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Acoustofluidic separation enables early diagnosis of traumatic brain injury based on circulating exosomes

Microsystems & Nanoengineering 2021年第2期7卷 59-69页

作者： Zeyu Wang Haichen Wang Ryan Becker Joseph Rufo Shujie Yang Brian E.Mace Mengxi Wu Jun Zou daniel t.laskowitz tony Jun Huang Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNC27708USA Department of Neurology Duke UniversityDurhamNC27708USA Department of Biomedical Engineering Duke UniversityDurhamNC27708USA Department of Geriatrics Duke UniversityDurhamNC27708USA Department of Electrical&Computer Engineering Texas A&M UniversityCollege StationTX77840USA

traumatic brain injury(tBI)is a global cause of morbidity and *** management and risk stratification of patients with tBI is made difficult by the relative insensitivity of screening radiographic studies as well as by the absence of a widely available,noninvasive diagnostic *** particular,a blood-based biomarker assay could provide a quick and minimally invasive process to stratify risk and guide early management strategies in patients with mild tBI(mtBI).Analysis of circulating exosomes allows the potential for rapid and specific identification of tissue *** applying acoustofluidic exosome separation—which uses a combination of microfluidics and acoustics to separate bioparticles based on differences in size and acoustic properties—we successfully isolated exosomes from plasma samples obtained from mice after *** isolation eliminated interference from other blood components,making it possible to detect exosomal biomarkers for tBI via flow *** cytometry analysis indicated that exosomal biomarkers for tBI increase in the first 24 h following head trauma,indicating the potential of using circulating exosomes for the rapid diagnosis of *** levels of tBI biomarkers were only detected in the samples separated via acoustofluidics;no changes were observed in the analysis of the raw plasma *** finding demonstrated the necessity of sample purification prior to exosomal biomarker *** acoustofluidic exosome separation can easily be integrated with downstream analysis methods,it shows great potential for improving early diagnosis and treatment decisions associated with tBI.

关键词： diagnosis separation injury

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拟apoE对小鼠蛛网膜下腔出血及脑血管痉挛的治疗作用

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第四军医大学学报 2007年第12期28卷 1071-1074页

作者：高俊玲高福禄 daniel t.laskowitz 河北医科大学组织学与胚胎学教研室承德医学院组织学与胚胎学教研室 Multidisciplinary Neuroprotection Laboratories Duke University Medical CenterDurhamNC27710

目的:探讨新合成的拟载脂蛋白E(apoE)对蛛网膜下腔出血(SAH)的治疗作用及机制.方法:55只C57BL6/JL小鼠随机分为:假手术组,SAH组,低剂量(SAH+apoE-1410,0.6mg/Kg)组和高剂量(SAH+apoE-1410,1.2mg/Kg)组.显微操作戳破右侧大脑中动脉(MCA)和大脑前动脉(ACA)分叉处造成SAH模型.术后30min开始经尾静脉给药,每12h一次,连用3d.每日检测小鼠的一般精神状态、神经功能评分、综合运动能力评分.术后第3日测量MCA直径.结果:术后SAH组小鼠精神萎靡,食欲下降,有的难进食水,体质量下降,死亡率为42.8%.高、低剂量组与SAH组比较,一般症状明显减轻,死亡率分别为14.2%和18.8%,与SAH组比较,显著降低(P0.05).综合运动能力评分在SAH组(58.8±25.7)明显低于假手术组(272.2±25.7,P<0.05);高剂量组(95.5±13.2),低剂量组(95.6±18.5)的综合运动能力分别明显高于单纯SAH组(58.8±20.9,P<0.05).结论:外源性拟apoE对SAH及脑血管痉挛有一定的治疗作用,其机制与降低神经系统对损伤的炎性反应有关,拟apoE有可能成为治疗SAH的新措施.

关键词：蛛网膜下腔出血拟apoE apoE基因脑血管痉孪

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神经重症患者感染诊治:美国临床神经医学手册(2017-2018)与中国专家共识(2017)的对比与解读

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中华神经医学杂志 2019年第1期18卷 2-11页

作者：葛歆瞳 daniel t.laskowitz 江荣才张建宁天津医科大学总医院神经外科、天津市神经病学研究所 300052 美国杜克大学医学中心神经内科、美国杜克大学医学院神经生物学系达勒姆27710

一、总论医院获得性感染(HAI)是医院内,尤其是重症监护病房(ICU)内患者的重要致死原因。神经重症监护病房(NICU)患者的感染多属于HAI,其发生与神经外科手术(如脑室外引流术)、机械通气、动脉导管的应用及类固醇/巴比妥类药物的使用密... 详细信息

一、总论医院获得性感染(HAI)是医院内,尤其是重症监护病房(ICU)内患者的重要致死原因。神经重症监护病房(NICU)患者的感染多属于HAI,其发生与神经外科手术(如脑室外引流术)、机械通气、动脉导管的应用及类固醇/巴比妥类药物的使用密切相关,其主要类型为中枢神经系统感染、手术切口感染、医院获得性肺炎(HAP)及呼吸机相关性肺炎(VAP),此外还包括尿路感染、导管相关性血流感染、消化道感染及压疮等。美国临床神经医学(HCN)手册指出,NICU中HAI的发病率为20%-30%,其是否发生及严重程度与NICU患者预后密切相关。在一项针对神经外科术后HAI患者的前瞻性观察队列研究中,NICU患者死亡率同HAI发病率显著相关,其相对危险度为2.04(95%置信区间:1.30-3.20,P<0.05)。此外,NICU感染患者的住院天数(中位数:54 d)显著高于未感染患者(中位数:11 d;P<0.05)。中国专家共识引用赵继宗院士牵头的研究指出,伴开放性颅骨骨折、头皮裂伤的脑外伤或头皮裂伤超过4 h的患者,手术部位感染发生率为10%-25%;清洁-污染手术(包括进入窦或乳突的手术、修补开放性颅骨骨折或无菌技术有明显缺陷的手术)感染发生率为6.8%-15.0%;清洁手术感染发生率为2.6%-5.0%。

关键词：神经重症监护感染美国临床神经医学手册中国专家共识

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A test of the species confidence hypothesis in dusky damselfish

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Current Zoology 2024年第1期70卷 79-86页

作者： Elle Overs Sydney Stump Isabel Severino daniel t.Blumstein Department of Ecology and Evolutionary Biology University of CaliforniaLos AngelesCA 90095-1606USA

Visual cues are important in both interspecific and intraspecific *** species confidence hypothesis proposes that animals are more attracted to conspecific colors and repelled by colors,not on their *** on terrestrial lizards and birds have tested the species confidence hypothesis and shown that conspecific colors elicit reduced antipredator *** date,the species confidence hypothesis has not been tested in the marine environment,specifically on coral reefs where color communication is of vital *** addressed this knowledge gap by measuring flight initiation distance(the distance an individual moves away from an approaching threat)in dusky damselfish(Stegastes nigricans)in response to an approaching disc of 1 of 4 different color treatments:conspecific,blue,yellow,and *** the species confidence hypothesis explained variation in damselfish flight initiation distance,then we expected individuals to tolerate closer approaches when approached by a conspecific *** addition,we calculated the color difference between each stimulus and its corresponding back-ground as a potential alternative explanation for flight *** tolerated the closest approach from the conspecific color stimulus;there were no significant differences between other colors and there was no support for the alternative color difference *** with similar terrestrial studies,these results are relevant to ecotourists'choice of swimsuit and wetsuit colors because color choice may modify naturalantipredatorbehavior.

关键词： antipredator behavior flight initiation distance risk assessment species confidence hypothesis Stegastes nigricans

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Evaluation of a hepatic biomarker of nutritional imbalance in juvenile red drum(Sciaenops ocellatus) fed 60% soybean meal-based diets using NMR-based metabolomics

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Animal Nutrition 2024年第1期16卷 45-61页

作者： Fabio Casu Aaron M.Watson Justin Yost t.Gibson Gaylord daniel W.Bearden Michael R.Denson Marine Resources Research Institute South Carolina Department of Natural Resources Bozeman Fish technology Center United States Fish and Wildlife Service Marine Biochemical Sciences Group Chemical Sciences Division National Institute of Standards and Technology Hollings Marine Laboratory

A 12-week feeding trial with juvenile red drum(Sciaenops ocellatus) fed high-soybean meal(SBM) diets was conducted to investigate a putative biomarker of nutritional imbalance, N-formimino-L-glutamate(FIGLU). three fishmeal-free, 60% SBM pelleted diets(named B12, Fol, and Met, respectively) were tested to evaluate the effects on growth performance and tissue metabolite profiles of supplementation of vitamin B12(0.012 mg/kg), folate(10 mg/kg), methionine(1 g/kg) respectively, above basal supplementation levels. A fourth SBM-based diet(named B12/Fol/Met) was formulated with a combination of B12, folate, and methionine to attain the above-mentioned target concentrations. A fifth 60% SBM diet(named FWS) with methionine supplementation(1 g/kg above basal supplementation levels), enriched with taurine, lysine and threonine as well as minerals, was also tested. this diet contained formulation targets and additives which have allowed for replacing fishmeal with plant proteins in rainbow trout feeds. Control diets included a fishmeal-based diet(named FM), an unsupplemented basal 60% SBM diet(named SBM60), and a “natural” diet(named N) made up of equal parts of fish(cigar minnows), squid and shrimp as a positive reference for growth performance. Formulated feeds contained approximately 37% total crude protein, approximately 14% total crude lipid and were energetically balanced. Standard growth performance metrics were measured, and tissues(liver, muscle) were collected at week 12 to evaluate diet-induced metabolic changes using nuclear magnetic resonance(NMR)-based *** results show that the FWS diet outperformed all other SBM diets and the FM diet under all performance metrics(Pt detected in fish fed the N diet but was detected in those fed the SBM diets and the FM diet. Fish fed the FWS diet and the Met diet showed lower hepatic levels of FIGLU compared with the other SBM-based diets(Pting that among the different supplementatio

关键词： Aquaculture Metabolomics Nuclear magnetic resonance Red drum Soybean meal N-Formimino-L-glutamate

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Elevation transition of aquatic insects closely matches a thermal feature in the Yungas of Northwestern Argentina

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Journal of Mountain Science 2024年第2期21卷 433-448页

作者： Alexandra BUItRAGO-GUACANAME Carlos MOLINERI Andrés LIRA-NORIEGA daniel Andrés DOS SANtOS Neotropical Biodiversity Institute(CONICEt-UNt) UNT-DomesHorco Molle S/N4107 TucumánArgentina CONACYt Research Fellow Network of Advanced Molecular StudiesInstitute of Ecology A.COld Road to Coatepec 351El HayaCP 91073XalapaVeracruzMexico Biostatistics Chair Faculty of Natural Sciences and IMLNational University of TucumánSan Miguel de TucumánMiguel Lillo 2054000 TucumánArgentina

temperature is a key factor that shapes the distribution of *** knowledge about how species respond to temperature is relevant to devise strategies for addressing the impacts of climate *** insects are particularly vulnerable to climate change,yet there is still much to learn about their ecology and *** the Yungas ecoregion of Northwestern Argentina,cold-and warm-adapted species of the orders Ephemeroptera,Plecoptera,and trichoptera(EPt)are segregated by *** modeled the ecological niche of South American EPt species in this region using available data and projected their potential distribution in geographic *** were grouped based on their ecogeographic similarity,and we analyzed their replacement pattern along elevation gradients,focusing on the ecotone where opposing thermal preferences *** this interface,we identified critical points where the combined incidence of cold and warm assemblages maximizes,indicating a significant transition *** found that the Montane Cloud Forest holds the interface,with a particularly greater suitability at its lower *** main axis of the interface runs in a N-S direction and falls between 14°C-16°C mean annual *** probability of a particular location within a basin being classified as part of the interface increases as Kira’s warmth index approaches a score around *** the interface is critical for defining the thermal limits of species distribution and designing biomonitoring *** in the location of thermal constants related to mountainous ecotones may cause vertical displacement of aquatic insects and vegetation *** have recognized significant temperature thresholds that serve as indicators of suitability for the *** global warming is anticipated to shift these indicators,we suggest using them to monitor the imprints of climate change on mountain ecosystems.

关键词： Austral Yungas Ecological Niche Model Ephemeroptera Kira’s warmth index Plecoptera trichoptera

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the Silk roads: phylogeography of Central Asian dice snakes (Serpentes: Natricidae) shaped by rivers in deserts and mountain valleys

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Current Zoology 2024年第2期70卷 150-162页

作者： daniel Jablonski Konrad Mebert Rafaqat Masroor Evgeniy Simonov Oleg Kukushkin timur Abduraupov Sylvia Hofmann Department of Zoology Comenius University in BratislavaBratislavaSlovakia Global Biology BirrSwitzerland Pakistan Museum of Natural History ShakarparianIslamabadPakistan Severtsov Institute of Ecology and Evolution Russian Academy of SciencesMoscowRussia t.I.Vyazemski Karadag Scientific Station-Nature Reserve—Branch of A.0.Kovalevsky Institute of Biology of the Southern Seas TheodosiaCrimea Zoological Institute of the RAS Saint PetersbourgRussia Institute of Zoology Academy of Sciences of the Republic of UzbekistanYunusabadTashkentUzbekistan Museum Koenig Bonn LIBLeibniz Institute for the Analysis of Biodiversity ChangeBonnGermany UFZ-Helmholtz Centre for Environmental Research Department of Conservation BiologyPermoserstrasse 1504318 LeipzigGermany

Influenced by rapid changes in climate and landscape features since the Miocene,widely distributed species provide suitable models to study the environmental impact on their evolution and current genetic *** dice snake Natrix tessellata,widely distributed in the Western Palearctic is one such *** aimed to resolve a detailed phylogeography of *** with a focus on the Central Asian clade with 4 and the Anatolia clade with 3 mitochondrial lineages,trace their origin,and correlate the environmental changes that affected their distribution through *** expected time of divergence of both clades began at 3.7 Mya in the Pliocene,reaching lineage differentiation approximately 1 million years *** genetic diversity in both clades is rich,suggesting different ancestral areas,glacial refugia,demographic changes,and colonization *** Caspian lineage is the most widespread lineage in Central Asia,distributed around the Caspian Sea and reaching the foothills of the Hindu Kush Mountains in Afghanistan,and Eastern European lowlands in the *** distribution is limited by deserts,moun-tains,and cold steppe ***,Kazakhstan and Uzbekistan lineages followed the Amu Darya and the Syr Darya water systems in Central Asia,with ranges delimited by the large Kyzylkum and Karakum *** the western side,there are several lineages within the Anatolia clade that converged in the central part of the peninsula with 2 being endemic to Western *** distribution of both main clades was affected by expansion from their Pleistocene glacial refugia around the Caspian Sea and in the valleys of Central Asia as well as by environmental changes,mostly through aridification.

关键词： biogeography colonization Eurasia genetic diversity mitochondrial DNA Paratethys refugia water snakes.

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RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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Bone Research 2024年第1期12卷 165-179页

作者： Luis F.de Castro Jarred M.Whitlock Zachary Michel Kristen Pan Jocelyn taylor Vivian Szymczuk Brendan Boyce daniel Martin Vardit Kram Rebeca Galisteo Kamran Melikov Leonid V.Chernomordik Michael t.Collins Alison M.Boyce Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Section on Membrane Biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA Metabolic Bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Department of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genomics and Computational Biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established *** evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment *** this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCt03571191)and in murine in vivo and ex vivo preclinical *** analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL *** sequencing of human and mouse tissue supported these *** interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on *** results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within *** findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

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the secondary injury cascade after spinal cord injury: an analysis of local cytokine/chemokine regulation

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Neural Regeneration Research 2024年第6期19卷 1308-1317页

作者： daniel J.Hellenbrand Charles M.Quinn Zachariah J.Piper Ryan t.Elder Raveena R.Mishra taylor L.Marti Phoebe M.Omuro Rylie M.Roddick Jae Sung Lee William L.Murphy Amgad S.Hanna Department of Neurosurgery University of Wisconsin-Madison School of Medicine and Public Health Department of Biomedical Engineering University of Wisconsin-Madison Department of Orthopedics and Rehabilitation University of Wisconsin-Madison Department of Materials Science and Engineering University of Wisconsin-Madison Forward BIO Institute University of Wisconsin-Madison

After spinal cord injury, there is an extensive infiltration of immune cells, which exacerbates the injury and leads to further neural degeneration. therefore, a major aim of current research involves targeting the immune response as a treatment for spinal cord injury. Although much research has been performed analyzing the complex inflammatory process following spinal cord injury, there remain major discrepancies within previous literature regarding the timeline of local cytokine regulation. the objectives of this study were to establish an overview of the timeline of cytokine regulation for 2 weeks after spinal cord injury, identify sexual dimorphisms in terms of cytokine levels, and determine local cytokines that significantly change based on the severity of spinal cord injury. Rats were inflicted with either a mild contusion, moderate contusion, severe contusion, or complete transection, 7 mm of spinal cord centered on the injury was harvested at varying times post-injury, and tissue homogenates were analyzed with a Cytokine/Chemokine 27-Plex assay. Results demonstrated pro-inflammatory cytokines including tumor necrosis factor α, interleukin-1β, and interleukin-6 were all upregulated after spinal cord injury, but returned to uninjured levels within approximately 24 hours post-injury, while chemokines including monocyte chemoattractant protein-1 remained upregulated for days post-injury. In contrast, several anti-inflammatory cytokines and growth factors including interleukin-10 and vascular endothelial growth factor were downregulated by 7 days post-injury. After spinal cord injury, tissue inhibitor of metalloproteinase-1, which specifically affects astrocytes involved in glial scar development, increased more than all other cytokines tested, reaching 26.9-fold higher than uninjured rats. After a mild injury, 11 cytokines demonstrated sexual dimorphisms; however, after a severe contusion only leptin levels were different between female and male rats. In conclus

关键词： astrocytes chemokines cytokines inflammation macrophages microglia secondary damage spinal cord injury

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Cheaper Precision Weapons: An Exploratory Study about the HESA Shahed 136

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Advances in Aerospace Science and technology 2024年第1期9卷 40-59页

作者： daniel Zampronha Aline Albuquerque National Institute for Applied Sciences Rouen Normandie Rouen France Programme of Pos-Graduation in Bioethics University of Brasília Brasília Brazil

the ability to hit a target with precision and from a great distance has been reserved for the world’s superpowers. However, this resource is increasingly being threatened as drones with this long-range and precision capability are becoming more accessible to those who don’t have this strategic ability. this article starts with an analysis of the Iranian HESA Shahed 136 drone to discuss the latest innovations in low-cost long-range precision weapons, specifically the use of kamikaze drones and loitering munitions. this is an exploratory study that starts by discussing the notion of a kamikaze drone and then analyses the design options for the Shahed 136, to reflect on the future of this new type of weapon and its implications for the economic and political relationship between weapon and cost. the conclusion is that the HESA Shahed 136 revolutionizes the concept of precise long-range strikes, a function that until now was reserved for expensive and technologically demanding tactical missiles and aircraft, and which can now be carried out with cheap drones. this creates an arms race not only in producing the most technological and precise weaponry but also the least expensive.

关键词： Drones Loitering Munitions

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