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Construction and application of high-quality genome-scale metabolic model of Zymomonas mobilis to guide rational design of microbial cell factories

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Synthetic and Systems Biotechnology 2023年第3期8卷 498-508页

作者： Yalun Wu qianqian yuan Yongfu Yang Defei Liu Shihui Yang Hongwu Ma State Key Laboratory of Biocatalysis and Enzyme Engineering School of Life SciencesHubei UniversityWuhan430062HubeiChina Biodesign Center Key Laboratory of Systems Microbial BiotechnologyTianjin Institute of Industrial BiotechnologyChinese Academy of SciencesTianjin300308China Hubei Key Laboratory of Applied Mathematics Faculty of Mathematics and StatisticsHubei UniversityWuhan430062HubeiChina Artificial Intelligence and Knowledge Engineering Lab School of Computer Science and Information EngineeringHubei UniversityWuhan430062HubeiChina

High-quality genome-scale metabolic models(GEMs)could play critical roles on rational design of microbial cell factories in the classical Design-Build-Test-Learn cycle of synthetic biology studies.Despite of the constant establishment and update of GEMs for model microorganisms such as Escherichia coli and Saccharomyces cerevisiae,high-quality GEMs for non-model industrial microorganisms are still scarce.Zymomonas mobilis subsp.mobilis ZM4 is a non-model ethanologenic microorganism with many excellent industrial characteristics that has been developing as microbial cell factories for biochemical production.Although five GEMs of Z.mobilis have been constructed,these models are either generating ATP incorrectly,or lacking information of plasmid genes,or not providing standard format file.In this study,a high-quality GEM iZM516 of Z.mobilis ZM4 was constructed.The information from the improved genome annotation,literature,datasets of Biolog Phenotype Microarray studies,and recently updated Gene-Protein-Reaction information was combined for the curation of iZM516.Finally,516 genes,1389 reactions,1437 metabolites,and 3 cell compartments are included in iZM516,which also had the highest MEMOTE score of 91%among all published GEMs of Z.mobilis.Cell growth was then predicted by iZM516,which had 79.4%agreement with the experimental results of the substrate utilization.In addition,the potential endogenous succinate synthesis pathway of Z.mobilis ZM4 was proposed through simulation and analysis using iZM516.Furthermore,metabolic engineering strategies to produce succinate and 1,4-butanediol(1,4-BDO)were designed and then simulated under anaerobic condition using iZM516.The results indicated that 1.68 mol/mol succinate and 1.07 mol/mol 1,4-BDO can be achieved through combinational metabolic engineering strategies,which was comparable to that of the model species E.coli.Our study thus not only established a high-quality GEM iZM516 to help understand and design microbial cell factories for economic biochemical production using

关键词： Genome-scale metabolic models(GEMSs) Non-model industrial microorganism Zymomonas mobilis Biolog phenotype microarray Succinate 1,4-Butanediol

Reconstruction and metabolic profiling of the genome-scale metabolic network model of Pseudomonas stutzeri A1501

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Synthetic and Systems Biotechnology 2023年第4期8卷 688-696页

作者： qianqian yuan Fan Wei Xiaogui Deng Aonan Li Zhenkun Shi Zhitao Mao Feiran Li Hongwu Ma Biodesign Center Key Laboratory of Engineering Biology for Low-carbon ManufacturingTianjin Institute of Industrial BiotechnologyChinese Academy of SciencesTianjin300308China University of Chinese Academy of Sciences Beijing100049China National Technology Innovation Center of Synthetic Biology Tianjin300308China School of Biological Engineering Tianjin University of Science and TechnologyTianjinChina Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen518055China

Pseudomonas stutzeri A1501 is a non-fluorescent denitrifying bacteria that belongs to the gram-negative bacterial group.As a prominent strain in the fields of agriculture and bioengineering,there is still a lack of comprehensive understanding regarding its metabolic capabilities,specifically in terms of central metabolism and substrate utilization.Therefore,further exploration and extensive studies are required to gain a detailed insight into these aspects.This study reconstructed a genome-scale metabolic network model for P.stutzeri A1501 and conducted extensive curations,including correcting energy generation cycles,respiratory chains,and biomass composition.The final model,iQY1018,was successfully developed,covering more genes and reactions and having higher prediction accuracy compared with the previously published model iPB890.The substrate utilization ability of 71 carbon sources was investigated by BIOLOG experiment and was utilized to validate the model quality.The model prediction accuracy of substrate utilization for P.stutzeri A1501 reached 90%.The model analysis revealed its new ability in central metabolism and predicted that the strain is a suitable chassis for the production of Acetyl CoA-derived products.This work provides an updated,high-quality model of P.stutzeri A1501for further research and will further enhance our understanding of the metabolic capabilities.

关键词： network prediction metabolism

A self-monitoring microneedle patch for light-controlled synergistic treatment of melanoma

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Bioactive Materials 2023年第9期27卷 58-71页

作者： Chenyuan Wang Yongnian Zeng Kai-Feng Chen Jiawei Lin qianqian yuan Xue Jiang Gaosong Wu Fubing Wang Yong-Guang Jia Wei Li Department of Thyroid and Breast Surgery Zhongnan Hospital of Wuhan UniversitySchool of Pharmaceutical SciencesWuhan UniversityWuhan430071China School of Materials Science and Engineering South China University of TechnologyGuangzhouGuangdong510641China TaiKang Center for Life and Medical Sciences Wuhan UniversityWuhanChina Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center Zhongnan Hospital of Wuhan UniversityWuhanChina Wuhan Research Center for Infectious Diseases and Cancer Chinese Academy of Medical SciencesWuhanChina

Melanoma is the most aggressive and malignant form of skin cancer.Current melanoma treatment methods generally suffer from frequent drug administration as well as difficulty in direct monitoring of drug release.Here,a self-monitoring microneedle(MN)-based drug delivery system,which integrates a dissolving MN patch with aggregation-induced emission(AIE)-active PATC microparticles,is designed to achieve light-controlled pulsatile chemo-photothermal synergistic therapy of melanoma.The PATC polymeric particles,termed D/I@PATC,encapsulate both of chemotherapeutic drug doxorubicin(DOX)and the photothermal agent indocyanine green(ICG).Upon light illumination,PATC gradually dissociates into smaller particles,causing the release of encapsulated DOX and subsequent fluorescence intensity change of PATC particles,thereby not only enabling direct observation of the drug release process under light stimuli,but also facilitating verification of drug release by fluorescence recovery after light trigger.Moreover,encapsulation of ICG in PATC particles displays significant improvement of its photothermal stability both in vitro and in vivo.In a tumor-bearing mouse,the application of one D/I@PATC MN patch combining with two cycles of light irradiation showed excellent controllable chemo-photothermal efficacy and exhibited~97%melanoma inhibition rate without inducing any evident systemic toxicity,suggesting a great potential for skin cancer treatment in clinics.

关键词： Microneedle Controlled release Melanoma AIE Photothermal therapy Chemotherapy

Estimating the quarantine failure rate for COVID-19

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Infectious Disease Modelling 2021年第1期6卷 924-929页

作者： Meili Li qianqian yuan Pian Chen Baojun Song Junling Ma College of Science Donghua UniversityShanghai201620China Department of Applied Mathematics and Statistics Montclair State UniversityMontclairNJ07043USA Department of Mathematics and Statistics University of VictoriaVictoriaBCV8W 2Y2Canada

Quarantine is a crucial control measure in reducing imported COVID-19 cases and community transmissions.However,some quarantined COVID-19 patients may show symptoms after finishing quarantine due to a long median incubation period,potentially causing community transmissions.To assess the recommended 14-day quarantine policy,we develop a formula to estimate the quarantine failure rate from the incubation period distribution and the epidemic curve.We found that the quarantine failure rate increases with the exponential growth rate of the epidemic curve.We apply our formula to United States,Canada,and Hubei Province,China.Before the lockdown of Wuhan City,the quarantine failure rate in Hubei Province is about 4.1%.If the epidemic curve flattens or slowly decreases,the failure rate is less than 2.8%.The failure rate in US may be as high as 8.3%-11.5%due to a shorter 10-day quarantine period,while the failure rate in Canada may be between 2.5%and 3.9%.A 21-day quarantine period may reduce the failure rate to 0.3%-0.5%.

关键词： Quarantine Incubation period Exponential growth rate Epidemic curve

Enzyme Commission Number Prediction and Benchmarking with Hierarchical Dual-core Multitask Learning Framework

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Research 2023年第3期2023卷 117-128页

作者： Zhenkun Shi Rui Deng qianqian yuan Zhitao Mao Ruoyu Wang Haoran Li Xiaoping Liao Hongwu Ma Biodesign Center Key Laboratory of Engineering Biology for Low-carbon ManufacturingTianjin Institute of Industrial BiotechnologyChinese Academy of Sciences300308TianjinChina National Center of Technology Innovation for Synthetic Biology 300308TianjinChina College of Biotechnology Tianjin University of Science&TechnologyTianjinChina Haihe Laboratory of Synthetic Biology 300308.TianjinChina

Enzyme commission(EC)numbers,which associate a protein sequence with the biochemical reactions it catalyzes,are essential for the accurate understanding of enzyme functions and cellular metabolism.Many ab initio computational approaches were proposed to predict EC numbers for given input protein sequences.However,the prediction performance(accuracy,recall,and precision),usability,and efficiency of existing methods decreased seriously when dealing with recently discovered proteins,thus still having much room to be improved.Here,we report HDMLF,a hierarchical dual-core multitask learning framework for accurately predicting EC numbers based on novel deep learning techniques.HDMLF is composed of an embedding core and a learning core;the embedding core adopts the latest protein language model for protein sequence embedding,and the learning core conducts the EC number prediction.Specifically,HDMLF is designed on the basis of a gated recurrent unit framework to perform EC number prediction in the multi-objective hierarchy,multitasking manner.Additionally,we introduced an attention layer to optimize the EC prediction and employed a greedy strategy to integrate and fine-tune the final model.Comparative analyses against 4 representative methods demonstrate that HDMLF stably delivers the highest performance,which improves accuracy and F1 score by 60%and 40%over the state of the art,respectively.An additional case study of tyrB predicted to compensate for the loss of aspartate aminotransferase aspC,as reported in a previous experimental study,shows that our model can also be used to uncover the enzyme promiscuity.Finally,we established a web platform,namely,ECRECer(https://***),using an entirely could-based serverless architecture and provided an offline bundle to improve usability.

关键词： server prediction entirely

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功能保护性甲状腺外科:技术难点与对策

中国实用外科杂志 2024年第6期44卷 625-629页

作者：袁芊芊贺青卿田文吴高松武汉大学中南医院甲状腺乳腺外科湖北武汉430071 中国人民解放军联勤保障部队第九六〇医院甲状腺乳腺外科山东济南250031 中国人民解放军总医院第一医学中心普通外科医学部甲状腺(疝)外科北京100853

甲状腺癌是预后较好的实体肿瘤之一,手术是主要治疗方式。降低甲状腺术后并发症发生率,提高病人术后生活质量至关重要。手术中保护甲状腺及其周围重要组织器官的功能完整性,减少并发症,是甲状腺外科面临的重大挑战。功能保护性甲状腺外... 详细信息

甲状腺癌是预后较好的实体肿瘤之一,手术是主要治疗方式。降低甲状腺术后并发症发生率,提高病人术后生活质量至关重要。手术中保护甲状腺及其周围重要组织器官的功能完整性,减少并发症,是甲状腺外科面临的重大挑战。功能保护性甲状腺外科强调在治疗甲状腺疾病的同时,尽可能保护甲状腺自身及周围组织器官的生理功能。为减少甲状腺病人术后发生出血和窒息,手术结束缝合切口时,保留颈白线下段3 cm敞开不缝闭,以保证气管前至颈部皮下疏松组织之间的通道通畅。甲状旁腺功能保护的关键是术中识别和保护其动静脉不被损伤。为提高甲状旁腺自体移植的生存率及分泌功能,建议采用带脂肪组织的甲状旁腺自体移植术,并应用个体化甲状旁腺移植位点技术提高评估移植物是否存活的敏感度及分泌功能评估的敏感度。对于喉返神经功能保护,除“包膜内切除技术”和神经监测仪等评估方法外,近年来出现了多种喉返神经监测评估新标准及新方法可更有效地评估喉返神经功能完整性。针对肿瘤侵犯喉返神经需要进行节段性切除的情况,劈离式选择性迷走神经-喉返神经吻合术可作为一种简单且效果明确的喉返神经损伤吻合修复方法。对于喉上神经外支保护,临床适用性喉上神经外支分型依据喉上神经外支最低点与甲状腺上极平面的最短距离进行分型,为术中喉上神经外支的常规显露、定位及功能保护提供了解剖学依据和方法。对于胸导管功能保护,针对胸导管意外损伤,除直接结扎胸导管等封堵策略外,胸导管显微修补术可作为一种疏通策略。对术后已发生乳糜漏的病人,可根据乳糜漏流量进行高、中、低流量分类,并采取个体化综合治疗方案,加速胸导管愈合。

关键词：甲状腺肿瘤甲状旁腺喉上神经外支喉返神经胸导管功能保护性甲状腺外科

细针穿刺细胞学检查与粗针穿刺活检术对甲状腺结节的诊断效能比较

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中国普通外科杂志 2024年第5期33卷 772-779页

作者：袁芊芊侯晋轩李金朋田文吴高松武汉大学中南医院甲状腺乳腺外科湖北武汉430071 中国人民解放军总医院第一医学中心普通外科医学部甲状腺(疝)外科北京100853

背景与目的:彩超引导下细针穿刺细胞学检查(FNAC)是术前评估甲状腺结节良恶性的主要方法,其缺点是取材不足,可能导致误诊或漏诊。粗针穿刺活检术(CNB)可弥补FNAC的不足,但其缺点是增加了疼痛和创伤。因此,本研究比较FNAC与CNB对甲状腺... 详细信息

背景与目的:彩超引导下细针穿刺细胞学检查(FNAC)是术前评估甲状腺结节良恶性的主要方法,其缺点是取材不足,可能导致误诊或漏诊。粗针穿刺活检术(CNB)可弥补FNAC的不足,但其缺点是增加了疼痛和创伤。因此,本研究比较FNAC与CNB对甲状腺结节诊断的诊断效能及各自特点,以期为临床合理选择提供参考。方法:回顾性分析2020年11月—2022年11月于武汉大学中南医院接受甲状腺手术的552例患者资料,所有患者术前均接受超声检查,并依次行FNAC与CNB,穿刺1周内行患侧甲状腺切除术。收集患者临床资料及甲状腺结节的超声特征、术前细胞学、组织病理学及术后常规病理结果,以术后常规病理为金标准,分析FNAC及CNB诊断效能。结果:总体上,FNAC与CNB对甲状腺结节诊断敏感度、特异度、准确率相近,差异均无统计学意义(88.7%vs.91.4%,P=0.283;90.6%vs.97.4%,P=0.226;85.3%vs.89.1%,P=0.058);对滤泡性肿瘤的良恶性判别,CNB优于FNAC(P=0.024)。当结节直径≤2.0 cm时,FNAC与CNB诊断效能基本无差异;当结节直径>2.0 cm时,CNB的敏感度明显高于FNAC(95.0%vs.79.2%,P2.0 cm、钙化结节、富血供及囊性或囊实性结节甲状腺结节诊断效能优于FNAC,对具备上述特征的结节联合FNAC与CNB检查可在一定程度上提高甲状腺结节术前诊断的准确率。

关键词：甲状腺结节活组织检查细针活组织检查粗针诊断鉴别

Effects of Polysaccharides from Enteromorpha prolifera on Hepatorenal Syndrome in Mice

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Medicinal Plant 2023年第1期14卷 50-54页

作者： Shanshan WANG Jiayan ZHOU Yue HE Yating ZHOU Qiuxi YANG qianqian yuan Qingying DU Hanchi CHENG Suduo JIANG Xiaojuan ZHAO School of Pharmacy Yancheng Teachers UniversityYancheng 224007China

[Objectives]This study was conducted to evaluate the protective effect of polysaccharides from Enteromorpha prolifera(PEP)on mice with hepatorenal syndrome induced by carbon tetrachloride.[Methods]A mouse hepatorenal syndrome model was induced by carbon tetrachloride.The serum levels of lipid,total antioxidant capacity,liver and kidney function,pathological changes of liver and kidney were selected to clarity the effectiveness of PEP on hepatorenal syndrome in mice.[Results]PEP effectively lowered the serum levels of lipid,increased total antioxidant capacity,improved liver and kidney injury,and alleviated pathological changes of liver and kidney of mice induced by carbon tetrachloride.[Conclusions]PEP has a potent preventive effect on hepatorenal syndrome induced by carbon tetrachloride in mice,which provides theoretical support for future clinical application of PEP.

关键词： Polysaccharides from Enteromorpha prolifera Carbon tetrachloride Hepatorenal syndrome

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电力监控网安设备策略统一管理体系及其实践

信息安全研究 2024年第5期10卷 481-488页

作者：冯陈佳朱江朱寅严威李雪妍张宇袁倩倩国网上海市电力公司市北供电公司上海200072

随着电力监控系统建设不断完善,部署在其中的网络、安全设备和业务应用场景不断增多,相关的网络边界安全策略也愈加繁杂,往往跨越多个供应商、多个设备厂商以及多个物理位置,运维难度大,依赖于“人”以及传统“手动”的安全管理方式准... 详细信息

随着电力监控系统建设不断完善,部署在其中的网络、安全设备和业务应用场景不断增多,相关的网络边界安全策略也愈加繁杂,往往跨越多个供应商、多个设备厂商以及多个物理位置,运维难度大,依赖于“人”以及传统“手动”的安全管理方式准确率低,极大增加了公司重要业务和核心数据资产遭受网络攻击的风险.因此,迫切需要加强网络边界安全策略管理体系的建设.结合电力监控系统的网络安全设备特性,提出一套基于网络安全设备资产分析、电力监控系统路由拓扑分析以及信息安全设备策略分析的安全边界策略统一管理体系,并开发了相应软件平台,在资产探测、路由策略采集、防护策略采集的基础上进行网络安全策略计算,实现了安全边界的策略统一管理.研究以及实践部署表明,该体系可以有效提升运维效率和系统安全性,对于电力监控系统具有较好的针对性、实用性和先进性.

关键词：电力监控系统安全边界策略统一管理体系风险监测策略优化