The single polycrystalline diamond compact(PDC)cutter test is widely used to investigate the mecha-nism of rock-breaking.The generated cuttings and cutting force are important indexes reflecting the rock failure proce...The single polycrystalline diamond compact(PDC)cutter test is widely used to investigate the mecha-nism of rock-breaking.The generated cuttings and cutting force are important indexes reflecting the rock failure process.However,they were treated as two separate parameters in previous publications.In this study,through a series of rock block cutting tests,the relationship between them was investigated to obtain an in-depth understanding of the formation of cuttings.In addition,to validate the standpoints obtained in the aforementioned experiments,rock sheet cutting tests were conducted and the rock failure process was monitored by a high-speed camera frame by frame.The cutting force was recorded with the same sampling rate as the camera.By this design,every sampled point of cutting force can match a picture captured by the camera,which reflects the interaction between the rock and the cutter.The results indicate that the increase in cutting depth results in a transition of rock failure modes.At shallow cutting depth,ductile failure dominates and all the cuttings are produced by the compression of the cutter.The corresponding cutting force fluctuates slightly.However,beyond the critical depth,brittle failure occurs and chunk-like cuttings appear,which leads to a sharp decrease in cutting force.After that,the generation of new surface results in a significant decrease in actual cutting depth,a parameter proposed to reflect the interaction between the rock and the cutter.Consequently,ductile failure dominates again and a slight fluctuation of cutting force can be detected.As the cutter moves to the rock,the actual cutting depth gradually increases,which results in the subsequent generation of chunk-like cuttings.It is accompanied by an obvious cutting force drop.That is,ductile failure and brittle failure,one following another,present at large cutting depth.The transition of rock failure mode can be correlated with the variation of cutting force.Based on the results of this paper,the real-time monitoring of torque may be helpful to determine the efficiency of PDc bits in the downhole.展开更多
In this paper the authors present the REE concentrations and Sr and Nd isotopic compositions of fluorites from the Bailashui tin deposit of the Furong ore field,southern Hunan Province. The results showed that the tot...In this paper the authors present the REE concentrations and Sr and Nd isotopic compositions of fluorites from the Bailashui tin deposit of the Furong ore field,southern Hunan Province. The results showed that the total amount of REE in fluorites is usually low,ranging from 0.705 to 8.785 μg/g with the chondrite-normalized REE dis-tribution patterns similar to those of the Qitianling granites in the study area,characterized by LREE-enrichment patterns with pronounced negative Eu anomalies. The fluorites vary in Sr isotopic composition within the range of 0.7083-0.7091,the values are lower than those of the granites and higher than those of the host carbonate rocks in this area. The εNd(t) values of fluorites vary between -9.4 and +10.3,revealing that both the crust-and mantle-source materials were involved in the ore-forming hydrothermal fluids. Combined with previous studies on this ore deposit,the Bailashui tin deposit is temporally and spatially closely related with granitic magmatism in this area. The hydro-thermal fluorites are the product of fluid/rock interactions between granitic magmatic hydrothermal fluid and marine carbonate rocks. The REE and F in the ore-forming fluid were derived from the granites,whereas Sr in the ore-forming fluid came mainly from the granitic magmatic hydrothermal fluid and marine carbonate rocks,although variations in Sr isotopic composition cannot be explained by a simple mixture of these two end-members. Evidence demonstrated that the ore-forming fluids are of crustal-mantle mixing origin,but that the fluids were probably in-completely homogenized and this may be caused by inhomogeneous mixing of the fluids of different sources.展开更多
The Jinding Pb-Zn deposit in Yunnan Province is the representative of a Cd-enriched area and mining activities lead to the release of Cd into the hypergenic ecosystem, resulting in Cd pollution. The concentrations of ...The Jinding Pb-Zn deposit in Yunnan Province is the representative of a Cd-enriched area and mining activities lead to the release of Cd into the hypergenic ecosystem, resulting in Cd pollution. The concentrations of Cd vary greatly from one type to another type of rocks in the mining district. In the host rock, Cd concentrations range from 50×10-6 to 650×10-6 with an average of 310×10-6. In primary ores, Cd concentrations range from 14×10-6 to 2800×10-6 with an average of 767×10-6. However, in oxidized ores, Cd concentrations are highest, varying within the range of 110×10-6 to 8200×10-6 , averaging 1661×10-6. It is shown that the oxidized ores are the main carrier and environmental source of Cd. Leaching test showed that Pb/Zn ores are easy to oxidize and thereafter release Cd and other harmful elements. These leached elements in the leachate may be precipitated rapidly in the order of Zn>Pb>Cd. As for the concentration distribution of Cd in the Bijiang River, it is estimated to be 15.7 μg/L Cd in water, 49.3 mg/L in suspended substances, and 203.7 mg/L in sediments. The average value of Cd in soil from the polluted area is 83.0 mg/kg. Natural weathering of Cd-rich rocks and minerals imposes a potential environmental risk on the aquatic ecosystem of the Bijiang catchment.展开更多
China began to implement the charging policy for postgraduate students in 2014.Various universities at all levels have formulated a scholarship and stipend system for postgraduate students,which is in line with the ne...China began to implement the charging policy for postgraduate students in 2014.Various universities at all levels have formulated a scholarship and stipend system for postgraduate students,which is in line with the needs of schools in talent training along with the spirit of relevant documents of the Ministry of Education and the actual situation of the schools.This study investigates and analyzes the advantages and disadvantages of the postgraduate funding by Wuhan University of Science and Technology.This article then provides advice for the reform of the scholarship and stipend system from improving the precision funding system,to increasing funding,to expanding the scope of postgraduate funding,and standardizing the treatment of deferred postgraduate students in hope that it would provide a basis for the funding system and provide guarantee for postgraduate students to complete their studies successfully.展开更多
Fe-based Fenton agents can generate highly reactive and toxic hydroxyl radicals(·OH)in the tumor microenvironment(TME)for chemodynamic therapy(CDT)with high specificity.However,the low pH environment and insuffic...Fe-based Fenton agents can generate highly reactive and toxic hydroxyl radicals(·OH)in the tumor microenvironment(TME)for chemodynamic therapy(CDT)with high specificity.However,the low pH environment and insufficient endogenous hydrogen peroxide(H_(2)O_(2))of the highly efficient Fenton reaction limits its practical application in clinic.Here,a Cu(Ⅱ)-doped mesoporous silica nanoagent(Cu-MSN)with excellent dispersity was successfully developed.After loaded with doxorubicin(DOX)and ascorbate(AA),Cu-MSN@DA was coated with active targeting ligand folic acid(FA),dimethyl maleic an-hydride(DMMA)and carboxymethyl chitosan(CMC)to obtain an active transporting nanoagent(FCDC@Cu-MSN@DA)with tunable charge-reversal property,which is more adaptable to the pH value of TME than Fe-based Fenton agents,and can self-supply exogenous H_(2)O_(2)by ascorbate to produce more toxic·OH to trigger the apoptosis of cancer cells.Meanwhile,the high level of glutathione(GSH)in TME can reduce Cu(Ⅱ)to Cu(I)by Fenton-like reaction,increasing the generation rate of·OH and relieving tumor antioxidant ability.The supply of exogenous H_(2)O_(2)significantly enhanced the synergistic effect of CDT by oxidative damage.Together with DOX-induced cell apoptosis,this novel nanoagent FCDC@Cu-MSN@DA can achieve maximum therapeutic efficacy,creating a new model of safe and effective tumor treatment with high specificity.展开更多
The Lianhuashan metallogenic belt in Eastern Guangdong Province(South China)is the most important Sn polymetallic district in the region,hosting many medium-sized deposits such as the Tashan,Xianshuili,and Jiangxikeng...The Lianhuashan metallogenic belt in Eastern Guangdong Province(South China)is the most important Sn polymetallic district in the region,hosting many medium-sized deposits such as the Tashan,Xianshuili,and Jiangxikeng.However,the metallogenic mechanism of these deposits remains hotly debated.In this paper,two types of cassiterites(Cst1 and Cst2)have been identified in the Xianshuili and Jiangxikeng Sn deposits,which are hosted in the biotite-mylonite and garnetcordierite-muscovite blastomylonite,respectively.The euhedral Cst1(0.50–1.8 mm)coexists with biotite,feldspar,and quartz.It is platy and zoned with a mosaic structure.The subhedral to anhedral Cst2(0.02–0.35 mm)coexists with metamorphic minerals such as garnet and cordierite,and it is characterized by well-developed porosity and has no zonation.In-situ U-Pb dating of the Cst1 and Cst2 yielded ages of 149.5±1.0 Ma(MSWD=1.6,n=45)and 125.1±2.3 Ma(MSWD=4.5,n=43),respectively.Cst1 is most likely to be related to the intermediate-felsic magmatism that formed Gaojiping Group,whereas Cst2 has relatively high Ta,Nb,Fe,and W contents with obvious rare earth tetragroup effect,and may have formed by the late Early Cretaceous dynamic metamorphism.Results presented here,when combined with regional geology and geochemistry,led us to suggest that the Mesozoic intermediate-felsic volcanic rocks in the LMB are significantly enriched in Sn and F,with high Sn-polymetallic mineralization potential which likely have contributed to the volcanic-related Cst1.In the late Early Cretaceous period,due to the NW-dipping subduction of the paleo-Pacific plate,the intermediate-felsic volcanic rocks underwent dynamic metamorphism that led to Sn mobilization,migration,and precipitation in the regional ductile shear zones,and eventually generating Sn mineralization.We propose that areas beneath Xianshuili and Jiangxikeng have great potential for discovery of new Sn resources.Our findings likely offer practical importance to regional geological ore prospecting.展开更多
We aimed to assess the associations of large artery stenosis(LAS)and cerebral small vessel disease(CSVD)with the risk of ischemic stroke and to investigate their respective and combined contributions.In the prospectiv...We aimed to assess the associations of large artery stenosis(LAS)and cerebral small vessel disease(CSVD)with the risk of ischemic stroke and to investigate their respective and combined contributions.In the prospective population-based Shunyi Study,1,082 stroke-free participants aged 55.9±9.1 years were included.Participants were followed for incident stroke throughout the study period(2013-2019).Total small vessel disease score was used to measure CSVD burden.Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound.We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models.During a mean follow-up of 4.2 years,34 participants(3.1%)experienced at least one ischemic stroke.Severe LAS(≥50% stenosis versus no stenosis:HR=3.27(95%CI:1.31-8.18))and high CSVD burden(total small vessel disease score 2-4 versus 0 point:HR=12.73(4.83-33.53))were associated with increased stroke risk independently.In multivariate models,CSVD burden(7.72%)explained a larger portion of the variation in stroke risk than severity of LAS(3.49%).Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects,while those with high CSVD burden deserve more attention in primary prevention of stroke.展开更多
Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that can be induced by viral infectionand interferons (IFNs). It inhibits the entry and replication of many viruses, which are independent of...Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that can be induced by viral infectionand interferons (IFNs). It inhibits the entry and replication of many viruses, which are independent of receptorusage but dependent on processes that occur in endosomes. In this study, we demonstrate that IFITM3 playsimportant roles in regulating the RNA-virus-triggered production of IFN-β in a negative-feedback manner.Overexpression of IFITM3 inhibited Sendai virus-triggered induction of IFN-β, whereas knockdown of IFITM3 hadthe opposite effect. We also showed that IFITM3 was constitutively associated with IRF3 and regulated thehomeostasis of IRF3 by mediating the autophagic degradation of IRF3. These findings suggest a novel inhibitoryfunction of IFITM3 on the RNA-virus-triggered production of type I IFNs and cellular antiviral responses.展开更多
Exonuclease 1(EXO1)can catalyze nucleotide chain excision with its conserved N-terminal domain of 5′ to 3′ exonuclease activity,enabling it to influence diverse biological processes facing the challenges of genotoxi...Exonuclease 1(EXO1)can catalyze nucleotide chain excision with its conserved N-terminal domain of 5′ to 3′ exonuclease activity,enabling it to influence diverse biological processes facing the challenges of genotoxic environmental factors such as ionizing radiation.This nuclease activity enables EXO1 to maintain replication forks and telomeres length,to facilitate post-replication DNA repair and to process the end resection step of homologous recombination of DNA double-strand breaks-induced by ionizing radiation.When DNA replication is disrupted or blocked,EXO1 can cleave the broken DNA ends to form 3’ssDNA,leading to repair pathways activation.Excess EXO1-mediated nucleotide excision,however,can introduce an abundance of single-stranded DNA that can cause mutation and recombination via micro-homology-mediated end joining or single-strand annealing mechanisms,contributing to a loss of genetic information.EXO1 activity must therefore be carefully regulated within healthy cells.The mutations and dysregulations of EXO1 can increase the sensitivity of cells to radiation injury and risk of oncogenic transformation,limit the adoption of specific treatments in a range of human diseases.As such,EXO1 represents a promising target for the treatment and prevention of cancer.In the present review,we delineate the structural properties and functional characteristics of EXO1,discuss the relationship between this exonuclease and cancer susceptibility as well as the second cancers related to radiotherapy.展开更多
Based on our previous work,a series of hydrazone moiety-bearing aminopyrimidines were synthesized.The compounds were evaluated for inhibitory activities against EGFRT790M/L858 R and antiproliferative activities agains...Based on our previous work,a series of hydrazone moiety-bearing aminopyrimidines were synthesized.The compounds were evaluated for inhibitory activities against EGFRT790M/L858 R and antiproliferative activities against H1975 and A549 NSCLC cell lines harboring different forms of EGFR.Compounds 7f and7 k exhibited potent and selective activity in inhibition of gefitinib-resistant H1975 cancer cells（IC50;0.45,0.2μmol/L） while were much less active on A549 cancer cells（IC50;52.83,〉100μmol/L）.Both compounds could be served as promising lead compounds for further investigation.展开更多
基金support from the National Natural Science Foundation of China(52204004)the National Science Fund for Distinguished Young Scholars(51725404)。
文摘The single polycrystalline diamond compact(PDC)cutter test is widely used to investigate the mecha-nism of rock-breaking.The generated cuttings and cutting force are important indexes reflecting the rock failure process.However,they were treated as two separate parameters in previous publications.In this study,through a series of rock block cutting tests,the relationship between them was investigated to obtain an in-depth understanding of the formation of cuttings.In addition,to validate the standpoints obtained in the aforementioned experiments,rock sheet cutting tests were conducted and the rock failure process was monitored by a high-speed camera frame by frame.The cutting force was recorded with the same sampling rate as the camera.By this design,every sampled point of cutting force can match a picture captured by the camera,which reflects the interaction between the rock and the cutter.The results indicate that the increase in cutting depth results in a transition of rock failure modes.At shallow cutting depth,ductile failure dominates and all the cuttings are produced by the compression of the cutter.The corresponding cutting force fluctuates slightly.However,beyond the critical depth,brittle failure occurs and chunk-like cuttings appear,which leads to a sharp decrease in cutting force.After that,the generation of new surface results in a significant decrease in actual cutting depth,a parameter proposed to reflect the interaction between the rock and the cutter.Consequently,ductile failure dominates again and a slight fluctuation of cutting force can be detected.As the cutter moves to the rock,the actual cutting depth gradually increases,which results in the subsequent generation of chunk-like cuttings.It is accompanied by an obvious cutting force drop.That is,ductile failure and brittle failure,one following another,present at large cutting depth.The transition of rock failure mode can be correlated with the variation of cutting force.Based on the results of this paper,the real-time monitoring of torque may be helpful to determine the efficiency of PDc bits in the downhole.
基金financially supported jointly by the Key Program of Knowledge Innovation from the Chinese Academy of Sciences (Grant KZCX-3-SW-125)the National Natural Science Foundation of China (Grant Nos.40472053 and 40673021)Special Foundation on Fundamental Scientific Research as Operating Expenses among Commonweal Scientific Research In-stitutes at National Level (Grant K2007-1-12)
文摘In this paper the authors present the REE concentrations and Sr and Nd isotopic compositions of fluorites from the Bailashui tin deposit of the Furong ore field,southern Hunan Province. The results showed that the total amount of REE in fluorites is usually low,ranging from 0.705 to 8.785 μg/g with the chondrite-normalized REE dis-tribution patterns similar to those of the Qitianling granites in the study area,characterized by LREE-enrichment patterns with pronounced negative Eu anomalies. The fluorites vary in Sr isotopic composition within the range of 0.7083-0.7091,the values are lower than those of the granites and higher than those of the host carbonate rocks in this area. The εNd(t) values of fluorites vary between -9.4 and +10.3,revealing that both the crust-and mantle-source materials were involved in the ore-forming hydrothermal fluids. Combined with previous studies on this ore deposit,the Bailashui tin deposit is temporally and spatially closely related with granitic magmatism in this area. The hydro-thermal fluorites are the product of fluid/rock interactions between granitic magmatic hydrothermal fluid and marine carbonate rocks. The REE and F in the ore-forming fluid were derived from the granites,whereas Sr in the ore-forming fluid came mainly from the granitic magmatic hydrothermal fluid and marine carbonate rocks,although variations in Sr isotopic composition cannot be explained by a simple mixture of these two end-members. Evidence demonstrated that the ore-forming fluids are of crustal-mantle mixing origin,but that the fluids were probably in-completely homogenized and this may be caused by inhomogeneous mixing of the fluids of different sources.
基金the National Natural Science Foundation of China（Grand No.40773072）；the “Western Talent Plan” sponsored by the Chinese Academy of Sciences（2006）；the Special Fund provided by the Chongqing Institute of Geology and Mineral Resources.
文摘The Jinding Pb-Zn deposit in Yunnan Province is the representative of a Cd-enriched area and mining activities lead to the release of Cd into the hypergenic ecosystem, resulting in Cd pollution. The concentrations of Cd vary greatly from one type to another type of rocks in the mining district. In the host rock, Cd concentrations range from 50×10-6 to 650×10-6 with an average of 310×10-6. In primary ores, Cd concentrations range from 14×10-6 to 2800×10-6 with an average of 767×10-6. However, in oxidized ores, Cd concentrations are highest, varying within the range of 110×10-6 to 8200×10-6 , averaging 1661×10-6. It is shown that the oxidized ores are the main carrier and environmental source of Cd. Leaching test showed that Pb/Zn ores are easy to oxidize and thereafter release Cd and other harmful elements. These leached elements in the leachate may be precipitated rapidly in the order of Zn>Pb>Cd. As for the concentration distribution of Cd in the Bijiang River, it is estimated to be 15.7 μg/L Cd in water, 49.3 mg/L in suspended substances, and 203.7 mg/L in sediments. The average value of Cd in soil from the polluted area is 83.0 mg/kg. Natural weathering of Cd-rich rocks and minerals imposes a potential environmental risk on the aquatic ecosystem of the Bijiang catchment.
基金the 2020 Graduate Education Teaching Reform Research Project of Wuhan University of Science and Technology(Project Number:Yjg202027)the first batch of Production-School Cooperative Education Project of the Ministry of Education in 2021(Project Number:202101263007 and 202101134017).
文摘China began to implement the charging policy for postgraduate students in 2014.Various universities at all levels have formulated a scholarship and stipend system for postgraduate students,which is in line with the needs of schools in talent training along with the spirit of relevant documents of the Ministry of Education and the actual situation of the schools.This study investigates and analyzes the advantages and disadvantages of the postgraduate funding by Wuhan University of Science and Technology.This article then provides advice for the reform of the scholarship and stipend system from improving the precision funding system,to increasing funding,to expanding the scope of postgraduate funding,and standardizing the treatment of deferred postgraduate students in hope that it would provide a basis for the funding system and provide guarantee for postgraduate students to complete their studies successfully.
基金financially supported by the National Key Research and Development Program of China(No.2019YFA0705803)the National Natural Science Foundation of China Youth Fund(Nos.51803174,82102470)+4 种基金the Natural Science Foundation of Sichuan Province(No.24NSFSC4798)the Foundation of Sichuan Engineering Technology Research Center of Basalt Fiber Composites Development and Application of Southwest Petroleum University(No.2022SCXWYXWFC002)the support from the School of New Energy and Materials of Southwest Petroleum UniversitySichuan International Science and Technology Cooperation BaseDalian Institute of Chemical Physics of Chinese Academy of Sciences。
文摘Fe-based Fenton agents can generate highly reactive and toxic hydroxyl radicals(·OH)in the tumor microenvironment(TME)for chemodynamic therapy(CDT)with high specificity.However,the low pH environment and insufficient endogenous hydrogen peroxide(H_(2)O_(2))of the highly efficient Fenton reaction limits its practical application in clinic.Here,a Cu(Ⅱ)-doped mesoporous silica nanoagent(Cu-MSN)with excellent dispersity was successfully developed.After loaded with doxorubicin(DOX)and ascorbate(AA),Cu-MSN@DA was coated with active targeting ligand folic acid(FA),dimethyl maleic an-hydride(DMMA)and carboxymethyl chitosan(CMC)to obtain an active transporting nanoagent(FCDC@Cu-MSN@DA)with tunable charge-reversal property,which is more adaptable to the pH value of TME than Fe-based Fenton agents,and can self-supply exogenous H_(2)O_(2)by ascorbate to produce more toxic·OH to trigger the apoptosis of cancer cells.Meanwhile,the high level of glutathione(GSH)in TME can reduce Cu(Ⅱ)to Cu(I)by Fenton-like reaction,increasing the generation rate of·OH and relieving tumor antioxidant ability.The supply of exogenous H_(2)O_(2)significantly enhanced the synergistic effect of CDT by oxidative damage.Together with DOX-induced cell apoptosis,this novel nanoagent FCDC@Cu-MSN@DA can achieve maximum therapeutic efficacy,creating a new model of safe and effective tumor treatment with high specificity.
基金supported by the Cooperative Research Fund of the CAS Key Laboratory of Mineralogy and Metallogeny(Grant No.KLMM20200201)the National Natural Science Foundation of China(Grant No.41903016)+2 种基金the President Youth Foundation from Guangzhou Institute of Geochemistry,Chinese Academy of Sciences(Grant No.2019SZJJ-08)the Guangdong Major Project of Basic and Applied Basic Research(Grant No.2019B030302013)the Mineral Geological Survey and Prospecting Prediction in Comprehensive Exploration Area of the China Geological Survey(Grant No.12120114015901)。
文摘The Lianhuashan metallogenic belt in Eastern Guangdong Province(South China)is the most important Sn polymetallic district in the region,hosting many medium-sized deposits such as the Tashan,Xianshuili,and Jiangxikeng.However,the metallogenic mechanism of these deposits remains hotly debated.In this paper,two types of cassiterites(Cst1 and Cst2)have been identified in the Xianshuili and Jiangxikeng Sn deposits,which are hosted in the biotite-mylonite and garnetcordierite-muscovite blastomylonite,respectively.The euhedral Cst1(0.50–1.8 mm)coexists with biotite,feldspar,and quartz.It is platy and zoned with a mosaic structure.The subhedral to anhedral Cst2(0.02–0.35 mm)coexists with metamorphic minerals such as garnet and cordierite,and it is characterized by well-developed porosity and has no zonation.In-situ U-Pb dating of the Cst1 and Cst2 yielded ages of 149.5±1.0 Ma(MSWD=1.6,n=45)and 125.1±2.3 Ma(MSWD=4.5,n=43),respectively.Cst1 is most likely to be related to the intermediate-felsic magmatism that formed Gaojiping Group,whereas Cst2 has relatively high Ta,Nb,Fe,and W contents with obvious rare earth tetragroup effect,and may have formed by the late Early Cretaceous dynamic metamorphism.Results presented here,when combined with regional geology and geochemistry,led us to suggest that the Mesozoic intermediate-felsic volcanic rocks in the LMB are significantly enriched in Sn and F,with high Sn-polymetallic mineralization potential which likely have contributed to the volcanic-related Cst1.In the late Early Cretaceous period,due to the NW-dipping subduction of the paleo-Pacific plate,the intermediate-felsic volcanic rocks underwent dynamic metamorphism that led to Sn mobilization,migration,and precipitation in the regional ductile shear zones,and eventually generating Sn mineralization.We propose that areas beneath Xianshuili and Jiangxikeng have great potential for discovery of new Sn resources.Our findings likely offer practical importance to regional geological ore prospecting.
基金supported by the National Key Research and Development Program of China(2016YFB1001402)National Natural Science Foundation of China(81971138)+2 种基金Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS)(2017-I2M-3-008)Strategic Priority Research Program(Pilot study)“Biological basis of aging and therapeutic strategies”of the Chinese Academy of Sciences(XDPB10)Research Foundation for Young Scholars of Peking Union Medical College Hospital(PUMCH201911275)。
文摘We aimed to assess the associations of large artery stenosis(LAS)and cerebral small vessel disease(CSVD)with the risk of ischemic stroke and to investigate their respective and combined contributions.In the prospective population-based Shunyi Study,1,082 stroke-free participants aged 55.9±9.1 years were included.Participants were followed for incident stroke throughout the study period(2013-2019).Total small vessel disease score was used to measure CSVD burden.Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound.We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models.During a mean follow-up of 4.2 years,34 participants(3.1%)experienced at least one ischemic stroke.Severe LAS(≥50% stenosis versus no stenosis:HR=3.27(95%CI:1.31-8.18))and high CSVD burden(total small vessel disease score 2-4 versus 0 point:HR=12.73(4.83-33.53))were associated with increased stroke risk independently.In multivariate models,CSVD burden(7.72%)explained a larger portion of the variation in stroke risk than severity of LAS(3.49%).Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects,while those with high CSVD burden deserve more attention in primary prevention of stroke.
基金This work was supported by grants from the Ministry of Science and Technology of China(2014CB910103)the National Natural Science Foundation of China(31370867,31521091)the Fundamental Research Funds for the Central University(2042015kf0182)。
文摘Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that can be induced by viral infectionand interferons (IFNs). It inhibits the entry and replication of many viruses, which are independent of receptorusage but dependent on processes that occur in endosomes. In this study, we demonstrate that IFITM3 playsimportant roles in regulating the RNA-virus-triggered production of IFN-β in a negative-feedback manner.Overexpression of IFITM3 inhibited Sendai virus-triggered induction of IFN-β, whereas knockdown of IFITM3 hadthe opposite effect. We also showed that IFITM3 was constitutively associated with IRF3 and regulated thehomeostasis of IRF3 by mediating the autophagic degradation of IRF3. These findings suggest a novel inhibitoryfunction of IFITM3 on the RNA-virus-triggered production of type I IFNs and cellular antiviral responses.
基金Acknowledgements This work is supported by the National Natural Science Foundation of China （No. 21471114）, the State Major Research Plan （973） of China （No. 2011CB932404） and the Key Laboratory of Tobacco Industry Cigarette Smoke （Shanghai Tobacco Group Co., Ltd. No. 00592）.
文摘为综合的一个过程 Fe <sub>2</sub > O <sub>3</sub> 基于 electrospinning 和难模板的方法被建议以便 Fe <sub>2</sub 的水晶阶段 > O <sub>3</sub> 能与精确被定制。Mesoporous -Fe<sub>2</sub>O<sub>3</sub>,-/-Fe<sub>2</sub>O<sub>3</sub>, 和 -Fe<sub>2</sub>O<sub>3</sub> nanofibers 能被改变合成参数成功地制作。扫描电子显微镜学，传播电子显微镜学， X 光检查衍射分析，拉曼光谱学，和氮 adsorptiondesorption 分析被用来描绘综合产品的结构。为与最高的乙醇反应准备 -/-Fe<sub>2</sub>O<sub>3</sub> nanofibers 的最佳的锻烧条件通过察觉到乙醇的大小被决定。混合阶段材料比相应 purephase 展出了显著地更高的敏感。-/-Fe<sub>2</sub>O<sub>3</sub> nanofibers 的优异察觉到乙醇的表演建议他们可能对在察觉到的酒精的使用合适。因此，为改进金属氧化物半导体的察觉到的表演的新奇策略是在一结构装配一样的金属氧化物的不同水晶的形式。最后，为比 -Fe<sub>2</sub>O<sub>3</sub> 和 -Fe<sub>2</sub>O<sub>3</sub> 的那些高的 -/-Fe<sub>2</sub>O<sub>3</sub> 的察觉到的性能负责的机制从 X 光检查光电子光谱学和抵抗大小根据数据被阐明。
基金supported by grants from the National Natural Science Foundation of China(Grant No.31870847).
文摘Exonuclease 1(EXO1)can catalyze nucleotide chain excision with its conserved N-terminal domain of 5′ to 3′ exonuclease activity,enabling it to influence diverse biological processes facing the challenges of genotoxic environmental factors such as ionizing radiation.This nuclease activity enables EXO1 to maintain replication forks and telomeres length,to facilitate post-replication DNA repair and to process the end resection step of homologous recombination of DNA double-strand breaks-induced by ionizing radiation.When DNA replication is disrupted or blocked,EXO1 can cleave the broken DNA ends to form 3’ssDNA,leading to repair pathways activation.Excess EXO1-mediated nucleotide excision,however,can introduce an abundance of single-stranded DNA that can cause mutation and recombination via micro-homology-mediated end joining or single-strand annealing mechanisms,contributing to a loss of genetic information.EXO1 activity must therefore be carefully regulated within healthy cells.The mutations and dysregulations of EXO1 can increase the sensitivity of cells to radiation injury and risk of oncogenic transformation,limit the adoption of specific treatments in a range of human diseases.As such,EXO1 represents a promising target for the treatment and prevention of cancer.In the present review,we delineate the structural properties and functional characteristics of EXO1,discuss the relationship between this exonuclease and cancer susceptibility as well as the second cancers related to radiotherapy.
基金supported by grants from Science Foundation of Shenyang Pharmaceutical University(No.QNJJ2014502)
文摘Based on our previous work,a series of hydrazone moiety-bearing aminopyrimidines were synthesized.The compounds were evaluated for inhibitory activities against EGFRT790M/L858 R and antiproliferative activities against H1975 and A549 NSCLC cell lines harboring different forms of EGFR.Compounds 7f and7 k exhibited potent and selective activity in inhibition of gefitinib-resistant H1975 cancer cells（IC50;0.45,0.2μmol/L） while were much less active on A549 cancer cells（IC50;52.83,〉100μmol/L）.Both compounds could be served as promising lead compounds for further investigation.
