目的克隆并表达分离于我国3种类型的利什曼原虫K26基因,并用其检测我国内脏利什曼病特异性抗体,同时进行效果评价。方法分别将我国新疆喀什(KS-6株)、四川九寨沟县(SC6株)和新疆伽师县(JIASHI-1株)K26基因进行全基因合成并加入Bam H I与...目的克隆并表达分离于我国3种类型的利什曼原虫K26基因,并用其检测我国内脏利什曼病特异性抗体,同时进行效果评价。方法分别将我国新疆喀什(KS-6株)、四川九寨沟县(SC6株)和新疆伽师县(JIASHI-1株)K26基因进行全基因合成并加入Bam H I与Xho I酶切位点,分别将K26基因连接至双酶切的pET32a表达载体,转入大肠埃希菌(E.coli)BL21(DE3)中经1 mmol/L的异丙基-β-D-半乳糖苷(IPTG)进行诱导表达,用组氨酸标签亲和纯化柱(Ni-NTA树脂)纯化重组蛋白。用制备的3种抗原分别作为包被抗原,以酶联免疫吸附试验(ELISA)检测病原学确诊的内脏利什曼病患者及其它寄生虫病患者和健康者的血清中和抗体,以评价其检测的敏感性和特异性。用美国InBios公司rK39试条进行平行检测,比较3种抗原检测的敏感性。结果成功构建利什曼原虫pET32a-K26重组质粒,并在原核细胞中成功表达。以KS-6株、SC6株、JIASHI-1株利什曼原虫重组K26蛋白为包被抗原的ELISA法和rK39试条法检测黑热病患者血清的敏感性分别为90.00%(99/110)、92.73%(102/110)、90.91%(100/110)和93.64%(103/110),共检测45份其他寄生虫病患者(包括日本血吸虫病、疟疾、细粒棘球蚴病、华支睾吸虫病、卫氏并殖吸虫病和弓形虫病)的血清均无交叉反应,健康者血清(40份)也无假阳性反应,特异性均为100.00%。KS-6株、SC6株和JIASHI-1株利什曼原虫重组K26蛋白ELISA法和rK39试条法的阳性检出率差异无统计学意义(χ^(2)_(KS)-6=0.97,P=0.33;χ^(2)_(SC6)=0.07,P=0.79;χ^(2)_(JIASHI)-1=0.57,P=0.45)。3种K26抗原的阳性检出率差异无统计学意义(χ^(2)=0.53,P=0.97)。结论重组K26抗原在内脏利什曼病诊断上具有潜在的应用价值。展开更多
Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk...Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk1/CTX-Lip).Methods:Physical and chemical properties of Rk1/CTX-Lip were investigated.We evaluated the biological functions of Rk1/CTXLip,both in vitro and in vivo.A subcutaneous prostate cancer(RM-1)-bearing mouse model was established to study the efficacy of Rk1/CTX-Lip inhibition in tumors.Simultaneously,a Candida albicans infection model was established in tumor-bearing mice to study the infection-relieving efficacy of Rk1/CTX-Lip.Finally,biocompatibility and in vivo safety of Rk1/CTX-Lip were evaluated.Results:We successfully prepared Rk1/CTX-Lip,achieving high CTX encapsulation efficiency(97.24±0.75)%and physical stability.Rk1/CTX-Lip demonstrated evasion of macrophage phagocytosis,effective tumor tissue targeting,and a significant reduction(>50%)in average tumor volume compared with Chol/CTX-Lip.Moreover,it relieved the concurrent infection burden and effectively regulated immune organs and cells,demonstrating superior biocompatibility.Conclusion:Rk1/CTX-Lip presents a promising new therapy for prostate cancer and holds potential for relieving concurrent fungal infections in cancer patients with low immunity.展开更多
This paper provides a study on the stability and time-step constraints of solving the linearized Korteweg-de Vries(KdV)equation,using implicit-explicit(IMEX)Runge-Kutta(RK)time integration methods combined with either...This paper provides a study on the stability and time-step constraints of solving the linearized Korteweg-de Vries(KdV)equation,using implicit-explicit(IMEX)Runge-Kutta(RK)time integration methods combined with either finite difference(FD)or local discontinuous Galerkin(DG)spatial discretization.We analyze the stability of the fully discrete scheme,on a uniform mesh with periodic boundary conditions,using the Fourier method.For the linearized KdV equation,the IMEX schemes are stable under the standard Courant-Friedrichs-Lewy(CFL)conditionτ≤λh.Here,λis the CFL number,τis the time-step size,and h is the spatial mesh size.We study several IMEX schemes and characterize their CFL number as a function ofθ=d/h^(2)with d being the dispersion coefficient,which leads to several interesting observations.We also investigate the asymptotic behaviors of the CFL number for sufficiently refined meshes and derive the necessary conditions for the asymptotic stability of the IMEX-RK methods.Some numerical experiments are provided in the paper to illustrate the performance of IMEX methods under different time-step constraints.展开更多
文摘目的克隆并表达分离于我国3种类型的利什曼原虫K26基因,并用其检测我国内脏利什曼病特异性抗体,同时进行效果评价。方法分别将我国新疆喀什(KS-6株)、四川九寨沟县(SC6株)和新疆伽师县(JIASHI-1株)K26基因进行全基因合成并加入Bam H I与Xho I酶切位点,分别将K26基因连接至双酶切的pET32a表达载体,转入大肠埃希菌(E.coli)BL21(DE3)中经1 mmol/L的异丙基-β-D-半乳糖苷(IPTG)进行诱导表达,用组氨酸标签亲和纯化柱(Ni-NTA树脂)纯化重组蛋白。用制备的3种抗原分别作为包被抗原,以酶联免疫吸附试验(ELISA)检测病原学确诊的内脏利什曼病患者及其它寄生虫病患者和健康者的血清中和抗体,以评价其检测的敏感性和特异性。用美国InBios公司rK39试条进行平行检测,比较3种抗原检测的敏感性。结果成功构建利什曼原虫pET32a-K26重组质粒,并在原核细胞中成功表达。以KS-6株、SC6株、JIASHI-1株利什曼原虫重组K26蛋白为包被抗原的ELISA法和rK39试条法检测黑热病患者血清的敏感性分别为90.00%(99/110)、92.73%(102/110)、90.91%(100/110)和93.64%(103/110),共检测45份其他寄生虫病患者(包括日本血吸虫病、疟疾、细粒棘球蚴病、华支睾吸虫病、卫氏并殖吸虫病和弓形虫病)的血清均无交叉反应,健康者血清(40份)也无假阳性反应,特异性均为100.00%。KS-6株、SC6株和JIASHI-1株利什曼原虫重组K26蛋白ELISA法和rK39试条法的阳性检出率差异无统计学意义(χ^(2)_(KS)-6=0.97,P=0.33;χ^(2)_(SC6)=0.07,P=0.79;χ^(2)_(JIASHI)-1=0.57,P=0.45)。3种K26抗原的阳性检出率差异无统计学意义(χ^(2)=0.53,P=0.97)。结论重组K26抗原在内脏利什曼病诊断上具有潜在的应用价值。
基金supported by the National Natural Science Foundation of China(82373808)Chongqing Natural Science Foundation(cstc2021jcyj-bshX0125)+1 种基金Fundamental Research Funds for the Central Universities(SWURC2020001)the project for Chongqing University Innovation Research Group,Chongqing Education Committee(CXQT20006).
文摘Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk1/CTX-Lip).Methods:Physical and chemical properties of Rk1/CTX-Lip were investigated.We evaluated the biological functions of Rk1/CTXLip,both in vitro and in vivo.A subcutaneous prostate cancer(RM-1)-bearing mouse model was established to study the efficacy of Rk1/CTX-Lip inhibition in tumors.Simultaneously,a Candida albicans infection model was established in tumor-bearing mice to study the infection-relieving efficacy of Rk1/CTX-Lip.Finally,biocompatibility and in vivo safety of Rk1/CTX-Lip were evaluated.Results:We successfully prepared Rk1/CTX-Lip,achieving high CTX encapsulation efficiency(97.24±0.75)%and physical stability.Rk1/CTX-Lip demonstrated evasion of macrophage phagocytosis,effective tumor tissue targeting,and a significant reduction(>50%)in average tumor volume compared with Chol/CTX-Lip.Moreover,it relieved the concurrent infection burden and effectively regulated immune organs and cells,demonstrating superior biocompatibility.Conclusion:Rk1/CTX-Lip presents a promising new therapy for prostate cancer and holds potential for relieving concurrent fungal infections in cancer patients with low immunity.
基金supported by the NSF under Grant DMS-2208391sponsored by the NSF under Grant DMS-1753581.
文摘This paper provides a study on the stability and time-step constraints of solving the linearized Korteweg-de Vries(KdV)equation,using implicit-explicit(IMEX)Runge-Kutta(RK)time integration methods combined with either finite difference(FD)or local discontinuous Galerkin(DG)spatial discretization.We analyze the stability of the fully discrete scheme,on a uniform mesh with periodic boundary conditions,using the Fourier method.For the linearized KdV equation,the IMEX schemes are stable under the standard Courant-Friedrichs-Lewy(CFL)conditionτ≤λh.Here,λis the CFL number,τis the time-step size,and h is the spatial mesh size.We study several IMEX schemes and characterize their CFL number as a function ofθ=d/h^(2)with d being the dispersion coefficient,which leads to several interesting observations.We also investigate the asymptotic behaviors of the CFL number for sufficiently refined meshes and derive the necessary conditions for the asymptotic stability of the IMEX-RK methods.Some numerical experiments are provided in the paper to illustrate the performance of IMEX methods under different time-step constraints.
