwhile,the hybrid offloading mode with less energy consumption supports much more ground user pairs to offload tasks compared to the binary mode.

关键词： Aerial edge computing Binary offloading Cognitive radio Hybrid offloading Resource management

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Distributed Event-triggered Secondary Control for Average Bus Voltage Regulation and Proportional Load Sharing of DC Microgrid

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Journal of Modern Power Systems and Clean Energy 2022年第3期10卷 678-688页

作者： Zhongwen Li Zhiping Cheng Jikai Si shuhui Li School of Electrical Engineering Zhengzhou UniversityZhengzhou 450001China Department of Electrical and Computer Engineering The University of AlabamaTuscaloosaAL 35487USA

This paper proposes a novel distributed event-triggered secondary control method to overcome the drawbacks of primary control for direct current(DC)microgrids.With eventtriggered distributed communication,the proposed control method can achieve system-wide control of parallel distrubted generators(DGs)with two main control objectives:①estimate the average bus voltage and regulate it at the nominal value;②achieve accurate current sharing among the DGs in proportion to their power output ratings.Furthermore,the proposed control strategy can be implemented in a distributed way that shares the required tasks among the DGs.Thus,it shows the advantages of being flexible and scalable.Furthermore,this paper proposes a simple event-triggered condition that does not need extra state estimator.Thus,limited communication among neighbors is required only when the event-triggered condition is satisfied,which significantly reduces the communication burden at the cyber layer.

关键词： Direct current(DC)microgrid droop control event-triggered secondary control distributed consensus load sharing

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Database Resources in BIG Data Center:Submission, Archiving, and Integration of Big Data in Plant Science

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Molecular Plant 2019年第3期12卷 279-281页

作者： shuhui Song Zhang Zhang BIG Data Center Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Genome Sciences and Information Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

With the rapid advancement of sequencing technologies and the growing volume of omics data in plants, there is much anticipation in digging out the treasure from such big data and accordingly refining the current agricultural practice to be applied in the near future. Toward this end, database resources that deliver web services for plant omics data submission, archiving, and integration are urgently needed. As a part of Beijing Institute of Genomics (BIG) of the Chinese Academy of Sciences (CAS), BIG Data Center (http://***) provides open access to a suite of database resources (Table 1), with the aim of supporting plant research activities for domestic and international users in both academia and industry to translate big data into big discoveries (BIG Data Center Members, 2017;BIG Data Center Members, 2018;BIG Data Center Members, 2019). Here, we give a brief introduction of plant-related database resources in BIG Data Center and appeal to plant research com丒 munities to make full use of these resources for plant data submission, archiving, and integration.

关键词： Database Resources BIG Data Center

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Strategies to achieve effective nitrogen activation

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Carbon Energy 2024年第5期6卷 137-163页

作者： Bin Chang Huabin Zhang shuhui Sun Gaixia Zhang KAUST Catalysis Center(KCC) King Abdullah University of Science and Technology(KAUST)ThuwalKingdom of Saudi Arabia Institut National de la Recherche Scientifique(INRS) CentreÉnergie Matériaux TélécommunicationsVarennesQuébecCanada Department of Electrical Engineering École de Technologie Supérieure(ÉTS)MontréalQuébecCanada

Ammonia serves as a crucial chemical raw material and hydrogen energy carrier.Aqueous electrocatalytic nitrogen reduction reaction(NRR),powered by renewable energy,has attracted tremendous interest during the past few years.Although some achievements have been revealed in aqueous NRR,significant challenges have also been identified.The activity and selectivity are fundamentally limited by nitrogen activation and competitive hydrogen evolution.This review focuses on the hurdles of nitrogen activation and delves into complementary strategies,including materials design and system optimization(reactor,electrolyte,and mediator).Then,it introduces advanced interdisciplinary technologies that have recently emerged for nitrogen activation using high-energy physics such as plasma and triboelectrification.With a better understanding of the corresponding reaction mechanisms in the coming years,these technologies have the potential to be extended in further applications.This review provides further insight into the reaction mechanisms of selectivity and stability of different reaction systems.We then recommend a rigorous and detailed protocol for investigating NRR performance and also highlight several potential research directions in this exciting field,coupling with advanced interdisciplinary applications,in situ/operando characterizations,and theoretical calculations.

关键词： activation via mediators catalyst optimization electrochemical nitrogen fixation high-energy activation of nitrogen nitrogen

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