Specifically, our results suggest that, while younger and older subjects both employ context-based lexical predictions, older subjects are significantly less likely to pre-activate the semantic features relating to upcoming words. Furthermore, across our group of older adults, we show that the weaker the neural signature of this semantic pre-activation mechanism, the lower a subject's semantic verbal fluency score. We interpret these findings as prediction playing a generally reduced role at a semantic level in the brains of older listeners during speech comprehension and that these changes may be part of an overall strategy to successfully comprehend speech with reduced cognitive resources.Fish culture in paddy fields is a traditional aquaculture mode, which has a long history in East Asia. Large-scale loach (Paramisgurnus dabryanus) fast growth is suitable for paddy fields aquaculture in China. The objective of this study was to identify differential expression genes (DEGs) in the brain, liver and muscle tissues between large (LG, top 5% of maximum total length) and small (SG, top 5% of minimum total length) groups using RNA-seq. In total, 150 fish were collected each week and 450 fish were collected at twelfth week from three paddy fields for all the experimental. Histological observation found that the muscle fibre diameter of LG loaches was greater than that of SG loaches. Transcriptome results revealed that the high expression genes (HEGs) in LG loaches (fold change ≥ 2, p  less then  0.05) were mainly concentrated in metabolic pathways, such as "Thyroid hormone signalling pathway", "Citrate cycle (TCA cycle)", "Carbon metabolism", "Fatty acid metabolism", and "Cholesterol metabolism", and the HEGs in SG loaches were enriched in the pathways related to environmental information processing such as "Cell adhesion molecules (CAMs)", "ECM- receptor interaction" and "Rap1 signalling pathway"; cellular processes such as "Tight junction", "Focal adhesion", "Phagosome" and "Adherens junction". Furthermore, IGFs gene family may play an important role in loach growth for their different expression pattern between the two groups. These findings can enhance our understanding about the molecular mechanism of different growth and development levels of loaches in paddy fields.Lymph node metastasis (LNM), a common metastatic gastric-cancer (GC) route, is closely related to poor prognosis in GC patients. Bone marrow-derived mesenchymal stem cells (BM-MSCs) preferentially engraft at metastatic lesions. Whether BM-MSCs are specifically reprogrammed by LNM-derived GC cells (LNM-GCs) and incorporated into metastatic LN microenvironment to prompt GC malignant progression remains unknown. Herein, we found that LNM-GCs specifically educated BM-MSCs via secretory exosomes. Exosomal Wnt5a was identified as key protein mediating LNM-GCs education of BM-MSCs, which was verified by analysis of serum exosomes collected from GC patients with LNM. Wnt5a-enriched exosomes induced YAP dephosphorylation in BM-MSCs, whereas Wnt5a-deficient exosomes exerted the opposite effect. Inhibition of YAP signaling by verteporfin blocked LNM-GC exosome- and serum exosome-mediated reprogramming in BM-MSCs. Analysis of MSC-like cells obtained from metastatic LN tissues of GC patients (GLN-MSCs) confirmed that BM-MSCs incorporated into metastatic LN microenvironment, and that YAP activation participated in maintaining their tumor-promoting phenotype and function. Collectively, our results show that LNM-GCs specifically educated BM-MSCs via exosomal Wnt5a-elicited activation of YAP signaling. This study provides new insights into the mechanisms of LNM in GC and BM-MSC reprogramming, and will provide potential therapeutic targets and detection indicators for GC patients with LNM.Peroxisome Proliferator-Activated Receptor Gamma (PPARG) is one of the three members of the PPAR family of transcription factors. Besides its roles in adipocyte differentiation and lipid metabolism, we recently demonstrated an association between PPARG and metastasis in prostate cancer. In this study a functional effect of PPARG on AKT serine/threonine kinase 3 (AKT3), which ultimately results in a more aggressive disease phenotype was identified. AKT3 has previously been shown to regulate PPARG co-activator 1 alpha (PGC1α) localisation and function through its action on chromosome maintenance region 1 (CRM1). AKT3 promotes PGC1α localisation to the nucleus through its inhibitory effects on CRM1, a known nuclear export protein. https://www.selleckchem.com/products/dasa-58.html Collectively our results demonstrate how PPARG over-expression drives an increase in AKT3 levels, which in turn has the downstream effect of increasing PGC1α localisation within the nucleus, driving mitochondrial biogenesis. Furthermore, this increase in mitochondrial mass provides higher energetic output in the form of elevated ATP levels which may fuel the progression of the tumour cell through epithelial to mesenchymal transition (EMT) and ultimately metastasis.Since their discovery, microRNAs (miRNAs) have been widely studied in almost every aspect of biology and medicine, leading to the identification of important gene regulation circuits and cellular mechanisms. However, investigations are generally focused on the analysis of their downstream targets and biological functions in overexpression and knockdown approaches, while miRNAs endogenous levels and activity remain poorly understood. Here, we used the cellular plasticity-regulating process of epithelial-to-mesenchymal transition (EMT) as a model to show the efficacy of a fluorescent sensor to separate cells with distinct EMT signatures, based on miR-200b/c activity. The system was further combined with a CRISPR-Cas9 screening platform to unbiasedly identify miR-200b/c upstream regulating genes. The sensor allows to infer miRNAs fundamental biological properties, as profiling of sorted cells indicated miR-200b/c as a molecular switch between EMT differentiation and proliferation, and suggested a role for metabolic enzymes in miR-200/EMT regulation. Analysis of miRNAs endogenous levels and activity for in vitro and in vivo applications could lead to a better understanding of their biological role in physiology and disease.