The influenza A virus (IAV), renowned for its high contagiousness and potential to catalyze global pandemics, poses significant challenges due to the emergence of drug-resistant strains. Given the critical role of RNA polymerase in IAV replication, it stands out as a promising target for anti-IAV therapies. In this study, we identified a novel C-3-substituted oleanolic acid benzyl amide derivative, A5, as a potent inhibitor of the PA_C-PB1_N polymerase subunit interaction, with an IC₅₀ value of 0.96 ± 0.21 μmol/L. A5 specifically targets the highly conserved PA_C domain and demonstrates remarkable efficacy against both laboratory-adapted and clinically isolated IAV strains, including multidrug-resistant strains, with EC₅₀ values ranging from 0.60 to 1.83 μmol/L. Notably, when combined with oseltamivir, A5 exhibits synergistic effects both in vitro and in vivo. In a murine model, dose-dependent administration of A5 leads to a significant reduction in IAV titers, resulting in a high survival rate among treated mice. Additionally, A5 treatment inhibits virus-induced Toll-like receptor 4 activation, attenuates cytokine responses, and protects against IAV-induced inflammatory responses in macrophages. In summary, A5 emerges as a novel inhibitor with high efficiency and broad-spectrum anti-influenza activity.

Although the diagnosis of glioma is constantly changing with the update of WHO diagnostic guidelines, the current treatment methods are still mainly surgical treatment, supplemented by radiotherapy and chemotherapy. It is a pity that the treatment effect of high-grade glioma is still unsatisfactory. How to improve the prognosis of patients is the key problem in the field of medical exploration of glioma. It is gratifying that many new ideas and methods have emerged in the diagnosis and treatment of glioma, in which some trials represented by tumor treating fields have achieved good results in clinical research, moreover, the fields of immunotherapy and targeted therapy have developed too. This paper aims to share and explore these new methods and summarize the progress of diagnosis and treatment of glioma.

We produced high pathogenic avian influenza H5N1 haemagglutinin protein HA1 in recombinant Pichia pastoris in a 10 L fermentor, to establish a high-density cell fermentation method. We studied the effects of different factors such as culture temperature, induced temperature, methanol feeding methods, trace elements on the growth of Pichia pastoris, the yield and the biologic activity of recombinant HA1 protein. The culture temperature in pre-induced and induced stage were optimized at 25 degrees C to adapt cell growth and recombinant protein expression, and induced temperature at 25 degrees C also resulted in higher biologic activity of rHA1 than at 30 degrees C. The binding activity of rHA1 against a wide-spectrum neutralizing antibody was susceptible to the presence of any trace elements, although trace elements would essentially benefit for the cell fermentation. As a conclusion, the expression level of rHA1 produced with optimized fermentation process reached 120 mg/L, which was 10.5 times higher than the one produced in regular shaking flask. The resultant high-density cell fermentation can likely produce rHA1 of H5N1 in large scale.
Fermentation ; Hemagglutinins, Viral ; biosynthesis ; genetics ; Influenza A Virus, H5N1 Subtype ; genetics ; metabolism ; Pichia ; genetics ; metabolism ; Recombinant Proteins ; biosynthesis

This study aims at restoring the skin from traumatism by use of the collagen(from piglet skin) and konjac glucomannan-chondroitin sulfate blend film. The 2 cm x 4 cm skin traumatism model was established on both sides of the waist spinal column in 14 New Zealand rabbits each weighing 1.5-2.0 kg. One side was covered with blend film, the other side was used as a control. Then the changes of the skin traumatism were observed at different time-points after the operation, the wound tissue samples were taken for histological examination. The blend film could prevent skin traumatism from bleeding and infection. The skin traumatism treated by blend film showed signs of rectangle scab and the control showed signs of linear scab after healing. No obvious immune rejection was seen. The collagen-konjac glucomannan-chondroitin sulfate blend film can accelerate the restoration of skin from traumatism.
Animals ; Chondroitin Sulfates ; therapeutic use ; Collagen ; therapeutic use ; Female ; Male ; Mannans ; therapeutic use ; Membranes, Artificial ; Rabbits ; Skin ; injuries ; Skin Ulcer ; drug therapy ; Wound Healing ; drug effects