MicroRNA-582-5p Contributes to the Maintenance of Neural Stem Cells Through Inhibiting Secretory Protein FAM19A1.

Epigenetic regulations on the maintenance of neural stem cells (NSCs) are complicated and far from been fully understood. Our previous findings have shown that after blocking Notch signaling in NSCs in vivo, the stemness of NSCs decreases, accompanied by the downregulated expression of miR-582-5p. In the current study, we further investigated the function and mechanism of miR-582-5p in the maintenance of NSCs in vitro and in vivo. After transfecting a mimic of miR-582-5p, the formation of neurospheres and proliferation of NSCs and intermediate progenitor cells (NS/PCs) were enhanced, and the expression of stemness markers such as Sox2, Nestin, and Pax6 also increased. The results were reversed after transfection of an inhibitor of miR-582-5p. We further generated miR-582 knock-out (KO) mice to investigate its function in vivo, and we found that the number of NSCs in the subventricular zone (SVZ) region decreased and the number of neuroblasts increased in miR-582 deficient mice, indicating reduced stemness and enhanced neurogenesis of NSCs. Moreover, RNA-sequencing and molecular biological analysis revealed that miR-582-5p regulates the stemness and proliferation of NSCs by inhibiting secretory protein FAM19A1. In summary, our research uncovered a new epigenetic mechanism that regulates the maintenance of NSCs, therefore providing novel targets to amplify NSCs in vitro and to promote neurogenesis in vivo during brain pathology and aging.

Early acute fat embolism syndrome caused by femoral fracture: A case report.

BACKGROUND: Fat embolism syndrome (FES) is a rare complication caused by the presence of fat particles in the microcirculation, which usually occurs within 12-72 h after trauma. At present, there have been few cases of fat embolism presenting within 3 h after trauma. Here, we report a case of femoral fracture complicated with an acute fat embolism caused by a car accident. CASE SUMMARY: A 29-year-old woman with pain, swelling and limited movement of her left lower limb after a car accident was taken by ambulance to our hospital. X-ray examination showed fracture of the middle and lower part of the left femur and fracture of the base of the left fifth metatarsal bone. She was hospitalized and admitted to the orthopedic ward. After the attending doctor performed tibial tubercle bone traction, the patient became confused, followed by respiratory distress. Finally, she was transferred to the intensive care unit. After nearly a month of treatment in the intensive care unit, the patient's cognitive function gradually recovered over 6 mo. CONCLUSION: For patients with early traumatic fractures, young emergency physicians and orthopedics should be aware of the possibility of FES.

Convolutional neural network for estimating physical parameters from Newton's rings.

By analyzing Newton's rings, often encountered in interferometry, the parameters of spherical surfaces such as the rings' center and the curvature radius can be estimated. First, the classical convolutional neural networks, visual geometry group (VGG) network and U-Net, are applied to parameter estimation of Newton's rings. After these models are trained, the rings' center and curvature radius can be obtained simultaneously. Compared with previous analysis methods of Newton's rings, it is shown that the proposed method has higher precision, better immunity to noise, and lower time consumption. For a Newton's rings pattern of ${{640}} \times {{480}}$ pixels comprising ${-}{{5}}\;{\rm{dB}}$ Gaussian noise or 60% salt-and-pepper noise, the parameters can be estimated by the VGG model in 0.01 s, the error of the rings' center is less than one pixel, and the error of curvature radius is lower than 0.5%.

Nano-elastic modulus of tendon measured directly in living mice.

The nano-biomechanical environment of the extracellular matrix is critical for cells to sense and respond to mechanical loading. However, to date, this important characteristic remains poorly understood in living tissue structures. This study reports the experimental measurement of the in vivo nano-elastic modulus of the tendon in a mouse tail model. The experiment was performed on the tail tendon of an 8-week-old C57BL/6 live mouse. Mechanical loading on tail tendons was regulated by changing both voltage and frequency of alternating current stimulation on the erector spinae. The nano-elastic modulus of the tail tendon was measured by atomic force microscope. The nano-elastic modulus showed significant variation (2.19-35.70 MPa) between different locations and up to 39% decrease under muscle contraction, suggesting a complicated biomechanical environment in which cells dwell. In addition, the nano-elastic modulus of the tail tendon measured in live mice was significantly lower than that measured in vitro, suggesting a disagreement of tissue mechanical properties in vivo and in vitro. This information is important for the designs of new extracellular biomaterial that can better mimic the biological environment, and improve clinical outcomes of musculoskeletal tissue degenerations and associated disorders.

Microstructure and mechanical properties of subchondral bone are negatively regulated by tramadol in osteoarthritis in mice.

OBJECTIVES: In the treatment of osteoarthritis (OA), tramadol, a common weak opioid, has become popular due to its effectiveness in inhibition of pain. In the present study, we aimed to explore the effect of tramadol on subchondral bone, especially changes in the microstructure and mechanical properties. METHODS: A mouse model of OA was established in the present study by destabilization of the medial meniscus (DMM). A vehicle or drug was administered for 4 weeks. Specimens were harvested and analyzed radiologically and histologically using micro-computed tomography (micro-CT), scanning electron microscopy (SEM), atomic force microscopy (AFM) and histological staining to evaluate the knee joints of mice undergoing different forms of intervention. RESULTS: In the early stages of OA induced by DMM, the subchondral bone volume fraction in the OA group was significantly higher than in the sham+vehicle (sham+veh) group, while the volume in the treatment groups was lower than in the DMM+vehicle (DMM+veh) and sham+veh groups. In addition, the elastic moduli in the treatment groups clearly decreased compared with the DMM+veh and sham+veh groups. Observations of the subchondral bone surface by SEM indicated serious destruction, principally manifesting as a decrease in lacunae and more numerous and scattered cracks. Histological staining demonstrated that there was no difference in the degeneration of either the articular cartilage or synovial cells whether tramadol was used or not. CONCLUSION: Although tramadol is effective in inhibiting pain in early OA, it negatively regulates the microstructure and mechanical properties of subchondral bone in joints.

A ketogenic diet attenuates proliferation and stemness of glioma stem­like cells by altering metabolism resulting in increased ROS production.

Abnormal metabolism serves a critical role in the development and progression of different types of malignancies including glioblastoma (GBM), and may therefore serve as a promising target for treatment of cancer. Preclinical studies have indicated that a ketogenic diet (KD) may exhibit beneficial effects in patients with GBM; however, the underlying mechanisms remain incompletely understood. The aim of the present study was to evaluate the effects of a KD on glioma stem­like cells (GSCs), by culturing patient­derived primary GSCs as well as a GSC cell line in glucose­restricted, ß­hydroxybutyrate­containing medium (BHB­Glow) which was used to mimic clinical KD treatment. GSCs cultured in BHB­Glow medium exhibited reduced proliferation and increased apoptosis compared with cells grown in the control medium. Furthermore, decreased expression of stem cell markers, diminished self­renewal in vitro, and reduced tumorigenic capacity in vivo, providing evidence that the stemness of GSCs was compromised. Mechanistically, culturing in BHB­Glow medium reduced glucose uptake and inhibited glycolysis in GSCs. Furthermore, culturing in the BHB­Glow medium resulted in morphological and functional disturbances to the mitochondria of GSCs. These metabolic changes may have reduced ATP production, promoted lactic acid accumulation, and thus, increased the production of reactive oxygen species (ROS) in GSCs. The expression levels and activation of mammalian target of rapamycin, hypoxia­inducible factor 1 and B­cell lymphoma 2 were decreased, consistent with the reduced proliferation of GSCs in BHB­Glow medium. ROS scavenging reversed the inhibitory effects of a KD on GSCs. Taken together, the results demonstrate that treatment with KD inhibited proliferation of GSCs, increased apoptosis and attenuated the stemness in GSCs by increasing ROS production.

Saponin 6 derived from Anemone taipaiensis induces U87 human malignant glioblastoma cell apoptosis via regulation of Fas and Bcl­2 family proteins.

Glioblastoma multiforme (GBM) is the most common and aggressive type of brain tumor, and is associated with a poor prognosis. Saponin 6, derived from Anemone taipaiensis, exerts potent cytotoxic effects against the human hepatocellular carcinoma HepG2 cell line and the human promyelocytic leukemia HL­60 cell line; however, the effects of saponin 6 on glioblastoma remain unknown. The present study aimed to evaluate the effects of saponin 6 on human U87 malignant glioblastoma (U87 MG) cells. The current study revealed that saponin 6 induced U87 MG cell death in a dose­ and time­dependent manner, with a half maximal inhibitory concentration (IC50) value of 2.83 µM after treatment for 48 h. However, saponin 6 was needed to be used at a lesser potency in HT­22 cells, with an IC50 value of 6.24 µM. Cell apoptosis was assessed by flow cytometry using Annexin V­fluorescein isothiocyanate/propidium iodide double staining. DNA fragmentation and alterations in nuclear morphology were examined by terminal deoxynucleotidyl transferase­mediated dUTP nick end labeling and transmission electron microscopy, respectively. The present study demonstrated that treatment with saponin 6 induced cell apoptosis in U87 MG cells, and resulted in DNA fragmentation and nuclear morphological alterations typical of apoptosis. In addition, flow cytometric analysis revealed that saponin 6 was able to induce cell cycle arrest. The present study also demonstrated that saponin 6­induced apoptosis of U87 MG cells was attributed to increases in the protein expression levels of Fas, Fas ligand, and cleaved caspase­3, ­8 and ­9, and decreases in the levels of B­cell lymphoma 2. The current study indicated that saponin 6 may exhibit selective cytotoxicity toward U87 MG cells by activating apoptosis via the extrinsic and intrinsic pathways. Therefore, saponin 6 derived from A. taipaiensis may possess therapeutic potential for the treatment of GBM.

Hif-1α and Hif-2α differentially regulate Notch signaling through competitive interaction with the intracellular domain of Notch receptors in glioma stem cells.

Hypoxia contributes to GSC expansion principally through Hif-1α and Hif-2α, but how these two factors work together has not been completely understood. We show that hypoxia promoted proliferation, self-renewal and inhibited the conversion of GSCs into INP-like cells through activating Notch signaling. Further data suggested that Hif-2α interacted with NICD and repressed the activity of Notch signaling, in contrast to the role of Hif-1α in Notch signaling. Together, our findings suggest that Hif-1α and Hif-2α competitively bind to NICD and dynamically regulate the activation of Notch signaling in GSCs likely depending on different oxygen tensions, providing improved therapeutic opportunities for malignant gliomas.

Self-assembly of three-dimensional interconnected graphene-based aerogels and its application in supercapacitors.

Homogeneously distributed self-assembling hybrid graphene-based aerogels with 3D interconnected pores, employing three types of carbohydrates (glucose, ß-cyclodextrin, and chitosan), have been fabricated by a simple hydrothermal route. Using three types of carbohydrates as morphology oriented agents and reductants can effectively tailor the microstructures, physical properties, and electrochemical performances of the products. The effects of different carbohydrates on graphene oxide reduction to form graphene-based aerogels with different microcosmic morphologies and physical properties were also systemically discussed. The electrochemical behaviors of all graphene-based aerogel samples showed remarkably strong and stable performances, which indicated that all the 3D interpenetrating microstructure graphene-based aerogel samples with well-developed porous nanostructures and interconnected conductive networks could provide fast ionic channels for electrochemical energy storage. These results demonstrate that this strategy would offer an easy and effective way to fabricate graphene-based materials.

A green and facile route for constructing flower-shaped TiO2 nanocrystals assembled on graphene oxide sheets for enhanced photocatalytic activity.

We have demonstrated an environmentally friendly in situ assembly method for the preparation of novel three-dimensional TiO2/graphene oxide (TiO2/GO) nanostructures with favorable flower-shaped architectures. Very little information on such a morphology of TiO2/GO nanostructures is available in the literature. The as-synthesized sample was characterized by x-ray diffraction, scanning electron microscopy, transmission electron microscopy, N2 adsorption-desorption measurements and Raman spectroscopy. Also the TiO2/GO composites exhibited enhanced photocatalytic properties.