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加权共表达网络分析与机器学习识别类风湿关节炎滑膜中的关键基因

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中国组织工程研究 2025年第2期29卷 294-301页

作者：武英楷史高龙谢宗刚苏州大学附属第二医院江苏省苏州市215000 宁阳县第一人民医院山东省泰安市271000

背景:类风湿关节炎是一种全身的免疫相关性疾病,主要病理特点是关节滑膜炎性增生及关节软骨的破坏,其发病机制目前尚不明确,迫切需要发现新的具有高度敏感性和特异性的诊断标志物。目的:联合使用生物信息学技术及计算机学习算法,识别并... 详细信息

背景:类风湿关节炎是一种全身的免疫相关性疾病,主要病理特点是关节滑膜炎性增生及关节软骨的破坏,其发病机制目前尚不明确,迫切需要发现新的具有高度敏感性和特异性的诊断标志物。目的:联合使用生物信息学技术及计算机学习算法,识别并筛选类风湿关节炎患者滑膜中的关键基因,构建类风湿关节炎预测模型并进行验证。方法:从基因表达综合数据库中下载3个包含类风湿关节炎患者滑膜的数据集(GSE77298、GSE55235、GSE55457),GSE77298和GSE55235作为训练集,GSE55457作为测试集,共纳入66个样本,其中类风湿关节炎患者滑膜样本39个,正常滑膜样本27个。应用R语言筛选训练集中的差异基因,然后使用加权共表达网络将训练集中的基因模块化,选出关键模块中的特征基因,将差异表达基因和特征基因取交集,交集基因进入下一步机器学习。采用3种机器学习方法:最小绝对值收敛和选择算子算法、支持向量机-递归特征消除和随机森林算法对交集基因进一步分析获得枢纽基因,将枢纽基因再次相交即得到类风湿关节炎滑膜中的关键基因。以关键基因为变量构建预测类风湿关节炎的列线图模型,推测患者发生类风湿关节炎的危险程度,使用受试者工作特征曲线确定类风湿关节炎预测模型及其关键基因的诊断价值。结果与结论:①通过差异分析,训练集中共筛选出差异基因730个,加权共表达网络分析得到特征基因185个,两者交集基因159个;②最小绝对值收敛和选择算子发现枢纽基因4个,支持向量机-递归特征消除发现枢纽基因11个,随机森林发现枢纽基因5个,取交集后获得关键基因2个(TNS3、SDC1);③基于2个关键基因,在训练集及测试集种构建列线图,其校准预测曲线与标准曲线贴合较好,且预测类风湿关节炎发生的临床效能良好;④上述结果证实,基于生物信息及机器学习算法获得的TNS3和SDC1有可能成为类风湿关节炎诊断和治疗的关键靶点。

关键词：加权基因共表达网络机器学习算法类风湿关节炎关键基因预测模型

P15——a new tumor suppressor gene

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Chinese Science Bulletin 1999年第13期44卷 1157-1163页

作者： yingkai Tong Huitu Liu Beijing Normal Univ State Key Lab Cell Proliferat & Regulat Biol Beijing 100875 Peoples R China

In addition to the tumor suppressor genes such as Rb and p53, it has been found that some molecules of the same class named CKI (cyclin-dependent kinase inhibitor) also play an important role in the inhibition of tumorigenesis and the tumor progression. In the KIP and INK4 families of CKIs, p15 shares extensive homology with p16. Findings in many tumors and their cell lines show that the inactivation of p15 (deletion, mutation, rearrangement, etc.) is very frequent, and inactive p15 is involved in the progress of some tumors. These studies provide evidence that the p15 is a new tumor suppressor gene. Furthermore, the research on the molecular mechanism of p15 in regulation of cell proliferation shows that p15 can inhibit the growth of some kinds of tumor cells, and p15 is the mediator of TGF-β-induced cell arrest. Investigations on p15 in cell differentiation suggest that increased p15 is related to the change of malignant phenotype. These results supply clues for further interpretation about the

关键词： pI5 CKI tumor suppressor gene cell cycle induction of tumor cell differentiation.

Brain metabolism in Alzheimer’s disease:biological mechanisms of exercise

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Translational Neurodegeneration 2023年第1期12卷 443-463页

作者： Longfei Xu Ran Liu yingkai Qin Tianhui Wang Institute of Environmental and Operational Medicine Academy of Military Medical SciencesAcademy of Military SciencesTianjin 300050China Tianjin Key Laboratory of Exercise Physiology&Sports Medicine Tianjin University of SportTianjin 301617China

Alzheimer’s disease(AD)is a major subtype of neurodegenerative dementia caused by long-term interactions and accumulation of multiple adverse factors,accompanied by dysregulation of numerous intracellular signaling and molecular pathways in the *** the cellular and molecular levels,the neuronal cellular milieu of the AD brain exhibits metabolic abnormalities,compromised bioenergetics,impaired lipid metabolism,and reduced overall metabolic capacity,which lead to abnormal neural network activity and impaired neuroplasticity,thus accelerating the formation of extracellular senile plaques and intracellular neurofibrillary *** current absence of effective pharmacological therapies for AD points to the urgent need to investigate the benefits of non-pharmacological approaches such as physical *** the evidence that regular physical activity can improve metabolic dysfunction in the AD state,inhibit different pathophysiological molecular pathways associated with AD,influence the pathological process of AD,and exert a protective effect,there is no clear consensus on the specific biological and molecular mechanisms underlying the advantages of physical ***,we review how physical exercise improves crucial molecular pathways and biological processes associated with metabolic disorders in AD,including glucose metabolism,lipid metabolism,Aβmetabolism and transport,iron metabolism and tau *** metabolic states influence brain health is also presented.A better knowledge on the neurophysiological mechanisms by which exercise improves AD metabolism can contribute to the development of novel drugs and improvement of non-pharmacological interventions.

关键词： Alzheimer’s disease Exercise Glucose and lipid metabolism Aβmetabolism Iron metabolism Tau pathology

Experimental and numerical study on ignition and combustion characteristics of boron-magnesium composite powders

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Particuology 2024年第1期84卷 12-29页

作者： Shuyuan Liu Luyang Han Hongmei Liu yingkai Song Linlin Liu Songqi Hu Science and Technology on Combustion Internal Flow and Thermo-Structure LaboratoryNorthwestern Polytechnical UniversityXi'an710072China School of Mechanical Engineering and Rail Transit Changzhou UniversityChangzhou213164China Shanghai Institute of Space Propulsion Shanghai201112China Shanghai Engineering Research Center of Space Engine Shanghai201112China

A high-pressure laser ignition and combustion system with adjustable oxidizer gas atmosphere is established to investigate the ignition and combustion characteristics of boron-magnesium(BM)com-posite *** ignition and combustion model of BM powders is established and validated in the present *** results show that increasing water content,O_(2) content and Mg content all result in shorter ignition delay time of BM powders,among which the effect of water content is the most ***,ignition delay time increases as pressure *** combustion time decreases with increasing Mg content and ambient pressure but increases with water *** the increase of O_(2) content,combustion time of BM powders first increases and then decreases,which means a critical O_(2) content exists above which combustion time *** results show that there exists a trade-off between ignition and combustion performance of BM composite powders.

关键词： Boron magnesium powder Laser ignition Ignition and combustion model Reaction mechanism Numerical model

B, Sr, O and H Isotopic Compositions of Formation Waters from the Bachu Bulge in the Tarim Basin

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Acta Geologica Sinica(English Edition) 2006年第4期80卷 550-556页

作者： CAI Chunfang PENG Licai MEI Bowen XIAO yingkai Key Laboratory of Mineral Resources Institute of Geology and Geophysics Chinese Academy of Sciences Beijing 100029 Department of Engineering Mechanics Tsinghua University Beijing 100084 Yangtze University Jingzhou Hubei 434023 Qinghai Institute of Salt Lake Chinese Academy of Sciences Xining Qinghai 810008

In order to elucidate the origin and migration of basinal brines in the Bachu Bulge, Tarim Basin, we have carried out analyses on chemical composition, and boron, hydrogen and oxygen isotopes of formation waters together with the XRD of clay minerals from the Paleozoic strata. The waters show Ca, B, Li and Sr enrichment and SO4 depletion in the Carboniferous and Ordovician and K enrichment in part of the Ordovician relative to seawater. The relationship between δD and δ^18O shows that all the data of the waters decline towards the Global Meteoric Water Line with the intersection of them close to the present-day local meteoric water, suggesting that modern meteoric water has mixed with evaporated seawater. The ^87Sr/^86Sr ratios range from 0.7090 to 0.7011, significantly higher than those of the contemporary seawater. The δ^11B values range from ＋19.7 to ＋32.3‰, showing a decrease with the depth and B concentrations. The results suggest that isotopically distinct B and Sr were derived from external sources. However, since the percentages of illite are shown to increase with depth among clay minerals in the study area, i.e., illite is due to precipitation rather than leaching during deeper burial, it is unlikely for illite to have contributed a significant amount of B to the waters. Thus, B with low δ^11B values is interpreted to have been added mainly from thermal degradation of kerogen or the basalts in the Cambrian and Lower Ordovician.

关键词： δ^11B formation water water-rock interaction Tarim Basin

High performance photodetector based on few-layer MoTe_(2)/CdS_(0.42)Se_(0.58) flake heterojunction

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Frontiers of physics 2024年第4期19卷 91-101页

作者： Ran Ma Qiuhong Tan Peizhi Yang yingkai Liu Qianjin Wang College of Physics and Electronic Information Yunnan Normal UniversityKunming 650500China Yunnan Provincial Key Laboratory for Photoelectric Information Technology Yunnan Normal UniversityKunming 650500China Key Laboratory of Advanced Technique&Preparation for Renewable Energy Materials Ministry of EducationYunnan Normal UniversityKunming 650500China

Two-dimensional(2D)transition metal dichalcogenides have been extensively studied due to their fascinating physical properties for constructing high-performance ***,their relatively low responsivities,current on/off ratios and response speeds have hindered their widespread ***,we fabricated a high-performance photodetector based on few-layer MoTe_(2) and CdS_(0.42)Se_(0.58) flake *** photodetector exhibited a high responsivity of 7221 A/W,a large current on/off ratio of 1.73×10^(4),a fast response speed of 90/120μs,external quantum efficiency(EQE)reaching up to 1.52×10^(6)%and detectivity(D*)reaching up to 1.67×10^(15) *** excellent performance of the heterojunction photodetector was analyzed by a photocurrent mapping test and first-principle ***,the visible light imaging function was successfully attained on the MoTe_(2)/CdS_(0.42)Se_(0.58) photodetectors,indicating that the device had practical imaging application *** findings provide a reference for the design of ultrahighperformance MoTe_(2)-based photodetectors.

关键词： photodetector MoTe_(2) heterojunction visible light imaging first-principles calculations

Boron Isotopic Fractionation and Trace Element Incorporation in Various Species of Modern Corals in Sanya Bay, South China Sea

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Journal of Earth Science 2014年第3期25卷 431-444页

作者： Haizhen Wei Shaoyong Jiang yingkai Xiao N Gary Hemming State Key Laboratory for Mineral Deposits Research Department of Earth Sciences Nanjing University State Key Laboratory of Geological Processes and Mineral Resources Faculty of Earth ResourcesChina University of Geosciences Wuhan Qinghai Institute of Salt Lakes Chinese Academy of Sciences Lamont-Doherty Earth Observatory of Columbia University Queens College School of Earth and Environmental Sciences

The boron isotope paleo-pH proxy has been extensively studied due to its potential for understanding past climate change, and further calibrations were considered for accurate applications of the proxy because of significant variability related to biocarbonate microstructure. In this work, we studied the boron isotopic fractionation between modern marine corals and their coexisting seawater collected along shallow area in Sanya Bay, South China Sea. The apparent partition coefficient of boron（KD） ranged from 0.83×10-3 to 1.69×10-3, which are in good agreement with previous studies. As the analyzed coral skeleton（~5 g） spanned the growth time period of 1–2 years, we discussed the boron isotopic fractionation between pristine corals and modern seawater using the annual mean seawater pH of 8.12 in this sea area. Without taking the vital effect into account,（11B/10B）coral values of all living corals spread over the curves of（11B/10B）borate vs.（11B/10B）sw with the α4-3 values ranging from 0.974 to 0.982. After calibrating the biological effect on the calcifying fluid pH, the field-based calcification on calcifying fluid pH（i.e., Δ（pHbiol-pHsw）） for coral species of Acropora, Pavona, Pocillopora, Faviidae, and others including Proites are 0.42, 0.33, 0.36, 0.19, respectively, and it is necessary to be validated by coral culturing experiment in the future. Correlations in B/Ca vs. Sr/Ca and B/Ca vs. pHbiol approve temperature and calcifying fluid pH influence on skeletal B/Ca. Fundamental understanding of the thermodynamic basis of the boron isotopes in marine carbonates and seawater will strengthen the confidence in the use of paleo-pH proxy as a powerful tool to monitor atmospheric CO2 variations in the past.

关键词： boron isotope paleo-pH proxy boron isotopic fractionation trace element modern coral.

Reduction of Space Debris Collision Prediction Uncertainty Based on Q-Sat Precise Orbit

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Space(Science & Technology) 2023年第1期3卷 1-9页

作者： Huang Pu Wen Guangwei Cai yingkai Wang Zhaokui School of Aerospace Engineering Tsinghua UniversityBeijingChina

Collision probability is employed for evaluating whether there will be a dangerous encounter between 2 space *** fidelity of the collision probability mainly depends on the accuracies of orbit prediction and covariance prediction for the space *** this paper,the collision probability between the Tsinghua Gravitation and Atmosphere Science Satellite,Q-Sat,and the space debris with a North American Aerospace Defense Command ID of 49863 on 2022 January 18 was *** 2 objects approached each other dangerously close and the event was ***,the atmospheric density model is modified by a dynamic approach-based inversion to improve the accuracy of orbit prediction for the ***,predictions of position error covariance are carried *** of the next 24 hours are predicted,and the predicted orbits are compared with the actual orbits of the *** neural network was trained for predicting the position error *** the space debris,the 2-line element data are *** predictions for the space debris are also conducted and compared with the actual *** backpropagation neural network for predicting the position error covariance for the space debris is *** the covariances from the backpropagation neural network,the error ellipsoids of the 2 objects are *** error ellipsoids are later projected to the encounter plane to calculate the collision *** from the reports from other institutes,the closest distance between the Q-Sat and the space debris calculated by the current method was 2.71 *** collision probability was 1.16×10−*** was not a dangerous encounter *** onboard precise orbit determination device enabled improved orbit determination precision and orbit prediction accuracy,which is important for space safety management.

关键词： collision precise debris

Computational exploration and screening of novel Janus MA2Z4 (M = Sc–Zn, Y–Ag, Hf–Au;A=Si, Ge;Z=N, P) monolayers and potential application as a photocatalyst

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Frontiers of physics 2022年第6期17卷 51-61页

作者： Weibin Zhang Woochul Yang yingkai Liu Zhiyong Liu Fuchun Zhang College of Physics and Electronics Information Yunnan Key Laboratory of Opto-Electronic Information TechnologyKey Laboratory of Advanced Technique&Preparation for Renewable Energy Materials-Ministry of EducationYunnan Normal UniversityKunming 650500China College of Physics and Electronic Information Yan’an UniversityYan’an 716000China Department of Physics Dongguk UniversitySeoul 04620Republic of Korea

By high-throughput calculations,13 thermally and environmentally stable Janus MA_(2)Z_(4) monolayers were screened from 104 types of *** 13 stable monolayers have very high charge carrier concentrations(×10^(15) cm^(–2)),which are better than those of the well-known graphene and TaS_(2).Because of their excellent conductivity,the 6 monolayers with band gaps less than 0.5 eV are identified as potential electrode materials for hydrogen evolution reaction *** potential applications as photoelectric or photocatalytic materials,bandgaps(Eg-HSE)higher than 0.5 eV remained,which resulted in 7 potential *** on optical absorption analysis in the visible-light range,H-HfSiGeP_(4) and HMoSiGeP_(4) have higher absorption ability and optical conductivity,which is quite impressive for optoelectronic,solar cell device,and photocatalysis ***,the transmittance coefficient of Janus MA_(2)Z_(4) monolayers is approximately 70%–80%in the visible-light range,which implies that these monolayers show good light *** potential applications as photocatalysts,the redox potential and charge effective mass analysis indicate that H-HfSiGeP_(4),HMoSiGeP_(4),T-ScSiGeN_(4),and T-ZrSiGeN_(4) are suitable photocatalysts for CO_(2) reduction *** high-throughput identification,13 types of new and stable Janus MA2Z4 monolayers were explored,and the basic properties and potential applications were investigated,which can reduce the time for experiments and provide basic data for the material genome initiative.

关键词： Janus MA2Z4 high-throughput identification charge carrier concentration electronic structure optical properties