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  • br Introduction Concern has been raised

    2019-08-06


    Introduction Concern has been raised over free estrogens (estrone [E1], 17ß-estradiol [E2] and 17α-ethynylestradiol [EE2] particularly) in the past decade due to their endocrine disrupting effects on environmental biota [1], [2]. Estrogens are excreted by vertebrates primarily as sulfate or glucuronide conjugates, which are biologically inactive and more water soluble than the active free estrogens [3], [4]. Nevertheless, microbially-mediated deconjugation of the conjugates to liberate potent free forms makes it imperative to understand the fate, persistence and dissipation of conjugates in the environment. Studies in this regard, however, are rare and incomplete. Human waste and livestock manure are important sources of 2580 conjugates. Up to 97% of conjugated estrogens from human waste were removed from wastewater treatment plants [5]. Estrogen conjugates tend to persist longer in concentrated animal feeding operations where they accounted for a considerable part to the total estrogen load [6]. Application of livestock manure or lagoon water to agriculture fields could be an important source of estrogen contamination [7], [8]. Laboratory batch studies revealed the effective removal of estrogens biologically and physically in sediment and soils [9], [10], still measurable estrogens were frequently reported in aquatic systems [11], [12]. Investigators ascribed these conflicting outcomes, at least partially, to the persistence of the estrogen precursors in soil-water systems [13]. So far, a handful of studies have dealt with the sorption and degradation of conjugated estrogens in soils. For example, Scherr, Sarmah, Di and Cameron [14] discussed the degradation kinetics of 17ß-estradiol-3-sulfate (E2-3S) in response to soil type and temperature. Shrestha, Casey, Hakk, Smith and Padmanabhan [13] investigated the fate and transformation of 17ß-estradiol-3-glucuronide (E2-3G) in the aqueous phase and solid phase of soil-water slurries. However, the previous work neither investigated the two conjugates under the same condition nor had new metabolites identified. The present study thus investigated the degradation of prototype estrogen conjugates E2-3G and E2-3S in laboratory-based soil microcosms at two initial concentrations with the high concentration for the sake of metabolite identification. To accomplish this, high performance liquid chromatography—tandem mass (HPLC–MS/MS) analysis with multiple reaction monitoring (MRM) mode was performed to quantify the target metabolites, while collision-induced dissociation (CID) mass spectrometry coupled with gas chromatography—mass spectrometry (GC–MS) were applied for the identification of unknown intermediates.
    Materials and methods
    Results and discussion
    Conclusions
    Funding sources This work was supported by the United States Department of Agriculture (USDA) under Project No: 2036-12130-010-00D. USDA is an equal opportunity provider and employer.
    Introduction Hepatitis C virus (HCV) is a global health burden affecting approximately 71 million people worldwide. Infection often leads to chronic hepatitis, with the subsequent risk of liver cirrhosis and hepatocellular carcinoma. Persistent HCV infection is now curable with the introduction of direct-acting antivirals. However, a prophylactic HCV vaccine is not available. Since viral re-infection is possible and as many HCV infected individuals are not diagnosed, a vaccine against HCV would facilitate global HCV eradication programs. The extreme diversity of HCV is a major obstacle for vaccine development. The HCV E1E2 proteins are essential for viral cell entry, they bind the HCV receptor CD81 and they are targets for neutralizing antibodies. Hence, immunogens based on E1E2 represent a major branch of vaccine development[3], [4] and numerous approaches to induce broadly neutralizing antibodies (bNabs) that target E1E2 have been explored. For recombinant E1E2, the most advanced HCV subunit vaccine candidate, induction of robust cross-binding and cross-neutralizing antibody responses was observed in multiple animal models and in humans.[4], [6], [7], [8]