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Background: Traditional toxicological studies have relied heavily on various animal models to understand the effect of various compounds in a biological context. Considering the great cost, complexity and time involved in experiments using higher order organisms. Researchers have been exploring alternative models that avoid these disadvantages. One example of such a model is the nematode Caenorhabditis elegans. There are some advantages of C. elegans, such as small size, short life cycle, well defined genome, ease of maintenance and efficient reproduction. Methods: As these benefits allow large scale studies to be initiated with relative ease, the problem of how to efficiently capture, organize and analyze the resulting large volumes of data must be addressed. We have developed a new method for quantitative screening of chemicals using C. elegans. 33 features were identified for each chemical treatment. Results: The compounds with different toxicities were shown to alter the phenotypes of C. elegans in distinct and detectable patterns. We found that phenotypic profiling revealed conserved functions to classify and predict the toxicity of different chemicals. Conclusions: Our results demonstrate the power of phenotypic profiling in C. elegans under different chemical environments. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae (K. pneumoniae) is an opportunistic pathogen and the major cause of healthcare-associated infections, which are increasingly complicated by the prevalence of highly invasive and hyper-virulent K. pneumoniae strains, necessitating the development of alternative strategies for combatting infections caused by this bacterium. In this study, we successfully constructed a fusion antigen called KP-Ag1, comprising three antigens (GlnH, FimA, and KPN_00466) that were previously identified through reverse vaccinology. Immunization with KP-Ag1 formulated with Al(OH) 3 adjuvant elicited robust humoral and cellular immune response in mice, and conferred protective immunity in a murine model of K. pneumoniae lung infection. Further analysis of serum IgG subtypes from mice immunized with KP-Ag1 revealed a predominant IgG1 response, indicating that KP-Ag1 predominantly induces a Th2-biased immune response. Additionally, opsonophagocytic killing assay suggested that humoral immune responses play a pivotal role in mediating protection conferred by KP-Ag1. Moreover, KP-Ag1 was found to promote the activation and maturation of BMDCs in vitro , which is essential for subsequent efficient antigen presentation. More importantly, vaccination with KP-Ag1 demonstrated cross-protective efficacy against clinical isolates of K. pneumoniae varying in serotypes, antibiotic resistance, and virulence profiles. Therefore, KP-Ag1 holds promise as a candidate for K. pneumoniae vaccine development. [ABSTRACT FROM AUTHOR]

Introduction: Exposure to fine particulate matter (PM), especially PM 2.5 , can induce various adverse health effects in populations, including diseases and premature death, but the mechanism of its toxicity is largely unknown., Methods: Water-soluble components of PM 2.5 (WS-PM 2.5 ) were collected in the north of China in winter, and combined in two groups with the final concentrations of 94 μg/mL (C L group, AQI ≤ 100) and 119 μg/mL (C H group, 100 < AQI ≤ 200), respectively. The acute and long-term toxic effects of WS-PM 2.5 samples were evaluated in several aspects such as development, lifespan, healthspan (locomotion behavior, heat stress tolerance, lipofucin). DAF mutants and genes were applied to verify the action of IIS pathway in WS-PM 2.5 induced-effects. RNA-Sequencing was performed to elucidate the molecular mechanisms, as well as ROS production and Oil red O staining were also served as means of mechanism exploration., Results: Body length and lifespan were shortened by exposure to WS-PM 2.5 . Healthspan of nematodes revealed adverse effects evaluated by head thrash, body bend, pharyngeal pump, as well as intestinal lipofuscin accumulation and survival time under heat stress. The abbreviated lifespan of daf-2(e1370) strain and reduced expression level of daf-16 and hsp-16.2 indicated that IIS pathway might be involved in the mechanism. Thirty-five abnormally expressed genes screened out by RNA-Sequencing techniques, were functionally enriched in lipid/lipid metabolism and transport, and may contribute substantially to the regulation of PM 2.5 induced adverse effects in nematodes., Conclusion: WS-PM 2.5 exposure induce varying degrees of toxic effects, such as body development, shorten lifespan and healthspan. The IIS pathway and lipid metabolism/transport were disturbed by WS-PM 2.5 during WS-PM 2.5 exposure, suggesting their regulatory role in lifespan determination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Li, Li, Kong, Jing, Zhang, Ning, Gao, Zhang, Wang and Tao.)