In elderly people particularly in postmenopausal women, inadequate bone formation by osteoblasts originating from bone marrow mesenchymal stem cells (BMSCs) for compensation of bone resorption by ...osteoclasts is a major reason for osteoporosis. Enhancing osteoblastic differentiation of BMSCs is a feasible therapeutic strategy for osteoporosis. Here, bone marrow stromal cell (ST)-derived exosomes (STExos) are found to remarkably enhance osteoblastic differentiation of BMSCs in vitro. However, intravenous injection of STExos is inefficient in ameliorating osteoporotic phenotypes in an ovariectomy (OVX)-induced postmenopausal osteoporosis mouse model, which may be because STExos are predominantly accumulated in the liver and lungs, but not in bone. Hereby, the STExo surface is conjugated with a BMSC-specific aptamer, which delivers STExos into BMSCs within bone marrow. Intravenous injection of the STExo-Aptamer complex enhances bone mass in OVX mice and accelerates bone healing in a femur fracture mouse model. These results demonstrate the efficiency of BMSC-specific aptamer-functionalized STExos in targeting bone to promote bone regeneration, providing a novel promising approach for the treatment of osteoporosis and fracture.
MicroRNAs (miRNAs) are small non-coding RNAs that regulate important physiological processes, and their dysregulation is associated with various human diseases. Simultaneous sensitive detection of ...multiple miRNAs may facilitate early clinical diagnosis. In this research, we demonstrate for the first time the integration of hyperbranched rolling circle amplification (HRCA) with quantum dot (QD)-based fluorescence resonance energy transfer (FRET) for the simultaneous detection of multiple microRNAs with a single-color QD as the donor and two fluorescent dyes as the acceptors. We used miR-21 and miR-221 as target miRNAs. We designed two circular templates which may specifically hybridize with miR-21 and miR-221, respectively, for the initiation of the HRCA reaction. The products of the HRCA reaction may hybridize with both capture probes and reporter probes to form the biotinylated acceptor-labeled sandwich hybrids. The resultant sandwich hybrids can assemble on the surface of the QD, enabling efficient FRET between the QD and the acceptors, with the Cy3 signal indicating the presence of miR-21 and the Texas Red signal indicating the presence of miR-221. This assay has significant advantages of simplicity and low cost. The HRCA reaction can be performed under isothermal conditions with the same reverse primer for different target miRNAs, and the products of the HRCA reaction for both miR-21 and miR-221 can specifically hybridize with the same capture probes. This assay exhibits excellent specificity and high sensitivity with a detection limit of 7.2 × 10
M for miR-21 and 1.6 × 10
M for miR-221, and it can be used for simultaneous detection of multiple miRNAs in human cancer cells, holding great potential in biomedical research and clinical diagnosis.
We put forward a concept to create highly collimated, nondispersive electron beams in pseudorelativistic Dirac materials such as graphene or topological insulator surfaces. Combining negative ...refraction and Klein collimation at a parabolic pn junction, the proposed lens generates beams, as narrow as the focal length, that stay focused over scales of several microns and can be steered by a magnetic field without losing collimation. We demonstrate the lens capabilities by applying it to two paradigmatic settings of graphene electron optics: We propose a setup for observing high-resolution angle-dependent Klein tunneling, and, exploiting the intimate quantum-to-classical correspondence of these focused electron waves, we consider high-fidelity transverse magnetic focusing accompanied by simulations for current mapping through scanning gate microscopy. Our proposal opens up new perspectives for next-generation graphene electron optics experiments.
The long noncoding RNA (lncRNA) OTUD6B antisense RNA 1 (OTUD6B-AS1) is oriented in an antisense direction to the protein-coding gene OTUD6B on the opposite DNA strand. TCGA database data show that ...the expression of the lncRNA OTUD6B-AS1 is downregulated and that OTUD6B-AS1 acts as an antioncogene in a variety of tumors. However, the expression and biological functions of the lncRNA OTUD6B-AS1 are still unknown in tumors, including clear cell renal cell carcinoma (ccRCC).
The expression level of OTUD6B-AS1 was measured in 75 paired human ccRCC tissue and corresponding adjacent normal renal tissue samples. The correlations between the OTUD6B-AS1 expression level and clinicopathological features were evaluated using the chi-square test. The effects of OTUD6B-AS1 on ccRCC cells were determined via MTT assay, clone formation assay, transwell assay, and flow cytometry. Furthermore, the impact of OTUD6B-AS1 overexpression on the activation of the Wnt/β-catenin signaling pathway was investigated. Finally, ACHN cells with OTUD6B-AS1 overexpression were subcutaneously injected into nude mice to evaluate the influence of OTUD6B-AS1 on tumor growth in vivo.
In this study, we found that the expression of the lncRNA OTUD6B-AS1 was downregulated in ccRCC tissue samples and that patients with low OTUD6B-AS1 expression had shorter overall survival than patients with high OTUD6B-AS1 expression, which showed that the different expression level of OTUD6B-AS1 indirectly correlated with survival of patients. Lentivirus-mediated OTUD6B-AS1 overexpression significantly decreased the proliferation of ccRCC cells and promoted the apoptosis of the cells. Furthermore, OTUD6B-AS1 overexpression partly inhibited cell migration and invasion. The overexpression of OTUD6B-AS1 decreased the activity of the Wnt/β-catenin pathway and suppressed the expression of epithelial-to-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Snail) in ccRCC cells. In addition, compared with the parental ACHN cells, OTUD6B-AS1-overexpressing ACHN cells injected into nude mice exhibited decreased tumor growth in vivo.
Taken together, our findings present a road map for targeting the newly identified lncRNA OTUD6B-AS1 to suppress ccRCC progression in cell lines, and these results elucidate a novel potential therapeutic target for ccRCC treatment.
NiFe‐based layered double hydroxides (LDHs) are among the most efficient oxygen evolution reaction (OER) catalysts in alkaline medium, but their long‐term OER stabilities are questionable. In this ...work, it is demonstrated that the layered structure makes bulk NiFe LDH intrinsically not stable in OER and the deactivation mechanism of NiFe LDH in OER is further revealed. Both operando electrochemical and structural characterizations show that the interlayer basal plane in bulk NiFe LDH contributes to the OER activity, and the slow diffusion of proton acceptors (e.g., OH−) within the NiFe LDH interlayers during OER causes dissolution of NiFe LDH and therefore decrease in OER activity with time. To improve diffusion of proton acceptors, it is proposed to delaminate NiFe LDH into atomically thin nanosheets, which is able to effectively improve OER stability of NiFe LDH especially at industrial operating conditions such as elevated operating temperatures (e.g., at 80 °C) and large current densities (e.g., at 500 mA cm−2).
The interlayer basal plane in bulk NiFe layered double hydroxide (LDH) contributes to the oxygen evolution reaction (OER) activity. Restricted diffusion of proton acceptors within the interlayers of bulk NiFe LDH causes catalyst dissolution. Exfoliating multilayered NiFe LDH into single‐layered nanosheets greatly improves the catalytic stability of NiFe LDH in alkaline OER.
Abstract
Photocatalytic reduction of CO
2
is a promising approach to achieve solar-to-chemical energy conversion. However, traditional catalysts usually suffer from low efficiency, poor stability, ...and selectivity. Here we demonstrate that a large porous and stable metal-organic framework featuring dinuclear Eu(III)
2
clusters as connecting nodes and Ru(phen)
3
-derived ligands as linkers is constructed to catalyze visible-light-driven CO
2
reduction. Photo-excitation of the metalloligands initiates electron injection into the nodes to generate dinuclear {Eu(II)}
2
active sites, which can selectively reduce CO
2
to formate in a two-electron process with a remarkable rate of 321.9 μmol h
−1
mmol
MOF
−1
. The electron transfer from Ru metalloligands to Eu(III)
2
catalytic centers are studied via transient absorption and theoretical calculations, shedding light on the photocatalytic mechanism. This work highlights opportunities in photo-generation of highly active lanthanide clusters stabilized in MOFs, which not only enables efficient photocatalysis but also facilitates mechanistic investigation of photo-driven charge separation processes.
We explore a network of electronic quantum valley Hall states in the moiré crystal of minimally twisted bilayer graphene. In our transport measurements, we observe Fabry-Pérot and Aharanov-Bohm ...oscillations that are robust in magnetic fields ranging from 0 to 8 T, which is in strong contrast to more conventional two-dimensional systems where trajectories in the bulk are bent by the Lorentz force. This persistence in magnetic field and the linear spacing in density indicate that charge carriers in the bulk flow in topologically protected, one-dimensional channels. With this work, we demonstrate coherent electronic transport in a lattice of topologically protected states.
Three-dimensional (3D) DNA scaffolds with well-defined structure and high controllability hold promising potentials for biosensing and drug delivery. However, most of 3D DNA scaffolds can detect only ...a single type of molecule with the involvement of complex logic operations. Herein, we develop a 3D DNA nanostructure with the capability of multiplexed detection by exploiting a multistep Förster resonance energy transfer (FRET). The tetrahedron-structured DNA is constructed by four oligonucleotide strands and is subsequently conjugated to a streptavidin-coated quantum dot (QD) to obtain a QD-Cy3-Texas Red-Cy5 tetrahedron DNA. This QD-Cy3-Texas Red-Cy5 tetrahedral DNA nanostructure has well-defined dye-to-dye spacing and high controllability for energy transfer between intermediary acceptors and terminal acceptors, enabling the generation of multistep FRET between the QD and three dyes (i.e., Cy3, Texas Red, and Cy5) for simultaneous detection of multiple endonucleases and methyltransferases even in complex biological samples as well as the screening of multiple enzyme inhibitors.
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