Tumor vaccine,a promising modality of tumor immunotherapy,needs to go through the process of tumor antigen generation and loading,antigen drainage to lymph nodes(LNs),antigen internalization by dendritic cells(DCs),DC...Tumor vaccine,a promising modality of tumor immunotherapy,needs to go through the process of tumor antigen generation and loading,antigen drainage to lymph nodes(LNs),antigen internalization by dendritic cells(DCs),DC maturation,and antigen cross-presentation to activate T-cells.However,tumor vaccines are often unable to satisfy all the steps,leading to the limitation of their application and efficacy.Herein,based on a smart nanogel system,an in situ nano-vaccine(CpG@Man-P/Tra/Gel)targeting LNs was constructed to induce potent anti-tumor immune effects and inhibit the recurrence and metastasis of ovarian cancer.The CpG@Man-P/Tra/Gel exhibited MMP-2-sensitive release of trametinib(Tra)and nano-adjuvant CPG@Man-P,which generated abundant in situ depot of whole-cell tumor antigens and formed in situ nano-vaccines with CpG@Man-P.Benefiting from mannose(Man)modification,the nano-vaccines targeted to LNs,promoted the uptake of antigens by DCs,further inducing the maturation of DCs and activation of T cells.Moreover,CpG@Man-P with different particle sizes were prepared and the effective size was selected to evaluate the antitumor effect and immune response in vivo.Notably,combined with PD-1 blocking,the vaccine effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis of ovarian cancer.展开更多
海上B油田上部存在薄的气层,海上作业成本高,限制了钻井的数量,因此采用3井对油气层同时进行开采。油管采油、环空采气的开采方式没有充分利用气层的能量。受气举采油的启发,利用井气来实现"自我气举",充分利用了上部凝析气...海上B油田上部存在薄的气层,海上作业成本高,限制了钻井的数量,因此采用3井对油气层同时进行开采。油管采油、环空采气的开采方式没有充分利用气层的能量。受气举采油的启发,利用井气来实现"自我气举",充分利用了上部凝析气层的能量。井气气举到地层压力为22 MPa时,气举采油达不到配产,此时采用井气气举+气举—电潜泵组合举升方案来接替采油。该方案较自喷+电潜泵接替举升(油管采油,环空采气)方案可节省功率49.45~58.42 k W,节能效果明显。井气气举+气举—电潜泵组合举升方案设计对海上油田高效、安全、经济的开发具有指导意义。展开更多
基金the National Natural Science Foundation of China(No.82102769)the 111 Project(No.B18035,China)the Fundamental of Research Funds for the Central Universities and Beijing Natural Science Foundation(No.L212054,China).
文摘Tumor vaccine,a promising modality of tumor immunotherapy,needs to go through the process of tumor antigen generation and loading,antigen drainage to lymph nodes(LNs),antigen internalization by dendritic cells(DCs),DC maturation,and antigen cross-presentation to activate T-cells.However,tumor vaccines are often unable to satisfy all the steps,leading to the limitation of their application and efficacy.Herein,based on a smart nanogel system,an in situ nano-vaccine(CpG@Man-P/Tra/Gel)targeting LNs was constructed to induce potent anti-tumor immune effects and inhibit the recurrence and metastasis of ovarian cancer.The CpG@Man-P/Tra/Gel exhibited MMP-2-sensitive release of trametinib(Tra)and nano-adjuvant CPG@Man-P,which generated abundant in situ depot of whole-cell tumor antigens and formed in situ nano-vaccines with CpG@Man-P.Benefiting from mannose(Man)modification,the nano-vaccines targeted to LNs,promoted the uptake of antigens by DCs,further inducing the maturation of DCs and activation of T cells.Moreover,CpG@Man-P with different particle sizes were prepared and the effective size was selected to evaluate the antitumor effect and immune response in vivo.Notably,combined with PD-1 blocking,the vaccine effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis of ovarian cancer.
文摘海上B油田上部存在薄的气层,海上作业成本高,限制了钻井的数量,因此采用3井对油气层同时进行开采。油管采油、环空采气的开采方式没有充分利用气层的能量。受气举采油的启发,利用井气来实现"自我气举",充分利用了上部凝析气层的能量。井气气举到地层压力为22 MPa时,气举采油达不到配产,此时采用井气气举+气举—电潜泵组合举升方案来接替采油。该方案较自喷+电潜泵接替举升(油管采油,环空采气)方案可节省功率49.45~58.42 k W,节能效果明显。井气气举+气举—电潜泵组合举升方案设计对海上油田高效、安全、经济的开发具有指导意义。
