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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.
Evaluation of the YOLO models for discrimination of the alfalfa pollinating bee species
Zhang Chuan-Jie,Liu Teng,Wang Jinxu,Zhai Danlan,Zhang Youxin,Gao Yang,Wu Hui-Zhen,Yu Jialin,Chen Min 한국응용곤충학회 2024 Journal of Asia-Pacific Entomology Vol.27 No.1
Identifying insect pollinators and their roles in mediating pollen flow is critical to understand the potential gene flow risks of insect pollination-dependent crop species, such as alfalfa. This study was conducted to evaluate and compare the feasibility of You Only Look Once (YOLO) version 3 (YOLOv3), YOLOv5, YOLOv7, and YOLO Representation (YOLOR) to discriminate the three most common alfalfa pollinating bee species, including honeybee, bumblebee, and leafcutting bee. The metrics comparison results showed YOLOv3 and YOLOv5 out performed YOLOv7 and YOLOR regarding model precision, recall, F 1 score, and mAP50 values. YOLOv3 and YOLOv5 could successfully discriminate the three different bee species with an accuracy of almost 100% (99.9%, 99.8%, and 100% accuracy for honeybee, bumblebee, and leafcutting bee for the two models, respectively). Comparatively, YOLOv7 could discriminate honeybee with an accuracy of 95% but was more likely to mistakenly discriminate bumblebee and leafcutting bee due to the relatively lower discriminating accuracy (87.3% and 66.2%, respectively). While the values of determined parameters for YOLOR were lower than YOLOv3 and YOLOv5, the higher precision (0.99680) along with recall (0.98721), F 1 (0.99198), mAP50 (0.99323), and mAP50-100 (0.89076) values indicate that this model could be able to obtain a favorable performance in discriminating the three bee species. In summary, the proposed method in this study has the potential for identifying the alfalfa pollinating bee species, studying the bees’ flower-visiting behaviors, evaluating the risks of insect-mediated pollen flow, and thus contributing to the management of genetically engineered (GE) alfalfa transgene flow.
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.
Physical properties and chemical composition of the cores in the California molecular cloud
Zhang, Guo-Yin,Xu, Jin-Long,Vasyunin, A. I.,Semenov, D. A.,Wang, Jun-Jie,Dib, Sami,Liu, Tie,Liu, Sheng-Yuan,Zhang, Chuan-Peng,Liu, Xiao-Lan,Wang, Ke,Li, Di,Wu, Zhong-Zu,Yuan, Jing-Hua,Li, Da-Lei,Gao, Springer-Verlag 2018 Astronomy and astrophysics Vol.620 No.-
<P><I>Aims.</I> We aim to reveal the physical properties and chemical composition of the cores in the California molecular cloud (CMC), so as to better understand the initial conditions of star formation.</P><P><I>Methods.</I> We made a high-resolution column density map (18.2′′) with <I>Herschel</I> data, and extracted a complete sample of the cores in the CMC with the fellwalker algorithm. We performed new single-pointing observations of molecular lines near 90 GHz with the IRAM 30m telescope along the main filament of the CMC. In addition, we also performed a numerical modeling of chemical evolution for the cores under the physical conditions.</P><P><I>Results.</I> We extracted 300 cores, of which 33 are protostellar and 267 are starless cores. About 51% (137 of 267) of the starless cores are prestellar cores. Three cores have the potential to evolve into high-mass stars. The prestellar core mass function (CMF) can be well fit by a log-normal form. The high-mass end of the prestellar CMF shows a power-law form with an index <I>α</I> = −0.9 ± 0.1 that is shallower than that of the Galactic field stellar mass function. Combining the mass transformation efficiency (<I>ε</I>) from the prestellar core to the star of 15 ± 1% and the core formation efficiency (CFE) of 5.5%, we suggest an overall star formation efficiency of about 1% in the CMC. In the single-pointing observations with the IRAM 30m telescope, we find that 6 cores show blue-skewed profile, while 4 cores show red-skewed profile. [HCO<SUP>+</SUP>]/[HNC] and [HCO<SUP>+</SUP>]/[N2H<SUP>+</SUP>] in protostellar cores are higher than those in prestellar cores; this can be used as chemical clocks. The best-fit chemical age of the cores with line observations is ~5 × 10<SUP>4</SUP> yr.</P>