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| 1 | COOH-terminal deletion of HBx gene is a frequent event in HBV-associated hepatocellular carcinoma显示文摘AIM:To investigate the hepatitis B virus (HBV) x gene (HBx) state in the tissues of HBV-related hepatocellular carcinoma (HCC) in Chinese patients and whether there were particular HBx mutations. METHODS: HBx gene was amplified and direct sequencing was used in genomic DNA samples from 20 HCC and corresponding non-cancerous liver tissues from HBsAg-positive patients. HBV DNA integration and HBx deleted mutation were validated in 45 HCC patients at different stages by Southern blot analysis and polymerase chain reaction methods. RESULTS: The frequencies of HBx point mutations were significantly lower in HCC than their corresponding non- cancerous liver tissues (11/19 vs 18/19, P = 0.019). In contrast, deletions in HBx gene were significantly higher in HCC than their non-cancerous liver tissues (16/19 vs 4/19, P < 0.001). The deletion of HBx COOH-terminal was detected in 14 HCC tissues. A specific integration of HBx at 17p13 locus was also found in 8 of 16 HCC, and all of them also exhibited full-length HBx deletions. Integrated or integrated coexistence with replicated pattern was obtained in 45.5% (20/45) - 56.8% (25/45) tumors and 40.9% (18/45) - 52.3% (23/45) non-tumor tissues. CONCLUSION: HBx deletion, especially the COOH- terminal deletion of HBx is a frequent event in HBV-associated HCC tissues in China. HBV integration had also taken place in partial HCC tissues. This supporting the hypothesis that deletion and probably integrated forms of the HBx gene may be implicated in liver carcinogenesis. | Xiao-Hong Liu Jing Lin Shu-Hui Zhang Shun-Min Zhang Mark A Feitelson Heng-Jun Gao Ming-Hua Zhu | 2008 | World Journal of Gastroenterology2008，14，9： | 24 |
| 2 | Global blue carbon accumulation in tidal wetlands increases with climate change显示文摘Coastal tidal wetlands produce and accumulate significant amounts of organic carbon(C)that help to mitigate climate change.However,previous data limitations have prevented a robust evaluation of the global rates and mechanisms driving C accumulation.Here,we go beyond recent soil C stock estimates to reveal global tidal wetland C accumulation and predict changes under relative sea level rise,temperature and precipitation.We use data from literature study sites and our new observations spanning wide latitudinal gradients and 20 countries.Globally,tidal wetlands accumulate 53.65(95%CI:48.52-59.01)Tg C yr^(-1),which is~30%of the organic C buried on the ocean floor.Modeling based on current climatic drivers and under projected emissions scenarios revealed a net increase in the global C accumulation by2100.This rapid increase is driven by sea level rise in tidal marshes,and higher temperature and precipitation in mangroves.Countries with large areas of coastal wetlands,like Indonesia and Mexico,are more susceptible to tidal wetland C losses under climate change,while regions such as Australia,Brazil,the USA and China will experience a significant C accumulation increase under all projected scenarios. | Faming Wang Christian J.Sanders Isaac R.Santos Jianwu Tang Mark Schuerch Matthew L.Kirwan Robert E.Kopp Kai Zhu Xiuzhen Li Jiacan Yuan Wenzhi Liu Zhian Li | 2021 | National Science Review2021，8，9： | 22 |
| 3 | Meeting 24-h movement guidelines: Prevalence, correlates, and the relationships with overweight and obesity among Chinese children and adolescents显示文摘Background:Meeting 24-h movement guidelines by children and adolescents has been associated with improved indicators of health,although it has been under-studied in China.Hence,this study aimed to investigate the prevalence of meeting the 24-h movement guidelines,its correlates,and its relationships with body mass index in children and adolescents in China.Methods:Cross-sectional data from the 2017 Youth Study in China of 114,072 children and adolescents(mean age=13.75 years,49.18%boys)were used.Meeting 24-h movement guidelines(60 min of daily moderate-to-vigorous physical activity,2 h of daily leisure screen time,911 h and 810 h nightly sleep duration for 613-year-olds and 1417-year-olds,respectively)and height and weight of all participants were assessed.The prevalence of meeting the 24-h movement guidelines and World Health Organization weight status categories were determined.Generalized linear models were used to determine the correlates of meeting the 24-h movement guidelines and the relationships of meeting the 24-h movement guidelines with overweight(OW)and obesity(OB).Results:Only 5.12%of Chinese children and adolescents met the 24-h movement guidelines,and 22.44%were classified as OW/OB.Older children and adolescents were less likely to meet the 24-h movement guidelines.Parental education level and family income were positively related to meeting the 24-h movement guidelines.Children and adolescents meeting the 24-h movement guidelines showed lower odds ratios for OW/OB.Compared with participants meeting the 24-h movement guidelines,boys in 4th6th grades met none of the recommendations(OR=1.22,95%CI:1.061.40),met the screen time recommendation only(OR=1.13,95%CI:1.011.28),met the nightly sleep duration recommendation only(OR=1.14,95%CI:1.031.28),and had significantly higher odds ratios for OW/OB.Similar trends were observed for girls in 4th6th grades:meeting none of the guidelines(OR=1.35,95%CI:1.141.59),meeting sleep duration guidelines only(OR=1.23,95%CI:1.081.39),and meeting moderate-to-vigorous physical activity+nightly sleep duration guidelines(OR=1.24,95%CI:1.011.54).For girls in 7th9th grades,the following trend was observed:meeting none of the guidelines(OR=1.30,95%CI:1.011.67).Conclusion:Very few Chinese children and adolescents met the 24-h movement guidelines.Age(negatively correlated),parental education level,and family income(both positively correlated)were correlates of meeting the 24-h movement guidelines.Children and adolescents meeting the 24-h movement guidelines were more likely to have lower risks for OW/OB,especially in the youngest age group(Grades 46);and girls in the middle age group(Grades 79)were also more likely to have lower risks for OW/OB.Further research studies should explore additional correlates and determinants for meeting the 24-h movement guidelines.Also,future studies should use longitudinal or interventional designs to determine the relationships between meeting the 24-h movement guidelines and OW/OB and other health indicators,while taking sex and age differences into account. | Si-Tong Chen Yang Liu Mark S.Tremblay Jin-Tao Hong Yan Tang Zhen-Bo Cao Jie Zhuang Zheng Zhu Xueping Wu Lijuan Wang Yujun Cai Peijie Chen | 2021 | Journal of Sport and Health Science2021，10，3： | 12 |
| 4 | Canadian Agility and Movement Skill Assessment(CAMSA):Validity, objectivity, and reliability evidence for children 8–12 years of age显示文摘Purpose: The primary aim of this study was to develop an assessment of the fundamental, combined, and complex movement skills required to support childhood physical literacy. The secondary aim was to establish the feasibility, objectivity, and reliability evidence for the assessment.Methods: An expert advisory group recommended a course format for the assessment that would require children to complete a series of dynamic movement skills. Criterion-referenced skill performance and completion time were the recommended forms of evaluation. Children, 8–12 years of age, self-reported their age and gender and then completed the study assessments while attending local schools or day camps. Face validity was previously established through a Delphi expert(n = 19, 21% female) review process. Convergent validity was evaluated by age and gender associations with assessment performance. Inter-and intra-rater(n = 53, 34% female) objectivity and test–retest(n = 60, 47% female) reliability were assessed through repeated test administration.Results: Median total score was 21 of 28 points(range 5–28). Median completion time was 17 s. Total scores were feasible for all 995 children who self-reported age and gender. Total score did not differ between inside and outside environments(95% confidence interval(CI) of difference:-0.7 to 0.6;p = 0.91) or with/without footwear(95%CI of difference:-2.5 to 1.9; p = 0.77). Older age(p < 0.001, η2= 0.15) and male gender(p < 0.001, η2= 0.02)were associated with a higher total score. Inter-rater objectivity evidence was excellent(intraclass correlation coefficient(ICC) = 0.99) for completion time and substantial for skill score(ICC = 0.69) for 104 attempts by 53 children(34% female). Intra-rater objectivity was moderate(ICC = 0.52) for skill score and excellent for completion time(ICC = 0.99). Reliability was excellent for completion time over a short(2–4 days; ICC = 0.84) or long(8–14days; ICC = 0.82) interval. Skill score reliability was moderate(ICC = 0.46) over a short interval, and substantial(ICC = 0.74) over a long interval.Conclusion: The Canadian Agility and Movement Skill Assessment is a feasible measure of selected fundamental, complex and combined movement skills, which are an important building block for childhood physical literacy. Moderate-to-excellent objectivity was demonstrated for children 8–12 years of age. Test–retest reliability has been established over an interval of at least 1 week. The time and skill scores can be accurately estimated by 1 trained examiner. | Patricia E.Longmuir Charles Boyer Meghann Lloyd Michael M.Borghese Emily Knight Travis J.Saunders Elena Boiarskaia Weimo Zhu Mark S.Tremblay | 2017 | Journal of Sport and Health Science2017，6，2： | 10 |
| 5 | Neuronal failure in Alzheimer's disease: a view through the oxidative stress looking-glass显示文摘Considerable debate and controversy surround the cause(s) of Alzheimer's disease(AD). To date, several theories have gained notoriety, however none is universally accepted. In this review, we provide evidence for the oxidative stress-induced AD cascade that posits aged mitochondria as the critical origin of neurodegeneration in AD. | David J. Bonda Xinglong Wang Hyoung-Gon Lee Mark A. Smith George Perry Xiongwei Zhu | 2014 | Neuroscience Bulletin2014，30，2： | 7 |
| 6 | A novel deletion mutation, c.1296delT in the BCOR gene, is associated with oculo-facio-cardio-dental syndrome显示文摘The purpose of the present study was to analyze the clinical phenotypes of a girl with oculo-facio-cardio-dental(OFCD)syndrome and to identify the potential pathogenic mutation responsible for her disease. The patient underwent detailed clinical examinations and phenotype data were collected over a follow-up period of 9 years. Mutation analysis of the candidate gene BCOR was performed with polymerase chain reaction and Sanger sequencing. BCOR of 60 unrelated normal individuals were also sequenced as a control group. Clinical phenotyping and follow-up study results indicate that this patient had multiple system anomalies including ocular, facial, cardiac, dental, and limb malformations. In addition, papilloma of the choroid plexus was identified, which represents the first report of this phenotype in an OFCD patient. A novel deletion mutation, c.1296 delT in exon4 of the BCOR gene, was identified in this patient and was not found in her parents or in 60 normal unrelated individuals. This deletion was a frameshift mutation and is proposed to encode a premature stop codon, thus producing a truncated protein. Our patient fitted the diagnostic criteria for OFCD syndrome and we report the first papilloma of the choroid plexus in an OFCD patient, expanding the recognized phenotypic spectrum of this disease. Meanwhile, we identified a novel deletion mutation that may cause OFCD syndrome. | Jingshang Zhang Hongyan Jia Jinda Wang Ying Xiong Jing Li Xiaoxia Li Jing Zhao Xiaohui Zhang Qisheng You Guyu Zhu Frank F.Tsai Mark Espina Xiuhua Wan | 2019 | Science China(Life Sciences)2019，62，1： | 6 |
| 7 | Direct laser writing of volumetric gradient index lenses and waveguides显示文摘Direct laser writing(DLW)has been shown to render 3D polymeric optical components,including lenses,beam expanders,and mirrors,with submicrometer precision.However,these printed structures are limited to the refractive index and dispersive properties of the photopolymer.Here,we present the subsurface controllable refractive index via beam exposure(SCRIBE)method,a lithographic approach that enables the tuning of the refractive index over a range of greater than 0.3 by performing DLW inside photoresist-filled nanoporous silicon and silica scaffolds.Adjusting the laser exposure during printing enables 3D submicron control of the polymer infilling and thus the refractive index and chromatic dispersion.Combining SCRIBE’s unprecedented index range and 3D writing accuracy has realized the world’s smallest(15μm diameter)spherical Luneburg lens operating at visible wavelengths.SCRIBE’s ability to tune the chromatic dispersion alongside the refractive index was leveraged to render achromatic doublets in a single printing step,eliminating the need for multiple photoresins and writing sequences.SCRIBE also has the potential to form multicomponent optics by cascading optical elements within a scaffold.As a demonstration,stacked focusing structures that generate photonic nanojets were fabricated inside porous silicon.Finally,an all-pass ring resonator was coupled to a subsurface 3D waveguide.The measured quality factor of 4600 at 1550 nm suggests the possibility of compact photonic systems with optical interconnects that traverse multiple planes.SCRIBE is uniquely suited for constructing such photonic integrated circuits due to its ability to integrate multiple optical components,including lenses and waveguides,without additional printed supports. | Christian R.Ocier Corey A.Richards Daniel A.Bacon-Brown Qing Ding Raman Kumar Tanner J.Garcia Jorik van de Groep Jung-Hwan Song Austin J.Cyphersmith Andrew Rhode Andrea N.Perry Alexander J.Littlefield Jinlong Zhu Dajie Xie Haibo Gao Jonah F.Messinger Mark L.Brongersma Kimani C.Toussaint Jr Lynford L.Goddard Paul V.Braun | 2020 | Light(Science & Applications)2020，9，1： | 6 |
| 8 | Human adenovirus(HAdV)infection in children with acute respiratory tract infections in Guangzhou,China,2010–2021:a molecular epidemiology study显示文摘Background Human adenovirus(HAdV)infection can cause a variety of diseases.It is a major pathogen of pediatric acute respiratory tract infections(ARIs)and can be life-threatening in younger children.We described the epidemiology and subtypes shifting of HAdV among children with ARI in Guangzhou,China.Methods We conducted a retrospective study of 161,079 children diagnosed with acute respiratory illness at the Guangzhou Women and Children’s Medical Center between 2010 and 2021.HAdV specimens were detected by real-time PCR and the hexon gene was used for phylogenetic analysis.Results Before the COVID-19 outbreak in Guangzhou,the annual frequency of adenovirus infection detected during this period ranged from 3.92%to 13.58%,with an epidemic peak every four to fve years.HAdV demonstrated a clear seasonal distribution,with the lowest positivity in March and peaking during summer(July or August)every year.A signifcant increase in HAdV cases was recorded for 2018 and 2019,which coincided with a shift in the dominant HAdV subtype from HAdV-3 to HAdV-7.The latter was associated with a more severe disease compared to HAdV-3.The average mortality proportion for children infected with HAdV from 2016 to 2019 was 0.38%but increased to 20%in severe cases.After COVID-19 emerged,HAdV cases dropped to 2.68%,suggesting that non-pharmaceutical interventions probably reduced the transmission of HAdV in the community.Conclusion Our study provides the foundation for the understanding of the epidemiology of HAdV and its associated risks in children in Southern China. | Yi Chen Tao Lin Chang‑Bing Wang Wan‑Li Liang Guang‑Wan Lian Mark Zanin Sook‑San Wong Xin‑Gui Tian Jia‑Yu Zhong Ying‑Ying Zhang Jia‑Hui Xie Ling‑Ling Zheng Fei‑Yan Chen Run Dang Ming‑Qi Zhao Yi‑Yu Yang Rong Zhou Bing Zhu | 2022 | World Journal of Pediatrics2022，18，8： | 5 |
| 9 | Suppressed oxygen extraction and degradation of LiNixMnyCo2O2 cathodes at high charge cut-off voltages显示文摘 | Jianming Zheng Pengfei Yan Jiandong Zhang Mark H. Engelhard Zihua Zhu Bryant J. Polzin Steve Trask Jie Xiao Chongmin Wang Jiguang Zhang | 2017 | Nano Research2017，10，12： | 5 |
| 10 | Divalent metal transporter, iron, and Parkinson's disease: A pathological relationship显示文摘 | Hyun-pil Lee Xiongwei Zhu Gang Liu Shu G Chen George Perry Mark A Smith Hyoung-gon Lee | 2010 | Cell Research2010，20，4： | 5 |
| 11 | Implementation of regional Acute Stroke Care Map increases thrombolysis rates for acute ischaemic stroke in Chinese urban area in only 3 months显示文摘Background The rate of intravenous thrombolysis for acute ischaemic stroke remains low in China.We investigated whether the implementation of a citywide Acute Stroke Care Map(ASCaM)is associated with an improvement of acute stroke care quality in a Chinese urban area.Methods The ASCaM comprises 10 improvement strategies and has been implemented through a network consisting of 20 tertiary hospitals.We identified 7827 patients with ischaemic stroke admitted from April to October 2017,and 506 patients underwent thrombolysis were finally included for analysis.Results Compared with‘pre-ASCaM period’,we observed an increased rate of administration of tissue plasminogen activator within 4.5 hours(65.4% vs 54.5%;adjusted OR,1.724;95% CI 1.21 to 2.45;p=0.003)during‘ASCaM period’.In multivariate analysis models,‘ASCaM period’was associated with a significant reduction in onset-to door time(114.1±55.7 vs 135.7±58.4 min,p=0.0002)and onset-to needle time(ONT)(169.2±58.1 vs 195.6±59.3 min,p<0.0001).Yet no change was found in door-to needle time.Clinical outcomes such as symptomatic intracranial haemorrhage,favourable functional outcome(modified Rankin Scale≤2)and in-hospital mortality remained unchanged.Conclusion The implementation of ASCaM was significantly associated with increased rates of intravenous thrombolysis and shorter ONT.The ASCaM may,in proof-of principle,serve as a model to reduce treatment delay and increase thrombolysis rates in Chinese urban areas and possibly other highly populated Asian regions. | Yi Sui Jianfeng Luo Chunyao Dong Liqiang Zheng Weijin Zhao Yao Zhang Ying Xian Huaguang Zheng Bernard Yan Mark Parsons Li Ren Ying Xiao Haoyue Zhu Lijie Ren Qi Fang Yi Yang Weidong Liu Bing Xu | 2021 | Stroke & Vascular Neurology2021，6，1： | 4 |
| 12 | Pyroptosis and pyroptosis-inducing cancer drugs显示文摘Pyroptosis,an inflammatory form of lytic cell death,is a type of cell death mediated by the gasdermin(GSDM)protein family.Upon recognizing exogenous or endogenous signals,cells undergo inflammasome assembly,GSDM cleavage,the release of proinflammatory cytokines and other cellular contents,eventually leading to inflammatory cell death.In this review,we discuss the roles of the GSDM family for anti-cancer functions and various antitumor drugs that could activate the pyroptosis pathways. | Fan Yang Sahana N.Bettadapura Mark SSmeltzer Hua Zhu Shanzhi Wang | 2022 | Acta Pharmacologica Sinica2022，43，10： | 4 |
| 13 | Neonatal vitamin A injection promotes cattle muscle growth and increases oxidative muscle fibers显示文摘Background: Vitamin A and its metabolite,retinoic acid(RA),are important regulators of cell differentiation and organ morphogenesis.Its impact on beef cattle muscle growth remains undefined.Method: Angus steer calves were administrated with 0(control) or 150,000 IU vitamin A(retinyl palmitate in glycerol,i.m.) per calf at birth and 1 month of age.At 2 months of age,a biopsy of the Biceps femoris muscle was obtained to analyze the immediate effects of vitamin A injection on myogenic capacity of muscle cells.The resulting steers were harvested at 14 months of age.Results: Vitamin A administration increased cattle growth at 2 months.At 2 months of age,Vitamin A increased PAX7 positive satellite cells and the expression of myogenic marker genes including PAX7,MYF5,MYOD and MYOG.Muscle derived mononuclear cells were further isolated and induced myogenesis in vitro.More myotubes and a higher degree of myogenesis was observed in vitamin A groups.Consistently,vitamin A increased Latissimus dorsi(LD) muscle fiber size at harvest.In addition,vitamin A increased the ratio of oxidative type I and type IIA fibers and reduced the glycolic type IIX fibers.Furthermore,we found that RA,a key bioactive metabolite of vitamin A,activated PPARGC1 A promoter,which explains the upregulated expression of PPARGC1 A in skeletal muscle.Conclusion: Vitamin A administration to neonatal calves enhanced postnatal muscle growth by promoting myogenesis and increasing satellite cell density,accompanied with a shift to oxidative muscle fibers. | Bo Wang Wei Nie Xing Fu Jeanene M de Avila Yannan Ma Mei-Jun Zhu Martin Maquivar Steven M Parish Jan R Busboom Mark L Nelson Min Du | 2019 | Journal of Animal Science and Biotechnology2019，10，1： | 3 |
| 14 | ICC density predicts bacterial overgrowth in a rat model of post-infectious IBS显示文摘AIM:To investigate the interstitial cells of Cajal(ICC) number using a new rat model.METHODS:Sprague-Dawley rats were assigned to two groups.The first group received gavage with Campylobacter jejuni(C.jejuni) 81-176.The second group was gavaged with placebo.Three months after clearance of Campylobacter from the stool,precise segments of duodenum,jejunum,and ileum were ligated in self-contained loops of bowel that were preserved in anaerobic bags.Deep muscular plexus ICC(DMP-ICC) were quantified by two blinded readers assessing the tissue in a random,coded order.The number of ICC per villus was compared among controls,Campylobacter recovered rats without small intestinal bacterial overgrowth(SIBO),and Campylobacter recovered rats with SIBO.RESULTS:Three months after recovery,27% of rats gavaged with C.jejuni had SIBO.The rats with SIBO had a lower number of DMP-ICC than controls in the jejunum and ileum.Additionally there appeared to be a density threshold of 0.12 DMP-ICC/villus that was associated with SIBO.If ileal density of DMP-ICC was < 0.12 ICC/villus,54% of rats had SIBO compared to 9% among ileal sections with > 0.12(P<0.05).If the density of ICC was < 0.12 DMP-ICC/villus in more than one location of the bowel,88% of these had SIBO compared to 6% in those who did not(P<0.001).CONCLUSION:In this post-infectious rat model,the development of SIBO appears to be associated with a reduction in DMP-ICC.Further study of this rat model might help understand the pathophysiology of postinfectious irritable bowel syndrome. | Sam-Ryong Jee Walter Morales Kimberly Low Christopher Chang Amy Zhu Venkata Pokkunuri Soumya Chatterjee Edy Soffer Jeffrey L Conklin Mark Pimentel | 2010 | World Journal of Gastroenterology2010，16，29： | 3 |
| 15 | Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: an open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study显示文摘 | Timothy Iveson Ross C Donehower Irina Davidenko Sergey Tjulandin Andrzej Deptala Mark Harrison Somanath Nirni Kuntegowdanahalli Lakshmaiah Anne Thomas Yizhou Jiang Min Zhu Rui Tang Abraham Anderson Sarita Dubey Kelly S Oliner Elwyn Loh | 2014 | Lancet Oncology2014，，9： | 3 |
| 16 | Dark,Beyond Deep:A Paradigm Shift to Cognitive AI with Humanlike Common Sense显示文摘Recent progress in deep learning is essentially based on a“big data for small tasks”paradigm,under which massive amounts of data are used to train a classifier for a single narrow task.In this paper,we call for a shift that flips this paradigm upside down.Specifically,we propose a“small data for big tasks”paradigm,wherein a single artificial intelligence(AI)system is challenged to develop“common sense,”enabling it to solve a wide range of tasks with little training data.We illustrate the potential power of this new paradigm by reviewing models of common sense that synthesize recent breakthroughs in both machine and human vision.We identify functionality,physics,intent,causality,and utility(FPICU)as the five core domains of cognitive AI with humanlike common sense.When taken as a unified concept,FPICU is concerned with the questions of“why”and“how,”beyond the dominant“what”and“where”framework for understanding vision.They are invisible in terms of pixels but nevertheless drive the creation,maintenance,and development of visual scenes.We therefore coin them the“dark matter”of vision.Just as our universe cannot be understood by merely studying observable matter,we argue that vision cannot be understood without studying FPICU.We demonstrate the power of this perspective to develop cognitive AI systems with humanlike common sense by showing how to observe and apply FPICU with little training data to solve a wide range of challenging tasks,including tool use,planning,utility inference,and social learning.In summary,we argue that the next generation of AI must embrace“dark”humanlike common sense for solving novel tasks. | Yixin Zhu Tao Gao Lifeng Fan Siyuan Huang Mark Edmonds Hangxin Liu Feng Gao Chi Zhang Siyuan Qi Ying Nian Wu Joshua B.Tenenbaum Song-Chun Zhu | 2020 | Engineering2020，6，3： | 3 |
| 17 | The efficacy and safety of pramipexole ER versus IR in Chinese patients with Parkinson’s disease: a randomized, double-blind, double-dummy, parallel-group study显示文摘Objective:To evaluate the non-inferiority of pramipexole extended-release(ER)versus immediate-release(IR)in Chinese patients with Parkinson’s disease(PD)in a double-blind,randomized,parallel-group study.Methods:Subjects were Chinese patients with idiopathic PD with diagnosis≥2 years prior to trial,age≥30 years old at diagnosis,and Modified Hoehn and Yahr score 2-4 during‘on’-time.Subjects received treatment with pramipexole ER(n=234)or IR(n=239).Non-inferiority was based on the primary endpoint,the change from baseline to end of maintenance(week 18)in the UPDRS(Parts II+III)total score.Results:For the primary endpoint,the adjusted mean changes(standard error)of UPDRS Parts II+III at week 18 were−13.81(0.655)and−13.05(0.643)for ER and IR formulations,respectively,using ANCOVA adjusted for treatment and centre(fixed effect)and baseline(covariate).The adjusted mean between group difference was 0.8 for the 2-sided 95%CI(−1.047,2.566).Since the lower limit of the 2-sided 95%CI(−1.047)for treatment difference was higher than the non-inferiority margin of−4,non-inferiority between pramipexole ER and IR was demonstrated.The incidence of adverse events(AEs)was 68.8%in the ER arm and 73.6%in the IR arm with few severe AEs(ER:2.1%;IR:3.8%).Conclusion:Based on the UPDRS II+III score,pramipexole ER was non-inferior to pramipexole IR.The safety profiles of pramipexole ER and IR were similar.These results were based on comparable mean daily doses and durations of treatment for both formulations. | Ying Wang Shenggang Sun Suiqiang Zhu Chunfeng Liu Yiming Liu Qing Di Huifang Shang Yan Ren Changhong Lu Mark Forrest Gordon Nolwenn Juhel Shengdi Chen for the Pramipexole ER Study Team | 2014 | Translational Neurodegeneration2014，3，1： | 3 |
| 18 | Elucidating the molecular responses of apple rootstock resistant to ARD pathogens:challenges and opportunities for development of genomics-assisted breeding tools显示文摘Apple replant disease(ARD)is a major limitation to the establishment of economically viable orchards on replant sites due to the buildup and long-term survival of pathogen inoculum.Several soilborne necrotrophic fungi and oomycetes are primarily responsible for ARD,and symptoms range from serious inhibition of growth to the death of young trees.Chemical fumigation has been the primary method used for control of ARD,and manipulating soil microbial ecology to reduce pathogen density and aggressiveness is being investigated.To date,innate resistance of apple rootstocks as a means to control this disease has not been carefully explored,partly due to the complex etiology and the difficulty in phenotyping the disease resistance.Molecular defense responses of plant roots to soilborne necrotrophic pathogens are largely elusive,although considerable progress has been achieved using foliar disease systems.Plant defense responses to necrotrophic pathogens consist of several interacting modules and operate as a network.Upon pathogen detection by plants,cellular signals such as the oscillation of Ca^(2+)concentration,reactive oxygen species(ROS)burst and protein kinase activity,lead to plant hormone biosynthesis and signaling.Jasmonic acid(JA)and ethylene(ET)are known to be fundamental to the induction and regulation of defense mechanisms toward invading necrotrophic pathogens.Complicated hormone crosstalk modulates the fine-tuning of transcriptional reprogramming and metabolic redirection,resulting in production of antimicrobial metabolites,enzyme inhibitors and cell wall refortification to restrict further pathogenesis.Transcriptome profiling of apple roots in response to inoculation with Pythium ultimum demonstrated that there is a high degree of conservation regarding the molecular framework of defense responses compared with those observed with foliar tissues.It is conceivable that the timing and intensity of genotype-specific defense responses may lead to different outcomes between rootstocks in response to invasion by necrotrophic pathogens.Elucidation of host defense mechanisms is critical in developing molecular tools for genomics-assisted breeding of resistant apple rootstocks.Due to their perennial nature,use of resistant rootstocks as a component for disease management might offer a durable and cost-effective benefit to tree performance than the standard practice of soil fumigation for control of ARD. | Yanmin Zhu Gennaro Fazio Mark Mazzola | 2014 | Horticulture Research2014，1，1： | 3 |
| 19 | Evolutionary transition between invertebrates and vertebrates via methylation reprogramming in embryogenesis显示文摘Major evolutionary transitions are enigmas,and the most notable enigma is between invertebrates and vertebrates,with numerous spectacular innovations.To search for the molecular connections involved,we asked whether global epigenetic changes may offer a clue by surveying the inheritance and reprogramming of parental DNA methylation across metazoans.We focused on gametes and early embryos,where the methylomes are known to evolve divergently between fish and mammals.Here,we find that methylome reprogramming during embryogenesis occurs neither in pre-bilaterians such as cnidarians nor in protostomes such as insects,but clearly presents in deuterostomes such as echinoderms and invertebrate chordates,and then becomes more evident in vertebrates.Functional association analysis suggests that DNA methylation reprogramming is associated with development,reproduction and adaptive immunity for vertebrates,but not for invertebrates.Interestingly,the single HOX cluster of invertebrates maintains unmethylated status in all stages examined.In contrast,the multiple HOX clusters show dramatic dynamics of DNA methylation during vertebrate embryogenesis.Notably,the methylation dynamics of HOX clusters are associated with their spatiotemporal expression in mammals.Our study reveals that DNA methylation reprogramming has evolved dramatically during animal evolution,especially after the evolutionary transitions from invertebrates to vertebrates,and then to mammals. | Xiaocui Xu Guoqiang Li Congru Li Jing Zhang Qiang Wang David KSimmons Xuepeng Chen Naveen Wijesena Wei Zhu Zhanyang Wang Zhenhua Wang Bao Ju Weimin Ci Xuemei Lu Daqi Yu Qian-fei Wang Neelakanteswar Aluru Paola Oliveri Yong EZhang Mark QMartindale Jiang Liu | 2019 | National Science Review2019，6，5： | 2 |
| 20 | Antisense Oligodeoxynucleotide Inhibits Expression of Re-com binantPorcine Follicle-Stim ulating Horm one Receptor显示文摘To assess the role of follicle stimulating hormone receptor(FSHR) gene expression in regulating expression of FSHR protein in the plasma membrane, the effects of a porcine FSHR cDNA antisense oligodeoxynucleotide (ODN) on FSHR mRNA levels and 125 I FSH binding were determined in Chinese hamster ovary cells expression recombinant porcine FSHR (pFSHR CHO cells). An 18 mer phosphorothioate endcapped antisense ODN that corresponded to the region surrounding the translation initiation codon of the porcine FSHR cDNA was synthesized. An 18 mer nonsense sequence of identical nucleotide composition, which had little homology to known DNA sequences, was synthesized for use as a control. pFSHR CHO cells were cultured in 24 well plates (10 5 cells/well) in the absence or presence of 1 20 μmol/L antisense or nonsense ODN for 24 h and then assayed for porcine FSHR mRNA, using quantitative reverse transcription and competitive polymerase chain reaction, and for 125 I FSH binding activity. Treatment with 10 μmol/L antisense ODN caused a paradoxical increase in porcine FSHR mRNA from 0.89±0.06 to 1.64±0.08 ng/mg total RNA ( P <0.05). Transfection with lipofectamine and 0.33 μmol/L antisense ODN caused an increase in porcine mRNA from 0.95±0.08 to 1.53±0.07 ng/mg total RAN. This was probably due to upregulation of mRNA synthesis resulting from inhibition of porcine FSHR protein translation. The nonsense ODN had no effect on porcine FSHR mRNA. Antisense, but not nonsense, ODN (10 μmol/L) inhibited membrane binding of 125 I FSH by 13.6± 0.8 % ( P <0.05) in 24 h. Treatment of cells with antisense ODN (10 μmol/L) for 48 h resulted in a 76±1.5 % ( P <0.05) inhibition of 125 I FSH binding. In contrast, transfection with lipofectamine and 0.33 μmol/L antisense ODN at 0 h caused a 76.1±1.3 % ( P <0.05) reduction in binding within 24 h. Binding had returned to 52.3±2.3 % ( P < 0.05) of normal by 48 h. These results indicate that an antisense ODN corresponding to the region of the translation start site of the porcine FSHR cDNA is an effective specific inhibitor of porcine FSHR synthesis and that inhibition of receptor synthesis causes a decrease in functional membrane bound FSHR. | ZHU Changhong 1, Mark D. Nixon 2, WANG Yifang 1, Andrew R. LaBarbera 3 1 Center of Reproductive Medicine, Tongji Hospital, Tongji Medical University, Wuhan 430030 2 Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267 0526 3 Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267 0526 | 1999 | Journal of Huazhong University of Science and Technology(Medical Sciences)1999，19，3： | 2 |
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