Bone Marrow Mesenchymal Stem Cell Extracellular Vesicle-derived miR-27b- 3p activates the Wnt/Β-catenin Pathway by Targeting SMAD4 and Aggravates Hepatic Ischemia-reperfusion Injury.

BACKGROUND: To investigate the roles of extracellular vesicles (EVs) secreted from bone marrow mesenchymal stem cells (BMSCs) and miR-27 (highly expressed in BMSC EVs) in hepatic ischemia‒ reperfusion injury (HIRI). APPROACHES AND RESULTS: We constructed a HIRI mouse model and pretreated it with an injection of agomir-miR-27-3p, agomir-NC, BMSC-EVs or control normal PBS into the abdominal cavity. Compared with the HIRI group, HIRI mice preinjected with BMSC-EVs had significantly decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and alleviated liver necrosis (P<0.05). However, compared with HIRI+NC mice, HIRI+miR-27b mice had significantly increased ALT and AST levels, aggravated liver necrosis, and increased apoptosis-related protein expression (P<0.05). The proliferation and apoptosis of AML-12 cells transfected with miR-27 were significantly higher than the proliferation and apoptosis of AML-12 cells in the mimic NC group (P<0.01) after hypoxia induction. SMAD4 was proven to be a miR-27 target gene. Furthermore, compared to HIRI+NC mice, HIRI+miR-27 mice displayed extremely reduced SMAD4 expression and increased levels of wnt1, ß-catenin, c-Myc, and Cyclin D1. CONCLUSION: Our findings reveal the role and mechanism of miR-27 in HIRI and provide novel insights for the prevention and treatment of HIRI; for example, EVs derived from BMSCs transfected with antimiR- 27 might demonstrate better protection against HIRI.

BMSC-exosomes miR-25-3p Regulates the p53 Signaling Pathway Through PTEN to Inhibit Cell Apoptosis and Ameliorate Liver Ischemia‒reperfusion Injury.

BACKGROUND: Hepatic ischemia‒reperfusion injury (HIRI) is a pathological phenomenon during liver surgery, and bone marrow-mesenchymal stem cell (BMSC) exosomes (BMSC-Exos) regulate cell apoptosis and reduce ischemia‒reperfusion injury. We aimed to investigate the roles of BMSC-Exos and miR-25b-3p (enriched in BMSC-Exos) in HIRI and elucidate the underlying mechanisms. APPROACHES AND RESULTS: An HIRI mouse model was constructed and preinjected with BMSC-Exos, agomir-miR-25, agomir-miR-NC, or PBS via the tail vein. Compared with mice with HIRI, mice with HIRI preinjected with BMSC-Exos had significantly decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and alleviated liver necrosis (P < 0.05). Quantitative hepatic transcriptomics showed that mice with HIRI preinjected with BMSC-Exos exhibited increased cell division, hematopoietic or lymphoid organ development and metabolic processes. miRNA sequencing of BMSC-Exos revealed that miR-25, which is related to I/R injury, was enriched in the exosomes. Compared with HIRI + NC mice, HIRI + miR-25b-3p mice had significantly increased miR-25b-3p expression, decreased ALT/AST levels and apoptosis-related protein expression (P < 0.05), and alleviated liver necrosis. The proliferation of AML-12 cells transfected with miR-25b-3p was significantly higher than that in the mimic NC group (P < 0.01) after hypoxia induction, and the apoptosis rate of cells was significantly lower than that in the NC group (P < 0.01). PTEN was identified as a miR-25b-3p target gene. PTEN expression was significantly diminished in miR-25b-3p-transfected AML12 cells (P < 0.05). HIRI + agomir-miR-25 mice displayed reduced PTEN expression and decreased p53 and cleaved caspase 3 levels compared to HIRI + NC mice. CONCLUSIONS: We revealed the roles and underlying mechanisms of BMSC-Exos and miR-25 in HIRI, contributing to the prevention and treatment of HIRI.

Borophene Nanosheets as High-Efficiency Catalysts for the Hydrogen Evolution Reaction.

Borophene has been predicted to have outstanding catalytic activity owing to its extreme electron deficiency and abundant active sites. However, no experimental results have been still reported for borophene application in high-efficiency catalysis. Here, a borophene nanosheet was prepared on a carbon cloth surface via chemical vapor deposition. The boron source is sodium borohydride and the carrier gas is hydrogen gas. The crystal structure of the borophene nanosheet highly matches that of a theoretical α'-borophene nanosheet. Borophene shows good electrocatalytic hydrogen evolution reaction (HER) ability with a 69 mV/dec Tafel slope and good cycling stability in a 0.5 M H2SO4 solution. The enhanced performance is ascribed to an abundant electrocatalytic active area and low resistance of charge transfer, which results from its rich surface active sites. The improvement has been revealed by first-principles calculations, which is originated from their inherent metallicity and abundant electrocatalytic active sites on the nanosheets' surface. Borophene's extraordinarily high activity and stability give rise to extensive investigation of the application of borophene in high-efficiency energy applications such as catalysts and batteries.

van der Waals Epitaxial Growth of Borophene on a Mica Substrate toward a High-Performance Photodetector.

The emergence of borophene has triggered soaring interest in the investigation of its superior structural anisotropy, a novel photoelectronic property for diverse potential applications. However, the structural instability and need of a metal substrate for depositing borophene restrict its large-scale applications toward high-performance electronic and optoelectric devices. van der Waals epitaxy is regarded as an efficient technique for growing superb two-dimensional materials onto extensive functional substrates, but the preparation of stable and controllable borophene on nonmetallic substrates is still not reported. Here, we demonstrate that borophene films can be synthesized onto a mica substrate by van der Waals epitaxy, where hydrogen and NaBH4 are respectively used as the carrier gas and the boron source. The lattice structure of the as-synthesized borophene coincides with the predicted α'-boron sheet. The borophene-based photodetector shows an excellent photoresponsivity of 1.04 A W-1 and a specific detectivity of 1.27 × 1011 Jones at a reversed bias of 4 V under illumination of a 625 nm light-emitting diode, which are remarkably superior to those of reported boron nanosheets. This work facilitates further studies of borophene toward its attractive properties and applications in novel optoelectronic devices and integrated circuits.

Integrated transcriptomic and metabolomic analyses of a wax deficient citrus mutant exhibiting jasmonic acid-mediated defense against fungal pathogens.

Naturally, resistant crop germplasms are important resources for managing the issues of agricultural product safety and environment deterioration. We found a spontaneous mutant of 'Newhall' navel orange (Citrus sinensis Osbeck) (MT) with broad-spectrum protections against fungal pathogens in the orchard, postharvest-storage, and artificial inoculation conditions. To understand the defense mechanism of MT fruit, we constructed a genome-scale metabolic network that integrated metabolome and transcriptome datasets. The coordinated transcriptomic and metabolic data were enriched in two sub-networks, showing the decrease in very long chain fatty acid (by 41.53%) and cuticular wax synthesis (by 81.34%), and increase in the synthesis of jasmonic acid (JA) (by 95.23%) and JA-induced metabolites such as 5-dimethylnobietin (by 28.37%) in MT. Furthermore, cytological and biochemical analyses confirmed that the response to fungal infection in MT was independent of wax deficiency and was correlated with the levels of jasmonates, and the expression of plant defensin gene PDF1.2. Results of exogenous application of MeJA and JA inhibitors such as propyl gallate proved that JA-mediated defense contributes to the strong tolerance against pathogens in MT. Our results indicated that jasmonate biosynthesis and signaling are stimulated by the fatty acid redirection of MT, and participate in the tolerance of pathogenic fungi.

Sig2GRN: a software tool linking signaling pathway with gene regulatory network for dynamic simulation.

BACKGROUND: Linking computational models of signaling pathways to predicted cellular responses such as gene expression regulation is a major challenge in computational systems biology. In this work, we present Sig2GRN, a Cytoscape plugin that is able to simulate time-course gene expression data given the user-defined external stimuli to the signaling pathways. METHODS: A generalized logical model is used in modeling the upstream signaling pathways. Then a Boolean model and a thermodynamics-based model are employed to predict the downstream changes in gene expression based on the simulated dynamics of transcription factors in signaling pathways. RESULTS: Our empirical case studies show that the simulation of Sig2GRN can predict changes in gene expression patterns induced by DNA damage signals and drug treatments. CONCLUSIONS: As a software tool for modeling cellular dynamics, Sig2GRN can facilitate studies in systems biology by hypotheses generation and wet-lab experimental design. AVAILABILITY: http://histone.scse.ntu.edu.sg/Sig2GRN/.

Comparative analysis of surface wax in mature fruits between Satsuma mandarin (Citrus unshiu) and 'Newhall' navel orange (Citrus sinensis) from the perspective of crystal morphology, chemical composition and key gene expression.

Surface wax of mature Satsuma mandarin (Citrus unshiu) and 'Newhall' navel orange (Citrus sinensis) was analysed by crystal morphology, chemical composition, and gene expression levels. The epicuticular and total waxes of both citrus cultivars were mostly composed of aldehydes, alkanes, fatty acids and primary alcohols. The epicuticular wax accounted for 80% of the total wax in the Newhall fruits and was higher than that in the Satsuma fruits. Scanning electron microscopy showed that larger and more wax platelets were deposited on the surface of Newhall fruits than on the Satsuma fruits. Moreover, the expression levels of genes involved in the wax formation were consistent with the biochemical and crystal morphological analyses. These diversities of fruit wax between the two cultivars may contribute to the differences of fruit postharvest storage properties, which can provide important information for the production of synthetic wax for citrus fruits.