Colorectal cancer(CRC), a malignant tumor worldwide consists of microsatellite instability(MSI) and stable(MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosupp...Colorectal cancer(CRC), a malignant tumor worldwide consists of microsatellite instability(MSI) and stable(MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing wasperformed to explore the role of SHP2 in all cell types of tumor microenvironment(TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68;macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively,our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.展开更多
Dear Editor,The recent outbreak of novel coronavirus disease 2019(COVID-19)has already become a global-scale epidemic.Since the case from China was reported on Dec 30th,2019(Huang et al.,2020;Li et al.,2020),the patho...Dear Editor,The recent outbreak of novel coronavirus disease 2019(COVID-19)has already become a global-scale epidemic.Since the case from China was reported on Dec 30th,2019(Huang et al.,2020;Li et al.,2020),the pathogen was soon identified as a new coronavirus on Jan 7th.展开更多
Gas chromatography-mass spectrometry method was developed for the qualitative and quantitative analyses of chlorpyrifos in human blood samples.The chlorpyrifos and parathion(internal standard)in human blood were extra...Gas chromatography-mass spectrometry method was developed for the qualitative and quantitative analyses of chlorpyrifos in human blood samples.The chlorpyrifos and parathion(internal standard)in human blood were extracted with a mixed solvent of hexane and acetonitrile.Chlorpyrifos was well separated from the internal standard.The linear range of chlorpyrifos was 0.01-2 μg/ml in blood.The limit of detection and limit of quantification were estimated at 0.002 and 0.01μg/ml,respectively.The inter-and intra-day precisions,accuracy,and recovery were assessed to verify this method.The results showed that the developed method is rapid,sensitive,and reliable.It is suitable for the determination of chlorpyrifos in forensic toxicological analysis and clinical diagnosis.展开更多
基金supported by National Natural Science Foundation of China(Nos.91853109,81730100,81872877,and 81673436)Mountain-Climbing Talents Project of Nanjing University(China)。
文摘Colorectal cancer(CRC), a malignant tumor worldwide consists of microsatellite instability(MSI) and stable(MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing wasperformed to explore the role of SHP2 in all cell types of tumor microenvironment(TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68;macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively,our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.
基金supported by the Fundamental Research Funds for the Central Universities(14380129)the National Natural Science Foundation of China(21877060)。
文摘Dear Editor,The recent outbreak of novel coronavirus disease 2019(COVID-19)has already become a global-scale epidemic.Since the case from China was reported on Dec 30th,2019(Huang et al.,2020;Li et al.,2020),the pathogen was soon identified as a new coronavirus on Jan 7th.
基金This study was financially supported by the Project of the National Natural Sciences Foundation of China(81373239).
文摘Gas chromatography-mass spectrometry method was developed for the qualitative and quantitative analyses of chlorpyrifos in human blood samples.The chlorpyrifos and parathion(internal standard)in human blood were extracted with a mixed solvent of hexane and acetonitrile.Chlorpyrifos was well separated from the internal standard.The linear range of chlorpyrifos was 0.01-2 μg/ml in blood.The limit of detection and limit of quantification were estimated at 0.002 and 0.01μg/ml,respectively.The inter-and intra-day precisions,accuracy,and recovery were assessed to verify this method.The results showed that the developed method is rapid,sensitive,and reliable.It is suitable for the determination of chlorpyrifos in forensic toxicological analysis and clinical diagnosis.
