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Translating bacteriophage-derived depolymerases into antibacterial therapeutics:Challenges and prospects

Acta Pharmaceutica Sinica B 2024年第1期14卷 155-169页

作者： Honglan Wang yannan liu Changqing Bai Sharon Shui Yee Leung School of Pharmacy the Chinese University of Hong KongHong Kong SARChina Emergency Medicine Clinical Research Center Beijing Chao-Yang HospitalCapital Medical UniversityBeijing 100020China Department of Respiratory Shenzhen University General HospitalShenzhen University Clinical Medical AcademyGuangdong 518055China

Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and deprotection.These depolymerases are enzymes responsible for degrading diverse bacterial surface carbohydrates.They are exploited as antibiofilm agents and antimicrobial adjuvants while rarely inducing bacterial resistance,making them an invaluable asset in the era of antibiotic resistance.Numerous depolymerases have been investigated preclinically,with evidence indicating that depolymerases with appropriate dose regimens can safely and effectively combat different multidrug-resistant pathogens in animal infection models.Additionally,some formulation approaches have been developed for improved stability and activity of depolymerases.However,depolymerase formulation is limited to liquid dosage form and remains in its infancy,posing a significant hurdle to their clinical translation,compounded by challenges in their applicability and manufacturing.Future development must address these obstacles for clinical utility.Here,after unravelling the history,diversity,and therapeutic use of depolymerases,we summarized the preclinical efficacy and existing formulation findings of recombinant depolymerases.Finally,the challenges and perspectives of depolymerases as therapeutics for humans were assessed to provide insights for their further development.

关键词： Phage-derived polysaccharide depolymerases Bacteriophage proteins Bacterial capsules Polysaccharide capsules Antibiotic resistance Biofilms Antibacterial therapy Antimicrobial adjuvants Combination treatment

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Optimal global regularity for minimal graphs over convex domains in hyperbolic space

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Frontiers of Mathematics in China 2022年第5期17卷 905-914页

作者： You LI yannan liu School of Mathematics and Statistics Beijing Technology and Business UniversityBeijing 100048China

We use the concept of the inside-(a,η,h)domain to construct a subsolution to the Dirichlet problem for minimal graphs over convex domains in hyperbolic space.As an application,we prove that the Hölder exponent max{1/... 详细信息

关键词： Minimal graph equation optimal regularity global regularity

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The advantages of crosstalk during the evolution of the BZR1–ARF6–PIF4 (BAP) module∞

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Journal of Integrative Plant Biology 2023年第12期65卷 2631-2644页

作者： Runjie Diao Mengru Zhao yannan liu Zhenhua Zhang Bojian Zhong College of Life Sciences Nanjing Normal UniversityNanjing 210023China

The BAP module,comprising BRASSINAZOLE RESISTANT 1(BZR1),AUXIN RESPONSE FACTOR 6(ARF6),and PHYTOCHROME‐INTERACTING FACTOR 4(PIF4),functions as a molecular hub to orchestrate plant growth and development.In Arabidopsis thaliana,components of the BAP module physically interact to form a complex system that integrates light,brassinosteroid(BR),and auxin signals.Little is known about the origin and evolution of the BAP module.Here,we conducted comparative genomic and transcriptomic analyses to investigate the evolution and functional diversification of the BAP module.Our results suggest that the BAP module originated in land plants and that theζ,ε,andγwhole‐genome duplication/triplication events contributed to the expansion of BAP module components in seed plants.Comparative transcriptomic analysis suggested that the prototype BAP module arose in Marchantia polymorpha,experienced stepwise evolution,and became established as a mature regulatory system in seed plants.We developed a formula to calculate the signal transduction productivity of the BAP module and demonstrate that more crosstalk among components enables higher signal transduction efficiency.Our results reveal the evolutionary history of the BAP module and provide insights into the evolution of plant signaling networks and the strategies employed by plants to integrate environmental and endogenous signals.

关键词： BAP module crosstalk origin and evolution signaling networks

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Four-birds-with-one-stone:A multifunctional Ti-based material for solar-driven water evaporation

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Nano Research 2024年第5期17卷 4498-4506页

作者： yannan Li Yaning Sun Dan Zhang Yu Xue Jie Wang Nan Zhang Jun Wang Jiangwei Zhang Yan Zhao Jun-Jie liu School of Physical Science and Technology College of Energy Materials and ChemistryInner Mongolia UniversityHohhot 010021China

Sustainable,environmentally friendly and low-energy desalination materials have important research value for the increasing demand of freshwater year by year.However,it is a huge challenge to maintain high heat energy transfer efficiency without reducing the heat conversion capacity of specific solar photothermal conversion materials.Moreover,their efficiency and durability are greatly limited by the problems of seawater corrosion,oil,and bacteria pollutions.Till now,no related work has been reported to solve all the aforementioned problems via a simple four-birds-with-one-stone strategy.Herein,a class of multifunctional porous photothermal silver(Ag)modified Ti foams(Tf-TA/Ag series materials)is prepared for the development of advanced solar water evaporation devices,and provides alternative materials for alleviating freshwater crisis and treating sewage.The oil contact angle(OCA)changes from 41°to 180°,which significantly reduces the adhesion of oil.In addition,Tf-TA2/Ag sample also shows an excellent and sustained antibacterial effect,which maintains above 99.9%of antibacterial rate after repeated 5 times.The surface temperature of the Tf-TA2/Ag sample reaches 52.5℃ after simulated sun irradiation for 20 min,which is significantly higher than that of the contact groups(water:36.4℃,Ti foam:38.2℃ and Tf-TA2:40.9℃).The capacity of seawater evaporation and salt removal is enhanced due to the excellent photothermal properties,low reflectance,and uniform heat dissipation pores.The water production efficiency of Tf-TA2/Ag sample is 1.41 kg·m^(-2)·h^(-1) in artificial seawater and 0.76 kg·m^(-2)·h^(-1) in oily sewage under simulated sun irradiation.Furthermore,the hydrophilic and oleophobic properties of Tf-TA2/Ag are critical to extracting water from oil/water mixture in diverse water environments.Ultimately,this four-birds-with-one-stone approach provides a new perspective for the improvement of solar seawater desalination performance.

关键词： four-birds-with-one-stone photothermal material antibacterial material antifouling property

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Ginsenoside Rk3 is a novel PI3K/AKT-targeting therapeutics agent that regulates autophagy and apoptosis in hepatocellular carcinoma

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Journal of Pharmaceutical Analysis 2023年第5期13卷 463-482页

作者： Linlin Qu yannan liu Jianjun Deng Xiaoxuan Ma Daidi Fan Shaanxi Key Laboratory of Degradable Biomedical Materials School of Chemical EngineeringNorthwest UniversityXi'an710069China Shaanxi R&D Centerof Biomaterials and Fermentation Engineering Schoolof Chemical EngineeringNorthwest UniversityXi'an710069China Biotech.&Biomed.Research Institute Northwest UniversityXi'an710069China Xi'an Giant Biotechnology Co. Ltd.Xi'an710076China

Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide.Ginsenoside Rk3,an important and rare saponin in heat-treated ginseng,is generated from Rg1 and has a smaller molecular weight.However,the anti-HCC efficacy and mechanisms of ginsenoside Rk3 have not yet been characterized.Here,we investigated the mechanism by which ginsenoside Rk3,a tetracyclic triterpenoid rare ginsenoside,inhibits the growth of HCC.We first explored the possible potential targets of Rk3 through network pharmacology.Both in vitro(HepG2 and HCC-LM3 cells)and in vivo(primary liver cancer mice and HCC-LM3 subcutaneous tumor-bearing mice)studies revealed that Rk3 significantly inhibits the proliferation of HCC.Meanwhile,Rk3 blocked the cell cycle in HCC at the G1 phase and induced autophagy and apoptosis in HCC.Further proteomics and siRNA experiments showed that Rk3 regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway to inhibit HCC growth,which was validated by molecular docking and surface plasmon resonance.In conclusion,we report the discovery that ginsenoside Rk3 binds to PI3K/AKT and promotes autophagy and apoptosis in HCC.Our data strongly support the translation of ginsenoside Rk3 into novel PI3K/AKT-targeting therapeutics for HCC treatment with low toxic side effects.

关键词： Hepatocellular carcinoma Ginsenoside Rk3 Apoptosis Autophagy PI3K/AKT pathway

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Origin and evolution of green plants in the light of key evolutionary events

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Journal of Integrative Plant Biology 2022年第2期64卷 516-535页

作者： Zhenhua Zhang Xiaoya Ma yannan liu Lingxiao Yang Xuan Shi Hao Wang Runjie Diao Bojian Zhong College of Life Sciences Nanjing Normal UniversityNanjing210023 China

Green plants(Viridiplantae)are ancient photosynthetic organisms that thrive both in aquatic and terrestrial ecosystems,greatly contributing to the changes in global climates and ecosystems.Significant progress has been made toward understanding the origin and evolution of green plants,and plant biologists have arrived at the consensus that green plants first originated in marine deep-water environments and later colonized fresh water and dry land.The origin of green plants,colonization of land by plants and rapid radiation of angiosperms are three key evolutionary events during the long history of green plants.However,the comprehensive understanding of evolutionary features and molecular innovations that enabled green plants to adapt to complex and changeable environments are still limited.Here,we review current knowledge of phylogenetic relationships and divergence times of green plants,and discuss key morphological innovations and distinct drivers in the evolution of green plants.Ultimately,we highlight fundamental questions to advance our understanding of the phenotypic novelty,environmental adaptation,and domestication of green plants.

关键词： adaptation divergence times green plants key innovations phylogenetics terrestrialization

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Gradient Flow for the Helfrich Functional

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数学年刊：B辑英文版 2012年第6期33卷 931-940页

作者： yannan liu Department of Mathematics Beijing Technology and Business University

The author studies the L2 gradient flow of the Helfrich functional,which is a functional describing the shapes of human red blood cells.For any λi≥0 and c0,the author obtains a lower bound on the lifespan of the smo... 详细信息

关键词：梯度流红血细胞作者溶液下界表面

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Evolution of hypersurfaces by powers of mean curvature minus an external force field

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Frontiers of Mathematics in China 2012年第4期7卷 717-723页

作者： yannan liu Department of Mathematics Beijing Technology and Business UniversityBeijing 100048China

在这份报纸，我们减一个外部力量领域由吝啬的弯曲的力量学习 hypersurfaces 的进化。我们证明当力量是 2 时，流动在一些条件下面在所有时间有一个长期的光滑的答案。那些条件是起始的 submanifolds 上的第二张基本表格不太大，与它的... 详细信息

在这份报纸，我们减一个外部力量领域由吝啬的弯曲的力量学习 hypersurfaces 的进化。我们证明当力量是 2 时，流动在一些条件下面在所有时间有一个长期的光滑的答案。那些条件是起始的 submanifolds 上的第二张基本表格不太大，与它的任何顺序衍生物，外部力量领域被围住，并且这个领域与它的特征值是凸的令人满意捏不平等。

关键词：平均曲率外力场超曲面演变权力第二基本形式子流形特征值

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In vivo oxidative stress alters thiol redox status of peroxiredoxin 1 and 6 and impairs rat sperm quality

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Asian Journal of Andrology 2017年第1期19卷 73-79页

作者： yannan liu Cristian O'Flaherty The Research Institute of the McGill University Health Centre Montreal QC H4A 3J1 Canada Department of Surgery (Urology Division) McGill University Montreal QC H4A 3J1 Canada Department of Obstetrics and Gynecology McGill University Montreal QC H4A 3J1 Canada Department of Pharmacology and Therapeutics McGill University Montreal QC H3G 1Y6 Canada

Oxidative stress, the imbalance between the production of reactive oxygen species （ROS） and antioxidant activity is a major culprit of male infertility. Peroxiredoxins （PRDXs） are major antioxidant enzymes of mammalian spermatozoa and are thiol oxidized and inactivated by ROS in a dose-dependent manner. Their deficiency and/or inactivation have been associated with men infertility. The aim of this study was to elucidate the impact of oxidative stress, generated by the in vivo tert-butyl hydroperoxide （tert-BHP） treatment on rat epididymal spermatozoa during their maturation process. Adult Sprague-Dawley males were treated with 300 -moles tert-BHP/kg or saline （control） per day intraperitoneal for 15 days. Lipid peroxidation （2-thibarbituric acid reactive substances assay）, total amount and thiol oxidation of PRDXs along with the total amount of superoxide dismutase （SOD）, motility and DNA oxidation （8-hydroxy-deoxyguanosine） were determined in epididymal spermatozoa. Total amount of PRDXs and catalase and thiol oxidation of PRDXs were determined in caput and cauda epididymis. While animals were not affected by treatment, their epididymal spermatozoa have decreased motility, increased levels of DNA oxidation and lipid peroxidation along with increased PRDXs （and not SOD） amounts. Moreover, sperm PRDXs were highly thiol oxidized. There was a differential regulation in the expression of PRDX1 and PRDX6 in the epididymis that suggests a segment-specific role for PRDXs. In conclusion, PRDXs are increased in epididymal spermatozoa in an attempt to fight against the oxidative stress generated by tert-BHP in the epididymis. These findings highlight the role of PRDXs in the protection of sperm function and DNA integrity during epididymal maturation.

关键词： antioxidant enzymes DNA oxidation epididymis reactive oxygen species spermatozoa thiol oxidation

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Research on Chaos of Nonlinear Singular Integral Equation

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Journal of Applied Mathematics and Physics 2023年第4期11卷 1152-1159页

作者： yannan liu Yu Wang School of Science Tianjin University of Technology and Education Tianjin China

In this paper, one class of nonlinear singular integral equation is discussed through Lagrange interpolation method. We research the connections between numerical solutions of the equations and chaos in the process of... 详细信息

关键词： Lagrange Interpolation Method Nonlinear Singular Integral Equation Iterative Method

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