Kinase Activity of Fibroblast Growth Factor Receptor 3 Regulates Activity of the Papillomavirus E2 Protein.

The papillomavirus (PV) E2 protein is a DNA binding, protein interaction platform that recruits viral and host factors necessary for transcription and replication. We recently discovered phosphorylation of a tyrosine (Y102) in bovine PV (BPV) E2. To identify the responsible factor, we tested several candidate tyrosine kinases that are highly expressed in keratinocytes for binding to BPV-1 E2. Fibroblast growth factor receptor 3 (FGFR3) coimmunoprecipitated with the BPV-1 E2 protein, as did human papillomavirus 31 (HPV-31) E2, which also colocalized with FGFR3 within the nucleus. A constitutively active mutant form of FGFR3 decreased BPV-1 and HPV-31 transient replication although this result also occurred in a BPV-1 E2 mutant lacking a previously identified phosphorylation site of interest (Y102). Furthermore, FGFR3 depletion in cell lines that maintain HPV-31 episomes increased viral copy number. These results suggest that FGFR3 kinase activity may regulate the PV reproductive program through phosphorylation of the E2 protein although this is unlikely to occur through the Y102 residue of HPV E2.IMPORTANCE The papillomavirus (PV) is a double-stranded DNA tumor virus infecting cervix, mouth, and throat tissues. The viral protein E2 is responsible for the replication of the virus. Understanding the mechanisms of the replicative life cycle of the virus may bring to light direct targets and treatments against viral infection. We recently found that the fibroblast growth factor receptor 3 (FGFR3) interacts with and mediates PV E2 function through phosphorylation of the E2 protein. Our study suggests that the function of the E2 protein may be regulated through a direct FGFR3 target during the maintenance stage of the PV life cycle.

An intranasal cationic liposomal polysaccharide vaccine elicits humoral immune responses against Streptococcus pneumoniae.

Diseases caused by S. pneumoniae are the leading cause of child mortality. As antibiotic resistance of S. pneumoniae is rising, vaccination remains the most recommended solution. However, the existing pneumococcal polysaccharides vaccine (Pneumovax® 23) proved only to induce T-independent immunity, and strict cold chain dependence of the protein conjugate vaccine impedes its promotion in developing countries, where infections are most problematic. Affordable and efficient vaccines against pneumococcus are therefore in high demand. Here, we present an intranasal vaccine Lipo+CPS12F&αGC, containing the capsular polysaccharides of S. pneumoniae 12F and the iNKT agonist α-galactosylceramide in cationic liposomes. In BALB/cJRj mice, the vaccine effectively activates iNKT cells and promotes B cells maturation, stimulates affinity-matured IgA and IgG production in both the respiratory tract and systemic blood, and displays sufficient protection both in vivo and in vitro. The designed vaccine is a promising, cost-effective solution against pneumococcus, which can be expanded to cover more serotypes and pathogens.

Treatment of Atlantoaxial Dislocation in Children with Down Syndrome Using Posterior Atlantoaxial Screw Fixation.

Background: To investigate the effect of posterior atlantoaxial screw fixation for the treatment of atlantoaxial dislocation in children with Down syndrome (DS). Methods: Children diagnosed with DS who underwent posterior atlantoaxial screw fixation or occipitocervical fusion from January 2017 to January 2020 in Hebei Children's Hospital were retrospectively included. Preoperative CT and MRI were performed to check the os odontoideum (OsO) and spinal cord compression, signal changes and spinal cord injury grade (ASIA grade). Results: All 5 children have atlantoaxial dislocation and OsO. Among which 60% (3/5) of children had changes in spinal cord signals and 40% (2/5) had dural sac compression. Every child underwent posterior atlantoaxial screw fixation (3.5-mm diameter), and the average fusion level was 1.8 (1-2). All 5 cases wore the head-neck-chest brace for 3-6 months after the operation. 1 case had dural tear and recovered well after timely suturing. 1 case had internal fixation breakage of the prosthetic joint and underwent revision surgery. At the last follow-up, all cases were fused and the neurological function were all ASIA grade E. Conclusion: After posterior atlantoaxial screw fixation, fusion and nerve recovery were achieved in all children with atlantoaxial dislocation and OsO. Postoperative head-neck-chest braces are necessary for children, especially those with occipitocervical fusion.

Effects of different sulfonation times and post-treatment methods on the characterization and cytocompatibility of sulfonated PEEK.

Polyetheretherketone (PEEK) has been becoming a popular implant material in orthopaedic applications. The lack of bioactivity affects PEEK's long-term lifetime, and appropriate surface modification is an effective way to enhance its bioactivity. Sulfonation of PEEK can endow PEEK with a 3 D porous network surface and improve its bioactivity. This study is aimed at exploring an optimal sulfonation time and a post-treatment method of PEEK sulfonation. PEEK was immersed into concentrated sulfuric acid for different sulfonation times and experienced different post-treatment methods to turn into sulfonated PEEK (SPEEK). The immersion times were 0.5 min (SPEEK0.5), 1 min (SPEEK1), 3 min (SPEEK3), 5 min (SPEEK5) and 7 min (SPEEK7), and the post-treatment methods were acetone rinsing (SPEEK-T1), hydrothermal treatment (SPEEK-T2) and NaOH immersion (SPEEK-T3). Scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy, hydrophilic property, ion release and cell viability evaluations were performed to optimize the sulfonation time, and the SEM, EDS, ion release and cell viability were analysed to optimize the post-treatment method. The results showed a porous network structure was formed on all samples of SPEEK, and the porous structure became more obvious and the S concentration increased with increasing sulfonation time. However, too long of an immersion time (SPEEK7) tended to damage the superficial porous structure and left a higher content of sulfuric acid, which could inhibit the growth of MC3T3E1 cells on its surface. In addition, the surface morphology, residual sulfuric acid and cytocompatibility of SPEEK-T1, SPEEK-T2 and SPEEK-T3 were not distinctly different. In conclusion, a 5-min sulfonation time was considered to be the optimal selection, and acetone rinsing, hydrothermal treatment and NaOH immersion showed the same effect in removing the residual sulfuric acid. The understanding of optimal sulfonation time and post-treatment method can provide a theoretical basis in preparing SPEEK for orthopaedic applications.