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Structure-guided manipulation of the regioselectivity of the cyclosporine A hydroxylase CYP-sb21 from Sebekia benihana

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Synthetic and Systems Biotechnology 2020年第3期5卷 236-243页

作者： Fengwei Li Li Ma Xingwang Zhang Jingfei Chen Feifei Qi Yinyue Huang zepeng qu Lishan Yao Wei Zhang Eung-Soo Kim Shengying Li State Key Laboratory of Microbial Technology Shandong UniversityQingdaoShandong266237China Shandong Provincial Key Laboratory of Synthetic Biology CAS Key Laboratory of BiofuelsQingdao Institute of Bioenergy and Bioprocess TechnologyChinese Academy of SciencesQingdaoShandong266101China Department of Biological Engineering Inha UniversityIncheon22212South Korea Laboratory for Marine Biology and Biotechnology Qingdao National Laboratory for Marine Science and TechnologyQingdaoShandong266237China

The cytochrome P450 enzyme CYP-sb21 from the rare actinomycete Sebekia benihana is capable of hydroxylating the immunosuppressive drug molecule cyclosporine A(CsA)primarily at the 4th N-methyl leucine(MeLeu4),giving rise toγ-hydroxy-N-methyl-L-Leu4-CsA(CsA-4-OH).This oxidative modification of CsA leads to dramatically reduced immunosuppressive activity while retaining the hair growth-promoting side-effect,thus demonstrating great application potential in both pharmaceutical and cosmetic ***,this P450 enzyme also hydroxylates CsA at the unwanted position of the 9th N-methyl leucine(MeLeu9),indicating that the regioselectivity needs to be improved for the development of CsA-4-OH into a commercial hair growth ***,we report the crystal structure of CYP-sb21 in its substrate-free form at 1.85Å.Together with sequence and 3D structure comparisons,Autodock-based substrate docking,molecular dynamics(MD)simulation,and site-directed mutagenesis,we identified a number of key residues including R294,E264,and M179 that can improve catalytic efficiency or change the regioselectivity of CYP-sb21 towards CsA,setting the stage for better enzymatic preparation of *** study also provides new insights into the substrate recognition and binding mechanism of P450 enzymes that accommodate bulky substrates.

关键词： Cytochrome P450 monooxygenase Crystal structure Cyclosporine A Regioselectivity Hair growth stimulator

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城市慢行交通发展问题和对策研究

物流科技 2023年第2期46卷 92-94页

作者：曲泽鹏山东建筑大学山东济南250101

我国城市交通规划一直以来是以机动车通行效率为首要目标,因此慢行交通系统一直处于缓慢发展的状态,没能发挥应有的作用。文章结合当前交通系统和现实生活中遇到的情况等方面分析了慢行交通系统存在的一些问题,又针对这些问题提出了一... 详细信息

我国城市交通规划一直以来是以机动车通行效率为首要目标,因此慢行交通系统一直处于缓慢发展的状态,没能发挥应有的作用。文章结合当前交通系统和现实生活中遇到的情况等方面分析了慢行交通系统存在的一些问题,又针对这些问题提出了一些解决对策。

关键词：慢行交通问题规划对策

转基因猪骨髓间充质干细胞的分离及与猪胰岛的共培养研究

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器官移植 2024年第1期15卷 55-62页

作者：朱淑芳曲泽澎陆赢潘登科牟丽莎广西中医药大学南宁530200 深圳市第二人民医院深圳转化医学研究院四川省医学科学院四川省人民医院临床免疫转化医学四川省重点实验室

目的探讨α-1,3-半乳糖基转移酶(GGTA1)基因敲除(GTKO)、GTKO/人补体调节蛋白hCD46插入、单磷酸胞嘧啶-N-乙酰神经氨酸羟化酶(CMAH)/GGTA1双基因敲除(Neu5GC/Gal)猪骨髓间充质干细胞(BMSC)的分离培养,以及与猪胰岛共培养对胰岛的保护作... 详细信息

目的探讨α-1,3-半乳糖基转移酶(GGTA1)基因敲除(GTKO)、GTKO/人补体调节蛋白hCD46插入、单磷酸胞嘧啶-N-乙酰神经氨酸羟化酶(CMAH)/GGTA1双基因敲除(Neu5GC/Gal)猪骨髓间充质干细胞(BMSC)的分离培养,以及与猪胰岛共培养对胰岛的保护作用。方法从不同转基因修饰GTKO、GTKO/hCD46及Neu5GC/Gal猪中提取骨髓,采用全骨髓法分离猪BMSC后进行培养。对BMSC进行形态学观察,并使用流式细胞术鉴定BMSC表面标志物。同时,观察BMSC诱导的多向分化,通过绿色荧光蛋白(GFP)转染标记猪BMSC来实现对BMSC的标记和示踪。将GFP转染标记的猪BMSC与猪胰岛细胞共培养,观察猪胰岛形态变化,与单纯猪胰岛细胞培养组进行比较。结果猪来源的BMSC在体外培养时呈梭形,表达标志物CD29、CD44、CD73、CD90、CD105及CD166,不表达CD34、CD45,具有向脂肪细胞、成骨细胞、软骨细胞分化的能力;通过GFP转染标记的猪BMSC能够实现BMSC的标记和示踪,且在细胞分裂后的子代细胞中也能够稳定表达。猪BMSC对胰岛细胞有一定保护能力。结论成功建立了GFP标记的GTKO、GTKO/hCD46及Neu5GC/Gal猪来源的BMSC,其对胰岛细胞具有一定的保护能力。

关键词：胰岛移植 1型糖尿病间充质干细胞基因修饰猪分离鉴定共培养排斥反应

电辅助膜生物反应器体系中Co纳米催化膜处理焦化废水研究

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环境科学研究 2021年第5期34卷 1129-1138页

作者：安路阳宋迪慧杨爽张立涛屈泽鹏李红欣柳丽芬中钢集团鞍山热能研究院有限公司辽宁省钢铁行业废水深度处理技术工程研究中心环境工程院士专家工作站辽宁鞍山114044 大连理工大学辽宁大连116024

为探究电辅助膜生物反应器(electrical membrane bioreactor, EMBR)处理难降解有机废水的效果、产电性能及抗膜污染性能,以金属有机骨架化合物(metal-organic frameworks, MOFs)为前驱体,通过碳化制备具有高催化氧还原(oxygen reduction... 详细信息

为探究电辅助膜生物反应器(electrical membrane bioreactor, EMBR)处理难降解有机废水的效果、产电性能及抗膜污染性能,以金属有机骨架化合物(metal-organic frameworks, MOFs)为前驱体,通过碳化制备具有高催化氧还原(oxygen reduction reaction, ORR)活性的负载Co纳米颗粒的氮掺杂碳催化剂(Co-NPs),以碳纤维布作为基体组装Co-NPs/PVDF碳纤维基催化膜,并构建催化膜耦合EMBR体系处理实际焦化废水.考察碳化温度、Co/N协同作用、N掺杂含量及形态对ORR活性的影响,探究了催化膜在EMBR体系中处理实际焦化废水的污染物去除效率、抗污染特性和产能效果.结果表明:①Co-NPs的ORR反应为4电子转移还原途径,还原产物为水.②Co-NPs/PVDF碳纤维基催化膜在微电场下保持稳定的高膜通量.催化膜污染在运行初期符合膜孔堵塞模型,后期表现为滤饼层污染模型控制,膜污染以滤饼层污染为主.微电场可以降低滤饼层比阻,能有效解决膜污染问题.③EMBR体系处理实际焦化废水,COD、TN、NH_(4)^(+)-N和挥发酚的去除率分别为97.2%、43.8%、82.9%和99.8%.④系统最大产电功率密度为823.8 mW/m^(3),库仑效率为8.3%.研究显示,以MOFs为前驱体制备的Co-NPs纳米催化剂,以碳纤维布作为基体制备Co-NPs/PVDF碳纤维基催化膜,耦合EMBR体系在焦化废水处理过程中表现出了高效的污染物降解效率、能源转化效率,并且微电场环境可达到抗膜污染效果.

关键词：电辅助膜生物反应器金属有机骨架纳米材料催化剂膜焦化废水

厌氧E-MBR反应器在焦化废水处理中的微生物特性研究

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微生物学报 2021年第8期61卷 2427-2441页

作者：杨爽宋迪慧安路阳张立涛柳丽芬屈泽鹏徐歆未李红欣中钢集团鞍山热能研究院有限公司环境工程院士专家工作站辽宁省钢铁行业废水深度处理技术工程研究中心辽宁鞍山1140002 大连理工大学海洋科学与技术学院辽宁大连116000

【目的】将厌氧的膜生物反应器(MBR)与微生物燃料电池(MFC)耦合的厌氧电辅助膜生物反应器(E-MBR)应用于实际工业焦化废水处理。【方法】通过正交实验优化了反应器进水的培养条件为PO_(4)^(3-)14.3 mg/L、Fe^(2+)0.2 mg/L、Fe^(3+)0.1 m... 详细信息

【目的】将厌氧的膜生物反应器(MBR)与微生物燃料电池(MFC)耦合的厌氧电辅助膜生物反应器(E-MBR)应用于实际工业焦化废水处理。【方法】通过正交实验优化了反应器进水的培养条件为PO_(4)^(3-)14.3 mg/L、Fe^(2+)0.2 mg/L、Fe^(3+)0.1 mg/L、Co^(2+)0.1 mg/L和Mn^(2+)0.2 mg/L。在此条件下考察了该反应器对系统中有机污染物的去除效率及厌氧污泥的污泥特性、产电性能、胞外聚合物(EPS)、微生物群落结构及膜污染的影响。【结果】结果表明,与未优化的培养条件相比,工业焦化废水COD的去除率提高了23%;污泥浓度(MLSS)、比重、沉降速度增加,污泥体积指数(SVI)降低,表明污泥颗粒化及沉降性能提高;污泥中溶解性EPS(SMP)、松散态EPS(LB-EPS)及紧密结合态EPS(TB-EPS)这3种组分中的蛋白质与多糖的比例(P/C)分别降低0.12、0.25和0.16,表明污泥更易于被降解;厌氧污泥的产电性能增强;高通量分子测序结果表明,反应器中污泥的群落结构发生了明显的变化,优势菌群突出;经扫描电镜(SEM)对比结果表明,反应器阴极膜的污染情况也得到了一定的减缓。【结论】优化进水培养条件可以达到使反应器污水处理效率提高、清理周期缩短和运行更稳定等效果,对于工业废水处理技术的节能环保方面提供一定的理论依据。

关键词：厌氧电辅助膜生物反应器正交优化实验污泥特性导电性能微生物群落结构膜污染

Self-reinforced Calcium Phosphate Cement Inspired by Sea Cucumber Dermis

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Journal of Wuhan University of Technology(Materials Science) 2024年第3期39卷 682-688页

作者：吴治文 WANG Zihao CAI zepeng qu Liting 于涛 College of Chemistry and Materials Science Jinan UniversityGuangzhou 510632China Guangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction The Fifth Affiliated Hospital(Heyuan Shenhe People’s Hospital)Jinan UniversityHeyuan 517000China

A composite bone cement based onα-TCP with self-reinforcing characteristics is prepared by compounding cellulose whiskers and polyvinyl alcohol in different *** this system,we are inspired by the sea cucumber,which can alter the stiffness of their inner dermis *** the formation of hydrogen bonds between the hydroxyl groups on the cellulose whiskers and PVA,the bone cement matrix can be strengthened during the curing process of *** the process of bone cement blending,there is more water,the hydrogen bond connection is destroyed,so the slurry has better fluidity at this *** the hydration of the bone cement progresses,the reduction of the water phase leads to the formation of a permeable network structure of hydrogen bond connections between the *** dual-phase action of PVA and whiskers greatly increases the mechanical strength of the bone cement system(5.5 to 23.8 MPa),while the presence of polyvinyl alcohol improves the toughness of the bone cement *** work was supposed to explore whether the chemoresponsive materials can be adapted to biomedical materials,for example,bone repair.

关键词： bone repair self-reinforce chemoresponsive hydrogen bond

Unraveling brain aging through the lens of oral microbiota

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Neural Regeneration Research 2025年第7期20卷 1930-1943页

作者： Qinchao Hu Si Wang Weiqi Zhang Jing qu Guang-Hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of Sciences BeijingChina Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijingChina Aging Biomarker Consortium BeijingChina State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing Institute for Stem Cell and Regenerative Medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis

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合成微生物群落研究进展

合成生物学 2020年第6期1卷 621-634页

作者：曲泽鹏陈沫先曹朝辉左文龙陈业戴磊中国科学院深圳先进技术研究院深圳合成生物学创新研究院中国科学院定量工程生物学重点实验室广东深圳518055

合成微生物群落属于合成生物学和微生物组学的交叉领域,是新兴的研究方向。合成微生物群落是人工合成的多个物种共培养的微生物体系,具有组成明确、可操控性高等特点,在研究微生物组的功能和生态机制方面有着明显的优势。本文将从以下... 详细信息

合成微生物群落属于合成生物学和微生物组学的交叉领域,是新兴的研究方向。合成微生物群落是人工合成的多个物种共培养的微生物体系,具有组成明确、可操控性高等特点,在研究微生物组的功能和生态机制方面有着明显的优势。本文将从以下几个方面介绍合成微生物群落的研究进展:①微生物群落生态学,包括微生物之间的相互作用、宿主和其他环境因素对群落结构的影响;②合成微生物群落的研究方法,围绕设计-构建-测试-学习循环;③合成微生物群落在多个领域的应用,包括人体疾病治疗、植物抗逆、工业生产、环境修复等多个领域。最后,提出了合成微生物群落领域有待解决的重要问题,包括如何构建可控和稳定的微生物互作网络、如何表征和控制微生物群落的空间结构以及如何精准地控制微生物群落的功能。

关键词：合成微生物群落微生物组工程菌群相互作用微生物组学合成生物学

Dynamic Regulation of Hydrogen Bonding Networks and Solvation Structures for Synergistic Solar‑Thermal Desalination of Seawater and Catalytic Degradation of Organic Pollutants

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Nano-Micro Letters 2025年第2期17卷 548-565页

作者： Ming‑Yuan Yu Jing Wu Guang Yin Fan‑Zhen Jiao Zhong‑Zhen Yu Jin qu Beijing Key Laboratory of Advanced Functional Polymer Composites Beijing University of Chemical TechnologyBeijing 100029People’s Republic of China State Key Laboratory of Organic‑Inorganic Composites College of Materials Science and EngineeringBeijing University of Chemical TechnologyBeijing 100029People’s Republic of China

Although solar steam generation strategy is efficient in desalinating seawater,it is still challenging to achieve continuous solar-thermal desalination of seawater and catalytic degradation of organic ***,dynamic regulations of hydrogen bonding networks and solvation structures are realized by designing an asymmetric bilayer membrane consisting of a bacterial cellulose/carbon nanotube/Co_(2)(OH)_(2)CO_(3)nanorod top layer and a bacterial cellulose/Co_(2)(OH)_(2)CO_(3)nanorod(BCH)bottom ***,the hydrogen bonding networks inside the membrane can be tuned by the rich surface–OH groups of the bacterial cellulose and Co_(2)(OH)_(2)CO_(3)as well as the ions and radicals in situ generated during the catalysis ***,both SO_(4)^(2−)and HSO_(5)−can regulate the solvation structure of Na^(+)and be adsorbed more preferentially on the evaporation surface than Cl^(−),thus hindering the de-solvation of the solvated Na^(+)and subsequent nucleation/growth of ***,the heat generated by the solar-thermal energy conversion can accelerate the reaction kinetics and enhance the catalytic degradation *** work provides a flow-bed water purification system with an asymmetric solar-thermal and catalytic membrane for synergistic solar thermal desalination of seawater/brine and catalytic degradation of organic pollutants.

关键词： Solar steam generation Seawater desalination Catalytic degradation Bacterial cellulose Cobalt hydroxycarbonate nanorods