| 1 | ZmMYC7 directly regulates ZmERF147 to increase maize resistance to Fusarium graminearum显示文摘The jasmonic acid(JA)signaling pathway is involved in plant growth,development,and response to abiotic or biotic stresses.MYC2,a bHLH transcription factor,is a regulatory hub in the pathway.The function of ZmMYC7,a putative MYC2 ortholog,in jasmonate-signaled defense responses of maize has not been reported.In this study,we found that ZmMYC7 possesses JID,TAD,bHLH and Zip domains and essential characteristics of transcription factors:a nuclear location and transactivation activity.The ZmMYC7mutants showed markedly increased sensitivity to Fusarium graminearum and Setosphaeria turcica.The expression levels of the defense-associated genes ZmPR1,ZmPR2,ZmPR3,ZmPR5,ZmPR6,and ZmPR7 in response to F.graminearum infection were downregulated in ZmMYC7 mutants,while ZmPR4 and ZmPR10 were up-regulated.ZmMYC7 interacted with members of the ZmJAZ family,including ZmJAZ8,ZmJAZ11,and ZmJAZ12.ZmMYC7 physically interacted with G-box cis-elements in the ZmERF147 promoter in vitro and transcriptional activation of ZmERF147 by ZmMYC7 was inhibited by ZmJAZ11 and ZmJAZ12.ZmERF147 mutants were more susceptible to F.graminearum infection than inbred line B73with concomitant down-regulation of all defense-associated ZmPRs except ZmPR4.These findings indicate that ZmMYC7 functions in maize resistance to F.graminearum and sheds light on maize defense responses to pathogenic fungi via the JA signaling pathway. | Hongzhe Cao Kang Zhang Wei Li Xi Pang Pengfei Liu Helong Si Jinping Zang Jihong Xing Jingao Dong | 2023 | The Crop Journal2023，11，1： | 0 |
| 2 | Safety and activity of WX-0593(Iruplinalkib)in patients with ALK-or ROS1-rearranged advanced non-small cell lung cancer:a phase 1 dose-escalation and dose-expansion trial显示文摘WX-0593(Iruplinalkib)is a novel,highly selective oral ALK and ROS1 tyrosine kinase inhibitor(TKI).In this study,the safety,antitumor activity,and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell lung cancer(NSCLC)patients with ALK or ROS1 rearrangement.In the dose-escalation phase and dose-expansion phase,patients were treated with WX-0593 until disease progression,unacceptable toxicity,or subject withdrawal.In the dose-escalation phase,the primary endpoints were maximum tolerated dose(MTD),dose-limiting toxicity(DLT),and safety assessed by investigators.In the dose-expansion phase,the primary endpoint was objective response rate(ORR)assessed by investigators.Between September 25,2017 and October 15,2018,a total of 153 patients received WX-0593 treatment.Two dose-limiting toxicities(DLTs)including one grade 3 QT interval prolonged and one grade 2 chronic heart failure were reported at the dose of 300 mg in one patient.MTD was not reached.Overall,140 of the 152(92%)patients experienced treatment-related adverse events(TRAEs)and 35 of the 152(23%)patients had TRAEs≥grade 3.The overall ORR was 59.3%(32 of 54)for the dose-escalation phase and 56.6%(56 of 99)for the dose-expansion phase.For patients who were ALK-rearranged and ALK TKI naive,the ORR were 81.0%(17 of 21)in the dose-escalation phase and 76.3%(29 of 38)in the dose-expansion phase,and for patients who previously received crizotinib as the only ALK TKI,the ORR were 38.1%(8 of 21)and 45.7%(21 of 46)for the two phases,respectively.For patients who were ROS1-rearranged,the ORR were 30.0%(3 of 10)in the dose-escalation phase and 44.4%(4 of 9)in the dose-expansion phase.WX-0593 showed favorable safety and promising antitumor activity in advanced NSCLC patients with ALK or ROS1 rearrangement. | Yuankai Shi Jian Fang Xuezhi Hao Shucai Zhang Yunpeng Liu Lin Wang Jianhua Chen Yi Hu Xiaosheng Hang Juan Li Chunling Liu Yiping Zhang Zhehai Wang Yanping Hu Kangsheng Gu Jian’an Huang Liangming Zhang Jinlu Shan Weiwei Ouyang Yanqiu Zhao Wu Zhuang Yan Yu Jun Zhao Helong Zhang Pei Lu Weidong Li Meimei Si Mingjing Ge Huaize Geng | 2022 | Signal Transduction and Targeted Therapy2022，7，2： | 0 |
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