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      • Regulation of 3-phosphoinositide-dependent protein kinase-1 (PDK1) by Src involves tyrosine phosphorylation of PDK1 and Src homology 2 domain binding.

        Yang, Keum-Jin,Shin, Sanghee,Piao, Longzhen,Shin, Eulsoon,Li, Yuwen,Park, Kyeong Ah,Byun, Hee Sun,Won, Minho,Hong, Janghee,Kweon, Gi Ryang,Hur, Gang Min,Seok, Jeong Ho,Chun, Taehoon,Brazil, Derek P,He American Society for Biochemistry and Molecular Bi 2008 The Journal of biological chemistry Vol.283 No.3

        <P>3-Phosphoinositide-dependent protein kinase-1 (PDK1) appears to play a central regulatory role in many cell signalings between phosphoinositide-3 kinase and various intracellular serine/threonine kinases. In resting cells, PDK1 is known to be constitutively active and is further activated by tyrosine phosphorylation (Tyr(9) and Tyr(373/376)) following the treatment of the cell with insulin or pervanadate. However, little is known about the mechanisms for this additional activation of PDK1. Here, we report that the SH2 domain of Src, Crk, and GAP recognized tyrosine-phosphorylated PDK1 in vitro. Destabilization of PDK1 induced by geldanamycin (a Hsp90 inhibitor) was partially blocked in HEK 293 cells expressing PDK1-Y9F. Co-expression of Hsp90 enhanced PDK1-Src complex formation and led to further increased PDK1 activity toward PKB and SGK. Immunohistochemical analysis with anti-phospho-Tyr(9) antibodies showed that the level of Tyr(9) phosphorylation was markedly increased in tumor samples compared with normal. Taken together, these data suggest that phosphorylation of PDK1 on Tyr(9), distinct from Tyr(373/376), is important for PDK1/Src complex formation, leading to PDK1 activation. Furthermore, Tyr(9) phosphorylation is critical for the stabilization of both PDK1 and the PDK1/Src complex via Hsp90-mediated protection of PDK1 degradation.</P>

      • KCI등재

        Modified exosomal SIRPα variants alleviate white matter injury after intracerebral hemorrhage via microglia/macrophages

        Xinjie Gao,Heng Yang,Weiping Xiao,Jiabin Su,Yuwen Zhang,He Wang,Wei Ni,Yuxiang Gu 한국생체재료학회 2022 생체재료학회지 Vol.26 No.4

        Background: Despite limited efficiency, modulation of microglia/macrophages has shown to attenuate neuroinflammation after intracerebral hemorrhage (ICH). In this context, we evaluated the efficacy of modified exosomal signal regulatory protein α (SIRPα) variants (SIRPα-v Exos) in microglia/macrophages and neuroinflammation-associated white matter injury after ICH. Methods: SIRPα-v Exos were engineered to block CD47-SIRPα interactions. After obtaining SIRPα-v Exos from lentivirus-infected mesenchymal stem cells, C57BL/6 mice suffering from ICH underwent consecutive intravenous injections of SIRPα-v Exos (6 mg/kg) for 14 days. Afterwards, the volume of hematoma and neurological dysfunctions were assessed in mice continuously until 35 days after ICH. In addition, demyelination, electrophysiology and neuroinflammation were evaluated. Furthermore, the mechanisms of microglial regulation by SIRPα-v Exos were investigated in vitro under coculture conditions. Results: The results demonstrated that the clearance of hematoma in mice suffering from ICH was accelerated after SIRPα-v Exo treatment. SIRPα-v Exos improved long-term neurological dysfunction by ameliorating white matter injury. In addition, SIRPα-v Exos recruited regulatory T cells (Tregs) to promote M2 polarization of microglia/macrophages in the peri-hematoma tissue. In vitro experiments further showed that SIRPα-v Exos regulated primary microglia in a direct and indirect manner in synergy with Tregs. Conclusion: Our studies revealed that SIRPα-v Exos could accelerate the clearance of hematoma and ameliorate secondary white matter injury after ICH through regulation of microglia/macrophages. SIRPα-v Exos may become a promising treatment for ICH in clinical practice.

      • KCI등재

        Epidemiological investigation and phylogenetic analysis of Classical Swine Fever virus in Yunnan province from 2015 to 2021

        Jun Yao,Linlin Su,Qiaoping Wang,Lin Gao,Jiarui Xie,Yuwen He,Xianghua Shu,Chunlian Song,Jun Chai,Yifang Zhang,Shibiao Yang 대한수의학회 2022 Journal of Veterinary Science Vol.23 No.4

        Background: Classical swine fever virus (CSFV), the causative agent of classical swine fever (CFS), is a highly contagious disease that poses a serious threat to Chinese pig populations. Objectives: Many provinces of China, such as Shandong, Henan, Hebei, Heilongjiang, and Liaoning provinces, have reported epidemics of CSFV, while the references to the epidemic of CSFV in Yunnan province are rare. This study examined the epidemic characteristics of the CSFV in Yunnan province. Methods: In this study, 326 tissue samples were collected from different regions in Yunnan province from 2015 to 2021. A reverse transcription-polymerase chain reaction (RT-PCR), sequences analysis, and phylogenetic analysis were performed for the pathogenic detection and analysis of these 326 clinical specimens. Results: Approximately 3.37% (11/326) of specimens tested positive for the CSFV by RT-PCR, which is lower than that of other regions of China. Sequence analysis of the partial E2 sequences of eleven CSFV strains showed that they shared 89.0–100.0% nucleotide (nt) and 95.0–100.0% amino acid (aa) homology, respectively. Phylogenetic analysis showed that these novel isolates belonged to the subgenotypes 2.1c and 2.1d, with subgenotype 2.1c being predominant. Conclusions: The CSFV was sporadic in China’s Yunnan province from 2015 to 2021. Both 2.1c and 2.1d subgenotypes were found in this region, but 2.1c was dominant.

      • SCIESCOPUSKCI등재

        Development of TREND dynamics code for molten salt reactors

        Yu, Wen,Ruan, Jian,He, Long,Kendrick, James,Zou, Yang,Xu, Hongjie Korean Nuclear Society 2021 Nuclear Engineering and Technology Vol.53 No.2

        The Molten Salt Reactor (MSR), one of the six advanced reactor types of the 4th generation nuclear energy systems, has many impressive features including economic advantages, inherent safety and nuclear non-proliferation. This paper introduces a system analysis code named TREND, which is developed and used for the steady and transient simulation of MSRs. The TREND code calculates the distributions of pressure, velocity and temperature of single-phase flows by solving the conservation equations of mass, momentum and energy, along with a fluid state equation. Heat structures coupled with the fluid dynamics model is sufficient to meet the demands of modeling MSR system-level thermal-hydraulics. The core power is based on the point reactor neutron kinetics model calculated by the typical Runge-Kutta method. An incremental PID controller is inserted to adjust the operation behaviors. The verification and validation of the TREND code have been carried out in two aspects: detailed code-to-code comparison with established thermal-hydraulic system codes such as RELAP5, and validation with the experimental data from MSRE and the CIET facility (the University of California, Berkeley's Compact Integral Effects Test facility).The results indicate that TREND can be used in analyzing the transient behaviors of MSRs and will be improved by validating with more experimental results with the support of SINAP.

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