Objectives:While programmed cell death 1(PD-1)inhibitors have improved cancer treatment,the function and mechanisms of programmed cell death ligand 1(PD-L1),particularly when expressed by cancer cells,remain unclear.T...Objectives:While programmed cell death 1(PD-1)inhibitors have improved cancer treatment,the function and mechanisms of programmed cell death ligand 1(PD-L1),particularly when expressed by cancer cells,remain unclear.This study aims to explore the role of PD-L1 within breast cancer cells and identify key targets for future immunotherapy.Methods:RNA-seq was performed on breast cancer cells with silenced PD-L1 to screen for differentially expressed genes,followed by bioinformatics analysis.Clinical specimens from breast cancer patients undergoing primary surgery without preoperative treatment were collected,along with in vitro analysis to validate the potential mechanism.Results:RNA-seq data revealed a significant positive correlation between Ecto-5′-nucleotidase(NT5E)expression and PD-L1.Bioinformatics analysis corroborated this positive correlation.Immunohistochemistry staining demonstrated higher NT5E expression associated with increased lymph node metastasis.High expression of the NT5E gene was associated with poor overall survival(OS)in breast cancer patients,as determined by KM plotter analysis.Following PD-L1 gene silencing by siRNA in breast cancer cells,NT5E mRNA and protein expression significantly decreased.Conversely,no significant changes were observed in PD-L1 expression after NT5E gene silencing.In vitro experiments confirmed that cancer cell proliferation and metastasis abilities were significantly reduced by either PD-L1 or NT5E gene down-regulation.Western blotting demonstrated that PD-L1 expressed by cancer cells regulates NT5E expression through the MAPK/ERK signaling pathway.Conclusion:This study proposes a potential mechanism wherein tumor-expressing PD-L1 regulates NT5E through the MAPK/ERK pathway.Downregulation of PD-L1 or NT5E can significantly inhibit the proliferation and metastatic ability of cancer cells,potentially providing practical therapeutic targets and prognostic markers for combined PD-L1 immunotherapy in breast cancer.展开更多
With the rapid development and popularization of new-generation technologies such as cloud computing,big data,and artificial intelligence,the construction of smart grids has become more diversified.Accurate quick read...With the rapid development and popularization of new-generation technologies such as cloud computing,big data,and artificial intelligence,the construction of smart grids has become more diversified.Accurate quick reading and classification of the electricity consumption of residential users can provide a more in-depth perception of the actual power consumption of residents,which is essential to ensure the normal operation of the power system,energy management and planning.Based on the distributed architecture of cloud computing,this paper designs an improved random forest residential electricity classification method.It uses the unique out-of-bag error of random forest and combines the Drosophila algorithm to optimize the internal parameters of the random forest,thereby improving the performance of the random forest algorithm.This method uses MapReduce to train an improved random forest model on the cloud computing platform,and then uses the trained model to analyze the residential electricity consumption data set,divides all residents into 5 categories,and verifies the effectiveness of the model through experiments and feasibility.展开更多
A two-photon fluorescent probe TPZn was developed for specific ratiometric imaging Zn2＋ in living cells and tissues. Significant ratiometric fluorescence change was based on photoinduced electron transfer and intramo...A two-photon fluorescent probe TPZn was developed for specific ratiometric imaging Zn2＋ in living cells and tissues. Significant ratiometric fluorescence change was based on photoinduced electron transfer and intramolecular charge transfer. The synthetic method of TPZn was simple. It was successfully used to selectively image Zn2＋ based on the higher binding affinity for Zn2＋ than for Cd2＋. TPZn was easily loaded into the living cell and tissues with high membrane permeability in a complex biological environment. TPZn could clearly visualize endogenous Zn2＋ by TP ratiometric imaging in hippocampal slices at a depth of 120 μm. Thus, TPZn is a useful tool to image of Zn2＋ in living cells and tissues without interference from Cd2＋.展开更多
To study immune reactions and the mechanism of anergy induced by recombinant enterotoxin A (rSEA) of Staphylococcus aureus. The gene encoding SEA was cloned from standard strain of S. aureus and high efficiently expre...To study immune reactions and the mechanism of anergy induced by recombinant enterotoxin A (rSEA) of Staphylococcus aureus. The gene encoding SEA was cloned from standard strain of S. aureus and high efficiently expressed in E. coli. After immunization with purified rSEA, mice were examined for production of specific antibody, subtype of IgG, cytokine mRNA levels such as IFN-γ, IL-2 secretion and T-cell surface PD-1 expression. Results showed that high levels of specific antibodies were produced in two weeks of primary immunization shot. During this time, humoral immune reactions prevailed (IgG2a/ IgG1 【1). During the early phase, Th1 type cytokine mRNA is expressed at a higher level than Th2 type, indicating cellular immune reaction prevailed. Splen- ocyte IFN-γ secretion was significantly decreased after boosting immunization. The PD-1 expression was detected by a flow cytometry examination in the surface of T- lymphocytes which were induced by rSEA, and the expression of PD-1 molecules increased along with the number of boosting and the time after immunization.展开更多
Plant diseases caused by vegetable viruses are an important threat to global food security,presenting a major challenge for the development of antiviral agrochemicals.Functional proteins of plant viruses play a crucia...Plant diseases caused by vegetable viruses are an important threat to global food security,presenting a major challenge for the development of antiviral agrochemicals.Functional proteins of plant viruses play a crucial role in the viral life cycle,and targeted inhibition of these proteins has emerged as a promising strategy.However,the current discovery of antiviral small molecules is hampered by the limitations of synthetic approaches and the narrow range of targets.Herein,we report a practical application of organocatalysis for serving pesticide discovery that bears a unique molecular basis.An N-heterocyclic carbene-modulated reaction is first designed to asymmetrically functionalize diverse natural phenols with phthalides.Our designed method is capable of producing a series of new phthalidyl ethers under mild conditions with good yields,enantioselectivity,and functional group tolerance.Among these,compound(R)-3w exhibits excellent and enantioselectivity-preferred curative activity against potato virus Y(PVY).Mechanistically,it is proposed that(R)-3w interacts with the nuclear inclusion body A(Nia)protein of PVY at the His150 residue.This binding impairs Nia’s function to cleavage polyprotein,thereby inhibiting formation of viral replication complex.The study provides insights into advancing synthetic protocol to facilitate agrochemical discovery,and our identified(R)-3w may serve as a potential lead for future research and development PVY-Nia inhibitors.展开更多
由于云的时空尺度非常宽广,云微物理参数化方案一直是气候模式中的薄弱环节.本文借鉴中尺度模式云微物理方案从双参数向三参数扩展的思路方法,发展了联合地球系统模式(Community Integrated Earth System Model,CIESM)三参数冰相云微物...由于云的时空尺度非常宽广,云微物理参数化方案一直是气候模式中的薄弱环节.本文借鉴中尺度模式云微物理方案从双参数向三参数扩展的思路方法,发展了联合地球系统模式(Community Integrated Earth System Model,CIESM)三参数冰相云微物理方案,弥补了默认双参数方案不能预报冰晶粒径分布谱形参数(μ)的不足,进而分析了双、三参数方案对气候模拟的影响.模拟结果表明,相较于双参数方案(μ为0),三参数方案预报得出的μ更为合理,其在垂直分布上整体呈现出“高层小低层大”的特点,高层的低值主要是由于冰晶核化以及较大的冰晶粒子沉降后粒子之间相互混合导致的,而低层的高值主要是由于冰晶粒子在沉降过程中的粒子分选机制导致的.与双、三参数方案中μ的差异相呼应,模式模拟的气候平均态出现明显差异,其中三参数方案模拟的总云云量、低云云量、中云云量和总降水相较于双参数方案更接近观测结果,高云云量的误差增大.其中总降水的改进主要是由于高云云量的增加,大气稳定度增加,对流性降水减少.此外,还调整了相关参数,以改善模式对辐射的模拟能力.总之,本文在全球气候模式中评估了双、三参数方案对于模拟气候平均态的不同影响,为气候模式中云微物理方案的发展改进提供了一定的参考意义.展开更多
In order to study the bearing performance of a new type of prefabricated subway station structure(PSSS),firstly,a three-dimensional finite element model of the PSSS was established to study the nonlinear mechanics and...In order to study the bearing performance of a new type of prefabricated subway station structure(PSSS),firstly,a three-dimensional finite element model of the PSSS was established to study the nonlinear mechanics and deformation performance.Secondly,the bearing mechanism of a PSSS was investigated in detail.Finally,the development law of damages to a thin-walled prefabricated component and the failure evolution mechanism of a PSSS were discussed.The results showed that this new type of the PSSS had good bearing capacity.The top arch structure was a three-hinged arch bearing system,and the enclosure structure and the substructure were respectively used as the horizontal and vertical support systems of the three-hinged arch structure to ensure the integrity and stability of the overall structure.Moreover,the tongue-and-groove joints could effectively transmit the internal force between the components and keep the components deformed in harmony.The rigidity degradation of the PSSS caused by the accumulation of damages to the spandrel,hance,arch foot,and enclosure structure was the main reason of its loss of bearing capacity.The existing thin-walled components design had significant advantages in weight reduction,concrete temperature control,components hoisting,transportation and assembly construction,which achieved a good balance between safety,usability and economy.展开更多
基金Provincial Natural Science Foundation J230016Provincial Natural Science Foundation H2023206441Hebei Province Major Science and Technology Support Program Project S&T Program of Hebei 242W7701Z.
文摘Objectives:While programmed cell death 1(PD-1)inhibitors have improved cancer treatment,the function and mechanisms of programmed cell death ligand 1(PD-L1),particularly when expressed by cancer cells,remain unclear.This study aims to explore the role of PD-L1 within breast cancer cells and identify key targets for future immunotherapy.Methods:RNA-seq was performed on breast cancer cells with silenced PD-L1 to screen for differentially expressed genes,followed by bioinformatics analysis.Clinical specimens from breast cancer patients undergoing primary surgery without preoperative treatment were collected,along with in vitro analysis to validate the potential mechanism.Results:RNA-seq data revealed a significant positive correlation between Ecto-5′-nucleotidase(NT5E)expression and PD-L1.Bioinformatics analysis corroborated this positive correlation.Immunohistochemistry staining demonstrated higher NT5E expression associated with increased lymph node metastasis.High expression of the NT5E gene was associated with poor overall survival(OS)in breast cancer patients,as determined by KM plotter analysis.Following PD-L1 gene silencing by siRNA in breast cancer cells,NT5E mRNA and protein expression significantly decreased.Conversely,no significant changes were observed in PD-L1 expression after NT5E gene silencing.In vitro experiments confirmed that cancer cell proliferation and metastasis abilities were significantly reduced by either PD-L1 or NT5E gene down-regulation.Western blotting demonstrated that PD-L1 expressed by cancer cells regulates NT5E expression through the MAPK/ERK signaling pathway.Conclusion:This study proposes a potential mechanism wherein tumor-expressing PD-L1 regulates NT5E through the MAPK/ERK pathway.Downregulation of PD-L1 or NT5E can significantly inhibit the proliferation and metastatic ability of cancer cells,potentially providing practical therapeutic targets and prognostic markers for combined PD-L1 immunotherapy in breast cancer.
基金This work was partially supported by the National Natural Science Foundation of China(61876089).
文摘With the rapid development and popularization of new-generation technologies such as cloud computing,big data,and artificial intelligence,the construction of smart grids has become more diversified.Accurate quick reading and classification of the electricity consumption of residential users can provide a more in-depth perception of the actual power consumption of residents,which is essential to ensure the normal operation of the power system,energy management and planning.Based on the distributed architecture of cloud computing,this paper designs an improved random forest residential electricity classification method.It uses the unique out-of-bag error of random forest and combines the Drosophila algorithm to optimize the internal parameters of the random forest,thereby improving the performance of the random forest algorithm.This method uses MapReduce to train an improved random forest model on the cloud computing platform,and then uses the trained model to analyze the residential electricity consumption data set,divides all residents into 5 categories,and verifies the effectiveness of the model through experiments and feasibility.
基金supported by the Introduction Research Item of Northwest University for Nationalities(No.xbmuyjrc201110)the Fundamental Research Funds for the Central Universities(Nos.zyz2012062 and 31920130024)the Young and Middle-Aged Scientists Research Fund of Northwest University for Nationalities(No.12XB34)
文摘A two-photon fluorescent probe TPZn was developed for specific ratiometric imaging Zn2＋ in living cells and tissues. Significant ratiometric fluorescence change was based on photoinduced electron transfer and intramolecular charge transfer. The synthetic method of TPZn was simple. It was successfully used to selectively image Zn2＋ based on the higher binding affinity for Zn2＋ than for Cd2＋. TPZn was easily loaded into the living cell and tissues with high membrane permeability in a complex biological environment. TPZn could clearly visualize endogenous Zn2＋ by TP ratiometric imaging in hippocampal slices at a depth of 120 μm. Thus, TPZn is a useful tool to image of Zn2＋ in living cells and tissues without interference from Cd2＋.
文摘To study immune reactions and the mechanism of anergy induced by recombinant enterotoxin A (rSEA) of Staphylococcus aureus. The gene encoding SEA was cloned from standard strain of S. aureus and high efficiently expressed in E. coli. After immunization with purified rSEA, mice were examined for production of specific antibody, subtype of IgG, cytokine mRNA levels such as IFN-γ, IL-2 secretion and T-cell surface PD-1 expression. Results showed that high levels of specific antibodies were produced in two weeks of primary immunization shot. During this time, humoral immune reactions prevailed (IgG2a/ IgG1 【1). During the early phase, Th1 type cytokine mRNA is expressed at a higher level than Th2 type, indicating cellular immune reaction prevailed. Splen- ocyte IFN-γ secretion was significantly decreased after boosting immunization. The PD-1 expression was detected by a flow cytometry examination in the surface of T- lymphocytes which were induced by rSEA, and the expression of PD-1 molecules increased along with the number of boosting and the time after immunization.
基金the National Natural Science Foundation of China(nos.32302388 and 32330087)the Scientific Research Innovation Team of Guizhou University(no.202403).
文摘Plant diseases caused by vegetable viruses are an important threat to global food security,presenting a major challenge for the development of antiviral agrochemicals.Functional proteins of plant viruses play a crucial role in the viral life cycle,and targeted inhibition of these proteins has emerged as a promising strategy.However,the current discovery of antiviral small molecules is hampered by the limitations of synthetic approaches and the narrow range of targets.Herein,we report a practical application of organocatalysis for serving pesticide discovery that bears a unique molecular basis.An N-heterocyclic carbene-modulated reaction is first designed to asymmetrically functionalize diverse natural phenols with phthalides.Our designed method is capable of producing a series of new phthalidyl ethers under mild conditions with good yields,enantioselectivity,and functional group tolerance.Among these,compound(R)-3w exhibits excellent and enantioselectivity-preferred curative activity against potato virus Y(PVY).Mechanistically,it is proposed that(R)-3w interacts with the nuclear inclusion body A(Nia)protein of PVY at the His150 residue.This binding impairs Nia’s function to cleavage polyprotein,thereby inhibiting formation of viral replication complex.The study provides insights into advancing synthetic protocol to facilitate agrochemical discovery,and our identified(R)-3w may serve as a potential lead for future research and development PVY-Nia inhibitors.
文摘由于云的时空尺度非常宽广,云微物理参数化方案一直是气候模式中的薄弱环节.本文借鉴中尺度模式云微物理方案从双参数向三参数扩展的思路方法,发展了联合地球系统模式(Community Integrated Earth System Model,CIESM)三参数冰相云微物理方案,弥补了默认双参数方案不能预报冰晶粒径分布谱形参数(μ)的不足,进而分析了双、三参数方案对气候模拟的影响.模拟结果表明,相较于双参数方案(μ为0),三参数方案预报得出的μ更为合理,其在垂直分布上整体呈现出“高层小低层大”的特点,高层的低值主要是由于冰晶核化以及较大的冰晶粒子沉降后粒子之间相互混合导致的,而低层的高值主要是由于冰晶粒子在沉降过程中的粒子分选机制导致的.与双、三参数方案中μ的差异相呼应,模式模拟的气候平均态出现明显差异,其中三参数方案模拟的总云云量、低云云量、中云云量和总降水相较于双参数方案更接近观测结果,高云云量的误差增大.其中总降水的改进主要是由于高云云量的增加,大气稳定度增加,对流性降水减少.此外,还调整了相关参数,以改善模式对辐射的模拟能力.总之,本文在全球气候模式中评估了双、三参数方案对于模拟气候平均态的不同影响,为气候模式中云微物理方案的发展改进提供了一定的参考意义.
基金the National Key R&D Program of China(Nos.2017YFC0805403 and 2019YFC1509704)the National Natural Science Foundation of China(Grant Nos.41877218 and 42072308).
文摘In order to study the bearing performance of a new type of prefabricated subway station structure(PSSS),firstly,a three-dimensional finite element model of the PSSS was established to study the nonlinear mechanics and deformation performance.Secondly,the bearing mechanism of a PSSS was investigated in detail.Finally,the development law of damages to a thin-walled prefabricated component and the failure evolution mechanism of a PSSS were discussed.The results showed that this new type of the PSSS had good bearing capacity.The top arch structure was a three-hinged arch bearing system,and the enclosure structure and the substructure were respectively used as the horizontal and vertical support systems of the three-hinged arch structure to ensure the integrity and stability of the overall structure.Moreover,the tongue-and-groove joints could effectively transmit the internal force between the components and keep the components deformed in harmony.The rigidity degradation of the PSSS caused by the accumulation of damages to the spandrel,hance,arch foot,and enclosure structure was the main reason of its loss of bearing capacity.The existing thin-walled components design had significant advantages in weight reduction,concrete temperature control,components hoisting,transportation and assembly construction,which achieved a good balance between safety,usability and economy.
