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.

Night time Vehicle Detection By Using Color Information Based on Tail-Light

Jun-Jie Zhang,Jae-Saek Oh,Jung-Ha Kim 제어로봇시스템학회 2015 제어로봇시스템학회 국제학술대회 논문집 Vol.2015 No.10

In this paper presents an algorithm, aims at practical applications, for the high speed processing and performance enhancement of vehicle detection base on vision processing system. As a preprocessing for high speed vehicle detection in the night, the vanishing line estimation and the optimal extraction of ROI (region of interest) for can be processed to reduction of detection region in which high speed processing is enabled. In order to get better performance the image need pre-processing. Legally vehicle tail light must be red color, so we use the red plane image with simultaneous processing of noise reduction and edge enhancement using the adv morphology function. And then give Dilation and Erosion eliminating the noise through the process of Morphology. Finally, using the Projection-Histogram information get the center of mass by restricting threshold detects a vehicle in the ROI. This method is more efficient than simply detecting and sliding the entire screen. Finally, the various real road experimental results are presented to evaluate the effectiveness of the proposed method.

Anomalous magnetization jumps in granular Pb superconducting films

Zhang An-Lei,Jiang Wan-Yan,Chen Xing-Hong,Zhang Xiao-Ke,Lu Wen-Lai,Chen Fei,Feng Zhen-Jie,Cao Shi-Xun,Zhang Jin-Cang,Ge Jun-Yi 한국물리학회 2022 Current Applied Physics Vol.35 No.-

In granular superconductors, the grain boundaries are closely related to the vortex dynamics and the macroscopic superconducting properties. In our research, Pb films with different grain sizes were prepared by tuning the substrate temperature. With the grain size decreasing, Pb films are prone to feature the anomalous magnetization jumps in the M − T curves, while in the M − H curves flux avalanche happens. Both phenomena appear in the same region of the H − T phase diagram and thus are considered to have the same origin. The further theoretical analysis shows that with grain size decreasing the pinning mechanism evolves from a mixed δTc and δl pinning to the δl pinning mechanism. The results shed light on the study of pinning mechanism for granular superconductors and is beneficial to the potential application of manipulating vortex pinning by regulation of intrinsic defects.

Mini-Array of Multiple Tumor-associated Antigens (TAAs) in the Immunodiagnosis of Esophageal Cancer

Qin, Jie-Jie,Wang, Xiao-Rui,Wang, Peng,Ren, Peng-Fei,Shi, Jian-Xiang,Zhang, Hong-Fei,Xia, Jun-Fen,Wang, Kai-Juan,Song, Chun-Hua,Dai, Li-Ping,Zhang, Jian-Ying Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6

Sera of cancer patients may contain antibodies that react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs). The present study aimed to determine whether a mini-array of multiple TAAs would enhance antibody detection and be a useful approach in esophageal cancer detection and diagnosis. Our mini-array of multiple TAAs consisted of eleven antigens, p53, pl6, Impl, CyclinB1, C-myc, RalA, p62, Survivin, Koc, CyclinD1 and CyclinE full-length recombinant proteins. Enzyme-linked immunosorbent assays (ELISA) were used to detect autoantibodies against eleven selected TAAs in 174 sera from patients with esophageal cancer, as well as 242 sera from normal individuals. In addition, positive results of ELISA were confirmed by Western blotting. In a parallel screening trial, with the successive addition of antigen to a final total of eleven TAAs, there was a stepwise increase in positive antibody reactions. The eleven TAAs were the best parallel combination, and the sensitivity and specificity in diagnosing esophageal cancer was 75.3% and 81.0%, respectively. The positive and negative predictive values were 74.0% and 82.0%, respectively, indicating that the parallel assay of eleven TAAs raised the diagnostic precision significantly. In addition, the levels of antibodies to seven antigens, comprising p53, Impl, C-myc, RalA, p62, Survivin, and CyclinD1, were significantly different in various stages of esophageal cancer, which showed that autoantibodies may be involved in the pathogenesis and progression of esophageal cancer. All in all, this study further supports our previous hypothesis that a combination of antibodies might acquire higher sensitivity for the diagnosis of certain types of cancer. A customized mini-array of multiple carefully-selected TAAs is able to enhance autoantibody detection in the immunodiagnosis of esophageal cancer and autoantibodies to TAAs might be reference indicators of clinical stage.

Study of seismic performance of super long-span partially earth-anchored cable-stayed bridges

Xin-Jun Zhang,Cong Yu,Jun-Jie Zhao 국제구조공학회 2019 Structural Engineering and Mechanics, An Int'l Jou Vol.72 No.1

To investigate the seismic performance of long-span partially earth-anchored cable-stayed bridge, a super long-span partially earth-anchored cable-stayed bridge scheme with main span of 1400m is taken as example, structural response of the bridge under E1 seismic action is investigated numerically by the multimode seismic response spectrum and time-history analysis, seismic behavior and also the effect of structural geometric nonlinearity on the seismic responses of super long-span partially earth-anchored cable-stayed bridges are revealed. The seismic responses are also compared to those of a fully self-anchored cable-stayed bridge with the same main span. The effects of structural parameters including the earth-anchored girder length, the girder width, the girder depth, the tower height to span ratio, the inclination of earth-anchored cables, the installation of auxiliary piers in the side spans and the connection between tower and girder on the seismic responses of partially ground-anchored cable-stayed bridges are investigated, and their reasonable values are also discussed in combination with static performance and structural stability. The results show that the horizontal seismic excitation produces significant seismic responses of the girder and tower, the seismic responses of the towers are greater than those of the girder, and thus the tower becomes the key structural member of seismic design, and more attentions should be paid to seismic design of these sections including the tower bottom, the tower and girder at the junction of tower and girder, the girder at the auxiliary piers in side spans; structural geometric nonlinearity has significant influence on the seismic responses of the bridge, and thus the nonlinear time history analysis is proposed to predict the seismic responses of super long-span partially earth-anchored cable-stayed bridges; as compared to the fully self-anchored cable-stayed bridge with the same main span, several stay cables in the side spans are changed to be earth-anchored, structural stiffness and natural frequency are both increased, the seismic responses of the towers and the longitudinal displacement of the girder are significantly reduced, structural seismic performance is improved, and therefore the partially earth-anchored cable-stayed bridge provides an ideal structural solution for super long-span cable-stayed bridges with kilometer-scale main span; under the case that the ratio of earth-anchored girder length to span is about 0.3, the wider and higher girder is employed, the tower height-to-span ratio is about 0.2, the larger inclination is set for the earth-anchored cables, 1 to 2 auxiliary piers are installed in each of the side spans and the fully floating system is employed, better overall structural performance is achieved for long-span partially earth-anchored cable-stayed bridges.

Elevated expression of WSB2 degrades p53 and activates the IGFBP3-AKT-mTOR-dependent pathway to drive hepatocellular carcinoma

Li Xun,Zhang Cheng-Cheng,Lin Xiao-Tong,Zhang Jie,Zhang Yu-Jun,Yu Hong-Qiang,Liu Ze-Yu,Gong Yi,Zhang Lei-Da,Xie Chuan-Ming 생화학분자생물학회 2024 Experimental and molecular medicine Vol.56 No.-

Dysregulation of wild-type p53 turnover is a key cause of hepatocellular carcinoma (HCC), yet its mechanism remains poorly understood. Here, we report that WD repeat and SOCS box containing protein 2 (WSB2), an E3 ubiquitin ligase, is an independent adverse prognostic factor in HCC patients. WSB2 drives HCC tumorigenesis and lung metastasis in vitro and in vivo. Mechanistically, WSB2 is a new p53 destabilizer that promotes K48-linked p53 polyubiquitination at the Lys291 and Lys292 sites in HCC cells, leading to p53 proteasomal degradation. Degradation of p53 causes IGFBP3-dependent AKT/mTOR signaling activation. Furthermore, WSB2 was found to bind to the p53 tetramerization domain via its SOCS box domain. Targeting mTOR with everolimus, an oral drug, significantly blocked WSB2-triggered HCC tumorigenesis and metastasis in vivo. In clinical samples, high expression of WSB2 was associated with low wild-type p53 expression and high p-mTOR expression. These findings demonstrate that WSB2 is overexpressed and degrades wild-type p53 and then activates the IGFBP3-AKT/mTOR axis, leading to HCC tumorigenesis and lung metastasis, which indicates that targeting mTOR could be a new therapeutic strategy for HCC patients with high WSB2 expression and wild-type p53.

Attenuation of Peripheral Regulatory T-Cell Suppression of Skin-Homing CD8+T Cells in Atopic Dermatitis

Bao-Xiang Zhang,Gang Ding,Jun-Cheng Lyu,Hai-Bo Liu,Dian-Cai Zhang,Dian-Cai Zhang,Xing-Jie Bi,Zhi-Wu Duan 연세대학교의과대학 2015 Yonsei medical journal Vol.56 No.1

Purpose: Cutaneous lymphocyte-associated antigen (CLA)-expressing CD8+T cells have been known to play an important role in the pathogenesis of atopic dermatitis(AD). However, the mechanisms underlying the loss of self-tolerance remainunclear. Regulatory T cells (Tregs) play a key role in the development of homeostasisin the immune system. We, therefore, hypothesized that a reduced ability of Tregs to inhibit autologous CD8+CLA+T cells might be underlying mechanism in AD. Materials and Methods: CD8+CLA+T cells and Tregs were obtained from the peripheral blood of AD patients and control volunteers. The frequenciesof CD8+CLA+T cells were evaluated. The proliferative responses of CD8+CLA+T cells were assessed by flow cytometry, and the levels of transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) in culture supernatants were detected by enzyme-linked immunosorbent assay. Results: Our results revealed higher frequency and increased expression of perforin and granzyme-B in peripheralCD8+CLA+T cells in AD, and lower inhibitory ability of Tregs on proliferation of CD8+CLA+T cells in AD. Meanwhile, the levels of TGF-β1 produced by Tregs were significantly lower in AD, and anti-TGF-β1 abolished such suppression. Conclusion: The attenuated inhibitory ability of Tregs on hyper-activated autologousCD8+CLA+T cells, mediated by TGF-β1, plays an important role in the pathogenesis of AD.

Two Luminescent Cd(II) Coordination Polymers: Enhancement Activity on Pancreatic Cancer Combined with Biliary Stent Placement and 125I Particles

Jie-Peng Jia,Quan Shao,Ying-Kai Wang,Bo Qian,Wen Zhang,Tao Hu,Ji-Jun Zhang 한국고분자학회 2021 Macromolecular Research Vol.29 No.11

With the reaction between bib ligands, 5-substituted isophthalic acid and Cd(II) ions, we produced two coordination polymers in success, that is, [Cd(5-meo-ip) (bib)0.5]n (2) and [Cd(5-me-ip)(bib)(H2O)]n·n(H2O) (1) (bib is 1,4-bis(imidazoly)butane, 5-meo-H2ip is 5-methoxyisophthalic acid, and 5-me-H2ip is 5-methylisophthalic acid). The luminescent performances and thermal stability of the two compounds were also explored. Their anti-pancreatic cancer activity combined with biliary stent placement and 125I particles was evaluated and the specific mechanism was explored as well. Firstly, after the model construction and compound treatment, the weight and volume of the tumor tissue was measured. Next, the apoptosis level of the cancer cells were evaluated with Annexin V-FITC/PI apoptosis assay.

Crack‑free TiO2 films prepared by adjusting processing parameters via liquid phase deposition technique

Jie Li,Hai‑Yan Xu,Ai‑Guo Wang,Feng‑Jun Zhang,Dao‑Sheng Sun,Won‑Chun Oh 한국세라믹학회 2020 한국세라믹학회지 Vol.57 No.2

TiO2 thin films with controllable morphology and grain size were prepared via a liquid phase deposition (LPD) technique. The effects of the processing parameters including the ( NH4)2TiF6 concentration, solution pH, and ( NH4)2TiF6:H3BO3 molar ratio on the grain size and morphology of the films were investigated. The prepared samples were characterized by X-ray diffraction, scanning electron microscopy, and ultraviolet–visible spectroscopy. The results showed that the deposition parameters significantly affected the growth and nucleation velocities of the crystalline grains, which resulted in the formation of TiO2 films with different morphologies and grain sizes. The capillary stress among the grains of the film, which resulted in the cracking of the film, depended on the size of the grains. Thus, the cracking of the LPD-derived TiO2 films could be mitigated by adjusting the deposition parameters.

Novel Phage Display-Derived H5N1-Specific scFvs with Potential Use in Rapid Avian Flu Diagnosis

( Jie Wu ),( Xian Qiao Zeng ),( Hong Bin Zhang ),( Han Zhong Ni ),( Lei Pei ),( Li Rong Zou ),( Li Jun Liang ),( Xin Zhang ),( Jin Yan Lin ),( Chang Wen Ke ) 한국미생물 · 생명공학회 2014 Journal of microbiology and biotechnology Vol.24 No.5

The highly pathogenic avian influenza A (HPAI) viruses of the H5N1 subtype infect poultry and have also been spreading to humans. Although new antiviral drugs and vaccinations can be effective, rapid detection would be more efficient to control the outbreak of infections. In this study, a phage-display library was applied to select antibody fragments for HPAI strain A/Hubei/1/2010. As a result, three clones were selected and sequenced. A hemagglutinin inhibition assay of the three scFvs revealed that none exhibited hemagglutination inhibition activity towards the H5N1 virus, yet they showed a higher binding affinity for several HPAI H5N1 strains compared with other influenza viruses. An ELISA confirmed that the HA protein was the target of the scFvs, and the results of a protein structure simulation showed that all the selected scFvs bound to the HA2 subunit of the HA protein. In conclusion, the three selected scFVs could be useful for developing a specific detection tool for the surveillance of HPAI epidemic strains.