As one of the crucial targets of epigenetics, histone lysine-specific demethylase 1 (LSD1) is significant in the occurrence and development of various tumors. Although several irreversible covalent LSD1 inhibitors have entered clinical trials, the large size and polarity of the FAD-binding pocket and undesired toxicity have focused interest on developing reversible LSD1 inhibitors. In this study, targeting the substrate-binding pocket of LSD1, structure-based and ligand-based virtual screenings were adopted to expand the potential novel structures with molecular docking and pharmacophore model strategies, respectively. Through drug-likeness evaluation, ADMET screening, molecular dynamics simulations, and binding free energy screening, we screened out one and four hit compounds from the databases of 2,029,554 compounds, respectively. Generally, these hit compounds can be divided into two categories, amide (Lig2 and Comp2) and 1,2,4-triazolo-4,3-α-quinazoline (Comp3, Comp4, Comp7). Among them, Comp4 exhibits the strongest binding affinity. Finally, the binding mechanisms of the hit compounds were further calculated in detail by the residue free energy decomposition. It was found that van der Waals interactions contribute most to the binding, and FAD is also helpful in stabilizing the binding and avoiding off-target effects. We believe this work not only provides a solid theoretical foundation for the design of LSD1 substrate reversible inhibitors, but also expands the diversity of parent nucleus, offering new insights for synthetic chemists.

The erm(B) gene in Campylobacter Spp., conferring resistance to macrolides, is of great concern worldwide. In this study, the prevalence of erm(B) in Campylobacter of retail chicken meat origin was investigated and the characterization of erm(B)-harboring Campylobacter isolates was analyzed. Antimicrobial susceptibility testing was performed to determine the susceptibility of Campylobacter isolates. Whole-genome sequencing and analysis were used to characterize sequence type (ST) and genetic context of erm(B). Natural transformation was conducted to evaluate transferability of the erm(B) gene. A total of 16 (11.8%) Campylobacter isolates were obtained from 136 samples collected from retail chicken meat, amongst which five erm(B)-positive isolates were identified as Campylobacter coli belonging to ST3753 (n = 4) and ST825 (n = 1). A total of 22 Campylobacter Spp. were erm(B)-positive in GenBank database; all isolates were collected in China except for one Campylobacter jejuni isolate. Diverse STs were involved in these erm(B)-carrying isolates. Comparison analysis indicated that 11 types of genetic environment for erm(B) were identified, mostly associated with multidrug-resistance genomic islands (MDRGIs). The genetic context of erm(B) in C. coli of retail chicken meat origin showed high nucleotide sequence similarity with that of C. coli from humans. This is the first report of prevalence and characterization for erm(B) in Campylobacter of retail chicken meat origin. The genetic context of erm(B) in C. coli isolates from retail chicken meat is highly homologous with that of C. coli from humans; this impies the possibility of zoonotic transmission of erm(B) in Campylobacter, which presents a threat to public health.

By blocking the DEK protein, DEK-targeted aptamers (DTAs) can reduce the formation of neutrophil extracellular traps (NETs) to reveal a strong anti-inflammatory efficacy in rheumatoid arthritis. However, the poor stability of DTA has greatly limited its clinical application. Thus, in order to design an aptamer with better stability, DTA was modified by methoxy groups (DTA_OMe) and then the exact DEK–DTA interaction mechanisms were explored through theoretical calculations. The corresponding 2′-OCH₃-modified nucleotide force field was established and the molecular dynamics (MD) simulations were performed. It was proved that the 2′-OCH₃-modification could definitely enhance the stability of DTA on the premise of comparative affinity. Furthermore, the electrostatic interaction contributed the most to the binding of DEK–DTA, which was the primary interaction to maintain stability, in addition to the non-specific interactions between positively-charged residues (e.g., Lys and Arg) of DEK and the negatively-charged phosphate backbone of aptamers. The H-bond network analysis reminded that eight bases could be mutated to probably enhance the affinity of DTA_OMe. Therein, replacing the 29th base from cytosine to thymine of DTA_OMe was theoretically confirmed to be with the best affinity and even better stability. These research studies imply to be a promising new aptamer design strategy for the treatment of inflammatory arthritis.