Activation of Orexin System Stimulates CaMKII Expression

Hyperactivity of the orexin system within the paraventricular nucleus (PVN) has been shown to contribute to increased sympathetic nerve activity (SNA) and blood pressure (BP) in rodent animals. However, the underlying molecular mechanisms remain unclear. Here, we test the hypothesis that orexin system activation stimulates calcium/calmodulin-dependent kinase II (CaMKII) expression and activation, and stimulation of CaMKII expressing PVN neurons increases SNA and BP. Real-time PCR and/or western blot were carried out to test the effect of orexin-A administration on CaMKII expression in the PVN of normal Sprague Dawley (SD) rats and orexin receptor 1 (OX1R) expressing PC12 cells. Immunostaining was performed to assess OX1R cellular localization in the PVN of SD rats as well as orexin-A treatment on CaMKII activation in cultured hypothalamic neurons. In vivo sympathetic nerve recordings were employed to test the impact of optogenetic stimulation of CaMKII-expressing PVN neurons on the renal SNA (RSNA) and BP. The results showed that intracerebroventricular injection of orexin-A into the SD rat increases mRNA expression of CaMKII subunits in the PVN. In addition, Orexin-A treatment increases CaMKII expression and its phosphorylation in OX1R-expressing PC12 cells. Furthermore, Orexin-A treatment increases CaMKII activation in cultured hypothalamic neurons from neonatal SD rats. Finally, optogenetic excitation of PVN CaMKII-expressing neurons results in robust increases in RSNA and BP in SD rats. Our results suggest that increased orexin system activity activates CaMKII expression in cardiovascular relevant regions, and this may be relevant to the downstream cardiovascular effects of CaMKII

Risk Assessment of Intermittent and Continuous Nasogastric Enteral Feeding Methods in Adult Inpatients: A Meta-Analysis

Diarrhea and pneumonia are common and serious complications in hospitalized patients requiring nasogastric enteral feeding. Our study aimed to compare the risk of diarrhea and pneumonia between intermittent nasogastric enteral feeding (IEF) and continuous nasogastric enteral feeding (CEF). We systematically searched PubMed, Web of Science, and Cochrane for relevant articles published from August 9, 1992, to September 1, 2019. A total of 637 IEF and CEF patients were included in our meta-analysis. Odds ratios (ORs) with associated 95% confidence intervals (CIs) were calculated to estimate the effects of diarrhea and pneumonia. We showed that hospital patients that required IEF had an increased risk of diarrhea compared with CEF. In the subgroup analyses, similar conclusions were identified in the non-China group and small sample size group (size < 100). However, our results showed no significant differences in the China group or large sample size group (size ≥ 100). Furthermore, our analysis showed that no significant association was observed for the risk of pneumonia between IEF and CEF patients. For inpatients requiring nasogastric enteral feeding, CEF is a better method of enteral nutrition compared with IEF, of which patients experience a significantly increased risk of diarrhea

Influences of MJO on the Diurnal Variation and Associated Offshore Propagation of Rainfall near Western Coast of Sumatra

Madden-Julian Oscillation (MJO) plays an important role in modulating precipitation at Maritime Continent (MC) not only on a larger scale, but also in the diurnal cycle. Diurnal rainfall offshore propagation is one of the most evident features near coasts. This study investigates the impacts of MJO on diurnal rainfall and its offshore propagation at the western coast of Sumatra during boreal winters using ERA5 reanalysis. The real-time multivariate MJO (RMM) index was applied to locate the active MJO convection through eight different phases, in the western hemisphere and Africa in P8&ndash;P1, at the Indian Ocean in P2&ndash;P3, at MC in P4&ndash;P5, and the western Pacific Ocean in P6&ndash;P7. The rainfall characteristics, including the daily rate, the absolute and normalized diurnal variation amplitudes, and the strengths of diurnal offshore propagation, not only depend on active/inactive MJO stages but also vary under different MJO phases, through the combined modulations of large-scale backgrounds and local-scale land&ndash;sea circulations. The offshore rainfall propagation is associated with meso-large-scale gravity waves generated from land&ndash;sea thermal contrast and thus is affected by the radiation effect of cloud under different MJO phases. The stronger wave signals in P8&ndash;P1 and P6&ndash;P7 enhance the diurnal rainfall variation amplitudes away from the coast, while the strong coupling of moist convection with gravity waves contributes greatly to the diurnal rainfall cycle in P2&ndash;P3

TTK, CDC25A, and ESPL1 as Prognostic Biomarkers for Endometrial Cancer

Objective. Endometrial cancer (EC) is one of the most common malignant gynaecological tumours worldwide. This study was aimed at identifying EC prognostic genes and investigating the molecular mechanisms of these genes in EC. Methods. Two mRNA datasets of EC were downloaded from the Gene Expression Omnibus (GEO). The GEO2R tool and Draw Venn Diagram were used to identify differentially expressed genes (DEGs) between normal endometrial tissues and EC tissues. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Next, the protein-protein interactions (PPIs) of these DEGs were determined by the Search Tool for the Retrieval of Interacting Genes (STRING) tool and Cytoscape with Molecular Complex Detection (MCODE). Furthermore, Kaplan-Meier survival analysis was performed by UALCAN to verify genes associated with significantly poor prognosis. Next, Gene Expression Profiling Interactive Analysis (GEPIA) was used to verify the expression levels of these selected genes. Additionally, a reanalysis of the KEGG pathways was performed to understand the potential biological functions of selected genes. Finally, the associations between these genes and clinical features were analysed based on TCGA cancer genomic datasets for EC. Results. In EC tissues, compared with normal endometrial tissues, 147 of 249 DEGs were upregulated and 102 were downregulated. A total of 64 upregulated genes were assembled into a PPI network. Next, 14 genes were found to be both associated with significantly poor prognosis and highly expressed in EC tissues. Reanalysis of the KEGG pathways found that three of these genes were enriched in the cell cycle pathway. TTK, CDC25A, and ESPL1 showed higher expression in cancers with late stage and higher tumour grade. Conclusion. In summary, through integrated bioinformatics approaches, we found three significant prognostic genes of EC, which might be potential therapeutic targets for EC patients

Influences of MJO on the Diurnal Variation and Associated Offshore Propagation of Rainfall near Western Coast of Sumatra

Madden-Julian Oscillation (MJO) plays an important role in modulating precipitation at Maritime Continent (MC) not only on a larger scale, but also in the diurnal cycle. Diurnal rainfall offshore propagation is one of the most evident features near coasts. This study investigates the impacts of MJO on diurnal rainfall and its offshore propagation at the western coast of Sumatra during boreal winters using ERA5 reanalysis. The real-time multivariate MJO (RMM) index was applied to locate the active MJO convection through eight different phases, in the western hemisphere and Africa in P8–P1, at the Indian Ocean in P2–P3, at MC in P4–P5, and the western Pacific Ocean in P6–P7. The rainfall characteristics, including the daily rate, the absolute and normalized diurnal variation amplitudes, and the strengths of diurnal offshore propagation, not only depend on active/inactive MJO stages but also vary under different MJO phases, through the combined modulations of large-scale backgrounds and local-scale land–sea circulations. The offshore rainfall propagation is associated with meso-large-scale gravity waves generated from land–sea thermal contrast and thus is affected by the radiation effect of cloud under different MJO phases. The stronger wave signals in P8–P1 and P6–P7 enhance the diurnal rainfall variation amplitudes away from the coast, while the strong coupling of moist convection with gravity waves contributes greatly to the diurnal rainfall cycle in P2–P3

Review and prospect about water resources operation research

The concept of water resources operation is expatiated and classified and the theories and methods with regard to water resources operation are also summarized. Research progress of water resources operation exists to analyse the problems and to take a look to the future of research directions in the field of water resources operation. In conclusion, the research on water resources operation needs a combination with the actual state of projects, climate change and increasing human activities, actually considering water resources demands and employing uniform control of water quantity and quality, which could ensure the sustainable utilization of water resources in China

Review and prospect about water resources operation research

The concept of water resources operation is expatiated and classified and the theories and methods with regard to water resources operation are also summarized. Research progress of water resources operation exists to analyse the problems and to take a look to the future of research directions in the field of water resources operation. In conclusion, the research on water resources operation needs a combination with the actual state of projects, climate change and increasing human activities, actually considering water resources demands and employing uniform control of water quantity and quality, which could ensure the sustainable utilization of water resources in China

Tanshinones induce tumor cell apoptosis via directly targeting FHIT

Abstract The liposoluble tanshinones are bioactive components in Salvia miltiorrhiza and are widely investigated as anti-cancer agents, while the molecular mechanism is to be clarified. In the present study, we identified that the human fragile histidine triad (FHIT) protein is a direct binding protein of sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of Tanshinone IIA (TSA), with a Kd value of 268.4 ± 42.59 nM. We also found that STS inhibited the diadenosine triphosphate (Ap3A) hydrolase activity of FHIT through competing for the substrate-binding site with an IC50 value of 2.2 ± 0.05 µM. Notably, near 100 times lower binding affinities were determined between STS and other HIT proteins, including GALT, DCPS, and phosphodiesterase ENPP1, while no direct binding was detected with HINT1. Moreover, TSA, Tanshinone I (TanI), and Cryptotanshinone (CST) exhibited similar inhibitory activity as STS. Finally, we demonstrated that depletion of FHIT significantly blocked TSA’s pro-apoptotic function in colorectal cancer HCT116 cells. Taken together, our study sheds new light on the molecular basis of the anti-cancer effects of the tanshinone compounds