Elevated FBXL6 expression in hepatocytes activates VRK2-transketolase-ROS-mTOR-mediated immune evasion and liver cancer metastasis in mice

Zhang Jie,Lin Xiao-Tong,Yu Hong-Qiang,Fang Lei,Wu Di,Luo Yuan-Deng,Zhang Yu-Jun,Xie Chuan-Ming 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Metastatic hepatocellular carcinoma (HCC) is the most lethal malignancy and lacks effective treatment. FBXL6 is overexpressed in human hepatocellular carcinoma (HCC), but whether this change drives liver tumorigenesis and lung metastasis in vivo remains unknown. In this study, we aimed to identify FBXL6 (F-Box and Leucine Rich Repeat Protein 6) as a key driver of HCC metastasis and to provide a new paradigm for HCC therapy. We found that elevated FBXL6 expression in hepatocytes drove HCC lung metastasis and was a much stronger driver than Kras mutation (KrasG12D/+;Alb-Cre), p53 haploinsufficiency (p53+/-) or Tsc1 loss (Tsc1fl/fl;Alb-Cre). Mechanistically, VRK2 promoted Thr287 phosphorylation of TKT and then recruited FBXL6 to promote TKT ubiquitination and activation. Activated TKT further increased PD-L1 and VRK2 expression via the ROS-mTOR axis, leading to immune evasion and HCC metastasis. Targeting or knockdown of TKT significantly blocked FBXL6-driven immune evasion and HCC metastasis in vitro and in vivo. Notably, the level of active TKT (p-Thr287 TKT) was increased and was positively correlated with the FBXL6 and VRK2 expression levels in HCC patients. Our work provides novel mechanistic insights into FBXL6-driven HCC metastasis and suggests that targeting the TKT-ROS-mTOR-PD-L1/VRK2 axis is a new paradigm for treating patients with metastatic HCC with high FBXL6 expression.

Chemokine Signaling Pathway Involved in CCL2 Expression in Patients with Rheumatoid Arthritis

Lin Zhang,Changyi Li,Min Yu,Jiayin Deng,Xing Lv,Jun Liu,Yu Xiao,Wenjie Yang,Yuru Zhang 연세대학교의과대학 2015 Yonsei medical journal Vol.56 No.4

Purpose: Rheumatoid arthritis (RA) is an inflammatory joint disorder, the progressionof which leads to the destruction of cartilage and bone. Chemokines are involvedin RA pathogenesis. In this study, we investigated the chemokine signaling pathway associated with CCL2 in peripheral blood (PB) and synovial tissues (ST) of RA patients based on our previous work about chemokine signaling pathway involvedin the activation of CCL2 production in collagen-induced arthritis rat ST. Materials and Methods: Total RNA was isolated from PB leukocytes and synoviumof the knee joint in both RA patients and control populations. Real-time polymerasechain reaction was used to determine CCL4, CCR5, c-Jun, c-Fos, and CCL2 expressions. Serum level of CCL2 was assessed by enzyme-linked immunosorbent assay, and the production of CCL2 in ST was analyzed immunohistochemically. Results: The expressions of CCL4, CCR5, c-Jun, c-Fos, and CCL2 messenger RNA in RA patients were significantly higher than those in healthy controls, both in ST and on PB leukocyte. Serum CCL2 levels were elevated in RA patients. Histological examination of rheumatoid joints revealed extensive CCL2 expression in RA ST. Conclusion: CCL2, CCL4, c-Jun, c-Fos, and CCR5 may play an important role in the recruitment of PB leukocytes into the RA joints. These data provide evidence that the chemokine signaling pathway is involved in CCL2 expression in RA patient tissues, which may contribute to chronic inflammation associated with RA. Targetingthis signaling pathway may provide a novel therapeutic avenue in RA.

지능정보사회에서의 중국지역간 정보격차와 지각된 학업성과에 관한 연구

YU DENG SHENG,ZHANG YUANYUAN,SONG ZHANMEI,임규건(Gyoo Gun Lim) 한국IT서비스학회 2019 한국IT서비스학회 학술대회 논문집 Vol.2019 No.2

2000년대부터 중국 경제성장을 주도하는 핵심적 산업인 정보통신산업에 대해 집중적으로 육성 및 지원함으로써 정보통신기술의 사회적 확산도 매우 빠른 속도로 진전되었다. 그러나 정보통신 기술산업의 생산품과 개인 소득의 측면에서 지역 간의 경제성장이 빠른 지역과 그렇지 못한 지역간의 정보통신기술의 확산 속도 및 보급의 격차는 여전히 심한 것으로 나타났다. 또한 중국인터넷발전상황통계보고에 따르면 도시와 농촌의 인터넷 보급률을 살펴보면 보급률은 모두 증가세를 보이지만 격차는 여전히 큰 것으로 확인할 수 있다. 본 연구는 정보격차가 지각된 학업성과에 어떠한 영향을 미치는 지에 파악하고자 한다. 또한지역 간의 정보격차에 따른 지각된 학업성과의 차이가 존재하는 지에 확인하고자 한다. 향후 중국 지역 간의 정보격차를 해소할 수 있는 방안을 모색함으로써 교육성과를 제고하고 교육역량 활성화에 기여할 수 있는 것으로 기대된다.

Mortality of Major Cancers in Guangxi, China: Sex, Age and Geographical Differences from 1971 and 2005

Deng, Wei,Long, Long,Li, Ji-Lin,Zheng, Dan,Yu, Jia-Hua,Zhang, Chun-Yan,Li, Ke-Zhi,Liu, Hai-Zhou,Huang, Tian-Ren Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.4

The incidence and mortality rates of liver and nasopharyngeal cancer in Guangxi province of China have always been among the highest in the world, and cancer is one of the major diseases that pose a threat to the health of residents in Guangxi. However, no systematic study has been performed to evaluate the time trends in the structure of cancer-related deaths and cancer mortality. In this study, we reveal sex, age and geography differences of cancers mortality between three death surveys (1971 to 1973, 1990 to 1992, and 2004 to 2005). The results show that the standardized mortality rate of cancer in Guangxi residents has risen from 43.3/100,000 to 84.2/100,000, the share of cancer deaths in all-cause deaths has increased from 13.3% to 20.7%, and cancer has become the second most common cause of death. The five major cancers, liver cancer, lung cancer, gastric cancer, nasopharyngeal cancer and colorectal cancer, account for 60% of all the cancer deaths. Cancers with growing mortality rates over the past 30 years include lung cancer, colorectal cancer, liver cancer and female breast cancer, of which lung cancer is associated with the sharpest rise in mortality, with a more than 600% rise in both men and women. Cancer death in Guangxi residents occurs mainly in the elderly population above 45 years of age, especially in people over the age of 65. The areas with the highest mortality rates for liver cancer and nasopharyngeal cancer, which feature regional high incidences, include Chongzuo and Wuzhou. Therefore, for major cancers such as liver cancer, lung cancer, gastric cancer, nasopharyngeal cancer and female breast cancer in Guangxi, we can select high-risk age groups as the target population for cancer prevention and control efforts in high-prevalence areas in a bid to achieve the ultimate goal of lowering cancer mortality in Guangxi.

The Data Processing and Remote Transmission Technologies for On-Line Monitoring Of Eurytopic Distributed

Yu-rong Deng,Qiu-li Wu,Wei Zhang,Ze-cheng Lv 보안공학연구지원센터 2015 International Journal of Grid and Distributed Comp Vol.8 No.5

Aiming at the provincial level within the grid wide-area distributed substation equipment on-line monitoring various types, processing of large amount of data and communication standard is not unified. Optimization of the structure of communication between the various levels, researched open communication format specification, established data interaction integration model. The paper studied the wide-area distributed on-line monitoring comprehensive processing unit of end stations with provincial level network of on-line monitoring system for the main platform of communication technology. Application shows that systems runs stability and meet online monitoring data collection, processing, transmission, and other functions, and has good maintainability and extensibility, adapt to various on-line monitoring in province level the development trend of the main platform for centralized management.

An Updated Meta-analysis Between the Association of XRCC1 Arg399Gln Polymorphism and Hepatocellular Carcinoma Risk

Zhang, Xiao-Lian,Lu, Yu,Yang, Shi,Peng, Qi-Liu,Wang, Jian,Xie, Li,Deng, Yan,He, Yu,Li, Tai-Jie,Qin, Xue,Li, Shan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Background: Various studies have evaluated the relationship between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and hepatocellular carcinoma (HCC) risk, but the conclusions have been inconsistent and underpowered. The purpose of this updated meta-analysis was to examine whether XRCC1 Arg399Gln polymorphism confers susceptibility to HCC. Methods: Eligible studies extracted from PubMed, Embase, Cochrane Library, VIP (chinese) and CNKI (chinese) up to November 2013 were included in the study. Pooled odds ratio (OR) together with their 95% confidence interval (CI) were estimated to evaluate XRCC1 Arg399Gln polymorphism and HCC risk. Results: Finally, 21 studies with 4,170 cases and 5,030 controls were involved in our meta-analysis. The results demonstrated that there was significant association between Arg399Gln polymorphism and HCC risk under two contrast models in overall populations (AG vs GG: OR=1.265, 95%CI=1.036-1.545, p=0.021; AA+AG vs GG: OR=1.240, 95%CI=1.021-1.506, p=0.030). In subgroup analyses, significant association was found in Asians (A vs G: OR=1.175, 95%CI=1.013-1.362, p=0.033; AG vs GG: OR=1.317, 95%CI=1.070-1.622, p=0.009; AA+AG vs GG: OR=1.289, 95%CI=1.055-1.575, p=0.013) and Caucasians (A vs G: OR=0.591, 95%CI=0.361-0.966, p=0.036; AA+AG vs GG: OR=0.468, 95%CI=0.234-0.934, p=0.031). Conclusions: The results suggest that XRCC1 Arg399Gln polymorphism may increase HCC risk especially among Asians. However, XRCC1 Arg399Gln polymorphism might act as a protective role against HCC among Caucasians.

Accurate Numerical Computation of Hot Deformation Behaviors by Integrating Finite Element Method with Artificial Neural Network

Yu Xiehua,Deng Linmao,Zhang Xiaoyun,Chen Meilong,Kuang Fengfei,Wang Yuan 한국정밀공학회 2018 International Journal of Precision Engineering and Vol.19 No.3

Accurate flow behaviors characterization plays a decisive role in the design and optimization of hot plastic forming processes with finite element method (FEM). In this study, the hot compression tests at elevated temperature were performed on a Gleeble 3500 thermo-physical test machine to acquire the true stress-strain data of GH4169 superalloy. Subsequently, an artificial neural network (ANN) with back-propagation algorithm was employed to learn the experimental true stress-strain data and then predict the constitutive relationships outside experimental conditions. It was revealed that the ANN can precisely track and predict the flow behaviors of GH4169 superalloy. The optimally-constructed and well-trained ANN model was written into a general finite element (FE) software platform via a user defined material subroutine programmed in Fortran language. Finally, the simulated hot compression tests with the FE model implanted ANN model were conducted. The intercomparisons between the experimental and simulated stroke-load curves revealed that integration of FEM with ANN is a feasible approach to conduct quality numerical computation for the varied hot plastic forming processes.

Biosynthesis of adipic acid in metabolically engineered Saccharomyces cerevisiae

Zhang Xi,Liu Yingli,Wang Jing,Zhao Yunying,Deng Yu 한국미생물학회 2020 The journal of microbiology Vol.58 No.12

Adipic Acid (AA) is a valued platform chemical compound, which can be used as a precursor of nylon-6,6. Due to the generation of an enormous amount of nitric oxide metabolites and the growing depletion of oil resources as a result of AA production from a mixture of cyclohexanol and cyclohexanone, the microbial methods for synthesizing AA have attracted significant attention. Of the several AA-producing pathways, the reverse adipate degradation pathway in Thermobifida fusca (Tfu RADP) is reported to be the most efficient, which has been confirmed in Escherichia coli. In this study, the heterologous Tfu RADP was constructed for producing AA in S. cerevisiae by co-expressing genes of Tfu_ 0875, Tfu_2399, Tfu_0067, Tfu_1647, Tfu_2576, and Tfu_ 2576. The AA titer combined with biomass, cofactors and other by-products was all determined after fermentation. During batch fermentation in a shake flask, the maximum AA titer was 3.83 mg/L, while the titer increased to 10.09 mg/L during fed-batch fermentation in a 5-L bioreactor after fermentation modification.

Energy spread minimization in a cascaded laser wakefield accelerator via velocity bunching

Zhang, Zhijun,Li, Wentao,Liu, Jiansheng,Wang, Wentao,Yu, Changhai,Tian, Ye,Nakajima, Kazuhisa,Deng, Aihua,Qi, Rong,Wang, Cheng,Qin, Zhiyong,Fang, Ming,Liu, Jiaqi,Xia, Changquan,Li, Ruxin,Xu, Zhizhan American Institute of Physics 2016 Physics of plasmas Vol.23 No.5

Effect of Sub-Structure and Precipitation Behavior on Mechanical Properties of Al–xCu–Li Alloys

Yu‑zhuo Li,Guang‑jun Zeng,Ding‑ding Lu,Zhen‑zhen Liu,San‑xi Deng,Peng‑cheng Ma,Yong‑lai Chen,Rui‑feng Zhang,Jin‑feng Li 대한금속·재료학회 2023 METALS AND MATERIALS International Vol.29 No.11

The tensile properties and microstructure of extruded and cold rolled 2A55 Al–Li alloys with different Cu content werestudied. After solution treatment, the strength of extruded sheets is slightly higher than that of cold rolled sheets due to strongdeformation texture and high density of substructure. However, the strength change order is different with the increase of Cucontent with T6-24 h. The extruded sample with higher Cu content have higher strength due to many dense T1precipitates. The δ′/θ′/δ′ composite precipitates and θ′ precipitates suppress the formation of T1precipitates, which cause cold rolled samplewith higher Cu content shows lower strength. Additionally, many fine T1precipitates nucleate at the sub-grain boundariesformed in the extrusion process, which have a significant effect on the mechanical property.