50 research outputs found

    BTK and PI3K Inhibitors Reveal Synergistic Inhibitory Anti-Tumoral Effects in Canine Diffuse Large B-Cell Lymphoma Cells

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    Bruton’s tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3K) in the B-cell receptor (BCR) signaling pathway are considered potential therapeutic targets for the treatment of B-cell lymphomas, among which, diffuse large B-cell lymphoma (DLBCL) is the most common type. Herein, we comparatively evaluated the single and combined application of the BTK inhibitor ibrutinib and the selective PI3Kγ inhibitor AS-605240 in the canine DLBCL cell line CLBL-1. For further comparison, key findings were additionally analyzed in canine B-cell leukemia GL-1 and human DLBCL cell line SU-DHL-4. While ibrutinib alone induced significant anti-proliferative effects on all cell lines in a dose-dependent manner, AS-605240 only induced anti-proliferative effects at high concentrations. Interestingly, ibrutinib and AS-605240 acted synergistically, reducing cell proliferation and increasing apoptosis/necrosis in all cell lines and inducing morphological changes in CLBL-1. Moreover, the combined application of ibrutinib and AS-605240 reduced relative phosphorylation and, in some instances, the levels of the BTK, AKT, GSK3β, and ERK proteins. Comparative variant analysis of RNA-seq data among canine B- and T-lymphoid cell lines and primary B-cell lymphoma samples revealed potentially high-impact somatic variants in the genes that encode PI3K, which may explain why AS-605240 does not singly inhibit the proliferation of cell lines. The combination of ibrutinib and AS-605240 represents a promising approach that warrants further in vivo evaluation in dogs, potentially bearing significant value for the treatment of human DLBCL

    Social Vulnerability Evaluation of Natural Disasters and Its Spatiotemporal Evolution in Zhejiang Province, China

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    Natural disasters present a significant challenge to the productivity of Zhejiang Province. This paper is the first to evaluate social vulnerability to natural disasters in Zhejiang Province and provides a scientific foundation for disaster prevention, mitigation, and risk management. In this paper, we construct an indicator system for evaluating social vulnerability of natural disasters in Zhejiang Province through demand analysis, frequency analysis, and applicability analysis. The methodology employed in this paper reduces errors arising from subjective indicator selection and provides a reference for future international research on evaluating social vulnerability to natural disasters. This study analyzes the spatiotemporal evolution of social vulnerability to natural disasters in 11 cities from 2011 to 2020. The results indicate an overall downward trend of social vulnerability to natural disasters in Zhejiang. Social vulnerability to natural disasters exhibits significant spatial variability. The evaluation can help to bridge the knowledge gap regarding the social vulnerability of Zhejiang Province to natural disasters. The analysis of the spatiotemporal evolution of social vulnerability provides insights into the contributing factors to vulnerability and the effectiveness of past disaster management strategies. The findings of this study can serve as a valuable reference for future research in Zhejiang Province and other regions facing similar challenges. The results can contribute to the advancement of comprehensive knowledge of social vulnerability to natural disasters, which can inform the development of policies and strategies aimed at mitigating disaster risk and promoting effective disaster management globally

    Evaluation of urban flood resilience and its Space-Time Evolution: A case study of Zhejiang Province, China

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    Urban floods have become increasingly frequent in recent years, highlighting the need for resilience evaluation and the identification of strategies to improve urban flood resilience. In this study, a system of resilience evaluation indicators is proposed to quantitatively evaluate the level of urban flood resilience. The entropy method used to calculate the resilience index and the space–time permutation scan method used to analyze the space–time aggregation characteristics of urban resilience levels are combined to establish a methodology for evaluating urban flood resilience. An evaluation indicator system for urban flood resilience is proposed, encompassing aspects of natural, economy, society, and infrastructure. This system attuned to the local needs of urban flood resilience evaluation, tests the applicability of the Guide for Safety Resilient City Evaluation (GB/T 40947–2021) in this study. Moreover, it incorporates key common indicators extracted from prior studies on urban flood resilience evaluation. Zhejiang Province, a flood-prone area in China, is selected as the study area, and the proposed evaluation indicator system is used to evaluate the urban flood resilience levels in Zhejiang and their space–time trends from 2011 to 2020. The results show that resilience levels have improved in the natural, economic, and infrastructure aspects, while the resilience levels of social aspect remain high. From 2011 to 2014, two distinct aggregation patterns emerged, delineated as inland-type and coastal-type aggregation areas. An analysis of both patterns was conducted, considering an array of influencing indicators, such as green coverage rate in built-up areas, population age structure index, gross domestic product, density of resident population in built-up areas, and per capita disposable income. The period from 2014 to 2020, however, did not reveal any significant aggregation characteristics. This study provides a reference for establishing an urban flood resilience evaluation indicator system and an in-depth understanding of urban flood resilience, and targeted recommendations to bolster urban flood resilience in the study area

    Transcriptomic Profiling Analysis of <i>Arabidopsis thaliana</i> Treated with Exogenous <i>Myo</i>-Inositol

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    <div><p><i>Myo</i>-insositol (MI) is a crucial substance in the growth and developmental processes in plants. It is commonly added to the culture medium to promote adventitious shoot development. In our previous work, MI was found in influencing <i>Agrobacterium</i>-mediated transformation. In this report, a high-throughput RNA sequencing technique (RNA-Seq) was used to investigate differently expressed genes in one-month-old <i>Arabidopsis</i> seedling grown on MI free or MI supplemented culture medium. The results showed that 21,288 and 21,299 genes were detected with and without MI treatment, respectively. The detected genes included 184 new genes that were not annotated in the <i>Arabidopsis thaliana</i> reference genome. Additionally, 183 differentially expressed genes were identified (DEGs, FDR ≤0.05, log<sub>2</sub> FC≥1), including 93 up-regulated genes and 90 down-regulated genes. The DEGs were involved in multiple pathways, such as cell wall biosynthesis, biotic and abiotic stress response, chromosome modification, and substrate transportation. Some significantly differently expressed genes provided us with valuable information for exploring the functions of exogenous MI. RNA-Seq results showed that exogenous MI could alter gene expression and signaling transduction in plant cells. These results provided a systematic understanding of the functions of exogenous MI in detail and provided a foundation for future studies.</p></div

    Reads number based on the RNA-Seq data in two libraries of <i>A</i>. <i>thaliana</i> wild-type (Col-0) under exogenous <i>myo</i>-inositol (MI+ or MI-).

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    <p>Reads number based on the RNA-Seq data in two libraries of <i>A</i>. <i>thaliana</i> wild-type (Col-0) under exogenous <i>myo</i>-inositol (MI+ or MI-).</p

    qRT–PCR validation of RNA-Seq results.

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    <p>Fifteen genes were randomly selected from the DEGs (<i>red columns</i>) from the RNA-Seq data and were analyzed for differential expression changes (<i>blue columns</i>) of the genes. The results were the average of two biological replicate samples in triplicate. <i>Error bars</i> indicate the standard error of two biological replicates in qRT–PCR.</p
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