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Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps:A pilot study

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 29-36页

作者： Jorge A.Gutierrez III Jeremy l.Barth Rodney J.Schlosser Thomas S.Edwards timothy l.smith Zachary M.Soler Department of Otolaryngology-Head and Neck Surgery Medical University of South CarolinaCharlestonSouth CarolinaUSA Department of Regenerative Medicine&Cell Biology Medical University of South CarolinaCharlestonSouth CarolinaUSA Department of Otolaryngology-Head and Neck Surgery Oregon Health&Science UniversityPortlandOregonUSA

Objectives:Prior research on olfactory dysfunction in chronic rhinosinusitis(CRS)has focused on patients with polyps and suggests that direct inflammation of the olfactory cleft mucosa plays a contributory role.The purpose of this study was to evaluate gene expression in superior turbinate mucosal specimens,comparing normosmic and dysosmic CRS patients without polyps(CRSsNP).Methods:Tissue samples were obtained from the superior turbinates of patients with CRSsNP at the time of endoscopic sinus surgery.Samples subsequently underwent RNA sequencing and functional analysis to investigate biological pathways associated with differentially expressed genes between dysosmic(n=7)and normosmic(n=4)patients.Results:Differential gene expression analysis comparing dysosmic and normosmic CRSsNP patients showed upregulation of 563 genes and downregulation of 327 genes.Using stringent criteria for multiple comparisons,one upregulated gene(Immediate Early Response 3[IER3])had an false discovery rate(FDR)correction adjustedP value considered statistically significant(Pld change 2.69).Reactome functional analysis revealed eight biological pathways significantly different between dysosmic and normosmic patients(Pluding Il-4 and Il-13 signaling,Il-10 signaling,and rhodopsin-like receptors.Conclusions:RNA sequencing of the superior turbinates in patients with CRSsNP can provide valuable information regarding biological pathways and genes involved in olfactory dysfunction.This study supports literature suggesting that Type 2 inflammation may play a role in olfactory dysfunction in at least some patients with CRSsNP.This study also prompts questions regarding the role of Il-10,rhodopsin-like receptors,andIER3 in the pathogenesis of olfactory dysfunction.

关键词： chronic rhinosinusitis without nasal polyps olfactory dysfunction RNA sequencing

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Impact of endoscopic sinus surgery on otologic symptoms associated with chronic rhinosinusitis

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2017年第1期3卷 -页

作者： Neville W.Teo Jess C.Mace timothy l.smith Peter H.Hwang Department of Otolaryngology Singapore General HospitalSingaporeDepartment of Otolaryngology-Head and Neck SurgeryStanford University School of MedicineStanfordCAUSA Department of Otolaryngology-Head and Neck Surgery Oregon Health & Science UniversityPortlandORUSA Department of Otolaryngology-Head and Neck Surgery Stanford University School of MedicineStanfordCAUSA

OBJECTIVE:To evaluate improvements in otologic symptoms after endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS), and identify differences in symptoms, if any, between CRS patients with (CRSwNP) and without (CRSsNP) nasal polyposis.;METHODS:Prospective multi-center observational cohort study.;METHODS:Academic tertiary medical centers.;METHODS:Adults with medically recalcitrant CRS who elected ESS were enrolled in a prospective, multi-center, observational cohort study between March, 2011 and October, 2014. Preoperative evaluation of subjects included assessment of clinical characteristics, measures of disease severity, and quality of life evaluation using the 22-item SinoNasal Outcome Test (SNOT-22). Postoperative improvement in otologic symptoms (ear fullness, dizziness, ear pain) scores were evaluated and compared between CRSwNP and CRSsNP subgroups.;RESUlTS:395 study patients completed both preoperative and postoperative evaluations, with an average follow-up of 13.9 months after ESS. The prevalence of patients reporting at least one otologic symptom preoperatively (87%) significantly decreased after ESS (63%; pll otologic scores was also reported (plative mean improvement in otologic symptom severity was similar for both CRSwNP and CRSsNP, except patients with CRSwNP reported significantly greater postoperative improvement in ear fullness compared to CRSsNP (54% vs. 41%; p=0.039). A total of 61%, 44%, and 43% of patients reported experiencing improvement in "ear fullness", "dizziness" and "ear pain", respectively.;CONClUSIONS:Sinus surgery significantly improves otologic symptoms associated with CRS. CRSwNP patients reported slightly greater relief of ear fullness than CRSsNP patients following ESS.

关键词： Ear symptoms chronic rhinosinusitis endoscopic sinus surgery

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In vivo measurement of NADH fluorescence lifetime in skeletal muscle via -ber-coupled time-correlated single photon counting

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Journal of Innovative Optical Health Sciences 2024年第1期17卷 121-134页

作者： Kathryn M.Priest Jacob V.Schluns Nathania Nischal Colton l.Gattis Jeffrey C.Wolchok timothy J.Muldoon Department of Biomedical Engineering University of Arkansas FayettevilleARUSA

Nicotinamide adenine dinucleotide(NADH)is a cofactor that serves to shuttle electrons during metabolic processes such as glycolysis,the tricarboxylic acid cycle,and oxidative phosphorylation(OXPHOS).NADH is autofluorescent,and itsfluorescence lifetime can be used to infer metabolic dynamics in living cells.Fiber-coupled time-correlated single photon counting(TCSPC)equipped with an implantable needle probe can be used to measure NADH lifetime in vivo,enabling investigation of changing metabolic demand during muscle contraction or tissue regeneration.This study illustrates a proof of concept for point-based,minimally-invasive NADHfluorescence lifetime measurement in vivo.Volumetric muscle loss(VMl)injuries were created in the left tibialis anterior(TA)muscle of male Sprague Dawley rats.NADH lifetime measurements were collected before,during,and after a 30 s tetanic contraction in the injured and uninjured TA muscles,which was subsequently-t to a biexponential decay model to yield a metric of NADH utilization(cytoplasmic vs protein-bound NADH,the A11/A22 ratio).On average,this ratio was higher during and after contraction in uninjured muscle compared to muscle at rest,suggesting higher levels of free NADH in contracting and recovering muscle,indicating increased rates of glycolysis.In injured muscle,this ratio was higher than uninjured muscle overall but decreased over time,which is consistent with current knowledge of inflammatory response to injury,suggesting tissue regeneration has occurred.These data suggest that-ber-coupled TCSPC has the potential to measure changes in NADH binding in vivo in a minimally invasive manner that requires further investigation.

关键词： Glycolysis oxidative phosphorylation energy metabolism volumetric muscle loss

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Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason Philip Appleton lisa J Woodhouse Craig S Anderson Sandeep Ankolekar lesley Cala Mark Dixon timothy J England Kailash Krishnan Grant Mair Keith W Muir John Potter Christopher I Price Marc Randall Thompson G Robinson Christine Roffe Else C Sandset Jeffrey l Saver Angela Shone Aloysius Niroshan Siriwardena Joanna M Wardlaw Nikola Sprigg Philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and Medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular Sciences and NIHR leicester Biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway Research and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is unclear.Here,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of onset.The primary outcome was a shift in scores on the modified Rankin scale(mRS)at day 90.Secondary outcomes included death;a global analysis(Wei-lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’markers.Data were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%CI.Results 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]min.Neuroimaging‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe stroke.Conclusions In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital trials.WHAT IS AlREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those with acute stroke treated within 6hours of stroke

关键词： Glasgow nitrate random

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Quantitative Applications of Weather Satellite Data for Nowcasting: Progress and Challenges

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Journal of Meteorological Research 2024年第3期38卷 399-413页

作者： Jun lI Jing ZHENG Bo lI Min MIN Yanan lIU Chian-Yi lIU Zhenglong lI W.Paul MENZEl timothy J.SCHMIT John l.CINTINEO Scott lINDSTROM Scott BACHMEIER Yunheng XUE Yayu MA Di DI Han lIN Key laboratory of Spatial Data Mining and Information Sharing of Ministry of Education National and Local Joint Engineering Research Center of Satellite Geospatial Information Technology Fuzhou University Innovation Centre for Fengyun Meteorological Satellite (FYSIC) National Satellite Meteorological Centre China Meteorological Administration School of Atmospheric Sciences and Guangdong Province Key laboratory for Climate Change and Natural Disaster Studies Sun Yat-sen University and Southern Laboratory of Ocean Science and Engineering Key laboratory of Geographic Information Science (Ministry of Education) East China Normal University Research Center for Environmental Changes Academia Sinica Cooperative Institute for Meteorological Satellite Studies University of Wisconsin-Madison Sensors and Calibration Branch STAR/NESDIS Wuxi University School of Computer Science Chengdu University of Information Technology Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters Nanjing University of Information Science & Technology

Monitoring and predicting highly localized weather events over a very short-term period, typically ranging from minutes to a few hours, are very important for decision makers and public action. Nowcasting these events usually relies on radar observations through monitoring and extrapolation. With advanced high-resolution imaging and sounding observations from weather satellites, nowcasting can be enhanced by combining radar, satellite, and other data,while quantitative applications of those data for nowcasting are advanced through using machine learning techniques.Those applications include monitoring the location, impact area, intensity, water vapor, atmospheric instability, precipitation, physical properties, and optical properties of the severe storm at different stages(pre-convection, initiation,development, and decaying), identification of storm types(wind, snow, hail, etc.), and predicting the occurrence and evolution of the storm. Satellite observations can provide information on the environmental characteristics in the preconvection stage and are very useful for situational awareness and storm warning. This paper provides an overview of recent progress on quantitative applications of satellite data in nowcasting and its challenges, and future perspectives are also addressed and discussed.

关键词： weather satellite quantitative applications nowcasting pre-convection

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l.B.兰德里高中美国巴吞鲁日

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世界建筑导报 2024年第1期39卷 84-87页

作者：无 timothy Hursley(摄影) EDR建筑事务所戴利•萨布利特景观建筑师有限公司不详

这座新的高中是路易斯安那州教育恢复学区的一部分,是卡特里娜飓风后的“快速启动”建设计划的一部分,旨在加速替换五所受损学校,时间紧迫(设计6个月,施工20个月),同时新奥尔良学校系统的全面总体规划正在进行中。

关键词：卡特里娜飓风路易斯安那州新奥尔良快速启动学区总体规划高中

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IFNγsignaling integrity in colorectal cancer immunity and immunotherapy

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Cellular & Molecular Immunology 2022年第1期19卷 23-32页

作者： Wan Du timothy l.Frankel Michael Green Weiping Zou Department of Surgery University of Michigan School of MedicineAnn ArborMIUSA Center of Excellence for Cancer Immunology and Immunotherapy Rogel Cancer CenterUniversity of Michigan School of MedicineAnn ArborMIUSA Department of Radiation Oncology University of Michigan School of MedicineAnn ArborMIUSA Veterans Affairs Ann Arbor Healthcare System University of Michigan School of MedicineAnn ArborMIUSA Graduate Programs in Immunology University of Michigan School of MedicineAnn ArborMIUSA Tumor Biology University of Michigan School of MedicineAnn ArborMIUSA Department of Pathology University of Michigan School of MedicineAnn ArborMIUSA

The majority of colorectal cancer patients are not responsive to immune checkpoint blockade(ICB).The interferon gamma(IFNγ)signaling pathway drives spontaneous and ICB-induced antitumor immunity.In this review,we summarize recent advances in the epigenetic,genetic,and functional integrity of the IFNγsignaling pathway in the colorectal cancer microenvironment and its immunological relevance in the therapeutic efficacy of and resistance to ICB.Moreover,we discuss how to target IFNγsignaling to inform novel clinical trials to treat patients with colorectal cancer.

关键词： IFNGR Interferon MHC Palmitoylation T cell EZH2 ARID1A PD-1 PD-l1 Apoptosis Ferroptosis Colorectal cancer Immunity

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Elite,transformable haploid inducers in maize

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The Crop Journal 2024年第1期12卷 314-319页

作者： Brent Delzer Dawei liang David Szwerdszarf Isadora Rodriguez Gonzalo Mardones Sivamani Elumalai Francine Johnson Samson Nalapalli Rachel Egger Erin Burch Kerry Meier Juan Wei Xiujuan Zhang Huaping Gui Huaibing Jin Huan Guo Kun Yu Yubo liu Becky Breitinger Ana Poets Jason Nichols Wan Shi David Skibbe Qiudeng Que timothy Kelliher Seeds Development Syngenta SeedsJanesvilleWI 53546USA Seeds Research Syngenta Biotechnology China Co.Ltd.Beijing 102206China Centro de Investigación de Cultivos Arica Syngenta R&DArica 1000000Chile Syngenta S.A. Proyecto la SoledadGraneros 2880000Chile Seeds Research Syngenta Crop Protection LLCRTPNC 27709USA Seeds Development Syngenta SeedsSlaterIA 50244USA

The introduction of alleles into commercial crop breeding pipelines is both time consuming and costly.Two technologies that are disrupting traditional breeding processes are doubled haploid(DH)breeding and genome editing(GE).Recently,these techniques were combined into a GE trait delivery system called HI-Edit(Haploid Inducer-Edit).In HI-Edit,the pollen of a haploid inducer line is reprogrammed to deliver GE traits to any variety,obviating recurrent selection.For HI-Edit to operate at scale,an efficient transformable HI line is needed,but most maize varieties are recalcitrant to transformation,and haploid inducers are especially difficult to transform given their aberrant reproductive behaviors.leveraging marker assisted selection and a three-tiered testing scheme,we report the development of new Iodent and Stiff Stalk maize germplasm that are transformable,have high haploid induction rates,and exhibit a robust,genetically-dominant anthocyanin native trait that may be used for rapid haploid identification.We show that transformation of these elite‘‘HI-Edit”lines is enhanced using the BABYBOOM and WUSCHEl morphogenetic factors.Finally,we evaluate the HI-Edit performance of one of the lines against both Stiff Stalk and non-Stiff Stalk testers.The strategy and results of this study should facilitate the development of commercially scalable HI-Edit systems in diverse crops.

关键词： Zea mays l Doubled haploids Transformation Genome editing QTl

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Coordination chemistry of surface-associated ligands for solid-liquid adsorption of rare-earth elements

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Journal of Rare Earths 2023年第1期41卷 1-18页

作者： Jessica l.Hovey timothy M.Dittrich Matthew J.Allen Department of Chemistry Wayne State University5101 Cass AvenueDetroitMI48202USA Department of Civil and Environmental Engineering 5050 Anthony Wayne DriveWayne State UniversityDetroitMIl48202USA

General guidelines for the design of ligands for the enrichment of rare-earth elements by solid-liquid adsorption are described using coordination chemistry.Relevant properties of ligands include selectivity of metal ions based on adjustment of donor atom polarizability,denticity,and the pKarange of the binding sites.The selectivity of solid-phase materials for the enrichment of rare-earth ions by the ligand design guidelines is outlined,with special consideration of additional variable factors including steric hindrance,saturated binding sites,variability in speciation caused by the identity of counterions and ionic strength,and size-exclusivity in ligands stemming from differences in bite angle,preo rganization of ligands,or intraligand interactions.This review analyzes some principles of selectivity of rare-earth elements with ligands organized by donor type from examples collected from reports published between 2009 and 2021.

关键词： Chelating ligand Coordination chemistry Solid-phase material Rare-earth element Separation Solid-liquid extraction

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应对可转移多黏菌素耐药性--饲料添加剂来源的白屈菜红碱具有双重效应

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Engineering 2024年第1期32卷 163-173页

作者： Huangwei Song Xueyang Wang Muchen Zhang Zhiyu Zou Siyuan Yang Tian Yi Jianfeng Wang Dejun liu Yingbo Shen Chongshan Dai Zhihai liu timothy R.Walsh Jianzhong Shen Congming Wu Yang Wang National Key laboratory of Veterinary Public Health and Safety College ofVeterinary MedicineChina Agricultural UniversityBeijing 100193China Guangdong laboratory for lingnan Modern Agriculture Guangzhou 510642China State Key laboratory for Zoonotic Diseases Key Laboratory of Zoonosis ResearchMinistry of EducationInstitute of ZoonosisCollege of Veterinary MedicineJilin UniversityChangchun 130015China College of Chemistry and Pharmaceutical Sciences Qingdao Agricultural University.Qingdao 266109China Ineos-Oxford Institute of Antimicrobial Research Department of BiologyUniversity of OxfordOxford OX13SZUK

The emergence and spread of the mobile colistin-resistance gene,mcr-1,and its variants pose achallenge to the use of colistin,a last-resort antibiotic used to treat severe infections caused by extensively drug-resistant(XDR)Gram-negative pathogens.Antibiotic adjuvants are a promising strategy to enhance the efficacy of colistin against colistin-resistant pathogens;however,few studies have considered the effects of adjuvants on limiting resistance-gene transmission.We found that chelerythrine(4 mg·l^(-1))derived from Macleaya cordata extract,which is used as an animal feed additive,reduced the minimal inhibitory concentration(MIC)of colistin against an mcr-1 positive Escherichia coli(E.coli)strain by 16-fold(from 2.000 to 0.125 mg·l^(-1)).eliminated approximately 10^(4) colony-forming units(CFUs)of an mcr-1-carrying strain in a murine intestinal infection model,and inhibited the conjugation of an mcr-1-bearing plasmid in vitro(by>100-fold)and in a mouse model(by up to 5-fold).A detailed analysis revealed that chelery-thrine binds to phospholipids on bacterial membranes and increases cytoplasmic membrane fluidity,thereby impairing respiration,disrupting proton motive force(PMF),generating reactive oxygen species(ROS),and decreasing intracellular adenosine triphosphate(ATP)levels,which subsequently downregu-lates mcr-1 and conjugation-associated genes.These dual effects of chelerythrine can expand the use of antibiotic adjuvants and may provide a new strategy for circumventing mobile colistin resistance.

关键词： Chelerythrine Antibiotic adjuvant Conjugation inhibitor Colistin mcr-1 Dual effects

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