Immunological evasion is one of the defining characteristics of cancers,as the immune modification of an immune checkpoint(IC)confers immune evasion capabilities to tumor cells.Multiple ICs,such as programmed cell dea...Immunological evasion is one of the defining characteristics of cancers,as the immune modification of an immune checkpoint(IC)confers immune evasion capabilities to tumor cells.Multiple ICs,such as programmed cell death protein-1(PD-1)and cytotoxic T-lymphocyte-associated antigen-4(CTLA-4),can bind to their respective receptors and reduce tumor immunity in a variety of ways,including blocking immune cell activation signals.IC blockade(ICB)therapies targeting these checkpoint molecules have demonstrated significant clinical benefits.This is because antibody-based IC inhibitors and a variety of specific small molecule inhibitors can inhibit key oncogenic signaling pathways and induce durable tumor remission in patients with a variety of cancers.Deciphering the roles and regulatory mechanisms of these IC molecules will provide crucial theoretical guidance for clinical treatment.In this review,we summarize the current knowledge on the functional and regulatory mechanisms of these IC molecules at multiple levels,including epigenetic regulation,transcriptional regulation,and post-translational modifications.In addition,we provide a summary of the medications targeting various nodes in the regulatory pathway,and highlight the potential of newly identified IC molecules,focusing on their potential implications for cancer diagnostics and immunotherapy.展开更多
Surface-enhanced Raman spectroscopy （SERS） as a powerful analytical tool has gained extensive attention. Despite of many efforts in the design of SERS substrates, it remains a great challenge for creating a universa...Surface-enhanced Raman spectroscopy （SERS） as a powerful analytical tool has gained extensive attention. Despite of many efforts in the design of SERS substrates, it remains a great challenge for creating a universal sub- strate with long-term stability and reproducible SERS signals. In this work, Ag nanocubes and graphene oxide （GO） suspension were mixed to form a stable solution and further vacuum filtrated to obtain a free-standing hybrid paper. The Ag/GO hybrid papers exhibit excellent SERS activity because of the synergistic effect of Ag nanocubes and GO sheets. GO sheets can act as both SERS enhancement substrate and framework for supporting Ag nanocubes. Moreover, GO sheets can protect Ag nanoparticles from oxidation under ambient condition for prolonged life time SERS substrate. Furthermore, we demonstrate the use of the free-standing and flexible Ag/GO hybrid paper to en- able direct, real-time and reliable detection of trace amounts of analytes in aqueous systems. This novel SERS sub- strate is expected to be applied in real-time analysis and expands the flexibility of SERS for useful applications in the materials and life science.展开更多
基金supported by the National Key Research and Development Program of China(No.2021YFC2700903)the National Natural Science Foundation of China(Nos.81672791 and 81872300)+2 种基金the Zhejiang Provincial Natural Science Fund for Distinguished Young Scholars of China(No.LR18C060002)the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China(No.LHDMY22H160006)the ZJU-QILU Joint Research Institute and Qilu Group.
文摘Immunological evasion is one of the defining characteristics of cancers,as the immune modification of an immune checkpoint(IC)confers immune evasion capabilities to tumor cells.Multiple ICs,such as programmed cell death protein-1(PD-1)and cytotoxic T-lymphocyte-associated antigen-4(CTLA-4),can bind to their respective receptors and reduce tumor immunity in a variety of ways,including blocking immune cell activation signals.IC blockade(ICB)therapies targeting these checkpoint molecules have demonstrated significant clinical benefits.This is because antibody-based IC inhibitors and a variety of specific small molecule inhibitors can inhibit key oncogenic signaling pathways and induce durable tumor remission in patients with a variety of cancers.Deciphering the roles and regulatory mechanisms of these IC molecules will provide crucial theoretical guidance for clinical treatment.In this review,we summarize the current knowledge on the functional and regulatory mechanisms of these IC molecules at multiple levels,including epigenetic regulation,transcriptional regulation,and post-translational modifications.In addition,we provide a summary of the medications targeting various nodes in the regulatory pathway,and highlight the potential of newly identified IC molecules,focusing on their potential implications for cancer diagnostics and immunotherapy.
基金Acknowledgement The authors are grateful for the financial support from the National Natural Science Foundation of China （Nos. 51125011, 51433001）, and the National Research Foundation, Singapore （No. NRF-NRFF2012-04）, Nanyang Technological University＇s start-up grant.
文摘Surface-enhanced Raman spectroscopy （SERS） as a powerful analytical tool has gained extensive attention. Despite of many efforts in the design of SERS substrates, it remains a great challenge for creating a universal sub- strate with long-term stability and reproducible SERS signals. In this work, Ag nanocubes and graphene oxide （GO） suspension were mixed to form a stable solution and further vacuum filtrated to obtain a free-standing hybrid paper. The Ag/GO hybrid papers exhibit excellent SERS activity because of the synergistic effect of Ag nanocubes and GO sheets. GO sheets can act as both SERS enhancement substrate and framework for supporting Ag nanocubes. Moreover, GO sheets can protect Ag nanoparticles from oxidation under ambient condition for prolonged life time SERS substrate. Furthermore, we demonstrate the use of the free-standing and flexible Ag/GO hybrid paper to en- able direct, real-time and reliable detection of trace amounts of analytes in aqueous systems. This novel SERS sub- strate is expected to be applied in real-time analysis and expands the flexibility of SERS for useful applications in the materials and life science.
