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| 1 | Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25显示文摘堵住抗体 ipilimumab 的细胞毒素的 T 淋巴细胞 antigen-4 (CTLA-4 ) 在很少的病人导致变形黑瘤的调停免疫者的长期的控制。尽管 ipilimumab 无疑经由 immunostimulation 施加它的治疗学的效果,这样远的临床上有用的、 immunologically 相关的 biomarkers 预言治疗效率是逃犯的。这里,我们显示出 IL-2 的那中立化或堵住 α并且 βIL-2 受体的子单元(CD25 和 CD122,分别地) 否则在现出症状之前的潜的老鼠模型由 CTLA-4 封锁导致了,废除了 antitumor 效果和 intratumoral T 受动器对规章的房间(Tregs ) 的比率的伴随的改进,它是。CTLA-4 封锁导致了在失去了 FoxP3 表示并且在 regressing 肿瘤积累了的 IL-2-producing 受动器房间与伴随物上升表示 Lag3, ICOS, IL-10 和 Egr2 的一个镇压 CD4 + T 房间子集的减小。当 recombinant IL-2 改进了 CTLA-4 封锁的治疗学的功效时,圈套 IL-2 受体 α(IL-2Rα, sCD25 ) 禁止了 CTLA-4 的 anticancer 效果封锁。在收到 ipilimumab 的 262 个变形黑瘤病人, sCD25 的基线浆液集中代表了全面幸存的独立指示物,与预言到治疗的抵抗的高水平。总的来说,这些结果解开为在 CTLA-4 的 anticancer 活动的 IL-2 和 IL-2 受体的一个角色封锁。重要地,我们的学习提供第一 immunologically 相关的 biomarker,也就是提高的浆液 sCD25,那与黑瘤在病人预言抵抗到 CTLA-4 封锁。 | Dalil Hannani Marie Vetizou David Enot Sylvie Rusakiewicz Nathalie Chaput David Klatzmann Melanie Desbois Nicolas Jacquelot Nadege Vimond Salem Chouaib Christine Mateus James P Allison Antoni Ribas Jedd D Wolchok Jianda Yuan Philip Wong Michael Postow Andrzej Mackiewicz Jacek Mackiewicz Dirk Schadendorff Dirk Jaeger Alan J Korman Keith Bahjat Michele Maio Luana Calabro Michele WL Teng Mark J Smyth Alexander Eggennont Caroline Robert Guido Kroemer Laurence Zitvogel | 2015 | Cell Research2015，25，2： | 14 |
| 2 | Cenozoic topography,monsoons and biodiversity conservation within the Tibetan Region:An evolving story显示文摘The biodiversity of the Himalaya,Hengduan Mountains and Tibet,here collectively termed the Tibetan Region,is exceptional in a global context.To contextualize and understand the origins of this biotic richness,and its conservation value,we examine recent fossil finds and review progress in understanding the orogeny of the Tibetan Region.We examine the deep-time origins of monsoons affecting Asia,climate variation over different timescales,and the establishment of environmental niche heterogeneity linked to topographic development.The origins of the modern biodiversity were established in the Eocene,concurrent with the formation of pronounced topographic relief across the Tibetan Region.High(>4 km)mountains to the north and south of what is now the Tibetan Plateau bounded a Paleogene central lowland(<2.5 km)hosting moist subtropical vegetation influenced by an intensifying monsoon.In mid Miocene times,before the Himalaya reached their current elevation,sediment infilling and compressional tectonics raised the floor of the central valley to above 3000 m,but central Tibet was still moist enough,and low enough,to host a warm temperate angiosperm-dominated woodland.After 15 Ma,global cooling,the further rise of central Tibet,and the rain shadow cast by the growing Himalaya,progressively led to more open,herb-rich vegetation as the modern high plateau formed with its cool,dry climate.In the moist monsoonal Hengduan Mountains,high and spatially extensive since the Eocene but subsequently deeply dissected by river incision,Neogene cooling depressed the tree line,compressed altitudinal zonation,and created strong environmental heterogeneity.This served as a cradle for the then newly-evolving alpine biota and favoured diversity within more thermophilic vegetation at lower elevations.This diversity has survived through a combination of minimal Quaternary glaciation,and complex relief-related environmental niche heterogeneity.The great antiquity and diversity of the Tibetan Region biota argues for its conservation,and the importance of that biota is demonstrated through our insights into its long temporal gestation provided by fossil archives and information written in surviving genomes.These data sources are worthy of conservation in their own right,but for the living biotic inventory we need to ask what it is we want to conserve.Is it 1)individual taxa for their intrinsic properties,2)their services in functioning ecosystems,or 3)their capacity to generate future new biodiversity?If 2 or 3 are our goal then landscape conservation at scale is required,and not just seed banks or botanical/zoological gardens. | Robert A.Spicer Alexander Farnsworth Tao Su | 2020 | Plant Diversity2020，42，4： | 14 |
| 3 | Current Status and Future Challenges of Weather Radar Polarimetry: Bridging the Gap between Radar Meteorology/Hydrology/Engineering and Numerical Weather Prediction显示文摘After decades of research and development, the WSR-88 D(NEXRAD) network in the United States was upgraded with dual-polarization capability, providing polarimetric radar data(PRD) that have the potential to improve weather observations,quantification, forecasting, and warnings. The weather radar networks in China and other countries are also being upgraded with dual-polarization capability. Now, with radar polarimetry technology having matured, and PRD available both nationally and globally, it is important to understand the current status and future challenges and opportunities. The potential impact of PRD has been limited by their oftentimes subjective and empirical use. More importantly, the community has not begun to regularly derive from PRD the state parameters, such as water mixing ratios and number concentrations, used in numerical weather prediction(NWP) models.In this review, we summarize the current status of weather radar polarimetry, discuss the issues and limitations of PRD usage, and explore potential approaches to more efficiently use PRD for quantitative precipitation estimation and forecasting based on statistical retrieval with physical constraints where prior information is used and observation error is included. This approach aligns the observation-based retrievals favored by the radar meteorology community with the model-based analysis of the NWP community. We also examine the challenges and opportunities of polarimetric phased array radar research and development for future weather observation. | Guifu ZHANG Vivek N.MAHALE Bryan J.PUTNAM Youcun QI Qing CAO ANDrew D.BYRD Petar BUKOVCIC Dusan S.ZRNIC Jidong GAO Ming XUE Youngsun JUNG Heather D.REEVES Pamela L.HEINSELMAN AlexANDer RYZHKOV Robert D.PALMER Pengfei ZHANG Mark WEBER Greg M.MCFARQUHAR Berrien MOORE III Yan ZHANG Jian ZHANG J.VIVEKANANDAN Yasser AL-RASHID Richard L.ICE Daniel S.BERKOWITZ Chong-chi TONG Caleb FULTON Richard J.DOVIAK | 2019 | Advances in Atmospheric Sciences2019，36，6： | 9 |
| 4 | Why ‘the uplift of the Tibetan Plateau’ is a myth显示文摘The often-used phrase‘the uplift of the Tibetan Plateau’implies a flat-surfaced Tibet rose as a coherent entity,and that uplift was driven entirely by the collision and northward movement of India.Here,we argue that these are misconceptions derived in large part from simplistic geodynamic and climate modeling,as well as proxy misinterpretation.The growth of Tibet was a complex process involving mostly Mesozoic collisions of several Gondwanan terranes with Asia,thickening the crust and generating complex relief before the arrival of India.In this review,Earth system modeling,paleoaltimetry proxies and fossil finds contribute to a new synthetic view of the topographic evolution of Tibet.A notable feature overlooked in previous models of plateau formation was the persistence through much of the Cenozoic of a wide east–west orientated deep central valley,and the formation of a plateau occurred only in the late Neogene through compression and internal sedimentation. | Robert A.Spicer Tao Su Paul J.Valdes Alexander Farnsworth Fei-Xiang Wu Gongle Shi Teresa E.V.Spicer Zhekun Zhou | 2021 | National Science Review2021，8，1： | 9 |
| 5 | Importance of bifurcation angle in bifurcation stenting显示文摘Bifurcation coronary lesions are relatively frequent in today's interventional cardiology practice,averaging between 10%-15% of all percutaneous coronary interventions(PCIs).1 Several problems inherent in the treatment of bifurcation lesions are periprocedural side branch(SB)compromise(composite of SB closure or appearance of significant ostial stenosis after main vessel(MV)stenting causing ischemia)frequently related to periprocedural myonecrosis,relatively higher restenosis rates especially in two-stent techniques,and higher rates of stent thrombosis in different time frames.1-4 The lead author and other investigators demonstrated that both periprocedural result and long-term results could be influenced by bifurcation angulations.The purpose of this study is to show why and how bifurcation angulations are important for bifurcation stenting. | Dobrin Vassilev Alexander Alexandrov Dan Le Katrina Nguyen James Nguyen Hung Phan Robert J. Gil | 2012 | Chinese Medical Journal2012，，22： | 7 |
| 6 | Efficacy and safety of tenofovir in chronic hepatitis B: Australian real world experience显示文摘AIM To evaluate the long-term treatment outcomes of tenofovir therapy in patients in a real world Australian tertiary care setting.METHODS We performed a retrospective analysis of treatment outcomes among treatment-na?ve and treatment-experienced patients receiving a minimum 3 mo tenofovir therapy through St Vincent's Hospital Melbourne, Australia. We included patients receiving tenofovir [tenofovir disoproxil fumarate(TDF)] monotherapy, as well as patients treated with TDF in combination with a second antiviral agent. Patients were excluded if they demonstrated human immune-deficiency virus/hepatitis C virus/hepatitis delta virus coinfection or were less than 18 years of age. We considered virological and biochemicalresponse, as well as safety outcomes. Virological response was determined by measurement of hepatitis B virus(HBV) DNA using sensitive assays; biochemical response was determined via serum liver function tests; histological response was determined from liver biopsy and fibroscan; safety analysis focused on glomerular renal function and bone mineral density. The primary efficacy endpoint was complete virological suppression over time, defined by HBV DNA < 20 IU/m L. Secondary efficacy endpoints included rates of biochemical response, and HB e antigen(HBe Ag)/HB surface antigen loss and seroconversion over time.RESULTS Ninety-two patients were identified who fulfilled the enrolment criteria. Median follow-up was 26 mo(range 3-114). Mean age was 46(24-78) years, 64(70%) were male and 77(84%) were of Asian origin. 55(60%) patients were treatment-na?ve and 62 patients(67%) were HBe Ag-negative. Complete virological suppression was achieved by 45/65(71%) patients at 12 mo, 37/46(80%) at 24 mo and 25/28(89%) at 36 mo. Partial virological response(HBV DNA 20-2000 IU/m L) was achieved by 89/92(96.7%) of patients. Multivariate analysis showed a significant relationship between virological suppression at end of follow-up and baseline HBV DNA level(OR = 0.897, 95%CI: 0.833-0.967, P = 0.0046) and HBe Ag positive status(OR = 0.373, 95%CI: 0.183-0.762, P = 0.0069). There was no difference in response comparing treatment-na?ve and treatment-experienced patients. Three episodes of virological breakthrough occurred in the setting of noncompliance. Tenofovir therapy was well tolerated.CONCLUSION Tenofovir is an efficacious, safe and well-tolerated treatment in an Australian real-world tertiary care setting. Our data are similar to the reported experience from registration trials. | Grace C Lovett Tin Nguyen David M Iser Jacinta A Holmes Robert Chen Barbara Demediuk Gideon Shaw Sally J Bell Paul V Desmond Alexander J Thompson | 2017 | World Journal of Hepatology2017，9，1： | 7 |
| 7 | Highly efficient derivation of ventricular cardiomyocytes from induced pluripotent stem cells with a distinct epigenetic signature显示文摘从 pluripotent 干细胞导出的 Cardiomyocytes 能在药测试,疾病建模和基于房间的治疗被使用。没有 procardiogenic 生长因素,然而,从 pluripotent 干细胞的 cardiomyogenesis 的效率通常是低的,产生 cardiomyocyte 人口是异构的。这里,我们证明导致的 pluripotent 干细胞( iPSCs )能从鼠科的室的 myocytes ( VM )被导出,并且与从各种各样的体的房间类型导出的 iPSCs 的另外的报告一致,自发地作为与遗传上匹配的胚胎的干细胞(转换字符)或 iPSCs 相比区分 cardiomyocytes 进跳动的显著地更高的倾向从尾巴尖端成纤维细胞导出的 导出VM 的 iPSCs ( ViPSCs )展览。惊人地,导出 ViPSC 的 cardiomyocytes 显示的多数室的显型。在 ViPSCs 的提高的室的 myogenesis 在区别的早阶段经由心血管的祖先的增加的数字被调停。以便从 ViPSCs 调查提高的室的 myogenesis 的机制,我们执行了全球基因表示和 DNA methylation 分析,它揭示了可以涉及在 pluripotent 干细胞指定 VM 命运的不同 epigenetic 签名。 | Huansheng Xu B Alexander Yi Hao Wu Christoph Bock Hongcang Gu Kathy O Lui Joo-Hye C Park Ying Shao Alyssa K Riley Ibrahim J Domian Erding Hu Robert Willette John Lepore Alexander Meissner Zhong Wang Kenneth R Chien | 2012 | Cell Research2012，22，1： | 7 |
| 8 | IL-33, an Interleukin-1-like Cytokine that Signals via the IL-1 Receptor-Related Protein ST2 and Induces T Helper Type 2-Associated Cytokines显示文摘 | Jochen Schmitz Alexander Owyang Elizabeth Oldham Yaoli Song Erin Murphy Terril K. McClanahan Gerard Zurawski Mehrdad Moshrefi Jinzhong Qin Xiaoxia Li Daniel M. Gorman J. Fernando Bazan Robert A. Kastelein | 2005 | Immunity2005，，5： | 6 |
| 9 | Methods for the extraction and RNA profiling of exosomes显示文摘AIM:To develop protocols for isolation of exosomes and characterization of their RNA content.METHODS:Exosomes were extracted from He La cell culture media and human blood serum using the Total exosome isolation(from cell culture media)reagent,and Total exosome isolation(from serum)reagent respectively.Identity and purity of the exosomes was confirmed by Nanosight?analysis,electron microscopy,and Western blots for CD63 marker.Exosomal RNA cargo was recovered with the Total exosome RNA and protein isolation kit.Finally,RNA was profiled using Bioanalyzer and quantitative reverse transcriptionpolymerase chain reaction(q RT-PCR)methodology.RESULTS:Here we describe a novel approach for robust and scalable isolation of exosomes from cell culture media and serum,with subsequent isolation and analysis of RNA residing within these vesicles.The isolation procedure is completed in a fraction of the time,compared to the current standard protocols utilizing ultracentrifugation,and allows to recover fully intact exosomes in higher yields.Exosomes were found tocontain a very diverse RNA cargo,primarily short sequences 20-200 nt(such as mi RNA and fragments of m RNA),however longer RNA species were detected as well,including full-length 18S and 28S r RNA.CONCLUSION:We have successfully developed a set of reagents and a workflow allowing fast and efficient extraction of exosomes,followed by isolation of RNA and its analysis by q RT-PCR and other techniques. | Emily Zeringer Mu Li Tim Barta Jeoffrey Schageman Ketil Winther Pedersen Axl Neurauter Susan Magdaleno Robert Setterquist Alexander V Vlassov | 2013 | World Journal of Methodology2013，3，1： | 5 |
| 10 | Clinical outcomes following salvage Gamma Knife radiosurgery for recurrent glioblastoma显示文摘Glioblastoma multiforme(GBM) is the most common malignant primary brain tumor with a survival prognosis of 14-16 mo for the highest functioning patients. Despite aggressive, multimodal upfront therapies, the majority of GBMs will recur in approximately six months. Salvage therapy options for recurrent GBM(r GBM) are an area of intense research. This study compares recent survival and quality of life outcomes following Gamma Knife radiosurgery(GKRS) salvage therapy. Following a Pub Med search for studies usingGKRS as salvage therapy for malignant gliomas, nine articles from 2005 to July 2013 were identified which evaluated rG BM treatment. In this review, we compare overall survival following diagnosis, overall survival following salvage treatment, progression-free survival, time to recurrence, local tumor control, and adverse radiation effects. This report discusses results for rG BM patient populations alone, not for mixed populations with other tumor histology grades. All nine studies reported median overall survival rates(from diagnosis, range:16.7-33.2 mo; from salvage, range:9-17.9 mo). Three studies identified median progression-free survival(range:4.6-14.9 mo). Two showed median time to recurrence of GBM. Two discussed local tumor control. Six studies reported adverse radiation effects(range:0%-46% of patients). The greatest survival advantages were seen in patients who received GKRS salvage along with other treatments, like resection or bevacizumab, suggesting that appropriately tailored multimodal therapy should be considered with each rG BM patient. However, there needs to be a randomized clinical trial to test GKRS for rG BM before the possibility of selection bias can be dismissed. | Erik W Larson Halloran E Peterson Wayne T Lamoreaux Alexander R MacKay Robert K Fairbanks Jason A Call Jonathan D Carlson Benjamin C Ling John J Demakas Barton S Cooke Christopher M Lee | 2014 | World Journal of Clinical Oncology2014，5，2： | 5 |
| 11 | Seasonality in human semen quality of smokers and non-smokers: effect of temperature显示文摘Aim: To analyse the possible effect of seasonal variation on semen parameters. Methods: The participants consisted of 1688 men attending the andrology laboratory between 1991 and 1997 for reduced fertility in the couple. Semen analysis was performed according to the WHO manual. The 84 individual months of the study period were each assigned to one of the three groups according to the average monthly outside temperature; Group A (temperature <4.4 ℃), Group B (4.4 ℃ - 13.3 ℃) and Group C (>13.3 ℃). Results: When comparing the different sperm parameters, the morphology was significantly better in Group C. However, when the smokers were analysed separately, this difference disappeared and significant seasonal variations were found in sperm density, total sperm count, motility and total motile sperm; they were deteriorated in the warmer season. In non-smokers, no such negative effect of increased temperature was observed. Conclusion: Sperm quality is influenced by seasonal factors.Increased environmental temperature, (maybe also light exposure) has an additional negative effect on the spermatogenesis in smokers, leading to reduced sperm quality in men with borderline fertility. (Asian J Androl 2004 Sep; 6:243-247) | Robert Kunzle Michael D.Mueller Alexander W.Huber Heinz Drescher Nick A.Bersinger | 2004 | Asian Journal of Andrology2004，6，3： | 5 |
| 12 | Cancer and age related colonic crypt deficiencies in cytochrome c oxidase Ⅰ显示文摘AIM: To investigate whether defi ciency of expressionof cytochrome c oxidase I (CcOI) in colonic crypts is associated with colon cancer.METHODS: The pattern and level of expression of CcOI in non-neoplastic colonic crypts,and in dysplastic tissues,was assessed using standard immunohis-tochemical methods.Biopsies were obtained from individuals undergoing colonoscopies for screening purposes or for a medically indicated reason.Tissue samples were also obtained from surgical colonic resections.Samples from resections were taken from colonic mucosa 1 and 10 cm from tumors and from the tumors themselves.Samples were evaluated for frequency of crypts with reduced or absent expression of CcOI.In most crypts the loss was apparent throughout the entire crypt,while in a small minority the loss was segmental.The strong immunoreactivity using this monoclonal antibody makes the scoring unambiguous.The percent of crypts with reduced or absent expression of CcOI or (infrequent) segmented loss of expression was then calculated.Data analyses were performed using SPSS statistical package 17.0.RESULTS: The average frequency of CcOI deficient crypts (CcOI-DC) is low in individuals between 20 and 39 years of age,with 0.48% ± 0.40% CcOI-DC for women and 1.80% ± 0.35% for men.CcOI-DC increases after age 40 years,so that between the ages of 40 and 44 years the average frequency of CcOI- DC goes up to 5.89% ± 0.84% in women and 2.15% ± 1.27% in men.By 80-84 years of age,the average frequency of CcOI-DC goes up in women to 15.77% ± 0.97% and in men to 22.6% ± 0.65%.The increases in CcOI-DC from ages 40-44 years compared to 80-84 years in women and men are significantly different with P < 0.01.For women over age 60 years,deficiency of CcOI expression is greater in those women who have had a cancer in their colon.The frequency of CcOI-DC,measured in men,increased in tissues adjacent to colon cancer,being 4.03% ± 0.27% in individuals free of neoplasia in the age range 55-64 yearsand 14.13% ± 0.35% in resected histologically normal tissue of men with cancer in the same age range,P < 0.001.Similar signifi cant differences were noted in older age ranges.The frequency of CcOI-DC crypts in the cecum and sigmoid colon of an individual are signifi cantly correlated,with an R2 = 0.414 for women and R2 = 0.528 for men,P < 0.001.This suggests that the factors determining the level of CcOI deficiency act throughout the colon.Most defective crypts are in clusters of two or more,a likely consequence of crypt fission.In the non-neoplastic margins of cancers,crypts are frequently defi cient for CcOI,and such crypts may appear in large clusters,some containing more than 100 defi cient crypts.CcOI defi ciency is also apparent in colon cancers and sometimes involves a large section of the tumor.Overall,CcOI deficient cells can be visualized in segments of crypts,in whole crypts that increase in frequency with age,in crypts undergoing f ission,in clusters of crypts where the clusters increase in size with age,in increased frequency near tumors,in large clusters in the intimate margins of tumors,and in the tumors themselves.There is no clear dividing line between early stages that can be considered aspects of aging and later stages that can be considered aspects of the progression to cancer.This ambiguity may re ect a rather general situation leading to adult cancer where the early stages of cellular change appear to be relatively innocuous features of the aging process but over decades may evolve into malignancy.CONCLUSION: CcOI defi cient crypts increase in frequency with age,and clusters of defi cient crypts are associated with,and may give rise to,colon cancer. | Carol Bernstein Alexander Facista Huy Nguyen Beryl Zaitlin Nadia Hassounah Cristy Loustaunau Claire Margaret Payne Bhaskar Banerjee Steve Goldschmid V Liana Tsikitis Robert Krouse Harris Bernstein | 2010 | World Journal of Gastrointestinal Oncology2010，2，12： | 5 |
| 13 | 汶川Ms8.0地震驱动的同震及震后地质灾害空间分布显示文摘汶川大地震驱动了大量的同震崩塌、滑坡等地质灾害,这些地质灾害同时造成了山谷中大量的松散堆积物堆积,并将以泥石流的形式进入河流系统,造成震后大规模的泥石流地质灾害,这也是地震灾区在震后面临的最为严峻的问题。根据本项目组的卫星影像处理和实地观测工作,以及前人对同震地质灾害研究获得的数量资料,对同震地质灾害数量在平行于断裂方向和垂直于断裂方向两个方向上的分布特征进行了精确刻画,据此确定了同震地质灾害引发的松散堆积物的空间分布情况,并根据震后三年来泥石流地质灾害发生区域,确定泥石流地质灾害高危区的宏观分布:在北东—南西方向上,映秀与北川之间、平通与青川之间为泥石流地质灾害高危区;在北西—南东方向上,北川—映秀断裂以东10~15km、以西16~37km的范围内为泥石流地质灾害高危区。这些宏观分布数据可为震后群发性泥石流地质灾害的预测和防治提供重要的参考依据。 | 颜照坤 李勇 黄润秋 李奋生 Densmore Alexander L. 张自力 张威 闫亮 Robert G.Hilton | 2011 | 四川地震2011，，4： | 4 |
| 14 | Protein misfolding in neurodegenerative diseases:implications and strategies显示文摘A hallmark of neurodegenerative proteinopathies is the formation of misfolded protein aggregates that cause cellular toxicity and contribute to cellular proteostatic collapse.Therapeutic options are currently being explored that target different steps in the production and processing of proteins implicated in neurodegenerative disease,including synthesis,chaperone-assisted folding and trafficking,and degradation via the proteasome and autophagy pathways.Other therapies,like mTOR inhibitors and activators of the heat shock response,can rebalance the entire proteostatic network.However,there are major challenges that impact the development of novel therapies,including incomplete knowledge of druggable disease targets and their mechanism of action as well as a lack of biomarkers to monitor disease progression and therapeutic response.A notable development is the creation of collaborative ecosystems that include patients,clinicians,basic and translational researchers,foundations and regulatory agencies to promote scientific rigor and clinical data to accelerate the development of therapies that prevent,reverse or delay the progression of neurodegenerative proteinopathies. | Patrick Sweeney Hyunsun Park Marc Baumann John Dunlop Judith Frydman Ron Kopito Alexander McCampbell Gabrielle Leblanc Anjli Venkateswaran Antti Nurmi Robert Hodgson | 2017 | Translational Neurodegeneration2017，6，1： | 4 |
| 15 | The R.E.N.A.L. Nephrometry Score: A Comprehensive Standardized System for Quantitating Renal Tumor Size, Location and Depth显示文摘 | Alexander Kutikov Robert G. Uzzo | 2009 | The Journal of Urology2009，，3： | 4 |
| 16 | Antifibrogenic effects of vitamin D derivatives on mouse pancreatic stellate cells显示文摘AIM To study the molecular effects of three different D-vitamins, vitamin D2, vitamin D3 and calcipotriol, in pancreatic stellate cells(PSCs).METHODS Quiescent PSCs were isolated from mouse pancreas and activated in vitro by seeding on plastic surfaces. The cells were exposed to D-vitamins as primary cultures(early-activated PSCs) and upon re-culturing(fullyactivated cells). Exhibition of vitamin A-containing lipid droplets was visualized by oil-red staining. Expression of α-smooth muscle actin(α-SMA), a marker of PSC activation, was monitored by immunofluorescence and immunoblot analysis. The rate of DNA synthesis was quantified by 5-bromo-2'-deoxyuridine(Brd U) incorporation assays. Real-time PCR was employed to monitor gene expression, and protein levels of interleukin-6(IL-6) were measured by ELISA. Uptake of proline was determined using 18 F-proline.RESULTS Sustained culture of originally quiescent PSCs inducedcell proliferation, loss of lipid droplets and exhibition of stress fibers, indicating cell activation. When added to PSCs in primary culture, all three D-vitamins diminished expression of α-SMA(to 32%-39% of the level of control cells; P < 0.05) and increased the storage of lipids(scores from 1.97-2.15 on a scale from 0-3; controls: 1.49; P < 0.05). No such effects were observed when D-vitamins were added to fully-activated cells, while incorporation of Brd U remained unaffected under both experimental conditions. Treatment of re-cultured PSCs with D-vitamins was associated with lower expression of IL-6(-42% to-49%; P < 0.05; also confirmed at the protein level) and increased expression of the vitamin D receptor gene(209%-321% vs controls; P < 0.05). There was no effect of D-vitamins on the expression of transforming growth factor-β1 and collagen type 1(chain α1). The lowest uptake of proline, a main component of collagen, was observed in calcipotriol-treated PSCs.CONCLUSION The three D-vitamins inhibit, with similar efficiencies, activation of PSCs in vitro, but cannot reverse the phenotype once the cells are fully activated. | Peter Wallbaum Sarah Rohde Luise Ehlers Falko Lange Alexander Hohn Carina Bergner Sarah Marie Schwarzenbock Bernd Joachim Krause Robert Jaster | 2018 | World Journal of Gastroenterology2018，24，2： | 3 |
| 17 | IL-33, an Interleukin-1-like Cytokine that Signals via the IL-1 Receptor-Related Protein ST2 and Induces T Helper Type 2-Associated Cytokines显示文摘 | Jochen Schmitz Alexander Owyang Elizabeth Oldham Yaoli Song Erin Murphy Terril K. McClanahan Gerard Zurawski Mehrdad Moshrefi Jinzhong Qin Xiaoxia Li Daniel M. Gorman J. Fernando Bazan Robert A. Kastelein | 2005 | Immunity2005，，5： | 3 |
| 18 | Geoclimatic factors influence the population genetic connectivity of Incarvillea arguta(Bignoniaceae)in the Himalaya-Hengduan Mountains biodiversity hotspot显示文摘Geoclimatic factors related to the uplift of the Himalaya and the Quaternary climatic oscillations in fluence the population genetic connectivity in the Himalaya-Hengduan Mountains(HHM)biodiversity hotspot.Therefore,to explore the relative roles played by these two factors,we examined the population dynamics and dispersal corridors of Incarvillea arguta(Royle)Royle incorporating ensemble species distribution modelling(SDM).Thirty-seven populations were genotyped using plastid chloroplast DNA and low copy nuclear gene(ncpCS)sequences.Phylogeographic analysis was carried out to reveal the genetic structure and lineage differentiation.Ensemble SDMs were carried out for distributional change in the last glacial maximum,present,and future.Finally,the least cost path method was used to trace out possible dispersal corridors.The haplotypes were divided into four clades with strong geographical structure.The late Miocene origin of I.arguta in the western Himalaya ca.7.92 Ma indicates lineage diversification related to the uplift of the HHM.The variability in habitat connectivity revealed by SDM is due to change in suitability since the Pleistocene.A putative dispersal corridor was detected along the drainage systems and river valleys,with strong support in the eastern Hengduan Mountains group.Our results support the signature of geoclimatic influence on population genetic connectivity of I.arguta in the HHM.We proposed that the major drainage systems might have assisted the rapid dispersal of isolated riverine plant species I.arguta in the HHM.The population genetic connectivity,using the fine-tuned ensemble SDMs,enables scientists and policymakers to develop conservation strategies for the species gene pool in the HHM biodiversity hotspots. | Santosh Kumar Rana Dong Luo Hum Kala Rana Alexander Robert O'Neill Hang Sun | 2021 | Journal of Systematics and Evolution2021，59，1： | 3 |
| 19 | Sofosbuvir and Ribavirin Prevent Recurrence of HCV Infection after Liver Transplantation: An Open-Label Study显示文摘 | Michael P. Curry Xavier Forns Raymond T. Chung Norah A. Terrault Robert Brown Jonathan M. Fenkel Fredric Gordon Jacqueline O’Leary Alexander Kuo Thomas Schiano Gregory Everson Eugene Schiff Alex Befeler Edward Gane Sammy Saab John G. McHutchison G. Mani S | 2014 | Gastroenterology2014，，： | 3 |
| 20 | Advances in minimally invasive treatment of hemorrhagic and ischemic stroke显示文摘Cerebrovascular diseases,including ischemic and hemorrhagic strokes,affect more than 6 million US adults annually.Strokes cause high rates of morbidity and mortality due to the central nervous system’s sensitivity to disruptions in blood flow,and are refractory to traditional surgical interventions.A variety of minimally invasive surgical and endovascular approaches have recently been developed to improve patient outcomes following stroke. | Robert C.Rennert J.Scott Pannell Alexander A.Khalessi | 2016 | Neural Regeneration Research2016，11，2： | 3 |
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