Integrative analysis of gene expression and DNA methylation through one-class logistic regression machine learning identifies stemness features in medulloblastoma.

Most human cancers develop from stem and progenitor cell populations through the sequential accumulation of various genetic and epigenetic alterations. Cancer stem cells have been identified from medulloblastoma (MB), but a comprehensive understanding of MB stemness, including the interactions between the tumor immune microenvironment and MB stemness, is lacking. Here, we employed a trained stemness index model based on an existent one-class logistic regression (OCLR) machine-learning method to score MB samples; we then obtained two stemness indices, a gene expression-based stemness index (mRNAsi) and a DNA methylation-based stemness index (mDNAsi), to perform an integrated analysis of MB stemness in a cohort of primary cancer samples (n = 763). We observed an inverse trend between mRNAsi and mDNAsi for MB subgroup and metastatic status. By applying the univariable Cox regression analysis, we found that mRNAsi significantly correlated with overall survival (OS) for all MB patients, whereas mDNAsi had no significant association with OS for all MB patients. In addition, by combining the Lasso-penalized Cox regression machine-learning approach with univariate and multivariate Cox regression analyses, we identified a stemness-related gene expression signature that accurately predicted survival in patients with Sonic hedgehog (SHH) MB. Furthermore, positive correlations between mRNAsi and prognostic copy number aberrations in SHH MB, including MYCN amplifications and GLI2 amplifications, were detected. Analyses of the immune microenvironment revealed unanticipated correlations of MB stemness with infiltrating immune cells. Lastly, using the Connectivity Map, we identified potential drugs targeting the MB stemness signature. Our findings based on stemness indices might advance the development of objective diagnostic tools for quantitating MB stemness and lead to novel biomarkers that predict the survival of patients with MB or the efficacy of strategies targeting MB stem cells.

Deciphering the Epitranscriptome in Cancer.

Technological and methodological advancements have recently revolutionized our understanding of widespread epitranscriptome including RNA modifications and editing. N6-methyladenosine (m6A) represents the most prevalent internal modification in mammalian RNAs. Adenosine to inosine (A-to-I) RNA editing is an important mechanism underlying RNA generation and protein diversity through the post-transcriptional modification of single nucleotides in RNA sequences. In this review, we attempt to summarize its functional importance in various fundamental bioprocesses of m6A and A-to-I editing. We also highlight some of the key findings that have helped shape our understanding of epitranscriptome in tumorigenesis, tumor progression, and metastasis. Finally, we discuss conceivable targets and future directions of m6A and A-to-I editing in cancer therapeutics.

Effects of Armillariella tabescens mycelia on the growth performance and intestinal immune response and microflora of early-weaned pigs.

This study was performed to evaluate effects of Armillariella tabescens (A. tabescens) on the growth performance and intestinal immune response and microflora in early-weaned pigs when used as feed additive. A. tabescens mycelia were added to basal diets at concentrations of 0%, 0.1%, 0.3% or 0.9% (w/w). A total of 144 commercial cross-bred piglets were randomly allocated to one of these four diets and fed for 30 days. The growth performance of early-weaned piglets displayed improvement with diets containing 0.1% and 0.3% dried mycelia powder from A. tabescens. Supplementing with 0.1% or 0.3% A. tabescens mycelia induced a 2.6- and three-fold increase in secretory immunoglobulin A (sIgA) content in the jejunal mucosa, respectively, but had only a marginal effect on sIgA in the ileal mucosa. Expression of interleukin-2, interferon-γ, and tumor necrosis factor-α in the jejunal mucosa were elevated with A. tabescens mycelia administration. Increased amounts of Lactobacillus spp. and Bifidobacterium spp. in the jejunum, and decreased amounts of Escherichia coli in the jejunum and ileum were observed with the administration of A. tabescens-containing diets. This study demonstrated that A. tabescens had beneficial effects on the growth performance and intestinal microflora of early-weaned pigs.

New anthracene derivatives as triplet acceptors for efficient green-to-blue low-power upconversion.

Three new anthracene derivatives [2-chloro-9,10-dip-tolylanthracene (DTACl), 9,10-dip-tolylanthracene-2-carbonitrile (DTACN), and 9,10-di(naphthalen-1-yl)anthracene-2-carbonitrile (DNACN)] were synthesized as triplet acceptors for low-power upconversion. Their linear absorption, single-photon-excited fluorescence, and upconversion fluorescence properties were studied. The acceptors exhibit high fluorescence yields in DMF. Selective excitation of the sensitizer Pd(II)octaethylporphyrin (PdOEP) in solution containing DTACl, DTACN, or DNA-CN at 532 nm with an ultralow excitation power density of 0.5 W cm(-2) results in anti-Stokes blue emission. The maximum upconversion quantum yield (Φ(UC) =17.4%) was obtained for the couple PdOEP/DTACl. In addition, the efficiency of the triplet-triplet energy transfer process was quantitatively studied by quenching experiments. Experimental results revealed that a highly effective acceptor for upconversion should combine high fluorescence quantum yields with efficient quenching of the sensitizer triplet.

[Legal-medical analysis of 147 homicidal cases].

147 homicidal cases were studied through case status, scene investigation, and postmortem examination. Its characters were then concluded for reference of detection in homicidal scene.