ABSTRACT
Tumor vasculature often exhibits disorder and inefficiency. Vascular normalization offers potential for alleviating hypoxia and optimizing drug delivery in tumors. However, identifying effective agents is hindered by a lack of robust screening. We aimed to establish a comprehensive method using the zebrafish functional xenograft vasculature platform (zFXVP) to visualize and quantify tumor vasculature changes. Employing zFXVP, we systematically screened compounds, identifying PF-502 as a robust vascular normalization agent. Mechanistic studies showed PF-502 induces endothelial cell-cycle arrest, streamlines vasculature, and activates Notch1 signaling, enhancing stability and hemodynamics. In murine models, PF-502 exhibited pronounced vascular normalization and improved drug delivery at a sub-maximum tolerated dose. These findings highlight zFXVP's utility and suggest PF-502 as a promising adjunctive for vascular normalization in clinical settings.
ABSTRACT
BACKGROUND: The objective of this study was to increase understanding about genetic mechanisms affecting calyx persistence in Korla fragrant pear (Pyrus brestschneideri Rehd). Flowers were collected at early bloom, full bloom, and late bloom. The RNA was extracted from the flowers and then combined according to calyx type. Transcriptome and digital gene expression (DGE) profiles of flowers, ovaries, and sepals with persistent calyx (SC_hua, SC_ep, and SC_zf, respectively) were compared with those of flowers, ovaries, and sepals with deciduous calyx (TL_hua, TL_ep, and TL_zf, respectively). Temporal changes in the expression of selected genes in floral organs with either persistent or deciduous calyx were compared using real-time quantitative PCR (qRT-PCR). RESULTS: Comparison of the transcriptome sequences for SC_hua and TL_hua indicated 26 differentially expressed genes (DEGs) with known relationship to abscission and 10 DEGs with unknown function. We identified 98 MYB and 21 SPL genes from the assembled unigenes. From SC_zf vs TL_zf, we identified 21 DEGs with known relationship to abscission and 18 DEGs with unknown function. From SC_ep vs TL_ep, 12 DEGs with known relationship to abscission were identified along with 11 DEGs with unknown function. Ten DEGs were identified by both transcriptome sequencing and DGE sequencing. CONCLUSIONS: More than 50 DEGs were observed that were related to calyx persistence in Korla fragrant pear. Some of the genes were related to cell wall degradation, plant hormone signal transduction, and stress response. Other DEGs were identified as zinc finger protein genes and lipid transfer protein genes. Further analysis showed that calyx persistence in Korla fragment pear was a metabolic process regulated by many genes related to cell wall degradation and plant hormones.
Subject(s)
Flowers/genetics , Pyrus/genetics , Transcriptome , Flowers/growth & development , Genes, Plant , Molecular Sequence Annotation , Pyrus/growth & development , RNA, Plant/genetics , Real-Time Polymerase Chain ReactionABSTRACT
A laboratory test was conducted to study the effects of different sea water temperature (17 grads) and salinity (19 grads) on the growth and survival of juvenile Meretrix meretrix. The suitable and optimum sea water salinities for the survival of juvenile M. meretrix were 6.5-39.5 and 9.0-31.0, and those for the juvenile growth were 7.3-38.7 and 15.0-23.0, respectively. The suitable sea water temperature for the survival of the juveniles was 4.0 degrees C-36.1 degrees C; the suitable temperature for the growth was 7.0 degrees C-35.4 degrees C, more suitable temperature was 17 degrees C-33.5 degrees C, and the optimum growth temperature was 24 degrees C-27 degrees C. Juvenile M. meretrix had stronger adaptability to high sea water temperature and low sea water salinity.
