美国医学遗传学与基因组学学会(The American College of Medical Genetics and Genomics,ACMG)曾制定过序列变异解读指南.在过去的十年中,随着新一代高通量测序的出现,测序技术有了快速发展.利用新一代测序技术,临床实验室检测遗传性...美国医学遗传学与基因组学学会(The American College of Medical Genetics and Genomics,ACMG)曾制定过序列变异解读指南.在过去的十年中,随着新一代高通量测序的出现,测序技术有了快速发展.利用新一代测序技术,临床实验室检测遗传性疾病的产品种类不断增加,包括基因分型、单基因、基因包、外显子组、基因组、转录组和表观遗传学检测.随着技术的复杂性日益增加,基因检测在序列解读方面不断面临着新的挑战.因此ACMG在2013年成立了一个工作组来重新审视和修订序列变异解读的标准和指南,工作组包括ACMG、分子病理协会(the Association for Molecular Pathology,AMP)和美国病理学家协会(the College of American Pathologists,CAP)的代表.该工作组由临床实验室主任和临床医生组成.本报告代表了工作组中来自ACMG,AMP和CAP的专家意见.本报告提出的建议可应用于临床实验室的各种基因检测方法,包括基因分型、单基因、基因包、外显子组和基因组.本报告建议使用特定标准术语来描述孟德尔疾病相关的基因变异"——致病的"、"可能致病的"、"意义不明确的"、"可能良性的"和"良性的".此外,本报告描述了基于典型的数据类型(如人群数据,计算数据,功能数据,共分离数据)对变异进行五级分类的标准过程.由于临床基因检测分析和解读中不断增加的复杂性,ACMG强烈建议临床分子基因检测应在符合临床实验室改进修正案(CLIA)认证的实验室中进行,其检测结果应由通过职业认证的临床分子遗传学家或分子遗传病理学家或相同职能的专业人员解读.展开更多
Background Clinical practice guidelines （CPGs） play an important role in healthcare in China as well as in the world. However, the current status and trends of Chinese CPGs are unknown. The aim of this study was to ...Background Clinical practice guidelines （CPGs） play an important role in healthcare in China as well as in the world. However, the current status and trends of Chinese CPGs are unknown. The aim of this study was to systematically review the present situation and the quality of Chinese CPGs published in the peer-reviewed medical literature. Methods To identify Chinese CPGs, a systematic search of relevant literature databases （CBM, WANFANG, VIP, and CNKI） was performed for the period January 1978 to December 2010. We used the AGREE II instrument to assess the quality of the included guidelines. Results We evaluated 269 guidelines published in 115 medical journals from 1993 to 2010 and produced by 256 different developers. Only four guidelines （1%） described the systematic methods for searching and selecting the evidence, 14 （5%） guidelines indicated an explicit link between the supporting evidence and the recommendations, only one guideline used the Grading of Recommendations Assessment, Development and Evaluation （GRADE） system. Thirty-one guidelines （12%） mentioned updates and the average frequency of update was 5.5 years; none described a procedure for updating the guideline. From the assessment with the Appraisal of Guidelines for Research and Ecaluation II （AGREE II）, the mean scores were low for the domains ＂scope and purpose＂ （19%） and ＂clarity of presentation＂ （26%） and very low for the other domains （＂rigour of development＂ 7%, ＂stakeholder involvement＂ 8%, ＂applicability＂ 6% and ＂editorial independence＂ 2%）. Conclusions Compared with other studies on the quality of guidelines assessed with the AGREE instrument in other countries, Chinese CPGs received lower scores, which indicates a relatively poor quality of the guidelines. However, there was some increase over time.展开更多
The aim of this paper is to review the development and state of the art in the application of certain organosilicon compounds known as trialkoxysilanes （or simply silanes） to the problems of the metal finishing indu...The aim of this paper is to review the development and state of the art in the application of certain organosilicon compounds known as trialkoxysilanes （or simply silanes） to the problems of the metal finishing industry. The ultimate goal of this work is the replacement of chromate passivation and paint pretreatments, as well as overcoming the shortcomings of organic coatings formulated in the modern environmentally friendly world, thus without chromate or chromated pigments, volatile organic carbon （VOC） containing compounds or harazardous air pollutants （HAPs）.展开更多
Problems due to the taste and odor in drinking water are common in treatment facilities around the world. Taste and odor are perceived by the public as the primary indicators of the safely and acceptability of drinkin...Problems due to the taste and odor in drinking water are common in treatment facilities around the world. Taste and odor are perceived by the public as the primary indicators of the safely and acceptability of drinking water and are mainly caused by the presence of two semi-volatile compounds - 2-methyl isobomeol （MIB） and geosmin. A review of these two taste and odor causing compounds in drinking water is presented. The sources for the formation of these compounds in water are discussed alongwith the health and regulatory implications. The recent developments in the analysis of MIB/geosmin in water which have allowed for rapid measurements in the nanogram per liter concentrations are also discussed. This review focuses on the relevant treatment alternatives, that are described in detail with emphasis on their respective advantages and problems associated with their implementation in a full- scale facility. Conventional treatment processes in water treatment plants, such as coagulation, sedimentation and chlorination have been found to be ineffective for removal of M1B/geosmin. Studies have shown powdered activated carbon, ozonation and biofiltration to be effective in treatment of these two compounds. Although some of these technologies are more effective and show more promise than the others, much work remains to be done to optimize these technologies so that they can be retrofitted or installed with minimal impact on the overall operation and effectiveness of the treatment system.展开更多
c-Jun,the most extensively studied protein of the activator protein-1(AP-1)complex,is involved in numerous cell activities,such as proliferation,apoptosis,survival,tumorigenesis and tissue morphogenesis.Earlier studie...c-Jun,the most extensively studied protein of the activator protein-1(AP-1)complex,is involved in numerous cell activities,such as proliferation,apoptosis,survival,tumorigenesis and tissue morphogenesis.Earlier studies focused on the structure and function have led to the identification of c-Jun as a basic leucine zipper(bZIP)transcription factor that acts as homo-or heterodimer,binding to DNA and regulating gene transcription.Later on,it was shown that extracellular signals can induce post-translational modifications of c-Jun,resulting in altered transcriptional activity and target gene expression.More recent work has uncovered multiple layers of a complex regulatory scheme in which c-Jun is able to crosstalk,amplify and integrate different signals for tissue development and disease.One example of such scheme is the autocrine amplification loop,in which signal-induced AP-1 activates the c-Jun gene promoter,while increased c-Jun expression feedbacks to potentiate AP-1 activity.Another example of such scheme,based on recent characterization of gene knockout mice,is that c-Jun integrates signals of several developmental pathways,including EGFR-ERK,EGFR-RhoA-ROCK,and activin B-MAP3K1-JNK for embryonic eyelid closure.After more than two decades of extensive research,c-Jun remains at the center stage of a molecular network with mysterious functional properties,some of which are yet to be discovered.In this article,we will provide a brief historical overview of studies on c-Jun regulation and function,and use eyelid development as an example to illustrate the complexity of c-Jun crosstalking with signaling pathways.展开更多
Herein,we define the role of ferroptosis in the pathogenesis of diabetic cardiomyopathy(DCM)by examining the expression of key regulators of ferroptosis in mice with DCM and a new ex vivo DCM model.Advanced glycation ...Herein,we define the role of ferroptosis in the pathogenesis of diabetic cardiomyopathy(DCM)by examining the expression of key regulators of ferroptosis in mice with DCM and a new ex vivo DCM model.Advanced glycation end-products(AGEs),an important pathogenic factor of DCM,were found to induce ferroptosis in engineered cardiac tissues(ECTs),as reflected through increased levels of Ptgs2 and lipid peroxides and decreased ferritin and SLC7 A11 levels.Typical morphological changes of ferroptosis in cardiomyocytes were observed using transmission electron microscopy.Inhibition of ferroptosis with ferrostatin-1 and deferoxamine prevented AGE-induced ECT remodeling and dysfunction.Ferroptosis was also evidenced in the heart of type 2 diabetic mice with DCM.Inhibition of ferroptosis by liproxstatin-1 prevented the development of diastolic dysfunction at 3 months after the onset of diabetes.Nuclear factor erythroid 2-related factor 2(NRF2)activated by sulforaphane inhibited cardiac cell ferroptosis in both AGE-treated ECTs and hearts of DCM mice by upregulating ferritin and SLC7 A11 levels.The protective effect of sulforaphane on ferroptosis was AMP-activated protein kinase(AMPK)-dependent.These findings suggest that ferroptosis plays an essential role in the pathogenesis of DCM;sulforaphane prevents ferroptosis and associated pathogenesis via AMPK-mediated NRF2 activation.This suggests a feasible therapeutic approach with sulforaphane to clinically prevent ferroptosis and DCM.展开更多
A SHRIMP U-Pb zircon age of 1437±21 Ma was obtained for a recently discovered K-bentonite bed in the Tieling Formation,situated northeast of Beijing at the boundary between Liaoning and Hebei provinces,on the nor...A SHRIMP U-Pb zircon age of 1437±21 Ma was obtained for a recently discovered K-bentonite bed in the Tieling Formation,situated northeast of Beijing at the boundary between Liaoning and Hebei provinces,on the northern margin of the North China Craton(NCC).The SHRIMP U-Pb age places Tieling Formation near the end of the Calymmian Period of the early Mesoproterozoic Era.In addition,a SHRIMP U-Pb zircon date of 1372±18 Ma was acquired for K-bentonite beds in the overlying,dark-shale-dominated Xiamaling Formation from the same location northeast of Beijing.This date assigns a similar Mid-Mesoproterozoic(Ectasian Period) age for the Xiamaling Formation,as have previously determined dates from other sections northwest of Beijing.These dates indicate that the Tieling and Xiamaling formations,as well as the related succession in the eastern part of the Yanshan Mountains,represented by the well-known Meso-to Neoproterozoic standard section in Jixian,can be correlated well with sections northwest of Beijing in the western part of the Yanshan Mountains.In other words,the boundary between the Calymmian and Ectasian periods in the northern parts of the NCC is marked by the unconformity between the Tieling and Xiamaling formations in the northern NCC.This boundary was previously ascribed to the "Qinyu Orogeny" and thought to be of Grenville age.In this regard,the conventional "Qinyu Orogeny" should now be regarded as a short-lived regional uplift during Early Mesoproterozoic time,rather than a result from the Grenvillian assembly of the NCC to the Rodinia Supercontinent(～1.0 Ga).展开更多
We report an improved measurement of the neutrino mixing angle θ13 from the Daya Bay Reactor Neutrino Experiment. We exclude a zero value for sin22θ13 with a significance of 7.7 standard deviations. Electron antineu...We report an improved measurement of the neutrino mixing angle θ13 from the Daya Bay Reactor Neutrino Experiment. We exclude a zero value for sin22θ13 with a significance of 7.7 standard deviations. Electron antineutrinos from six reactors of 2.9 GWm th were detected in six antineutrino detectors deployed in two near （flux-weighted baselines of 470 m and 576 m） and one far （1648 m） underground experimental halls. Using 139 days of data, 28909 （205308） electron antineutrino candidates were detected at the far hall （near halls）. The ratio of the observed to the expected number of antineutrinos assuming no oscillations at the far hall is 0.944± 0.007（stat.） ± 0.003（syst.）. An analysis of the relative rates in six detectors finds sin22θ13=0.089± 0.010（stat.）±0.005（syst.） in a three-neutrino framework.展开更多
文摘美国医学遗传学与基因组学学会(The American College of Medical Genetics and Genomics,ACMG)曾制定过序列变异解读指南.在过去的十年中,随着新一代高通量测序的出现,测序技术有了快速发展.利用新一代测序技术,临床实验室检测遗传性疾病的产品种类不断增加,包括基因分型、单基因、基因包、外显子组、基因组、转录组和表观遗传学检测.随着技术的复杂性日益增加,基因检测在序列解读方面不断面临着新的挑战.因此ACMG在2013年成立了一个工作组来重新审视和修订序列变异解读的标准和指南,工作组包括ACMG、分子病理协会(the Association for Molecular Pathology,AMP)和美国病理学家协会(the College of American Pathologists,CAP)的代表.该工作组由临床实验室主任和临床医生组成.本报告代表了工作组中来自ACMG,AMP和CAP的专家意见.本报告提出的建议可应用于临床实验室的各种基因检测方法,包括基因分型、单基因、基因包、外显子组和基因组.本报告建议使用特定标准术语来描述孟德尔疾病相关的基因变异"——致病的"、"可能致病的"、"意义不明确的"、"可能良性的"和"良性的".此外,本报告描述了基于典型的数据类型(如人群数据,计算数据,功能数据,共分离数据)对变异进行五级分类的标准过程.由于临床基因检测分析和解读中不断增加的复杂性,ACMG强烈建议临床分子基因检测应在符合临床实验室改进修正案(CLIA)认证的实验室中进行,其检测结果应由通过职业认证的临床分子遗传学家或分子遗传病理学家或相同职能的专业人员解读.
文摘Background Clinical practice guidelines （CPGs） play an important role in healthcare in China as well as in the world. However, the current status and trends of Chinese CPGs are unknown. The aim of this study was to systematically review the present situation and the quality of Chinese CPGs published in the peer-reviewed medical literature. Methods To identify Chinese CPGs, a systematic search of relevant literature databases （CBM, WANFANG, VIP, and CNKI） was performed for the period January 1978 to December 2010. We used the AGREE II instrument to assess the quality of the included guidelines. Results We evaluated 269 guidelines published in 115 medical journals from 1993 to 2010 and produced by 256 different developers. Only four guidelines （1%） described the systematic methods for searching and selecting the evidence, 14 （5%） guidelines indicated an explicit link between the supporting evidence and the recommendations, only one guideline used the Grading of Recommendations Assessment, Development and Evaluation （GRADE） system. Thirty-one guidelines （12%） mentioned updates and the average frequency of update was 5.5 years; none described a procedure for updating the guideline. From the assessment with the Appraisal of Guidelines for Research and Ecaluation II （AGREE II）, the mean scores were low for the domains ＂scope and purpose＂ （19%） and ＂clarity of presentation＂ （26%） and very low for the other domains （＂rigour of development＂ 7%, ＂stakeholder involvement＂ 8%, ＂applicability＂ 6% and ＂editorial independence＂ 2%）. Conclusions Compared with other studies on the quality of guidelines assessed with the AGREE instrument in other countries, Chinese CPGs received lower scores, which indicates a relatively poor quality of the guidelines. However, there was some increase over time.
文摘The aim of this paper is to review the development and state of the art in the application of certain organosilicon compounds known as trialkoxysilanes （or simply silanes） to the problems of the metal finishing industry. The ultimate goal of this work is the replacement of chromate passivation and paint pretreatments, as well as overcoming the shortcomings of organic coatings formulated in the modern environmentally friendly world, thus without chromate or chromated pigments, volatile organic carbon （VOC） containing compounds or harazardous air pollutants （HAPs）.
文摘Problems due to the taste and odor in drinking water are common in treatment facilities around the world. Taste and odor are perceived by the public as the primary indicators of the safely and acceptability of drinking water and are mainly caused by the presence of two semi-volatile compounds - 2-methyl isobomeol （MIB） and geosmin. A review of these two taste and odor causing compounds in drinking water is presented. The sources for the formation of these compounds in water are discussed alongwith the health and regulatory implications. The recent developments in the analysis of MIB/geosmin in water which have allowed for rapid measurements in the nanogram per liter concentrations are also discussed. This review focuses on the relevant treatment alternatives, that are described in detail with emphasis on their respective advantages and problems associated with their implementation in a full- scale facility. Conventional treatment processes in water treatment plants, such as coagulation, sedimentation and chlorination have been found to be ineffective for removal of M1B/geosmin. Studies have shown powdered activated carbon, ozonation and biofiltration to be effective in treatment of these two compounds. Although some of these technologies are more effective and show more promise than the others, much work remains to be done to optimize these technologies so that they can be retrofitted or installed with minimal impact on the overall operation and effectiveness of the treatment system.
文摘c-Jun,the most extensively studied protein of the activator protein-1(AP-1)complex,is involved in numerous cell activities,such as proliferation,apoptosis,survival,tumorigenesis and tissue morphogenesis.Earlier studies focused on the structure and function have led to the identification of c-Jun as a basic leucine zipper(bZIP)transcription factor that acts as homo-or heterodimer,binding to DNA and regulating gene transcription.Later on,it was shown that extracellular signals can induce post-translational modifications of c-Jun,resulting in altered transcriptional activity and target gene expression.More recent work has uncovered multiple layers of a complex regulatory scheme in which c-Jun is able to crosstalk,amplify and integrate different signals for tissue development and disease.One example of such scheme is the autocrine amplification loop,in which signal-induced AP-1 activates the c-Jun gene promoter,while increased c-Jun expression feedbacks to potentiate AP-1 activity.Another example of such scheme,based on recent characterization of gene knockout mice,is that c-Jun integrates signals of several developmental pathways,including EGFR-ERK,EGFR-RhoA-ROCK,and activin B-MAP3K1-JNK for embryonic eyelid closure.After more than two decades of extensive research,c-Jun remains at the center stage of a molecular network with mysterious functional properties,some of which are yet to be discovered.In this article,we will provide a brief historical overview of studies on c-Jun regulation and function,and use eyelid development as an example to illustrate the complexity of c-Jun crosstalking with signaling pathways.
基金supported in part by American Diabetes Association(1-18-IBS-082 to LC,USA)the National Key R&D Program of China(2016YFC0900903 to YZ,China)。
文摘Herein,we define the role of ferroptosis in the pathogenesis of diabetic cardiomyopathy(DCM)by examining the expression of key regulators of ferroptosis in mice with DCM and a new ex vivo DCM model.Advanced glycation end-products(AGEs),an important pathogenic factor of DCM,were found to induce ferroptosis in engineered cardiac tissues(ECTs),as reflected through increased levels of Ptgs2 and lipid peroxides and decreased ferritin and SLC7 A11 levels.Typical morphological changes of ferroptosis in cardiomyocytes were observed using transmission electron microscopy.Inhibition of ferroptosis with ferrostatin-1 and deferoxamine prevented AGE-induced ECT remodeling and dysfunction.Ferroptosis was also evidenced in the heart of type 2 diabetic mice with DCM.Inhibition of ferroptosis by liproxstatin-1 prevented the development of diastolic dysfunction at 3 months after the onset of diabetes.Nuclear factor erythroid 2-related factor 2(NRF2)activated by sulforaphane inhibited cardiac cell ferroptosis in both AGE-treated ECTs and hearts of DCM mice by upregulating ferritin and SLC7 A11 levels.The protective effect of sulforaphane on ferroptosis was AMP-activated protein kinase(AMPK)-dependent.These findings suggest that ferroptosis plays an essential role in the pathogenesis of DCM;sulforaphane prevents ferroptosis and associated pathogenesis via AMPK-mediated NRF2 activation.This suggests a feasible therapeutic approach with sulforaphane to clinically prevent ferroptosis and DCM.
基金supported by the National Natural Science Foundation of China (40372057 and 40772076)the SINOPEC Project (G0800-06-ZS-319)the China Geological Survey (CGS) project (1212010611802)
文摘A SHRIMP U-Pb zircon age of 1437±21 Ma was obtained for a recently discovered K-bentonite bed in the Tieling Formation,situated northeast of Beijing at the boundary between Liaoning and Hebei provinces,on the northern margin of the North China Craton(NCC).The SHRIMP U-Pb age places Tieling Formation near the end of the Calymmian Period of the early Mesoproterozoic Era.In addition,a SHRIMP U-Pb zircon date of 1372±18 Ma was acquired for K-bentonite beds in the overlying,dark-shale-dominated Xiamaling Formation from the same location northeast of Beijing.This date assigns a similar Mid-Mesoproterozoic(Ectasian Period) age for the Xiamaling Formation,as have previously determined dates from other sections northwest of Beijing.These dates indicate that the Tieling and Xiamaling formations,as well as the related succession in the eastern part of the Yanshan Mountains,represented by the well-known Meso-to Neoproterozoic standard section in Jixian,can be correlated well with sections northwest of Beijing in the western part of the Yanshan Mountains.In other words,the boundary between the Calymmian and Ectasian periods in the northern parts of the NCC is marked by the unconformity between the Tieling and Xiamaling formations in the northern NCC.This boundary was previously ascribed to the "Qinyu Orogeny" and thought to be of Grenville age.In this regard,the conventional "Qinyu Orogeny" should now be regarded as a short-lived regional uplift during Early Mesoproterozoic time,rather than a result from the Grenvillian assembly of the NCC to the Rodinia Supercontinent(～1.0 Ga).
基金Supported by the Ministry of Science and Technology of Chinathe United States Department of Energy+15 种基金the Chinese Academy of Sciencesthe National Natural Science Foundation of Chinathe Guangdong provincial governmentthe Shenzhen municipal governmentthe China Guangdong Nuclear Power GroupShanghai Laboratory for Particle Physics and Cosmologythe Research Grants Council of the Hong Kong Special Administrative Region of ChinaUniversity Development Fund of The University of Hong Kongthe MOE program for Research of Excellence at NTU, NCTUNSC fund support from Taipeithe U.S. National Science Foundationthe Alfred P. Sloan Foundationthe Ministry of EducationYouth and Sports of the Czech Republicthe Czech Science Foundationthe Joint Institute of Nuclear Research in Dubna,Russia
文摘We report an improved measurement of the neutrino mixing angle θ13 from the Daya Bay Reactor Neutrino Experiment. We exclude a zero value for sin22θ13 with a significance of 7.7 standard deviations. Electron antineutrinos from six reactors of 2.9 GWm th were detected in six antineutrino detectors deployed in two near （flux-weighted baselines of 470 m and 576 m） and one far （1648 m） underground experimental halls. Using 139 days of data, 28909 （205308） electron antineutrino candidates were detected at the far hall （near halls）. The ratio of the observed to the expected number of antineutrinos assuming no oscillations at the far hall is 0.944± 0.007（stat.） ± 0.003（syst.）. An analysis of the relative rates in six detectors finds sin22θ13=0.089± 0.010（stat.）±0.005（syst.） in a three-neutrino framework.
