No abstract

The objective of this study was to examine the expression of preproenkephalin (ppENK) in the heart in cardiac hypertrophy and the effects on cardiac contractility and blood pressure regulation of its peptide products. The ppENK-derived peptides Leu5-enkephalin (LE), Met5-enkephalin (ME), Met5-enkephalin-Arg6-Gly7-Leu8 (MEAGL), and Met5-enkephalin-Arg6-Phe7 (MEAP) were administered intravenously to unanesthetized Sprague-Dawley rats and to an isolated heart preparation from the same species. LE, ME, MEAGL, or MEAP (360 nmol iv) produced an immediate decrease in heart rate, reaching its maximum within 10 s and returning to baseline by 30 s. The blood pressure response for each enkephalin was a small initial decrease followed by a marked and significant increase (P < 0.05 for MEAP). In the isolated heart preparation, neither LE, ME, MEAGL, nor MEAP altered left ventricular contractility. Cardiac hypertrophy was produced in the Dahl salt-dependent model of hypertension with a significantly greater heart weight-to-body weight ratio in the Dahl salt-sensitive (S) compared with the Dahl salt-resistant (R) rat on a high-salt diet (P < 0.05). Tissue RNA was extracted, and Northern blot analysis identified and quantitated mRNA with a 0.93-kilobase cDNA of ppENK A. There was more ppENK mRNA in the left than in the right ventricle and much less in the atria than in the ventricles. The amount of ppENK mRNA was markedly and significantly increased in the left ventricle of the Dahl S compared with the Dahl R rat (P < 0.05). In contrast, there were no differences in ppENK mRNA levels in different brain regions between the R and S rats on a high-salt diet. Interestingly, a larger ppENK mRNA of 1.75 kilobases was abundantly expressed in testicular tissue. These data showing increased ppENK expression raise the possibilities of 1) an autocrine/paracrine role for enkephalins in cardiac hypertrophy and 2) an endocrine role for the hypertrophic heart, with an increased production of enkephalins, especially MEAP, that produces vasoconstriction and further increases in blood pressure.

Rapid and accurate mapping of the spatial distribution of cotton fields is helpful to ensure safe production of cotton fields and the rationalization of land-resource planning. As cotton is an important economic pillar in Xinjiang, accurate and efficient mapping of cotton fields helps the implementation of rural revitalization strategy in Xinjiang region. In this paper, based on the Google Earth Engine cloud computing platform, we use a random forest machine-learning algorithm to classify Landsat 5 and 8 and Sentinel 2 satellite images to obtain the spatial distribution characteristics of cotton fields in 2011, 2015 and 2020 in the Ogan-Kucha River oasis, Xinjiang. Unlike previous studies, the mulching process was considered when using cotton field phenology information as a classification feature. The results show that both Landsat 5, Landsat 8 and Sentinel 2 satellites can successfully classify cotton field information when the mulching process is considered, but Sentinel 2 satellite classification results have the best user accuracy of 0.947. Sentinel 2 images can distinguish some cotton fields from roads well because they have higher spatial resolution than Landsat 8. After the cotton fields were mulched, there was a significant increase in spectral reflectance in the visible, red-edge and near-infrared bands, and a decrease in the short-wave infrared band. The increase in the area of oasis cotton fields and the extensive use of mulched drip-irrigation water saving facilities may lead to a decrease in the groundwater level. Overall, the use of mulch as a phenological feature for classification mapping is a good indicator in cotton-growing areas covered by mulch, and mulch drip irrigation may lead to a decrease in groundwater levels in oases in arid areas.

Choline has been shown to mediate damage of the chondrocyte matrix and degradation enzymes of mice exposed to fluoride (F). To test the action of choline, pregnant mice were treated with differing amounts of F and choline. Newborn mice were weaned at 21 days after birth and treated with the same doses of F and choline as they mothers for 12 weeks. Using hematoxylin-eosin (HE) staining, real-time PCR (RT-PCR), and western blotting, changes in the structure of the cartilage, the expression of mRNA and protein related to proteoglycans (PG), and degradation enzymes were detected. The RT-PCR results show that the expression of the Aggrecan (Acan), transforming growth factor beta (TGF-β1), and Aggrecanases-1 gene were abnormal in the high fluoride (HiF) group, and treatments with choline reversed this phenomenon. The western blotting results show that the protein expression of Aggrecanases-1 was significantly increased in the HiF group (p < 0.01). These findings suggest that F can change the morphology of cartilage tissue, the gene expression of the Acan, TGF-β1, Aggrecanases-1, and the protein expression of the Acan, and that choline can attenuate the effect of F. This may provide the basis for the treatment and prevention of fluorosis.

Acute myeloid leukemia (AML) is a group of heterogeneous hematological malignancies. We identified key genes as ITGAM and lncRNA ITGB2-AS1 through different bioinformatics tools. Furthermore, qPCR was performed to verify the expression level of essential genes in clinical samples. Retrospective research on 179 AML cases was used to investigate the relationship between the expression of ITGAM and the characteristics of AML. The critical gene relationship with immune infiltration in AML was estimated. The clinical validation and prognostic investigation showed that ITGAM, PPBP, and ITGB2-AS1 are highly expressed in AML (P < 0.001) and significantly associated with the overall survival in AML. Moreover, the retrospective research on 179 clinical cases showed that positive expression of ITGAM is substantially related to AML classification (P < 0.001), higher count of white blood cells (P < 0.01), and poor chemotherapy outcome (P < 0.05). Furthermore, based on grouping ITGAM as the high and low expression in TCGA-LAML profile, we found that genes in the highly expressed ITGAM group are mainly involved in immune infiltration and inflammationrelated signaling pathways. Finally, we discovered that the expression level of ITGAM and lncRNA ITGB2-AS1 are not just closely related to the immune score and stromal score (P < 0.001) but also significantly positively correlated with various Immune signatures in AML (P < 0.001), indicating the association of these genes with immunosuppression in AML. The prediction of candidate drugs indicated that certain immunosuppressive drugs have potential therapeutic effects for AML. The critical genes could be used as potential biomarkers to evaluate the survival and prognosis of AML.

Introduction: Essential thrombocytosis (ET) is a group of myeloproliferative neoplasms characterized by abnormal proliferation of platelet and megakaryocytes. Research on potential key genes and novel regulatory markers in essential thrombocythemia (ET) is still limited. Methods: Downloading array profiles from the Gene Expression Omnibus database, we identified the differentially expressed genes (DEGs) through comprehensive bioinformatic analysis. GO, and REACTOME pathway enrichment analysis was used to predict the potential functions of DEGs. Besides, constructing a protein-protein interaction (PPI) network through the STRING database, we validated the expression level of hub genes in an independent cohort of ET, and the transcription factors (TFs) were detected in the regulatory networks of TFs and DEGs. And the candidate drugs that are targeting hub genes were identified using the DGIdb database. Results: We identified 63 overlap DEGs that included 21 common up-regulated and 42 common down-regulated genes from two datasets. Functional enrichment analysis shows that the DEGs are mainly enriched in the immune system and inflammatory processes. Through PPI network analysis, ACTB, PTPRC, ACTR2, FYB, STAT1, ETS1, IL7R, IKZF1, FGL2, and CTSS were selected as hub genes. Interestingly, we found that the dysregulated hub genes are also aberrantly expressed in a bone marrow cohort of ET. Moreover, we found that the expression of CTSS, FGL2, IKZF1, STAT1, FYB, ACTR2, PTPRC, and ACTB genes were significantly underexpressed in ET (P<0.05), which is consistent with our bioinformatics analysis. The ROC curve analysis also shows that these hub genes have good diagnostic value. Besides, we identified 4 TFs (SPI1, IRF4, SRF, and AR) as master transcriptional regulators that were associated with regulating the DEGs in ET. Cyclophosphamide, prednisone, fluorouracil, ruxolitinib, and lenalidomide were predicted as potential candidate drugs for the treatment of ET. Discussion: These dysregulated genes and predicted key regulators had a significant relationship with the occurrence of ET with affecting the immune system and inflammation of the processes. Some of the immunomodulatory drugs have potential value by targeting ACTB, PTPRC, IL7R, and IKZF1 genes in the treatment of ET.

The influence of semi-continuous culture on root growth and production of saikosaponins was investigated using root cultures of Bupleurum chinense DC. When fresh medium, consisting of half-strength of Murashige and Skoog liquid medium and 5% sucrose, was added at day 30, numerous new young roots developed and grew. Also, an increase in root weight and the total amount of saikosaponins was observed at day 60. Both the concentration and time of adding sucrose to the culture medium had significant effects on root growth and production of total saikosaponins. The sucrose concentration was controlled by multiple additions of fresh sucrose at different time points during root culture. Compared to other reported methods, by which sucrose concentration was controlled in culture, sequential increases of 1% sucrose at days 5, 10, 15, and 20 promoted both root growth and the production of saikosaponins.

Acute myeloid leukemia (AML) with RARG rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four AML with RARG rearrangements were identified. Bleeding or ecchymosis was present at 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and 26.5% of cases, respectively. Immunophenotyping showed following characteristics: positive for CD33, CD13, and MPO but negative for CD38, CD11b, CD34, and HLA-DR. Cytogenetics showed normal karyotype in 38% and t(11;12) in 26% of patients. The partner genes of RARG were diverse and included CPSF6 (n=14), NUP98 (n=11), HNRNPc (n=6), HNRNPm (n=1), PML (n=1), and NPM1 (n=1). WT1- and NRAS/KRAS-mutations were common co-mutations. None of the 34 patients responded to ATRA and/or ATO. Death within 45 days from diagnosis occurred in 10 patients (~29%). At the last follow-up, 23 patients had died, and the estimated 2-year cumulative incidence of relapse, event-free survival, and overall survival were 68.7%, 26.7%, and 33.5%, respectively. Unsupervised hierarchical clustering using RNA-seq data from 201 AML patients showed that 81.8% of the RARG fusion samples clustered together, suggesting a new molecular subtype. RARG rearrangement is a novel entity of AML that confers a poor prognosis.