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Functional mechanism study of the allelochemical myrigalone A identifies a group of ultrapotent inhibitors of ethylene biosynthesis in plants

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Plant Communications 2024年第6期5卷 246-262页

作者： George Heslop-Harrison Kazumi Nakabayashi Ana Espinosa-Ruiz Francesca robertson robert baines Christopher R.L.Thompson Katrin Hermann David Alabadí Gerhard Leubner-Metzger Robin S.b.Williams Centre for biomedical Sciences Department of Biological SciencesRoyal Holloway University of LondonEgham TW200EXUK Centre for Plant Molecular Sciences Department of Biological SciencesRoyal Holloway University of LondonEgham TW200EXUK Instituto de biología Molecular y Celular de Plantas(CSIC-UPV) 46022 ValenciaSpain Centre for Life’s Origins and Evolution Department of GeneticsEvolution and EnvironmentUniversity College LondonLondonUK Syngenta Crop Protection AGSteinSwitzerland

Allelochemicals represent a class of natural products released by plants as root,leaf,and fruit exudates that interfere with the growth and survival of neighboring *** how allelochemicals function to regulate plant responses may provide valuable new approaches to better control plant *** such allelochemical,Myrigalone A(MyA)produced by Myrica gale,inhibits seed germination and seedling growth through an unknown ***,we investigate MyA using the tractable modelDictyostelium discoideum and reveal that its activity depends on the conserved homolog of the plant ethylenesynthesis protein 1-aminocyclopropane-1-carboxylic acid oxidase(ACO).Furthermore,in silico modeling predicts the direct binding of MyA to ACO within the catalytic *** ***,ablation of ACO mimics the MyA-dependent developmental delay,which is partially restored by exogenous ethylene,and MyA reduces ethylene *** Arabidopsis thaliana,MyA treatment delays seed germination,and this effect is rescued by exogenous *** also mimics the effect of established ACO inhibitors on root and hypocotyl extension,blocks ethylenedependent root hair production,and reduces ethylene ***,in silico binding analyses identify a rangeof highlypotentethylene inhibitorsthatblock ethylene-dependent responseand reduce ethyleneproduction in ***,we demonstrate a molecular mechanism by which the allelochemical MyA reduces ethylene biosynthesis and identify a range of ultrapotent inhibitors of ethylene-regulated responses.

关键词： 1-aminocyclopropane-1-carboxylic acid ACC ACC oxidase ACO allelochemicals ethylene synthesis inhibitors structure-activity relationship

Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques,levels of LDL,and cardiorespiratory fitness in the elderly

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Journal of Sport and Health Science 2024年第3期13卷 288-296,I0002页

作者： Tim böttrich Pascal bauer Vincent Gröβer Magdalena Huber Hartmann Raifer Torsten Frech Svenja Nolte Theresa Dombrowski Franz Cemic Natascha Sommer robert Ringseis Klaus Eder Karsten Krüger Christopher Weyh Department of Exercise Physiology and Sports Therapy Institute of Sports ScienceJustus-Liebig-UniversityGiessen 35394Germany Department of Cardiology and Angiology Justus-Liebig-University GiessenGiessen 35392Germany Institute for Systems Immunology Center for Tumor und ImmunologyMarburg 35032Germany TH Mittelhessen Department of Computer ScienceUniversity of Applied Sciences GiessenGiessen 35390Germany Department of Internal Medicine Universities of Giessen and Marburg Lung Center(UGMLC)Member of the German Center for Lung Research(DZL)Giessen 35394Germany Excellence Cluster Cardio-Pulmonary Institute(CPI) Justus-Liebig UniversityGiessen 35394Germany Institute of Animal Nutrition and Nutrition Physiology Justus-Liebig-University GiessenGiessen 35390Germany

background:Atherosclerosis forms the pathological basis for the development of cardiovascular *** pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early *** is evidence that regulatory T cells(Tregs)are involved in the development of ***,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated ***:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking *** of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were ***,tests were conducted to assess blood lipids and determine glucose *** of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow *** were categorized according to atherosclerotic plaque *** and logistic regression models were used to analyze associations between ***:SAP was detected in a total of 29 *** participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and

关键词： Cardiorespiratory fitness Elderly Regulatory T cells Subclinical atherosclerosis

The Sigma-1 Receptor as a Pharmacologic Chaperone: Energetics

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Journal of biosciences and Medicines 2024年第8期12卷 347-356页

作者： robert b. Raffa Joseph V. Pergolizzi Jr. School of Pharmacy (Emeritus) Temple University Philadelphia PA USA College of Pharmacy (Adjunct) University of Arizona Tucson AZ USA NEMA Research Naples FL USA

Initially thought to be an opioid receptor subtype, Sigma-1 receptors (S1R) are now known to be unique proteins that have chaperone-like properties. As such, they play critical roles in cellular signaling, homeostasis, and cell survival. These roles offer significant insight for understanding homeostasis of normal physiologic processes, and the pathophysiologic consequences of disruption of normal function. because of the broad nature of chaperone action, S1R agonists and antagonists represent potential drug discovery goals for the pharmacotherapeutic treatment of a variety of disorders that result from dysfunctional proteins. The present study summarizes the S1R as a pharmacologic chaperone crucial for protein folding and cellular homeostasis. Through literature review and thermodynamic analysis, it explores how S1R stabilizes target proteins, influencing neuroprotection and potential drug therapies. The binding of chaperones to target proteins is thermodynamically favorable, offering insights into treating diseases linked to protein misfolding.

关键词： Chaperone Sigma-1 Receptor Energetics Thermodynamics Isothermal Titration Microcalorimetry

Advances in discovery of novel investigational agents for functional cure of chronic hepatitis b:A comprehensive review of phases II and III therapeutic agents

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World Journal of Hepatology 2024年第3期16卷 331-343页

作者： robert Lam Joseph K Lim Section of Digestive Diseases Yale University School of MedicineNew HavenCT 06520United States

Chronic hepatitis b virus(HbV)infection affects over 295 million people globally and an estimated 1.6 million people in the United *** is associated with significant morbidity and mortality due to cirrhosis,liver failure,and liver *** therapy with oral nucleos(t)ide analogues is associated with high rates of virologic suppression,which in turn has been associated with a decreased risk of liver ***,current antiviral regimens are limited by concerns with adverse effects,adherence,resistance,long-term treatment,and ongoing risk for liver *** investigational agents are currently in development and are targeted at achieving functional cure with sustained hepatitis b surface antigen(HbsAg)loss and suppression of HbV *** we review key evidence from phases II and III trials defining the efficacy and safety profiles for key investigational agents for functional cure of chronic hepatitis b,including core/capsid inhibitors,entry inhibitors,RNA interference(siRNA/ASO),HbsAg inhibitors,Toll-like receptor agonists,checkpoint inhibitors,and therapeutic vaccines.

关键词： Hepatitis b virus Treatment Clinical trials RNA interference Entry inhibitors Core inhibitors Immunomodulators

Coated boron layers by boronization and a real-time boron coating using an impurity powder dropper in the LHD

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Plasma Science and Technology 2024年第8期26卷 25-31页

作者： Naoko ASHIKAWA robert LUNSFORD Federico NESPOLI Erik GILSON Yaowei YU Jiansheng HU Shinichiro KADO National Institute for Fusion Science Toki 509-5292Japan Princeton Plasma Physics Laboratory Princeton NJ 08540United States of America Institute of Plasma Physics Chinese Academy of SciencesHefei 230031People’s Republic of China Institute of Advanced Energy Kyoto UniversityKyoto 611-0011Japan

In the Large Helical Device(LHD),diborane(b2H6)is used as a standard boron source for boronization,which is assisted by helium glow *** 2019,a new Impurity Powder Dropper(IPD)system was installed and is under evaluation as a real-time wall conditioning *** the LHD,which is a large-sized heliotron device,an additional helium(He)glow discharge cleaning(GDC)after boronization was operated for a reduction in hydrogen recycling from the coated boron *** operational time of 3 h was determined by spectroscopic data during glow discharges.A flat hydrogen profile is obtained on the top surface of the coated boron on the specimen exposed to *** results suggest a reduction in hydrogen at the top surface by *** oxygen in coated boron was obtained by boronization,and the coated boron,which has boron-oxide,on the first wall by b-IPD was also *** the difference in coating areas between b2H6 boronization and b-IPD operation,it would be most effective to use the IPD and b2H6 boronization coating together for optimized wall conditioning.

关键词： boron layer oxygen impurity hydrogen recycling impurity powder dropper LHD EAST

Effects of soil metal(loid)s pollution on microbial activities and environmental risks in an abandoned chemical smelting site

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Journal of Environmental Sciences 2024年第9期143卷 60-70页

作者： Hao Li Jun Yao Jianli Liu Ning Min Geoffrey Sunahara Dongyang Men robert Duran School of Water Resources and Environment Research Center of Environmental Science and EngineeringChina University of Geosciences(Beijing)Beijing 100083China Department of Natural Resource Sciences McGill University21111Lakeshore DriveSte-Anne-de-BellevueQuebecH9X 3V9Canada Equipe Environnement et Microbiologie MELODY groupUniversitéde Pau et des Pays de l’AdourE2S-UPPAIPREM UMR CNRS 5254BP 115564013 Pau CedexFrance

Abandoned chemical smelting sites containing toxic substances can seriously threaten and pose a risk to the surrounding ecological *** samples were collected from different depths(0 to 13 m)and analyzed for metal(loid)s content and fractionation,as well as microbial *** potential ecological risk indices for the different soil depths(ordered from high to low)were:1 m(D-1)>surface(S-0)>5 m(D-5)>13 m(D-13)>9 m(D-9),ranging between 1840.65-13,089.62,and representing extremely high environmental risks,of which Cd(and probably not arsenic)contributed to the highest environmental risk.A modified combined pollution risk index(MCR)combining total content and mobile proportion of metal(loid)s,and relative toxicities,was used to evaluate the degree of contamination and potential environmental *** the near-surface samples(S-0 and D-1 layers),the MCR considered that As,Cd,Pb,Sb,and Zn achieved high and alarming degrees of contamination,whereas Fe,Mn,and Ti were negligible or low to moderate pollution *** microcalorimetry and enzymatic activity measurements of contaminated soil samples were used to assess the microbial metabolic activity *** analysis elucidated the relationship between metal(loid)s exchangeable fraction or content and microbial activity characteristics(pbial metabolic activity in the D-1 layer was low presumably due to heavy metal *** activity indicators and microcalorimetric growth rate(k)measurements were considered sensitive indicators to reflect the soil microbial activities in abandoned chemical smelting sites.

关键词： Abandoned chemical smelting sites Microbial activities Modified combined pollution risk Microcalorimetry Enzymatic activities

Storylines of family medicine Ⅹ:standing up for diversity,equity and inclusion

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Family Medicine and Community Health 2024年第S3期12卷 89-98页

作者： William b Ventres Leslie A Stone Wayne W bryant Jr Mario F Pacheco Edgar Figueroa Francis N Chu Shailendra Prasad David N blane Na'amah Razon Ranit Mishori robert L Ferrer Garrett S Kneese Family and Preventive Medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA Family and Community Medicine University of New Mexico School of MedicineAlbuquerqueNew MexicoUSA Medicine Weill Cornell Medical CollegeNew YorkNew YorkUSA San Jose Family Medicine Residency Kaiser PermanenteSan JoseCaliforniaUSA Family Medicine and Community Health University of Minnesota Medical School—Twin Cities CampusMinneapolisMinnesotaUSA School of Health and Wellbeing University of GlasgowGlasgowUK Family and Community Medicine University of CaliforniaDavisSacramentoCaliforniaUSA Family Medicine Georgetown University School of MedicineWashingtonDistrict of ColumbiaUSA Family and Community Medicine UT Health San Antonio Long School of MedicineSan AntonioTexasUSA UC San Diego Family Medicine Residency Program San DiegoCaliforniaUSA

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine as interpreted by individual family physicians and medical educators in the USA and elsewhere around the ***‘Ⅹ:standing up for diversity,equity and inclusion’,authors address the following themes:‘The power of diversity—why inclusivity is essential to equity in healthcare’,‘Medical education for whom?’,‘Growing a diverse and inclusive workforce’,‘Therapeutic judo—an inclusive approach to patient care’,‘Global family medicine—seeing the world“upside down”’,‘The inverse care law‘,‘Social determinants of health as a lens for care’,‘Why family physicians should care about human rights’and‘Toward health equity—the opportunome’.May the essays that follow inspire readers to promote change.

关键词： illustration education family

Effect of biochar Type and bradyrhizobium japonicum Seed Inoculation on Soybean Growth, Nodulation and Yield in a Tropical Ferric Acrisol

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Agricultural Sciences 2024年第6期15卷 635-675页

作者： Gbadebo Monday Elebiyo robert Thomas bachmann Department of Crop and Soil Sciences Kwame Nkrumah University of Science and Technology Kumasi Ghana branch Campus Malaysian Institute of Chemical and bio-Engineering Technology Green Chemistry and Sustainable Engineering Technology Cluster Universiti Kuala Lumpur Alor Gajah Malaysia

In tropical environments, most soybean growth studies have utilized rice husk biochar (RHb) in soil, even though it is low in nitrogen, potassium, and phosphorous. This may not give short-term agronomic performance relative to enriched biochar. Moreover, the impact of inoculating soybean seeds with atmospheric nitrogen-fixing bacterium bradyrhizobium japonicum on nodulation and grain yield has produced inconclusive findings in the literature. This research therefore aims to assess the effect of poultry manure (PM), poultry manure biochar (PMb) and RHb alone and in combinations on grain yield, dry shoot and root biomass of soybeans in the semi-deciduous agro-ecological zone. In addition, the effect of b. japonicum inoculated and non-inoculated soybean seeds on nodulation and grain yield was also investigated. The treatments followed a split plot design studying inoculation and non-inoculation, soil amendments (eight), and control subplot factors, respectively. The results show that the amendment of a ferric acrisol with 4 Mg∙ha−1 PM, 10 Mg∙ha−1 RHb + 2 Mg∙ha−1 PM, and 5 Mg∙ha−1 RHb + 4 Mg∙ha−1 PMb with b. japonicum inoculated seed produced significantly greater grain yield (p = 0.05). PM treatment had a significant (p b. japonicum-inoculated soybean seeds significantly (p = 0.014) increased soybean nodulation. This study suggests that RHb combined with PM or PMb provides a beneficial source of N, P, and K, resulting in improved soybean yield and nodulation in a tropical ferric acrisol.

关键词： biochar Poultry Manure Soil Fertility Soil Microorganism Soybean Production

High-Intensity Focused Ultrasound-Induced Disulfide Mechanophore Activation in Polymeric Nanostructures for Molecule Release

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CCS Chemistry 2024年第8期6卷 1895-1907页

作者： Jilin Fan Kuan Zhang Mingjun Xuan Xiang Gao Rostislav Vinokur robert Göstl Lifei Zheng Andreas Herrmann DWI—Leibniz Institute for Interactive Materials 52056 Aachen Institute of Technical and Macromolecular Chemistry RWTH Aachen University52074 Aachen Wenzhou Institute University of Chinese Academy of Sciences325001 Wenzhou

Ultrasound(US)activation of mechanophores in polymers that initiates cascade chemical reactions is a promising strategy for on-demand molecule ***,the typical US frequency used for mechanochemistry is around 20 kHz,producing inertial cavitation that exceeds the tolerance threshold of biological ***,high-intensity focused US(HIFU)as a mechanical stimulus is introduced to drive the activation of disulfide mechanophores in hyperbranched star polymers(HbSPs)and microgels(MGLs).The mechanism of molecular release is attributed to the thiol-disulfide exchange reaction and subsequent intramolecular *** reveal that HbSPs and MGLs effectively transduce HIFU as mechanical input to chemical output,demonstrated by the quantification of the release of fluorescent umbelliferone(UMb).Moreover,an in vitro study of drug release is carried out using camptothecin as the model drug,which is covalently loaded in MGLs,demonstrating the potential of our system for controlled drug delivery to cancer cells.

关键词： mechanophores polymer mechanochemistry polymeric nanostructures ultrasound drug release sonopharmacology