loanbirth6
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Therefore, our studies provided a source to study the phosphorylation and histone acetylation underlying the regulatory network of AMPK, which could be beneficial to understand the exact role of AMPK in DDR.The gut microbiota of intensive care unit (ICU) patients displays extreme dysbiosis associated with increased susceptibility to organ failure, sepsis, and septic shock. However, such dysbiosis is difficult to characterize owing to the high dimensional complexity of the gut microbiota. We tested whether the concept of enterotype can be applied to the gut microbiota of ICU patients to describe the dysbiosis. We collected 131 fecal samples from 64 ICU patients diagnosed with sepsis or septic shock and performed 16S rRNA gene sequencing to dissect their gut microbiota compositions. ML162 During the development of sepsis or septic shock and during various medical treatments, the ICU patients always exhibited two dysbiotic microbiota patterns, or ICU-enterotypes, which could not be explained by host properties such as age, sex, and body mass index, or external stressors such as infection site and antibiotic use. ICU-enterotype I (ICU E1) comprised predominantly Bacteroides and an unclassified genus of Enterobacteriaceae, while ICU-enterotype II (ICU E2) comprised predominantly Enterococcus. Among more critically ill patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores > 18, septic shock was more likely to occur with ICU E1 (P = 0.041). Additionally, ICU E1 was correlated with high serum lactate levels (P = 0.007). Therefore, different patterns of dysbiosis were correlated with different clinical outcomes, suggesting that ICU-enterotypes should be diagnosed as independent clinical indices. Thus, the microbial-based human index classifier we propose is precise and effective for timely monitoring of ICU-enterotypes of individual patients. This work is a first step toward precision medicine for septic patients based on their gut microbiota profiles.The recent advancement of single-cell RNA sequencing (scRNA-seq) technologies facilitates the study of cell lineages in developmental processes and cancer. In this study, we developed a computational method, called redPATH, to reconstruct the pseudo developmental time of cell lineages using a consensus asymmetric Hamiltonian path algorithm. Besides, we developed a novel approach to visualize the trajectory development and implemented visualization methods to provide biological insights. We validated the performance of redPATH by segmenting different stages of cell development on multiple neural stem cell and cancer datasets, as well as other single-cell transcriptome data. In particular, we identified a stem cell-like subpopulation in malignant glioma cells. These cells express known proliferative markers, such as GFAP, ATP1A2, IGFBPL1, and ALDOC, and remain silenced for quiescent markers such as ID3. Furthermore, we identified MCL1 as a significant gene that regulates cell apoptosis and CSF1R for reprogramming macrophages to control tumor growth. In conclusion, redPATH is a comprehensive tool for analyzing scRNA-seq datasets along the pseudo developmental time. redPATH is available at https//github.com/tinglabs/redPATH.Gastric cancer (GC) is known as a top malignant type of tumors worldwide. Despite the recent decrease in mortality rates, the prognosis remains poor. Therefore, it is necessary to find novel biomarkers with early diagnostic value for GC. In this study, we present a large-scale proteomic analysis of 30 GC tissues and 30 matched healthy tissues using label-free global proteome profiling. Our results identified 537 differentially expressed proteins, including 280 upregulated and 257 downregulated proteins. The ingenuity pathway analysis (IPA) results indicated that the sirtuin signaling pathway was the most activated pathway in GC tissues whereas oxidative phosphorylation was the most inhibited. Moreover, the most activated molecular function was cellular movement, including tissue invasion by tumor cell lines. Based on IPA results, 15 hub proteins were screened. Using the receiver operating characteristic curve, most of hub proteins showed a high diagnostic power in distinguishing between tumors and healthy controls. A four-protein (ATP5B-ATP5O-NDUFB4-NDUFB8) diagnostic signature was built using a random forest model. The area under the curve (AUC) values of this model were 0.996 and 0.886 for the training and testing sets, respectively, suggesting that the four-protein signature has a high diagnostic power. This signature was further tested with independent datasets using plasma enzyme-linked immune sorbent assays, resulting in an AUC value of 0.778 for distinguishing GC tissues from healthy controls, and using immunohistochemical tissue microarray analysis, resulting in an AUC value of 0.805. In conclusion, this study identifies potential biomarkers and improves our understanding of the pathogenesis, providing novel therapeutic targets for GC. Engaging in physical activity (PA) and avoiding sedentary behavior (SB) are important for healthy ageing with benefits including the mitigation of disability and mortality. Whether benefits extend to key determinants of disability and mortality, namely muscle strength and muscle power, is unclear. This systematic review aimed to describe the association of objective measures of PA and SB with measures of skeletal muscle strength and muscle power in community-dwelling older adults. Six databases were searched from their inception to June 21 , 2020 for articles reporting associations between objectively measured PA and SB and upper body or lower body muscle strength or muscle power in community dwelling adults aged 60 years and older. An overview of associations was visualized by effect direction heat maps, standardized effect sizes were estimated with albatross plots and summarized in box plots. Articles reporting adjusted standardized regression coefficients (β) were included in meta-analyses. A totaower SB are associated with greater skeletal muscle strength and muscle power, particularly with the chair stand test.

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