The dynamic cell–cell communication is essential for tissue homeostasis in normal physiological circumstances and contributes to a diversified tumor microenvironment. Although exosomes are ...extracellular vesicles that actively participate in cell–cell interaction by shutting cellular components, impacts of tumor exosomes in the context of cancer stemness remain elusive. Here, we expand colorectal cancer stem cells (CRCSCs) as cancer spheroids and demonstrate that the β‐catenin/Tcf‐4‐activated RAB27B expression is required for the secretion of CRCSC exosomes. In an exosomal RNA sequencing analysis, a switch of exosomal RNA species from retrotransposons to microRNAs (miRNAs) is identified upon expanding CRCSCs. miRNA‐146a‐5p (miR‐146a) is the major miRNA in CRCSC exosomes and exosomal miR‐146a promotes stem‐like properties and tumorigenicity by targeting Numb in recipient CRC cells. Among 53 CRC patients, those with abundant exosomal miR‐146a expression in serum exhibits higher miR‐146aHigh/NumbLow CRCSC traits, an increased number of tumor‐filtrating CD66(+) neutrophils and a decreased number of tumor‐infiltrating CD8(+) T cells. Our study elucidates a unique mechanism of tumor exosome‐mediated stemness expansion.
What's new?
The tumor microenvironment (TME) is composed of heterogeneous tumor cells and host cells interacting with each other to promote disease progression. However, diagnostic and prognostic biomarkers to monitor the cancer stem cells (CSCs)‐host interplay are lacking. Here, the authors explore the role of tumor exosomes in cancer stemness and demonstrate that RAB27B‐assisted secretion of miRNA‐dominant exosomes is one critical feature of CSCs. Importantly, they show that colorectal cancer stem cells release miR‐146a‐loaded oncogenic exosomes for reprogramming non‐CSC cells and demonstrate the clinical relevance of exosomal miR‐146a in predicting the TME of CRC patients.
Sweet potato (
) is one of the most important food crops worldwide and its leaves provide a dietary source of nutrients and various bioactive compounds. These constituents of sweet potato leaves ...(SPL) vary among varieties and play important roles in treating and preventing various diseases. Recently, more attentions in health-promoting benefits have led to several in vitro and in vivo investigations, as well as the identification and quantification of bioactive compounds in SPL. Among them, many new compounds have been reported as the first identified compounds from SPL with their dominant bioactivities. This review summarizes the current knowledge of the bioactive compositions of SPL and their health benefits. Since SPL serve as a potential source of micronutrients and functional compounds, they can be further developed as a sustainable crop for food and medicinal industries.
Metagenomics, the application of shotgun sequencing, facilitates the reconstruction of the genomes of individual species from natural environments. A major challenge in the genome recovery domain is ...to agglomerate or 'bin' sequences assembled from metagenomic reads into individual groups. Metagenomic binning without consideration of reference sequences enables the comprehensive discovery of new microbial organisms and aids in the microbial genome reconstruction process. Here we present MyCC, an automated binning tool that combines genomic signatures, marker genes and optional contig coverages within one or multiple samples, in order to visualize the metagenomes and to identify the reconstructed genomic fragments. We demonstrate the superior performance of MyCC compared to other binning tools including CONCOCT, GroopM, MaxBin and MetaBAT on both synthetic and real human gut communities with a small sample size (one to 11 samples), as well as on a large metagenome dataset (over 250 samples). Moreover, we demonstrate the visualization of metagenomes in MyCC to aid in the reconstruction of genomes from distinct bins. MyCC is freely available at http://sourceforge.net/projects/sb2nhri/files/MyCC/.
MicroRNAs (miRNAs) are small noncoding RNAs which post-transcriptionally regulate gene expression by directing mRNA cleavage or translational inhibition. miRNAs play multiple roles in the growth, ...development and stress responses in plants. However, little is known of the wounding-responsive miRNAs and their regulation.
Here, we investigated the expression patterns of microR828 (miR828) on wounding in sweet potato (Ipomoea batatas cv Tainung 57). The expression of miR828 was only detected in leaves, and was induced by wounding rather than by ethylene, hydrogen peroxide (H2O2), methyl jasmonate or nitric oxide (NO). Moreover, cyclic guanosine monophosphate (cGMP) was necessary for miR828 accumulation in leaves on wounding.
Two miR828 target candidates, named IbMYB and IbTLD, were obtained by cDNA cloning, and their mRNA cleavage caused by miR828 was confirmed by cleavage site mapping, agro-infiltration and transgenics studies. The reduction in IbMYB and IbTLD expression coincided with the induction of miR828, demonstrating thatIbMYB and IbTLD might be miR828 targets. Furthermore, transgenic sweet potato overexpressing miR828 precursor affected lignin and H2O2 contents.
These results showed that cGMP could regulate wounding-responsive miR828, which repressed the expression of IbMYB and IbTLD. Subsequently, lignin and H2O2 were accumulated to participate in defense mechanisms.
Fluorescent nanodiamond (FND) is attracting much attention as a bioimaging agent because of its inherent biocompatibility and superior optical properties (e.g., excellent photostability and far‐red ...emission). However, for practical use in life science research, some issues such as higher brightness and ease of bioconjugation have to be solved. Here, it is shown that the 100‐nm FND particles fabricated by using nitrogen‐rich type Ib diamonds and high‐energy proton irradiation are highly fluorescent and readily functionalizable with proteins for biological applications. In the first approach, acid‐treated FND is noncovalently coated with glycoproteins or neoglycoproteins (i.e., proteins chemically modified with multiple sugar residues) for targeting hepatocytes via carbohydrate receptors. In the second approach, FND is first PEGylated and then covalently conjugated with streptavidin, to which biotin‐labeled antibodies of interest are linked. High targeting specificity of the bioconjugated FND is demonstrated with the human hepatoma cell line, HepG2, and breast cancer cell lines, ASB145‐1R, MCF‐7, and MDA‐MB‐231 cells. These approaches should be widely applicable to a variety of situations for specific targeting and labeling of cells.
Strategies are developed to functionalize fluorescent nanodiamond (FND) with proteins of various types for biological applications. In the first approach, ligand‐based targeting, FND is noncovalently coated with (neo)glycoproteins to target hepatocytes via their carbohydrate‐specific receptors. In the second approach, antibody‐based targeting, FND is conjugated with antibodies for high specific targeting of antigens on human breast cancer cell surfaces. These two approaches are expected to be widely applicable for specific targeting and labeling of live cells.
Summary
Viruses cause severe damage on crops, and identification of key gene(s) that can comprehensively activate antiviral immunity will provide insights for designing effective antiviral ...strategies. Salicylic acid (SA)‐mediated antiviral immunity and RNA interference (RNAi) are two independently discovered antiviral pathways. Previously, we identified the orchid stress‐associated protein (SAP), Pha13, which serves as a hub in SA‐mediated antiviral immunity. As SAPs exist as a protein family, whether duplicated SAPs have redundant or distinctive functions in antiviral immunity remains elusive.
We performed functional assays on orchid Pha21, a homolog of Pha13, using transient and transgenic approaches on orchid, Arabidopsis and Nicotiana benthamiana to overexpress and/or silence Pha21.
The SA treatment induced the expression of both Pha13 and Pha21, whereas Pha21 was found to play a key role in the initiation of the RNAi pathway in Phalaenopsis orchids. We demonstrated that Pha21‐mediated antiviral immunity and enhancement of the RNAi pathway is conserved between dicotyledons and monocotyledons.
We provide new insight that orchid SAPs confer distinctive functions to coordinate both SA‐signaling and RNAi for comprehensive activation of antiviral immunity, and this information will help us develop antiviral strategies on crops.
Mutations in genes involved in the production, migration, or differentiation of cortical neurons often lead to malformations of cortical development (MCDs). However, many genetic mutations involved ...in MCD pathogenesis remain unidentified. Here we developed a genetic screening paradigm based on transposon-mediated somatic mutagenesis by in utero electroporation and the inability of mutant neuronal precursors to migrate to the cortex and identified 33 candidate MCD genes. Consistent with the screen, several genes have already been implicated in neural development and disorders. Functional disruption of the candidate genes by RNAi or CRISPR/Cas9 causes altered neuronal distributions that resemble human cortical dysplasia. To verify potential clinical relevance of these candidate genes, we analyzed somatic mutations in brain tissue from patients with focal cortical dysplasia and found that mutations are enriched in these candidate genes. These results demonstrate that this approach is able to identify potential mouse genes involved in cortical development and MCD pathogenesis.
Since its discovery nearly a century ago, antibiotics has been one of the most effective methods in treating infectious diseases and limiting pathogen spread. However, pathogens often build up ...antibiotic resistance over time, leading to serious failure of the treatment. Silver nanoparticle (AgNP) is an appealing alternative, but successful treatment of the bacterial infection requires a plentiful supply of AgNP, which can negatively impact human health if people are excessively exposed to the particles. Here, we present a method to overcome this challenge by synthesizing nanodiamond-supported AgNP noncovalently conjugated with albumin molecules to achieve enhanced antibacterial activity and strengthened biocompatibility. Using Escherichia coli as a model bacterium, we found that the albumin-conjugated silver-diamond nanohybrids showed a long-term bactericidal effect after 36 days of the treatment at the AgNP concentration of 250 µg mL
. Moreover, the toxicity of the nanohybrids to human cells (including human fibroblasts, lung adenocarcinoma epithelial cells, and breast adenocarcinoma cells) is low even at the particle concentration of 500 µg mL
. The method provides a general and practical solution to the concerns of bacterial resistance against AgNP and issues associated with the size, shape, aggregation, and toxicity of AgNP are largely resolved. Finally, we demonstrate that the nanohybrids can be readily incorporated into natural polysaccharides (such as guar gum) to form three-in-one hydrogels, showing promising applications in nanomedicine.
During the color design process, it is critical to create diversified color schemes for various consumer groups. It is also important to allow members in a design team to brainstorm for creative ...ideas. A theory of inspecting natural color elements was proposed in this study based on the CIE 1976 (L*,a*,b*) (CIE 1976) color space and the fuzzy c‐means clustering method. A calculation model was built to determine people's preference for colors based on a serialized system. To determine which factors affect the prediction of consumers' preference for a series of products, a gray relational color preference system was used in combination with gray relational grade so that a designer can obtain reasonable prediction results. The proposed system recommends not only the optimal colors for a product but also the optimal color scheme for a series of products.
Network is a useful way for presenting many types of biological data including protein-protein interactions, gene regulations, cellular pathways, and signal transductions. We can measure nodes by ...their network features to infer their importance in the network, and it can help us identify central elements of biological networks.
We introduce a novel Cytoscape plugin cytoHubba for ranking nodes in a network by their network features. CytoHubba provides 11 topological analysis methods including Degree, Edge Percolated Component, Maximum Neighborhood Component, Density of Maximum Neighborhood Component, Maximal Clique Centrality and six centralities (Bottleneck, EcCentricity, Closeness, Radiality, Betweenness, and Stress) based on shortest paths. Among the eleven methods, the new proposed method, MCC, has a better performance on the precision of predicting essential proteins from the yeast PPI network.
CytoHubba provide a user-friendly interface to explore important nodes in biological networks. It computes all eleven methods in one stop shopping way. Besides, researchers are able to combine cytoHubba with and other plugins into a novel analysis scheme. The network and sub-networks caught by this topological analysis strategy will lead to new insights on essential regulatory networks and protein drug targets for experimental biologists. According to cytoscape plugin download statistics, the accumulated number of cytoHubba is around 6,700 times since 2010.
PDF
