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High-throughput screening against thioredoxin glutathione reductase identifies novel inhibitors with potential therapeutic value for schistosomiasis

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Infectious Diseases of Poverty 2015年第1期4卷 300-315页

作者： Ting li Peter D.Ziniel Pan-qing He Valerie P.Kommer gregory J.Crowther Min He Qing liu Wesley C.Van Voorhis David l.Williams Ming-Wei Wang The National Center for Drug Screening Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Immunology and Microbiology Rush University Medical CenterChicagoIL 60612USA Division of Allergy and Infectious Diseases University of WashingtonSeattleWA 98195USA

Background:Schistosomiasis,a parasitic disease also known as bilharzia and snail fever,is caused by different species of flatworms,such as Schistosoma mansoni(***).Thioredoxin glutathione reductase(TGR)from ***(SmTGR)is a well-characterized drug target for schistosomiasis,yet no anti-SmTGR compounds have reached clinical trials,suggesting that therapeutic development against schistosomiasis might benefit from additional scaffolds targeting this ***:A high-throughput screening(HTS)assay in vitro against SmTGR was developed and applied to a diverse compound *** activity was quantified with ThioGlo®,a reagent that fluoresces upon binding to the free sulfhydryl groups of the reaction product GSH(reduced glutathione).Results:We implemented an HTS effort against 59,360 synthetic *** the primary screening,initial hits(928 or 1.56%)showing greater than 90%inhibition on SmTGR activity at a final concentration of 10μM for each compound were *** tests were carried out to confirm the effects of these hits and to explore the concentration-dependent response *** a result,74 of them(0.12%)representing 17 chemical scaffolds were confirmed and showed a great concentration-dependent inhibitory trend against SmTGR,including structures previously shown to be lethal to schistosomal *** these,two scaffolds displayed a limited structure-activity *** tested in cultured larvae,39 compounds had cidal activity in 48 h,and five of them killed larvae completely at 3.125μ*** these,three compounds also killed adult worms ex vivo at concentrations between 5μM and 10μ***:These confirmed hits may serve as starting points for the development of novel therapeutics to combat schistosomiasis.

关键词： High-throughput screening Schistosomiasis Inhibitor Thioredoxin glutathione reductase

Self-healable stretchable printed electronic cryogels for in-vivo plant monitoring

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npj Flexible Electronics 2023年第1期7卷 59-69页

作者： Eloïse Bihar Elliot J.Strand Catherine A.Crichton Megan N.Renny Ignacy Bonter Tai Tran Madhur Atreya Adrian Gestos Jim Haseloff Robert R.Mcleod gregory l.Whiting Paul M.Rady Department of Mechanical Engineering University of Colorado Boulder1111 Engineering DriveBoulderCO 80309USA Materials Science and Engineering University of Colorado Boulder4001 Discovery DriveBoulderCO 80303USA Department of Plant Sciences University of CambridgeDowning StreetCambridge CB23EAUK Materials Instrumentation and Multimodal Imaging Core Facility University of Colorado Boulder1111 Engineering Drive BoulderBoulderCO 80309USA Department of Electrical Computerand Energy EngineeringUniversity of Colorado Boulder1111 Engineering DriveBoulderCO 80309USA

A key challenge in bioelectronics is to establish and improve the interface between electronic devices and living tissues,enabling a direct assessment of biological *** integrated with plant tissue can provide valuable information about the plant itself as well as the surrounding environment,including air and soil *** obstacle in developing interfaces to plant tissue is mitigating the formation of fibrotic tissues,which can hinder continuous and accurate sensor operation over extended *** systems that utilize suitable biocompatible materials alongside appropriate fabrication techniques to establish plantelectronic interfaces could provide for enhanced environmental understanding and ecosystem management *** meet these demands,this study introduces an approach for integrating printed electronic materials with biocompatible cryogels,resulting in stable implantable hydrogel-based bioelectronic devices capable of long-term operation within plant *** inkjet-printed cryogels can be customized to provide various electronic functionalities,including electrodes and organic electrochemical transistors(OECTs),that exhibit high electrical conductivity for embedded conducting polymer traces(up to 350 S/cm),transconductance for OECTs in the mS range,a capacitance of up to 4.2mF g−1 in suitable structures,high stretchability(up to 330%strain),and selfhealing *** biocompatible functionalized cryogel-based electrodes and transistors were successfully implanted in plant tissue,and ionic activity in tomato plant stems was collected for over two months with minimal scar tissue formation,making these cryogel-based printed electronic devices excellent candidates for continuous,in-situ monitoring of plant and environmental status and health.

关键词： electronic utilize integrating

Nanostructured 3-D Collagen/Nanotube Biocomposites for Future Bone Regeneration Scaffolds

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Nano Research 2009年第6期2卷 462-473页

作者： Edelma E.da Silva Heloisa H.M.Della Colleta Andre S.Ferlauto Roberto l.Moreira Rodrigo R.Resende Sergio Oliveira gregory T.Kitten Rodrigo G.lacerda luiz O.ladeira Universidade Federal de Minas Gerais Departamento de FísicaLaboratório de NanomateriaisAv.Antônio Carlos662730123-970Belo HorizonteMGBrazil Universidade Federal de Minas Gerais Departamento de MorfologiaAv.Antônio Carlos662730123-970Belo HorizonteMGBrazil

The fi eld of bionanotechnology has been rapidly growing during the last few years and we can now envision a controllable integration between biological and artificial matter,where new biomimetic structures with a wide range of chemical and physical properties will promote the development of a novel generation of medical *** this work we describe a collagen/carbon nanotube composite which has the potential to be used as a scaffold for tissue *** this biocomposite incorporates the advantageous properties of both collagen and carbon nanotubes,it has most of the characteristics that an ideal biomaterial requires in order to be used as an osteoinductive *** biocomposite is bioresorbable and biodegradable and has the desired mechanical rigidity while maintaining a three-dimensional(3-D)nanostructured *** stability and swelling were achieved under fluid environments by varying the amount of carbon nanotubes(CNTs)incorporated into the *** variations can dictate the degree of interaction between fibroblastic cells and the ***-of-concept was shown by performing an in vitro induced mineralization of hydroxylapatite crystals under physiological ***,the ability to attach biofunctional groups to the CNT walls can open a new road for tissue regeneration since the combination of CNTs with specific growth factors or cellular ligands can create an environment capable of signaling and infl uencing specifi c cell *** observations suggest that collagen/carbon nanotube biocomposites will have important uses in a wide range of biotechnological areas.

关键词： Biomaterials carbon nanotubes collagen tissue engineering biocompatibility

Drivers and breaks in the cholangiocarcinoma immune microenvironment

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Hepatobiliary Surgery and Nutrition 2022年第2期11卷 320-323页

作者： Caitlin B.Conboy Sumera I.Ilyas gregory J.Gores Division of Medical Oncology Mayo ClinicRochesterMinnesotaUSA Division of Gastroenterology and Hepatology Mayo ClinicRochesterMNUSA

Clinically effective immune checkpoint inhibitors(ICI)have transformed cancer treatment over the last *** progress was built on a foundation of understanding tumor immunology,immune checkpoint biology,and biomarkers for sensitivity to ICI(1).Monoclonal antibodies disrupting the PD-l1/PD-1 axis or CTlA-4 are highly effective in tumors that are primed for an anti-tumor immune response but suppressed by immune checkpoints(1).This is the case for cancer types with abundant neoantigens,such as melanoma and lung cancer,and in tumors regardless of histology that have elevated tumor mutation burden(TMB)or microsatellite instability(MSI)due to mismatch repair deficiency(dMMR).Elevated expression of PD-l1 is a biomarker of immunosuppression and predicts sensitivity to PD-(l)1 blockade in several tumor types,including lung and gastroesophageal *** cholangiocarcinoma(CCA),the immune landscape and factors predicting response to immunotherapy are less well understood(2).

关键词： lung elevated landscape

Is Hypothyroidism Overlooked in Cardiac Surgery Patients?

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Open Journal of Thoracic Surgery 2012年第2期2卷 29-35页

作者： Aarne Jyrala Robert E. Weiss Robin A. Jeffries gregory l. Kay Heart Institute Department of Cardiothoracic Surgery Good Samaritan Hospital Los Angeles Heart Institute Department of Cardiothoracic Surgery Good Samaritan Hospital Los Angeles USA School of Public Medicine Department of Biostatistics University of California Los Angeles USA

Objectives: to analyze adequacy of preoperative thyroid screening of cardiac surgery patients (pts) with hypothyroidism (HT) and compare with pts without HT by demographic data, EuroSCORE (ES) scores, early and late outcomes. Patients: From 1000 cardiac surgery pts from Jan 1999 through May 2000 pts with HT were identified (Group 1, n = 80). 920 pts (Group 2) had no HT. Results Group 1 pts were older (p 60 years (p = 0.004), more females (p laboratory tests. 15 (18.8%) had no tests and 18 (22.5%) inadequate tests. 10 (12.5%) pts had no replacement therapy. There was no operative mortality in Group 1 and 14 (1.5%) in Group 2 (p = 0.70). Hospital mortality was higher in Group 1 (6/7.5% vs 37/4.5%), p = 0.03. Stay in postoperative intensive care unit and hospital were similar (p = 0.66 and 0.53). More pts in Group 1 needed prolonged ICU and lOS (p llow-up mortality was higher in Group 1 (45/58.1% vs 378/43.5%, p = 0.02). Conclusions HT is overlooked in cardiac surgery patients. long-term mortality is higher in pts with HT. Resource utilization is higher in pts with HT.

关键词： Hypothyroidism Cardiac Surgery Outcome Differences

Nitrogen Dioxide and Ozone Pollution in the Chicago Metropolitan Area

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Journal of Environmental Protection 2020年第8期11卷 551-569页

作者： Zixian Wang Jennifer l. Anthony larry E. Erickson Michael J. Higgins gregory l. Newmark Tim Taylor Department of Chemical Engineering Kansas State University Manhattan KS USA Department of Statistics Kansas State University Manhattan KS USA Department of landscape Architecture/Regional and Community Planning Kansas State University Manhattan KS USA

Ground-level ozone is a harmful air pollutant associated with several health issues. Ozone concentrations have exceeded the National Ambient Air Quality Standards (NAAQS) in the Chicago metropolitan area on hot summer days for many years because of nitrogen oxide and volatile organic compound emissions. Annual fourth highest 8-hour ozone concentrations have been between 0.070 and 0.084 ppm at several monitoring sites in Cook county, during the 2016-2018 time period. The continuous measurement of nitrogen dioxide (NO2) and ozone (O3) was conducted in several communities in Chicago in 2017. The air pollution impacts the health of all who live in the area. The data were used to analyze correlations between the O3 distribution and its association with ambient concentrations of NO2 from transportation emissions. Higher concentrations in NO2 and O3 occurred in succession in the daytime. The diurnal variation of O3 concentration was analyzed. The daily cycle of NO2 concentration reaches a maximum in the late morning and has smaller nighttime concentrations. The daily cycle of ozone concentration reaches the maximum in the afternoon and also becomes smaller for nighttime concentrations. In addition, relationships were found between O3 and NO2. Monthly variations of ozone and NO2 are presented. Some options to reduce ozone pollution are presented.

关键词： Volatile Organic Compounds Health Vehicle Emissions Daily Transient Cycles Ozone Precursors Photochemical Reactions

Cryptogenic liver cirrhosis diagnosed in pregnancy and khat consumption

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Open Journal of Obstetrics and Gynecology 2013年第1期3卷 32-34页

作者： Tarek Khalife gregory l. Goyert Roopina Sangha Ronald C. Strickler Department of Obstetrics and Gynecology Division of Maternal and Fetal Medicine Henry Ford Health System Detroit USA Department of Obstetrics and Gynecology Henry Ford Health System Detroit USA Departments of Obstetrics and Gynecology Division of Reproductive Medicine Henry Ford Health System Detroit USA

We report a case of cryptogenic liver cirrhosis likely due to khat consumption diagnosed in the setting of chronic hypertension and giving the appearance of atypical superimposed preeclampsia.

关键词： Superimposed Preeclampsia HEllP Syndrome liver Cirrhosis Elevated liver Enzymes Khat

Removing harvest residues from hardwood stands affects tree growth, wood density and stem wood nutrient concentration in European beech (Fagus sylvatica) and oak (Quercus spp.)

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Forest Ecosystems 2022年第2期9卷 147-159页

作者： Sanjoy Roy Jean-Michel leban Bernhard Zeller gregory van der Heijden Arnaud Reichard Marie-Christine Gehin Philippe Santenoise laurent Saint-Andre INRAE BEFF-54000 NancyFrance IGN Laboratoire de l’Inventaire ForestierNancyF-54000France Universite de lorraine AgroParisTechINRAESILVAF-54000 NancyFrance

Background:Higher exportation of harvest residues from forests due to increased demand for woody biomass,has reportedly diminished soil mineral resources and may lead to degraded tree nutrition as well as ***,as nutrients become less available in the soil,the remobilization of nutrients in biomass tissues(plant internal cycling)helps sustain tree *** study aims to quantify the impact of Removing Harvest Residues and litter(RHRl)during five years on tree growth,wood density,and stem wood nutrient concentrations in young beech and oak forest ***:Our study found that,RHRl significantly decreased tree growth ring width by 14%,and wood density by 3%,in beech trees,in near bark *** also significantly reduced nutrient concentration in near bark and near pith areas of both studied ***,Na and S were found lower by 44%,76%,and 56%,respectively,in near bark area of beech *** near bark area of oak trees,K,Ca,Mg,Na,S,and Fe were lower by 20%,25%,41%,48%,41%,and 16%,respectively.K and Mg concentrations decreased more strongly in near pith area compared to near bark area suggesting internal translocation of these two ***:In beech trees,wood density proved to be an important factor while quantifying the effect of removing harvest residuals on tree growth and *** nutrient loss intensified the remobilization of nutrients con-tained in older tree rings(close to the pith)towards newly formed rings(close to bark).In our study,in beech trees,K was found to be the most recycled major *** results demonstrate the potential of such analysis for providing valuable insight into the effect of RHRl in premature stands on the physiological adaptive strategies of trees and an indication of soil fertility status.

关键词： Harvest residues Fagus sylvatica Quercus petraea Dendroecology Dendrochemistry Radial growth Wood density Tree growth Ring width Translocation

Smartphone-Imaged HIV-1 Reverse-Transcription loop-Mediated Isothermal Ampliflcation(RT-lAMP) on a Chip from Whole Blood

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Engineering 2015年第3期1卷 324-335页

作者： gregory l.Damhorst Carlos Duarte-Guevara Weili Chen Tanmay Ghonge Brian T.Cunningham Rashid Bashir Department of Bioengineering The University of Illinois at Urbana-Champaign Micro and Nanotechnology laboratory The University of Illinois at Urbana-Champaign Department of Electrical and Computer Engineering The University of Illinois at Urbana-Champaign

Viral load measurements are an essential tool for the long-term clinical care of human immunodeficiency virus （HIV）-positive individuals. The gold standards in viral load instrumentation, however, are still too limited by their size, cost, and sophisticated operation for these measurements to be ubiquitous in remote settings with poor healthcare infrastructure, including parts of the world that are disproportionately affected by HIV infection. The challenge of developing a point-of-care platform capable of making viral load more accessible has been frequently approached but no solution has yet emerged that meets the practical requirements of low cost, portability, and ease-of-use. In this paper, we perform reverse-transcription loop-mediated isothermal amplification （RT-lAMP） on minimally processed HIV-spiked whole blood samples with a microfluidic and silicon microchip platform, and perform fluorescence measurements with a consumer smartphone. Our integrated assay shows amplification from as few as three viruses in a - 60 nl RT- lAMP droplet, corresponding to a whole blood concentration of 670 viruses per μl of whole blood. The technology contains greater power in a digital RT-lAMP approach that could be scaled up for the determination of viral load from a finger prick of blood in the clinical care of HIV-positive individuals. We demonstrate that all aspects of this viral load approach, from a drop of blood to imaging the RT-lAMP reaction, are compatible with lab-on-a-chip components and mobile instrumentation.

关键词： human immunodeficiency virus (HIV) viral load loop-mediated isothermal amplification smartphone point-of-care