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Development of an active-site titrant for SARS-CoV-2 main protease as an indispensable tool for evaluating enzyme kinetics

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2349-2357页

作者： Rabea Voget Julian Breidenbach Tobias Claff alexandra Hingst Katharina Sylvester Christian Steinebach Lan Phuong Vu Renato H.Weiße Ulrike Bartz Norbert Sträter Christa E.Müller Michael Gütschow Pharmaceutical Institute Pharmaceutical&Medicinal ChemistryUniversity of BonnBonn 53121Germany Institute of Bioanalytical Chemistry Center for Biotechnology and BiomedicineLeipzig UniversityLeipzig 04103Germany Department of Natural Sciences University of Applied Sciences Bonn-Rhein-SiegRheinbach 53359Germany

A titrant for the SARS-CoV-2 main protease(M^(pro))was developed that enables,for the first time,the exact determination of the concentration of the enzymatically active M^(pro) by active-site *** covalent binding mode of the tetrapeptidic titrant was elucidated by the determination of the crystal structure of the enzyme–titrant *** fluorogenic substrates of M^(pro),including a prototypical,internally quenched Dabcyl-EDANS peptide,were compared in terms of solubility under typical assay *** exploiting the new titrant,key kinetic parameters for the M^(pro)-catalyzed cleavage of these substrates were determined.

关键词： COVID-19 SARS-CoV-2 Main protease Peptide nitriles Fluorogenic substrates Active-site titration X-ray crystallography Inner filter effect

The Impact of Psychosocial Influences on Chronic Wound Healing

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Open Journal of Medical Psychology 2024年第3期13卷 39-57页

作者： Kelly Frasier Vivian Li Sara Christoforides Kathleen Daly alexandra Loperfito Karina Stech Milena Dragovic Nuvance Health/Vassar Brothers Medical Center Poughkeepsie NY USA Lake Erie College of Osteopathic Medicine New York NY USA Medical College of Georgia Augusta University Augusta GA USA Edward Via College of Osteopathic Medicine Blacksburg VA USA Lewis Katz School of Medicine Temple University Philadelphia PA USA College of Osteopathic Medicine California Health Sciences University Clovis CA USA

This comprehensive review explores the intricate dynamics between psychosocial factors and chronic wound healing processes, specifically focusing on prevalent conditions such as pressure ulcers, diabetic foot ulcers, and venous leg ulcers. By examining the roles of psychiatric conditions, including depression, anxiety, and post-traumatic stress disorder (PTSD), this paper illuminates how these factors intricately influence wound healing dynamics, including mechanisms of pain perception and inflammatory responses. Furthermore, we evaluate the effectiveness of integrated biopsychosocial interventions, which encompass a holistic approach to wound care, thereby enhancing healing outcomes for dermatology patients. Future studies should focus on investigating the specific psychosocial determinants that significantly influence wound healing, exploring novel therapeutic strategies, and implementing personalized interventions to meet the unique needs of each patient. Such endeavors hold promise in advancing the fields of psychodermatology and wound management, fostering a deeper understanding and application of psychosocial considerations in dermatological care.

关键词： Psychosocial Factors Chronic Wound Healing Biopsychosocial Interventions Psychiatric Conditions Dermatology Patients

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滑板公园进化正当时

商业周刊（中文版） 2024年第13期 34-38页

作者： alexandra Lange 程玺(译) 不详

在奥运会的推动下,这项街头朋克运动已经蔚为风潮,“滑板公园”这一配套设施也悄然兴起.滑板族的舞台,包括楼梯、栏杆、长凳、坡道、涵洞,乃至1970年代中期夏日旱季里那些干涸了的泳池。滑板公园往往隐匿于城市的角落:高架桥和立交桥下... 详细信息

在奥运会的推动下,这项街头朋克运动已经蔚为风潮,“滑板公园”这一配套设施也悄然兴起.滑板族的舞台,包括楼梯、栏杆、长凳、坡道、涵洞,乃至1970年代中期夏日旱季里那些干涸了的泳池。滑板公园往往隐匿于城市的角落:高架桥和立交桥下,通风管道和港口码头旁,抑或城市边陲的公园里。

关键词：港口码头通风管道高架桥和立交桥配套设施奥运会涵洞滑板

Utility of Preoperative Positron Emission Tomography (PET) in Localizing Perforator Vessels of Anterolateral Thigh Free Flap

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International Journal of Otolaryngology and Head & Neck Surgery 2024年第4期13卷 275-284页

作者： alexandra McMillan Sameer A. Alvi Zaid Al-Qurayshi Zachary Fleishacker Nitin A. Pagedar Marisa R. Buchakjian Department of Otolaryngology University of Iowa Hospitals and Clinics Iowa City IA USA Division of Otolaryngology-Head & Neck Surgery North Shore University Health System Evanston IL USA Pritzker School of Medicine The University of Chicago Chicago IL USA Holden Comprehensive Cancer Center University of Iowa Iowa City IA USA

Objectives: The anterolateral thigh (ALT) flap is often considered the workhorse in soft tissue reconstruction of head and neck defects secondary to trauma, infection, or tumor resection. Despite its many advantages, ALT flaps have been criticized due to variability in vasculature, which may result in inadequate or non-existent perforators. This retrospective study aims to investigate the utility and validity of positron emission tomography (PET) scan to identify the location and characteristics of perforators to the ALT flap. Methods: We performed a 10-year retrospective review of ALT flaps at our institution to identify patients with preoperative PET scans available for analysis. Three reviewers (attending physician, fellow, and resident) were asked to identify the number, location, and characteristics (myocutaneous versus septocutaneous) of ALT perforators on imaging, and reviewer agreement was assessed. Results were then compared to available operative data. Results: One hundred twenty-one patients were identified who underwent ALT free flap surgery. Thirty-eight preoperative PET scans were identified for review. At least one perforator was identified in 92.1% of scans. Agreement percentages regarding the number of perforators ranged from 53% - 61% whereas agreement regarding the location of a single perforator ranged from 79% - 90%. However, reviewers did not agree regarding the type of perforator, with agreement ranging from 34% - 53%. Poor agreement was observed when compared to intraoperative data, with the number of perforators ranging from 26% - 34% and the type of perforator 11% - 24%. These findings are likely due to insufficient data available in operative reports. Conclusion: Although initial studies suggest that PET scan shows promising evidence to support the capacity to preoperatively identify ALT perforators, future prospective studies are warranted to fully validate these findings.

关键词： Anterolateral Thigh Flaps Positron Emission Tomography Head and Neck Defects Perforator Mapping

Macroalgal deep genomics illuminate multiple paths to aquatic,photosynthetic multicellularity

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Molecular Plant 2024年第5期17卷 747-771页

作者： David R.Nelson alexandra Mystikou Ashish Jaiswal Cecilia Rad-Menendez Michael J.Preston Frederik De Boever Diana C.El Assal Sarah Daakour Michael W.Lomas Jean-Claude Twizere David H.Green William C.Ratcliff Kourosh Salehi-Ashtiani Division of Science and Math New York University Abu DhabiAbu DhabiUAE Center for Genomics and Systems Biology(CGSB) New York University Abu DhabiAbu DhabiUAE Biotechnology Research Center Technology Innovation InstitutePO Box 9639Masdar CityAbu DhabiUAE Culture Collection of Algae and Protozoa Scottish Association for Marine ScienceObanScotlandUK National Center for Marine Algae and Microbiota Bigelow Laboratory for Ocean SciencesEast BoothbayMEUSA Laboratory of Viral Interactomes GIGA InstituteUniversity of LiegeLiegeBelgium School of Biological Sciences Georgia Institute of TechnologyAtlantaGAUSA

Macroalgae are multicellular,aquatic autotrophs that play vital roles in global climate maintenance and have diverse applications in biotechnology and eco-engineering,which are directly linked to their multicellularity ***,their genomic diversity and the evolutionary mechanisms underlying multicellularity in these organisms remain *** this study,we sequenced 110 macroalgal genomes from diverse climates and phyla,and identified key genomic features that distinguish them from their microalgal *** for cell adhesion,extracellular matrix formation,cell polarity,transport,and cell differentiation distinguish macroalgae from microalgae across all three major phyla,constituting conserved and unique gene sets supporting multicellular *** genes show phylum-and climate-specific expansions that may facilitate niche ***,our study reveals genetic determinants of convergent and divergent evolutionary trajectories that have shaped morphological diversity in macroalgae and provides genome-wide frameworks to understand photosynthetic multicellular evolution in aquatic environments.

关键词： macroalgae multicellularity comparative genomics evolution adhesome endogenous viral elements

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带着孩子出差

科学新闻 2024年第4期 56-57页

作者： alexandra Hogan 倪伟波澳大利亚悉尼新南威尔士大学

我的职业梦想实现了。我收到一封电子邮件，通知我被任命为世界卫生组织（WHO）疫苗规划委员会成员。我很兴奋，在新冠病毒感染大流行期间，作为一名传染病建模师，我一直努力工作，想为全球疫苗政策作出贡献。但当认识到疫苗规划委员...

我的职业梦想实现了。我收到一封电子邮件，通知我被任命为世界卫生组织（WHO）疫苗规划委员会成员。我很兴奋，在新冠病毒感染大流行期间，作为一名传染病建模师，我一直努力工作，想为全球疫苗政策作出贡献。但当认识到疫苗规划委员会成员的职责时，我的心一沉。我需要从澳大利亚坐飞机24小时前往瑞士参加一个为期3天的会议。当时我正在休产假，6个月前我生了孩子，生活围绕着母乳喂养和全天候育儿。我怎么能大老远去瑞士呢？

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科技型中小企业专业培训对研发人员离职倾向的影响研究——以工作嵌入为中介变量

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西华大学学报（哲学社会科学版） 2024年第2期43卷 64-87页

作者：谷昊 alexandra Fernandes 丁奕文电子科技大学经济与管理学院四川成都611731 University Institute of Lisbon Lisbon 1649-026 成都信息工程大学管理学院四川成都610103

为寻求降低科技型中小企业研发人员离职倾向的路径,文章构建“专业培训—工作嵌入—离职倾向”的研究框架,并考虑员工性别、教育程度和职位层级的调节作用,采用大规模调查问卷的实证方法,通过数据分析发现:专业培训显著降低了研发人员... 详细信息

为寻求降低科技型中小企业研发人员离职倾向的路径,文章构建“专业培训—工作嵌入—离职倾向”的研究框架,并考虑员工性别、教育程度和职位层级的调节作用,采用大规模调查问卷的实证方法,通过数据分析发现:专业培训显著降低了研发人员离职倾向,工作嵌入发挥了中介作用,不同特征的员工接受专业培训的效果不同。文章的研究成果丰富了专业培训、工作嵌入等理论内涵并拓展其应用情境,系统地剖析了专业培训针对不同特征研发人员离职倾向的作用机制,具有深刻的理论与实践价值。

关键词：专业培训离职倾向工作嵌入员工特征科技型中小企业

Genome-wide Studies Reveal Genetic Risk Factors for Hepatic Fat Content

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Genomics, Proteomics & Bioinformatics 2024年第2期22卷 57-68页

作者： Yanni Li Eline H.van den Berg Alexander Kurilshikov Dasha V.Zhernakova Ranko Gacesa Shixian Hu Esteban A.Lopera-Maya alexandra Zhernakova Lifelines Cohort Study Vincent E.de Meijer Serena Sanna Robin P.F.Dullaart Hans Blokzijl Eleonora A.M.Festen Jingyuan Fu Rinse K.Weersma Department of Gastroenterology and Hepatology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Genetics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300052China Laboratory of Genomic Diversity Center for Computer TechnologiesITMO UniversitySaint Petersburg 199034Russia Institute of Precision Medicine the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Department of Surgery Section of Hepatobiliary Surgery and Liver TransplantationUniversity of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Endocrinology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Pediatrics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands 不详

Genetic susceptibility to metabolic associated fatty liver disease(MAFLD)is complex and poorly *** characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk *** performed genome-wide association study(GWAS)on two noninvasive definitions of hepatic fat content:magnetic resonance imaging proton density fat fraction(MRI-PDFF)in 16,050 participants and fatty liver index(FLI)in 388,701 participants from the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic fat content phenotypes were analyzed,and replicated in 10,398 participants from the University Medical Center Groningen(UMCG)Genetics Lifelines Initiative(UGLI).Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci,including two novel genomic loci harboring CREB3L1(rs72910057-T,P=5.40E−09)and GCM1(rs1491489378-T,P=3.16E−09),respectively,as well as three previously reported loci:PNPLA3,TM6SF2,and *** of FLI in UKBB identified 196 genome-wide significant loci,of which 49 were replicated in UGLI,with top signals in ZPR1(P=3.35E−13)and FTO(P=2.11E−09).Statistically significant genetic correlation(rg)between MRI-PDFF(UKBB)and FLI(UGLI)GWAS results was found(rg=0.5276,P=1.45E−03).Novel MRI-PDFF genetic signals(CREB3L1 and GCM1)were replicated in the FLI *** identified two novel genes for MRI-PDFF and 49 replicable loci for *** a difference in hepatic fat content assessment between MRI-PDFF and FLI,a substantial similar genetic architecture was *** is identified as an easy and reliable approach to study hepatic fat content at the population level.

关键词： Hepatic fat content MAFLD Genome-wide association study Fatty liver index Magnetic resonance imaging proton density fat fraction

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霉菌毒素如何威胁家禽健康和生产性能

国外畜牧学（猪与禽） 2024年第1期44卷 41-43页

作者： Kayla Price alexandra Weaver 蔡霞(译) 范美红(校) 李红(审) 不详

霉菌毒素是霉菌在受到应激或环境刺激时产生的代谢物。霉菌毒素一旦产生,就会非常稳定,在作物的整个收获、储存、加工和饲喂过程中都会残留在饲料中,对蛋鸡、种鸡和肉鸡都会造成危害。不同的霉菌会产生不同的霉菌毒素,这些霉菌毒素会影... 详细信息

霉菌毒素是霉菌在受到应激或环境刺激时产生的代谢物。霉菌毒素一旦产生,就会非常稳定,在作物的整个收获、储存、加工和饲喂过程中都会残留在饲料中,对蛋鸡、种鸡和肉鸡都会造成危害。不同的霉菌会产生不同的霉菌毒素,这些霉菌毒素会影响家禽的健康和生产性能。霉菌毒素污染是可控的,但必须采取从田间到农场的综合方法。

关键词：霉菌霉菌毒素家禽生产性能控制