CTHRC1增强结直肠癌细胞侵袭能力促进结直肠癌转移的机制研究

目的:探讨胶原三股螺旋重叠蛋白1(collagen triple helix repeat containing 1,CTHRC1)对结直肠癌细胞生物学特性的影响及可能的调控机制。方法:采用实时定量PCR技术检测上调或抑制miR-520d-5P的表达,探讨其对基因CTHRC1的调控作用,双荧光素酶实验验证miR-520d-5P与基因CTHRC1的3'UTR区之间是否相互结合。采用Western blot法检测6株不同结直肠癌细胞系及临床结直肠癌配对标本中基因CTHRC1的蛋白表达水平。构建稳定转染基因CTHRC1的结直肠癌细胞系;CCK-8、Transwell等方法检测稳定转染目的基因后结直肠癌细胞的增殖、侵袭能力的变化。结果:在配对结直肠癌患者组织中发现,正常组织中miR-520d-5P的表达高于癌组织(P<0.001),基因CTHRC1的表达趋势相反(P<0.001),且两者的表达呈负相关。通过miR-520d-5P模拟类似物mimics及抑制物inhibitor的瞬时转染实验发现其对基因CTHRC1的蛋白表达有负向调节作用。双荧光素酶实验验证miR-520d-5P与CTHRC1的3'UTR之间存在相互结合。稳定转染基因CTHRC1后,细胞的增殖能力下降,但侵袭能力提高,差异具有统计学意义(P<0.05)。在配对结直肠癌标本中,原发癌组织中基因CTHRC1的蛋白表达水平高于正常组织(P=0.003)。结论:miR-520d-5P对基因CTHRC1蛋白表达具有负调控作用。基因CTHRC1可以增强结直肠癌细胞的侵袭能力,抑制结直肠癌细胞的增殖能力,且与miR-520d-5P具有临床相关性。

High Ba-Sr adakitic charnockite suite from the Nagercoil Block,southern India:Vestiges of Paleoproterozoic arc and implications for Columbia to Gondwana

The Nagercoil block is the southernmost crustal segment of the Southern Granulite Terrane(SGT)in India and is mainly composed of charnockitic rocks and felsic gneisses(charnockite suite).In this study,we present petrologic,geochemical,zircon U-Pb,REE,and Hf isotopic studies on the charnockites and leucogneiss from the Nagercoil block.Based on field investigations and petrologic studies,the charnockites can be divided into garnet-bearing and garnet-absent anhydrous granulite facies rocks with orthopyroxene.The charnockites and leucogneiss show transition from adakites to non-adakitic magmatic rocks,with enrichment in LREEs(light rare earth elements)and LILEs(large ion lithophile elements),and depletion in HREEs(heavy rare earth elements)and HFSEs(high field strength elements).Some of the charnockites and the leucogneiss show typical HSA(high silica adakite)characters,(high SiO_(2),Al_(2)O_(3),Ba-Sr,La/Yb,and Sr/Y).The HSA is considered to have formed from the interaction of slab derived melts and peridotitic mantle wedge.The high Ba-Sr features were possibly inherited from subducted oceanic crust melting under high thermal gradient during Precambrian.The magmas were underplated and subjected to fractional crystallization.Zircon grains from the charnockite and leucogneiss show zoned magmatic cores surrounded by structureless metamorphic rims.Magmatic zircon grains from the charnockites show ages ranging from 1983±8.8 Ma to 2046±14 Ma,and the metamorphic domains show an age range of 502±14 Ma to 547±8.7 Ma.Zircon from the leucogneiss yielded magmatic and metamorphic ages of 1860±20 Ma and 575.6±8.8 Ma.Both charnockites and leucogneiss show two prominent age peaks at 1987 Ma and 568 Ma.The REE data of the zircon grains show LREE depletion and HREE enrichment,with the metamorphic grains showing more depletion in HREE.Zircon Hf isotopic data of the magmatic cores of zircon grains from the charnockite yieldedε_(Hf)(t)values from-1.17 to 0.46 with T_(DM)and T_(DM)~C and age peaks at 2392 Ma and 2638 Ma,suggesting Neoarchean to Paleoproterozoic juvenile sources.We suggest that the high Ba-Sr adakitic charnockite suite from the Nagercoil block formed in a Paleoproterozoic magmatic arc setting during the assembly of the Columbia supercontinent,and underwent high-grade metamorphism associated with the amalgamation of the Gondwana supercontinent during the late Neoproterozoic-Cambrian.Our study provides new insights into the vestiges of Columbia fragments within the Gondwana assembly with two distinct cycles of crustal evolution.

Nickel-catalyzed carbonylative four-component 1,4-dicarbofunctionalization of 1,3-enynes

An efficient Ni-catalyzed four-component 1,4-carbocarbonylation of 1,3-enynes with activated alkyl halides and arylboronic acids under atmospheric pressure of CO is presented.By tuning the electronic and steric effects of alkyl radicals,both electronrich and electron-deficient 1,3-enynes were compatible with this cascade.This protocol features mild conditions,broad substrate scope,excellent functional group compatibility and facile gram-scale synthesis,providing a practical approach to the quaternary carbon center-containing allenyl ketones.Mechanistic study revealed that the acyl-NiIIspecies plays an important role in both the coupling and the alkyl radical generation processes.

Pentacoordinate Phosphoranes as Versatile Reagents in Fluoroalkylation Reactions

A general method for the synthesis of bench-stable bis(difluoromethyl)pentacoordinate phosphoranes has been developed.The reaction is rapid,operationally simple,and easily scalable.The pentacoordinate phosphoranes can generate both difluoromethyl radical(·CF_(2)H)and difluorocarbene(:CF_(2))intermediates.Thus,a variety of fluoroalkylation transformations havebeen achieved by·CF_(2)H,such asoxidativedifluoromethylation of electron-deficient heterocycles,nickel/photoredox dual-catalyzed difluoromethylation of aryl bromides,and photoredox difluoromethylation of alkenes,or by:CF_(2),such as gem-difluorocyclopropanation of alkenes,base-promoted difluoromethylation of heteroatom nucleophiles,Pd-catalyzed difluoromethylation of arylboronic acids,and Cu-mediated trifluoromethylation of aryl iodides(via:CF_(2) and recombined CF_(3)-).These fluoroalkylation methods have been successfully applied to late-stage fluoroalkylation of drugs and drug-like molecules.

Root-associated(rhizosphere and endosphere) microbiomes of the Miscanthus sinensis and their response to the heavy metal contamination

The plant root-associated microbiomes, including both the rhizosphere and the root endosphere microbial community, are considered as a critical extension of the plant genome. Comparing to the well-studied rhizosphere microbiome, the understanding of the root endophytic microbiome is still in its infancy. Miscanthus sinensis is a pioneering plant that could thrive on metal contaminated lands and holds the potential for phytoremediation applications. Characterizing its root-associated microbiome, especially the root endophytic microbiome, could provide pivotal knowledge for phytoremediation of mine tailings. In the current study, M. sinensis residing in two Pb/Zn tailings and one uncontaminated site were collected. The results demonstrated that the metal contaminant fractions exposed strong impacts on the microbial community structures. Their influences on the microbial community, however, gradually decreases from the bulk soil through the rhizosphere soil and finally to the endosphere, which resulting in distinct root endophytic microbial community structures compared to both the bulk and rhizosphere soil. Diverse members affiliated with the order Rhizobiales was identified as the core microbiome residing in the root of M. sinensis. In addition, enrichment of plant-growth promoting functions within the root endosphere were predicted, suggesting the root endophytes may provide critical services to the host plant. The current study provides new insights into taxonomy and potential functions of the root-associated microbiomes of the pioneer plant, M. sinensis, which may facilitate future phytoremediation practices.

Association of a complete breast cancer pathologic response with axillary lymph node metastasis via neoadjuvant chemotherapy:Results from the CSBrS-012 study

To the Editor:In the last decade,neoadjuvant chemotherapy(NAC)has become a well-accepted treatment option for breast cancer,although few detailed description of NAC in China has yet been reported.[1]A previous study found that among patients with clinically node-negative(cN0)breast cancer,97.7%(432/442)with breast pathologic complete response(bpCR)had ypN0(absence of metastases in the axillary lymph nodes);and 71.6%(882/1232)without bpCR achieved ypN0(P<0.001).As for human epidermal growth factor receptor 2(HER2)positive or triple-negative breast cancer(TNBC)that achieved bpCR.