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| 1 | INT-767 improves histopathological features in a dietinduced ob/ob mouse model of biopsy-confirmed nonalcoholic steatohepatitis显示文摘AIM To characterize the efficacy of the dual FXR/TGR5 receptor agonist INT-767 upon histological endpoints in a rodent model of diet-induced and biopsy-confirmed non-alcoholic steatohepatitis(NASH).METHODS The effects of INT-767 on histological features of NASH were assessed in two studies using Lep^(ob/ob)(ob/ob) NASH mice fed the AMLN diet(high fat with transfat, cholesterol and fructose). In a proof-of-conceptstudy, Lep^(ob/ob)(ob/ob) NASH mice were first dosed with INT-767(3 or 10 mg/kg for 8 wk). A second ob/ob NASH study compared INT-767(3 and 10 mg/kg) to obeticholic acid(OCA)(10 or 30 mg/kg; 16 wk). Primary histological endpoints included qualitative and quantitative assessments of NASH. Other metabolic and plasma endpoints were also assessed. A comparative assessment of INT-767 and OCA effects on drug distribution and hepatic gene expression was performed in C57 Bl/6 mice on standard chow. C57 Bl/6 mice were orally dosed with INT-767 or OCA(1-30 mg/kg) for 2 wk, and expression levels of candidate genes were assessed by RNA sequencing and tissue drug levels were measured by liquid chromatography tandem-mass spectrometry.RESULTS INT-767 dose-dependently(3 and 10 mg/kg, PO, QD, 8 wk) improved qualitative morphometric scores on steatohepatitis severity, inflammatory infiltrates and fibrosis stage. Quantitative morphometric analyses revealed that INT-767 reduced parenchymal collagen area, collagen fiber density, inflammation(assessed by Galectin-3 immunohistochemistry) and hepatocyte lipid droplet area following INT-767 treatment. In a comparative study(16 wk), the FXR agonists OCA(10 and 30 mg/kg) and INT-767(3 and 10 mg/kg) both improved NASH histopathology, with INT-767 exerting greater therapeutic potency and efficacy than OCA. Mechanistic studies suggest that both drugs accumulate similarly within the liver and ileum, however, the effects of INT-767 may be driven by enhanced hepatic, but not ileal, FXR function. CONCLUSION These findings confirm the potential utility of FXR and dual FXR/TGR5 activation as disease intervention strategies in NASH. | Jonathan D Roth Michael Feigh Sanne S Veidal Louise KD Fensholdt Kristoffer T Rigbolt Henrik H Hansen Li C Chen Mathieu Petitjean Weslyn Friley Niels Vrang Jacob Jelsing Mark Young | 2018 | World Journal of Gastroenterology2018，24，2： | 7 |
| 2 | Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a double-blind randomised phase 3 study显示文摘 | Hedy L Kindler Tatsuya Ioka Dirk J Richel Jaafar Bennouna Richard Létourneau Takuji Okusaka Akihiro Funakoshi Junji Furuse Young Suk Park Shinichi Ohkawa Gregory M Springett Harpreet S Wasan Peter C Trask Paul Bycott Alejandro D Ricart Sinil Kim Eric Van | 2011 | Lancet Oncology2011，，3： | 4 |
| 3 | Insulin-induced translocation of glucose transporters in rat hindlimb muscles显示文摘 | Klip A Ramlal T Young D A | 1987 | FEBS Lett1987，224，1： | 2 |
| 4 | Engineering of dendritic dopant-free hole transport molecules:enabling ultrahigh fill factor in perovskite solar cells with optimized dendron construction显示文摘Developing dopant-free hole-transporting materials(HTMs)for high-performance perovskite solar cells(PVSCs)has been a very active research topic in recent years since HTMs play a critical role in optimizing interfacial charge carrier kinetics and in turn determining device performance.Here,a novel dendritic engineering strategy is first utilized to design HTMs with a D-A type molecular framework,and diphenylamine and/or carbazole is selected as the building block for constructing dendrons.All HTMs show good thermal stability and excellent film morphology,and the key optoelectronic properties could be fine-tuned by varying the dendron structure.Among them,MPA-Cz-BTI and MCz-Cz-BTI exhibit an improved interfacial contact with the perovskite active layer,and non-radiative recombination loss and charge transport loss can be effectively suppressed.Consequently,high power conversion efficiencies(PCEs)of 20.8%and 21.35%are achieved for MPA-Cz-BTI and MCz-Cz-BTI based devices,respectively,accompanied by excellent long-term storage stability.More encouragingly,ultrahigh fill factors of 85.2%and 83.5%are recorded for both devices,which are among the highest values reported to date.This work demonstrates the great potential of dendritic materials as a new type of dopant-free HTMs for high-performance PVSCs with excellent FF. | Wei Chen Yang Wang Bin Liu Yajun Gao Ziang Wu Yongqiang Shi Yumin Tang Kun Yang Yujie Zhang Weipeng Sun Xiyuan Feng Frédéric Laquai Han Young Woo Aleksandra B.Djurisic Xugang Guo Zhubing He | 2021 | Science China Chemistry2021，64，1： | 2 |
| 5 | Thin film transistor and diode addressed AMLCDs on polymer substrates显示文摘 | Young N D Bunn B M Wilks R W | 1997 | Journal of the Society for Information Display1997，5，3： | 2 |
| 6 | Polyp detection rates using magnification with narrow band imaging and white light显示文摘AIM: To compare the yield of adenomas between narrow band imaging and white light when using high definition/magnification. METHODS: This prospective, non-randomized comparative study was performed at the endoscopy unit of veteran affairs medical center in Phoenix, Arizona. Consecutive patients undergoing first average risk colorectal cancer screening colonoscopy were selected. Two experienced gastroenterologists performed all the procedures that were blinded to each other's findings. Demographic details were recorded. Data are presented as mean ± SEM. Proportional data were compared using the χ2 test and means were compared using the Student's t test. Tandem colonoscopy was performed in a sequential and segmental fashion using one of 3 strategies: white light followed by narrow band imaging [Group A: white light(WL) → narrow band imaging(NBI)]; narrow band imaging followed by white light(Group B: NBI → WL) and, white light followed by white light(Group C: WL → WL). Detection rate of missed polyps and adenomas were evaluated in all three groups. RESULTS: Three hundred patients were studied(100 in each Group). Although the total time for the colonoscopy was similar in the 3 groups(23.8 ± 0.7, 22.2 ± 0.5 and 24.1 ± 0.7 min for Groups A, B and C, respectively), it reached statistical significance between Groups B and C(P < 0.05). The cecal intubation time in Groups B and C was longer than for Group A(6.5 ± 0.4 min and 6.5 ± 0.4 min vs 4.9 ± 0.3 min; P < 0.05). The withdrawal time for Groups A and C was longer than Group B(18.9 ± 0.7 min and 17.6 ± 0.6min vs 15.7 ± 0.4 min; P < 0.05). Overall miss rate for polyps and adenomas detected in three groups during the second look was 18% and 17%, respectively(P = NS). Detection rate for polyps and adenomas after first look with white light was similar irrespective of the light used during the second look(WL → WL: 13.7% for polyps, 12.6% for adenomas; WL → NBI: 14.2% for polyps, 11.3% for adenomas). Miss rate of polyps and adenomas however was significantly higher when NBI was used first(29.3% and 30.3%, respectively; P < 0.05). Most missed adenomas were ≤ 5 mm in size. There was only one advanced neoplasia(defined by size only) missed during the first look. CONCLUSION: Our data suggest that the tandem nature of the procedure rather than the optical techniques was associated with the detection of additional polyps' and adenomas. | Nooman Gilani Sally Stipho James D Panetta Sorin Petre Michele A Young Francisco C Ramirez | 2015 | World Journal of Gastrointestinal Endoscopy2015，7，5： | 2 |
| 7 | Rootstook and seion chilling effects on apple and peach bud break显示文摘 | YOUNG E WERNER D J | 1984 | Compact Fruit Tree1984，17，： | 2 |
| 8 | Dendritic cells 显示文摘 | Bell D Young JW Banchereau J | 1999 | Adv Immunol1999，72，： | 1 |
| 9 | Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community based study显示文摘 | Nieto F J Young TB Lind BK Shahar E Samet JM Redline S D’ Agostino RB Newman AB Lebowitz MD Picketing TG | 2000 | JAMA2000，283，： | 1 |
| 10 | Calibration of near infrared reflectance spectroscopy to estimate nitrogen concentration in potato tissues显示文摘 | YOUNG M W MACKRRON D K L DAVIES H V | 1997 | PotatoResearch1997，，40： | 1 |
| 11 | High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever显示文摘 | Young PR Pickering D | 2002 | J Infect Dis2002，186，8： | 1 |
| 12 | Time-dependent fundamental solutions for homogeneous diffusion problems显示文摘 | Young D L Tsai C C Murugesan K Fan C M Chen C W | 2004 | Engineering Analysis with Boundary Elements2004，28，： | 1 |
| 13 | A rapid,sensitive method for the quantitation of specific metabolites of sulfur mustard in human urine using isotope-dilution gas chromatography-tandem mass spectrometry显示文摘 | YOUNG C L ASH D DRISKELL W J BOYER A E MARTINEZ R A SILKS L A BARR J R | 2004 | Anal Toxicol2004，28，5： | 1 |
| 14 | Immunolocalization of type III collagen in human articular cartilage prepared by high- pressure eryofixation, freeze-substitution, and low-temperature embedding显示文摘 | Young R D Lawrence P A Duanee V C | 1995 | J Histochem Cytochem1995，43，4： | 1 |
| 15 | Influence of cytokines and growth factor in ANG II - mediated collagen upragulation by fibroblasts in rats : role of myocytes 显示文摘 | Sarkar S Vellaichamy E Young D | 2004 | Am J Physiol Heart Ciro Physiol2004，287，： | 1 |
| 16 | Topical treatment for vaginal candidiasis (thrush) in pregnancy显示文摘 | Young G L Jewell D | 2001 | Cochrane Database Syst Rev2001，4，00： | 1 |
| 17 | Two-state option pricing: binomial models revisited 显示文摘 | JABBOUR G M KRAMIN M V YOUNG S D | 2001 | Journal of Futures Markets2001，21，11： | 1 |
| 18 | Impact of ND-YAG laser drilled holes on the strength and stiffness of laminar flow carbon fibre reinforced composite panels显示文摘 | Young T O'Driscoll D | 2002 | Coznposite2002，33，1： | 1 |
| 19 | Fatty acid genotypes of Virginia-type peanut cultivars显示文摘 | Isleib T G Young C T Knauft D A | 1996 | Crop Sci1996，36，3： | 1 |
| 20 | Application of a Microbial Selective-Plugging Process at the North Burbank Unit:Prepilot Tests显示文摘 | Jenneman G E Moffitt P D Young G R | 1994 | SPE 27 8271994，，： | 1 |
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