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Introduction: Brucellosis, an infectious zoonotic disease caused by members of the genus Brucella , results in chronic multi-organ injury. Improving the specificity and sensitivity of serological methods for diagnosing brucellosis necessitates the development of novel diagnostic antigens. The twin-arginine translocation (Tat) pathway is responsible for transporting folded proteins across the cytoplasmic membrane and has been implicated in the virulence of Brucella. Three Tat substrate proteins—L,D-transpeptidase ErfK (A0577), linear amide C-N hydrolase YxeI (A1479), and thioesterase domain-containing protein EntF (B0249)—contribute significantly to Brucella virulence. However, the roles of these Tat substrate proteins in diagnosing brucellosis remain unclear. Methods: In this study, ErfK, YxeI, and EntF were expressed in prokaryotic cells and utilized as diagnostic antigens. The clinical sera from bovines and sheep diagnosed with brucellosis were analyzed using indirect ELISA with these proteins. Results: For bovine serum, the combined protein group (ErfK + YxeI + EntF) and YxeI demonstrated the highest diagnostic accuracy of 94.23% and 93.58%, respectively. Meanwhile, the combined protein group showed the strongest ability to detect Brucella in sheep serum, achieving an accuracy of 88.10%. Both the combined protein group and YxeI displayed no cross-reactivity with rabbit serum immunized against Yersinia enterocolitica O9, Escherichia coli O157:H7, Mycobacterium tuberculosis , Vibrio cholerae , Legionella , and Salmonella , indicating relatively good specificity. Conclusion: The findings of this study suggest that Tat substrate proteins serve as promising candidate antigens with significant potential value for the clinical diagnosis of brucellosis. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an idiopathic and chronic autoimmune disease for which there are currently no effective treatments. Oxypeucedanin hydrate (OXH) is a natural coumarin known for its potent anti-inflammatory properties. However, further investigations are needed to determine its therapeutic efficacy in treating RA. In this study, we evaluate the anti-inflammatory activity of OXH by treating LPS-induced RAW264.7 macrophages. Our results show that OXH treatment reverses the changes in iNOS, COX-2, IL-1β, IL-6, and TNF-α levels. Additionally, OXH reduces ROS production. Further analysis reveals that OXH suppresses the activation of the NF-κB/MAPK pathway. CETSA results show that OXH competes with LPS for binding to the TLR4/MD2 complex. MST experiments demonstrate the specific affinity of OXH for the TLR4/MD2 complex, with a Kd value of 33.7 μM. Molecular docking analysis suggests that OXH binds to the pocket of the TLR4/MD2 complex and interacts with specific amino acids, such as GLY-343, LYS-388, and PHE-345. Molecular dynamics simulations further confirm this conclusion. Finally, we investigate the potential of OXH in treating RA using a collagen-induced arthritis (CIA) model in rats. OXH effectively ameliorates the symptoms of CIA, including improving body weight, reducing swelling and redness, increasing talus volume, and decreasing bone erosion. OXH also decreases the mRNA levels of pro-inflammatory factors in synovial tissue. Transcriptome enrichment analysis and western blot analysis confirm that OXH suppresses the NF-κB/MAPK pathway, which is consistent with our in vitro findings.

HoBi‐like pestivirus is an emerging atypical pestivirus in cattle and small ruminants, causing clinical signs similar to those observed in bovine viral diarrhoea virus infections. Natural infection of HoBi‐like pestivirus has been reported in cattle herds and small ruminants in multiple countries in South America, Europe and Asia. However, HoBi‐like pestiviruses were only identified from contaminated bovine serum and small ruminants in China. So far, no clinical cases induced by HoBi‐like pestivirus infection were reported in Chinese cattle herds. Here, for the first time, we reported natural infection of HoBi‐like pestivirus in a cattle herd in China. Sick cattle with severe respiratory and diarrhoea and high fatality rate were found in a beef cattle herd in Shandong province in November 2017. RT‐PCR, viral isolation, sequencing and phylogenetic analysis showed that the primary causative agent was HoBi‐like pestivirus. The isolated HoBi‐like pestivirus strain, SDJN‐China‐2019, shared 94.1%–97.5% homology with the LV168‐20_16RN strain from Brazil in nucleotide of 5′UTR, Npro and E2 while it shared only 88.5%–92.1% homology with Asian HoBi‐like virus strain Th/04‐Khonkaen. Multiple unique mutations of amino acid were observed in Npro and E2 proteins of SDJN‐China‐2019, which were different from that of other reference strains. In summary, this study provides the first evidence of HoBi‐like pestivirus infection in Chinese cattle herds, raising potential threat to the cattle industry in China. [ABSTRACT FROM AUTHOR]

Pseudorabies virus (PRV) infects numerous species of domestic and wild animals leading to severe diseases especially in swine and cattle. Since 2011, the variant PRVs were identified in pigs, which were genetically different from classic strains. Although variant PRV infection is widely observed in pigs, there is still no report of variant PRV infection in cattle. Here, we reported a natural infection of variant PRV leading to acute bovine death in Eastern China. Our study suggests that the new variant PRV strains could be a potential threat to cattle industry and possibly to the public health of human. [ABSTRACT FROM AUTHOR]