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Journal of Labelled Compounds &... May 2024An in-loop C-carbonylation process for the radiosynthesis of C-carboxylic acids and esters from halide precursors has been developed. The reaction proceeds at room...
An in-loop C-carbonylation process for the radiosynthesis of C-carboxylic acids and esters from halide precursors has been developed. The reaction proceeds at room temperature under mild conditions and enables C-carbonylation of both electron deficient and electron rich (hetero)aromatic halides to provide C-carboxylic acids and esters in good to excellent radiochemical yields, high radiochemical purity, and excellent molar activity. The process has been fully automated using commercial radiochemistry synthesis modules, and application to clinical production is demonstrated via validated cGMP radiosyntheses of [C]bexarotene and [C]acetoacetic acid.
Topics: Carboxylic Acids; Esters; Carbon Radioisotopes; Chemistry Techniques, Synthetic; Isotope Labeling; Automation; Radiopharmaceuticals
PubMed: 37608567
DOI: 10.1002/jlcr.4058 -
RSC Advances Aug 2023AlCl-loaded ZnO nanoparticles have been explored as an efficient catalyst for 1,4-dihydropyridine synthesis under ambient temperature and solvent-free conditions. For...
AlCl-loaded ZnO nanoparticles have been explored as an efficient catalyst for 1,4-dihydropyridine synthesis under ambient temperature and solvent-free conditions. For this purpose, ZnO nanoparticles were synthesized by a simple solution-based precipitation technique using a stoichiometric amount of zinc sulfate and oxalic acid. The AlCl@ZnO nanocrystalline catalyst was prepared by loading 20% AlCl on ZnO nanoparticles by a simple wet-impregnation technique. This catalyst efficiently performed Hantzsch pyridine reactions with various aromatic aldehydes, ethyl acetoacetate and ammonium acetate. The nanostructured AlCl-loaded ZnO catalyst was characterized by UV-DRS, XRD, FESEM, EDS, FETEM-STEM-EDS and XPS techniques. The comprehensive characterization reveals the formation of AlCl-loaded ZnO catalysts with an average particle size of 70-80 nm. The loading of AlCl on the ZnO surface was confirmed by minor shifts in the XPS and XRD peaks. FETEM-STEM-EDS also indicates reasonable AlCl loading on ZnO nanoparticles. The 20% AlCl-loaded ZnO nanocatalyst (AlCl@ZnO) confers 92% yield for the synthesis of 1,4-dihydropyridine under solvent-free and ambient temperature conditions. The synthesized 1,4-dihydropyridines were characterized by H-NMR, C-NMR, HRMS and FT-IR spectroscopic techniques. The reported catalyst is highly efficient, environmentally friendly and could become an alternative to homogenous and heterogenous catalytic reactions.
PubMed: 37601590
DOI: 10.1039/d3ra04277d -
Frontiers in Microbiology 2023Xenobiotics often challenge the principle of microbial infallibility. One example is acesulfame introduced in the 1980s as zero-calorie sweetener, which was recalcitrant...
Xenobiotics often challenge the principle of microbial infallibility. One example is acesulfame introduced in the 1980s as zero-calorie sweetener, which was recalcitrant in wastewater treatment plants until the early 2010s. Then, efficient removal has been reported with increasing frequency. By studying acesulfame metabolism in alphaproteobacterial degraders of the genera and , we experimentally confirmed the previously postulated route of two subsequent hydrolysis steps via acetoacetamide-N-sulfonate (ANSA) to acetoacetate and sulfamate. Genome comparison of wildtype sp. 100-5 and an acesulfame degradation-defective mutant revealed the involvement of two plasmid-borne gene clusters. The acesulfame-hydrolyzing sulfatase is strictly manganese-dependent and belongs to the metallo beta-lactamase family. In all degraders analyzed, it is encoded on a highly conserved gene cluster embedded in a composite transposon. The ANSA amidase, on the other hand, is an amidase signature domain enzyme encoded in another gene cluster showing variable length among degrading strains. Transposition of the sulfatase gene cluster between chromosome and plasmid explains how the two catabolic gene clusters recently combined for the degradation of acesulfame. Searching available genomes and metagenomes for the two hydrolases and associated genes indicates that the acesulfame plasmid evolved and spread worldwide in short time. While the sulfatase is unprecedented and unique for acesulfame degraders, the amidase occurs in different genetic environments and likely evolved for the degradation of other substrates. Evolution of the acesulfame degradation pathway might have been supported by the presence of structurally related natural and anthropogenic compounds, such as aminoacyl sulfamate ribonucleotide or sulfonamide antibiotics.
PubMed: 37577448
DOI: 10.3389/fmicb.2023.1223838 -
Frontiers in Molecular Neuroscience 2023A growing body of evidence supports the beneficial effects of the ketone bodies (KBs), acetoacetate and β-hydroxybutyrate (BHB), on diverse physiological processes and... (Review)
Review
A growing body of evidence supports the beneficial effects of the ketone bodies (KBs), acetoacetate and β-hydroxybutyrate (BHB), on diverse physiological processes and diseases. Hence, KBs have been suggested as therapeutic tools for neurodegenerative diseases. KBs are an alternative fuel during fasting and starvation as they can be converted to Ac-CoA to produce ATP. A ketogenic diet (KD), enriched in fats and low in carbohydrates, induces KB production in the liver and favors their use in the brain. BHB is the most abundant KB in the circulation; in addition to its role as energy fuel, it exerts many actions that impact the set of proteins in the cell and tissue. BHB can covalently bind to proteins in lysine residues as a new post-translational modification (PTM) named β-hydroxybutyrylation (Kbhb). Kbhb has been identified in many proteins where Kbhb sites can be critical for binding to other proteins or cofactors. Kbhb is mostly found in proteins involved in chromatin structure, DNA repair, regulation of spliceosome, transcription, and oxidative phosphorylation. Histones are the most studied family of proteins with this PTM, and H3K9bhb is the best studied histone mark. Their target genes are mainly related to cell metabolism, chromatin remodeling and the control of circadian rhythms. The role of Kbhb on physiological processes is poorly known, but it might link KB metabolism to cell signaling and genome regulation. BHB also impacts the proteome by influencing proteostasis. This KB can modulate the Unfolded Protein Response (UPR) and autophagy, two processes involved in the maintenance of protein homeostasis through the clearance of accumulated unfolded and damaged proteins. BHB can support proteostasis and regulate the UPR to promote metabolism adaptation in the liver and prevent cell damage in the brain. Also, BHB stimulates autophagy aiding to the degradation of accumulated proteins. Protein aggregation is common to proteinopathies like Alzheimer's (AD) and Parkinson's (PD) diseases, where the KD and BHB treatment have shown favorable effects. In the present review, the current literature supporting the effects of KBs on proteome conformation and proteostasis is discussed, as well as its possible impact on AD and PD.
PubMed: 37575967
DOI: 10.3389/fnmol.2023.1214092 -
Molecules (Basel, Switzerland) Jul 2023Ulcerative colitis (UC) is a chronic inflammatory disease significantly impacting patients' lives. This study aimed to elucidate the alleviating effect of ethyl acetate...
Ulcerative colitis (UC) is a chronic inflammatory disease significantly impacting patients' lives. This study aimed to elucidate the alleviating effect of ethyl acetate extract (TBEA) from fruit on UC and to explore its mechanism. TBEA was the fraction with the best anti-inflammatory activity screened using in vitro anti-inflammatory assays, and HPLC initially characterized its composition. The mice model of ulcerative colitis was established after free drinking of 2.5% dextran sulfate sodium for six days, and the experimental group was treated with 50 mg/kg and 100 mg/kg TBEA for seven days. We found that TBEA significantly alleviated symptoms in UC mice, including a physiologically significant reduction in disease activity index and pathological damage to colonic tissue. TBEA dramatically slowed down oxidative stress and inflammatory process in UC mice, as evidenced by decreasing myeloperoxidase and malondialdehyde activities and increasing glutathione and catalase levels by reducing the concentrations of IL-6, IL-1β, TNF-α, and NO in UC mice, as well as by regulating key proteins in the IL-6/JAK2/STAT3 pathway. Meanwhile, TBEA maintained intestinal homeostasis by regulating intestinal flora structure. Our study provides new ideas for developing TBEA into a new drug to treat UC.
Topics: Animals; Mice; Colitis, Ulcerative; Cytokines; Gastrointestinal Microbiome; Terminalia; Inflammation Mediators; Interleukin-6; Fruit; Colon; Anti-Inflammatory Agents; Dextran Sulfate; Mice, Inbred C57BL; Disease Models, Animal; Colitis
PubMed: 37570753
DOI: 10.3390/molecules28155783 -
Scientific Reports Aug 2023To investigate the effect of the antioxidant N-acetylcysteine (NAC) on the proliferation and apoptosis in CG8005 gene-interfering Drosophila S2 embryonic cells by...
To investigate the effect of the antioxidant N-acetylcysteine (NAC) on the proliferation and apoptosis in CG8005 gene-interfering Drosophila S2 embryonic cells by scavenging intracellular reactive oxygen species (ROS). The interfering efficiency of CG8005 gene in Drosophila S2 embryonic cells was verified by real-time quantitative PCR (qRT-PCR). Different concentrations of NAC and phosphate buffered saline (PBS) were used to affect the Drosophila S2 embryonic cells. The growth state of Drosophila S2 embryonic cells was observed by light microscope. Two probes dihydroethidium (DHE) and 2,7-dichlorodihydrofluorescein-acetoacetate (DCFH-DA) were used to observe the ROS production in each group after immunofluorescence staining. TUNEL staining and flow cytometry were used to investigate the apoptosis level of Drosophila S2 embryos, and CCK-8 (Cell Counting Kit-8) was used to detect the cell viability of Drosophila S2 embryos. The knockdown efficiency of siCG8005-2 fragment was high and stable, which was verified by interference efficiency (P < 0.05). There was no significant change in the growth of Drosophila S2 embryonic cells after the treatment of NAC as compared to PBS group. Moreover, knockdowning CG8005 gene resulted in an increase in ROS and apoptosis in Drosophila S2 embryonic cells (P < 0.05) and a decrease in proliferation activity (P < 0.05). In addition, the pretreatment of antioxidant NAC could inhibit ROS production in Drosophila S2 embryonic cells (P < 0.05), reduce cell apoptosis (P < 0.05), and improve cell survival (P < 0.05). The CG8005 gene in Drosophila S2 embryonic cells could regulate the proliferation and apoptosis of S2 embryonic cells by disrupting the redox homeostasis, and antioxidant NAC could inhibit cell apoptosis and promotes cell proliferation by scavenging ROS in Drosophila S2 embryonic cells, which is expected to provide novel insights for the pathogenesis of male infertility and spermatogenesis.
Topics: Animals; Male; Acetylcysteine; Antioxidants; Apoptosis; Cell Proliferation; Drosophila; Reactive Oxygen Species; Signal Transduction; Drosophila Proteins
PubMed: 37532734
DOI: 10.1038/s41598-023-39668-4 -
Immunity Sep 2023Environmental nutrient availability influences T cell metabolism, impacting T cell function and shaping immune outcomes. Here, we identified ketone bodies...
Environmental nutrient availability influences T cell metabolism, impacting T cell function and shaping immune outcomes. Here, we identified ketone bodies (KBs)-including β-hydroxybutyrate (βOHB) and acetoacetate (AcAc)-as essential fuels supporting CD8 T cell metabolism and effector function. βOHB directly increased CD8 T effector (Teff) cell cytokine production and cytolytic activity, and KB oxidation (ketolysis) was required for Teff cell responses to bacterial infection and tumor challenge. CD8 Teff cells preferentially used KBs over glucose to fuel the tricarboxylic acid (TCA) cycle in vitro and in vivo. KBs directly boosted the respiratory capacity and TCA cycle-dependent metabolic pathways that fuel CD8 T cell function. Mechanistically, βOHB was a major substrate for acetyl-CoA production in CD8 T cells and regulated effector responses through effects on histone acetylation. Together, our results identify cell-intrinsic ketolysis as a metabolic and epigenetic driver of optimal CD8 T cell effector responses.
Topics: 3-Hydroxybutyric Acid; Acetylation; CD8-Positive T-Lymphocytes; Histones; Ketone Bodies; Animals; Mice
PubMed: 37516105
DOI: 10.1016/j.immuni.2023.07.002