Black cutworm (BCW), Agrotis ipsilon (Hufnagel), is an occasional pest of maize that can cause considerable economic loss and injury to corn seedlings. This research mainly assessed the susceptibility of BCW neonates to 11 Bt toxins (Cry1Ab, Cry1Ac, Cry1Ah, Cry1F, Cry1Ie, Cry1B, Cry2Aa, Vip3_ch1, Vip3_ch4, Vip3Ca2, Vip3Aa19) by exposing neonates to an artificial diet containing Bt toxins and evaluated the efficacy of three transgenic maize events (C008, C009, C010) expressing Vip3Aa19 toxin against BCW. The toxin-diet bioassay data indicated that Vip3Aa19 protein (LC50 = 0.43 μg/g) was the most active against BCW. Chimeric protein Vip3_ch1 (LC50 = 5.53 μg/g), Cry1F (LC50 = 83.62 μg/g) and Cry1Ac (LC50 = 184.77 μg/g) were less toxic. BCW was very tolerant to the other Bt toxins tested, with LC50 values more than 200 μg/g. Greenhouse studies were conducted with artificial infestations at the whorl stage by placing second-instar BCW larvae into whorl leaf and the fourth-instar larvae at the base of maize seedings. These results suggest that these transgenic maize events expressing Vip3Aa19 can provide effective control for BCW.
RNA 5-methylcytosine (m5C) modification plays critical roles in the pathogenesis of various tumors. However, the function and molecular mechanism of RNA m5C modification in tumor drug resistance remain unclear.The correlation between RNA m5C methylation, m5C writer NOP2/Sun RNA methyltransferase family member 2 (NSUN2) and EGFR-TKIs resistance was determined in non-small-cell lung cancer (NSCLC) cell lines and patient samples. The effects of NSUN2 on EGFR-TKIs resistance were investigated by gain- and loss-of-function assays in vitro and in vivo. RNA-sequencing (RNA-seq), RNA bisulfite sequencing (RNA-BisSeq) and m5C methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) were performed to identify the target gene of NSUN2 involved in EGFR-TKIs resistance. Furthermore, the regulatory mechanism of NSUN2 modulating the target gene expression was investigated by functional rescue and puromycin incorporation assays.RNA m5C hypermethylation and NSUN2 were significantly correlated with intrinsic resistance to EGFR-TKIs. Overexpression of NSUN2 resulted in gefitinib resistance and tumor recurrence, while genetic inhibition of NSUN2 led to tumor regression and overcame intrinsic resistance to gefitinib in vitro and in vivo. Integrated RNA-seq and m5C-BisSeq analyses identified quiescin sulfhydryl oxidase 1 (QSOX1) as a potential target of aberrant m5C modification. NSUN2 methylated QSOX1 coding sequence region, leading to enhanced QSOX1 translation through m5C reader Y-box binding protein 1 (YBX1).Our study reveals a critical function of aberrant RNA m5C modification via the NSUN2-YBX1-QSOX1 axis in mediating intrinsic resistance to gefitinib in EGFR-mutant NSCLC.
Appling structural equation model,this paper conducts an empirical study on the influential factors of LED industrial technology learning in Guangdong province.Evidences indicate that:(1) the tacitness and complexity of knowledge have negative effects on technology learning performance in Guangdong LED industry;(2) although Guangdong LED enterprises make full use of the centrality of their position in the LED industrial network to acquire external knowledge with high tacitness,the network centrality has no obvious adjustment effect as to external knowledge with high complexity;(3) stong ties with external innovation resources are helpful for Guangdong LED industry to get external tacit knowledge and core industrial technology with high complexity.
Since expanding the use of appropriate and effective health technologies will greatly benefit the diagnosis and treatment of some major diseases at an early stage, understanding the mechanism of technology use is crucial for its successful implementation. Few previous studies focused on the healthcare providers and involved multi-facets factors at individual, technical, organizational, and environmental levels.To examine the influencing mechanism of technology use among Chinese physicians by integrating multilevel factors, Des-gamma-Carboxy Prothrombin (DCP) was taken as an example.Through multistage random sampling, a cross-sectional questionnaire survey was conducted among physicians in charge of direct use of DCP of sampled secondary and tertiary hospitals. Since the sample data comprised two hierarchical levels (physicians and hospitals), multilevel structural equation modeling was used to link five aspects of factors with physicians' technology use and estimate the effects.Totally, 229 physicians completed the investigation. The use of DCP appears to be at a relatively low level. Intra-class coefficients of the null model (unadjusted baseline model) suggested that physicians' DCP use has a significant variation between hospitals. The final model identified that value cognition (B = 0.447, P < 0.01), experienced organizational practice (B = 0.203, P < 0.05), and perceived organizational atmosphere (B = -0.237, P < 0.01) contributed directly to physicians' DCP use. Additionally, technical assessment, perceived organizational atmosphere, and perceived environmental pressure had indirect impacts on physicians' DCP use that were mediated by value cognition and experienced organizational practice (P < 0.05).This study incorporated and determined the significant direct or indirect role of value cognition, technical assessment, experienced organizational practice, perceived organizational atmosphere, and perceived environmental pressure. This influencing mechanism with integrated multilevel factors could serve as a theoretical basis for tailoring interventions to promote technology use among Chinese physicians.
Over the past decade, therapies targeting the VEGF/VEGFR and mTOR pathways have served as the standard of care for the clinical management of renal cell carcinoma (RCC) patients.Albeit promising, these targeted drugs have attained only modest clinical benefits with limited prolonged progression-free survival.Therefore, alternative reasonable and applicable therapeutic approaches should be introduced to improve the clinical outcome of RCC patients.Methods: FDA approved kinase inhibitors were screened to evaluate their abilities to suppress the proliferation of RCC cells.Then, the downstream effector, therapeutic target and signaling pathway of the selected drug were identified by gene expression array, RNAi, kinase profile and rescue verification.Finally, the in vivo effectiveness of the drug was assessed in cell line-based xenograft models and patient-derived xenograft models.Results: In this study, we discovered that dasatinib is a potent agent that can impair RCC cell viability in vitro and decrease tumor growth in vivo.Mechanistically, we improved the understanding of the precise mechanistic role of YAP as a pivotal effector of dasatinib-induced anti-proliferation through Src-JNK-LIMD1-LATS signaling cascade in RCC cells.Meanwhile, our results indicated that the alteration of p-YAP is closely correlated to the growth inhibition caused by dasatinib in sensitive RCC models.Conclusion: Our findings provide evidence that dasatinib may serve as a powerful drug candidate to treat subgroups of RCC patients with hyper-activated Src-YAP signaling axis, and the alteration of p-YAP could serve as a functional response biomarker of dasatinib in RCC.
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