Reprogrammed glucose metabolism as a result of increased glycolysis and glucose uptake is a hallmark of cancer. Here we show that cancer cells can suppress glucose uptake by non-tumour cells in the pre-metastatic niche, by secreting vesicles that carry high levels of the miR-122 microRNA. High miR-122 levels in the circulation have been associated with metastasis in breast cancer patients and we show that cancer-cell-secreted miR-122 facilitates metastasis by increasing nutrient availability in the pre-metastatic niche. Mechanistically cancer-cell-derived miR-122 suppresses glucose uptake by niche cells in vitro and in vivo by downregulating the glycolytic enzyme pyruvate kinase (PKM). In vivo inhibition of miR-122 restores glucose uptake in distant organs, including brain and lungs, and decreases the incidence of metastasis. These results demonstrate that by modifying glucose utilization by recipient pre-metastatic niche cells, cancer-derived extracellular miR-122 is able to reprogram systemic energy metabolism to facilitate disease progression.

Induction of type I interferons by the bacterial secondary messengers cyclic-di-GMP (c-di-GMP) or cyclic-di-AMP (c-di-AMP) is dependent on a signaling axis involving the STING adaptor, TBK1 kinase and IRF3 transcription factor. Here we identified the helicase DEAD box polypeptide 41 (DDX41) as a pattern recognition receptor (PRR) that sensed both c-di-GMP and c-di-AMP. DDX41 specifically and directly interacted with c-di-GMP. Knockdown of DDX41 via shRNA in murine or human cells inhibited the induction of innate immune genes and resulted in defective STING, TBK1 and IRF3 activation in response to c-di-GMP or c-di-AMP. These results suggest a mechanism whereby c-di-GMP and c-di-AMP are detected by the DDX41 PRR, which complexes with STING to signal to TBK1-IRF3 and activate the interferon response.

Fluorescence-based detection is the most common method utilized in biosensing because of its high sensitivity, simplicity, and diversity. In the era of nanotechnology, nanomaterials are starting to replace traditional organic dyes as detection labels because they offer superior optical properties, such as brighter fluorescence, wider selections of excitation and emission wavelengths, higher photostability, etc. Their size-or shape-controllable optical characteristics also facilitate the selection of diverse probes for higher assay throughput. Furthermore, the nanostructure can provide a solid support for sensing assays with multiple probe molecules attached to each nanostructure, simplifying assay design and increasing the labeling ratio for higher sensitivity. The current review summarizes the applications of nanomaterialsincluding quantum dots, metal nanoparticles, and silica nanoparticles-in biosensing using detection techniques such as fluorescence, fluorescence resonance energy transfer (FRET), fluorescence lifetime measurement, and multiphoton microscopy. The advantages nanomaterials bring to the field of biosensing are discussed. The review also points out the importance of analytical separations in the preparation of nanomaterials with fine optical and physical properties for biosensing. In conclusion, nanotechnology provides a great opportunity to analytical chemists to develop better sensing strategies, but also relies on modern analytical techniques to pave its way to practical applications.Keywords Nanomaterials . Quantum dots . Gold nanoparticle . Silica nanoparticle . Fluorescence . FRET . Biosensing OverviewSensitive detection of target analytes present at trace levels in biological samples often requires the labeling of reporter molecules with fluorescent dyes, because fluorescence detection is by far the dominant detection method in the field of sensing technology, due to its simplicity, the convenience of transducing the optical signal, the availability of organic dyes with diverse spectral properties, and the rapid advances made in optical imaging. However, it can be difficult to obtain a low detection limit in fluorescence detection due to the limited extinction coefficients or quantum yields of organic dyes and the low dye-toreporter molecule labeling ratio. The recent explosion of nanotechnology, leading to the development of materials with submicron-sized dimensions and unique optical properties, has opened up new horizons for fluorescence detection. Nanomaterials can be made from both inorganic and organic materials and are less than 100 nm in length

Mesoporous oxides have been used for selective separation and adsorption of biomolecules. [1][2][3][4][5][6][7][8][9][10][11] Inorganic oxide materials such as silica can be synthesized into highly ordered mesoporous structures featuring high in-pore surface areas, narrow pore size distributions, adjustable pore sizes, and modifiable surface properties. [10,[12][13][14][15] Such unique properties favor the selective enrichment of proteins or peptides based on the size-exclusion mechanism. Classic mesoporous silica structures with narrow pore size distributions, such as MCM-41 and SBA-15, have been used to selectively enrich peptides from human plasma and exclude other proteins according to an accurate molecular weight (MW) cutoff. [2][3][4][5][6][7][8][9] However, this type of enrichment method is limited mainly to silica and alumina because currently it is still difficult to extend broadly the surfactant-templating method to the synthesis of mesoporous structures of many other oxides in a convenient, controllable, and scalable manner (although the literature does contain some relevant procedures [16][17][18] ). The limited choice of materials makes it difficult to further enhance the selectivity by taking advantage of both the size-exclusion effect and the specific binding between many oxides and proteins or peptides.Herein, we propose a general strategy for the fabrication of novel porous nanostructured materials for the efficient separation of biomolecules such as proteins, peptides, and DNA. Briefly, nanoparticles of various nanostructured materials with uniform sizes and shapes are firstly synthesized and then self-assembled into three-dimensional submicrometer clusters containing uniform mesoscale pores. Thanks to rapid progress in colloidal nanostructure synthesis, a great number of materials can now be routinely produced in the form of nanoparticles with excellent control over size, shape, and surface properties, [19][20][21][22] making it possible to utilize specific material-protein/peptide interactions to enhance the selectivity in protein/peptide enrichment. [23,24] Additionally, size exclusion can also be achieved by controlling the dimensions of the pores produced by the packing of constituent nanoparticles, [25,26] allowing selective enrichment of biomolecules based on their sizes. The outer surface of each cluster can be made highly hydrophilic, so that nonspecific binding of many hydrophobic proteins/peptides can be avoided. The selfassembly process also brings the convenience of incorporation of multiple components into the clusters to further facilitate separation and detection. For example, the incorporation of fluorescent nanocrystals, such as quantum dots, during the assembly process may produce multifunctional microspheres that are able not only to selectively enrich but also to easily identify the targeted biomolecules. Also, adding superparamagnetic iron oxide nanocrystals to the clusters allows their efficient removal from the analyte solution after selective adsorption by using an exter...

Extracellular vesicles (EVs) actively participate in intercellular communication and pathological processes. Studying the molecular signatures of EVs is the key to reveal their biological functions and clinical values, which, however, is greatly hindered by their sub-100-nm dimensions, the low quantities of biomolecules each EV carries, and the large population heterogeneity. Here, we report the single-EV Flow Cytometry Analysis technique that realizes single EV counting and phenotyping in a conventional flow cytometer for the first time, enabled by Target-Initiated Engineering (TIE) of DNA nanostructures on each EV. By illuminating multiple markers on single EVs, we reveal statistically significant differences among the molecular signatures of EVs originated from several breast cancer cell lines, and successfully recognize the cancer cell-derived EVs among the heterogeneous EV populations. Thus, our approach holds great potential for various biological and biomedical applications.