背景：以前的血管内超声（intravascular ultrasound，IVUS）试验证实，他汀治疗可减缓或阻止动脉粥样硬化的进展，但是迄今尚无应用动脉粥样斑块体积百分比（percent atheroma volume，PAV）证实粥样硬化消退的确切证据。PAV是最严格...背景：以前的血管内超声（intravascular ultrasound，IVUS）试验证实，他汀治疗可减缓或阻止动脉粥样硬化的进展，但是迄今尚无应用动脉粥样斑块体积百分比（percent atheroma volume，PAV）证实粥样硬化消退的确切证据。PAV是最严格的评价病变进展和消退的IVUS测量指标。
目标：评价极高强度他汀治疗是否能逆转IVUS确定的冠状动脉粥样硬化。
设计和地点：于美国、加拿大、欧洲和澳大利亚53个社区和3级保健中心进行前瞻性开标盲法终点试验（A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden，ASTEROID）。应用马达驱动回撤IVUS评价基线和治疗24个月时冠状动脉粥样斑块负荷。每对基线和随访IVUS测量结果均进行盲法分析。
病例：从2002年11月到2003年10月，507例患者有基线IVUS检查结果，并接受至少1个剂量的研究药物。在24个月后，349例患者具有可用于评估的系列IVUS检查结果。
干预：所有患者均接受瑞舒伐他汀40ms／d强化治疗。
主要观测指标：预先设定了两个一级疗效指标：PAV变化和基线最严重病变10min节段动脉粥样斑块体积变化。二级疗效指标为整个动脉标准化总斑块体积的变化。结果：平均（SD）LDL—C水平由基线时的130．4（34．3）ms／dL降至60．8（20．0）ms／扎，平均下降了53．2％（P〈0．001）。平均（SD）HDL-C水平从基线时的43．1（11．1）ms／dL升至49．0（12．6）ms／dL，平均增加了14．7％（P〈0．001）。整个血管PAV平均（SD）变化为-0．98％（3．15％），中位数为-0．79％（97．5％CI，-1．21％～-0．53％）（与基线比较，P〈0．001）。最严重病变10min节段斑块体积平均（SD）变化为-6．1（10．1）mm^3，中位数为-5．6mm^3（97．5％CI，-6．8～-4．0mm^3）（与基线比较，P〈0．001）。总斑块体积变化中位数降低了6．8％，�展开更多
The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve...The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve as a nexus for signal transduction and play a vital role in numerous biological processes. In this review, we highlight the known characteristics and components of the p38 pathway along with the mechanism and consequences of p38 activation. We focus on the role of p38 as a signal transduction mediator and examine the evidence linking p38 to inflammation, cell cycle, cell death, development, cell differentiation, senescence and tumorigenesis in specific cell types. Upstream and downstream components of p38 are described and questions remaining to be answered are posed. Finally, we propose several directions for future research on p38.展开更多
The term adakite was originally pro- posed to define silica-rich, high Sr/Y and La/Yb vol- canic and plutonic rocks derived from melting of the basaltic portion of oceanic crust subducted beneath volcanic arcs. It was...The term adakite was originally pro- posed to define silica-rich, high Sr/Y and La/Yb vol- canic and plutonic rocks derived from melting of the basaltic portion of oceanic crust subducted beneath volcanic arcs. It was also initially believed that ada- kite only occurs in convergent margins where young and thus still hot oceanic slabs are being subducted, but later studies have proposed that it also occurs in other arc settings where unusual tectonic conditions can lower the solidus of older slabs. Currently, ada- kite covers a range of arc rocks ranging from pristine slab melt, to adakite-peridotite hybrid melt, to melt derived from peridotite metasomatized by slab melt. Adakite studies have generated some confusions because (1) the definition of adakite combines com- positional criteria with a genetic interpretation (melt- ing of subducted basalt), (2) the definition is fairly broad and relies on chemistry as its distinguishing characteristic, (3) the use of high pressure melting experiment results on wet basalts as unequivocal proofs of slab melting and (4) the existence of ada- kitic rocks with chemical characteristics similar to adakites but are clearly unrelated to slab melting. Other studies have shown that adakitic rocks and a number of the previously reported adakites are pro- duced through melting of the mafic lower crust or ponded basaltic magma, high-pressure crystal frac- tionation of basaltic magma and low-pressure crystal fractionation of basaltic magma plus magma mixing processes in both arc or non-arc tectonic environ- ments. Despite the confusing interpretations on the petrogenesis of adakite and adakitic rocks, their in- vestigations have enriched our understanding of material recycling at subduction zones, crustal evolu- tionary processes and economic mineralization.展开更多
Dear Editor,Genome editing technologies enable precise modifications of DNA sequences in vivo and offer great promise for crop improvement. CRISPR/Cas9 （Clustered Regularly Interspaced Short Palindromic Repeats/CRISP...Dear Editor,Genome editing technologies enable precise modifications of DNA sequences in vivo and offer great promise for crop improvement. CRISPR/Cas9 （Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated Cas9） has revolution- ized genome editing because of its simplicity and versatility （Cong et al., 2013）.展开更多
Transforming growth factor-beta （TGF-β）/bone morphogenic protein （BMP） signaling is involved in the vast majority of cellular processes and is fundamentally important during the entire life of all metazoans. Dere...Transforming growth factor-beta （TGF-β）/bone morphogenic protein （BMP） signaling is involved in the vast majority of cellular processes and is fundamentally important during the entire life of all metazoans. Deregulation of TGF-β/ BMP activity almost invariably leads to developmental defects and/or diseases, including cancer. The proper functioning of the TGF-β/BMP pathway depends on its constitutive and extensive communication with other signaling pathways, leading to synergistic or antagonistic effects and eventually desirable biological outcomes. The nature of such signaling cross-talk is overwhelmingly complex and highly context-dependent. Here we review the different modes of cross-talk between TGF-β/BMP and the signaling pathways of Mitogen-activated protein kinase, phosphatidylinositol-3 kinase/ Akt, Wnt, Hedgehog, Notch, and the interleukin/interferon-gamma/tumor necrosis factor-alpha cytokines, with an emphasis on the underlying molecular mechanisms.展开更多
The Chinese Tianshan belt is a major part of the southern Central Asian Orogenic Belt, extending westward to Kyrgyzstan and Kazakhstan. Its Paleozoic tectonic evolution, crucial for understanding the amalgamation of C...The Chinese Tianshan belt is a major part of the southern Central Asian Orogenic Belt, extending westward to Kyrgyzstan and Kazakhstan. Its Paleozoic tectonic evolution, crucial for understanding the amalgamation of Central Asia, comprises two stages of subduction-collision. The first collisional stage built the Eo-Tianshan Mountains, before a Visean unconformity, in which all structures are verging north. It implied a southward subduction of the Central Tianshan Ocean beneath the Tarim active margin, that induced the Ordovician-Early Devonian Central Tianshan arc, to the south of which the South Tianshan back-arc basin opened. During the Late Devonian, the closure of this ocean led to a collision between Central Tianshan arc and the Kazakhstan-Yili-North Tianshan Block, and subsequently closure of the South Tianhan back-arc basin, producing two suture zones, namely the Central Tianshan and South Tianshan suture zones where ophiolitic melanges and HP metamorphic rocks were emplaced northward. The second stage included the Late Devonian-Carboniferous southward subduction of North Tianshan Ocean beneath the Eo-Tianshan active margin, underlined by the Yili-North Tianshan arc, leading to the collision between the Kazakhstan-Yili-NTS plate and an inferred Junggar Block at Late Carboniferous-Early Permian time. The North Tianshan Suture Zone underlines likely the last oceanic closure of Central Asia Orogenic Belt; all the oceanic domains were consumed before the Middle Permian. The amalgamated units were affected by a Permian major wrenching, dextral in the Tianshan. The correlation with the Kazakh and Kyrgyz Tianshan is clarified. The Kyrgyz South Tianshan is equivalent to the whole part of Chinese Tianshan （CTS and STS） located to the south of Narat Fault and Main Tianshan Shear Zone; the so-called Middle Tianshan thins out toward the east. The South Tianshan Suture of Kyrgyzstan correlates with the Central Tianshan Suture of Chinese Tianshan. The evolution of this southern domain remains similar from east （Ga展开更多
CRISPR/Cas9 （Clustered Regularly Interspaced Short Palin- dromic Repeats/CRISPR-associated Cas9 endonuclease）- mediated genome editing has revolutionized biological research and crop improvement because of its speci...CRISPR/Cas9 （Clustered Regularly Interspaced Short Palin- dromic Repeats/CRISPR-associated Cas9 endonuclease）- mediated genome editing has revolutionized biological research and crop improvement because of its specificity, simplicity, and versatility （reviewed in Komor et al., 2016a）.展开更多
The Trans-North China Belt （TNCB） is a Paleoproterozoic collisional orogen （ca. 1.9-1.8 Ga） responsible for the amalgamation of the North China Craton. Detailed field works in Liiliangshan, Hengshan, Wutaishan and...The Trans-North China Belt （TNCB） is a Paleoproterozoic collisional orogen （ca. 1.9-1.8 Ga） responsible for the amalgamation of the North China Craton. Detailed field works in Liiliangshan, Hengshan, Wutaishan and Fuping massifs where the belt is well exposed, allow us to draw a new tectonic map and crustal-scale cross sections. The available petrologic, radiometric, geochronologic data are integrated in a geodynamic evolution scheme for this orogen. The Low Grade Mafic Unit （LGMU） is interpreted as an ophiolitic nappe rooted in a suture zone located in the western part of the Lüliangshan. This ophiolitic nappe overthrusts to the SE upon the Orthogneiss-Volcanites Unit （OVU） that consists of a bimodal volcanic-sedimentary series metamorphosed under amphibolite facies conditions intruded by calcalkaline orthogneiss. The OVU is a composite Neoarchean-Paleoproterozoic magmatic arc developed during two stages （ca. 2500 and 2100 Ma） upon a continental basement corresponding to the western extension of the Neoarchean Fuping massif The OVU overthrusts to the SE the Fuping massif along the Longquanguan shear zone. This stack of nappes, coeval with an amphibolite facies metamorphism, is dated at ca. 1880 Ma. Subsequently, the metamorphic series experienced a widespread migmatization at 1850 Ma and was intruded by post-orogenic plutons dated at 1800 Ma. The weakly to unmetamorphosed Hutuo Supergroup unconformably overlies the metamorphosed and ductilely deformed units （OVU and LGMU）, but it is also involved in a second tectonic phase developed in subsurface conditions. These structural features lead us to question the ca. 2090 Ma age attributed to the Hutuo supergroup. Moreover, in the Fuping massif several structural and magmatic lines of evidence argue for an earlier orogenic event at ca. 2100 Ma that we relate to an older west-directed subduction below the Fuping Block. The Taihangshan Fault might be the location of a possible suture zone between the Fuping Block and an eastern one. A geodynamic展开更多
Gastric cancer remains one of the most common cancers worldwide and one of the leading cause for cancerrelated deaths. Gastric adenocarcinoma is a multifactorial disease that is genetically, cytologically and architec...Gastric cancer remains one of the most common cancers worldwide and one of the leading cause for cancerrelated deaths. Gastric adenocarcinoma is a multifactorial disease that is genetically, cytologically and architecturally more heterogeneous than other gastrointestinal carcinomas.The aberrant activation of the Wnt/β-catenin signaling pathway is involved in the development and progression of a significant proportion of gastric cancer cases. This review focuses on the participation of the Wnt/b-catenin pathway in gastric cancer by offering an analysis of the relevant literature published in this field. Indeed, it is discussed the role of key factors in Wnt/β-catenin signaling and their downstream effectors regulating processes involved in tumor initiation, tumor growth, metastasis and resistance to therapy. Available data indicate that constitutive Wnt signalling resulting from Helicobacter pylori infection and inactivation of Wnt inhibitors(mainly by inactivating mutations and promoter hypermethylation) play an important role in gastric cancer. Moreover, a number of recent studies confirmed CTNNB1 and APC as driver genes in gastric cancer. The identification of specific membrane, intracellular, and extracellular components of the Wnt pathway has revealed potential targets for gastric cancer therapy. High-throughput "omics" approaches will help in the search for Wnt pathway antagonist in the near future.展开更多
文摘背景：以前的血管内超声（intravascular ultrasound，IVUS）试验证实，他汀治疗可减缓或阻止动脉粥样硬化的进展，但是迄今尚无应用动脉粥样斑块体积百分比（percent atheroma volume，PAV）证实粥样硬化消退的确切证据。PAV是最严格的评价病变进展和消退的IVUS测量指标。
目标：评价极高强度他汀治疗是否能逆转IVUS确定的冠状动脉粥样硬化。
设计和地点：于美国、加拿大、欧洲和澳大利亚53个社区和3级保健中心进行前瞻性开标盲法终点试验（A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden，ASTEROID）。应用马达驱动回撤IVUS评价基线和治疗24个月时冠状动脉粥样斑块负荷。每对基线和随访IVUS测量结果均进行盲法分析。
病例：从2002年11月到2003年10月，507例患者有基线IVUS检查结果，并接受至少1个剂量的研究药物。在24个月后，349例患者具有可用于评估的系列IVUS检查结果。
干预：所有患者均接受瑞舒伐他汀40ms／d强化治疗。
主要观测指标：预先设定了两个一级疗效指标：PAV变化和基线最严重病变10min节段动脉粥样斑块体积变化。二级疗效指标为整个动脉标准化总斑块体积的变化。结果：平均（SD）LDL—C水平由基线时的130．4（34．3）ms／dL降至60．8（20．0）ms／扎，平均下降了53．2％（P〈0．001）。平均（SD）HDL-C水平从基线时的43．1（11．1）ms／dL升至49．0（12．6）ms／dL，平均增加了14．7％（P〈0．001）。整个血管PAV平均（SD）变化为-0．98％（3．15％），中位数为-0．79％（97．5％CI，-1．21％～-0．53％）（与基线比较，P〈0．001）。最严重病变10min节段斑块体积平均（SD）变化为-6．1（10．1）mm^3，中位数为-5．6mm^3（97．5％CI，-6．8～-4．0mm^3）（与基线比较，P〈0．001）。总斑块体积变化中位数降低了6．8％，�
文摘The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve as a nexus for signal transduction and play a vital role in numerous biological processes. In this review, we highlight the known characteristics and components of the p38 pathway along with the mechanism and consequences of p38 activation. We focus on the role of p38 as a signal transduction mediator and examine the evidence linking p38 to inflammation, cell cycle, cell death, development, cell differentiation, senescence and tumorigenesis in specific cell types. Upstream and downstream components of p38 are described and questions remaining to be answered are posed. Finally, we propose several directions for future research on p38.
文摘The term adakite was originally pro- posed to define silica-rich, high Sr/Y and La/Yb vol- canic and plutonic rocks derived from melting of the basaltic portion of oceanic crust subducted beneath volcanic arcs. It was also initially believed that ada- kite only occurs in convergent margins where young and thus still hot oceanic slabs are being subducted, but later studies have proposed that it also occurs in other arc settings where unusual tectonic conditions can lower the solidus of older slabs. Currently, ada- kite covers a range of arc rocks ranging from pristine slab melt, to adakite-peridotite hybrid melt, to melt derived from peridotite metasomatized by slab melt. Adakite studies have generated some confusions because (1) the definition of adakite combines com- positional criteria with a genetic interpretation (melt- ing of subducted basalt), (2) the definition is fairly broad and relies on chemistry as its distinguishing characteristic, (3) the use of high pressure melting experiment results on wet basalts as unequivocal proofs of slab melting and (4) the existence of ada- kitic rocks with chemical characteristics similar to adakites but are clearly unrelated to slab melting. Other studies have shown that adakitic rocks and a number of the previously reported adakites are pro- duced through melting of the mafic lower crust or ponded basaltic magma, high-pressure crystal frac- tionation of basaltic magma and low-pressure crystal fractionation of basaltic magma plus magma mixing processes in both arc or non-arc tectonic environ- ments. Despite the confusing interpretations on the petrogenesis of adakite and adakitic rocks, their in- vestigations have enriched our understanding of material recycling at subduction zones, crustal evolu- tionary processes and economic mineralization.
文摘Dear Editor,Genome editing technologies enable precise modifications of DNA sequences in vivo and offer great promise for crop improvement. CRISPR/Cas9 （Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated Cas9） has revolution- ized genome editing because of its simplicity and versatility （Cong et al., 2013）.
文摘Transforming growth factor-beta （TGF-β）/bone morphogenic protein （BMP） signaling is involved in the vast majority of cellular processes and is fundamentally important during the entire life of all metazoans. Deregulation of TGF-β/ BMP activity almost invariably leads to developmental defects and/or diseases, including cancer. The proper functioning of the TGF-β/BMP pathway depends on its constitutive and extensive communication with other signaling pathways, leading to synergistic or antagonistic effects and eventually desirable biological outcomes. The nature of such signaling cross-talk is overwhelmingly complex and highly context-dependent. Here we review the different modes of cross-talk between TGF-β/BMP and the signaling pathways of Mitogen-activated protein kinase, phosphatidylinositol-3 kinase/ Akt, Wnt, Hedgehog, Notch, and the interleukin/interferon-gamma/tumor necrosis factor-alpha cytokines, with an emphasis on the underlying molecular mechanisms.
基金supported by National Basic Research Program of China (Grant No. 2007CB411301)the Bureau of China Geological Survey (Grant No. 1212010611806)ISTO
文摘The Chinese Tianshan belt is a major part of the southern Central Asian Orogenic Belt, extending westward to Kyrgyzstan and Kazakhstan. Its Paleozoic tectonic evolution, crucial for understanding the amalgamation of Central Asia, comprises two stages of subduction-collision. The first collisional stage built the Eo-Tianshan Mountains, before a Visean unconformity, in which all structures are verging north. It implied a southward subduction of the Central Tianshan Ocean beneath the Tarim active margin, that induced the Ordovician-Early Devonian Central Tianshan arc, to the south of which the South Tianshan back-arc basin opened. During the Late Devonian, the closure of this ocean led to a collision between Central Tianshan arc and the Kazakhstan-Yili-North Tianshan Block, and subsequently closure of the South Tianhan back-arc basin, producing two suture zones, namely the Central Tianshan and South Tianshan suture zones where ophiolitic melanges and HP metamorphic rocks were emplaced northward. The second stage included the Late Devonian-Carboniferous southward subduction of North Tianshan Ocean beneath the Eo-Tianshan active margin, underlined by the Yili-North Tianshan arc, leading to the collision between the Kazakhstan-Yili-NTS plate and an inferred Junggar Block at Late Carboniferous-Early Permian time. The North Tianshan Suture Zone underlines likely the last oceanic closure of Central Asia Orogenic Belt; all the oceanic domains were consumed before the Middle Permian. The amalgamated units were affected by a Permian major wrenching, dextral in the Tianshan. The correlation with the Kazakh and Kyrgyz Tianshan is clarified. The Kyrgyz South Tianshan is equivalent to the whole part of Chinese Tianshan （CTS and STS） located to the south of Narat Fault and Main Tianshan Shear Zone; the so-called Middle Tianshan thins out toward the east. The South Tianshan Suture of Kyrgyzstan correlates with the Central Tianshan Suture of Chinese Tianshan. The evolution of this southern domain remains similar from east （Ga
文摘CRISPR/Cas9 （Clustered Regularly Interspaced Short Palin- dromic Repeats/CRISPR-associated Cas9 endonuclease）- mediated genome editing has revolutionized biological research and crop improvement because of its specificity, simplicity, and versatility （reviewed in Komor et al., 2016a）.
文摘The Trans-North China Belt （TNCB） is a Paleoproterozoic collisional orogen （ca. 1.9-1.8 Ga） responsible for the amalgamation of the North China Craton. Detailed field works in Liiliangshan, Hengshan, Wutaishan and Fuping massifs where the belt is well exposed, allow us to draw a new tectonic map and crustal-scale cross sections. The available petrologic, radiometric, geochronologic data are integrated in a geodynamic evolution scheme for this orogen. The Low Grade Mafic Unit （LGMU） is interpreted as an ophiolitic nappe rooted in a suture zone located in the western part of the Lüliangshan. This ophiolitic nappe overthrusts to the SE upon the Orthogneiss-Volcanites Unit （OVU） that consists of a bimodal volcanic-sedimentary series metamorphosed under amphibolite facies conditions intruded by calcalkaline orthogneiss. The OVU is a composite Neoarchean-Paleoproterozoic magmatic arc developed during two stages （ca. 2500 and 2100 Ma） upon a continental basement corresponding to the western extension of the Neoarchean Fuping massif The OVU overthrusts to the SE the Fuping massif along the Longquanguan shear zone. This stack of nappes, coeval with an amphibolite facies metamorphism, is dated at ca. 1880 Ma. Subsequently, the metamorphic series experienced a widespread migmatization at 1850 Ma and was intruded by post-orogenic plutons dated at 1800 Ma. The weakly to unmetamorphosed Hutuo Supergroup unconformably overlies the metamorphosed and ductilely deformed units （OVU and LGMU）, but it is also involved in a second tectonic phase developed in subsurface conditions. These structural features lead us to question the ca. 2090 Ma age attributed to the Hutuo supergroup. Moreover, in the Fuping massif several structural and magmatic lines of evidence argue for an earlier orogenic event at ca. 2100 Ma that we relate to an older west-directed subduction below the Fuping Block. The Taihangshan Fault might be the location of a possible suture zone between the Fuping Block and an eastern one. A geodynamic
文摘Gastric cancer remains one of the most common cancers worldwide and one of the leading cause for cancerrelated deaths. Gastric adenocarcinoma is a multifactorial disease that is genetically, cytologically and architecturally more heterogeneous than other gastrointestinal carcinomas.The aberrant activation of the Wnt/β-catenin signaling pathway is involved in the development and progression of a significant proportion of gastric cancer cases. This review focuses on the participation of the Wnt/b-catenin pathway in gastric cancer by offering an analysis of the relevant literature published in this field. Indeed, it is discussed the role of key factors in Wnt/β-catenin signaling and their downstream effectors regulating processes involved in tumor initiation, tumor growth, metastasis and resistance to therapy. Available data indicate that constitutive Wnt signalling resulting from Helicobacter pylori infection and inactivation of Wnt inhibitors(mainly by inactivating mutations and promoter hypermethylation) play an important role in gastric cancer. Moreover, a number of recent studies confirmed CTNNB1 and APC as driver genes in gastric cancer. The identification of specific membrane, intracellular, and extracellular components of the Wnt pathway has revealed potential targets for gastric cancer therapy. High-throughput "omics" approaches will help in the search for Wnt pathway antagonist in the near future.
