Chinese Spallation Neutron Source(CSNS) has successfully produced its first neutron beam in 28th August 2017. It has been running steadily from March, 2018. According to the construction plan, the engineering material...Chinese Spallation Neutron Source(CSNS) has successfully produced its first neutron beam in 28th August 2017. It has been running steadily from March, 2018. According to the construction plan, the engineering materials diffractometer(EMD) will be installed between 2019–2023. This instrument requires the neutron detectors with the cover area near3 m2in two 90° neutron diffraction angle positions, the neutron detecting efficiency is better than 40%@1A, and the spatial resolution is better than 4 mm×200 mm in horizontal and vertical directions respectively. We have developed a onedimensional position-sensitive neutron detector based on the oblique6Li F/Zn S(Ag) scintillators, wavelength shifting fibers,and Si PMs(silicon photomultipliers) readout. The inhomogeneity of the neutron detection efficiency between each pixel and each detector module, which caused by the inconsistency of the wave-length shifting fibers in collecting scintillation photons, needs to be mitigated before the installation. A performance optimization experiment of the detector modules was carried out on the BL20(beam line 20) of CSNS. Using water sample, the neutron beam with Φ5 mm exit hole was dispersed related evenly into the forward space. According to the neutron counts of each pixel of the detector module, the readout electronics threshold of each pixel is adjusted. Compared with the unadjusted detector module, the inhomogeneity of the detection efficiency for the adjusted one has been improved from 69% to 90%. The test result of the diffraction peak of the standard sample Si showed that the adjusted detector module works well.展开更多
Regulatory T(T_(reg))cells constitute a dynamic population that is critical in autoimmunity.T_(reg) cell therapies for autoimmune diseases are mainly focused on enhancing their suppressive activities.However,recent st...Regulatory T(T_(reg))cells constitute a dynamic population that is critical in autoimmunity.T_(reg) cell therapies for autoimmune diseases are mainly focused on enhancing their suppressive activities.However,recent studies demonstrated that certain inflammatory conditions induce T_(reg) cell instability with diminished FoxP3 expression and convert them into pathogenic effector cells.Therefore,the identification of novel targets crucial to both T_(reg) cell function and plasticity is of vital importance to the development of therapeutic approaches in autoimmunity.In this study,we found that conditional Pp6 knockout(cKO)in T_(reg) cells led to spontaneous autoinflammation,immune cell activation,and diminished levels of FoxP3 in CD4^(+)T cells in mice.Loss of Pp6 in T_(reg) cells exacerbated two classical mouse models of T_(reg)-related autoinflammation.Mechanistically,Pp6 deficiency increased CpG motif methylation of the FoxP3 locus by dephosphorylating Dnmt1 and enhancing Akt phosphorylation at Ser473/Thr308,leading to impaired FoxP3 expression in T_(reg) cells.In summary,our study proposes Pp6 as a critical positive regulator of FoxP3 that acts by decreasing DNA methylation of the FoxP3 gene enhancer and inhibiting Akt signaling,thus maintaining T_(reg) cell stability and preventing autoimmune diseases.展开更多
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 11975255 and 11875273)Guangdong Basic and Applied Basic Research Foundation (Grant No. 2020B1515120025)。
文摘Chinese Spallation Neutron Source(CSNS) has successfully produced its first neutron beam in 28th August 2017. It has been running steadily from March, 2018. According to the construction plan, the engineering materials diffractometer(EMD) will be installed between 2019–2023. This instrument requires the neutron detectors with the cover area near3 m2in two 90° neutron diffraction angle positions, the neutron detecting efficiency is better than 40%@1A, and the spatial resolution is better than 4 mm×200 mm in horizontal and vertical directions respectively. We have developed a onedimensional position-sensitive neutron detector based on the oblique6Li F/Zn S(Ag) scintillators, wavelength shifting fibers,and Si PMs(silicon photomultipliers) readout. The inhomogeneity of the neutron detection efficiency between each pixel and each detector module, which caused by the inconsistency of the wave-length shifting fibers in collecting scintillation photons, needs to be mitigated before the installation. A performance optimization experiment of the detector modules was carried out on the BL20(beam line 20) of CSNS. Using water sample, the neutron beam with Φ5 mm exit hole was dispersed related evenly into the forward space. According to the neutron counts of each pixel of the detector module, the readout electronics threshold of each pixel is adjusted. Compared with the unadjusted detector module, the inhomogeneity of the detection efficiency for the adjusted one has been improved from 69% to 90%. The test result of the diffraction peak of the standard sample Si showed that the adjusted detector module works well.
基金This work is supported by grants from the National Natural Science Foundation of China(No.82070509,81930088,81725018)Innovative Research Team of High-Level Local Universities in Shanghai,and the Natural Science Foundation of Shanghai Science and Technology Committee,China(No.20ZR1447400).
文摘Regulatory T(T_(reg))cells constitute a dynamic population that is critical in autoimmunity.T_(reg) cell therapies for autoimmune diseases are mainly focused on enhancing their suppressive activities.However,recent studies demonstrated that certain inflammatory conditions induce T_(reg) cell instability with diminished FoxP3 expression and convert them into pathogenic effector cells.Therefore,the identification of novel targets crucial to both T_(reg) cell function and plasticity is of vital importance to the development of therapeutic approaches in autoimmunity.In this study,we found that conditional Pp6 knockout(cKO)in T_(reg) cells led to spontaneous autoinflammation,immune cell activation,and diminished levels of FoxP3 in CD4^(+)T cells in mice.Loss of Pp6 in T_(reg) cells exacerbated two classical mouse models of T_(reg)-related autoinflammation.Mechanistically,Pp6 deficiency increased CpG motif methylation of the FoxP3 locus by dephosphorylating Dnmt1 and enhancing Akt phosphorylation at Ser473/Thr308,leading to impaired FoxP3 expression in T_(reg) cells.In summary,our study proposes Pp6 as a critical positive regulator of FoxP3 that acts by decreasing DNA methylation of the FoxP3 gene enhancer and inhibiting Akt signaling,thus maintaining T_(reg) cell stability and preventing autoimmune diseases.
