The toxicological impact of TiO nanoparticles on the environment and human health has been extensively studied in the last few decades, but the mechanistic details were unknown. In this study, we evaluated the impact of industrially prepared TiO nanoparticles on the biological system using zebrafish embryo as an model. The industrial synthesis of TiO nanoparticles was mimicked on the lab scale using the high energy ball milling (HEBM) method by milling bulk TiO particles for 5 h, 10 h, and 15 h in an ambient environment. The physiochemical properties were characterized by standard methods like field emission scanning electron microscopy (FESEM), dynamic light scattering (DLS), X-ray diffraction (XRD) and UV-Visible spectroscopy. cytotoxicity was assessed on zebrafish embryos by the evaluation of their mortality rate and hatching rate. Experimental and computational analysis of reactive oxygen species (ROS) induction, apoptosis, and neutral lipid alteration was done to study the effects on the cellular level of zebrafish larvae. The analysis depicted the change in size and surface charge of TiO nanoparticles with respect to the increase in milling time. investigations revealed the significant role of ROS quenching and altered neutral lipid accumulation functionalised by the molecular interaction of respective metabolic proteins in the cytotoxicity of TiO nanoparticles with zebrafish embryos. The results reveal the hidden effect of industrially synthesized TiO nanoparticle exposure on the alteration of lipid accumulation and ROS in developing zebrafish embryos. Moreover, the assessment provided a detailed mechanistic analysis of cytotoxicity at the molecular level.

There is the notion that infection with a virulent intestinal pathogen induces generally stronger mucosal adaptive immunity than the exposure to an avirulent strain. Whether the associated mucosal inflammation is important or redundant for effective induction of immunity is, however, still unclear. Here we use a model of auxotrophic Salmonella infection in germ-free mice to show that live bacterial virulence factor-driven immunogenicity can be uncoupled from inflammatory pathogenicity. Although live auxotrophic Salmonella no longer causes inflammation, its mucosal virulence factors remain the main drivers of protective mucosal immunity; virulence factor-deficient, like killed, bacteria show reduced efficacy. Assessing the involvement of innate pathogen sensing mechanisms, we show MYD88/TRIF, Caspase-1/Caspase-11 inflammasome, and NOD1/NOD2 nodosome signaling to be individually redundant. In colonized animals we show that microbiota metabolite cross-feeding may recover intestinal luminal colonization but not pathogenicity. Consequent immunoglobulin A immunity and microbial niche competition synergistically protect against Salmonella wild-type infection.

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