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Establishing cell suitability for high-level production of licorice triterpenoids in yeast

Acta Pharmaceutica Sinica B 2024年第9期14卷 4134-4148页

作者： Wentao Sun Shengtong wan.Chuyan Liu ruwen wan. Haocheng Zhang Lei Qin Runming wan. Bo Lv Chun Li Department of Chemical Engineering Tsinghua UniversityBeijing 100084China Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering Ministry of Industry and Information TechnologyInstitute of Biochemical EngineeringSchool of Chemistry and Chemical EngineeringBeijing Institute of TechnologyBeijing 100081China The University of Chicago ChicagoIL 60637USA Key Lab for Industrial Biocatalysis Ministry of EducationTsinghua UniversityBeijing 100084China Center for Synthetic and Systems Biology Tsinghua UniversityBeijing 100084China Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen 518055China

Yeast has been an indispensable host for synthesizing complex plant-derived naturalcompounds, yet the yields remained largely constrained. This limitation mainly arises from overlookingthe importance of cell and pathway suitability during the optimization of enzymes and pathways. Herein,beyond conventional enzyme engineering, we dissected metabolic suitability with a framework forsimultaneously augmenting cofactors and carbon flux to enhance the biosynthesis of heterogenoustriterpenoids. We further developed phospholipid microenvironment engineering strategies, dramaticallyimproving yeast’s suitability for the high performance of endoplasmic reticulum (ER)-localized, ratelimitingplant P450s. Combining metabolic and microenvironment suitability by manipulating only threegenes, NHMGR (NADH-dependent HMG-CoA reductase), SIP4 (a DNA-binding transcription factor)andGPP1 (Glycerol-1-phosphate phosphohydrolase 1), we enabled the high-level production of 4.92 g/L rarelicorice triterpenoids derived from consecutive oxidation of b-amyrin by two P450 enzymes afterfermentation optimization. This production holds substantial commercial value, highlighting the criticalrole of establishing cell suitability in enhancing triterpenoid biosynthesis and offering a versatileframework applicable to various plant natural product biosynthetic pathways.

关键词： Cell suitability Phospholipid microenvironment Cytochrome P450 Triterpenoids Saccharomyces cerevisiae

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Exercise-induced microbial changes in preventing type 2 diabetes

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Science China(Life Sciences) 2024年第5期67卷 892-899页

作者： Ting Yao Hui wan. Kaiqing Lin ruwen wan. Shanshan Guo Peijie Chen Hao Wu Tiemin Liu Ru wan. School of Exercise and Health Shanghai Frontiers Science Research Base of Exercise and Metabolic HealthShanghai University of SportShanghai 200438China Department of Physiology and Pathophysiology School of Basic Medical SciencesXi’an Jiaotong University School of MedicineXi’an 710061China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism&Integrative BiologyFudan UniversityShanghai 200433China State Key Laboratory of Genetic Engineering Human Phenome InstituteFudan Microbiome Centerand Department of Bariatric and Metabolic SurgeryHuashan HospitalFudan UniversityShanghai 201203China State Key Laboratory of Genetic Engineering Department of Endocrinology and MetabolismHuman Phenome Instituteand School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200032China

The metabolic benefits associated with long-term physical activity are well appreciated and growing evidence suggests that it involves the gut *** we re-evaluated the link between exercise-induced microbial changes and those associated with prediabetes and *** found that the relative abundances of substantial amounts of diabetes-associated metagenomic species associated negatively with physical fitness in a Chinese athlete students *** additionally showed that those microbial changes correlated more with handgrip strength,a simple but valuable biomarker suggestive of the diabetes states,than maximum oxygen intake,one of the key surrogates for endurance ***,the causal relationships among exercise,risks for diabetes,and gut microbiota were explored based on mediation *** propose that the protective roles of exercise against type 2 diabetes are mediated,at least partly,by the gut microbiota.

关键词： gut microbiota body fat diabetes handgrip maximum oxygen intake

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Two-fold symmetry of the in-plane resistance in kagome superconductor Cs(V_(1-x)Ta_(x))_(3)Sb_(5) with enhanced superconductivity

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Chinese Physics B 2024年第7期33卷 9-14页

作者：赵振王汝文张宇航祝轲余维琪韩烨超刘家利胡国静郭辉林晓董晓莉陈辉杨海涛高鸿钧 Beijing National Center for Condensed Matter Physics and Institute of Physics Chinese Academy of SciencesBeijing 100190China School of Physical Sciences University of Chinese Academy of SciencesBeijing 100049China Songshan Lake Materials Laboratory Dongguan 523808China

The kagome superconductor CsV_(3)Sb_(5) has attracted widespread attention due to its rich correlated electron states including superconductivity, charge density wave(CDW), nematicity, and pair density wave. Notably, the modulation of the intertwined electronic orders by the chemical doping is significant to illuminate the cooperation/competition between multiple phases in kagome superconductors. In this study, we have synthesized a series of tantalum-substituted Cs(V_(1-x)Ta_(x))_(3)Sb_(5) by a modified self-flux method. Electrical transport measurements reveal that CDW is suppressed gradually and becomes undetectable as the doping content of x is over 0.07. Concurrently, the superconductivity is enhanced monotonically from T_(c) ~ 2.8 K at x = 0 to 5.2 K at x = 0.12. Intriguingly, in the absence of CDW, Cs(V_(1-x)Ta_(x))_(3)Sb_(5)(x = 0.12) crystals exhibit a pronounced two-fold symmetry of the in-plane angular-dependent magnetoresistance(AMR) in the superconducting state, indicating the anisotropic superconducting properties in the Cs(V_(1-x)Ta_(x))_(3)Sb_(5). Our findings demonstrate that Cs(V_(1-x)Ta_(x))_(3)Sb_(5) with the non-trivial band topology is an excellent platform to explore the superconductivity mechanism and intertwined electronic orders in quantum materials.

关键词： kagome superconductor charge density wave rotation symmetry breaking

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Sliding mode control for consensus tracking of second-order nonlinear multi-agent systems driven by Brownian motion

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Science China(Information Sciences) 2018年第7期61卷 172-179页

作者： Birong ZHAO Yunjian PENG Yanan SONG ruwen QIN School of Mathematics and Information Science Guangzhou University School of Automation South China University of Technology College of Automation Guangdong University of Technology Department of Engineering Management and Systems Engineering Missouri University of Science and Technology

The consensus tracking problem of nonlinear stochastic multi-agent systems with directed topologies is investigated in this study. To solve the consensus tracking problem, first, an innovative concept of sub-reachability is introduced, and then, the specified sliding hyperplane is designed. A novel consensus tracking protocol is then proposed by using sliding mode techniques. With the help of It?o integral techniques and stochastic Lyapunov method, the sub-reachability of sliding motion and consensus tracking are proved;that is, the sliding mode variable structure control protocol steers the consensus errors to the given sliding surface in a finite time, and the sliding motion is exponentially stable in the sense of mean square. The efficacy of the proposed method is tested by a numerical case.

关键词： stochastic nonlinear multi-agent systems sub-reachability sliding hyperplane sliding mode variable structure control protocol it?o integral techniques consensus tracking errors

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糖尿病患者运动前测试与评估临床路径构建的经验启示与实现框架

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上海体育大学学报 2024年第5期48卷 81-93页

作者：邢晓蕊成玮田海丽徐炳祥颜红梅刘诚孙钦王汝雯万康张译尹王茹上海体育大学运动健康学院上海200438 同济大学附属杨浦医院内分泌科上海200090 复旦大学附属中山医院内分泌科上海200032

运动是防治糖尿病的重要手段,但运动在带来显著健康效益的同时,也伴随有运动损伤、心源性猝死等的发生风险。作为运动处方制定的第一步,运动前测试与评估可通过筛选出患有运动禁忌证、需要医疗许可或医务监督的患者,以减少运动不良事件... 详细信息

运动是防治糖尿病的重要手段,但运动在带来显著健康效益的同时,也伴随有运动损伤、心源性猝死等的发生风险。作为运动处方制定的第一步,运动前测试与评估可通过筛选出患有运动禁忌证、需要医疗许可或医务监督的患者,以减少运动不良事件的发生。目前,针对糖尿病患者的运动前测试与评估体系存在内容不完整、路径待规范等现实问题,构建规范操作体系有利于提高患者运动的安全性。参照临床路径构建方法,以卫生技术评估为目标导向,提出糖尿病患者运动前测试与评估临床路径构建的原则和内容。以建立操作流程为例,运用德尔菲法开展糖尿病患者运动前测试与评估临床路径构建的初步探索。

关键词：糖尿病运动不良事件运动前测试与评估临床路径

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发酵酒糟对西威牛血液、分泌型免疫球蛋白A和肠道黏膜相关菌群的影响

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中国饲料 2024年第7期 121-125页

作者：禹光美郑如雯吴道义王彬黄涛贵州大学动物科学学院贵州贵阳550025 毕节市畜牧兽医科学研究所贵州毕节551700

为研究发酵酒糟对西威牛免疫指标、炎症指标以及十二指肠细菌群落的影响,试验将18头西威公牛随机分为3组,对照组饲喂基础饲粮,试验1、2组分别添加15%、30%发酵酒糟,预试期15 d,正试期90 d。结果表明:与对照组相比,试验1组免疫球蛋白G(I... 详细信息

为研究发酵酒糟对西威牛免疫指标、炎症指标以及十二指肠细菌群落的影响,试验将18头西威公牛随机分为3组,对照组饲喂基础饲粮,试验1、2组分别添加15%、30%发酵酒糟,预试期15 d,正试期90 d。结果表明:与对照组相比,试验1组免疫球蛋白G(IgG)、分泌型免疫球蛋白A(SIgA)、Muribaculaceae分别显著提高了18.83%、27.99%、25.77%(P<0.05),试验1组疣微菌科UCG-010极显著降低了10.43%(P<0.01),试验2组白介素2、白介素4、白介素6、CD8、免疫球蛋白A、变形菌门、放线菌门、纤维杆菌门、疣微菌门和Muribaculaceae分别显著提高了22.22%、17.43%、19.31%、11.91%、18.91%、31.64%、41.5%、50%、42.86%和25.41%(P<0.05),试验2组瘤胃菌科显著降低了27.17%(P<0.05),试验2组CD4分子、IgG、SIgA和毛螺菌科分别极显著提高了14.53%、24.89%、38.52%和50%(P<0.01),试验2组疣微菌科UCG-010极显著降低24.51%(P<0.01)。与试验1组相比,试验2组CD4分子、毛螺菌科分别显著提高了6.01%、21.36%(P<0.05),试验2组普雷沃氏菌科显著降低了29.20%(P<0.05),试验2组疣微菌科UCG-010极显著降低了12.75%(P<0.01)。由此可见,饲粮添加30%发酵酒糟可提高西威牛的免疫力、降低炎症反应、改善十二指肠菌群,效果优于添加15%发酵酒糟。

关键词：发酵酒糟西威牛免疫肠道菌群

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浅谈呼伦贝尔蘑菇山墓地出土的汉代夹金箔玻璃珠

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草原文物 2024年第2期 104-110页

作者：马健王欣媛杜儒雯呼伦贝尔博物院呼伦贝尔历史博物馆呼伦贝尔民族博物馆

本文分析了呼伦贝尔蘑菇山墓地出土的汉代夹金箔玻璃珠的美学特征。这些珠子形态多样，夹金工艺增加了珠子的光泽度和高贵感，同时夹金层反射出的光线呈现了非常好的视觉效果。夹金箔玻璃珠在中国古代艺术史上具有重要地位，是研究汉代... 详细信息

本文分析了呼伦贝尔蘑菇山墓地出土的汉代夹金箔玻璃珠的美学特征。这些珠子形态多样，夹金工艺增加了珠子的光泽度和高贵感，同时夹金层反射出的光线呈现了非常好的视觉效果。夹金箔玻璃珠在中国古代艺术史上具有重要地位，是研究汉代玻璃艺术的珍贵实物，也是更好地理解汉代社会文化交流背景的重要实物资料。

关键词：呼伦贝尔蘑菇山汉代鲜卑夹金箔玻璃珠

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Making structured metals transparent for broadband electromagnetic waves

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Science China(Information Sciences) 2013年第12期56卷 43-51页

作者： MENG Chong PENG ruwen FAN RenHao HUANG XianRong wan. Mu National Laboratory of Solid State Microstructures and Department of Physics Nanjing University Advanced Photon Source Argonne National Laboratory Argonne Illinois 60439 USA

In this review,we present our recent work on making structured metals transparent for broadband electromagnetic waves by surface plasmons(SPs)or spoof surface plasmons(SSPs).First,we demonstrate that the interference between the localized and propagating SPs plays an important role in the optical transmission through arrays of sub-wavelength *** observed phenomena belong to the category of plasmonic Fano ***,we show that the transmission enhancement originates not only from the coupling between the incident light and the excited SPs but also from the coupling among these SPs in multiple nano-aperture ***,we demonstrate that metallic plates with narrow slit arrays can become transparent within extremely broad spectral bandwidths,and high transmission efciency is insensitive to the thickness of the *** phenomenon explicitly demonstrates the conversion between light and *** investigations provide guidelines to develop many novel materials and devices,such as transparent conducting panels,antireflective solar cells,and other broadband metamaterials.

关键词： transparent metal structures broadband transmission surface plasmons

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中医药干预慢性萎缩性胃炎“炎癌转化”研究进展

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中国医药科学 2024年第2期14卷 44-47页

作者：杨茹文蒋佳伟任南鑫席彪江苏省镇江市中医院脾胃病科江苏镇江212000

慢性萎缩性胃炎(CAG)是一种难治性消化系统疾病,在此基础上伴发的肠上皮化生、异型增生/上皮内瘤变则视为癌前病变。CAG向胃癌的演变过程被认为是炎癌转化启动、发展及转归的主要环节,癌变的发生与CAG的严重程度呈正相关。积极干预CAG... 详细信息

慢性萎缩性胃炎(CAG)是一种难治性消化系统疾病,在此基础上伴发的肠上皮化生、异型增生/上皮内瘤变则视为癌前病变。CAG向胃癌的演变过程被认为是炎癌转化启动、发展及转归的主要环节,癌变的发生与CAG的严重程度呈正相关。积极干预CAG是胃癌防治的突破口。目前现代医学对CAG“炎癌转化”的发病机制尚不明确,亦缺乏理想的治疗手段。近年来,传统医学凭借多靶点、多通路的特点,在延缓、阻断甚至逆转CAG“炎癌转化”进程方面取得了显著进展,为临床治疗提供新的理论基础和新的防治思路。本文通过梳理相关文献,从病因病机及治疗机制着手,阐述中医药干预CAG“炎癌转化”的相关研究进展,以期为临床逆转胃癌前病变、降低胃癌发生率提供更多客观理论依据。

关键词：慢性萎缩性胃炎炎癌转化中医治疗研究进展

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Impacts of exercise intervention on various diseases in rats

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Journal of Sport and Health Science 2020年第3期9卷 211-227页

作者： ruwen wan. Haili Tian Dandan Guo Qianqian Tian Ting Yao Xingxing Kong School of Kinesiology Shanghai University of SportShanghai 200438China Division of Pediatric Endocrinology Department of PediatricsUCLA Children's Discovery and Innovation InstituteDavid Geffen School of Medicine at UCLALos AngelesCA 90095USA

Background:Exercise is considered as an important intervention for treatment and prevention of several diseases,such as osteoarthritis,obesity,hypertension,and Alzheimer's *** review summarizes decadal exercise intervention studies with various rat models across 6 major systems to provide a better understanding of the mechanisms behind the effects that exercise ***:PubMed was utilized as the data *** collect research articles,we used the following terms to create the search:(exercise[Title]OR physical activity[Title]OR training[Title])AND(rats[Title/Abstract]OR rat[Title/Abstract]OR rattus[Title/Abstract]).To best cover targeted studies,publication dates were limited to"within 11 years."The exercise intervention methods used for different diseases were sorted according to the mode,frequency,and intensity of ***:The collected articles were categorized into studies related to 6 systems or disease types:motor system(17 articles),metabolic system(110 articles),cardiocerebral vascular system(171 articles),nervous system(71 articles),urinary system(2 articles),and cancer(21 articles).Our review found that,for different diseases,exercise intervention mostly had a positive ***,the most powerful effect was achieved by using a specific mode of exercise that addressed the characteristics of the ***:As a model animal,rats not only provide a convenient resource for studying human diseases but also provide the possibility for exploring the molecular mechanisms of exercise intervention on *** review also aims to provide exercise intervention frameworks and optimal exercise dose recommendations for further human exercise intervention research.

关键词： Cancer Disease Exercise intervention Method Rats System

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