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Harnessing antimicrobial peptide-coupled photosensitizer to combat drug-resistant biofilm infections through enhanced photodynamic therapy

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1759-1771页

作者： Duoyang Fan Xiaohui Liu Yueming Ren Ziheng Luo Yanbing Li Jie Dong seraphine vwegner Fei Chen Wenbin Zeng Xiangya School of Pharmaceutical Sciences Central South UniversityChangsha 410013China Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases Central South UniversityChangsha 410013China Sir William Dunn School of Pathology University of OxfordOxford OX13REUK Xiangya Hospital of Central South University Changsha 410013China Institute of Physiological Chemistry and Pathobiochemistry University of MünsterMünster 48149Germany

Bacterial biofilm-associated infection was one of the most serious threats to human health. However, effective drugs for drug-resistance bacteria or biofilms remain rarely reported. Here, we propose an innovative strategy to develop a multifunctional antimicrobial agent with broad-spectrum antibacterial activity by coupling photosensitizers (PSs) with antimicrobial peptides (AMPs). This strategy capitalizes on the ability of PSs to generate reactive oxygen species (ROS) and the membrane-targeting property of AMPs (KRWWKWIRW, a peptide screened by an artificial neural network), synergistically enhancing the antimicrobial activity. In addition, unlike conventional aggregation-caused quenching (ACQ) photosensitizers, aggregation-induced emission (AIE) PSs show stronger fluorescence emission in the aggregated state to help visualize the antibacterial mechanism. In vitro antibacterial experiments demonstrated the excellent killing effects of the developed agent against both Gram-positive (G^(+)) and Gram-negative (G^(–)) bacteria. The bacterial-aggregations induced ability enhanced the photoactivatable antibacterial activity against G^(–) bacteria. Notably, it exhibited a significant effect on destroying MRSA biofilms. Moreover, it also showed remarkable efficacy in treating wound infections in mice in vivo. This multifunctional antimicrobial agent holds significant potential in addressing the challenges posed by bacterial biofilm-associated infections and drug-resistant bacteria.

关键词： Photodynamic therapy Antimicrobial peptides Multidrug-resistant bacteria Aggregation-induced emission Anti-biofilm

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Genetically Encoded Copper（Ⅰ） Reporters with Improved Response for Use in Imaging

Genetically Encoded Copper（Ⅰ） Reporters with Improved Res...

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第八届全国化学生物学学术会议

作者： Jun Liu Jason Karpus seraphine v.wegner Peng R.Chen Chuan He Beijing National Laboratory for Molecular Sciences Synthetic and Functional Biomolecules CenterCollege of Chemistry and Molecular EngineeringPeking University Department of Chemistry and Institute for Biophysical Dynamics The University of Chicago

＜正＞Copper represents one of the most important biological metal ions due to its role as a catalytic cofactor in a multitude of ***,an excess of copper is highly ***,copper is heavily regulated,and copper homeostasis is controlled by many metalloregulatory proteins in various *** we report a genetically encoded copper（I） probe capable of monitoring copper fluctuations inside living cells. We insert the copper regulatory protein Ace1 into a yellow fluorescent protein,which selectively binds copper（I） and generates improved copper（I） *** have

关键词： Copper sensor Genetically-encoded

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Retrospective review of total neoadjuvant therapy

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World Journal of Gastrointestinal Oncology 2019年第10期11卷 857-865页

作者： Laila Babar veli Bakalov Stephen Abel Obaid Ashraf Gene Grant Finley Moses S Raj Kristina Lundeen Dulabh K Monga Alexander v Kirichenko Rodney E wegner Department of Internal Medicine Allegheny General HospitalPittsburghPA 15212United States Department of Radiation Oncology Allegheny General HospitalPittsburghPA 15212United States Department of Medical Oncology Allegheny General HospitalPittsburghPA 15212United States

BACKGROUND Neoadjuvant chemoradiotherapy(nCRT)followed by resection and postoperative multi-agent chemotherapy(maChT)is the standard of care for locally advanced rectal *** this approach,maChT administration can be delayed for several months,leading to concern for distant *** counteract this,a novel treatment approach known as total neoadjuvant therapy(TNT)has gained popularity,in which patients receive both maChT and nCRT prior to *** utilized the National Cancer Database to examine temporal trends in TNT usage,and any potential effect on *** To study the temporal trends in the usage of TNT and evaluate its efficacy compared to neoadjuvant *** We queried the National Cancer Database for patients with locally advanced rectal cancer,Stage II-III,from 2004-2015 treated with nCRT or *** was defined as maChT initiated≥90 d prior to nCRT *** survival was calculated from the date of diagnosis to the date of last contact or death using Kaplan-Meier curves to present the cumulative probability of survival,with logrank statistics to assess *** cox regression was used to identify predictors of survival and propensity score analysis accounted for *** We identified 9066 eligible patients,with 8812 and 254 patients receiving neoadjuvant chemoradiation followed by maChT and TNT,*** involvement,stage III disease,and treatment in recent years were predictive of TNT *** was greater use of TNT with more advanced stage,specifically>1 node involved(odds ratio[OR]=2.88,95%confidence interval[CI]:2.11-3.93,Pvant chemoradiation arms had a similar 5-year survival at 76%and 78%*** analysis with propensity score de

关键词： Total neoadjuvant therapy Neoadjuvant chemoradiation Multi-agent chemotherapy Locally advanced rectal cancer National cancer database Colorectal cancer Retrospective review Gastrointestinal oncology Temporal trends Surgical excision

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Auxetic Plate with a Crack under Shear Loading

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材料科学与工程（中英文B版） 2011年第5期1卷 565-574页

作者： Sukhwinder Kaur Bhullar Joanne wegner Andrew Mioduchowski Department of Mechanical Engineering University of Victoria Victoria B. C. V8W 3P6 Canada Department of Mechanical Engineering University of Alberta Edmonton AB T6G 2G8 Canada

Auxetic materials have special and desirable mechanical properties. For example, if the material has a crack, when it is being pulled apart, it expands and closes up the crack. A mathematical model of an infinite plate with a line crack subjected to the mechanical and thermal loading is developed to compare crack resistance to fracture of auxetic material with non auxetic material. The results are obtained for both insulating and uninsulating cracks using complex function method in the context of thermoelastic theory. Polyurethane foam (PU) is the material chosen for numerical calculations and results are presented in the graphical form.

关键词：载荷作用裂缝剪切板带复变函数方法热弹性理论聚氨酯泡沫力学性能

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Gene variants of the phosphatidylcholine synthesis pathway do not contribute to RDS in the Chinese population

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World Journal of Pediatrics 2018年第1期14卷 52-56页

作者： Yu-Jun Chen Julia Meyer Jennifer A.Wambach Kelcey DePass Daniel J.wegner Xin Fan Qun-Yuan Zhang Heins Hillary F.Sessions Cole Aaron Hamvas Neonatology the First Affliated Hospital of GuangxiMedical UniversityNanningChina Division of Newborn Medicine Edward MallinckrodtDepartment of PediatricsWashington University Schoolof MedicineSt.LouisUSA

Background To determine population-based prevalence and disease contribution of phosphatidylcholine synthetic pathway-associated gene variants in a native southern Chinese cohort. Methods We used bloodspots from 2010 that were obtained from the Guangxi Neonatal Screening Center in Nannning China and included the Han (n = 443) and Zhuang (n = 313) ethnic groups. We sequenced the exons of cholinephosphate cytidylyltransferase (PCYT1B) lysophospholipid acyltransferase 1 (LPCAT1), and cholinephosphotransferase (CHPT1) genes, and analyzed both rare and common exonic variants. Results We obtained five mutations (G199D, A299v, G434C, Y490C, L312S) with eight alleles in the three candidate genes. The collapsed minor allele frequency for candidate genes was not significantly different between the Han and Zhuang popula-tions (0.0045 vs. 0.0064, respectively,P = 0.725). The combined Han and Zhuang pool collapsed carrier frequency of rare mutation allele was found to be 1.06%, which is much higher than previously reported for the Missouri population (0.1%). Further, we detected six exonic common variants (three in LPCAT1 and three in CHPT1), with three non-synonymous vari-ants (F162S, F341L, M427K) among them. Two of the non-synonymous exonic variants (F341L, M427K) were not found in CHB;F341L was also not previously reported in exome sequencing project. Conclusions The population-based frequency of mutations in the phosphatidylcholine synthesis pathway-associated genes PCYT1B LPCAT1,CHPT1 is low in southern Chinese newborns and there is no evidence of contribution to population-based disease burden of respiratory distress syndrome. As a population-based study of rare mutations and common variants, this work is valuable in directing future research.

关键词： Genetic epidemiology Human population genetics Neonatal respiratory distress syndrome Pulmonary surfactant

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肺表面活性物质相关基因变异在中国人群的研究

肺表面活性物质相关基因变异在中国人群的研究

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中华医学会第十七次全国儿科学术大会

作者：陈玉君 Kelcey DePass Daniel J.wegner 陈少科 Jennifer A.Wambach Qunyuan Zhang F.Sessions Cole Aaron Hamvas 广西医科大学第一附属医院儿科美国圣路易斯华盛顿大学医学院儿科系广西壮族自治区妇女儿童医院儿科

目的探讨肺表面活性物质相关基因功能性变异在中国人群中的携带并与国外不同人群比较。方法以756例中国新生儿为研究对象(标本来自广西新生儿疾病筛查中心的干血片),提取基因组DNA,将每例DNA按等摩尔量混合形成混合DNA(pool-DNA),本研...

目的探讨肺表面活性物质相关基因功能性变异在中国人群中的携带并与国外不同人群比较。方法以756例中国新生儿为研究对象(标本来自广西新生儿疾病筛查中心的干血片),提取基因组DNA,将每例DNA按等摩尔量混合形成混合DNA(pool-DNA),本研究共建立4个pool-DNA。以pool-DNA为模板,以表面活性蛋白B(SFTPB)、表面活性蛋白C(SFTPC)、ATP连接盒转运子A3(ABCA3)为目的基因,应用PCR方法扩增全外显子及侧翼端,并将产物再次混合,建立测序文库,应用Illumina第二代测序平台对目的基因进行全外显子深度测序,应用SIFT和Polyphen预测软件筛选出功能性变异,应用TaqMan方法对预测的功能性变异再次进行基因型验证,应用collapsed(合并等位基因)统计分析方法 ,获取每个基因上功能性变异的等位基因频率并应用卡方检验方法将中国人群携带的功能性变异的基因频率与美国外显子检测项目(NHLBI GO Exome Sequencing Project,ESP)公布的欧洲裔人群及非洲裔人群数据进行比较。结果 1、本研究在三个目的基因中共检测出7种杂合稀有功能性变异且均发现于ABCA3基因,共包含10个变异的等位基因,有3种变异出现2次;SFTPB和SFTPC基因未发现变异;2、每个变异的等位基因在该携带的个体中只出现一次,未发现单个研究对象携带两种或两个变异的等位基因;3、在7种变异中,有2种(E292v,L654v)是既往国外研究中曾发现的变异类型,其余5种是本研究中发现的新变异类型;4、合并后ABCA3基因变异的最小等位基因频率为0.00661,显著低于欧洲裔人群(0.0248)和非洲裔人群(0.0193),P均<0.01。结论 1、肺表面活性物质基因变异属稀有低频变异,与国外研究相符;2、中国人群在肺表面活性物质相关基因变异携带率较欧洲裔和非洲裔人群低,且携带的变异类型有所差异,可能是中国人群新生儿肺透明膜病发病率较低的原因之一;3、ABCA3是主要发生变异的基因,与国外研究相似;4、第二代测序技术是发现稀有变异的有效手段

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On Auxetic versus Non-auxetic Indentation by a Rigid Conical Cylinder

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材料科学与工程（中英文版） 2011年第5期5卷 593-598页

作者： Sukhwinder Bhullar Joanne wegner Andrew Mioduchowski Department of Mechanical Engineering University of Victoria Vtctoria Canada V8W 3P6 Department of Mechanical Engineering University of Alberta Edmonton AB Canada T6G 2G8

In this paper, we consider a mathematical model of a metallic implant in a layered substrate modeled by a layer of isotropic auxetic material perfectly bonded to non-auxetic half space. The implant is considered to be rigid, undeformable conical element. The results are obtained for variety of parameters including the sizes of indenting cone and angle of contact. The resulting forces due to conical indentation are shown in graphical form and comparison is made between results for auxetic material versus non auxetic material.

关键词：锥形压痕刚性圆柱各向同性数学模型植入物半空间

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