GNA13 inhibits glioblastoma metastasis via the ERKs/FOXO3 signaling pathway.

Glioblastoma (GBM) is a malignant tumor characterized by poor prognosis and low overall survival (OS) rate. Identification of novel biological markers for the diagnosis and treatment of GBM is crucial to developing interventions to improve patient survival. GNA13, a member of the G12 family, has been reported to play important roles in a variety of biological processes involved in tumorigenesis and development. However, its role in GBM is currently unknown. Here, we explored the expression patterns and functions of GNA13 in GBM, as wells its impact on metastasis process. Results showed that GNA13 was downregulated in GBM tissues and correlated with poor prognosis of GBM. Downregulation of GNA13 promoted the migration, invasion and proliferation of GBM cells; whereas its overexpression abolished these effects. Western blots revealed that GNA13 knockdown and overexpression upregulated and inhibited the phosphorylation of ERKs, respectively. Moreover, GNA13 was the upstream of ERKs signaling to regulating ERKs phosphorylation level. Furthermore, U0126 alleviated the metastasis effect induced by GNA13 knockdown. Bioinformatics analyses and qRT-PCR experiments demonstrated that GNA13 could regulate FOXO3, a downstream signaling molecule of ERKs pathway. Overall, our results demonstrate that GNA13 expression is negatively correlated with GBM and can suppress tumor metastasis by inhibiting the ERKs signaling pathway and upregulating FOXO3 expression.

Dual-mode photoelectrochemical/electrochemical sensor based on Z-scheme AgBr/AgI-Ag-CNTs and aptamer structure switch for the determination of kanamycin.

A "signal-on" dual-mode aptasensor based on photoelectrochemical (PEC) and electrochemical (EC) signals was established for kanamycin (Kana) assay by using a novel Z-scheme AgBr/AgI-Ag-CNTs composite as sensing platform, an aptamer structure switch, and K3[Fe(CN)6] as photoelectron acceptor and electrochemical signal indicator. The aptamer structure switch was designed to obtain a "signal-off" state, which included an extended Kana aptamer (APT), one immobilized probe (P1), and one blocking probe (P2) covalently linked with graphdiyne oxide (GDYO) nanosheets. P1, P2, and aptamer formed the double helix structure, which resulted in the inhibited photocurrent intensity because of the weak conductivity of double helix layer and serious electrostatic repulsion of GDYO towards K3[Fe(CN)6]. In the presence of Kana, APT specifically bound to the target and dissociated from P1 and P2, and thus, a "signal-on" state was initiated by releasing P2-GDYO from the platform. Based on the sensing platform and the aptamer structure switch, the dual-mode aptasensor realized the linear determination ranges of 1.0 pM-2.0 µM with a detection limit (LOD) of 0.4 pM (for PEC method) and 10 pM-5.0 µM with a LOD of 5 pM (for EC method). The aptasensor displayed good application potential for Kana test in real samples.

Surfactant without Endotracheal Tube Intubation (SurE) versus Intubation-Surfactant-Extubation (InSurE) in Neonatal Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

Neonatal respiratory distress syndrome (NRDS) is generally treated with surfactant by intubation-surfactant-extubation (InSurE) technique, an invasive method of surfactant administration. Surfactant without endotracheal tube intubation (SurE) is a noninvasive technique that avoids intubation and has been found to have improved the delivery of exogenous surfactants, thereby decreasing lung damage in neonates. This systematic review aimed to provide insights into the efficacy of SurE over InSurE in neonates who received respiratory support and to evaluate the progression and onset of concurrent diseases after treatment. The CENTRAL, PubMed, and Embase databases were searched for data collection. In all, 21 research articles were eligible, comprising 19,976 study participants. The data showed a significant reduction in the composite outcome of stage 2 necrotizing enterocolitis, bronchopulmonary dysplasia, and onset of hemodynamically significant patent ductus arteriosus when treated with SurE. The trend towards lower pneumothorax rates with SurE was also evident. These findings were robust due to the sensitivity analyses performed. There were no differences in the outcome of death or rates of other neonatal morbidities. Overall, SurE was identified as a better substitute for InSurE to treat neonates with RDS.

Mesoporous N-P Codoped Carbon Nanosheets as Superior Cathodic Catalysts of Neutral Metal-Air Batteries.

Development of high-efficiency oxygen reduction reaction (ORR) catalysts under neutral conditions has made little research progress. In this work, we synthesized a three-dimensional porous N/P codoped carbon nanosheet composites (CNP@PNS) by high-temperature thermal treatment of dicyandiamide, starch, and triphenylphosphine and subsequent porous structure-making treatment using the NaCl molten salt template. In the neutral solution, the electrocatalytic performance of the CNP@PNS-4 catalyst exhibits an onset potential of 0.98 V (vs reversible hydrogen electrode) and a half-wave potential of 0.91 V for ORR, which greatly surpasses commercial Pt/C (40%). Three kinds of neutral metal-air batteries (Zn-air, Al-air, and Fe-air) using the prepared samples as cathodic catalysts were constructed, corresponding to the maximum power density of 120.2, 78.3, and 18.9 mW·cm-2, respectively. Also, they reveal outstanding discharge stability under different current densities. The density functional theory calculation depicts the reduction of the free energy of the determining step and subsequent decline of the overpotential for ORR.

CoNi Nanoparticles Supported on N-Doped Bifunctional Hollow Carbon Composites as High-Performance ORR/OER Catalysts for Rechargeable Zn-Air Batteries.

Searching for high-quality air electrode catalysts is the long-term goal for the practical application of Zn-air batteries. Here, a series of coexistent composite materials (CoNi/NHCS-TUC-x) of cobalt-nickel supported on nitrogen-doped hollow spherical carbon and tubular carbon are obtained using a simple pyrolysis strategy. Co and Ni in the composites are mainly present in the form of alloy nanoparticles, M-Nx and M-Cx (M = Co or Ni) species, with high oxygen reduction reaction (ORR)/oxygen evolution reaction (OER) electroactivity. The materials containing different proportions of spherical carbon and tubular carbon obtained by simply adjusting the raw materials for generating tubular carbon exhibit interesting bifunctional performance: samples with an abundant tubular content have the highest ORR onset potential (0.91 V vs reversible hydrogen electrode), while those with a rich spherical content have the highest ORR current density (5.13 mA·cm-2). Furthermore, CoNi/NHCS-TUC-3 provides the lowest potential difference (ΔE = Ej=10 - E1/2) of 0.806 V. We then test the potential possibility of CoNi/NHCS-TUC-3 as an air electrode for primary and rechargeable Zn-air batteries. The primary battery delivers an open-circuit potential of 1.59 V, a peak power density of 361.8 mA·cm-2, and a specific capacity of 756.5 mA h·gZn-1. The rechargeable battery could be cycled stably for more than 55 h at 10 mA·cm-2. These characteristics make CoNi/NHCS-TUC-3 a superior electrocatalyst for both the ORR and OER, as well as a suitable bifunctional electrode applied to a rechargeable Zn-air battery.

Tunable graphdiyne for DNA surface adsorption: affinities, displacement, and applications for fluorescence sensing.

Graphdiyne (GDY) adsorbed DNA probes have been used as a fluorescent sensing platform, but topics including DNA adsorption affinities, DNA probe displacement, and fluorescence quenching ability were rarely researched. Herein, the adsorption affinity of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) on a tremella-like GDY was tuned by modulating the surface chemistry of GDY. The fluorescence quenching ability of GDY with different oxidation degrees was compared. The nonspecific displacement of DNA probes on GDY was studied. Under the same concentrations, GDY with low oxidation degree exhibited stronger adsorption affinity and higher adsorption capacity to both ssDNA and dsDNA than highly oxidized GDY. DNA adsorbed on low-oxidized GDY was more resistant to displacement by other DNAs. Protein showed strong interaction with different GDY and could displace DNA probes on GDY. Based on these findings, an ideal GDY with proper oxidation degree, exhibiting high surface affinity for ssDNA and low affinity for dsDNA, was used as scavenger of redundant ssDNA fluorescent probe in an enzyme-assisted amplification system for sensitive ochratoxin (OTA) detection. This study has enhanced our fundamental understanding of DNA adsorption by GDY. It also provided a rational way to apply GDY for fluorescence sensing in a complicated system.

A cathode photoelectrochemical assay of terminal deoxynucleotidyl transferase activity based on Ag-AgI-CNTs composite and surface multisite strand displacement amplification.

Photocathode-based assay is anti-interference for real sample detection. Photocathode produces low photocurrent signal and gives rise to poor sensitivity. Herein, a novel cathode photoelectrochemical (CPEC) sensing platform based on Ag-AgI-CNTs as photocathode material and K3[Fe(CN)6] as photoelectron acceptor was established. Since [Fe(CN)6]3- effectively accepted photoelectrons from Ag-AgI-CNTs, it greatly enhanced the CPEC response. Combining a surface multisite strand displacement amplification (SMSDA) strategy, the CPEC platform was applied for the activity assay of terminal deoxynucleotidyl transferase (TdT). In this proposal, oligo dT primer tethered on CPEC platform was in-situ extended to generate a polyA tail. Then the polyA tail formed a stable multi-point hybrid structure with the adjacent oligo dT. After launching the SMSDA, the CPEC platform was covered by more elongated polynucleotide chains and network, which acutely hampered the photoelectron transfer (eT) between photocathode and electron acceptor and caused a reduced photocurrent. The CPEC sensor possessed a satisfactory linear response from 6 × 10-5-0.1 U and a low detection limit of 1.1 × 10-5 U. The strategy offered a more specific and sensitive method for TdT activity assay. It was feasible in the field of TdT-based biochemical research, drug screening, and disease diagnosis.

N-terminal region of Helicobacter pylori CagA induces IL-8 production in gastric epithelial cells via the ß1 integrin receptor.

Introduction. Helicobacter pylori is associated with gastrointestinal disease, most notably gastric cancer. Cytotoxin-associated antigen A (CagA), an important virulence factor for H. pylori pathogenicity, induces host cells to release inflammatory factors, especially interleukin-8 (IL-8). The mechanism by which C-terminal CagA induces IL-8 production has been studied extensively, but little is known about the role of the N-terminus.Aim. To investigate the effect of CagA303-456aa (a peptide in the N-terminal CagA) on IL-8 production by gastric epithelial cells.Methodology. CagA303-456aa was produced by a prokaryotic expression system and purified by Strep-tag affinity chromatography. An integrin ß1 (ITGB1)-deficient AGS cell line was constructed using the CRISPR/Cas9 technique, and NCTC 11637 cagA and/or cagL knockout mutants were constructed via homologous recombination. The levels of IL-8 production were determined by enzyme-linked immunosorbent assay (ELISA), and p38 and ERK1/2 phosphorylation were examined by Western blot.Results. CagA303-456aa induced IL-8 expression by AGS cells. IL-8 induction by CagA303-456aawas specifically inhibited by ITGB1 deficiency. Notably, CagA303-456aa activated the phosphorylation of both p38 and ERK1/2, and blocking p38 and ERK1/2 activity significantly reduced IL-8 induction by CagA303-456aa. ITGB1 deficiency also inhibited the activation of p38 phosphorylation by CagA303-456aa. Finally, experiments in CagA and/or CagL knockout bacterial lines demonstrated that extracellular CagA might induce IL-8 production by AGS cells.Conclusion. Residues 303-456 of the N-terminal region of CagA induce IL-8 production via a CagA303-456-ITGB1-p38-IL-8 pathway, and ERK1/2 is also involved in the release of IL-8. Extracellular CagA might induce IL-8 production before translocation into AGS cells.

Evaluation of the potential cytotoxicity of metals associated with implanted biomaterials (II).

The effects of metal ions on the cell DNA and RNA synthetic functions and the destruction of cell defensive system caused by metal ions were studied on the investigation of the effects of metal ions on cell alkaline phosphatase (ALP) activity and cell metabolism ability. The poisonous behaviours of metal ions [Cr (VI), Ni, V, Cr (III), Ag, and Al] on living tissue were both quantitatively and qualitatively measured. It was shown that Cr (VI) has a notable action on both cellular DNA and RNA synthetic functions, and following that, were Ni, V. The limitation action of Cr (III) on the synthetic abilities of DNA and RNA increased with the increase of Cr (III) concentration. Different to other five metal ions, the limitation of Al ion on RNA was greater than that on DNA. The limitation of V, Ag ions on DNA was same to that on RNA. Trace Cr (VI), in culture medium resulted in the decreasing of GSH in living tissue. Similar to that, a little higher Ni ion concentration seriously reduced the GSH content in living tissue. It was suggested that Cr (VI), Ni, might destroy and/or disturb the orientation of the microtubulin in cell skeleton. For other four metal ions, together with increasing the concentration in culture medium, the osmotic pressure increased. Consequently, more metal ions entered cell membrane, more GSH were lost in cell.