EV71 5'UTR interacts with 3D protein affecting replication through the AKT-mTOR pathway.

BACKGROUND: EV71 is one of the important pathogens of Hand-foot-and-mouth disease (HFMD), which causes serious neurological symptoms. Several studies have speculated that there will be interaction between 5'UTR and 3D protein. However, whether 5'UTR interacts with the 3D protein in regulating virus replication has not been clarified. METHODS: Four 5'UTR mutation sites (nt88C/T, nt90-102-3C, nt157G/A and nt574T/A) and two 3D protein mutation sites (S37N and R142K) were mutated or co-mutated using virulent strains as templates. The replication of these mutant viruses and their effect on autophagy were determined. RESULTS: 5'UTR single-point mutant strains, except for EGFP-EV71(nt90-102-3C), triggered replication attenuation. The replication ability of them was weaker than that of the parent strain the virulent strain SDLY107 which is the fatal strain that can cause severe neurological complications. While the replication level of the co-mutant strains showed different characteristics. 5 co-mutant strains with interaction were screened: EGFP-EV71(S37N-nt88C/T), EGFP-EV71(S37N-nt574T/A), EGFP-EV71(R142K-nt574T/A), EGFP-EV71(R142K-nt88C/T), and EGFP-EV71(R142K-nt157G/A). The results showed that the high replicative strains significantly promoted the accumulation of autophagosomes in host cells and hindered the degradation of autolysosomes. The low replicative strains had a low ability to regulate the autophagy of host cells. In addition, the high replicative strains also significantly inhibited the phosphorylation of AKT and mTOR. CONCLUSIONS: EV71 5'UTR interacted with the 3D protein during virus replication. The co-mutation of S37N and nt88C/T, S37N and nt574T/ A, R142K and nt574T/A induced incomplete autophagy of host cells and promoted virus replication by inhibiting the autophagy pathway AKT-mTOR. The co-mutation of R142K and nt88C/T, and R142K and nt157G/A significantly reduced the inhibitory effect of EV71 on the AKT-mTOR pathway and reduced the replication ability of the virus.

Synergistic photodynamic/photothermal bacterial inactivation over heterogeneous quaternized chitosan/silver/cobalt phosphide nanocomposites.

Globally, drug-resistant bacteria are a potential threat to human society owing to the overuse of antibiotics and thus, non-antibiotic bactericides are urgently needed. Herein, an innovative antibacterial nanoplatform based on quaternized chitosan (QCS)/ silver (Ag)/ cobalt phosphide (CoP) nanocomposites is envisaged for achieving near-infrared (NIR) laser-inducible rapid sterilisation. In the core-shell hybrids, Ag nanoparticles (NPs) with a size of âˆ¼ 25 nm were uniformly deposited on CoP nanoneedles, upon which a layer of QCS (approximately 10 wt%), is coated. Numerical calculations revealed that under NIR irradiation, high-energy hot electrons arising from the surface plasmon resonance effect of Ag migrate into the interface between Ag and CoP, and amplify the photothermal effect of CoP. Meanwhile, photo-excited electrons from CoP are transported onto Ag NPs because the Schottky heterostructure facilitates the production of reactive oxygen species. Ag loading simultaneously enhances the photocatalytic and photothermal effects of CoP, achieving rapid antibacterial activity synergistically. The QCS coating improves the dispersibility of power in an aqueous system and provides contact between the antiseptics and bacteria. The ternary QCS/Ag/CoP nanocomposites achieved greater than 99.6% inactivation against S. aureus and E. coli within 10 min. In addition, the nanocomposites were confirmed to be noncytotoxic to mammals. Consequently, the QCS/Ag/CoP nanoplatforms possess great potential for rapid and effective antibacterial applications.

Scoring Model for Predicting the Occurrence of Severe Illness in Hospitalized Patients with Severe Fever with Thrombocytopenia Syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever with high mortality. Severe cases progressed rapidly, with deaths occurring within 2 weeks. Therefore, constructing a model to predict disease progression among hospitalized patients plays an important role in clinical practice. The development cohort included 121 patients with SFTS, 25 with severe SFTS, and 96 with mild SFTS. Two of the 64 variables were independent risk factors, including neurological symptoms (odds ratio [OR], 12.915; 95% confidence interval [CI], 3.342-49.916; P < 0.001) and aspartate aminotransferase/alanine aminotransferase levels (OR, 1.891; 95% CI, 1.272-2.813; P = 0.002). The model's area under the curve (AUC) was 0.882 (95% CI: 0.808-0.956). The mean AUC value obtained from the internal validation was 0.883 (95% CI: 0.809-0.957). The AUC in the external validation cohort was 0.873 (95% CI: 0.775-0.972). This model can be used to identify severely ill patients as early as possible with high predictive value, stability, and repeatability. This model can help clinicians with their treatment plans.