Fluoroquinolones (FQs) and tetracyclines (TCs), the two b-diketone antibiotics (DKAs), are two frequently detected pollutants in the environment; however, little data are available on their combined toxicity to zebrafish (Danio rerio). This study reports that toxicologic effects of combined DKA (FQs-TCs) exposure on zebrafish were comparable with or slightly less than those of TCs alone, showing that TCs played a major toxicologic role in the mixtures. The effects of FQs, TCs, and DKAs on malformation rates of zebrafish were dose dependent, with EC 50 values of 481.3, 16.4, and 135.1 mg/L, respectively. According to the combined effects of DKAs on zebrafish hatching, mortality, and malformation rates, the interaction between FQs and TCs was shown to be antagonistic based on three assessment methods: Toxic Unit, Additional Index, and Mixture Toxic Index. The 1.56 mg/L TC and 9.38 mg/L DKA treatments resulted in higher zebrafish basal swimming rate compared with the control group at 120 hours postfertilization (hpf). in both light and light-to-dark photoperiod experiments. Under conditions of no obvious abnormality in cardiac development, the heart beats were decreased significantly because of DKA exposure, such as decreasing by 20% at 150 mg/L DKAs. Transmission electron microscopy observation of myocytes from DKA-exposed hearts displayed prominent interruptions and myofibrillar disorganization of the normal parallel alignment of thick and thin filaments, and partial edematous and dissolved membranes of cell nuclear tissues. At 90 mg/L DKAs, the transcriptional levels of the acta1a, myl7, and gle1b genes, related to heart development and skeletal muscle formation, were significantly changed. This is consistent with the swimming behavior and histopathologic results obtained by transmission electron microscopy. In summary, the toxicity of the combined DKAs to zebrafish was comparable with or less than that of TCs
β-Diketone antibiotics (DKAs) can produce chronic toxicity in aquatic ecosystems due to their pseudo-persistent in the environment. In this study, after long-term DKA exposure to zebrafish (Danio rerio), 47 protein spots had greater than 2-fold differential expression as compared to the control; there were 26 positive proteins with 14 up-regulated and 12 down-regulated. The main functions of the differentially expressed proteins were related to signal transduction mechanisms and the cytoskeleton. Of the 26 target genes, 11 genes were consistent between their transcriptional and translational levels. Low dose DKA exposure (4.69 and 9.38 mg/L) stimulated spontaneous movement in zebrafish. Changes in both creatine kinase activity and creatine concentration showed a similar trend to zebrafish activity. There was no obvious change in SV-BA after DKA exposure, while a reduction of heart rate was concomitant with increasing DKA concentrations. DKAs also induced severe histopathological changes in zebrafish heart tissue, such as dissolution of cristae and vacuolation of mitochondria. These results demonstrated that trace-level DKA exposure affects a variety of cellular and biological processes in zebrafish.
Described here is the first example of a rhodium-catalyzed carboacylation/aromatization cascade of a C=O bond by C-C activation. In this transformation, a reactive rhodaindanone complex is regioselectively generated and adds across a C=O bond with subsequent elimination, thus providing a unique strategy to access a multisubstituted benzofuran scaffold. A diverse range of benzofuran analogues were obtained in good yields. Mechanistic studies show a tricyclic lactone was a viable intermediate. Application of this methodology to the total synthesis of C13-deOH-viniferifuran and C13-deOH-diptoindonesin G was achieved.
Serine/arginine-rich (SR) proteins have an essential role in the splicing of pre-messenger RNA (pre-mRNA) in eukaryote. Pre-mRNA with introns can be alternatively spliced to generate multiple transcripts, thereby increasing adaptation to the external stress conditions in planta. However, pre-mRNA of SR proteins can also be alternatively spliced in different plant tissues and in response to diverse stress treatments, indicating that SR proteins might be involved in regulating plant development and adaptation to environmental changes. We identified and named 18 SR proteins in cassava and systematically studied their splicing and transcriptional changes under tissue-specific and abiotic stress conditions. Fifteen out of 18 SR genes showed alternative splicing in the tissues. 45 transcripts were found from 18 SR genes under normal conditions, whereas 55 transcripts were identified, and 21 transcripts were alternate spliced in some SR genes under salt stress, suggesting that SR proteins might participate in the plant adaptation to salt stress. We then found that overexpression of MeSR34 in Arabidopsis enhanced the tolerance to salt stress through maintaining reactive oxygen species homeostasis and increasing the expression of calcineurin B-like proteins (CBL)–CBL-interacting protein kinases and osmotic stress-related genes. Therefore, our findings highlight the critical role of cassava SR proteins as regulators of RNA splicing and salt tolerance in planta.
Functional stay‐green is generally regarded as a desirable trait of varieties in major crops including maize. In this study, we used an F3:4 recombinant inbred line population with 165 lines from a cross between a stay‐green inbred line (Zheng58) and a model inbred line (B73) using 211 polymorphic simple sequence repeat markers to map quantitative trait loci for three stay‐green‐associated parameters, chlorophyll content, photosystem II photochemical efficiency and stay‐green area, at maturity stage, detected a total of 23 quantitative trait loci (QTL) on nine chromosomes. Single QTL explained 3.7–13.5% of the phenotypic variance. Additionally, we validated some important stay‐green QTL using a heterogeneous inbred family approach and found that the stay‐green‐associated parameters were significantly correlated with the plant yield. This study may contribute to a better insight into the regulatory mechanism behind leaf stay‐green in maize and a novel development of elite maize varieties with delayed leaf senescence through molecular marker‐assisted selection.
Multilayer films composed of azide-functional polymer and polyphenylene dendrimer-stabilized gold nanoparticles with alkynes in their peripheries have been fabricated using a layer-by-layer (LBL) approach via "click" chemistry. This method permits facile covalent linking of the polymer/nanoparticle interlayers in the mixture of DMF and water, which provides a general and powerful technique for preparing uniform nanoparticle (NP) thin films. The deposition process is linearly related to the number of bilayers as monitored by UV-vis spectroscopy. The multilayer structure and morphology have been characterized by X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and contact angle.
Background: Fasudil, a Rho kinase inhibitor, exerts therapeutic effects in a mouse model of Alzheimer's disease (AD), a chronic neurodegenerative disease with progressive loss of memory. However, the mechanisms remain unclear. In addition, the gut microbiota and its metabolites have been implicated in AD.Methods: We examined the effect of fasudil on learning and memory using the Morris water-maze (MWM) test in APPswe/PSEN1dE9 transgenic (APP/PS1) mice (8 months old) treated (i.p.) with fasudil (25 mg/kg/day; ADF) or saline (ADNS) and in age- and gender-matched wild-type (WT) mice. Fecal metagenomics and metabolites were performed to identify novel biomarkers of AD and elucidate the mechanisms of fasudil induced beneficial effects in AD mice.Results: The MWM test showed significant improvement of spatial memory in APP/PS1 mice treated with fasudil as compared to ADNS. The metagenomic analysis revealed the abundance of the dominant phyla in all the three groups, including Bacteroidetes (23.7–44%) and Firmicutes (6.4–26.6%), and the increased relative abundance ratio of Firmicutes/Bacteroidetes in ADNS (59.1%) compared to WT (31.7%). In contrast, the Firmicutes/Bacteroidetes ratio was decreased to the WT level in ADF (32.8%). Lefse analysis of metagenomics identified s_Prevotella_sp_CAG873 as an ADF potential biomarker, while s_Helicobacter_typhlonius and s_Helicobacter_sp_MIT_03-1616 as ADNS potential biomarkers. Metabolite analysis revealed the increment of various metabolites, including glutamate, hypoxanthine, thymine, hexanoyl-CoA, and leukotriene, which were relative to ADNS or ADF microbiota potential biomarkers and mainly involved in the metabolism of nucleotide, lipids and sugars, and the inflammatory pathway.Conclusions: Memory deficit in APP/PS1 mice was correlated with the gut microbiome and metabolite status. Fasudil reversed the abnormal gut microbiota and subsequently regulated the related metabolisms to normal in the AD mice. It is believed that fasudil can be a novel strategy for the treatment of AD via remodeling of the gut microbiota and metabolites. The novel results also provide valuable references for the use of gut microbiota and metabolites as diagnostic biomarkers and/or therapeutic targets in clinical studies of AD.
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