The diagnostic delays pose a huge challenge to human brucellosis (HB), which increases the risk of chronicity and complications with a heavy disease burden. This study aimed to quantify and identify the associated factors in the diagnostic delays to its prevention, reduction, and elimination. This study analyzed risk factors associated with the diagnostic delays in a cross-sectional study with data collected from Tongliao City, Inner Mongolia Autonomous Region of China. Diagnostic delays were defined with a cutoff of 30, 60, and 90 days. In different delay groups, risk factors of diagnostic delays were analyzed by univariate analysis and modeled by multivariate logistic regression analysis. A total of 14,506 cases were collected between January 1, 2005, and December 31, 2017, of which the median diagnostic delays was 29 days [interquartile range (IQR): 14–54 days]. Logistic regression analysis indicated that the older age category was associated with longer diagnostic delays across all groups. Longer diagnostic delays increase with age among three delay groups (p for trend <0.001). Occupation as herdsman was associated with shorter diagnostic delays in group 1 with 30 days [adjusted odds ratio (aOR), 0.890 (95% CI 0.804–0.986)]. Diagnostic delays was shorter in patients with brucellosis who were reported in CDC in all delay groups [aOR 0.738 (95% CI 0.690–0.790), 0.539 (95% CI 0.497–0.586), and 0.559 (95% CI 0.504–0.621)]. Pastoral/agricultural area was associated with shorter diagnostic delays in group 1 with 30 days [aOR, 0.889 (95%CI 0.831–0.951)] and group 3 with 90 days [aOR, 0.806 (95%CI 0.727–0.893)]. Stratified analysis showed that the older age category was associated with an increased risk of a long delay in both genders (p < 0.05). The older age group-to-youth group OR increased along with increased delay time (p for trend <0.001). Furthermore, the pastoral/agricultural area was associated with a shorter delay in males (p < 0.05). Delays exist in the diagnosis of HB. We should pay great attention to the risk factors of diagnostic delays, such as older population, non-herdsman, non-pastoral/agricultural area, non-disease prevention, and control agencies. Effective measures should shorten the diagnostic delays, achieve early detection, diagnosis, and treatment, and reduce the risk of HB's chronicity, complications, and economic burden.

The African Swine Fever virus (ASFV) causes an infectious viral disease in pigs of all ages. The development of antiviral drugs primarily aimed at inhibition of proteases required for the proteolysis of viral polyproteins. In this study, the conformation of the pS273R protease in physiological states were investigated, virtually screened the multi-protein conformation of pS273R target proteins, combined various molecular docking scoring functions, and identified five potential drugs from the Food and Drug Administration drug library that may inhibit pS273R. Subsequent validation of the dynamic interactions of pS273R with the five putative inhibitors was achieved using molecular dynamics simulations and binding free energy calculations using the molecular mechanics/Poison-Boltzmann (Generalized Born) (MM/PB(GB)SA) surface area. These findings demonstrate that the arm domain and Thr159-Lys167 loop region of pS273R are significantly more flexible compared to the core structural domain, and the Thr159-Lys167 loop region can serve as a “gatekeeper” in the substrate channel. Leucovorin, Carboprost, Protirelin, Flavin Mononucleotide, and Lovastatin Acid all have Gibbs binding free energies with pS273R that were less than −20 Kcal/mol according to the MM/PBSA analyses. In contrast to pS273R in the free energy landscape, the inhibitor and drug complexes of pS273R showed distinct structural group distributions. These five drugs may be used as potential inhibitors of pS273R and may serve as future drug candidates for treating ASFV.