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10-week SS resulted in complete absence of HISS-dependent glucose uptake and produced a model of gestational obesity and prediabetes. 22-week SS did not produce hyperglycemia or worsen hyperinsulinemia but did increase hypertriglyceridemia above 10-week SS. This substantiates the use of 10-week SS as a model of gestational obesity/prediabetes, allowing further studies into treatments of gestational obesity and insulin resistance.Objective MicroRNAs (miRNAs) are known to participate in the progression of human cancers, such as pancreatic cancer (PC), while the mechanisms of miR-223 in PC remain largely unknown. This study was for the investigation of the status of microRNA (miR)-223 in the growth of PC with the involvement of ZIC1 and the PI3K/Akt/mTOR pathway. Methods MiR-223 and ZIC1 expression in PC tissue and cell lines was detected. PANC-1 cells and SW1990 cells were screened for subsequent experiments. Screened cells were transfected with miR-223- or ZIC1-related oligonucleotides or plasmids, or AZD8055, the dual inhibitor of the PI3K/Akt/mTOR signaling pathway to test the functions of miR-223, ZIC1 or PI3K/Akt/mTOR signaling pathway in the biological functions of PC cells. The expression of miR-223, ZIC1, or PI3K/Akt/mTOR signaling pathway-related proteins was examined. Tumor xenograft in nude mice was conducted for the detection of tumor growth of PC. #link# WithaferinA Up-regulated miR-223 and declined ZIC1 existed in PC tissues of patients and cell lines. ZIC1 was determined to be a target gene of miR-223. Down-regulated miR-223 or up-regulated ZIC1 led to suppressed proliferation, migration, invasion, and cell cycle entry, volume and weight of tumors, while elevated apoptosis in PC cells through declining phosphorylation levels of PI3K, Akt and mTOR. MiR-223 up-regulation or ZIC1 down-regulation induced opposite results on PC cells. Conclusion This study highlights that down-regulated miR-223 or elevated ZIC1 inhibits the development of PC via restricting activation of the PI3K/Akt/mTOR pathway, which has important meanings for exploring the mechanism of PC.FGF13, a member of the FGF subfamily, has been found to be highly expressed in cancer cells such as prostate cancer, melanoma, glioma and multiple myeloma. However, the mechanism of FGF13 function during cancer cell proliferation remains to be unexplored, especially Non-small cell lung cancer (NSCLC). link2 In this study, the cell proliferation effect of FGF13 on A549 cells was checked by CCK-8, clone formation, Ki67 immunofluorescence staining and Flow Cytometry assay. Localization of FGF13 within A549 cells was performed with confocal laser scanning microscope. The protein variations and interaction were measured by western blotting and co-immunoprecipitation analysis. It showed that FGF13 was mainly distributed in the cytoplasm and exhibited a high expression level in A549 cells. High expression of FGF13 activated AKT-GSK3 signaling pathway, and inhibited the activity of p21 and p27. Thus, FGF13 enhanced the process of transition from G1 to S phase and promoted A549 cells proliferation. Furthermore, the interaction between FGF13 and SHCBP1 was confirmed. Meanwhile, FGF13 and SHCBP1 had a cooperative effect to accelerate the cell cycle progression, especially the ability to promote cell proliferation is significantly enhanced via protein interaction. Hence, we conclude that FGF13 played a positive regulation role during A549 cells proliferation. FGF13 interacted with SHCBP1 to facilitate cell cycle progression, providing new insights into deep understanding of non-small cell lung cancer mechanisms of proliferation and regulation function of FGF13.Directional stress is an effective measure to evolve community structure and improve bioactivity of pit mud (PM). In this study, adding fortified Daqu in artificial PM (APM) was to disturb the microbial community and affect the metabolites furthermore. To evaluate the effect of fortified Daqu on culturing APM, microbial communities of APMs with/without adding fortified Daqu were investigated by fluorescence in situ hybridization and Illumina Miseq. These results indicated that microbes (Clostridium sp., Clostridium kluyveri, hydrogenotrophic methanogens, and acetotrophic methanogens) related to the production of key aroma compounds increased notably when fortified Daqu was added. Especially the hydrogenotrophic and acetotrophic methanogens increased by 5.19- and 4.63-fold after 30-days' culture. Then metabolites (organic acids, volatile compounds) were also analyzed by HPLC and HS-SPME-GC-MS. Results showed that the content of butyric acid and hexanoic acid was significantly higher when adding fortified Daqu. What's more, the proportion of esters and phenols were higher compared with the APM without adding fortified Daqu as well. The microbial compositions of APMs with/without adding fortified Daqu were observed in this study, which indicated the microbial community evolving in functional community in favor of liquor-brewing and suggested a novelty process was developed by disturbing the community diversity.The Solar System is becoming increasingly accessible to exploration by robotic missions to search for life. However, astrobiologists currently lack well-defined frameworks to quantitatively assess the chemical space accessible to life in these alien environments. Such frameworks will be critical for developing concrete predictions needed for future mission planning, both to determine the potential viability of life on other worlds and to anticipate the molecular biosignatures that life could produce. Here, we describe how uniting existing methods provides a framework to study the accessibility of biochemical space across diverse planetary environments. Our approach combines observational data from planetary missions with genomic data catalogued from across Earth and analyzed using computational methods from network theory. To demonstrate this, we use 307 biochemical networks generated from genomic data collected across Earth and "seed" these networks with molecules confirmed to be present on Saturn's moon Enceladus. By expanding through known biochemical reaction space starting from these seed compounds, we are able to determine which products of Earth's biochemistry are, in principle, reachable from compounds available in the environment on Enceladus, and how this varies across different examples of life from Earth (organisms, ecosystems, planetary-scale biochemistry). While we find that none of the 307 prokaryotes analyzed meet the threshold for viability, the reaction space covered by this process can provide a map of possible targets for detection of Earth-like life on Enceladus, as well as targets for synthetic biology approaches to seed life on Enceladus. In cases where biochemistry is not viable because key compounds are missing, we identify the environmental precursors required to make it viable, thus providing a set of compounds to prioritize for detection in future planetary exploration missions aimed at assessing the ability of Enceladus to sustain Earth-like life or directed panspermia.
There are at least four key pathophysiological endotypes that contribute to obstructive sleep apnea (OSA) pathophysiology. These include 1) upper-airway collapsibility (Pcrit), 2) arousal threshold, 3) loop gain and 4) pharyngeal muscle responsiveness. However, an easily interpretable model to examine the different ways and extent to which these OSA endotypes contribute to conventional polysomnography defined OSA severity (i.e. the apnea/hypopnea index AHI) has not been investigated. Additionally, clinically deployable approaches to estimate OSA endotypes to advance knowledge on OSA pathogenesis and targeted therapy at scale are not currently available.
Develop an interpretable data-driven model to 1) determine the different ways and extent to which the four key OSA endotypes contribute to polysomnographic defined OSA severity and 2) gain insight into how standard polysomnographic and clinical variables contribute to OSA endotypes and whether they can be used to predict OSA endotypes.
Age, BMI plus stansomnographic defined OSA severity. While further validation work is required, these findings also highlight the potential for routine sleep study and clinical data to estimate at least two of the key OSA endotypes using data driven predictive analysis methodology as part of a clinical decision support system to inform scalable research studies to advance OSA pathophysiology and targeted therapy for OSA.
This novel approach provides new insights into the different ways in which OSA endotypes can contribute to polysomnographic defined OSA severity. While further validation work is required, these findings also highlight the potential for routine sleep study and clinical data to estimate at least two of the key OSA endotypes using data driven predictive analysis methodology as part of a clinical decision support system to inform scalable research studies to advance OSA pathophysiology and targeted therapy for OSA.
Single-center studies demonstrated that methamphetamine use is associated with pulmonary arterial hypertension (Meth-APAH). We used the Pulmonary Hypertension Association Registry to evaluate the national distribution of Meth-APAH, and to compare its impact on patient-reported and clinical outcomes relative to idiopathic PAH.
To determine if patients with Meth-APAH differ from those with idiopathic PAH in demographics, regional distribution in the US, hemodynamics, health-related quality of life, PAH-specific treatment, and health care utilization.
The Pulmonary Hypertension Association Registry is a US-based prospective cohort of patients new to care at a Pulmonary Hypertension Care Center. The registry collects baseline demographics, clinical parameters, and repeated measures of health-related quality of life, World Health Organization functional class, six-minute walk distance, therapy, and health care utilization. Repeated measures of functional class, health-related quality of life, type of therapy1.10 to 1.83).
Meth-APAH represents a unique clinical phenotype of PAH, most common in the Western US. It accounts for a notable proportion of PAH in expert centers. Assessment for methamphetamine use is necessary in patients with PAH.
Meth-APAH represents a unique clinical phenotype of PAH, most common in the Western US. It accounts for a notable proportion of PAH in expert centers. Assessment for methamphetamine use is necessary in patients with PAH.Scale formation is an important challenge in water and wastewater treatment systems. However, due to the complex nature of membrane surfaces, the effects of specific membrane surface characteristics on scale formation are poorly understood. In this study, the independent effect of surface hydrophobicity on gypsum (CaSO4·2H2O) scale formation via surface-induced nucleation and bulk homogeneous nucleation was investigated using quartz crystal microbalance with dissipation (QCM-D) on self-assembled monolayers (SAMs) terminated with -OH, -CH3, and -CF3 functional groups. Results show that higher surface hydrophobicity enhances both surface-induced nucleation of gypsum and attachment of gypsum crystals formed from homogeneous nucleation in the bulk solution. link3 The enhanced surface-induced nucleation is attributed to the lower nucleation energy barrier on a hydrophobic surface, while the increased gypsum crystal attachment results from the favorable hydrophobic interactions between gypsum and more hydrophobic surfaces.
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