Background Accumulating evidence shows that microRNA-210 (miR-210) holds great promise to improve angiogenesis for brain tissue repair after cerebral ischemia. However, safe and efficient delivery of miR-210 via intravenous administration is still a challenge. In the past decade, exosomes have emerged as a novel endogenous delivery system. Here, c(RGDyK) peptide is conjugated to exosomes, and they are loaded with cholesterol-modified miR-210 (RGD-exo:miR-210). Results In a transient middle cerebral artery occlusion (MCAO) mouse model, the RGD-exo:miR-210 targets the lesion region of the ischemic brain after intravenous administration, resulting in an increase in miR-210 at the site. Furthermore, RGD-exo:miR-210 are administered once every other day for 14 days, and the expressions of integrin β 3 , vascular endothelial growth factor (VEGF) and CD34 are significantly upregulated. The animal survival rate is also enhanced. Conclusions These results suggest a strategy for the targeted delivery of miR-210 to ischemic brain and provide an angiogenic agent for the treatment of ischemic stroke. Electronic supplementary material The online version of this article (10.1186/s12951-019-0461-7) contains supplementary material, which is available to authorized users.

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Traditional microbiology analysis is usually hindered by the long time-cost and lack of portability in many urgent situations. In this work, we developed a novel electrochemical DNA biosensor (E-biosensor) for sensitive analysis of the 16S rRNA gene of five bacteria, using a consecutive adenine (polyA) probe. The polyA probe consists of a polyA tail and a recognition part. The polyA tail can combine onto the gold surface with improved controllability of the surface density, by conveniently changing the length of polyA. The recognition part of the capture probe together with two biotin-labeled reporter probes hybridize with the target DNA and form a stable DNA-tetramer sandwich structure, and then avidin-HRP enzyme was added to produce a redox current signal for the following electrochemical detection. Finally, we realized sensitive quantification of artificial target DNA with a limit of detection (LOD) of 10 fM, and excellent selectivity and reusability were also demonstrated. Importantly, the detection capability was equally good when facing bacterial genomic DNA, due to the base-stacking force of our multireporter-probe system, which can help to break the second structure and stabilize the probe-target complexes. Our biosensor was constructed on a 16-channel electrode chip without any polymerase chain reaction (PCR) process needed, which took a significant step toward a portable bacteria biosensor.

Isolation of leaf-color mutants is important in understanding the mechanisms of chloroplast biogenesis and development. In this study, we identified and characterized a rice (Oryza sativa) mutant, yellow leaf 2 (yl2), exhibiting pale yellow leaves with a few longitudinal white stripes at the early seedling stage then gradually turning yellow. Genetic analyses revealed that YL2 encodes a thylakoid membrane-localized protein with significant sequence similarity to UMP kinase proteins in prokaryotes and eukaryotes. Prokaryotic UMP kinase activity was subsequently confirmed, with YL2 deficiency causing a significant reduction in chlorophyll accumulation and photochemical efficiency. Moreover, YL2 is also light dependent and preferentially expressed in green tissues. Chloroplast development was abnormal in the yl2 mutant, possibly due to reduced accumulation of thylakoid membranes and a lack of normal stroma lamellae. 2D Blue-Native SDS-PAGE and immunoblot analyses revealed a reduction in several subunits of photosynthetic complexes, in particular, the AtpB subunit of ATP synthase, while mRNA levels of corresponding genes were unchanged or increased compared with the wild type. In addition, we observed a significant decrease (ca. 36.3%) in cpATPase activity in the yl2 mutant compared with the wild type. Taken together, our results suggest that UMP kinase activity plays an essential role in chloroplast development and regulating cpATPase biogenesis in rice.Electronic supplementary materialThe online version of this article (10.1007/s11120-017-0477-5) contains supplementary material, which is available to authorized users.

Glucocorticoid (GC) therapy is the leading cause of secondary osteoporosis and the therapeutic and preventative drugs for GC-induced osteoporosis are limited. In this study, we investigated the protective effects of geniposide on dexamethasone (DEX)-induced osteogenic inhibition in MC3T3-E1 cells. The results showed that there was no obvious toxicity on MC3T3-E1 cells when geniposide was used at the doses ranging from 1 to 75 μM. In DEX-treated MC3T3-E1 cells, geniposide promoted the alkaline phosphatase (ALP) activity and the mineralization. In addition, geniposide also significantly increased the mRNA and protein expression of osteopontin (OPN), Runt-related transcription factor 2 (Runx2), and Osterix (Osx) in DEX-treated MC3T3-E1 cells. Furthermore, geniposide activated ERK pathway in DEX-treated MC3T3-E1 cells. The ERK activation inhibitor U0126 and glucagon-like peptide-1 (GLP-1) receptor antagonist exendin 9-39 abolished the geniposide-induced activation of ERK and inhibited the protective effect of geniposide. Taken together, our study revealed that geniposide alleviated GC-induced osteogenic suppression in MC3T3-E1 cells. The effect of geniposide was at least partially associated with activating ERK signaling pathway via GLP-1 receptor. Geniposide might be a potential therapeutic agent for GC-induced osteoporosis.