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| 1 | Erianin suppresses constitutive activation of MAPK signaling pathway by inhibition of CRAF and MEK1/2显示文摘Constitutive activation of RAS-RAF-MEK-ERK signaling pathway(MAPK pathway)frequently occurs in many cancers harboring RAS or RAF oncogenic mutations.Because of the paradoxical activation induced by a single use of BRAF or MEK inhibitors,dual-target RAF and MEK treatment is thought to be a promising strategy.In this work,we evaluated erianin is a novel inhibitor of CRAF and MEK1/2 kinases,thus suppressing constitutive activation of the MAPK signaling pathway induced by BRAF V600E or RAS mutations.KinaseProfiler enzyme profiling,surface plasmon resonance(SPR),isothermal titration calorimetry(ITC),cellular thermal shift assay,computational docking,and molecular dynamics simulations were utilized to screen and identify erianin binding to CRAF and MEK1/2.Kinase assay,luminescent ADP detection assay,and enzyme kinetics assay were investigated to identify the efficiency of erianin in CRAF and MEK1/2 kinase activity.Notably,erianin suppressed BRAF V600E or RAS mutant melanoma and colorectal cancer cell by inhibiting MEK1/2 and CRAF but not BRAF kinase activity.Moreover,erianin attenuated melanoma and colorectal cancer in vivo.Overall,we provide a promising leading compound for BRAF V600E or RAS mutant melanoma and colorectal cancer through dual targeting of CRAF and MEK1/2. | Penglei Wang Xuechao Jia Bingbing Lu Han Huang Jialin Liu Xuejiao Liu Qiong Wu Yamei Hu Pan Li Huifang Wei Tingting Liu Dengyun Zhao Lingwei Zhang Xueli Tian Yanan Jiang Yan Qiao Wenna Nie Xinli Ma Ruihua Bai Cong Peng Zigang Dong Kangdong Liu | 2023 | Signal Transduction and Targeted Therapy2023,8,4: | 1 |
| 2 | Overexpression of PvWOX3a in switchgrass promotes stem development and increases plant height显示文摘Switchgrass(Panicum virgatum L.)is an important perennial,noninvasive,tall ornamental grass that adds color and texture to gardens and landscapes.Moreover,switchgrass has been considered a forage and bioenergy crop because of its vigorous growth,low-input requirements,and broad geography.Here,we identified PvWOX3a from switchgrass,which encodes a WUSCHEL-related homeobox transcription factor.Transgenic overexpression of PvWOX3a in switchgrass increased stem length,internode diameter,and leaf blade length and width,all of which contributed to a 95%average increase in dry weight biomass compared with control plants.Yeast one-hybrid and transient dual-luciferase assays showed that PvWOX3a can repress the expression of gibberellin 2-oxidase and cytokinin oxidase/dehydrogenase through apparently direct interaction with their promoter sequences.These results suggested that overexpression of PvWOX3a could increase gibberellin and cytokinin levels in transgenic switchgrass plants,which promotes cell division,elongation,and vascular bundle development.We also overexpressed PvWOX3a in a transgenic miR156-overexpressing switchgrass line that characteristically exhibited more tillers,thinner internodes,and narrower leaf blades.Double transgenic switchgrass plants displayed significant increases in internode length and diameter,leaf blade width,and plant height but retained a tiller number comparable to that of plants expressing miR156 alone.Ultimately,the double transgenic switchgrass plants produced 174%more dry-weight biomass and 162%more solubilized sugars on average than control plants.These findings indicated that PvWOX3a is a viable potential genetic target for engineering improved shoot architecture and biomass yield of horticulture,fodder,and biofuel crops. | Ruijuan Yang Zhenying Wu Chen Bai Zhichao Sun Mengqi Wang Yuzhu Huo Hailing Zhang Yamei Wang Huapeng Zhou Shaojun Dai Wenwen Liu Chunxiang Fu | 2021 | Horticulture Research2021,8,1: | 1 |
| 3 | Optimization of PCR System in EST-SSR Analysis of Phytophthora infestans显示文摘Late blight caused by the oomycete Phytophthora infestans Montagne de Bary is a devastating disease on potato production. A total of six parameters affecting the PCR system in P. infestans were investigated based on the template DNA of the isolate HH06-23 and EST-SSR primer pair Pi08N. The results showed that the optimal annealing temperature was 63℃, and the optimum PCR system of EST-SSR was 25 ng template DNA, 0.5 mmol·L-1 dNTPs, 2 μL 10×Buffer (Mg 2+ free), 1.75 mmol·L-1 MgCl 2 , 15 pmol primer, and 1.2 U Taq DNA polymerase in total 20 μL reaction system. The PCR program was initial denaturation at 94℃ for 2 min, followed by 35 cycles of 94℃ for 30 s, 63℃ for 30 s, and 72℃ for 30 s, then a final extension step was 72℃ for 7 min, and held at 4℃. In addition, using the optimal PCR system, a total of 20 isolates of P. infestans were used for testing the stability and polymorphism of the PCR amplification. The clarity and abundant polymorphism indicated that this system was stable and suitable for researching the genetic diversity of P. infestans population. | WANG Jianan LU Wenhe JIN Guanghui BAI Yamei LI Wenxia HAN Yingpeng | 2010 | Journal of Northeast Agricultural University(English Edition)2010,17,1: | 0 |
| 4 | Wood forming tissue-specific expression of PdSuSy and HCHL increases holocellulose content and improves saccharification in Populus显示文摘Development of strategies to deconstruct lignocellulosic biomass in tree species is essential for biofuels and biomaterials production.We applied a wood forming tissue-specific system in a hybrid poplar to express both PdSuSy(a sucrose synthase gene from Populus deltoides×P.euramericana that has not been functionally characterized)and HCHL(the hydroxycinnamoyl-CoA hydratase-lyase gene from Pseudomonas fluorescens,which inhibits lignin polymerization in Arabidopsis).The PdSuSy-HCHL overexpression poplars correspondingly driven by the promoters of Arabidopsis AtCesA7 and AtC4 H resulted in a significant increase in cellulose(>8%),xylan(>12%)and glucose(>29%)content,accompanying a reduction in galacturonic acid(>36%)content,compared to control plants.The saccharification efficiency of these overexpression poplars was dramatically increased by up to 27%,but total lignin content was unaffected.These transgenic poplars showed inhibited growth characteristics,including>16%reduced plant height,>10% reduced number of internodes,and>18% reduced fresh weight after growth of 4 months,possibly due to relatively low expression of HCHL in secondary xylem.Our results demonstrate the structural complexity and interaction of the cell wall polymers in wood tissue and outline a potential method to increase biomass saccharification in woody species. | Yang Zhang Hua Xu Yingzhen Kong Jiawen Hua Xianfeng Tang Yamei Zhuang Yue Bai Gongke Zhou Guohua Chai | 2021 | Journal of Forestry Research2021,32,4: | 0 |