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The increasing prevalence of drug-resistant bacteria has prompted the search for alternative approaches to address bacterial infections. Lanthipeptides, which are small molecule peptides, are biosynthesized and post-translationally modified by ribosomes in gram-positive bacteria. These compounds possess distinctive target recognition properties, making them highly potential candidates for combating antimicrobial resistance. Consequently, they hold promising potential as innovative substitutes for traditional antibiotics. We conducted a comprehensive analysis of 65 publicly available Bacillus amyloliquefaciens genomes' data to explore the potential for lanthipeptide synthesis in this species. We annotated 21 putative precursor peptide genes for these novel lanthipeptides. Through heterologous expression experiments, we successfully obtained a novel lanthipeptide named amyA3. We accomplished a novel co-transformation strategy by introducing the synthetic enzyme obtained from B. amyloliquefaciens WS-8 into the E. coli BL21 (DE3) strain along with the heterologous precursor peptide amyA3. Through mass spectrometry analysis, we confirmed the successful modification of amyA3 by the synthetic enzyme derived from B. amyloliquefaciens WS-8, which represents a significant breakthrough in this research field. The identification and characterization of the lanthipeptide amyA3 along with the elucidation of its biosynthetic pathway provide novel perspectives into the discovery of naturally derived products and the intricate processes of translation and post-translational modifications. [ABSTRACT FROM AUTHOR]

Echinococcus granulosus causes echinococcosis, an important zoonotic disease worldwide and a major public health issue. Vaccination is an economical and practical approach for controlling E. granulosus. We have previously revealed that a recombinant protein P29 (rEg.P29) is a good vaccine candidate against E. granulosus. However, T cell immunogenic epitopes have not been identified. In the present study, we use rEg.P29-immunized mice as models to screen immunogenic epitopes for the construction of a novel multi-epitope vaccine. We search for immunodominant epitopes from an overlapping peptide library to screen the peptides of rEg.P29. Our results confirm that rEg.P29 immunization in mice elicits the activation of T cells and induces cellular immune responses. Further analyses show that a T cell epitope within amino acids 86–100 of rEg.P29 elicits significant antigen-specific IFN-γ production in CD4+ and CD8+ T cells and promotes specific T-cell activation and proliferation. Collectively, these results provide a reference for the construction of a novel vaccine against broad E. granulosus genotypes based on epitopes of rEg.P29.

Aims: Traumatic brain injury (TBI) stands as a significant concern in public health, frequently leading to enduring neurological deficits. Long non‐coding RNA H19 (lncRNA H19) exerts a potential regulator role in the pathology of brain injury. This study investigates the effects of lncRNA H19 knockdown (H19‐KD) on the pathophysiology of TBI and its potential neuroprotective mechanisms. Methods: Controlled cortical impact was employed to establish a stable TBI mouse model. The expression levels of various genes in perilesional cortex and striatum tissue after TBI was detected by RT‐qPCR. AAV9‐shRNA‐H19 was injected into the lateral ventricle of mice to knockdown the expression of lncRNA H19. Various behavioral tests were performed to evaluate sensorimotor and cognitive functions after TBI. Immunofluorescence and Nissl staining were performed to assess brain tissue damage and neuroinflammation. The Nrf2 and HO‐1 expression was performed by Western blot. Results: After TBI, the expression of lncRNA H19 was elevated in perilesional tissue and gradually reverted to baseline. Behavioral tests demonstrated that H19‐KD significantly promoted the recovery of sensorimotor and cognitive functions after TBI. Besides, H19‐KD reduced brain tissue loss, preserved neuronal integrity, and ameliorated white matter damage at the histological level. In addition, H19‐KD restrained the pro‐inflammatory and facilitated anti‐inflammatory phenotypes of microglia/macrophages, attenuating the neuroinflammatory response after TBI. Furthermore, H19‐KD promoted activation of the Nrf2/HO‐1 axis after TBI, while suppression of Nrf2 partially abolished the neuroprotective effect. Conclusion: H19‐KD exerts neuroprotective effects after TBI in mice, partially mediated by the activation of the Nrf2/HO‐1 axis. [ABSTRACT FROM AUTHOR]

Background: Hemifacial macrosomia (HFM, OMIM 164210) is a complex and highly heterogeneous disease. FORKHEAD BOX I3 (FOXI3) is a susceptibility gene for HFM, and mice with loss of function of Foxi3 did exhibit a phenotype similar to craniofacial dysmorphism. However, the specific pathogenesis of HFM caused by FOXI3 deficiency remains unclear till now. Method: In this study, we first constructed a Foxi3 deficiency (Foxi3−/−) mouse model to verify the craniofacial phenotype of Foxi3−/− mice, and then used RNAseq data for gene differential expression analysis to screen candidate pathogenic genes, and conducted gene expression verification analysis using quantitative real‐time PCR. Results: By observing the phenotype of Foxi3−/− mice, we found that craniofacial dysmorphism was present. The results of comprehensive bioinformatics analysis suggested that the craniofacial dysmorphism caused by Foxi3 deficiency may be involved in the PI3K‐Akt signaling pathway. Quantitative real‐time PCR results showed that the expression of PI3K‐Akt signaling pathway‐related gene Akt2 was significantly increased in Foxi3−/− mice. Conclusion: The craniofacial dysmorphism caused by the deficiency of Foxi3 may be related to the expression of Akt2 and PI3K‐Akt signaling pathway. This study laid a foundation for understanding the function of FOXI3 and the pathogenesis and treatment of related craniofacial dysmorphism caused by FOXI3 dysfunction. [ABSTRACT FROM AUTHOR]