Objective and Impact Statement.Molecular signatures are needed for early diagnosis and improved treatment of metastatic melanoma.By high-resolution multimodal chemical imaging of human melanoma samples,we identify a m...Objective and Impact Statement.Molecular signatures are needed for early diagnosis and improved treatment of metastatic melanoma.By high-resolution multimodal chemical imaging of human melanoma samples,we identify a metabolic reprogramming from pigmentation to lipid droplet(LD)accumulation in metastatic melanoma.Introduction.Metabolic plasticity promotes cancer survival and metastasis,which promises to serve as a prognostic marker and/or therapeutic target.However,identifying metabolic alterations has been challenged by difficulties in mapping localized metabolites with high spatial resolution.Methods.We developed a multimodal stimulated Raman scattering and pump-probe imaging platform.By time-domain measurement and phasor analysis,our platform allows simultaneous mapping of lipids and pigments at a subcellular level.Furthermore,we identify the sources of these metabolic signatures by tracking deuterium metabolites at a subcellular level.By validation with mass spectrometry,a specific fatty acid desaturase pathway was identified.Results.We identified metabolic reprogramming from a pigment-containing phenotype in low-grade melanoma to an LD-rich phenotype in metastatic melanoma.The LDs contain high levels of cholesteryl ester and unsaturated fatty acids.Elevated fatty acid uptake,but not de novo lipogenesis,contributes to the LD-rich phenotype.Monounsaturated sapienate,mediated by FADS2,is identified as an essential fatty acid that promotes cancer migration.Blocking such metabolic signatures effectively suppresses the migration capacity both in vitro and in vivo.Conclusion.By multimodal spectroscopic imaging and lipidomic analysis,the current study reveals lipid accumulation,mediated by fatty acid uptake,as a metabolic signature that can be harnessed for early diagnosis and improved treatment of metastatic melanoma.展开更多
Mechanoluminescent(ML)materials,which have the ability to convert mechanical energy to optical energy,have found huge promising applications such as in stress imaging and anti-counterfeiting.However,the main reported ...Mechanoluminescent(ML)materials,which have the ability to convert mechanical energy to optical energy,have found huge promising applications such as in stress imaging and anti-counterfeiting.However,the main reported ML phosphors are based on trap-related ones,thus hindering the practical applications due to the requirement of complex light pre-irradiation process.Here,a self-recoverable near infrared(NIR)ML material of Lali-xO:xCr^(3+)(x=0.2%,0.4%,0.6%,0.8%,1.0%,and 1.2%)has been developed.Based on the preheating method and corresponding ML performance analysis,the influences of residual carriers are eliminated and the detailed dynamic luminescence process analysis is realized.Systematic experiments are conducted to reveal the origin of the ML emissions,demonstrating that ML is dictated more by the non-centrosymmetric piezoelectric crystal characteristic.In general,this work has provided significant references for exploring more efficient NIR ML materials,which may provide potential applications in anti-counterfeiting and bio-stress sensing.展开更多
Synthetic biology is an emerging field focusing on engineering genetic devices and biomolecular systems for a variety of applications from basic biology to biotechnology and medicine.Thanks to the tremendous advances ...Synthetic biology is an emerging field focusing on engineering genetic devices and biomolecular systems for a variety of applications from basic biology to biotechnology and medicine.Thanks to the tremendous advances in genomics and the chemical synthesis of DNA in the past decade,scientists are now able to engineer genetic devices and circuits for cancer research and intervention,which offer promising therapeutic strategies for cancer treatment.In this article,we provide a systemic review on recent development achieved by the synthetic biologists,oncologists and clinicians of one National“973”Plan.We expand the synthetic biology toolkits involving DNA,RNA and protein bio-parts to explore various issues in cancer research,such as elucidation of mechanisms and pathways,creation of new diagnostic tools and invention of novel therapeutic approaches.We claimed that the Chinese synthetic biologists are promoting the basic research productions of tumor synthetic biology into the clinic.展开更多
基金the IUSCC Cancer Center at Indiana University School of Medicine funded by the IU Simon Cancer Center Support Grant P30 CA082709,for the use of the Tissue Procurement and Distribution Core,which provided Frozen Tissue Sample servicesupported by NIH grants R33 CA223581 and R35 GM136223 to JXC。
文摘Objective and Impact Statement.Molecular signatures are needed for early diagnosis and improved treatment of metastatic melanoma.By high-resolution multimodal chemical imaging of human melanoma samples,we identify a metabolic reprogramming from pigmentation to lipid droplet(LD)accumulation in metastatic melanoma.Introduction.Metabolic plasticity promotes cancer survival and metastasis,which promises to serve as a prognostic marker and/or therapeutic target.However,identifying metabolic alterations has been challenged by difficulties in mapping localized metabolites with high spatial resolution.Methods.We developed a multimodal stimulated Raman scattering and pump-probe imaging platform.By time-domain measurement and phasor analysis,our platform allows simultaneous mapping of lipids and pigments at a subcellular level.Furthermore,we identify the sources of these metabolic signatures by tracking deuterium metabolites at a subcellular level.By validation with mass spectrometry,a specific fatty acid desaturase pathway was identified.Results.We identified metabolic reprogramming from a pigment-containing phenotype in low-grade melanoma to an LD-rich phenotype in metastatic melanoma.The LDs contain high levels of cholesteryl ester and unsaturated fatty acids.Elevated fatty acid uptake,but not de novo lipogenesis,contributes to the LD-rich phenotype.Monounsaturated sapienate,mediated by FADS2,is identified as an essential fatty acid that promotes cancer migration.Blocking such metabolic signatures effectively suppresses the migration capacity both in vitro and in vivo.Conclusion.By multimodal spectroscopic imaging and lipidomic analysis,the current study reveals lipid accumulation,mediated by fatty acid uptake,as a metabolic signature that can be harnessed for early diagnosis and improved treatment of metastatic melanoma.
基金We gratefully acknowledge the financial support from the National Natural Science Foundation of China(No.52202003)Guangdong Basic and Applied Basic Research Foundation(No.2023A1515011893)+1 种基金State Key Laboratory of Powder Metallurgy,Central South University,Changsha,China(No.Sklpm-KF-27)Guangzhou Basic and Applied Basic Research Foundation(No.SL2022A04J00746)。
文摘Mechanoluminescent(ML)materials,which have the ability to convert mechanical energy to optical energy,have found huge promising applications such as in stress imaging and anti-counterfeiting.However,the main reported ML phosphors are based on trap-related ones,thus hindering the practical applications due to the requirement of complex light pre-irradiation process.Here,a self-recoverable near infrared(NIR)ML material of Lali-xO:xCr^(3+)(x=0.2%,0.4%,0.6%,0.8%,1.0%,and 1.2%)has been developed.Based on the preheating method and corresponding ML performance analysis,the influences of residual carriers are eliminated and the detailed dynamic luminescence process analysis is realized.Systematic experiments are conducted to reveal the origin of the ML emissions,demonstrating that ML is dictated more by the non-centrosymmetric piezoelectric crystal characteristic.In general,this work has provided significant references for exploring more efficient NIR ML materials,which may provide potential applications in anti-counterfeiting and bio-stress sensing.
文摘Synthetic biology is an emerging field focusing on engineering genetic devices and biomolecular systems for a variety of applications from basic biology to biotechnology and medicine.Thanks to the tremendous advances in genomics and the chemical synthesis of DNA in the past decade,scientists are now able to engineer genetic devices and circuits for cancer research and intervention,which offer promising therapeutic strategies for cancer treatment.In this article,we provide a systemic review on recent development achieved by the synthetic biologists,oncologists and clinicians of one National“973”Plan.We expand the synthetic biology toolkits involving DNA,RNA and protein bio-parts to explore various issues in cancer research,such as elucidation of mechanisms and pathways,creation of new diagnostic tools and invention of novel therapeutic approaches.We claimed that the Chinese synthetic biologists are promoting the basic research productions of tumor synthetic biology into the clinic.
