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| 1 | Regulation of NF-κB signaling by the A20 deubiquitinase显示文摘NF-κ B 抄写因素是煽动性、天生的有免疫力的发信号小径的一个中央调停人。NF-κ 的激活; B 被哪个的关键发信号的分子的连接 K63 的 polyubiquitination 完成接着激活 Iκ 的成员 kinase 建筑群; B kinase (IKK ) 。Ubiquitination 是一个高度有活力的过程并且被 deubiquitinases 平衡劈开 polyubiquitin 链并且终止下游地发信号的事件。A20 deubiquitinase 是 NF-κ 的一个批评否定管理者; B 和发炎,后来 A20 缺乏的老鼠开发不受管束、自发的多器官发炎。而且,在 A20 genomic 地点的特定的多型性预先安排人到自体免疫的疾病。最近的研究也显示 A20 是在 B 房间淋巴瘤被使失去活性的重要肿瘤 suppressor。因此,指向 A20 可以为自体免疫的疾病和淋巴瘤形成新奇治疗的基础。 | Noula Shembade Edward W Harhaj | 2012 | Cellular & Molecular Immunology2012，9，2： | 22 |
| 2 | Inhibition of Mcl-1 enhances cell death induced by the Bcl-2-selective inhibitor ABT-199 in acute myeloid leukemia cells显示文摘Acute myeloid leukemia(AML)is a serious disease.The 5-year survival rates remain frustratingly low(65%for children and 26%for adults).Resistance to frontline chemotherapy(usually cytarabine)often develops;therefore a new treatment modality is needed.Bcl-2 family proteins play an important role in balancing cell survival and apoptosis.The antiapoptotic Bcl-2 family proteins have been found to be dysregulated in AML.ABT-199,a BH3 mimetic,was developed to target antiapoptotic protein Bcl-2.Although ABT-199 has demonstrated promising results,resistance occurs.Previous studies in AML show that ABT-199 alone decreases the association of proapoptotic protein Bim with Bcl-2,but this is compensated by increased association of Bim with prosurvival protein Mcl-1,stabilizing Mcl-1,resulting in resistance to ABT-199.In this study,we investigated the antileukemic activity of the Mcl-1-selective inhibitor A-1210477 in combination with ABT-199 in AML cells.We found that A-1210477 synergistically induced apoptosis with ABT-199 in AML cell lines and primary patient samples.The synergistic induction of apoptosis was decreased upon Bak,Bax and Bim knockdown.While A-1210477 treatment alone also increased Mcl-1 protein levels,combination with ABT-199 reduced binding of Bim to Mcl-1.Our results demonstrate that sequestration of Bim by Mcl-1,a mechanism of ABT-199 resistance,can be abrogated by combined treatment with the Mcl-1 inhibitor A-1201477. | Daniel A Luedtke Xiaojia Niu Yihang Pan Jianyun Zhao Shuang Liu Holly Edwards Kang Chen Hai Lin Jeffrey W Taub Yubin Ge | 2017 | Signal Transduction and Targeted Therapy2017，2，1： | 11 |
| 3 | Abnormal subchondral bone remodeling and its association with articular cartilage degradation in knees of type 2 diabetes patients显示文摘Type 2 diabetes(T2 D) is associated with systemic abnormal bone remodeling and bone loss. Meanwhile,abnormal subchondral bone remodeling induces cartilage degradation, resulting in osteoarthritis(OA).Accordingly, we investigated alterations in subchondral bone remodeling, microstructure and strength in knees from T2 D patients and their association with cartilage degradation. Tibial plateaus were collected from knee OA patients undergoing total knee arthroplasty and divided into non-diabetic(n = 70) and diabetes(n = 51) groups. Tibial plateaus were also collected from cadaver donors(n = 20) and used as controls.Subchondral bone microstructure was assessed using micro-computed tomography. Bone strength was evaluated by micro-finite-element analysis. Cartilage degradation was estimated using histology. The expression of tartrate-resistant acidic phosphatase(TRAP), osterix, and osteocalcin were calculated using immunohistochemistry. Osteoarthritis Research Society International(OARSI) scores of lateral tibial plateau did not differ between non-diabetic and diabetes groups, while higher OARSI scores on medial side were detected in diabetes group. Lower bone volume fraction and trabecular number and higher structure model index were found on both sides in diabetes group. These microstructural alterations translated into lower elastic modulus in diabetes group. Moreover, diabetes group had a larger number of TRAP^+ osteoclasts and lower number of Osterix^+ osteoprogenitors and Osteocalcin^+ osteoblasts. T2 D knees are characterized by abnormal subchondral bone remodeling and microstructural and mechanical impairments, which were associated with exacerbated cartilage degradation. In regions with intact cartilage the underlying bone still had abnormal remodeling in diabetes group, suggesting that abnormal bone remodeling may contribute to the early pathogenesis of T2 D-associated knee OA. | Yan Chen Yong-Can Huang Chun Hoi Yan Kwong Yuen Chiu Qingjun Wei Jingmin Zhao X Edward Guo Frankie Leung William W Lu | 2017 | Bone Research2017，5，4： | 10 |
| 4 | Structural basis of AMPK regulation by adenine nucleotides and glycogen显示文摘激活安培的蛋白质 kinase (AMPK ) 为糖尿病,肥胖,和癌症的治疗是一个中央细胞的精力传感器和精力动态平衡,和一个有希望的药目标的管理者。这里我们人的 α 的现在的低分辨率的水晶结构; 1 β 2 γ 1 holo-AMPK 建筑群跳了到它的 allosteric 调节的人安培和肝糖模仿 cyclodextrin,两个在 phosphorylated (4.05 Å) 并且 non-phosphorylated (4.60 Å) 状态。另外,我们解决了 2.95 Å人的 kinase 领域(KD ) 的结构跳了到邻近的 autoinhibitory 领域(帮助) 并且表现了广泛生物化学并且 mutational 研究。一起,这些研究由安培和肝糖说明 allosteric AMPK 调整的内在的机制,其绑定改变在交替的帮助(安培) 和糖类绑定模块(肝糖) 之间的 equilibria 相互作用。 | Xiaodan Li Lili Wang X Edward Zhou Jiyuan Ke Parker W de Waal Xin Gu M H Eileen Tan Dongye Wang Donghai Wu H Eric Xu Karsten Melcher | 2015 | Cell Research2015，25，1： | 8 |
| 5 | Nationwide trends and predictors of inpatient mortality in 83884 transjugular intrahepatic portosystemic shunt显示文摘AIM: To evaluate and validate the national trends and predictors of in-patient mortality of transjugular intrahepatic portosystemic shunt(TIPS) in 15 years.METHODS: Using the National Inpatient Sample which is a part of Health Cost and Utilization Project, we identified a discharge-weighted national estimate of 83884 TIPS procedures performed in the United States from 1998 to 2012 using international classification of diseases-9 procedural code 39.1. The demographic, hospital and co-morbility data were analyzed using a multivariant analysis. Using multi-nominal logistic regression analysis, we determined predictive factors related to increases in-hospital mortality. Comorbidity measures are in accordance to the Comorbidity Software designed by the Agency for Healthcare Research and Quality.RESULTS: Overall, 12.3% of patients died during hospitalization with downward trend in-hospitalmortality with the mean length of stay of 10.8 ± 13.1 d. Notable, African American patients(OR = 1.809 vs Caucasian patients, P < 0.001), transferred patients(OR = 1.347 vs non-transferred, P < 0.001), emergency admissions(OR = 3.032 vs elective cases, P < 0.001), patients in the Northeast region(OR = 1.449 vs West, P < 0.001) had significantly higher odds of inhospital mortality. Number of diagnoses and number of procedures showed positive correlations with in-hospital death(OR = 1.249 per one increase in number of procedures). Patients diagnosed with acute respiratory failure(OR = 8.246), acute kidney failure(OR = 4.359), hepatic encephalopathy(OR = 2.217) and esophageal variceal bleeding(OR = 2.187) were at considerably higher odds of in-hospital death compared with ascites(OR = 0.136, P < 0.001). Comorbidity measures with the highest odds of in-hospital death were fluid and electrolyte disorders(OR = 2.823), coagulopathy(OR = 2.016), and lymphoma(OR = 1.842).CONCLUSION: The overall mortality of the TIPS procedure is steadily decreasing, though the length of stay has remained relatively constant. Specific patient ethnicity, location, transfer status, primary diagnosis and comorbidities correlate with increased odds of TIPS in-hospital death. | Edward Wolfgang Lee Andrew Kuei Sammy Saab Ronald W Busuttil Francisco Durazo Steven-Huy Han Mohamed M El-Kabany Justin P Mc Williams Stephen T Kee | 2016 | World Journal of Gastroenterology2016，22，25： | 7 |
| 6 | Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-1igase signaling effector DWARF3显示文摘 | Li-Hua Zhao X Edward Zhou Wei Yi Zhongshan Wu Yue Liu Yanyong Kang Li Hou Parker W de Waal Suling Li Yi Jiang Adrian Scaffidi Gavin R Flematti Steven M Smith Vinh Q Lam Patrick R Griffin YonghongWang Jiayang Li Karsten Melcher H Eric Xu | 2015 | Cell Research2015，25，11： | 7 |
| 7 | Utilization of longitudinal ultrasound to quantify joint soft-tissue changes in a mouse model of posttraumatic osteoarthritis显示文摘To assess the utility of longitudinal ultrasound(US) to quantify volumetric changes in joint soft tissues during the progression of posttraumatic osteoarthritis(PTOA) in mice, and validate the US results with histological findings. A longitudinal cohort of 3-month-old wild-type C57 BL/6 male mice received the Hulth-Telhag surgical procedure on right knee to induce PTOA, and sham surgery on their left knee as control. US scans were performed on both knees before, 2, 4, 6, and 8 weeks post-surgery. Joint space volume and Power-Doppler(PD) volume were obtained from US images via Amira software. A parallel cross-sectional cohort of mice was killed at each US time point, and knee joints were subjected to histological analysis to obtain synovial soft-tissue area and OARSI scores. The correlation between US joint space volume and histological synovial soft-tissue area or OARSI score was assessed via linear regression analysis. US images indicated increased joint space volume in PTOA joints over time, which was associated with synovial inflammation and cartilage damage by histology. These changes started from 2 weeks post-surgery and gradually became more severe. No change was detected in sham joints. Increased joint space volume was significantly correlated with increased synovial soft-tissue area and the OARSI score(P o 0.001). PD signal was detected in the joint space of PTOA joints at 6 weeks post-surgery, which was consistent with the location of blood vessels that stained positively for CD31 and alpha-smooth muscle actin in the synovium.This study indicates that US is a cost-effective longitudinal outcome measure of volumetric and vascular changes in joint soft tissues during PTOA progression in mice, which positively correlates with synovial inflammation and cartilage damage. | Hao Xu Echoe M Bouta Ronald W Wood Edward M Schwarz Yongjun Wang Lianping Xing | 2017 | Bone Research2017，5，3： | 7 |
| 8 | Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial显示文摘 | Wendy S Atkin Rob Edwards Ines Kralj-Hans Kate Wooldrage Andrew R Hart John MA Northover D Max Parkin Jane Wardle Stephen W Duffy Jack Cuzick | 2010 | The Lancet2010，，9726： | 4 |
| 9 | Gastric intestinal metaplasia is associated with gastric dysplasia but is inversely correlated with esophageal dysplasia显示文摘AIM To determine which clinical factors might be associated with gastric intestinal metaplasia(IM) in a North American population.METHODS Pathology and endoscopy databases at an academicmedical center were reviewed to identify patients with and without gastric IM on biopsies for a retrospective cohort study. Patient demographics, insurance status, and other clinical factors were reviewed.RESULTS Four hundred and sixty-eight patients with gastric IM(mean age: 61.0 years ± 14.4 years, 55.5% female) and 171 without gastric IM(mean age: 48.8 years ± 20.8 years, 55.0% female) were compared. The endoscopic appearance of atrophic gastritis correlated with finding gastric IM on histopathology(OR = 2.05, P = 0.051). Gastric IM was associated with histologic findings of chronic gastritis(OR = 2.56, P < 0.001), gastric ulcer(OR = 6.97, P = 0.015), gastric dysplasia(OR = 6.11, P = 0.038), and gastric cancer(OR = 6.53, P = 0.027). Histologic findings of Barrett's esophagus(OR = 0.28, P = 0.003) and esophageal dysplasia(OR = 0.11, P = 0.014) were inversely associated with gastric IM. Tobacco use(OR = 1.73, P = 0.005) was associated with gastric IM.CONCLUSION Patients who smoke or have the endoscopic finding of atrophic gastritis are more likely to have gastric IM and should have screening gastric biopsies during esophagogastroduodenoscopy(EGD). Patients with gastric IM are at increased risk for having gastric dysplasia and cancer, and surveillance EGD with gastric biopsies in these patients might be reasonable. | Justin M Gomez James T Patrie Wissam Bleibel Jeanetta W Frye Bryan G Sauer Vanessa M Shami Edward B Stelow Christopher A Moskaluk Andrew Y Wang | 2017 | World Journal of Gastrointestinal Endoscopy2017，9，2： | 3 |
| 10 | Regnase-1, a rapid response ribonuclease regulating nflammation and stress responses显示文摘 | Renfang Mao Riyun Yang Xia Chen Edward W Harhaj Xiaoying Wang Yihui Fan | 2017 | Cellular & Molecular Immunology2017，14，5： | 3 |
| 11 | Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial显示文摘 | Wendy S Atkin Rob Edwards Ines Kralj-Hans Kate Wooldrage Andrew R Hart John MA Northover D Max Parkin Jane Wardle Stephen W Duffy Jack Cuzick | 2010 | 2010 (9726)2010，，9726： | 3 |
| 12 | The structural basis of the dominant negative phenotype of the Gαi1β1Y2 G203A/A326S heterotrimer显示文摘 | Ping LIU Ming-zhu JIA X Edward ZHOU Parker W DE WAAL Bradley M DICKSON Bo LlU Li HOU Yan-ting YIN Ya n-yong KANG Yi SHI Karsten MELCHER H Eric XU Yi JIANG | 2016 | Acta Pharmacologica Sinica2016，37，9： | 3 |
| 13 | Stratification of outcomes for mucinous appendiceal adenocarcinoma with peritoneal metastasis by histological grade显示文摘AIM To investigate the importance of a three-tiered histologic grade on outcomes for patients with mucinous appendiceal adenocarcinoma(MAA).METHODS Two hundred and sixty-five patients with MAA undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were identified from a prospective database from 2004 through 2014. All pathology was reviewed by our gastrointestinal subspecialty pathologists and histological grade was classified as well-differentiated, moderately differentiated, and poorly differentiated. Survival analysis was performed using Cox proportional hazards regression.RESULTS There were 201(75.8%) well-, 45(16.9%) moderatelyand 19(7.2%) poorly-differentiated tumors. Histological grade significantly stratified the 5-year overall survival(OS), 94%, 71% and 30% respectively(P < 0.001) as well as the 5-year disease-free survival(DFS) 66%, 21% and 0%, respectively(P < 0.001). Independent predictors of DFS included tumor grade(HR = 1.78, 95%CI: 1.21-2.63, P = 0.008), lymph node involvement(HR = 0.33, 95%CI: 0.11-0.98, P < 0.02), previous surgical score(HR = 1.31, 95%CI: 1.1-1.65, P = 0.03) and peritoneal carcinomatosis index(PCI)(HR = 1.05, 95%CI: 1.02-1.08, P = 0.002). Independent predictors of OS include tumor grade(HR = 2.79, 95%CI: 1.26-6.21, P = 0.01), PCI(HR = 1.10, 95%CI: 1.03-1.16, P = 0.002), and complete cytoreduction(HR = 0.32, 95%CI: 0.11-0.92, P = 0.03). Tumor grade and PCI were the only independent predictors of both DFS and OS. Furthermore, histological grade and lymphovascular invasion stratified the risk of lymph node metastasis into a low(6%) and high(40%) risk groups. CONCLUSION Our data demonstrates that moderately differentiated MAA have a clinical behavior and outcome that is distinct from well-and poorly-differentiated MAA. The threetier grade classification provides improved prognostic stratification and should be incorporated into patient selection and treatment algorithms. | Travis Edward Grotz Richard E Royal Paul F Mansfield Michael James Overman Gary N Mann Kristen Ashlee Robinson Karen A Beaty Safiea Rafeeq Auerlio Matamoros Michelle W Taggart Keith Francis Fournier | 2017 | World Journal of Gastrointestinal Oncology2017，9，9： | 2 |
| 14 | Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial显示文摘 | Wendy S Atkin Rob Edwards Ines Kralj-Hans Kate Wooldrage Andrew R Hart John MA Northover D Max Parkin Jane Wardle Stephen W Duffy Jack Cuzick | 2010 | The Lancet . 2010 (9726)2010，，： | 2 |
| 15 | The NLRP4-DTX4 axis: a key suppressor of TBK1 and innate antiviral signaling显示文摘 | Soratree Charoenthongtrakul Linlin Gao Edward W Harhaj | 2012 | Cellular & Molecular Immunology2012，9，6： | 2 |
| 16 | Radial variation in the axial conductivity of Populus and its significance in heat pulse velocity measurement显示文摘 | Edwards W R N R E Booker | 1984 | Journal of Experimental Botany1984，33，153： | 2 |
| 17 | Technology of Cellulose Esters Pennsylvania 显示文摘 | EDWARD C W | 1921 | Eschenhach Printing Company1921，，： | 1 |
| 18 | A new technique for measuring the mechanical properties of thin films 显示文摘 | Shape W N Bin Y Edwards R L | 1997 | Journal of Microelectromech System1997，，6： | 1 |
| 19 | Quantitative assessment of factors affects the recovery of indigenous and released thermophilic bacteria from compost 显示文摘 | AMNER W MCCARTHY A J EDWARDS C | 1988 | Applied Environmentd Microbiology1988，54，12： | 1 |
| 20 | Myocarditis:A histopathologic definition and classification显示文摘 | Billingham ME Edwards W | 1986 | J Cardiovasc Pathol1986，1，1： | 1 |
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