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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 *** depolymerases are enzymes responsible for degrading diverse bacterial surface *** are exploited as antibiofilm agents and antimicrobial adjuvants while rarely inducing bacterial resistance,making them an invaluable asset in the era of antibiotic *** 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 ***,some formulation approaches have been developed for improved stability and activity of ***,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 *** development must address these obstacles for clinical ***,after unravelling the history,diversity,and therapeutic use of depolymerases,we summarized the preclinical efficacy and existing formulation findings of recombinant ***,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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Ginsenoside Rk3 modulates gut microbiota and regulates immune response of group 3 innate lymphoid cells to against colorectal tumorigenesis

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Journal of Pharmaceutical Analysis 2024年第2期14卷 259-275页

作者： Xue Bai Rongzhan Fu yannan liu Jianjun Deng Qiang Fei Zhiguang Duan Chenhui Zhu Daidi Fan Shaanxi Key Laboratory of Degradable Biomedical Materials School of Chemical EngineeringNorthwest UniversityXi'an710069China Biotech&Biomed Research Institute Northwest UniversityXi'an710069China School of Chemical Engineering and Technology Xi'an Jiaotong UniversityXi'an710069China

The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer(CRC).However,the effect of ginsenoside Rk3(Rk3)on CRC and gut microbiota remains ***,the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune *** results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors,repairs intestinal barrier damage,and regulates the gut microbiota imbalance caused by CRC,including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis,and clearance of pathogenic *** metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids,particularly by upregulating glutamine,which has the potential to regulate the immune ***,we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells(ILC3s)and T helper 17(Th17)signaling pathways,which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3(JAK-STAT3)signaling *** results indicate that Rk3 modulates gut microbiota,regulates ILC3s immune response,and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon *** importantly,the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut *** summary,these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.

关键词： Colorectal cancer Ginsenoside Immune cells Gut microbiota

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高职产业学院发展的运行逻辑与治理机制——基于交易成本的理论视角

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教育发展研究 2024年第1期44卷 58-66页

作者：刘燕楠贾天枝池春阳温州大学教育学院温州305000 温州职业技术学院温州305000

产业学院是高职院校产教融合、校企合作、协同育人的新型组织形态,只有将企业的产业、科技与技术等资源要素与学校的教育资源优势在产业学院这一组织形态中融合,才能建立产教融合、协同育人的新机制。以交易成本经济学为视角,运用交易... 详细信息

产业学院是高职院校产教融合、校企合作、协同育人的新型组织形态,只有将企业的产业、科技与技术等资源要素与学校的教育资源优势在产业学院这一组织形态中融合,才能建立产教融合、协同育人的新机制。以交易成本经济学为视角,运用交易成本理论重构高职产业学院的治理机制,通过建立科层治理、文化治理、绩效治理、关系治理等多元治理机制,为学院发展的多重主体提供理性选择,从而解决产业学院在合作发展中的矛盾与困境,提高交易效率,降低交易成本,构建我国职业教育发展的新格局。

关键词：产业学院交易成本高职院校产教融合治理机制

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Gradient Flow for the Helfrich Functional

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Chinese Annals of Mathematics,Series B 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 co, the author obtains a lower bound on the lifespan of th... 详细信息

关键词： Geometric evolution equation Fourth order Energy estimate

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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

In this paper, we study the evolution of hypersurfaces by powers of mean curvature minus an external force field. We prove that when the power is 2, the flow has a long-time smooth solution for all time under some conditions. Those conditions are that the second fundamental form on the initial submanifolds is not too large, the external force field, with its any order derivatives, is bounded, and the field is convex with its eigenvalues satisfying a pinch inequality.

关键词： Parabolic equation mean curvature flow maximum principle (for tensor)

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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 *** an application,we prove that the Hölder exponent max{1/a,1/(... 详细信息

关键词： Minimal graph equation optimal regularity global regularity

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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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A curve flow evolved by a fourth order parabolic equation

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Science China Mathematics 2009年第10期52卷 2177-2184页

作者： liu yannan JIAN HuaiYu School of computer science and information engineering Beijing Technology and Business UniversityBeijing 100048China Department of Mathematical Sciences Tsinghua UniversityBeijing 100084China

We study a fourth order curve flow, which is the gradient flow of a functional describing the shapes of human red blood cells. We prove that for any smooth closed initial curve in ?2, the flow has a smooth solution fo... 详细信息

关键词： geometric evolution equations fourth order energy estimate 35J60 35K45 52K44 53A05

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去势抵抗性前列腺癌患者血清TRAF6、CGRP水平与骨转移及预后的关系

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现代肿瘤医学 2024年第19期32卷 3752-3756页

作者：景琼刘燕南庆阳市人民医院泌尿外科甘肃庆阳745000

目的:探讨TNF受体相关因子6(TNF receptor-associated factor 6,TRAF6)、神经元降钙素基因相关肽(neuronal calcitonin gene-related peptide,CGRP)与老年去势抵抗性前列腺癌患者骨转移以及预后的关系分析。方法:选择2020年01月至2023年01月我院收治的157例老年去势抵抗性前列腺癌患者(前列腺癌组)和101例健康志愿者(对照组),根据是否发生骨转移分为骨转移(84例)和非骨转移组(73例)。检测血清TRAF6、CGRP水平,出院后随访去势抵抗性前列腺癌患者生存情况。结果:前列腺癌组血清TRAF6、CGRP水平高于对照组(P<0.01)。Gleason评分≥8分、TNM分期Ⅲc-Ⅳb期去势抵抗性前列腺癌患者血清TRAF6、CGRP水平高于Gleason评分<8分、TNM分期Ⅲa-Ⅲb期期患者(P<0.05)。骨转移组血清TRAF6、CGRP水平高于非骨转移组(P<0.01)。Kaplan-Meier生存分析显示高TRAF6水平组、高CGRP水平组OS生存率低于低RAF6水平组、低CGRP水平组(P<0.05)。多因素COX回归分析结果显示TNM分期Ⅲc-Ⅳb期、骨转移、高水平TRAF6、高水平CGRP是去势抵抗性前列腺癌患者预后的危险因素(P<0.05)。结论:老年前列腺癌患者血清TRAF6、CGRP水平增高与前列腺癌恶性临床病理特征、骨转移和不良预后有关,可作为骨转移和预后评估的标志物。

关键词：前列腺癌骨转移预后 TNF受体相关因子6 神经元降钙素基因相关肽

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结节性硬化症相关神经精神障碍研究进展

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中华实用儿科临床杂志 2024年第9期39卷 697-700页

作者：付洁刘砚南张根福杨志仙秦炯北京大学人民医院儿科北京100044 北京大学人民医院癫痫中心北京100044

结节性硬化症(TSC)是一种罕见的常染色体显性遗传病,皮肤和中枢神经系统最常受累,可累及心脏、肺、肾等多个器官。绝大多数TSC患者在一生中会出现一些神经精神症状,包括行为、精神、智力、学习、神经心理及心理社会功能障碍,统称为TSC... 详细信息

结节性硬化症(TSC)是一种罕见的常染色体显性遗传病,皮肤和中枢神经系统最常受累,可累及心脏、肺、肾等多个器官。绝大多数TSC患者在一生中会出现一些神经精神症状,包括行为、精神、智力、学习、神经心理及心理社会功能障碍,统称为TSC相关神经精神障碍(TAND)。TAND清单作为一种筛查工具,通过指导TSC患者及家属与临床医师之间进行对话来识别所有潜在的神经精神障碍。现围绕TAND的概念、研究历史及筛查工具TAND清单进行综述,以期为临床开展全面系统的评估及了解患儿预后提供帮助。

关键词：结节性硬化症神经精神障碍性疾病结节性硬化症相关神经精神障碍清单

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