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Foot-and-mouth disease virus (FMDV) poses a significant threat to the livestock industry. Through their recognition of the conserved epitopes presented by the swine leukocyte antigen (SLA), T cells play a pivotal role in the antiviral immunity of pigs. Herein, based on the peptide binding motif of SLA-2*HB01, from an original SLA-2 allele, a series of functional T-cell epitopes derived from the dominant antigen VP1 of FMDV with high binding capacity to SLA-2 were identified. Two parallel peptides, Hu64 and As64, from the O and Asia I serotypes, respectively, were both crystallized with SLA-2*HB01. Compared to SLA-1 and SLA-3, the SLA-2 structures showed the flexibility of residues in the P4, P6, and P8 positions and in their potential interface with TCR. Notably, the peptides Hu64 and As64 adopted quite similar overall conformation when bound to SLA-2*HB01. Hu64 has two different conformations, a more stable 'chair' conformation and an unstable 'boat' conformation observed in the two molecules of one asymmetric unit, whereas only a single 'chair' conformation was observed for As64. Both Hu64 and As64 could induce similar dominant T-cell activities. Our interdisciplinary study establishes a basis for the in-depth interpretation of the peptide presentation of SLA-I, which can be used toward the development of universal vaccines. [ABSTRACT FROM AUTHOR]

Thiopurine dose optimization by thiopurine‐S‐methyltransferase (TPMT) or nudix hydrolase‐15 (NUDT15) significantly reduced early leucopenia in Asia. However, it fails to avoid the late incidence (> 2 months). Although laboratory monitoring of 6‐thioguanine nucleotides (6TGN) to optimize thiopurine dose was suggested in White patients the exact association between leucopenia and 6TGN was controversial in Asian patients. In the present study, we aimed to explore whether DNA‐thioguanine nucleotides (DNA‐TGs) in leukocytes, compared with 6TGN in erythrocytes, can be a better biomarker for late leucopenia. This was a prospective, observational study. Patients with inflammatory bowel disease (IBD) prescribed thiopurine from February 2019 to December 2019 were recruited. Thiopurine dose was optimized by NUDT15 C415T (rs116855232). DNA‐TG and 6TGN levels were determined at the time of late leucopenia or 2 months after the stable dose was obtained. A total of 308 patients were included. Thiopurine induced late leucopenia (white blood cells < 3.5 × 109/L) were observed in 43 patients (14.0%), who had significantly higher DNA‐TG concentration than those without leucopenia (P = 4.1 × 10–9, 423.3 (~ 342.2 to 565.7) vs. 270.5 (~ 188.1 to 394.3) fmol/μg DNA). No difference in 6TGN concentrations between leucopenia and non‐leucopenia was found. With a DNA‐TG threshold of 340.1 fmol/μg DNA, 83.7% of leucopenia cases could be identified. Multivariate analysis showed that DNA‐TG was an independent risk factor for late leucopenia. Quantification of DNA‐TG, rather than 6TGN, can be applied to gauge thiopurine therapy after NUDT15 screening in Chinese patients with IBD. [ABSTRACT FROM AUTHOR]

The sea cucumber Apostichopus japonicus is an economically important species in Asia. Large growth differences have been recorded for A. japonicus during field surveys and culture practices. These growth differences can seriously impact the recovery of wild populations and breeding efficiencies in aquaculture systems. This study explored differences in movement behavior, feeding behavior, digestive ability and intestinal microbes of A. japonicus that displayed obvious differences in growth under the same culture conditions. The results showed that there was no significant difference in the movement behavior of A. japonicus with different growth rates, but the feeding behavior of slow-growing A. japonicus was significantly reduced. The activity of trypsin, the main digestive enzyme in A. japonicus , was significantly decreased in slow-growing individuals. There was a marked variation in the gut microbiota composition of sea cucumbers with different growth rates. Compared with slow-growing A. japonicus , fast-growing A. japonicus had a higher α diversity, and abundance of Rhodobacteraceae, Rubritaleaceae, and Pirellulaceae. Many of these bacteria were related to the algal polysaccharide degradation. However, the abundance of Vibrionaceae and Burkholderiaceae was higher in slow-growing A. japonicus, which contained potential pathogenic bacteria. This indicated the differences in feeding behavior, digestive ability and intestinal microbiota was related to different growth rates of A. japonicus. These differences will continue to promote growth differences over time. This research provided new insights for understanding the large growth differences in A. japonicus. • New insights for the large growth differences of sea cucumbers were provided. • The feeding behavior of slow-growing sea cucumbers is significantly reduced. • The reduction of digestive ability and the quality of intestinal microbiota was related to the slow growth of sea cucumbers. [ABSTRACT FROM AUTHOR]