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Chlorogenic acid induces hepatocellular carcinoma cell ferroptosis via PTGS2/AKR1C3/GPX4 axis-mediated reprogramming of arachidonic acid metabolism

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World Journal of Gastrointestinal Oncology 2025年第3期17卷 202-220页

作者： Ling Wu Hong-Yao Chen Jing-Ting Zhang Ren-Yi Yang Zhi-Bin Wang Pei-Sen Xue Wei Peng Ke-Xiong Li Wen-Hui Gao Pu-Hua Zeng College of Traditional Chinese Medicine Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina Department of Oncology Hunan Provincial Hospital of Integrated Traditional Chinese and Western ChineseChangsha 410006Hunan ProvinceChina Cancer Research Institute of hunan Academy of Traditional Chinese Medicine Hunan Provincial Hospital of Integrated Traditional Chinese and Western ChineseChangsha 410006Hunan ProvinceChina

BACKGROUND Ferroptosis is an iron-dependent programmed non-apoptotic cell death characterized by the accumulation of free iron ions and lipid *** is associated with the inactivation of glutathione peroxidase(GPX)and the accumulation of lipid peroxides within *** is closely related to the occurrence and development of hepatocellular carcinoma(HCC).Chlorogenic acid(CGA),an important bioactive component found in 61 traditional Chinese medicines such as Eucommia ulmoides,has been extensively studied for its effects on various malignant ***,the specific role and potential mechanism of CGA in HCC remain *** To elucidate the anti-tumor characteristics and potential mechanisms of CGA in inducing ferroptosis in HCC *** The effects of CGA on the proliferation,migration,and invasion of HCC cells were evaluated through in vitro *** analysis combined with network pharmacology was used to study the potential targets and molecular mechanisms of CGA intervention in HCC *** vitro experiments were conducted to verify and explore the anti-HCC effects and mechanisms of CGA through the ferroptosis *** In vitro experiments showed that CGA dose-dependently inhibited the proliferation,invasion,and migration of HCC *** analysis combined with network pharmacology revealed that the pathway of CGA intervention in HCC cell ferroptosis was mainly enriched in the prostaglandin endoperoxide synthase 2(PTGS2)/aldoketo reductase family 1 member C3(AKR1C3)/GPX4 signaling pathway,which was associated with arachidonic *** vitro experiments further confirmed that CGA-induced ferroptosis in HCC cells was related to mitochondrial damage through the reprogramming of arachidonic acid metabolism by regulating the PTGS2/AKR1C3/GPX4 signaling *** This study demonstrates that CGA inhibits HCC cell proliferation,migration,and invasion by inducing ferroptosis through the PTGS2/A

关键词： Chlorogenic acid Hepatocellular carcinoma Ferroptosis Prostaglandin endoperoxide synthase 2/aldo-keto reductase family 1 member C3/glutathione peroxidase 4 axis bioinformatics In vitro experiment

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Improved kernels for triangle packing in tournaments

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Science China(Information Sciences) 2023年第5期66卷 100-113页

作者： Hanchun YUAN Qilong FENG Jianxin WANG School of Computer Science and Engineering Central South University hunan provincial key lab on bioinformatics Central South University

Triangle packing problem has been paid lots of attention to in the literature. In this paper, we study the kernelization of the triangle packing problem in tournaments. For the parameterized arc-disjoint triangle packing problem in tournaments, we find a maximal arc-disjoint triangle packing with the number of vertices bounded by 2.5k. Based on the relation between the maximal arc-disjoint triangle packing and the vertices outside of the packing, a kernel of size 3.5k for the problem is obtained, improving the previous best one 6k. For the parameterized vertex-disjoint triangle packing problem in sparse tournaments, several new properties between the triangles in maximal vertex-disjoint triangle packing and the arcs in the feedback arc set are presented, which result in a kernel of size 7k for the problem, improving the previous best one of *** also give a 7k vertex kernel for the parameterized feedback vertex set problem in sparse *** kernelization process presented in this paper for the parameterized arc-disjoint triangle packing can be applied to solve the parameterized arc-disjoint triangle packing problem on other restricted directed graph classes.

关键词： tournaments triangle packing kernelization fixed-parameter tractable graph algorithms

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DeepRetention:A Deep Learning Approach for Intron Retention Detection

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Big Data Mining and Analytics 2023年第2期6卷 115-126页

作者： Zhenpeng Wu Jiantao Zheng Jiashu Liu Cuixiang Lin Hong-Dong Li hunan provincial key lab on bioinformatics School of Computer Science and EngineeringCentral South UniversityChangsha 410083China

As the least understood mode of alternative splicing,Intron Retention(IR)is emerging as an interesting area and has attracted more and more attention in the field of gene regulation and disease *** methods detect IR exclusively based on one or a few predefined metrics describing local or summarized characteristics of retained *** metrics are not able to describe the pattern of sequencing depth of intronic reads,which is an intuitive and informative characteristic of retained *** hypothesize that incorporating the distribution pattern of intronic reads will improve the accuracy of IR *** we present DeepRetention,a novel approach for IR detection by modeling the pattern of sequencing depth of *** to the lack of a gold standard dataset of IR,we first compare DeepRetention with two state-of-the-art methods,*** and IRFinder,on simulated RNA-seq datasets with retained *** results show that DeepRetention outperforms these two ***,DeepRetention performs well when it is applied to third-generation long-read RNA-seq data,while IRFinder and iREAD are not applicable to detecting IR from the third-generation sequencing ***,we show that IRs predicted by DeepRetention are biologically meaningful on an RNA-seq dataset from Alzheimer’s Disease(AD)*** differential IRs are found to be significantly associated with AD based on statistical evaluation of an AD-specific functional gene *** parent genes of differential IRs are enriched in AD-related *** summary,DeepRetention detects IR from a new angle of view,providing a valuable tool for IR analysis.

关键词： Alternative Splicing(AS) Intron Retention(IR) intronic reads distribution pattern RNA-seq

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Ten computational challenges in human virome studies

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Virologica Sinica 2024年第6期39卷 845-850页

作者： Yifan Wu Yousong Peng bioinformatics Center College of BiologyHunan Provincial Key Laboratory of Medical VirologyHunan UniversityChangsha 410082China

In recent years,substantial advancements have been achieved in understanding the diversity of the human virome and its intricate roles in human health and *** this progress,the field of human virome research remains nascent,primarily hindered by the lack of effective methods,particularly in the domain of computational *** perspective systematically outlines ten computational challenges spanning various types of virome *** challenges arise due to the vast diversity of viromes,the absence of a universal marker gene in viral genomes,the low abundance of virus populations,the remote or minimal homology of viral proteins to known proteins,and the highly dynamic and heterogeneous nature of *** each computational challenge,we discuss the underlying reasons,current research progress,and potential *** resolution of these challenges necessitates ongoing collaboration among computational scientists,virologists,and multidisciplinary *** essence,this perspective serves as a comprehensive guide for directing computational efforts in human virome studies.

关键词： Human virome Computational biology Computational viromics Artificial intelligence

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Prediction of coronavirus 3C-like protease cleavage sites using machine-learning algorithms

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Virologica Sinica 2022年第3期37卷 437-444页

作者： Huiting Chen Zhaozhong Zhu Ye Qiu Xingyi Ge Heping Zheng Yousong Peng bioinformatics Center College of BiologyHunan Provincial Key Laboratory of Medical VirologyHunan UniversityChangsha410082China

The coronavirus 3C-like(3CL)protease,a cysteine protease,plays an important role in viral infection and immune ***,there is still a lack of effective tools for determining the cleavage sites of the 3CL *** study systematically investigated the diversity of the cleavage sites of the coronavirus 3CL protease on the viral polyprotein,and found that the cleavage motif were highly conserved for viruses in the genera of Alphacoronavirus,Betacoronavirus and *** residue preferences were observed at the neighboring positions of the cleavage sites.A random forest(RF)model was built to predict the cleavage sites of the coronavirus 3CL protease based on the representation of residues in cleavage motifs by amino acid indexes,and the model achieved an AUC of 0.96 in *** RF model was further tested on an independent test dataset which were composed of cleavage sites on 99 proteins from multiple coronavirus *** achieved an AUC of 0.95 and predicted correctly 80%of the cleavage ***,1,352 human proteins were predicted to be cleaved by the 3CL protease by the RF *** proteins were enriched in several GO terms related to the cytoskeleton,such as the microtubule,actin and ***,a webserver named 3CLP was built to predict the cleavage sites of the coronavirus 3CL protease based on the RF ***,the study provides an effective tool for identifying cleavage sites of the 3CL protease and provides insights into the molecular mechanism underlying the pathogenicity of coronaviruses.

关键词： Coronavirus 3C-like protease Cleavage sites Machine-learning algorithms 3CLP webserver

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Computational Viromics: Applications of the Computational Biology in Viromics Studies

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Virologica Sinica 2021年第5期36卷 1256-1260页

作者： Congyu Lu Yousong Peng bioinformatics Center College of BiologyHunan Provincial Key Laboratory of Medical VirologyHunan UniversityChangsha 410082China

Viruses are a kind of biological entities which rely on host cells for *** on the genetic materials and replication mode,they can be grouped into double-stranded DNA(dsDNA),single-stranded DNA(ssDNA),doublestranded RNA(dsRNA),positive-sense single-stranded RNA(+ssRNA),negative-sense single-stranded RNA(-ssRNA),ssRNA reverse transcriptase viruses(ssRNART)and dsDNA reverse transcriptase viruses(dsDNA-RT)(Walker et al.2020).Viruses can infect most kinds of biological entities,including viruses,bacteria,archaea and eukaryote(La Scola et al.2008;Fermin,2018).

关键词： al. dsDNA stranded

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A Comparison of Computational Approaches for Intron Retention Detection

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Big Data Mining and Analytics 2022年第1期5卷 15-31页

作者： Jiantao Zheng Cuixiang Lin Zhenpeng Wu Hong-Dong Li the hunan provincial key lab on bioinformatics School of Computer Science and EngineeringCentral South UniversityChangsha 410083China

Intron Retention(IR)is an alternative splicing mode through which introns are retained in mature RNAs rather than being spliced in most *** has been gaining increasing attention in recent years because of its recognized association with gene expression regulation and complex *** efforts have been dedicated to the development of IR detection *** methods differ in their metrics to quantify retention propensity,performance to detect IR events,functional enrichment of detected IRs,and computational speed.A systematic experimental comparison would be valuable to the selection and use of existing *** this work,we conduct an experimental comparison of existing IR detection *** the unavailability of a gold standard dataset of intron retention,we compare the IR detection performance on simulation ***,we compare the IR detection results with real RNA-Seq *** also describe the use of differential analysis methods to identify disease-associated IRs and compare differential IRs along with their Gene Ontology enrichment,which is illustrated on an Alzheimer’s disease RNA-Seq *** discuss key principles and features of existing approaches and outline their *** systematic analysis provides helpful guidance for interrogating transcriptomic data from the point of view of IR.

关键词： alternative splicing intron retention gene expression RNA-Seq

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Triad mode resonant interactions in suspended cables

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Science China(Physics,Mechanics & Astronomy) 2016年第3期59卷 75-88页

作者： Tie Ding Guo Hou Jun Kang Lian Hua Wang Yue Yu Zhao College of Civil Engineering Hunan University hunan provincial key lab on Damage Diagnosis for Engineering Structures Hunan University

A triad mode resonance, or three-wave resonance, is typical of dynamical systems with quadratic nonlinearities. Suspended cables are found to be rich in triad mode resonant dynamics. In this paper, modulation equations for cable's triad resonance are formulated by the multiple scale method. Dynamic conservative quantities, i.e., mode energy and Manley-Rowe relations, are then constructed. Equilibrium/dynamic solutions of the modulation equations are obtained, and full investigations into their stability and bifurcation characteristics are presented. Various bifurcation behaviors are detected in cable's triad resonant responses, such as saddle-node, Hopf, pitchfork and period-doubling bifurcations. Nonlinear behaviors, like jump and saturation phenomena, are also found in cable's responses. Based upon the bifurcation analysis, two interesting properties associated with activation of cable's triad resonance are also proposed, i.e., energy barrier and directional dependence. The first gives the critical amplitude of high-frequency mode to activate cable's triad resonance, and the second characterizes the degree of difficulty for activating cable's triad resonance in two opposite directions, i.e., with positive or negative internal detuning parameter.

关键词： suspended cables triad mode interaction multiple scale method

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Cutting force modeling in high-speed machining of selective laser melted Ti6Al4V alloys based on a modified constitutive model considering thermally activated effect

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Science China Technological Sciences 2025年第3期68卷 142-159页

作者： Dejian LIU Chenbing NI Youqiang WANG Lida ZHU Zhongpeng ZHENG Wei LU Naixin ZHANG Xingbao HUANG School of Mechanical and Automotive Engineering Qingdao University of Technology key lab of Industrial Fluid Energy Conservation and Pollution Control Ministry of Education School of Mechanical Engineering and Automation Northeastern University School of Mechanical Engineering Tsinghua University Shandong Zhongheng Jingxin Carbon Fiber Technology Development Co. Ltd State key laboratory of Bridge Safety and Resilience College of Civil Engineering Hunan University

The thermally activated effect can produce a vital influence on the mechanical property and cutting force of metal materials in the machining process. An insight can be gained into the action criteria of the thermally activated effect on the cutting force, which provides a solid basis of the research of material performance and machinability. In this study, a cutting force model of selective laser melted(SLMed) Ti6Al4V alloy is proposed by introducing the modified constitutive model with thermally activated effects and the analytical model of the deformation zone into the cutting force model. The anisotropic properties of SLMed Ti6Al4V alloy under different scanning strategies(0°, 67.5°, and 90°) are explored by combining with the cutting force model, constitutive model and analytical model of deformation zone(primary deformation and tool-chip contact area). The action of thermally activated effects on the cutting force, primary deformation and tool-chip contact zone is also researched in detail. Milling experiments and predictions of SLMed Ti6Al4V alloy under different scanning strategies have been implemented to reveal the effectiveness of this new model. The comparison results indicate that the proposed milling force model can effectively predict milling force and reflect well on the anisotropy of SLMed Ti6Al4V *** addition, this proposed force model can well analyze the action mechanism of the thermally activated effect on the milling force of SLMed Ti6Al4V alloy, which is significantly essential for the machining mechanism research in terms of a microscopic perspective.

关键词： cutting force model modified constitutive model thermally activated effect SLMed Ti6Al4V alloy laser scanning strategies anisotropic properties

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A Data-Driven Clustering Recommendation Method for Single-Cell RNA-Sequencing Data

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Tsinghua Science and Technology 2021年第5期26卷 772-789页

作者： Yu Tian Ruiqing Zheng Zhenlan Liang Suning Li Fang-Xiang Wu Min Li the hunan provincial key lab on bioinformatics School of Computer Science and EngineeringCentral South UniversityHunan 410083China the Division of Biomedical Engineering and Department of Mechanical Engineering University of SaskatchewanSKS7N5A9Canada

Recently,the emergence of single-cell RNA-sequencing(scRNA-seq)technology makes it possible to solve biological problems at the single-cell *** of the critical steps in cellular heterogeneity analysis is the cell type *** scRNA-seq clustering methods have been proposed to partition cells into *** all the methods,hierarchical clustering and spectral clustering are the most popular approaches in the downstream clustering analysis with different preprocessing strategies such as similarity learning,dropout imputation,and dimensionality *** this study,we carry out a comprehensive analysis by combining different strategies with these two categories of clustering methods on scRNA-seq datasets under different biological *** analysis results show that the methods with spectral clustering tend to perform better on datasets with continuous shapes in two-dimension,while those with hierarchical clustering achieve better results on datasets with obvious boundaries between clusters in *** by this finding,a new strategy,called QRS,is developed to quantitatively evaluate the latent representative shape of a dataset to distinguish whether it has clear boundaries or ***,a data-driven clustering recommendation method,called DDCR,is proposed to recommend hierarchical clustering or spectral clustering for scRNA-seq *** perform DDCR on two typical single cell clustering methods,SC3 and RAFSIL,and the results show that DDCR recommends a more suitable downstream clustering method for different scRNA-seq datasets and obtains more robust and accurate results.

关键词： single-cel RNA-sequencing(sc RNA-seq) cel ular heterogeneity cel type identification data latent shape clustering

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