目的研究呼出气一氧化氮(FeNO)、血清免疫球蛋白E(IgE)和基质金属蛋白酶9(MMP9)的水平与儿童哮喘急性发作之间的关系,为儿童哮喘的预防及治疗提供依据。方法选取沈阳市妇婴医院于2020年11月至2022年11月收治的98例支气管哮喘急性发作期...目的研究呼出气一氧化氮(FeNO)、血清免疫球蛋白E(IgE)和基质金属蛋白酶9(MMP9)的水平与儿童哮喘急性发作之间的关系,为儿童哮喘的预防及治疗提供依据。方法选取沈阳市妇婴医院于2020年11月至2022年11月收治的98例支气管哮喘急性发作期儿童作为急性组,按照病情程度分成轻度组(n=32)、中度组(n=38)和重度组(n=28),按照2∶1的比例选出49例同期在门诊治疗的处于支气管哮喘缓解期的儿童作为缓解组,随机选取健康体检儿童49例作为健康对照组,分别对他们进行FeNO、MMP9和血清IgE及肺功能[用力肺活量(FVC)、1秒用力呼气量(FEV_(1))、FEV_(1)/FVC%、最大呼气流量(PEF)]检测。应用Pearson相关分析探讨哮喘急性发作期FeNO、MMP9及血清IgE和肺功能之间的联系,并对三者在支气管哮喘急性发作中的预测价值进行分析。结果急性组、缓解组和对照组的年龄、性别、体重指数和病程的比较,差异无统计学意义(P>0.05)。急性组FeNO、MMP9、血清IgE分别为(59.95±12.65)ppb、(4.87±1.44)pg/ml、(330.63±74.88)IU/ml,缓解组分别为(25.23±8.23)ppb、(1.21±0.02)pg/ml、(152.23±32.12)IU/ml,均高于对照组的(12.43±4.09)ppb、(0.53±0.24)pg/ml、(126.34±57.33)IU/ml,差异具有统计学意义(P<0.05)。急性期和缓解期FVC、FEV1、FEV1/FVC%、PEF均低于对照组,差异具有统计学意义(P<0.05)。支气管哮喘急性发作中度组FeNO、MMP9、血清IgE水平分别为(49.23±6.23)ppb、(1.21±0.02)pg/ml、(282.61±59.83)IU/ml,重度组分别为(67.43±10.09)ppb、(0.53±0.24)pg/ml、(356.49±70.82)IU/ml,均高于轻度组的(34.62±10.65)ppb、(4.87±1.44)pg/ml,(189.21±14.33)IU/ml,差异具有统计学意义(P<0.05)。在轻度组中FeNO、MMP9和血清IgE水平均较低,而在中度组中这些指标均较高,其中FVC、FEV_(1)、FEV_(1)/FVC%和PEF均较低,差异具有统计学意义(P<0.05)。FeNO以及MMP9与血清IgE水平呈正相关(P<0.05),FeNO、MMP9以及血清IgE水平与FVC、FEV_(1)、FEV_(1)/FVC%、PEF均呈负相关(P<0.05)。MMP9在支气管哮喘的诊断中表现出了显著的优势,当达到最大约登指数时,对应的截断值为1.17,曲线下面积(Area under curve,AUC)为0.83,敏感度和特异性也分别达到了90.13%和86.5%。结论支气管哮喘急性发作的儿童血清中的FeNO、MMP9以及血清IgE水平显著增高,随肺部功能恶化程度加重而上升,可能与支气管哮喘急性发作患儿肺功能损害程度有关。展开更多
Background Genome editing has been considered as powerful tool in agricultural fields.However,genome editing progress in cattle has not been fast as in other mammal species,for some disadvantages including long gestat...Background Genome editing has been considered as powerful tool in agricultural fields.However,genome editing progress in cattle has not been fast as in other mammal species,for some disadvantages including long gestational periods,single pregnancy,and high raising cost.Furthermore,technically demanding methods such as microinjection and somatic cell nuclear transfer(SCNT)are needed for gene editing in cattle.In this point of view,electroporation in embryos has been risen as an alternative.Results First,editing efficiency of our electroporation methods were tested for embryos.Presence of mutation on embryo was confirmed by T7E1 assay.With first combination,mutation rates for MSTN and PRNP were 57.6%±13.7%and 54.6%±13.5%,respectively.In case of MSTN/BLG,mutation rates were 83.9%±23.6%for MSTN,84.5%±18.0%for BLG.Afterwards,the double-KO embryos were transferred to surrogates and mutation rate was identified in resultant calves by targeted deep sequencing.Thirteen recipients were transferred for MSTN/PRNP,4 calves were delivered,and one calf underwent an induction for double KO.Ten surrogates were given double-KO embryos for MSTN/BLG,and four of the six calves that were born had mutations in both genes.Conclusions These data demonstrated that production of genome edited cattle via electroporation of RNP could be effectively applied.Finally,MSTN and PRNP from beef cattle and MSTN and BLG from dairy cattle have been born and they will be valuable resources for future precision breeding.展开更多
The development and maturation of the CRISPR/Cas genome editing system provides a valuable tool for plant functional genomics and genetic improvement.Currently available genome-editing tools have a limited number of t...The development and maturation of the CRISPR/Cas genome editing system provides a valuable tool for plant functional genomics and genetic improvement.Currently available genome-editing tools have a limited number of targets,restricting their application in genetic research.In this study,we developed a novel CRISPR/Cas9 plant ultra-multiplex genome editing system consisting of two template vectors,eight donor vectors,four destination vectors,and one primer-design software package.By combining the advantages of Golden Gate cloning to assemble multiple repetitive fragments and Gateway recombination to assemble large fragments and by changing the structure of the amplicons used to assemble sg RNA expression cassettes,the plant ultra-multiplex genome editing system can assemble a single binary vector targeting more than 40 genomic loci.A rice knockout vector containing 49 sg RNA expression cassettes was assembled and a high co-editing efficiency was observed.This plant ultra-multiplex genome editing system advances synthetic biology and plant genetic engineering.展开更多
Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emerge...Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19-9)and tumor size changes pre-and post-neoadjuvant therapy(NAT).METHODS This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment,Chongqing University Cancer Hospital.This study specifically assessed CA19-9 levels and tumor size before and after NAT.RESULTS A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study.The average age was 65.4±10.6 years and 72(46.2%)patients were female.Before survival analysis,we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio(CR).The patients were divided into three groups:CR<0.5,CR>0.5 and<1 and CR>1.With regard to tumor size measured by both computed tomography and magnetic resonance imaging,we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio(TR).The patients were then divided into three groups:TR<0.5,TR>0.5 and<1 and TR>1.Based on these groups divided according to CR and TR,we performed both overall survival(OS)and disease-free survival(DFS)analyses.Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR(P<0.05).CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response.Moreover,CR(hazard ratio:1.721,95%CI:1.373-3.762;P=0.006),and TR(hazard ratio:1.435,95%CI:1.275-4.363;P=0.014)were identified as independent factors associated with OS.CONCLUSION This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.展开更多
Developing reliable and efficient anode materials is essential for the successfully practical application of sodium-ion batteries.Herein,employing a straightforward and rapid chemical vapor deposition technique,two-di...Developing reliable and efficient anode materials is essential for the successfully practical application of sodium-ion batteries.Herein,employing a straightforward and rapid chemical vapor deposition technique,two-dimensional layered ternary indium phosphorus sulfide(In_(2)P_(3)S_(9)) nanosheets are prepared.The layered structure and ternary composition of the In_(2)P_(3)S_(9) electrode result in impressive electrochemical performance,including a high reversible capacity of 704 mA h g^(-1) at 0.1 A g^(-1),an outstanding rate capability with 425 mA h g^(-1) at 5 A g^(-1),and an exceptional cycling stability with a capacity retention of88% after 350 cycles at 1 A g^(-1).Furthermore,sodium-ion full cell also affords a high capacity of 308 and114 mA h g^(-1) at 0.1 and 5 A g^(-1).Ex-situ X-ray diffraction and ex-situ high-resolution transmission electron microscopy tests are conducted to investigate the underlying Na-storage mechanism of In_(2)P_(3)S_(9).The results reveal that during the first cycle,the P-S bond is broken to form the elemental P and In_(2)S_(3),collectively contributing to a remarkably high reversible specific capacity.The excellent electrochemical energy storage results corroborate the practical application potential of In_(2)P_(3)S_(9) for sodium-ion batteries.展开更多
文摘目的研究呼出气一氧化氮(FeNO)、血清免疫球蛋白E(IgE)和基质金属蛋白酶9(MMP9)的水平与儿童哮喘急性发作之间的关系,为儿童哮喘的预防及治疗提供依据。方法选取沈阳市妇婴医院于2020年11月至2022年11月收治的98例支气管哮喘急性发作期儿童作为急性组,按照病情程度分成轻度组(n=32)、中度组(n=38)和重度组(n=28),按照2∶1的比例选出49例同期在门诊治疗的处于支气管哮喘缓解期的儿童作为缓解组,随机选取健康体检儿童49例作为健康对照组,分别对他们进行FeNO、MMP9和血清IgE及肺功能[用力肺活量(FVC)、1秒用力呼气量(FEV_(1))、FEV_(1)/FVC%、最大呼气流量(PEF)]检测。应用Pearson相关分析探讨哮喘急性发作期FeNO、MMP9及血清IgE和肺功能之间的联系,并对三者在支气管哮喘急性发作中的预测价值进行分析。结果急性组、缓解组和对照组的年龄、性别、体重指数和病程的比较,差异无统计学意义(P>0.05)。急性组FeNO、MMP9、血清IgE分别为(59.95±12.65)ppb、(4.87±1.44)pg/ml、(330.63±74.88)IU/ml,缓解组分别为(25.23±8.23)ppb、(1.21±0.02)pg/ml、(152.23±32.12)IU/ml,均高于对照组的(12.43±4.09)ppb、(0.53±0.24)pg/ml、(126.34±57.33)IU/ml,差异具有统计学意义(P<0.05)。急性期和缓解期FVC、FEV1、FEV1/FVC%、PEF均低于对照组,差异具有统计学意义(P<0.05)。支气管哮喘急性发作中度组FeNO、MMP9、血清IgE水平分别为(49.23±6.23)ppb、(1.21±0.02)pg/ml、(282.61±59.83)IU/ml,重度组分别为(67.43±10.09)ppb、(0.53±0.24)pg/ml、(356.49±70.82)IU/ml,均高于轻度组的(34.62±10.65)ppb、(4.87±1.44)pg/ml,(189.21±14.33)IU/ml,差异具有统计学意义(P<0.05)。在轻度组中FeNO、MMP9和血清IgE水平均较低,而在中度组中这些指标均较高,其中FVC、FEV_(1)、FEV_(1)/FVC%和PEF均较低,差异具有统计学意义(P<0.05)。FeNO以及MMP9与血清IgE水平呈正相关(P<0.05),FeNO、MMP9以及血清IgE水平与FVC、FEV_(1)、FEV_(1)/FVC%、PEF均呈负相关(P<0.05)。MMP9在支气管哮喘的诊断中表现出了显著的优势,当达到最大约登指数时,对应的截断值为1.17,曲线下面积(Area under curve,AUC)为0.83,敏感度和特异性也分别达到了90.13%和86.5%。结论支气管哮喘急性发作的儿童血清中的FeNO、MMP9以及血清IgE水平显著增高,随肺部功能恶化程度加重而上升,可能与支气管哮喘急性发作患儿肺功能损害程度有关。
基金financially supported by the National Research Foundation of Korea(NRF-2021R1A5A1033157 for SRC program:382 Comparative medicine Disease Research Center,NRF-2021R1F1A105195313)the Research Institute of Veterinary Science,the BK21 Four for Future Veterinary Medicine Leading Education and Research Center,and a Seoul National University(SNU)grant(#550e2020005)。
文摘Background Genome editing has been considered as powerful tool in agricultural fields.However,genome editing progress in cattle has not been fast as in other mammal species,for some disadvantages including long gestational periods,single pregnancy,and high raising cost.Furthermore,technically demanding methods such as microinjection and somatic cell nuclear transfer(SCNT)are needed for gene editing in cattle.In this point of view,electroporation in embryos has been risen as an alternative.Results First,editing efficiency of our electroporation methods were tested for embryos.Presence of mutation on embryo was confirmed by T7E1 assay.With first combination,mutation rates for MSTN and PRNP were 57.6%±13.7%and 54.6%±13.5%,respectively.In case of MSTN/BLG,mutation rates were 83.9%±23.6%for MSTN,84.5%±18.0%for BLG.Afterwards,the double-KO embryos were transferred to surrogates and mutation rate was identified in resultant calves by targeted deep sequencing.Thirteen recipients were transferred for MSTN/PRNP,4 calves were delivered,and one calf underwent an induction for double KO.Ten surrogates were given double-KO embryos for MSTN/BLG,and four of the six calves that were born had mutations in both genes.Conclusions These data demonstrated that production of genome edited cattle via electroporation of RNP could be effectively applied.Finally,MSTN and PRNP from beef cattle and MSTN and BLG from dairy cattle have been born and they will be valuable resources for future precision breeding.
基金supported by the National Natural Science Foundation of China(32001532 and 31860411)the National Key Research and Development Program of China,(2022YFF1000020)+1 种基金Hunan Seed Industry Innovation Project(2021NK1012)the Yunnan Tobacco Company Project(2020530000241009)。
文摘The development and maturation of the CRISPR/Cas genome editing system provides a valuable tool for plant functional genomics and genetic improvement.Currently available genome-editing tools have a limited number of targets,restricting their application in genetic research.In this study,we developed a novel CRISPR/Cas9 plant ultra-multiplex genome editing system consisting of two template vectors,eight donor vectors,four destination vectors,and one primer-design software package.By combining the advantages of Golden Gate cloning to assemble multiple repetitive fragments and Gateway recombination to assemble large fragments and by changing the structure of the amplicons used to assemble sg RNA expression cassettes,the plant ultra-multiplex genome editing system can assemble a single binary vector targeting more than 40 genomic loci.A rice knockout vector containing 49 sg RNA expression cassettes was assembled and a high co-editing efficiency was observed.This plant ultra-multiplex genome editing system advances synthetic biology and plant genetic engineering.
文摘Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.
基金Natural Science Foundation of Chongqing,China,No.cstc2021jcyj-msxmX0501Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science and Technology Bureau),No.2022QNXM074.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19-9)and tumor size changes pre-and post-neoadjuvant therapy(NAT).METHODS This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment,Chongqing University Cancer Hospital.This study specifically assessed CA19-9 levels and tumor size before and after NAT.RESULTS A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study.The average age was 65.4±10.6 years and 72(46.2%)patients were female.Before survival analysis,we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio(CR).The patients were divided into three groups:CR<0.5,CR>0.5 and<1 and CR>1.With regard to tumor size measured by both computed tomography and magnetic resonance imaging,we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio(TR).The patients were then divided into three groups:TR<0.5,TR>0.5 and<1 and TR>1.Based on these groups divided according to CR and TR,we performed both overall survival(OS)and disease-free survival(DFS)analyses.Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR(P<0.05).CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response.Moreover,CR(hazard ratio:1.721,95%CI:1.373-3.762;P=0.006),and TR(hazard ratio:1.435,95%CI:1.275-4.363;P=0.014)were identified as independent factors associated with OS.CONCLUSION This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.
基金Financial supports from the National Natural Science Foundation of China(22265018 and 21961019)the Key Project of Natural Science Foundation of Jiangxi Province(20232ACB204010)。
文摘Developing reliable and efficient anode materials is essential for the successfully practical application of sodium-ion batteries.Herein,employing a straightforward and rapid chemical vapor deposition technique,two-dimensional layered ternary indium phosphorus sulfide(In_(2)P_(3)S_(9)) nanosheets are prepared.The layered structure and ternary composition of the In_(2)P_(3)S_(9) electrode result in impressive electrochemical performance,including a high reversible capacity of 704 mA h g^(-1) at 0.1 A g^(-1),an outstanding rate capability with 425 mA h g^(-1) at 5 A g^(-1),and an exceptional cycling stability with a capacity retention of88% after 350 cycles at 1 A g^(-1).Furthermore,sodium-ion full cell also affords a high capacity of 308 and114 mA h g^(-1) at 0.1 and 5 A g^(-1).Ex-situ X-ray diffraction and ex-situ high-resolution transmission electron microscopy tests are conducted to investigate the underlying Na-storage mechanism of In_(2)P_(3)S_(9).The results reveal that during the first cycle,the P-S bond is broken to form the elemental P and In_(2)S_(3),collectively contributing to a remarkably high reversible specific capacity.The excellent electrochemical energy storage results corroborate the practical application potential of In_(2)P_(3)S_(9) for sodium-ion batteries.
