The inhibition of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) potentially represents a new treatment option for malaria, as P. falciparum relies entirely on a de novo pyrimidine biosynthetic pathway for survival. Herein, we report a series of pyrimidone derivatives as novel inhibitors of PfDHODH. The most potent compound, 26, showed high inhibition activity against PfDHODH (IC₅₀ = 23 nM), with >400-fold species selectivity over human dihydroorotate dehydrogenase (hDHODH). The brand-new inhibitor scaffold targeting PfDHODH reported in this work may lead to the discovery of new antimalarial agents.

Background: Small non-coding RNAs play critical regulatory roles in post-transcription. However, their characteristics in Trichomonas vaginalis, the causative agent of human sexually transmitted trichomoniasis, still remain to be determined. Methods: Small RNA transcriptomes from Trichomonas trophozoites were deep sequenced using the Illumina NextSeq 500 system and comprehensively analyzed to identify Trichomonas microRNAs (miRNAs) and transfer RNA (tRNA)-derived small RNAs (tsRNAs). The tsRNA candidates were confirmed by stem-loop quantitative reverse transcription-PCR, and motifs to guide the cleavage of tsRNAs were predicted using the GLAM2 algorithm. Results: The miRNAs were found to be present in T. vaginalis but at an extremely low abundance (0.0046%). Three categories of endogenous Trichomonas tsRNAs were identified, namely 5′tritsRNAs, mid-tritsRNAs and 3′tritsRNAs, with the 5′tritsRNAs constituting the dominant category (67.63%) of tsRNAs. Interestingly, the cleavage site analysis verified both conventional classes of tRNA-derived fragments (tRFs) and tRNA-halves in tritsRNAs, indicating the expression of tRNA-halves in the non-stress condition. A total of 25 tritsRNAs were experimentally confirmed, accounting for 78.1% of all tested candidates. Three motifs were predicted to guide the production of tritsRNAs. The results prove the expression of tRFs and tRNA-halves in the T. vaginalis transcriptome. Conclusions: This is the first report of genome-wide investigation of small RNAs, particularly tsRNAs and miRNAs, from Trichomonas parasites. Our findings demonstrate the expression profile of tsRNAs in T. vaginalis, while miRNA was barely detected. These results may promote further research aimed at gaining a better understanding of the evolution of small non-coding RNA in T. vaginalis and their functions in the pathogenesis of trichomoniasis. Graphical

Background: Milk powder is a key food source, especially for infants and vulnerable groups. However, Bacillus contamination during production, storage, or handling can cause spoilage, quality issues, or health risks. This study identified and isolated Bacillus subtilis from commercially available Chinese milk powder. Methods: A pure colony of Bacillus subtilis was isolated from an LB agar plate supplemented with milk powder and identified using mass spectrometry. The genome of this strain was sequenced using third-generation sequencing technology. Following assembly, the genome was functionally annotated and subjected to comprehensive bioinformatic analysis. Results: Genomic analysis classified the strain as Bacillus subtilis via MALDI-TOF and ANI (98.82% with B. subtilis AMR1). Its genome features a 4.26 Mbp chromosome and 97.6 kbp plasmid encoding 4,539 genes, including virulence factors (209 genes), antibiotic resistance genes (19 genes), and carbohydrate-active enzymes (253 genes). Key virulence mechanisms include immune modulation, stress adaptation, toxin production, and biofilm formation. Antibiotic resistance involves efflux pumps (eg, qacJ, bmr), enzymatic inactivation (eg, FosBx1, aadK), and target modification (eg, vanG cluster, tet(45)). Phylogenetically (LIN78), the strain clusters with foodborne B. subtilis isolates (eg, from Korean gochujang and soybean), diverging from B. cereus and environmental Bacillus clades. Comparative genomics revealed 53 LIN78-specific genes, encompassing defense mechanisms and mobile elements, and synteny in all homologs except B. subtilis ATCC 11774. Genomic islands, CRISPR arrays, and recombination-associated repeats indicate adaptive evolution. Conclusion: This study characterizes Bacillus subtilis LIN78, a genomically plastic strain isolated from Chinese milk powder. It exhibits adaptation to food environments via horizontal gene transfer, stress tolerance, and spoilage traits, while carrying antimicrobial resistance risks and potential biotechnological applications. The findings necessitate genomic monitoring to manage food safety, resistance spread, and leverage its dual role as both a spoilage organism and source of bioactive compounds..

Objective: To systematically evaluate and integrate the real experience of burn patients during rehabilitation, and to provide theoretical guidance for the continual nursing care for burn patients. Methods: The systematic evaluation method was adopted. Databases including the China National Knowledge Internet, Wanfang Database, China Biology Medicine disc were retrieved with the search terms in Chinese version of "/, //, ////", and PubMed, Embase, CINAHL, PsycINFO, Cochrane Library were retrieved with the search terms of "burn/burns, rehabilitation/recovery/survivor/survive, experience/views/perceptions/, qualitative/phenomenon/interview/grounded theory". The qualitative studies on the real experience of burn patients during rehabilitation published from the establishment of each database to June 2020 were searched. The quality of the included studies was evaluated according to the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence-Based Health Care Center. The research country, research method, research object, research content, and main research result were summarized, and meta-synthesis of the research results was conducted with the aggregative integration method. Results: A total of 12 studies were included, and the quality of all the studies was grade B. The studies were conducted in 8 countries including Australia, Canada, Norway, etc., the research method mainly was phenomenological research method, and all the studies were focused on adult burn patients. A total of 46 specific themes were extracted with totally 10 new categories formed after summarization, and 3 integrated results were obtained as follows: burn patients suffered from both physical and psychological burdens, and their normal life was broken; burn patients gained post-traumatic growth and could actively adjust to cope with life difficulties; burn patients had multiple needs. Conclusions: Burn patients experience both physical and psychological pains during rehabilitation, so they long for multiple support from family and society. Medical staff, social groups, and family members should pay attention to the psychological experience and needs of burn patients with different characteristics during rehabilitation, and build a multi-directional social support system to help patients return to the society and rebuild their lives.