Inactivation of the fliY gene encoding a flagellar motor switch protein attenuates mobility and virulence of Leptospira interrogans strain Lai

<p>Abstract</p> <p>Background</p> <p>Pathogenic <it>Leptospira </it>species cause leptospirosis, a zoonotic disease of global importance. The spirochete displays active rotative mobility which may contribute to invasion and diffusion of the pathogen in hosts. FliY is a flagellar motor switch protein that controls flagellar motor direction in other microbes, but its role in <it>Leptospira</it>, and paricularly in pathogenicity remains unknown.</p> <p>Results</p> <p>A suicide plasmid for the <it>fliY </it>gene of <it>Leptospira interrogans </it>serogroup Icterohaemorrhagiae serovar Lai strain Lai that was disrupted by inserting the ampicillin resistance gene (<it>bla</it>) was constructed, and the inactivation of <it>fliY </it>gene in a mutant (<it>fliY</it>^-) was confirmed by PCR and Western Blot analysis. The inactivation resulted in the mRNA absence of <it>fliP </it>and <it>fliQ </it>genes which are located downstream of the <it>fliY </it>gene in the same operon. The mutant displayed visibly weakened rotative motion in liquid medium and its migration on semisolid medium was also markedly attenuated compared to the wild-type strain. Compared to the wild-type strain, the mutant showed much lower levels of adhesion to murine macrophages and apoptosis-inducing ability, and its lethality to guinea pigs was also significantly decreased.</p> <p>Conclusion</p> <p>Inactivation of <it>fliY</it>, by the method used in this paper, clearly had polar effects on downstream genes. The phentotypes observed, including lower pathogenicity, could be a consequence of <it>fliY </it>inactivation, but also a consequence of the polar effects.</p

Unveiling the therapeutic potential of airpotato yam rhizome against colorectal cancer: a network pharmacology approach

ObjectiveThe objective of this investigation was to elucidate the key active compounds and molecular mechanisms underlying the therapeutic potential of airpotato yam rhizome (AYR) in colorectal cancer (CRC) treatment.MethodsBy utilizing network pharmacology and molecular docking, key targets and signaling pathways of AYR against CRC were predicted and subsequently validated in cellular and mouse xenograft models.ResultsThis study initially predicted that quercetin was the primary compound in AYR that might have potential efficacy against CRC and that EGFR and AKT1 could be the main targets of AYR, with the EGF/EGFR-induced PI3K/AKT signaling pathway potentially playing a crucial role in the anti-CRC effects of AYR. Molecular docking analysis further indicated a strong binding affinity between quercetin and EGFR, primarily through hydrogen bonds. Additionally, the AYR-derived drug-containing serum was found to inhibit the PI3K/AKT signaling pathway, as demonstrated by decreased levels of p-PI3K, p-AKT, and BCL2, which ultimately led to enhanced apoptosis of HCT116 and HT29 cells. The potential antitumor effects of AYR were investigated in nude mouse xenograft models of human HCT116 and HT29 cells, in which AYR was found to induce tumor cell apoptosis and inhibit tumor formation.ConclusionAYR may promote CRC cell apoptosis by suppressing the PI3K/AKT signaling pathway, which provides a basis for further research on the safe and effective use of AYR for the treatment of CRC

High order Fano resonances and giant magnetic fields in dielectric microspheres

We show that weakly dissipating dielectric spheres made of materials such as glass, quartz, etc. can support high order Fano resonances associated with internal Mie modes. These resonances, happening for specific values of the size parameter, yield field-intensity enhancement factors on the order of 104–107, which can be directly obtained from analytical calculations. Associated to these “super-resonances”, we analyze the emergence of magnetic nanojets with giant magnetic fields, which might be attractive for many photonic applications.Published versio