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Objective: This study analyzed the relationship between bone marrow microvessel density (MVD) and the expression of four miRNAs with chronic myelogenous leukemia (CML) resistance after tyrosine kinase inhibitor (TKI) treatment. Methods: 234 CML patients were divided into resistance and non-resistance groups in terms of the results of the 5-year follow-up. Patients were divided into the Optimum response group and the Warning/Failure group based on TKI response. MVD was determined by immunohistochemistry, and the expression levels of four miRNAs (miR-106a, miR-155, miR-146a, and miR-340) in bone marrow biopsy specimens were examined by qPCR. We evaluated the association of MVD with four miRNAs and them predictive value for CML resistance after TKI treatment. Results: The MVD and the levels of miR-106a, miR-155, and miR-146a were significantly higher while the miR-340 level was lower in the resistance group than the non-resistance group. Besides, MVD had a significant correlation with the levels of miR-340 and miR-155. According to the results of survival analysis, MVD as well as miR-340 and miR-155 levels were observably correlated with 5-year survival of patients without TKI resistance. The results of the ROC curve indicated that the MVD, miR-106a, miR-340, and miR-155 had good predictive accuracy for CML resistance after TKI treatment. As for the results of multivariate analysis, disease stage, risk level (high risk), high MVD, low miR-340 expression, and high miR-155 expression were all independent risk factors for CML resistance. Conclusion: MVD and the expression of miR-340 and miR-155 are closely associated with CML resistance after TKI treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: The emerald ash borer (EAB, Agrilus planipennis Fairmaire) is currently a highly destructive forest pest, causing substantial economic losses. Ash species (Fraxinus spp.) are economically invaluable components of natural forests and urban environments. However, these trees have been severely damaged by EAB. Endophytes, which are prevalent in plants, are hypothesized to contribute to the complex relationships between insects and plants. However, research on the effect of EAB infestation on the community changes in endophytic fungi and bacteria in phloem of Fraxinus is scarce. To bridge this gap, we compare changes in fungi and bacteria diversity, community makeup, and the potential roles of various endophytic fungi and bacteria in both EAB-infested and uninfected Fraxinus bungeana trees. We observed an elevation in bacterial richness, without notable changes in diversity, whereas fungal richness and diversity remained unaffected. Furthermore, we identified four key microbial genera undergoing substantial shifts post-infestation. The functional roles of endophytic fungi and bacteria also exhibited changes, with a decline in beneficial activities and an emergence of potentially detrimental functions. Network analyses have shown elevated negative correlations and core genera shift in EAB-infected phloem. The findings of our study contribute to a better understanding of the complex interactions between plants, insects, and endophytic microorganisms. Endophytes, prevalent in plants, mediate plant–insect interactions. Nevertheless, our understanding of the key members of endophyte communities involved in inhibiting or assisting EAB infestation remains limited. Employing ITS and 16S rRNA high-throughput sequencing, along with network analysis techniques, we conducted a comprehensive investigation into the reaction of endophytic fungi and bacteria within F. bungeana phloem by comparing EAB-infested and uninfected samples. Our findings reveal that EAB infestation significantly impacts the endophytic communities, altering both their diversity and overall structure. Interestingly, both endophytic fungi and bacteria exhibited distinct patterns in response to the infestation. For instance, in the EAB-infested phloem, the fungi abundance remained unchanged, but diversity decreased significantly. Conversely, bacterial abundance increased, without significant diversity changes. The fungi community structure altered significantly, which was not observed in bacteria. The bacterial composition in the infested phloem underwent significant changes, characterized by a substantial decrease in beneficial species abundance, whereas the fungal composition remained largely unaffected. In network analysis, the endophytes in infested phloem exhibited a modular topology, demonstrating greater complexity due to an augmented number of network nodes, elevated negative correlations, and a core genera shift compared to those observed in healthy phloem. Our findings increase understanding of plant–insect–microorganism relationships, crucial for pest control, considering endophytic roles in plant defense. [ABSTRACT FROM AUTHOR]

Objective:  To discover the mechanism of the sirtuin 1 (SIRT1)-mediated nuclear factor-κB (NF-κB) pathway in the protection against necrotizing enterocolitis (NEC) in neonatal mice.Materials and Methods:  Neonatal mice were treated with EX527 (an inhibitor of SIRT1) and/or pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB). The survival rate of the mice was recorded. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the intestines. Furthermore, western blotting, enzyme-linked immunosorbent assay, and real-time quantitative polymerase chain reaction were conducted to measure the protein and gene expression, while corresponding kits were used to detect the levels of oxidative stress indicators.Results:  PDTC increased the survival rate of NEC mice. When compared with the NEC+ EX527 + PDTC group, the histological NEC score was higher in the NEC + EX527 group but lower in the NEC + PDTC group. SIRT1 expression in the intestines of NEC mice was downregulated, with an increase in p65 nuclear translocation. Additionally, malondialdehyde increased and glutathione peroxidase decreased in the intestines of NEC mice, with the upregulation of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α, as well as the downregulation of ZO-1, occludin, and claudin-4 in the intestines. However, the above changes could be improved by PDTC, which could be further reversed by EX527.Conclusion:  SIRT1 can mitigate inflammation and the oxidative stress response and improve intestinal permeability by mediating the NF-κB pathway, playing an important role in the alleviation of NEC. [ABSTRACT FROM AUTHOR]

ABSTRACT A July-May precipitation reconstruction for the period AD 1816-2010 was developed from a tree-ring width chronology of Picea wilsonii for the Xinglong Mountains area of Lanzhou. The reconstruction explains 55.8% of the actual precipitation variance during the calibration period from 1951 to 2010. Wet conditions prevailed during the periods 1822-1835, 1843-1858, 1870-1877, 1884-1891, 1911-1921, 1933-1938, 1944-1979 and 2009-2010. Dry episodes occurred during 1816-1821, 1836-1842, 1859-1869, 1878-1883, 1892-1910, 1922-1932, 1939-1943 and 1980-2008. Multi-taper method spectral analysis indicates the existence of some significant peaks at 2.8, 3.0 and 3.5 years. Spatial correlations with gridded land surface precipitation data revealed that our reconstruction represents regional precipitation signal for a large area of North China linked to the East Asian summer monsoon (EASM). Comparison with other tree-ring-based precipitation/drought reconstructions from surrounding areas implies a high degree of confidence for our reconstruction. Precipitation variations in the study area are significantly correlated with sea surface temperatures in eastern equatorial Pacific Ocean and tropical western Pacific Ocean, suggesting a possible connection of regional precipitation variations to the EASM and the El Niño-Southern Oscillation (ENSO). [ABSTRACT FROM AUTHOR]