We report on the design, synthesis, and biological evaluation of a series of nucleotide-binding oligomerization-domain-containing protein 2 (NOD2) desmuramylpeptide agonists with improved in vitro and in vivo adjuvant properties. We identified two promising compounds: 68 , a potent nanomolar in vitro NOD2 agonist, and the more lipophilic 75 , which shows superior adjuvant activity in vivo . Both compounds had immunostimulatory effects on peripheral blood mononuclear cells at the protein and transcriptional levels, and augmented dendritic-cell-mediated activation of T cells, while 75 additionally enhanced the cytotoxic activity of peripheral blood mononuclear cells against malignant cells. The C 18 lipophilic tail of 75 is identified as a pivotal structural element that confers in vivo adjuvant activity in conjunction with a liposomal delivery system. Accordingly, liposome-encapsulated 75 showed promising adjuvant activity in mice, surpassing that of muramyl dipeptide, while achieving a more balanced Th1/Th2 immune response, thus highlighting its potential as a vaccine adjuvant.

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The continuous use of household and personal care products (HPCPs) produces an immense amount of chemicals, such as parabens, bisphenols, UV filters, and alkylphenol ethoxylates, which are of great concern due to their well-known endocrine-disrupting properties. These chemicals easily enter the environment through man-made activities, thus contaminating the biota, including soil, water, plants and animals. Thus, on top of the direct exposure on account of their presence in HPCPs, humans are also susceptible to secondary indirect exposure attributed to the ubiquitous environmental contamination. The aim of this review is therefore to examine the sources and occurrence of these noteworthy contaminants (i.e., parabens, bisphenols, UV filters, alkylphenol ethoxylates), to summarize the available research on their environmental presence and to highlight the potential exposure pathways.

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