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Multiomics analysis reveals metabolic subtypes and identifies diacylglycerol kinase α (DGKA) as a potential therapeutic target for intrahepatic cholangiocarcinoma

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Cancer Communications 2024年第2期44卷 226-250页

作者： weiren liu Huqiang Wang Qianfu Zhao Chenyang Tao Weifeng Qu Yushan Hou Run Huang Zimei Sun Guiqi Zhu Xifei Jiang Yuan Fang Jun Gao Xiaoling Wu Zhixiang Yang Rongyu Ping Jiafeng Chen Rui Yang Tianhao Chu Jian Zhou Jia Fan Zheng Tang Dong Yang Yinghong Shi Department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityKey Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationShanghaiP.R.China Research Unit of Liver cancer Recurrence and Metastasis Chinese Academy of Medical SciencesBeijingP.R.China State Key Laboratory of Medical Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijingP.R.China

Background:Intrahepatic cholangiocarcinoma(iCCA)is a highly heteroge-neous and lethal hepatobiliary tumor with few therapeutic strategies.The metabolic reprogramming of tumor cells plays an essential role in the develop-ment of tumors,while the metabolic molecular classification of iCCA is largely unknown.Here,we performed an integrated multiomics analysis and metabolic classification to depict differences in metabolic characteristics of iCCA patients,hoping to provide a novel perspective to understand and treat iCCA.Methods:We performed integrated multiomics analysis in 116 iCCA samples,including whole-exome sequencing,bulk RNA-sequencing and proteome anal-ysis.Based on the non-negative matrix factorization method and the protein abundance of metabolic genes in human genome-scale metabolic models,the metabolic subtype of iCCA was determined.Survival and prognostic gene analy-ses were used to compare overall survival(OS)differences between metabolic subtypes.Cell proliferation analysis,5-ethynyl-2’-deoxyuridine(EdU)assay,colony formation assay,RNA-sequencing and Western blotting were performed to investigate the molecular mechanisms of diacylglycerol kinaseα(DGKA)in iCCA cells.Results:Three metabolic subtypes(S1-S3)with subtype-specific biomarkers of iCCA were identified.These metabolic subtypes presented with distinct prog-noses,metabolic features,immune microenvironments,and genetic alterations.The S2 subtype with the worst survival showed the activation of some special metabolic processes,immune-suppressed microenvironment and Kirsten ratsar-coma viral oncogene homolog(KRAS)/AT-rich interactive domain 1A(ARID1A)mutations.Among the S2 subtype-specific upregulated proteins,DGKA was further identified as a potential drug target for iCCA,which promoted cell proliferation by enhancing phosphatidic acid(PA)metabolism and activating mitogen-activated protein kinase(MAPK)signaling.Conclusion:Viamultiomics analyses,we identified three metabolic subtypes of iCCA,revealing that the S2 subtype exhibited the poorest surviv

关键词： diacylglycerol kinaseα intrahepatic cholangiocarcinoma MAPK signaling metabolic classifi-cation multiomics analysis phosphatidic acid metabolism

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Immunotherapy of hepatocellular carcinoma: strategies for combinatorial intervention

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Science China(Life Sciences) 2019年第9期62卷 1138-1143页

作者： Mengxin Tian Yinghong Shi weiren liu Jia Fan Department of Liver Surgery & Transplantation Center Liver Cancer InstituteZhongshan HospitalFudan University/Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationShanghai 200032China Institute of Biomedical Sciences Fudan UniversityShanghai 200032China

Hepatocellular carcinoma(HCC) is the most frequent primary liver cancer,leading to 74.6 thousand deaths annually.The prognosis of HCC over the last few decades has remained unsatisfactory,and over half of patients with early-stage HCC develop recurrence by the time of follow-up.Immunotherapeutic intervention has emerged as a novel,effective treatment to delay the progression of aggressive tumors and suppress tumor recurrence and metastasis.However,few clinical immunotherapy trials have been conducted in HCC patients,and there is an unmet need for novel therapeutic strategies.The combination of conventional treatments with specific immunotherapeutic approaches may dramatically improve the efficacy of HCC treatment and the clinical outcome of HCC patients.In this review,we briefly summarize immunotherapy strategies and discuss new advances in combined immunotherapeutic approaches for the treatment of patients with liver cancer.

关键词： hepatocellular carcinoma immunotherapy immune checkpoint inhibitor strategy combination therapy

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Design and implementation of Chinese libration point missions

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Science China(Information Sciences) 2023年第9期66卷 100-114页

作者： Lei liu weiren WU Yong liu Beijing Aerospace Control Center Lunar Exploration and Space Program Center

Libration points are vital for lunar and deep space explorations because of their unique positions and dynamics. This paper first traces the development of relevant missions since ISEE-3 and then presents the details of the trajectory design and implementation of four Chinese libration point missions in the lunar exploration project: the two Sun-Earth libration point missions by CHANG’E-2 and CHANG’E-5 and the two lunar libration point missions accomplished by CHANG’E-5T1 and Queqiao. The orbit technologies for these libration point missions are also elaborated on regarding trajectory design, maneuvering, and tracking,as well as orbit determination. This paper is expected to provide a reference for future cislunar and deep space exploration.

关键词： libration point three-body problem lunar exploration cislunar space flight scheme

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股前外侧或股前内侧穿支皮瓣修复皮肤鳞状细胞癌切除后皮肤软组织缺损的临床效果

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中华烧伤与创面修复杂志 2024年第6期40卷 564-571页

作者：柳若冰郑德义王宝云李伟人贵州医科大学附属金阳医院皮肤科贵阳550001 贵州医科大学临床医学院贵阳550001 贵州省人民医院烧伤整形科贵阳550002

目的探讨股前外侧或股前内侧穿支皮瓣修复皮肤鳞状细胞癌(CSCC)切除后皮肤软组织缺损的临床效果。方法该研究为回顾性观察性研究。2015年7月-2022年7月,贵州省人民医院烧伤整形科收治21例CSCC患者,其中男15例、女6例,年龄27~74岁。CSCC... 详细信息

目的探讨股前外侧或股前内侧穿支皮瓣修复皮肤鳞状细胞癌(CSCC)切除后皮肤软组织缺损的临床效果。方法该研究为回顾性观察性研究。2015年7月-2022年7月,贵州省人民医院烧伤整形科收治21例CSCC患者,其中男15例、女6例,年龄27~74岁。CSCC扩大切除后皮肤软组织缺损面积为7.5 cm×4.0 cm~23.0 cm×8.5 cm。18例患者创面采用股前外侧穿支皮瓣修复;术中观察到3例患者旋股外侧动脉降支穿支血管存在变异,采用股前内侧穿支皮瓣修复创面。皮瓣面积为8.0 cm×5.0 cm~25.0 cm×10.0 cm。将19例患者供瓣区创面直接缝合,采用对侧大腿薄中厚皮片修复2例患者供瓣区创面。观察术后皮瓣成活情况及血管危象发生情况。记录手术时长和住院天数。术后随访时,观察患者肿瘤复发情况、供受区外形、供瓣区功能等。末次随访时,评估患者对疗效的满意度。结果20例患者术后皮瓣成活;1例患者于术后48 h内发生血管危象,立即行急诊手术处理后皮瓣成活。患者手术时长为4~5 h,住院15~38 d。术后随访1~6年见局部肿瘤无复发;皮瓣色泽、质地与周围组织差异不大,弹性良好,外形较佳;2例患者供瓣区皮片存活良好,出现局部色素沉着;所有患者供瓣区仅有线状瘢痕,感觉及运动功能无明显影响。末次随访时,对疗效满意者15例、一般者6例。结论对于CSCC切除后皮肤软组织缺损,可优先采用股前外侧穿支皮瓣修复,在旋股外侧动脉降支穿支血管存在变异的情况下,选择股前内侧穿支皮瓣修复。2种皮瓣切取面积大,可根据缺损组织量调整皮瓣面积,精准有效修复CSCC切除后皮肤软组织缺损,术后外观及功能良好。

关键词：创伤和损伤穿支皮瓣癌皮肤鳞状细胞癌血管变异创面修复

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基于小样本数据驱动的弹壳打凹—平底成形工艺参数优化决策方法

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中国机械工程 2024年第6期35卷 1086-1096页

作者：梁强李雄王海洋王伟任徐永航刘新杜彦斌重庆工商大学机械工程学院重庆400067 重庆长江电工工业集团有限公司重庆401336 驻重庆地区第三军事代表室重庆400000

针对某外贸款弹壳在调试生产中加工质量差和模具寿命短的问题,提出一种基于小样本数据驱动的弹壳打凹-平底成形工艺参数多目标优化与决策方法。首先,利用中心复合试验法设计试验,将各试验方案代入有限元模型中进行数值模拟,以仿真结果... 详细信息

针对某外贸款弹壳在调试生产中加工质量差和模具寿命短的问题,提出一种基于小样本数据驱动的弹壳打凹-平底成形工艺参数多目标优化与决策方法。首先,利用中心复合试验法设计试验,将各试验方案代入有限元模型中进行数值模拟,以仿真结果为基础采用随机森林算法建立弹壳打凹-平底成形工艺参数与打凹下冲头最大等效应力、平底上冲头最大等效应力和平底成形后弹壳内圆角的多目标优化模型。其次,应用改进多目标灰狼优化算法对多目标优化模型进行寻优并获得非劣解集,采用主客观综合熵权-优劣解距离法评价决策出最优工艺参数组合。最后,采用该优化工艺参数组合进行数值模拟和工艺试验,结果显示,模拟结果与工艺试验结果吻合,弹壳底部内圆角充填饱满,模具使用寿命得到提高。

关键词：弹壳小样本驱动改进多目标灰狼优化算法打凹-平底成形

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In-Situ Synchrotron Radiation Infrared Spectroscopic Identification of Reactive Intermediates over Multiphase Electrocatalytic Interfaces

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Chinese Journal of Structural Chemistry 2022年第10期41卷 4-15页

作者： Wanlin Zhou Jingjing Jiang weiren Cheng Hui Su Qinghua liu National Synchrotron Radiation Laboratory University of Science and Technology of ChinaHefei 230029China

A comprehensive understanding of the microscopic reaction mechanisms at the gas-solid-liquid electrochemical interfaces is urgently required for the development of advanced electrocatalysts applied in burgeoning sustainable energy conversion systems. In-situ synchrotron radiation Fourier transform infrared(SR-FTIR) spectroscopy is one of the most powerful techniques for investigating the evolving dynamics of reactive intermediates during electrocatalytic reactions. In this review, we methodically summarize the recent progress in the research of dynamic mechanisms for valuable electrocatalytic reactions based on in-situ SR-FTIR methodology. Moreover, the merits and drawbacks of SRFTIR spectroscopy, the design principles of infrared beam setups and in-situ cells, as well as the in-situ measurement criteria are also discussed in detail. Lastly, the potential challenges and opportunities in this field are prudently stated. This review is expected to stimulate a broad interest in the material science and electrochemistry communities for exploring the dynamic mechanisms of prominent catalysis at the atomic/molecular level by using SR-based spectroscopy.

关键词： synchrotron radiation infrared spectroscopy in-situ reaction dynamics

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数字式配流摆线液压马达特性研究

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机床与液压 2024年第5期52卷 194-198页

作者：陈宝刘万星陈刚付江华马维忍重庆理工大学车辆工程学院重庆400054 重庆工商职业学院智能制造与汽车学院重庆401520 金康新能源动力有限公司重庆400000

传统摆线液压马达由于采用机械配流,造成机械损失和容积损失高,同时马达结构尺寸大,加工难度较高。基于此,研究一种采用高速电磁开关阀组实现数字式配流与调速一体化的摆线液压马达。分析数字式配流摆线液压马达运行机制与结构特点;在... 详细信息

传统摆线液压马达由于采用机械配流,造成机械损失和容积损失高,同时马达结构尺寸大,加工难度较高。基于此,研究一种采用高速电磁开关阀组实现数字式配流与调速一体化的摆线液压马达。分析数字式配流摆线液压马达运行机制与结构特点;在对摆线马达和电磁阀流量特性理论分析的基础上,建立阀-马达动力学模型,针对所提出的模型进行仿真;在此基础上研究摆线马达的配流与转向切换的特性,通过改变PWM占空比,摆线马达可以较好实现双向调速。相比于机械配流式摆线马达,数字式配流摆线马达结构复杂度大大降低,配流与调速的灵活性得到增强。

关键词：摆线液压马达数字式配流高速电磁阀模型仿真

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Time-Modulated Transmissive Programmable Metasurface for Low Sidelobe Beam Scanning

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Research 2022年第4期2022卷 547-555页

作者： Xudong Baio Fuli Zhang Li Sun Anjie Cao Jin Zhang Chong He Longhai liu Jianquan Yao weiren Zhu School of Microelectronics Northwestern Polytechnical UniversityTaicang215400 SuzhouChina School of Physical Science and Technology Northwestern Polytechnical UniversityXian 710072China Shanghai Institute of Satelite Engineering Shanghai 201109China Department of Electronic Engineering Shanghai Jiao Tong UniversityShanghai 200240China Colege of Precision Instruments and Opto-Electronics Engineering Institute of Laser and OptoelectronicsTianjin UniversityTianjin300072China

Programmable metasurfaces have great potential for the implementation of low-complexity and low-cost phased arrays.Due to the difficulty of multiple-bit phase control,conventional programmable metasurfaces suffer a relatively high sidelobe level(SLL).In this manuscript,a time modulation strategy is introduced in the 1-bit transmissive programmable metasurface for reducing the SLLs of the generated patterns.After the periodic time modulation,harmonics are generated in each reconfigurable unit and the phase of the first-order harmonic can be dynamically controlled by applying different modulation sequences onto the corresponding unit.Through the high-speed modulation of the real-time periodic coding sequences on the metasurface by the programmable bias circuit,the equivalent phase shift accuracy to each metasurface unit can be improved to 6-bit and thus the SLLs of the metasurface could be reduced remarkably.The proposed time-modulated strategy is verified both numerically and experimentally with a transmissive programmable metasurface,which obtains an aperture efficiency over 34%and reduced SLLs of about-2o dB.The proposed design could offer a novel approach of a programmable metasurface framework for radar detection and secure communication applications.

关键词： surface periodic harmonics

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皮肤鳞状细胞癌免疫细胞浸润与基因富集分析

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医学综述 2024年第6期30卷 761-768页

作者：柳若冰郑德义李伟人贵州医科大学临床医学院贵阳550000 贵州省人民医院烧伤整形科贵阳550000

目的通过生物信息学方法分析皮肤鳞状细胞癌(CSCC)中免疫细胞浸润相关基因差异表达及其意义。方法从基因表达数据库(GEO)搜索并下载CSCC数据集,经过检索及筛选得到临床信息GSE45216和GSE108008两个数据集,使用R语言CIBERSORT函数分析免... 详细信息

目的通过生物信息学方法分析皮肤鳞状细胞癌(CSCC)中免疫细胞浸润相关基因差异表达及其意义。方法从基因表达数据库(GEO)搜索并下载CSCC数据集,经过检索及筛选得到临床信息GSE45216和GSE108008两个数据集,使用R语言CIBERSORT函数分析免疫细胞浸润情况,以及它们在CSCC组和对照组中的差异性。使用vioplot软件绘制差异细胞的小提琴图,R软件clusterProfiler包对靶基因通过基因本体(GO)功能注释和基于京都基因与基因组百科全书(KEGG)通路数据库进行信号通路富集分析。结果与对照组相比,CSCC组中380个差异表达基因,其中76个上调基因、304个下调基因,通过分析差异表达基因筛选排名前10的关键基因分别为人乳铁蛋白、G蛋白偶联受体1、RPTN、天冬氨酰氨基葡糖苷酶、PAN3、烟酰胺N-甲基转移酶、分泌粒蛋白5、叶酸受体3、维甲酸诱导蛋白14、多肽N-乙酰半乳糖氨基转移酶14;CSCC发生发展中导致浆细胞数量增加,M1型巨噬细胞数量减少,记忆性CD4+T细胞为高浸润性,且细胞溶解活性与嗜酸粒细胞呈正相关(r=0.530,P<0.001),而与M2型巨噬细胞呈显著负相关(r=-0.570,P<0.001),影响CSCC预后。GO富集分析显示,基因功能主要与角质细胞分化、细胞防御、存在于细胞膜或细胞核内的蛋白酶体有关。KEGG信号通路富集显示,差异表达基因主要参与胆固醇代谢、脂肪酸等脂质代谢通路。结论部分免疫细胞浸润及其相关基因差异表达在CSCC发生过程及其预后中起重要作用,角质细胞分化、脂质代谢信号通路改变可能与CSCC的发病机制密切相关。

关键词：皮肤鳞状细胞癌免疫细胞浸润差异表达基因 GEO数据库生物信息分析

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Automated pipeline for superalloy data by text mining

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npj Computational Materials 2022年第1期8卷 58-69页

作者： weiren Wang Xue Jiang Shaohan Tian Pei liu Depeng Dang Yanjing Su Turab Lookman Jianxin Xie Beijing Advanced Innovation Center for Materials Genome Engineering Institute for Advanced Materials and TechnologyUniversity of Science and Technology BeijingBeijing100083China Collaborative Innovation Center of Steel Technology University of Science and Technology BeijingBeijing100083China Beijing Key Laboratory of Materials Genome Engineering University of Science and Technology BeijingBeijing100083China School of Artificial Intelligence Beijing Normal UniversityBeijing100875China AiMaterials Research LLC Santa FeNM87501USA

Data provides a foundation for machine learning,which has accelerated data-driven materials design.The scientific literature contains a large amount of high-quality,reliable data,and automatically extracting data from the literature continues to be a challenge.We propose a natural language processing pipeline to capture both chemical composition and property data that allows analysis and prediction of superalloys.Within 3 h,2531 records with both composition and property are extracted from 14,425 articles,coveringγ′solvus temperature,density,solidus,and liquidus temperatures.A data-driven model forγ′solvus temperature is built to predict unexplored Co-based superalloys with highγ′solvus temperatures within a relative error of 0.81%.We test the predictions via synthesis and characterization of three alloys.A web-based toolkit as an online open-source platform is provided and expected to serve as the basis for a general method to search for targeted materials using data extracted from the literature.

关键词： superalloy property pipeline

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