Background The multidrug resistance （MDR） associated with the expression of the mdr1 gene and its product P-glycoprotein is a major factor in the prognosis of hepatocellular carcinoma cell （HCC） patients treated w...Background The multidrug resistance （MDR） associated with the expression of the mdr1 gene and its product P-glycoprotein is a major factor in the prognosis of hepatocellular carcinoma cell （HCC） patients treated with chemotherapy. Our study was to establish a stable HCC MDR cell line where a de novo acquisition of multidrug resistance specifically related to overexpression of a transgenic mdr1. Methods The 4.5-kb mdrl cDNA obtained from the plasmid pHaMDR1-1 was cloned into the PCl-neo mammalian expression vector, later was transferred by liposome to human hepatocarcinoma cell line HepG2. Then the transfected HepG2 cells resisting G418 were clustered and cultured and the specific fragment of mdr1 cDNA, mRNA and the P-glycoprotein （Pgp） in these HepG2 cells were detected by PCR, RT-PCR and flow cytometry, respectively. The accumulation of the daunorubicin was determinated by flow cytometry simultaneously. The nude mice model of grafting tumour was established by injecting subcutaneously HepG2/mdr1 cells in the right axilla. When the tumour diameter reached 5 mm, adriamycin was injected into peritoneal cavity. The size and growth inhibition of tumour were evaluated. Results The mdr1 expression vector was constructed successfully and the MDR HCC line HepG2/mdr1 developed. The PCR analysis showed that the specific fragment of mdrl cDNA in HepG2/mdr1 cells, but not in the control group HepG2 cells. Furthermore, the content of the specific fragment of mdr1 mRNA and Pgp expression in HepG2/mdr1 cells were （59.7±7.9）% and （12.28±2.09）%, respectively, compared with （16.9±3.2）% and （3.07±1.06）% in HepG2 cells. In the nude mice HCC model, the tumour genes of both groups were identified. After ADM therapy, the mean size of HepG2 cell tumours was significantly smaller than HepG2/mdr1 cell tumours. Conclusion The approach using the transfer of mdr1 cDNA may be applicable to the development of MDR hepatocarcinoma cell line, whose MDR mechanism is known. This would provide the experimental basis o展开更多
In order to control the low frequency vibration of railway vehicles, a vertical two degrees of freedom(2DOF) low frequency dynamic vibration absorber(DVA) based on acceleration is proposed. Parameters of the dynamic v...In order to control the low frequency vibration of railway vehicles, a vertical two degrees of freedom(2DOF) low frequency dynamic vibration absorber(DVA) based on acceleration is proposed. Parameters of the dynamic vibration absorber are put forth to control the low frequency vibration of car body bouncing and pitching. Next, the acceleration power spectrum density(PSD)and ride quality of the car body are calculated based on the pseudo excitation method(PEM) and covariance algorithm,respectively. According to the requirement of 2DOF low frequency DVA, the isolators with high static low dynamic stiffness(HSLDS) are designed. A high-speed train dynamic model containing HSLDS isolators is established to validate the effects on the car body vibration. The results reveal that the 2D low frequency DVA can significantly reduce the vibration of the car body bouncing and pitching. Thus, the ride quality of the vehicle is increased, and passenger comfort is improved.展开更多
We conducted a two-year study of deficit irrigation impact on peach yield and quality in semi-arid northwest China. Over two years, four-year-old peach trees were irrigated at 100, 75, 50 and 25% of peach evapotranspi...We conducted a two-year study of deficit irrigation impact on peach yield and quality in semi-arid northwest China. Over two years, four-year-old peach trees were irrigated at 100, 75, 50 and 25% of peach evapotranspiration （ETc）, here, ETc= Coefficient （Kc）×Local reference evapotranspiration （ET0）. During the April-July fruit production season we measured root zone soil water depletion, sap flow velocity, net photosynthetic rate （Pn）, transpiration rate （Tr）, stomatal conductance （Gs）, water use efficiency （WUE=Pn/Tr）, fruit quality, and yield under a mobile rain-out shelter. Increased soil water depletion reasonably mirrored decreasing irrigation rates both years, causing progressively greater water stress. Progressive water stress lowered Gs, which in turn translated into lower T as measured by sap flow. However, mild deficit irrigation （75% ETc） constricted T more than Pn. Pn was not different between 100 and 75% ETc treatments in both years, and it decreased only 5-8% in June with higher temperature than that in May with cooler temperature. Concurrently under 75% ETc treatment, was reduced, and WUE was up to 13% higher than that under 100% ETc treatment. While total fruit yield was not different under the two treatments, because 75% ETc treatment had fewer but larger fruit than 100% ETc trees, suggesting mild water stress thinned fruit load. By contrast, sharply decreased T and Pn of the driest treatments （50 and 25% ETo） increased WUE, but less carbon uptake impacted total fruit yield, resulting 13 and 33% lower yield compared to that of 100% ETc treatment. Irrigation rates affected fruit quality, particularly between the 100 and 75% ETc trees. Fewer but larger fruit in the mildly water stressed trees （75% ETc） resulted in more soluble solids and vitamin C, firmer fruit, and improved sugar：acid ratio and fruit color compared to the 100% ETo treatment. Overall, trees deficit irrigated at 75% ETc maintained yield while improving fruit quality and using less water.展开更多
Neuropeptides are crucial in regulation of a rich variety of developmental,physiological,and behavioral functions throughout the life cycle of insects.Using an integrated approach of multiomics,we identified neuropept...Neuropeptides are crucial in regulation of a rich variety of developmental,physiological,and behavioral functions throughout the life cycle of insects.Using an integrated approach of multiomics,we identified neuropeptide precursors in the greater wax moth Galleria mellonella,which is a harmful pest of honeybee hives with a worldwide distribution.Here,a total of 63 and 67 neuropeptide precursors were predicted and annotated in the G.mellonella genome and transcriptome,in which 40 neuropeptide precursors were confirmed in the G.mellonella peptidome.Interestingly,we identified 12 neuropeptide precursor genes present in G.mellonella but absent in honeybees,which may be potential novel pesticide target sites.Honeybee hives were contaminated with heavy metals such as lead,enabling its bioaccumulation in G.mellonella bodies through the food chain,we performed transcriptome sequencing to analyze the effects of Pb stress on the mRNA expression level of G.mellonella neuropeptide precursors.After treatment by Pb,the expression of neuropeptide F1 was found to be significantly downregulated,implying that this neuropeptide might be associated with responding to the heavy metal stress in G.mellonella.This study comprehensively identified neuropeptide precursors in G.mellonella,and discussed the effects of heavy metals on insect neuropeptides,with the example of G.mellonella.The results are valuable for future elucidation of how neuropeptides regulate physiological functions in G.mellonella and contribute to our understanding of the insect's environmental plasticity and identify potential new biomarkers to assess heavy metal toxicity in insects.展开更多
The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 3...The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs factory.In its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs bosons.Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of magnitude.This Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering aspects.Additionally,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection procedures.Construction is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 years.The commencement of experiments and data collection could potentially be initiated in the mid-2030s.展开更多
高速动车组车体的弹性振动控制对车辆运行品质的提升具有重要意义,依据车体主要弹性模态振动贡献,一种借由现有不同悬挂设备作为动力吸振器,且通过对设备的悬挂参数设计实现车体精准弹性振动控制的方法被提出。基于模态叠加理论,提出基...高速动车组车体的弹性振动控制对车辆运行品质的提升具有重要意义,依据车体主要弹性模态振动贡献,一种借由现有不同悬挂设备作为动力吸振器,且通过对设备的悬挂参数设计实现车体精准弹性振动控制的方法被提出。基于模态叠加理论,提出基于奇异值分解(Singular value decomposition,SVD)及最小二乘拟合的模态振动提取方法,将动车组车体物理振动解耦为模态振动,提取出车体各阶模态振动。分析不同车体模态对车上、车下设备安装位置处振动的贡献,据此,将设备考虑为动力吸振器,确定各设备所要制振的目标车体模态。采用固有模态法,辨识制振的目标车体模态在各设备安装位置处的等价质量,基于动力吸振理论,设计各设备的垂向和横向最优固有频率及阻尼比,并通过仿真试验对振动控制效果进行验证。结果表明,基于动力吸振的设备减振设计能够有效降低目标模态的振动,提高车辆运行平稳性。同时,在设备最优阻尼比作用下,作为动力吸振器的设备自身振动并不剧烈。展开更多
Global longitudinal strain （GLS） at rest on two-dimensional speckle tracking echocardiography （2D STE） was demonstrated to help detect coronary artery disease （CAD）. However, the optimal cut-off point of GLS and...Global longitudinal strain （GLS） at rest on two-dimensional speckle tracking echocardiography （2D STE） was demonstrated to help detect coronary artery disease （CAD）. However, the optimal cut-off point of GLS and its diagnostic power for detecting critical CAD in non-diabetes mellitus （DM） patients are unknown. In the present study, 211 patients with suspected CAD were prospectively included, with DM patients excluded. All patients underwent echocardiography and subsequently coronary angiography within 3 days. Left ventricular （LV） GLSs were quantified by 2D STE. Territorial peak systolic longitudinal strains （TLSs） were calculated based on the perfusion territories of the 3-epicardial coronary arteries in a 17-segment LV model. Critical CAD was defined as an area stenosis _〉70% in _〉1 epicardial coronary artery （_〉50% in left main coronary artery）. Totally 145 patients were diagnosed as having critical CAD by coronary angiography. Significant differences were observed in all strain parameters between patients with and without critical CAD. The area under the receiver operating charcteristic （ROC） curve （AUC） for GLS in the detection of left main （LM） or threevessel CAD was 0.875 at a cut-off value of-19.05% with sensitivity of 78.1% and specificity of 72.7%, which increased to 0.926 after exclusion of apical segments （cut-off value -18.66%; sensitivity 84.4% and specificity 81.8%）. The values of TLSs were significantly lower in regions supplied by stenotic arteries than in those by non-stenotic arteries. The AUC for the TLSs to identify critical stenosis of left circumflex （LCX） artery, left anterior descending （LAD） artery and right coronary artery （RCA）, in order of diagnostic accuracy, was 0.818 for LCX, 0.764 for LAD and 0.723 for RCA, respectively. In conclusion, in non-DM patients with suspected CAD, GLS assessed by 2D STE is an excellent predictor for LM or three-vessel CAD with high diagnostic accuracy, and a higher cut-off point than reported 展开更多
基金the grants from the National Natural Science Foundation of China(No.30170925)China Postdoctoral Science Foundation(No.20060390678)
文摘Background The multidrug resistance （MDR） associated with the expression of the mdr1 gene and its product P-glycoprotein is a major factor in the prognosis of hepatocellular carcinoma cell （HCC） patients treated with chemotherapy. Our study was to establish a stable HCC MDR cell line where a de novo acquisition of multidrug resistance specifically related to overexpression of a transgenic mdr1. Methods The 4.5-kb mdrl cDNA obtained from the plasmid pHaMDR1-1 was cloned into the PCl-neo mammalian expression vector, later was transferred by liposome to human hepatocarcinoma cell line HepG2. Then the transfected HepG2 cells resisting G418 were clustered and cultured and the specific fragment of mdr1 cDNA, mRNA and the P-glycoprotein （Pgp） in these HepG2 cells were detected by PCR, RT-PCR and flow cytometry, respectively. The accumulation of the daunorubicin was determinated by flow cytometry simultaneously. The nude mice model of grafting tumour was established by injecting subcutaneously HepG2/mdr1 cells in the right axilla. When the tumour diameter reached 5 mm, adriamycin was injected into peritoneal cavity. The size and growth inhibition of tumour were evaluated. Results The mdr1 expression vector was constructed successfully and the MDR HCC line HepG2/mdr1 developed. The PCR analysis showed that the specific fragment of mdrl cDNA in HepG2/mdr1 cells, but not in the control group HepG2 cells. Furthermore, the content of the specific fragment of mdr1 mRNA and Pgp expression in HepG2/mdr1 cells were （59.7±7.9）% and （12.28±2.09）%, respectively, compared with （16.9±3.2）% and （3.07±1.06）% in HepG2 cells. In the nude mice HCC model, the tumour genes of both groups were identified. After ADM therapy, the mean size of HepG2 cell tumours was significantly smaller than HepG2/mdr1 cell tumours. Conclusion The approach using the transfer of mdr1 cDNA may be applicable to the development of MDR hepatocarcinoma cell line, whose MDR mechanism is known. This would provide the experimental basis o
基金supported by the National Natural Science Foundation of China(Grant No.51805373)
文摘In order to control the low frequency vibration of railway vehicles, a vertical two degrees of freedom(2DOF) low frequency dynamic vibration absorber(DVA) based on acceleration is proposed. Parameters of the dynamic vibration absorber are put forth to control the low frequency vibration of car body bouncing and pitching. Next, the acceleration power spectrum density(PSD)and ride quality of the car body are calculated based on the pseudo excitation method(PEM) and covariance algorithm,respectively. According to the requirement of 2DOF low frequency DVA, the isolators with high static low dynamic stiffness(HSLDS) are designed. A high-speed train dynamic model containing HSLDS isolators is established to validate the effects on the car body vibration. The results reveal that the 2D low frequency DVA can significantly reduce the vibration of the car body bouncing and pitching. Thus, the ride quality of the vehicle is increased, and passenger comfort is improved.
基金the financial support from the National High-Tech R&D Program,China(863 Program,2011AA100504)the National Natural Science Foundation of China(51579211)+3 种基金the Key Research Project of Universities in Henan Province,China(16A416005)the 111 Project of the Chinese Education Ministry(B12007)the Initial Fund for Doctoral Reserch of Henan University of Science and Technology,China(13480016)the China Scholarship Council and USDA Agricultural Experiment Station CRIS Project(01129)
文摘We conducted a two-year study of deficit irrigation impact on peach yield and quality in semi-arid northwest China. Over two years, four-year-old peach trees were irrigated at 100, 75, 50 and 25% of peach evapotranspiration （ETc）, here, ETc= Coefficient （Kc）×Local reference evapotranspiration （ET0）. During the April-July fruit production season we measured root zone soil water depletion, sap flow velocity, net photosynthetic rate （Pn）, transpiration rate （Tr）, stomatal conductance （Gs）, water use efficiency （WUE=Pn/Tr）, fruit quality, and yield under a mobile rain-out shelter. Increased soil water depletion reasonably mirrored decreasing irrigation rates both years, causing progressively greater water stress. Progressive water stress lowered Gs, which in turn translated into lower T as measured by sap flow. However, mild deficit irrigation （75% ETc） constricted T more than Pn. Pn was not different between 100 and 75% ETc treatments in both years, and it decreased only 5-8% in June with higher temperature than that in May with cooler temperature. Concurrently under 75% ETc treatment, was reduced, and WUE was up to 13% higher than that under 100% ETc treatment. While total fruit yield was not different under the two treatments, because 75% ETc treatment had fewer but larger fruit than 100% ETc trees, suggesting mild water stress thinned fruit load. By contrast, sharply decreased T and Pn of the driest treatments （50 and 25% ETo） increased WUE, but less carbon uptake impacted total fruit yield, resulting 13 and 33% lower yield compared to that of 100% ETc treatment. Irrigation rates affected fruit quality, particularly between the 100 and 75% ETc trees. Fewer but larger fruit in the mildly water stressed trees （75% ETc） resulted in more soluble solids and vitamin C, firmer fruit, and improved sugar：acid ratio and fruit color compared to the 100% ETo treatment. Overall, trees deficit irrigated at 75% ETc maintained yield while improving fruit quality and using less water.
基金supported in part by the National Natural Science Foundation of China(32202295)Guizhou Provincial Science and Technology Projects(Qian Ke He Ji Chu-ZK[2022]General 051)+1 种基金Scientific Research Foundation for Talent Introduced in Guizhou University(Gui Da Te Gang He Zi[2021]22)Guizhou Provincial Science and Technology Projects(Qian Ke He Support[2019]2292,Qian Ke He NY[2013]3040).
文摘Neuropeptides are crucial in regulation of a rich variety of developmental,physiological,and behavioral functions throughout the life cycle of insects.Using an integrated approach of multiomics,we identified neuropeptide precursors in the greater wax moth Galleria mellonella,which is a harmful pest of honeybee hives with a worldwide distribution.Here,a total of 63 and 67 neuropeptide precursors were predicted and annotated in the G.mellonella genome and transcriptome,in which 40 neuropeptide precursors were confirmed in the G.mellonella peptidome.Interestingly,we identified 12 neuropeptide precursor genes present in G.mellonella but absent in honeybees,which may be potential novel pesticide target sites.Honeybee hives were contaminated with heavy metals such as lead,enabling its bioaccumulation in G.mellonella bodies through the food chain,we performed transcriptome sequencing to analyze the effects of Pb stress on the mRNA expression level of G.mellonella neuropeptide precursors.After treatment by Pb,the expression of neuropeptide F1 was found to be significantly downregulated,implying that this neuropeptide might be associated with responding to the heavy metal stress in G.mellonella.This study comprehensively identified neuropeptide precursors in G.mellonella,and discussed the effects of heavy metals on insect neuropeptides,with the example of G.mellonella.The results are valuable for future elucidation of how neuropeptides regulate physiological functions in G.mellonella and contribute to our understanding of the insect's environmental plasticity and identify potential new biomarkers to assess heavy metal toxicity in insects.
基金support from diverse funding sources,including the National Key Program for S&T Research and Development of the Ministry of Science and Technology(MOST),Yifang Wang's Science Studio of the Ten Thousand Talents Project,the CAS Key Foreign Cooperation Grant,the National Natural Science Foundation of China(NSFC)Beijing Municipal Science&Technology Commission,the CAS Focused Science Grant,the IHEP Innovation Grant,the CAS Lead Special Training Programthe CAS Center for Excellence in Particle Physics,the CAS International Partnership Program,and the CAS/SAFEA International Partnership Program for Creative Research Teams.
文摘The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs factory.In its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs bosons.Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of magnitude.This Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering aspects.Additionally,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection procedures.Construction is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 years.The commencement of experiments and data collection could potentially be initiated in the mid-2030s.
文摘高速动车组车体的弹性振动控制对车辆运行品质的提升具有重要意义,依据车体主要弹性模态振动贡献,一种借由现有不同悬挂设备作为动力吸振器,且通过对设备的悬挂参数设计实现车体精准弹性振动控制的方法被提出。基于模态叠加理论,提出基于奇异值分解(Singular value decomposition,SVD)及最小二乘拟合的模态振动提取方法,将动车组车体物理振动解耦为模态振动,提取出车体各阶模态振动。分析不同车体模态对车上、车下设备安装位置处振动的贡献,据此,将设备考虑为动力吸振器,确定各设备所要制振的目标车体模态。采用固有模态法,辨识制振的目标车体模态在各设备安装位置处的等价质量,基于动力吸振理论,设计各设备的垂向和横向最优固有频率及阻尼比,并通过仿真试验对振动控制效果进行验证。结果表明,基于动力吸振的设备减振设计能够有效降低目标模态的振动,提高车辆运行平稳性。同时,在设备最优阻尼比作用下,作为动力吸振器的设备自身振动并不剧烈。
文摘Global longitudinal strain （GLS） at rest on two-dimensional speckle tracking echocardiography （2D STE） was demonstrated to help detect coronary artery disease （CAD）. However, the optimal cut-off point of GLS and its diagnostic power for detecting critical CAD in non-diabetes mellitus （DM） patients are unknown. In the present study, 211 patients with suspected CAD were prospectively included, with DM patients excluded. All patients underwent echocardiography and subsequently coronary angiography within 3 days. Left ventricular （LV） GLSs were quantified by 2D STE. Territorial peak systolic longitudinal strains （TLSs） were calculated based on the perfusion territories of the 3-epicardial coronary arteries in a 17-segment LV model. Critical CAD was defined as an area stenosis _〉70% in _〉1 epicardial coronary artery （_〉50% in left main coronary artery）. Totally 145 patients were diagnosed as having critical CAD by coronary angiography. Significant differences were observed in all strain parameters between patients with and without critical CAD. The area under the receiver operating charcteristic （ROC） curve （AUC） for GLS in the detection of left main （LM） or threevessel CAD was 0.875 at a cut-off value of-19.05% with sensitivity of 78.1% and specificity of 72.7%, which increased to 0.926 after exclusion of apical segments （cut-off value -18.66%; sensitivity 84.4% and specificity 81.8%）. The values of TLSs were significantly lower in regions supplied by stenotic arteries than in those by non-stenotic arteries. The AUC for the TLSs to identify critical stenosis of left circumflex （LCX） artery, left anterior descending （LAD） artery and right coronary artery （RCA）, in order of diagnostic accuracy, was 0.818 for LCX, 0.764 for LAD and 0.723 for RCA, respectively. In conclusion, in non-DM patients with suspected CAD, GLS assessed by 2D STE is an excellent predictor for LM or three-vessel CAD with high diagnostic accuracy, and a higher cut-off point than reported
