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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 ***,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 *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** 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’*** were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%*** 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]***‘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 *** 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 *** IS AlREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

Promoting the production of challenging proteins via induced expression in CHO cells and modified cell-free lysates harboring T7 RNA polymerase and mutant eIF2α

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Synthetic and Systems Biotechnology 2024年第3期9卷 416-424页

作者： jeffrey l.Schloßhauer lena Tholen Alexander Korner Stefan Kubick Sofia Chatzopoulou Anja Honow Anne Zemella Fraunhofer Project Group PZ-Syn of the Fraunhofer Institute for Cell Therapy and Immunology-IZI Branch Bioanalytics and Bioprocesses-IZI-BBAm MühlenbergPotsdamGermany Fraunhofer Institute for Cell Therapy and Immunology-IZI Branch Bioanalytics and Bioprocesses-IZI-BBAm MühlenbergPotsdamGermany Faculty of Health Sciences Joint Faculty of the Brandenburg University of Technology Cottbus-SenftenbergThe Brandenburg Medical School Theodor FontaneUniversity of PotsdamPotsdamGermany Institute for Chemistry and Biochemistry Laboratory of Protein BiochemistryFreie Universitat BerlinThielallee 6314195BerlinGermany Institute of Biotechnology Technische Universit¨at BerlinStraße des 17.Juni 13510623BerlinGermany New/era/mabs GmbH August-Bebel-Str.8914482PotsdamGermany

Chinese hamster ovary(CHO)cells are crucial in biopharmaceutical production due to their scalability and capacity for human-like post-translational ***,toxic proteins and membrane proteins are often difficult-to-express in living ***,cell-free protein synthesis can be *** study explores innovative strategies for enhancing the production of challenging proteins through the modification of CHO cells by investigating both,cell-based and cell-free approaches.A major result in our study involves the integration of a mutant eIF2 translation initiation factor and T7 RNA polymerase into CHO cell lysates for cell-free protein *** resulted in elevated yields,while eliminating the necessity for exogenous additions during cell-free production,thereby substantially enhancing ***,we explore the potential of the Rosa26 genomic site for the integration of T7 RNA polymerase and cell-based tetracycline-controlled protein *** findings provide promising advancements in bioproduction technologies,offering flexibility to switch between cell-free and cell-based protein production as needed.

关键词： Inducible expression CHO cells Cell-free protein synthesis CRISPR T7 RNA polymerase eIF2 Rosa26

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 ***-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 *** study illustrates a proof of concept for point-based,minimally-invasive NADHfluorescence lifetime measurement in *** muscle loss(VMl)injuries were created in the left tibialis anterior(TA)muscle of male Sprague Dawley *** 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 *** 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 *** 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

Supplementation of vitamin E or a botanical extract as antioxidants to improve growth performance and health of growing pigs housed under thermoneutral or heat-stressed conditions

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1101-1118页

作者： Ysenia V.Silva‑Guillen Consuelo Arellano jeffrey Wiegert R.Dean Boyd Gabriela E.Martinez Eric van Heugten Department of Animal Science North Carolina State UniversityRaleighNC 27695USA Department of Statistics North Carolina State UniversityRaleighNC 27695USA Department of Animal Science Texas A&M UniversityCollege StationTX 77843USA Animal Nutrition Research LLCAlvatonKY 42122USA.

Background Heat stress has severe negative consequences on performance and health of pigs,leading to significant economic *** objective of this study was to investigate the effects of supplemental vitamin E and a botanical extract in feed or drinking water on growth performance,intestinal health,and oxidative and immune status in grow-ing pigs housed under heat stress *** Duplicate experiments were conducted,each using 64 crossbred pigs with an initial body weight of 50.7±3.8 and 43.9±3.6 kg and age of 13-week and 12-week,***(n=128)were housed individually and assigned within weight blocks and sex to a 2×4 factorial arrangement consisting of 2 environments(thermo-neutral(21.2℃)or heat-stressed(30.9℃))and 4 supplementation treatments(control diet;control+100 IU/l of D-α-tocopherol in water;control+200 IU/kg of Dl-α-tocopheryl-acetate in feed;or control+400 mg/kg of a botanical extract in feed).Results Heat stress for 28 d reduced(P≤0.001)final body weight,average daily gain,and average daily feed intake(-7.4 kg,-26.7%,and-25.4%,respectively)but no effects of supplementation were detected(P>0.05).Serum vitamin E increased(Plementation in water and in feed(1.64 vs.3.59 and 1.64 vs.3.24),but not for the botanical extract(1.64 vs.1.67 mg/kg)and was greater when supplemented in water ***(P=0.002).liver vitamin E increased(Plementations in water(3.9 vs.31.8)and feed(3.9 vs.18.0),but not with the botanical extract(3.9 vs.4.9 mg/kg).Serum malondialdehyde was reduced with heat stress on d 2,but increased on d 28(interaction,Plementation compared to *** proliferation was reduced(P=0.037)in the jejunum under heat stress,but increased in the ileum when vitamin E was supplemented in feed and water under heat stress(interaction,P=0.04).Tumor necrosis factor-αin jejunum and ileum mucosa decreased by heat stress(P<0.05)and was re

关键词： Botanical extract Growing pigs Heat stress Immune status Oxidative status Tocopherol Water

Remodeling Tumor Immune Microenvironment by Using Polymer-lipid-Manganese Dioxide Nanoparticles with Radiation Therapy to Boost Immune Response of Castration-Resistant Prostate Cancer

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Research 2024年第3期2023卷 83-96页

作者： Abdulmottaleb E.Zetrini HoYin lip Azhar Z.Abbasi Ibrahim Alradwan Taksim Ahmed Chunsheng He jeffrey T.Henderson Andrew M.Rauth Xiao Yu Wu Advanced Pharmaceutics and Drug Delivery laboratory Leslie Dan Faculty of PharmacyUniversity of TorontoM5S 3M2TorontoONCanada. Departments of Medical Biophysics and Radiation Oncology University of TorontoM5G 1L7TorontoONCanada.

Despite substantial progress in the treatment of castration-resistant prostate cancer (CRPC), including radiation therapy and immunotherapy alone or in combination, the response to treatment remains poor due to the hypoxic and immunosuppressive nature of the tumor microenvironment. Herein, we exploited the bioreactivity of novel polymer–lipid manganese dioxide nanoparticles (PlMDs) to remodel the tumor immune microenvironment (TIME) by increasing the local oxygen levels and extracellular pH and enhancing radiation-induced immunogenic cell death. This study demonstrated that PlMD treatment sensitized hypoxic human and murine CRPC cells to radiation, significantly increasing radiation-induced DNA double-strand breaks and ultimately cell death, which enhanced the secretion of damage-associated molecular patterns, attributable to the induction of autophagy and endoplasmic reticulum stress. Reoxygenation via PlMDs also polarized hypoxic murine RAW264.7 macrophages toward the M1 phenotype, enhancing tumor necrosis factor alpha release, and thus reducing the viability of murine CRPC TRAMP-C2 cells. In a syngeneic TRAMP-C2 tumor model, intravenous injection of PlMDs suppressed, while radiation alone enhanced recruitment of regulatory T cells and myeloid-derived suppressor cells. Pretreatment with PlMDs followed by radiation down-regulated programmed death-ligand 1 and promoted the infiltration of antitumor CD8+ T cells and M1 macrophages to tumor sites. Taken together, TIME modulation by PlMDs plus radiation profoundly delayed tumor growth and prolonged median survival compared with radiation alone. These results suggest that PlMDs plus radiation is a promising treatment modality for improving therapeutic efficacy in radioresistant and immunosuppressive solid tumors.

关键词： RAW264.7 alone treatment

The American Heart Association’s Get With the Guidelines(GWTG)-Stroke development and impact on stroke care

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Stroke & Vascular Neurology 2017年第2期2卷 94-105页

作者： Cora H Ormseth Kevin N Sheth jeffrey l.saver Gregg C Fonarow lee H Schwamm Neurology Yale University School of MedicineNew HavenConnecticutUSA Department of Neurology UCLA Medical CenterLos AngelesCaliforniaUSA Department of Cardiology UCLA Medical CenterLos AngelesCaliforniaUSA Department of Neurology Massachusetts General HospitalBostonMassachusettsUSA

The American Heart Association’s Get With the Guidelines(GWTG)-Stroke programme has changed stroke care delivery in the USA since its establishment in *** is a voluntary registry and continuous quality improvement initiative that collects data on patient characteristics,hospital adherence to guidelines and inpatient *** of the programme saw increased provision of evidence-based care and improved patient *** review will describe the development of the programme and discuss the impact on stroke outcomes and transformation of stroke care delivery that followed its implementation.

关键词： impact programme

短暂性脑缺血发作的定义和评价:美国心脏协会/美国卒中协会卒中委员会、心血管外科和麻醉委员会、心血管放射学和介入委员会、心血管护理委员会和外周血管病跨学科委员会对医疗卫生专业人员发布的科学声明:美国神经病学学会确认该声明作为神经科医生继续教育工具的价值

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国际脑血管病杂志 2009年第9期17卷 643-660页

作者： J.Donald Easton jeffrey l.saver Gregory W.Albers Mark J.Alberts Seemant Chaturvedi Edward Feldmann Thomas S.Hatsukami Randall T.Higashida S.Claibome Johnston Chelsea S.Kidwell Helmi l.lutsep Elaine Miller Ralph l.Sacco 李海峰(译) 高翔(译) 不详青岛大学医学院附属医院神经内科 266003

本科学声明面向为短暂性脑缺血发作(transient ischemic attacks,TIA)患者提供医疗诊治的临床医生和相关医疗卫生人员。采用正规的证据复习方法对1990-2007年7月期间Medline数据库进行系统的文献检索,并运用证据表、汇总分析和病例资料... 详细信息

本科学声明面向为短暂性脑缺血发作(transient ischemic attacks,TIA)患者提供医疗诊治的临床医生和相关医疗卫生人员。采用正规的证据复习方法对1990-2007年7月期间Medline数据库进行系统的文献检索,并运用证据表、汇总分析和病例资料的合并分析,对数据进行综合处理。本文支持以下基于组织学的TIA定义:局灶性脑、脊髓或视网膜缺血引起的短暂性神经功能障碍发作,且无急性脑梗死。TIA患者的近期卒中风险较高,可根据临床量表、血管影像学和磁共振弥散加权成像进行风险分层。诊断推荐包括:TIA患者应在发病24h内接受神经影像学评价,最好是应用包括弥散序列在内的MRI;应进行无创性颈部血管成像检查,最好是无创性颅内血管成像;对于未能确定血管病因的患者,TIA发病后应尽快进行心电图检查,也应考虑持续心电监测和超声心动图检查;应进行常规血液化验;对于发病72h内就诊并且ABCD^(2)评分≥3分(提示近期复发风险较高)或在门诊不能迅速完成诊断评价的TIA患者,应收入院治疗。

关键词：美国心脏协会科学声明脑脑缺血缺血卒中短暂性脑缺血发作急性卒中综合征急性脑血管综合征

Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

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Genes & Diseases 2024年第1期11卷 103-134页

作者： Kevin Qin Michael Yu Jiaming Fan Hongwei Wang Piao Zhao Guozhi Zhaoo Wei Zeng Connie Chen Yonghui Wang Annie Wang Zander Schwartz jeffrey Hong lily Song William Wagstaff Rex C.Haydon Hue H.luu Sherwin H.Ho Jason Strelzow Russell R.Reid Tong-Chuan He lewis l.Shi Chicago Medical School Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of Clinical laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA laboratory of Craniofacial Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt signaling plays a major role in regulating cell proliferation and *** Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and lRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical *** of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling *** crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ ***-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic *** complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic ***,both stimulatory and inhibitory treatments come with potential risks that need to be *** review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt *** thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+*** description involved each of its components and their involvement in other cellular ***,this review explained the various other pathways and processes that crosstalk with Wnt signaling.

关键词： β-catenin Canonical Wnt Noncanonical Wnt Signal transduction Signaling crosstalk

Reflections on COPD comorbidities

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Chinese Medical Journal 2024年第12期137卷 1504-1506页

作者： Zhenming He Yue Wang lin Shan Yan Mou Yunhuan liu Guanhua Ma Yanxu Wu Huili Zhu jeffrey l.Curtis Shilei Cui Haiyan Ge Department of Pulmonary and Critical Care Medicine Huadong HospitalFudan UniversityShanghai 200040China Medical Service VA Ann Arbor Healthcare SystemAnn ArborMI 48105USA Pulmonary&Critical Care Medicine Division Department of Internal MedicineUniversity of MichiganAnn ArborMI 48109USA Graduate Program in Immunology University of MichiganAnn ArborMI 48109USA

To the Editor:Chronic obstructive pulmonary disease(COPD)is a common disease among the elderly,affecting over one-third of the elderly population *** progressive decline in lung function characteristic of COPD significantly impacts the quality of life and employability of affected individuals,resulting in a substantial direct and indirect socioeconomic *** frequently has comorbidities involving other organ *** all elderly COPD patients present with one or more comorbid conditions,collectively exacerbating health and economic *** viral and bacterial infections remain the most common triggers for COPD exacerbations(ECOPD).

关键词： morbid lung collective