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Flux Balance Analysis Reveals Potential Anti-HIV-1 Metabolic Targets

Infectious Diseases & Immunity 2024年第2期4卷 61-68页

作者： Runpeng Han Fei Luo Haisheng Yu Yajun Yan Yan Gong conghua xie Liang Cheng Department of Radiation and Medical Oncology Medical Research InstituteZhongnan Hospital of Wuhan UniversityWuhan UniversityWuhan 430071China Frontier Science Center for Immunology and Metabolism Zhongnan Hospital of Wuhan UniversityState Key Laboratory of VirologyWuhan UniversityWuhan 430071China Guangzhou Eighth People's Hospital Guangzhou Medical UniversityGuangzhou 510440China Department of Infectious Diseases Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Biological Repositories Zhongnan Hospital of Wuhan UniversityWuhan 430071China Wuhan Research Center for Infectious Diseases and Cancer Chinese Academy of Medical SciencesWuhan 430071China

Background:Human immunodeficiency virus type 1(HIV-1)remains a persistent global health ***,a continuous exploration of novel therapeutic strategies is essential.A comprehensive understanding of how HIV-1 utilizes the cellular metabolism machinery for replication can provide insights into new therapeutic ***:In this study,we performed a flux balance analysis using a genome-scale metabolic model(GEM)integrated with an HIV-1 viral biomass objective function to identify potential targets for anti–HIV-1 *** generated a GEM by integrating an HIV-1 production reaction into CD4+T cells and optimized for both host and virus optimal states as objective functions to depict metabolic profiles of cells in the status for optimal host biomass maintenance or for optimal HIV-1 virion *** analysis was used to predict biochemical reactions altered optimal for HIV-1 *** addition,we conducted in silico simulations involving gene and reaction knock-outs to identify potential anti–HIV-1 targets,which were subsequently validated by human phytohemagglutinin(PHA)blasts infected with ***:Differential analysis identified several altered biochemical reactions,including increased lysine uptake and oxidative phosphorylation(OXPHOS)activities in the virus optima compared with the host *** silico gene and reaction knock-out simulations revealed de novo pyrimidine synthesis,and OXPHOS could serve as potential anti–HIV-1 metabolic *** vitro assay confirmed that targeting OXPHOS using metformin could suppress the replication of HIV-1 by 56.6%(385.4±67.5 pg/mL in the metformintreated group vs.888.4±32.3 pg/mL in the control group,P<0.001).Conclusion:Our integrated host-virus genome-scale metabolic study provides insights on potential targets(OXPHOS)for anti-HIV therapies.

关键词： HIV-1 Flux balance analysis Genome-scale metabolic models Viral biomass objective function Therapeutic target

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炎症标志物的变化趋势对一线接受免疫联合化疗的晚期非小细胞肺癌患者预后的预测价值

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国际肿瘤学杂志 2024年第5期51卷 257-266页

作者：范志鹏余静胡静廖正凯徐禹欧阳雯谢丛华武汉大学中南医院肺部肿瘤放化疗科武汉430061

目的探讨一线接受免疫联合化疗的非小细胞肺癌(NSCLC)患者外周血炎症标志物治疗前后的变化趋势与疗效的相关性及对预后的预测价值。方法回顾性分析2018年10月至2023年5月就诊于武汉大学中南医院肺部肿瘤放化疗科的NSCLC患者的临床资料... 详细信息

目的探讨一线接受免疫联合化疗的非小细胞肺癌(NSCLC)患者外周血炎症标志物治疗前后的变化趋势与疗效的相关性及对预后的预测价值。方法回顾性分析2018年10月至2023年5月就诊于武汉大学中南医院肺部肿瘤放化疗科的NSCLC患者的临床资料。采用χ^(2)检验分析外周血炎症标志物的变化趋势与免疫联合化疗疗效之间的关系。使用二分类logistic回归评估客观缓解率(ORR)的影响因素。采用Kaplan-Meier曲线和Cox比例风险模型评价外周血炎症标志物的变化趋势对患者预后的预测价值。结果本研究共纳入102例接受一线免疫联合化疗的NSCLC患者。淋巴细胞与单核细胞比值(LMR)下降组(n=50)的骨转移患者比例比上升组(n=52)更高(χ^(2)=4.28,P=0.039);与上升组(n=51)患者相比,血小板与淋巴细胞比值(PLR)下降组(n=51)患者的病理类型以鳞状细胞癌多见(χ^(2)=18.99,P<0.001);预后营养指数(PNI)下降组(n=46)的女性患者比例比上升组(n=56)更高(χ^(2)=4.29,P=0.038),差异均具有统计学意义。LMR上升组和下降组患者的2周期客观缓解率(ORR)分别为63.5%(33/52)和44.0%(22/50)(χ^(2)=3.89,P=0.049),中性粒细胞与淋巴细胞比值(NLR)上升组(n=24)和下降组(n=78)患者的2周期ORR分别为29.2%(7/24)和61.5%(48/78)(χ^(2)=7.74,P=0.005),系统免疫炎症指数(SII)上升组(n=27)和下降组(n=75)患者的2周期ORR分别为33.3%(9/27)和61.3%(46/75)(χ^(2)=6.26,P=0.012),差异均具有统计学意义。多因素分析显示,外周血炎症标志物的变化趋势均与患者ORR无关。Kaplan-Meier生存曲线显示,SII下降组患者的中位无进展生存期(PFS)(未达到比7.1个月,χ^(2)=9.35,P=0.002)和中位总生存期(OS)(未达到比16.6个月,χ^(2)=11.08,P<0.001)均长于SII上升组,NLR下降组患者的中位OS比NLR上升组更长(未达到比22.2个月,χ^(2)=4.56,P=0.033)。单因素分析显示,同时伴有脑、骨转移(HR=4.04,95%CI为1.23~13.35,P=0.022),SII上升(HR=2.83,95%CI为1.41~5.66,P=0.003)是NSCLC患者PFS的影响因素,同时伴有脑、骨转移(HR=3.47,95%CI为1.05~11.45,P=0.041),NLR上升(HR=2.17,95%CI为1.05~4.51,P=0.037)和SII上升(HR=3.12,95%CI为1.54~6.30,P=0.002)是NSCLC患者OS的影响因素。多因素分析结果显示,同时伴有脑、骨转移(HR=4.32,95%CI为1.30~14.40,P=0.017)和SII上升(HR=2.89,95%CI为1.44~5.81,P=0.003)均是NSCLC患者PFS的独立危险因素,同时伴有脑、骨转移(HR=3.76,95%CI为1.13~12.50,P=0.031)和SII上升(HR=3.47,95%CI为1.28~9.41,P=0.014)是NSCLC患者OS的独立危险因素。结论NSCLC患者外周血炎症标志物的变化趋势不能独立预测2周期免疫联合化疗的疗效。同时脑、骨转移和SII的变化趋势可作为预测一线接受免疫联合化疗治疗的晚期NSCLC患者PFS、OS的重要指标。同时发生脑、骨转移和SII上升提示NSCLC患者预后较差。

关键词：癌非小细胞肺免疫疗法预后炎症标志物生存分析

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SETD2 mediates immunotherapy and radiotherapy efficacy via regulating DNA damage responses and genomic stability in lung adenocarcinoma

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Genes & Diseases 2023年第2期10卷 336-339页

作者： Zihang Zeng Yanping Gao Jiali Li Jianguo Zhang Yangyi Li Fajian He Zhengrong Huang Linzhi Han Yan Gong conghua xie Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan UniversityWuhanHubei 430071China Department of Biological Repositories Zhongnan Hospital of Wuhan UniversityWuhanHubei 430071China Tumor Precision Diagnosis and Treatment Technology and Translational Medicine Hubei Engineering Research CenterZhongnan Hospital of Wuhan UniversityWuhanHubei 430071China Hubei Key Laboratory of Tumor Biological Behaviors Zhongnan Hospital of Wuhan UniversityWuhanHubei 430071China Hubei Cancer Clinical Study Center Zhongnan Hospital of Wuhan UniversityWuhanHubei 430071China

SETD2 is the main transferase for the trimethylation of histone H3 at lysine 36 (H3K36me3) in mammals. SETD2 plays important role in repairing DNA double strand breaks and maintaining chromatin integrity.1 In renal carcinoma, SETD2 deficiency caused DNA replication fork instability and DNA damage.2 The absence of SETD2 was also reported to have strong tumor-promoting effects in lung adenocarcinomas (LUAD).3 However, the other roles of SETD2 remain poorly understood in LUAD. In this study, we utilized comprehensive omics-data analysis to determine that SETD2 was associated with DNA damage and immune-related signals in LUAD. SETD2 knockdown induced DNA damage and cGAS activation in LUAD cells, and reduced the number of cells at the G1 phase. Moreover, SETD2 deficiency was conducive to mutation burden, immune cell infiltration, and immunotherapy responses. High SETD2 expression was associated with high radiocurability. These findings suggest that SETD2 may be a promising biomarker of therapeutic responses for LUAD patients, and offer novel insights into immunotherapy and radiotherapy.

关键词： SETD2 damage immunotherapy

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Rapid assembly of 1,3-indanedione-based spirocyclic tetrahydroquinolines for inducing human lung cancer cell apoptosis

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Green Synthesis and Catalysis 2022年第4期3卷 357-372页

作者： Fen Tan Luojia Chen Yuncong Yuan Xiaoyu He Yiwen Su Shuqiang Cao conghua xie Meijia Gu Youquan Zou Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan UniversitySchool of Pharmaceutical SciencesWuhan UniversityWuhan 430071China Hubei Key Laboratory of Purification and Application of Plant Anti-cancer Active Ingredients Hubei University of EducationWuhan 430205China Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of EducationWuhan UniversityWuhan 430071China Hubei Key Laboratory of Tumor Biological Behaviors Hubei Cancer Clinical Study CenterZhongnan Hospital of Wuhan UniversityWuhan 430071China TaiKang Center for Life and Medical Sciences Wuhan UniversityWuhan 430071China

The rapid collection of a library of biologically relevant molecules is essential in new drug *** we show a variety of bioactive 1,3-indanedione-based spirocyclic tetrahydroquinolines that have been concisely and efficiently constructed under the guidance of biology-oriented synthesis(BIOS).Using Pd(PPh_(3))_(4) as a catalyst,various 2-arylidene-1,3-indanediones can react with vinyl benzoxazinanones under the mild condition to afford a new class of spirocyclic tetrahydroquinolines in moderate to excellent yields(45%-99%)with high stereocontrol(>95:5 diastereoselectivity).Their structures were unambiguously confirmed by X-ray single crystal *** biological evaluation revealed that two of the 1,3-indanedione-based spirocyclic tetrahydroquinolines show remarkable apoptosis-inducing activities over A549 human lung cancer cells,exceeding that of *** antitur activities were triggered by reactive oxygen species,commonly overproduced in cancer *** clinical demand for antitumor chemotherapy for lung cancer has encouraged an all-out search for analogues with lower toxcity,improved therapeutic index and increased activity.

关键词： Spirocyclic tetrahydroquinoline 1,3-Indanedione Lung cancer Apoptosis Mitochondria

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A New Method of Semantic Feature Extraction for Medical Images Data

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Wuhan University Journal of Natural Sciences 2006年第5期11卷 1152-1156页

作者： xie conghua SONG Yuqing CHANG Jinyi Department of Computer Science and Engineering Changshu Institute of Technology Changshu 215500Jiangsu China School of Computer Science Jiangsu UniversityZhenjiang 212013 Jiangsu China

In order to overcome the disadvantages of color, shape and texture-based features definition for medical images, this paper defines a new kind of semantic feature and its extraction algorithm. We firstly use kernel density estimation statistical model to describe the complicated medical image data, secondly, define some typical representative pixels of images as feature and finally, take hill-climbing strategy of Artificial Intelligence to extract those semantic features. Results of a content-based medial image retrieve system show that our semantic features have better distinguishing ability than those color, shape and texture-based features and can improve the ratios of recall and precision of this system smartly.

关键词： feature extraction kernel density estimation hill-climbing algorithm content-based image retrieve

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Mapping QTL underlying tuber starch content and plant maturity in tetraploid potato

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The Crop Journal 2019年第2期7卷 261-272页

作者： Jianwu Li Yihang Wang Guohong Wen Gaofeng Li Zhang Li Rong Zhang Sheng Ma Jun Zhou conghua xie Key Laboratory of Potato Biology and Biotechnology Ministry of Agriculture and Rural Affairs Key Laboratory of Horticultural Plant Biology Huazhong Agricultural University Ministry of Education College of Horticulture and Forestry Sciences Huazhong Agricultural University Gansu Academy of Agricultural Sciences

Tuber starch content and plant maturity are two important agronomic traits of potato. To investigate the complex genetic basis of these traits in the cultivated potato, as well as the relationship between them, we developed a linkage map in a tetraploid population of 192 clones derived from the cross Longshu 8 × Zaodabai and mapped quantitative trait loci(QTL) for tuber starch content and plant maturity using data collected in three diverse environments over two years. We detected eleven QTL for tuber starch content distributed on seven chromosomes, of which four, on chromosomes I, II, and VIII, were expressed in at least three environments. For plant maturity, we identified six QTL on chromosomes II, IV,V, VII, and XI, one of which, on chromosome V, showed LOD peaks ranging from 45.2 to 62.5 cM and explained 21.6%–26.6% of phenotypic variation was expressed in five of the six environments. Because the reproducible QTL for plant maturity and tuber starch content mapped to different chromosomes and neither overlapping QTL, nor any genetic interaction between QTL were detected, we infer that tuber starch content and plant maturity are controlled by independent genetic loci. This inference supports the prospect of breeding potato for both early maturity and high starch content.

关键词： Potato QTL Tetraploid Tuber starch content Plant maturity

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面向教学评价的课堂视频镜头边界检测新方法

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数据采集与处理 2023年第1期38卷 174-185页

作者：谢从华罗德凤方雨洁常熟理工学院计算机科学与工程学院苏州215500 重庆三峡学院外国语学院万州404100

课堂视频镜头边界检测对教学评价具有重要意义。针对教学视频视觉信息变化不明显、镜头边界信息不足、检测结果不利于教学评价等问题,引入注意力机制,提出了基于视觉和文本特征描述学习的课堂视频镜头边界检测方法。首先,提出了层次视觉... 详细信息

课堂视频镜头边界检测对教学评价具有重要意义。针对教学视频视觉信息变化不明显、镜头边界信息不足、检测结果不利于教学评价等问题,引入注意力机制,提出了基于视觉和文本特征描述学习的课堂视频镜头边界检测方法。首先,提出了层次视觉Transformer模型学习教学评价关注的屏幕、教师和学生等感兴趣区域的视觉特征。其次,提出了层次文本Transformer模型从屏幕和语音文本中学习教学评价关注的文本特征。最后,构建基于二值交叉熵的镜头分类和边界检测损失函数。在数据集CLShots上的实验结果表明,本文方法在准确率、召回率、F1分数和平均交并比等指标比当前先进的教学镜头检测方法SBLV分别提高了23.3%、22.4%、22%和35.7%,比通用领域深度学习方法TransNet V2分别提高了13.8%、14.5%、14.3%和21.3%。

关键词：教学评价课堂视频分割注意力机制模型镜头边界检测

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Clinical outcomes of coronavirus disease 2019 (COVID-19) in cancer patients with prior exposure to immune checkpoint inhibitors

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Cancer Communications 2020年第8期40卷 374-379页

作者： Qiuji Wu Qian Chu Hongyan Zhang Bin Yang Xudong He Yahua Zhong Xianglin Yuan Melvin L.K.Chua conghua xie Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan UniversityWuhanHubei 430071P.R.China Hubei Key Laboratory of Tumor Biological Behaviors Zhongnan Hospital ofWuhan UniversityWuhanHubei 430071P.R.China Hubei Cancer Clinical Study Center Zhongnan Hospital ofWuhan UniversityWuhanHubei 430071P.R.China Department of Oncology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030P.R.China Department of Medical Oncology Hubei Cancer HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430079P.R.China Department of Gastroenterology Dongfeng HospitalHubei University of MedicineShiyanHubei 442000P.R.China Divisions of Radiation Oncology and Medical Sciences National Cancer Centre SingaporeSingapore 169610Singapore Oncology Academic Programme Duke-NUS Medical SchoolSingapore 169857Singapore

Dear Editor,The coronavirus disease 2019(COVID-19)pandemic has affected over 6,000,000 people globally[1].Patients with COVID-19 manifest with symptoms of fever,dry cough,dyspnea,and present with radiological changes that are consistent with atypical pneumonia[2].Pathogenetic mechanisms for these abnormalities involve the systemic immune response that is associated with the hyperactivation of peripheral CD8+and CD4+T cells,and a cytokine storm[3].Globally,the reported prevalence of patients with COVID-19 and cancer ranges from 0.5%to 6.0%in the different case series[4].

关键词： patients cancer immune

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植物Rab蛋白的研究进展

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西北植物学报 2013年第12期33卷 2558-2566页

作者：高文谢从华华中农业大学园艺林学学院武汉430070 河南科技大学林学院河南洛阳471003

Rab蛋白是小G蛋白超级家族中的成员之一。通过Rab蛋白氨基酸序列的系统进化分析表明,植物Rab家族又可分为8个亚家族,分别为RabA、RabB、RabC、RabD、RabE、RabF、RabG和RabH。Rab蛋白一般位于胞内特异膜系统的胞质面,它们是小泡运输的... 详细信息

Rab蛋白是小G蛋白超级家族中的成员之一。通过Rab蛋白氨基酸序列的系统进化分析表明,植物Rab家族又可分为8个亚家族,分别为RabA、RabB、RabC、RabD、RabE、RabF、RabG和RabH。Rab蛋白一般位于胞内特异膜系统的胞质面,它们是小泡运输的关键调节因子。Rab蛋白有非常保守的结构域,同时又具有功能多样性,它们在细胞分化、顶端优势、花粉管发育、根瘤形成以及生物和非生物胁迫反应中均起着非常重要的作用。该文对近年来国内外有关植物Rab蛋白的结构特点及其多样性功能的研究进展进行综述。

关键词：小G蛋白 Rab蛋白结构分析功能多样性

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Application of Variance Component Analysis (ANOVA) in Setup Errors and PTV Margins for Lung Cancer with Stereotactic Body Radiation Therapy (SBRT)

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International Journal of Medical Physics, Clinical Engineering and Radiation Oncology 2018年第4期7卷 522-538页

作者： Xiaotian Huang Jun Zhang conghua xie Yunfeng Zhou Hong Quan School of Physics and Technology Wuhan University Wuhan China Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan University Wuhan China

Purpose: To investigate the feasibility of applying ANOVA newly proposed by Yukinori to verify the setup errors, PTV (Planning Target Volume) margins, DVH for lung cancer with SBRT. Methods: 20 patients receiving SBRT to 50 Gy in 5 fractions with a Varian iX linear acceleration were selected. Each patient was scanned with kV-CBCT before the daily treatment to verify the setup position. Two other error calculation methods raised by Van Herk and Remeijer were also compared to discover the statistical difference in systematic errors (Σ), random errors (σ), PTV margins and DVH. Results: Utilizing two PTV margin calculation formulas (Stroom, Van Herk), PTV calculated by Yukinori method in three directions were (5.89 and 3.95), (5.54 and 3.55), (3.24 and 0.78) mm;Van Herk method were (6.10 and 4.25), (5.73 and 3.83), (3.51 and 1.13) mm;Remeijer method were (6.39 and 4.57), (5.98 and 4.10), (3.69 and 1.33) mm. The volumes of PTV using Yukinori method were significantly smaller (P 0.05) among three methods. Conclusions: In lung SBRT treatment, due to fraction reduction and high level of dose per fraction, ANOVA was able to offset the effect of random factors in systematic errors, reducing the PTV margins and volumes. However, no distinct dose distribution improvement was founded in target volume and organs at risk.

关键词： SBRT KV-CBCT PTV Margin Setup Errors DVH

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