Mesenchymal stem cells (MSCs) are an attractive cell source for tissue regeneration and repair. However, their low differentiation efficacy currently impedes the development of MSC therapy. Therefore, in this study, we investigated the effects of differentiation-inducing factor-1 (DIF-1) on the differentiation efficacy of bone marrow-derived MSCs (BM-MSCs) into adipogenic or osteogenic lineages. BM-MSCs, which were obtained from Sprague-Dawley rats, were positive for the MSC markers (CD29, CD73, and CD90). DIF-1 alone neither affected cell surface antigen expression nor induced adipogenic or osteogenic differentiation. However, DIF-1 significantly enhanced the effects of adipogenic differentiation stimuli, which were evaluated as the number of oil red-O positive cells and the expression of adipocyte differentiation markers (peroxisome proliferator-activated receptor gamma, adipocyte fatty acid-binding protein, and adiponectin). In contrast, DIF-1 significantly attenuated the effects of osteogenic differentiation stimuli, which were evaluated as alizarin red-S positive calcium deposition, and the expression of osteoblast differentiation markers alkaline phosphatase, runt-related transcription factor 2, and osteopontin. We further investigated the mechanism by which DIF-1 affects MSC differentiation efficacy and found that glycogen synthase kinase-3 was the main factor mediating the action of DIF-1 on the adipogenic differentiation of BM-MSCs, whereas it was only partially involved in osteogenic differentiation. These results suggest that DIF-1 supports MSC differentiation toward the desired cell fate by enhancing the differentiation efficacy.Positioned at the axis between the cell and its environment, mTOR directs a wide range of cellular activity in response to nutrients, growth factors, and stress. Our understanding of the role of mTOR is evolving beyond the spatial confines of the cytosol, and its role in the nucleus becoming ever more apparent. In this review, we will address various studies that explore the role of nuclear mTOR (nmTOR) in specific cellular programs and how these pathways influence one another. To understand the emerging roles of nuclear mTOR, we discuss data and propose plausible mechanisms to offer novel ideas, hypotheses, and future research directions.While humans have developed a sophisticated and unique system of verbal auditory communication, they also share a more common and evolutionarily important nonverbal channel of voice signaling with many other mammalian and vertebrate species. This nonverbal communication is mediated and modulated by the acoustic properties of a voice signal, and is a powerful – yet often neglected – means of sending and perceiving socially relevant information. From the viewpoint of dyadic (involving a sender and a signal receiver) voice signal communication, we discuss the integrated neural dynamics in primate nonverbal voice signal production and perception. Most previous neurobiological models of voice communication modelled these neural dynamics from the limited perspective of either voice production or perception, largely disregarding the neural and cognitive commonalities of both functions. Taking a dyadic perspective on nonverbal communication, however, it turns out that the neural systems for voice production and perception are surprisingly similar. Based on the interdependence of both production and perception functions in communication, we first propose a re-grouping of the neural mechanisms of communication into auditory, limbic, and paramotor systems, with special consideration for a subsidiary basal-ganglia-centered system. Second, we propose that the similarity in the neural systems involved in voice signal production and perception is the result of the co-evolution of nonverbal voice production and perception systems promoted by their strong interdependence in dyadic interactions.The human brain is a complex, adaptive system comprised of billions of cells with trillions of connections. The interactions between the elements of the system oppose this seemingly limitless capacity by constraining the system’s dynamic repertoire, enforcing distributed neural states that balance integration and differentiation. How this trade-off is mediated by the brain, and how the emergent, distributed neural patterns give rise to cognition and awareness, remains poorly understood. Here, I argue that the thalamus is well-placed to arbitrate the interactions between distributed neural assemblies in the cerebral cortex. Different classes of thalamocortical connections are hypothesized to promote either feed-forward or feedback processing modes in the cerebral cortex. This activity can be conceptualized as emerging dynamically from an evolving attractor landscape, with the relative engagement of distinct distributed circuits providing differing constraints over the manner in which brain state trajectories change over time. In addition, inputs to the distinct thalamic populations from the cerebellum and basal ganglia, respectively, are proposed to differentially shape the attractor landscape, and hence, the temporal evolution of cortical assemblies. The coordinated engagement of these neural macrosystems is then shown to share key characteristics with prominent models of cognition, attention and conscious awareness. In this way, the crucial role of the thalamus in mediating the distributed, multi-scale network organization of the central nervous system can be related to higher brain function.The extremely high proliferation rate of tumor cells contributes to pancreatic cancer (PC) progression. Runt-related transcription factor 1(RUNX1), a key factor in hematopoiesis that was correlated with tumor progression. However, the role of RUNX1 in PC proliferation was still unclear. We found that RUNX1 was significantly upregulated in PC tissues and its expression was negatively associated with prognosis of PC patients in a multicenter analysis according to immunohistochemical (IHC). RUNX1 downregulation in PC resulted in a significantly reduced cell proliferation rate, which was consistent with in vivo subcutaneous tumor formation assay results. RNA-seq and ChIP-seq results revealed that a portion of target genes, including HAP1, GPRC5B, PTPN21, VHL and EN2, were regulated by RUNX1, a finding successfully validated by ChIP-qPCR, qRT-PCR and Western blot. Subsequently, IHC and proliferation assays showed these target genes to be dysregulated in PC, affecting tumor growth. Our data suggest that RUNX1 plays an oncogenic role in tumor proliferation and is a potential prognostic biomarker and therapeutic target for PC.Type I and type II keratins are subgroups of intermediate filament proteins that provide toughness to the epidermis and protect it from water loss. In terrestrial vertebrates, the keratin genes form two major clusters, clusters 1 and 2, each of which is dominated by type I and II keratin genes. By contrast, such clusters are not observed in teleost fish. Although the diversification of keratins is believed to have made a substantial contribution to terrestrial adaptation, its evolutionary process has not been clarified. Here, we performed a comprehensive genomic survey of the keratin genes of a broad range of vertebrates. As a result, we found that ancient fish lineages such as elephant shark, reedfish, spotted gar, and coelacanth share both keratin gene clusters. We also discovered an expansion of keratin genes that form a novel subcluster in reedfish. Syntenic and phylogenetic analyses revealed that two pairs of krt18/krt8 keratin genes were shared among all vertebrates, thus implying that they encode ancestral type I and II keratin protein sets. We further revealed that distinct keratin gene subclusters, which show specific expressions in the epidermis of adult amphibians, stemmed from canonical keratin genes in non-terrestrial ancestors. Molecular evolutionary analyses suggested that the selective constraints were relaxed in the adult epidermal subclusters of amphibians as well as the novel subcluster of reedfish. The results of the present study represent the process of diversification of keratins through a series of gene duplications that could have facilitated the terrestrial adaptation of vertebrates.Deregulation of protein synthesis may be involved in multiple aspects of cancer, such as gene expression, signal transduction and drive specific cell biological responses, resulting in promoting cancer growth, invasion and metastasis. Study the molecular mechanisms about translational control may help us to find more effective anti-cancer drugs and develop novel therapeutic opportunities. Recently, the researchers had focused on targeting translational machinery to overcome cancer, and various small molecular inhibitors targeting translation factors or pathways have been tested in clinical trials and exhibited improving outcomes in several cancer types. There is no doubt that an insight into the class of translation regulation protein would provide new target for pharmacologic intervention and further provide opportunities to develop novel anti-tumor therapeutic interventions. In this review, we summarized the developments of translational control in cancer survival and progression et al, and highlighted the therapeutic approach targeted translation regulation to overcome the cancer.Bone morphogenetic protein 1 (BMP1) is a secreted metalloprotease of the astacin M12A family of bone morphogenetic proteins (BMPs). BMP1 activates transforming growth factor-β (TGF-β) and BMP signaling pathways by proteolytic cleavage, which has dual roles in gastrointestinal tumor development and progression.TGF-β promotes invasion and metastasis of gastric cancer (GC) by the help of BMP1, so upregulation of the BMP1 may increase cancer invasiveness in GC. In this study,the transcriptional expression, mutations, survival rate, TFs, miRNAs, gene ontology, and signaling pathways of BMP1 were analyzed by using different web servers. We found higher transcriptional and clinicopathological characteristics expression compared to normal tissues, worsening survival rate in GC. We detected 25 missenses, 15 truncating mutations, 23 TFs, and 8 miRNAs. Finally, we identified and analyzed the co-expressed genes and found that the leukemia inhibitory factor is the most positively correlated gene. The gene ontological features and signaling pathways involved in GC development were evaluated as well. We believe that this study will provide a basis for BMP1 to be a significant biomarker for human GC prognosis.COVID-19 pandemic caused by SARS-CoV-2 has already claimed millions of lives worldwide due to the absence of a suitable anti-viral therapy. The CoV envelope (E) protein, which has not received much attention so far, is a 75 amino acid long integral membrane protein involved in assembly and release of the virus inside the host. Here we have used artificial intelligence (AI) and pattern recognition techniques for initial screening of FDA approved pharmaceuticals and nutraceuticals to target this E protein. Subsequently, molecular docking simulations have been performed between the ligands and target protein to screen a set of 9 ligand molecules. Finally, we have provided detailed insight into their mechanisms of action related to the varied symptoms of infected patients.