PMicroRNA-124a regulates LPS-induced septic cardiac dysfunction by targeting STX2

Objective

To examine the role of miR-124a in LPS-induced septic cardiac insufficiency where underlying mechanism is unclear.

Results

Expression of miR-124a was decreased in myocardium of LPS-induced septic cardiac dysfunction model. miR-124a antagomiR or agomiR were injected via tail vein to induce miR-124a-dysregulated model. miR-124a antagomiR aggravated LPS-induced cardiac dysfunction and apoptosis, while miR-124a agomiR had the opposite effect. Syntaxin-2 (STX2) was indicated as a candidate target gene by bioinformatic software. Further experiments confirmed that STX2 was downregulated in miR-124a agomiR-treated rats but upregulated in miR-124a antagomiR-treated rats, and STX2 inhibition could strongly block the miR-124a antagomiR-associated increase in cell apoptosis. Luciferase reporter activity assay indicated that STX2 was a direct target of miR-124a. Serological detection reveled that miR-124a was down-regulated in the plasma of septic cardiac dysfunction rats.

Conclusions

miR-124a aggravates LPS-induced cardiac dysfunction and the miR-124a/STX2 pathway might serve as the potential diagnostic and therapeutic targets for septic cardiac dysfunction.

     

Bioluminescent imaging of hepatocellular carcinoma in live mice

A non-invasive orthotopic hepatocellular carcinoma (HCC) model was created with human HCC cells (HepG-Luc) constitutively expressing luciferase (Luc) in nude mice. Development of tumor growth and response to anti-tumor therapy combined with 5-fluorouracil and cisplatin was monitored by whole-body bioluminescent imaging (BLI). Luciferase activity in the tumor, determined by BLI, correlated with the tumor volume and weight. The anti-tumor therapy proved effective by BLI monitoring. In conclusion, BLI by luciferase provides a non-invasive method of monitoring tumor activities that can prove useful for therapeutic intervention studies.     

Viral tegument proteins restrict cGAS-DNA phase separation to mediate immune evasion

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Stable Li Metal Anode Enabled by Space Confinement and Uniform Curvature through Lithiophilic Nanotube Arrays

The application of lithium (Li) metal anodes in rechargeable batteries is primarily restricted by Li dendrite growth on the metal's surface, which leads to shortened cycle life and safety concerns. Herein, well‐spaced nanotubes with ultrauniform surface curvature are introduced as a Li metal anode structure. The ultrauniform nanotubular surface generates uniform local electric fields that evenly attract Li‐ions to the surface, thereby inducing even current density distribution. Moreover, the well‐defined nanotube spacing offers Li diffusion pathways to the electroactive areas as well as the confined spaces to host deposited Li. These structural attributes create a unique electrodeposition manner; i.e., Li metal homogenously deposits on the nanotubular wall, causing each Li nanotube to grow in circumference without obvious sign of dendritic formation. Thus, the full‐cell battery with the spaced Li nanotubes exhibits a high specific capacity of 132 mA h g^?1 at 1 C and an excellent coulombic efficiency of ≈99.85% over 400 cycles.     

Experimental Study of Low Dose Ultrashortwave Promoting Nerve Regeneration after Acellular Nerve Allografts Repairing the Sciatic Nerve Gap of Rats

Objectives To observe the effect of ultrashortwave (USW) therapy on nerve regeneration after acellular nerve allografts(ANA) repairing the sciatic nerve gap of rats and discuss its acting mechanisms. Methods Sixteen Wistar rats weighing 180–220 g were randomly divided into four groups with four rats in each group: normal control group; acellular group (ANA, treated by hypotonic-chemical detergent, was applied for bridging a 10 mm-long sciatic nerve defect); USW group (After 24 h of ANA repairing the sciatic nerve gap, low dose USW was administrated for 7 min, once a day, 20 times a course of treatment, three courses of treatment in all); and autografts group. 12 weeks after operation, a series of examinations was performed, including electrophysiological methods, the restoring rate of tibialis anterior muscle wet weight, histopathological observation (myelinated nerve number, myelin sheath thickness, and axon diameter), vascular endothelial growth factor (VEGF) mRNA expression of spinal cord, and muscle at injury site, and analyzed statistically. Results Compared to acellular nerve allografts alone, USW therapy can increase nerve conductive velocity, the restoring rate of tibialis anterior muscle wet weight, myelinated nerve number, axon diameter, VEGF mRNA expression of spinal cord, and muscle at injury site, the difference is significant. There were no differences between USW group and autografts group except myelin sheath thickness. Conclusions USW therapy can promote nerve axon regeneration and Schwann cells proliferation after ANA repairing the sciatic nerve gap of rats, the upregulation of VEGF mRNA expression of spinal cord and muscle may play an important role.     

Compositional reasoning of performance in component-based distributed systems

Rapid prototyping of distributed systems can be achieved by integrating commercial off-the-shelf (COTS) components. With components as the building blocks, it is important to predict the performance of the system based on the performance of individual components. In this paper, performance prediction of a system consisting of a small number of components is investigated under different inter-component communication patterns, and the number of threads provided by components. Based on the experimental results, it can be inferred that the proposed composition rules provide a reasonably accurate prediction of the performance of a system made out of these components.

Selenium-containing 15-mer peptides with high glutathione peroxidase-like activity

Glutathione peroxidase (GPX) is one of the most crucial antioxidant enzymes in a variety of organisms. Here we described a new strategy for generating a novel GPX mimic by combination of a phage-displayed random 15-mer peptide library followed by computer-aided rational design and chemical mutation. The novel GPX mimic is a homodimer consisting of a 15-mer selenopeptide with an appropriate catalytic center, a specific binding site for substrates, and high catalytic efficiency. Its steady state kinetics was also studied, and the values of k(cat)/K(m)(GSH) and k(cat)/ K(mH(2)O(2)) were found to be similar to that of native GPX and the highest among the existing GPX mimics. Moreover, the novel GPX mimic was confirmed to have a strong antioxidant ability to inhibit lipid peroxidation by measuring the content of malondialdehyde, cell viability, and lactate dehydrogenase activity. Importantly, the novel GPX mimic can penetrate into the cell membrane because of its small molecular size. These characteristics endue the novel mimic with potential perspective for pharmaceutical applications.     

Adriamycin effects on transplasma membrane redox functions in porcine neutrophils

Transplasma membrane electron transport, as assayed by external ferricyanide reduction, has been related to control of growth and hormone response of cells. Elicitor-stimulated transmembrane NADPH oxidase is important for bacteriocidal superoxide production by neutrophils. Since adriamycin is myelosuppressive and can stimulate superoxide production, its effects on the two redox systems of porcine neutrophil plasma membranes were compared. Adriamycin inhibits transplasma membrane ferricyanide and stimulates superoxide production activated by phorbol myristate acetate (PMA). Ferricyanide reduction in PMA-treated cells becomes resistant to inhibition by adriamycin. These results provide evidence for an independent effect of adriamycin on transmembrane ferricyanide reduction and on superoxide generation.     

Nuclear envelope dispersion triggered by deregulated Cdk5 precedes neuronal death

Nuclear fragmentation is a common feature in many neurodegenerative diseases, including Alzheimer's disease (AD). In this study, we show that nuclear lamina dispersion is an early and irreversible trigger for cell death initiated by deregulated Cdk5, rather than a consequence of apoptosis. Cyclin-dependent kinase 5 (Cdk5) activity is significantly increased in AD and contributes to all three hallmarks: neurotoxic amyloid-β (Aβ), neurofibrillary tangles (NFT), and extensive cell death. Using Aβ and glutamate as the neurotoxic stimuli, we show that deregulated Cdk5 induces nuclear lamina dispersion by direct phosphorylation of lamin A and lamin B1 in neuronal cells and primary cortical neurons. Phosphorylation-resistant mutants of lamins confer resistance to nuclear dispersion and cell death on neurotoxic stimulation, highlighting this as a major mechanism for neuronal death. Rapid alteration of lamin localization pattern and nuclear membrane change are further supported by in vivo data using an AD mouse model. After p25 induction, the pattern of lamin localization was significantly altered, preceding neuronal death, suggesting that it is an early pathological event in p25-inducible transgenic mice. Importantly, lamin dispersion is coupled with Cdk5 nuclear localization, which is highly neurotoxic. Inhibition of nuclear dispersion rescues neuronal cells from cell death, underscoring the significance of this event to Cdk5-mediated neurotoxicity.