A sequence-based machine learning model for predicting antigenic distance for H3N2 influenza virus

IntroductionSeasonal influenza A H3N2 viruses are constantly changing, reducing the effectiveness of existing vaccines. As a result, the World Health Organization (WHO) needs to frequently update the vaccine strains to match the antigenicity of emerged H3N2 variants. Traditional assessments of antigenicity rely on serological methods, which are both labor-intensive and time-consuming. Although numerous computational models aim to simplify antigenicity determination, they either lack a robust quantitative linkage between antigenicity and viral sequences or focus restrictively on selected features.MethodsHere, we propose a novel computational method to predict antigenic distances using multiple features, including not only viral sequence attributes but also integrating four distinct categories of features that significantly affect viral antigenicity in sequences.ResultsThis method exhibits low error in virus antigenicity prediction and achieves superior accuracy in discerning antigenic drift. Utilizing this method, we investigated the evolution process of the H3N2 influenza viruses and identified a total of 21 major antigenic clusters from 1968 to 2022.DiscussionInterestingly, our predicted antigenic map aligns closely with the antigenic map generated with serological data. Thus, our method is a promising tool for detecting antigenic variants and guiding the selection of vaccine candidates

Growth performance, digestive capacity and intestinal health of juvenile spotted seabass (Lateolabrax maculatus) fed dietary laminarin supplement

Laminarin has antioxidant and immunomodulatory properties and favorably impacts gut microbial composition, providing a potential solution for the treatment of intestinal diseases in fish. The aim of this study was to investigate the effects of laminarin on the growth and intestinal health of juvenile spotted seabass, Lateolabrax maculatus. A total of 450 juveniles (initial body weight: 7.14 ± 0.10 g) were randomly divided into 6 groups with 3 replicates per group and 25 fish per replicate. Six diets were prepared with laminarin supplementation at doses of 0% (Control), 0.4% (P0.4), 0.8% (P0.8), 1.2% (P1.2), 1.6% (P1.6), and 2% (P2). Each group was fed the corresponding diet for 8 weeks. The results indicated that dietary laminarin supplementation of 0.4-1.6% enhanced the specific growth rate (SGR), weight gain rate (WGR), and feed conversion ratio (FCR) of juvenile spotted seabass, and the difference was significant in the P0.8 group (P<0.05). Significantly higher intestinal amylase activity was measured in P0.8 compared with the control group. Trypsin activity was significantly increased in P0.4 and P0.8 groups in contrast to the control (P<0.05). Lipase activity was significantly increased in P0.4, P0.8, P1.6, and P2 groups in contrast to the control (P<0.05). Total antioxidant capacity was significantly increased in the P0.8, P1.2, and P1.6 groups compared to the control group (P<0.05). The P0.8 group exhibited significant increases in reduced glutathione, alkaline phosphatase, and lysozyme levels (P<0.05), whereas the concentrations of diamine oxidase and D-lactate were significantly decreased (P<0.05). Furthermore, intestinal villus height, villus width, and crypt depth were significantly increased in P0.8 and P2 groups (P<0.05), and muscular thickness was significantly increased in the P1.2 group (P<0.05). Intestinal microbial analysis revealed that the alpha diversity of the laminarin supplemented groups was significantly higher than that of the control group. Moreover, the abundance of intestinal beneficial bacteria Lactobacillus and Klebsiella in P0.4 and P0.8 groups was significantly increased (P<0.05), indicating that laminarin altered the composition of intestinal flora and the abundance of dominant bacteria, with a low dose being more conducive to the formation of beneficial bacteria. In conclusion, dietary laminarin supplementation can improve the growth performance and intestinal function of juvenile spotted seabass. Based on the regression analyses of weight gain rate and specific growth rate, the optimal supplemental level of laminarin was estimated to be 0.97% and 0.98%, respectively

Characterizing Emerging Canine H3 Influenza Viruses.

The continual emergence of novel influenza A strains from non-human hosts requires constant vigilance and the need for ongoing research to identify strains that may pose a human public health risk. Since 1999, canine H3 influenza A viruses (CIVs) have caused many thousands or millions of respiratory infections in dogs in the United States. While no human infections with CIVs have been reported to date, these viruses could pose a zoonotic risk. In these studies, the National Institutes of Allergy and Infectious Diseases (NIAID) Centers of Excellence for Influenza Research and Surveillance (CEIRS) network collaboratively demonstrated that CIVs replicated in some primary human cells and transmitted effectively in mammalian models. While people born after 1970 had little or no pre-existing humoral immunity against CIVs, the viruses were sensitive to existing antivirals and we identified a panel of H3 cross-reactive human monoclonal antibodies (hmAbs) that could have prophylactic and/or therapeutic value. Our data predict these CIVs posed a low risk to humans. Importantly, we showed that the CEIRS network could work together to provide basic research information important for characterizing emerging influenza viruses, although there were valuable lessons learned

Regulation of ryanodine receptors by luminal calcium

Bibliography: p. 153-163Some pages are in colour

Influence of drying–wetting cycles on soil-water characteristic curve of undisturbed granite residual soils and microstructure mechanism by nuclear magnetic resonance (NMR) spin-spin relaxation time (T2) relaxometry

Due to the formational environment and climatic variability, granite residual soils with grain size distribution ranging from gravel to clay, are experienced by multiple drying-wetting cycles. The Influences of multiple drying-wetting cycles on the soil-water characteristic curve (SWCC) and pore size distribution (POSD) of undisturbed granite residual soils are investigated using the pressure plate test and nuclear magnetic resonance (NMR) spin-spin relaxation time (T2) distribution measurement, respectively. The result shows that the water-retention capacity, air entry value decreases and pores become more uniform with increasing drying-wetting cycles. After 4 drying-wetting cycles, the soil reaches to a nearly constant state. The POSD change of multiple drying-wetting cycle samples possesses consistency with the SWCC of the soils. Furthermore, a modified van Genuchten model in terms of cumulative pore volume is used to obtain the best-fit POSD of the drying-wetting cycle samples. The shape and changing tendency of both curves of SWCC and POSD are quite similar and observed a better correlation. It can be concluded that the SWCC is strongly dependent on the POSD of the soil and NMR T2 relaxometry can be used as an alternative for the assessment of micro-structural variation of residual soils subjected to the periodic drying and wetting process.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

IL-6/IFN-γ double knockdown CAR-T cells reduce the release of multiple cytokines from PBMCs in vitro

CD19-targeted chimeric antigen receptor T (anti-CD19 CAR-T) cells have shown good therapeutic results in the treatment of CD19 + B cell acute lymphocytic leukemia and lymphoma. However, severe side reactions and cytotoxicity are great challenges in the application of anti-CD19 CAR-T cell therapy. Cytokine release syndrome (CRS) is the main side effect of CAR-T cell treatment, and interleukin-6 (IL-6) and interferon γ (IFN-γ) are cytokines that play major roles in CRS. Therefore, we investigated double knockdown (KD) of IL-6 and IFN-γ as a potential strategy to manage anti-CD19 CAR-T cell-associated CRS. These improved anti-CD19 CAR-T cells therapy retained the advantages of the original anti-CD19 CAR-T cells and additionally reduced the release of cytokines from CAR-T cells and other immune cells. Moreover, this study presented a novel approach to abrogate CRS through IL-6 and IFN-γ KD, which may potentially inhibit the release of multiple cytokines from CAR-T cells and peripheral blood mononuclear cells (PBMCs), a model of CRS correlate with in vivo features of the CAR-T therapy, thereby reducing the impact of CRS, improving the safety of CAR-T cell treatment, reducing toxicities, and maintaining the function of CAR-T cells