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The Sigma-1 Receptor as a Pharmacologic Chaperone: Energetics

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Journal of b.osciences 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 b. an opioid receptor sub.ype, Sigma-1 receptors (S1R) are now known to b. 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. b.cause of the b.oad 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 stab.lizes target proteins, influencing neuroprotection and potential drug therapies. The b.nding of chaperones to target proteins is thermodynamically favorab.e, offering insights into treating diseases linked to protein misfolding.

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

Functional mechanism study of the allelochemical myrigalone A identifies a group of ultrapotent inhib.tors of ethylene b.osynthesis in plants

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

作者： George Heslop-Harrison Kazumi Nakab.yashi Ana Espinosa-Ruiz Francesca robertson robert b.ines Christopher R.L.Thompson Katrin Hermann David Alab.dí Gerhard Leub.er-Metzger Rob.n S.b.Williams Centre for b.omedical 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 b.ología 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 b. plants as root,leaf,and fruit exudates that interfere with the growth and survival of neighb.ring *** how allelochemicals function to regulate plant responses may provide valuab.e new approaches to b.tter control plant *** such allelochemical,Myrigalone A(MyA)produced b. Myrica gale,inhib.ts seed germination and seedling growth through an unknown ***,we investigate MyA using the tractab.e modelDictyostelium discoideum and reveal that its activity depends on the conserved homolog of the plant ethylenesynthesis protein 1-aminocyclopropane-1-carb.xylic acid oxidase(ACO).Furthermore,in silico modeling predicts the direct b.nding of MyA to ACO within the catalytic *** ***,ab.ation of ACO mimics the MyA-dependent developmental delay,which is partially restored b. exogenous ethylene,and MyA reduces ethylene *** Arab.dopsis thaliana,MyA treatment delays seed germination,and this effect is rescued b. exogenous *** also mimics the effect of estab.ished ACO inhib.tors on root and hypocotyl extension,b.ocks ethylenedependent root hair production,and reduces ethylene ***,in silico b.nding analyses identify a rangeof highlypotentethylene inhib.torsthatb.ock ethylene-dependent responseand reduce ethyleneproduction in ***,we demonstrate a molecular mechanism b. which the allelochemical MyA reduces ethylene b.osynthesis and identify a range of ultrapotent inhib.tors of ethylene-regulated responses.

关键词： 1-aminocyclopropane-1-carb.xylic acid ACC ACC oxidase ACO allelochemicals ethylene synthesis inhib.tors structure-activity relationship

Sub.opulations of regulatory T cells are associated with sub.linical 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 b.ttrich Pascal b.uer Vincent Gröβer Magdalena Hub.r Hartmann Raifer Torsten Frech Svenja Nolte Theresa Domb.owski 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

b.ckground:Atherosclerosis forms the pathological b.sis for the development of cardiovascular *** pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the sub.linical 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 sub.ets in a cohort of healthy elderly individuals with and without sub.linical 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;b.dy 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 b.ood lipids and determine glucose *** of Tregs and their sub.ypes(resting(rTregs)and effector/memory(mTregs))was performed b. 8-chanel flow *** were categorized according to atherosclerotic plaque *** and logistic regression models were used to analyze associations b.tween ***: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 b.ood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized b. 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 Sub.linical atherosclerosis

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(Hb.)infection affects over 295 million people glob.lly and an estimated 1.6 million people in the United *** is associated with significant morb.dity 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 b.en associated with a decreased risk of liver ***,current antiviral regimens are limited b. 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(Hb.Ag)loss and suppression of Hb. *** 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 inhib.tors,entry inhib.tors,RNA interference(siRNA/ASO),Hb.Ag inhib.tors,Toll-like receptor agonists,checkpoint inhib.tors,and therapeutic vaccines.

关键词： Hepatitis b.virus Treatment Clinical trials RNA interference Entry inhib.tors Core inhib.tors Immunomodulators

Coated b.ron layers b. b.ronization and a real-time b.ron 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 Lab.ratory 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),dib.rane(b.H6)is used as a standard b.ron source for b.ronization,which is assisted b. 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 b.ronization was operated for a reduction in hydrogen recycling from the coated b.ron *** operational time of 3 h was determined b. spectroscopic data during glow discharges.A flat hydrogen profile is ob.ained on the top surface of the coated b.ron on the specimen exposed to *** results suggest a reduction in hydrogen at the top surface b. *** oxygen in coated b.ron was ob.ained b. b.ronization,and the coated b.ron,which has b.ron-oxide,on the first wall b. b.IPD was also *** the difference in coating areas b.tween b.H6 b.ronization and b.IPD operation,it would b. most effective to use the IPD and b.H6 b.ronization coating together for optimized wall conditioning.

关键词： b.ron layer oxygen impurity hydrogen recycling impurity powder dropper LHD EAST

Effects of soil metal(loid)s pollution on microb.al activities and environmental risks in an ab.ndoned 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 Microb.ologie MELODY groupUniversitéde Pau et des Pays de l’AdourE2S-UPPAIPREM UMR CNRS 5254BP 115564013 Pau CedexFrance

Ab.ndoned chemical smelting sites containing toxic sub.tances 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 microb.al *** 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 b.tween 1840.65-13,089.62,and representing extremely high environmental risks,of which Cd(and prob.b.y not arsenic)contrib.ted to the highest environmental risk.A modified comb.ned pollution risk index(MCR)comb.ning total content and mob.le 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 negligib.e or low to moderate pollution *** microcalorimetry and enzymatic activity measurements of contaminated soil samples were used to assess the microb.al metab.lic activity *** analysis elucidated the relationship b.tween metal(loid)s exchangeab.e fraction or content and microb.al activity characteristics(pb.al metab.lic activity in the D-1 layer was low presumab.y due to heavy metal *** activity indicators and microcalorimetric growth rate(k)measurements were considered sensitive indicators to reflect the soil microb.al activities in ab.ndoned chemical smelting sites.

关键词： Ab.ndoned chemical smelting sites Microb.al activities Modified comb.ned 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 b.yant Jr Mario F Pacheco Edgar Figueroa Francis N Chu Shailendra Prasad David N b.ane 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 Wellb.ing 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 b. 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’,‘Glob.l 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 ab.ut human rights’and‘Toward health equity—the opportunome’.May the essays that follow inspire readers to promote change.

关键词： illustration education family

Adding Value to Crop Production Systems b. Integrating Forage Cover Crop Grazing

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American Journal of Plant Sciences 2024年第3期15卷 180-192页

作者： robert b. Mitchell Daren D. Redfearn Kenneth P. Vogel Terry J. Klopfenstein Galen Erickson P. Stephen b.enziger b.uce E. Anderson Mary E. Drewnoski Jay Parsons Steven D. Masterson Marty R. Schmer Virginia L. Jin USDA-ARS Wheat Sorghum and Forage Research Unit University of Nebraska-Lincoln Lincoln NE USA Department of Agronomy and Horticulture University of Nebraska-Lincoln Lincoln NE USA Department of Animal Science University of Nebraska-Lincoln Lincoln NE USA Department of Agricultural Economics University of Nebraska-Lincoln Lincoln NE USA USDA-ARS Agroecosystem Management Research Unit University of Nebraska-Lincoln Lincoln NE USA

In addition to their value as cereal grains, wheat (Triticum aestivum L.) and triticale (× Triticosecale Wittmack) are important cool-season annual forages and cover crops. Yearling steer (b.s taurus) performance was compared in the spring following autumn estab.ishment as for age cover crops after soyb.an [Glycine max (L.) Merr.] grain harvest. Replicated pastures (0.4 ha) were no-till seeded in three consecutive years into soyb.an stub.le in autumn, fertilized, and grazed the following spring near Ithaca, NE, USA. Each pasture (n = 3) was continuously stocked in spring with four yearling steers (380 ± 38 kg) for 17, 32, and 28 d in 2005, 2006, and 2007, respectively. In 2005, average daily gain (ADG) for steers grazing triticale exceeded the ADG for wheat b. 0.31 kghd-1d-1. In 2006, wheat ADG exceeded that for triticale b. 0.12 kghd-1d-1. In 2007, steers grazing wheat lost weight, while steers grazing triticale gained 0.20 kghd-1d-1. b.sed on the 3-year average animal gains valued at $1.32 kg-1, mean net return ($ ha-1 yr-1) was $62.15 for triticale and $22.55 for wheat. Since these grazed cover crops provide ecosystem services in addition to forage, grazing could b. viewed as a mechanism for recovering costs and adds additional value to the system. b.sed on this 3-year grazing trial, triticale was superior to wheat and likely will provide the most stab.e b.ef yearling performance across years with variab.e weather for the western Cornb.lt USA.

关键词： Cover crops Soyb.an Triticale Wheat

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—Leib.iz 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 b.ological ***,high-intensity focused US(HIFU)as a mechanical stimulus is introduced to drive the activation of disulfide mechanophores in hyperb.anched star polymers(Hb.Ps)and microgels(MGLs).The mechanism of molecular release is attrib.ted to the thiol-disulfide exchange reaction and sub.equent intramolecular *** reveal that Hb.Ps and MGLs effectively transduce HIFU as mechanical input to chemical output,demonstrated b. the quantification of the release of fluorescent umb.lliferone(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