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Organic Letters Aug 2023A novel stereoselective synthetic approach to pentahydroxyazepane iminosugars is described. The strategy relies on a key osmium-catalyzed aminohydroxylation reaction of...
A novel stereoselective synthetic approach to pentahydroxyazepane iminosugars is described. The strategy relies on a key osmium-catalyzed aminohydroxylation reaction of allylic alcohols obtained via addition of vinylmagnesium bromide to a d-mannose-derived aldehyde, which forms the new C-N bond with complete regio- and stereocontrol according to the tethering approach. Subsequent intramolecular reductive amination afforded the desired azepanes. This method represents the first application of the osmium-catalyzed tethered aminohydroxylation reaction to the synthesis of iminosugars.
PubMed: 37515782
DOI: 10.1021/acs.orglett.3c02087 -
Antioxidants (Basel, Switzerland) Jul 2023Altered levels of heavy metals and essential elements have been associated with oxidative stress (OS) and metabolic and hormonal changes in women with polycystic ovary... (Review)
Review
Altered levels of heavy metals and essential elements have been associated with oxidative stress (OS) and metabolic and hormonal changes in women with polycystic ovary syndrome (PCOS). We aimed to summarize the knowledge on the association of heavy metals and essential elements with OS in PCOS. An electronic literature search using PubMed for studies published between January 2008 and April 2023 was conducted. We evaluated heavy metals and essential elements in relation to OS in PCOS in 15 articles. PCOS women had increased antimonium (Sb), cadmium (Cd), lead (Pb), mercury (Hg), arsenic (As), tellurium (Te), thallium (Tl) and osmium (Os) blood levels and decreased zinc (Zn) blood levels; the results of copper (Cu) blood levels were conflicting. Some studies showed a significant correlation between heavy metals (Sb, Cd, Pb, Hg, As, Te and Tl) and essential elements (Se, Zn, Cr, Ca, Mg and Cu) and markers of OS and chronic inflammation. Heavy metals (Sb, Cd, Pb and Hg) and essential elements (Zn, Cr, Se, Ca, Mg and Cu) were associated with metabolic and hormonal characteristics in PCOS. There might be a possible benefit from supplementation therapy in reducing OS and endocrinological problems related to PCOS. Our review confirmed an association between heavy metals and essential elements with OS in PCOS women. This systematic review is registered in PROSPERO under number CRD42023418453.
PubMed: 37507937
DOI: 10.3390/antiox12071398 -
Zoologischer Anzeiger May 2023Female are freshwater, sessile, colonial rotifers that possess two pairs of distinctive glands (warts) located below the corona. Previous studies demonstrated that...
Female are freshwater, sessile, colonial rotifers that possess two pairs of distinctive glands (warts) located below the corona. Previous studies demonstrated that colonies are unpalatable to many invertebrate and vertebrate predators; those authors suggested that the warts were a possible source of a chemical deterrent to predation. Here we explore wart ultrastructure and cytochemisty to determine whether the warts function as exocrine glands and if their contents display any allomone-like chemistry, respectively. Externally, the warts appear as elevated bulges without pores. Internally, the warts are specialized regions of the integumental syncytium and therefore acellular. The lipid stain Nile Red labels all four warts. Two lipid membrane probes (sphingomyelin and phosphatidylinositol) also bind the warts and may be staining internal secretion vesicle membranes. In fact, wart ultrastructure is defined by hundreds of membrane-bound secretion vesicles packed tightly together. The vesicles are mostly electron-lucent and crowded into a well-defined cytoplasmic space. The cytoplasm also contains abundant ribosomes, rough endoplasmic reticulum, mitochondria, and Golgi, but nuclei are generally positioned peripheral to the packed vesicles. Absence of muscles around the warts or any signs of direct innervation suggests expulsion of gland contents is forced by general body contraction. A single specimen with 'empty' warts implies that secretions are released en masse from all glands simultaneously. The identity of the chemical secretion remains to be determined, but the lack of osmium and uranyl acetate staining suggests a low abundance or absence of phenols, unsaturated lipids, or NH and -COOH groups. This absence, combined with the positive Nile Red staining, is interpreted as evidence that vesicles contain saturated fatty acids such as lactones that are unpalatable to predators.
PubMed: 37484813
DOI: 10.1016/j.jcz.2023.03.001 -
Nano-micro Letters Jul 2023Precisely tuning the spacing of the active centers on the atomic scale is of great significance to improve the catalytic activity and deepen the understanding of the...
Precisely tuning the spacing of the active centers on the atomic scale is of great significance to improve the catalytic activity and deepen the understanding of the catalytic mechanism, but still remains a challenge. Here, we develop a strategy to dilute catalytically active metal interatomic spacing (d) with light atoms and discover the unusual adsorption patterns. For example, by elevating the content of boron as interstitial atoms, the atomic spacing of osmium (d) gradually increases from 2.73 to 2.96 Å. More importantly, we find that, with the increase in d, the hydrogen adsorption-distance relationship is reversed via downshifting d-band states, which breaks the traditional cognition, thereby optimizing the H adsorption and HO dissociation on the electrode surface during the catalytic process; this finally leads to a nearly linear increase in hydrogen evolution reaction activity. Namely, the maximum d of 2.96 Å presents the optimal HER activity (8 mV @ 10 mA cm) in alkaline media as well as suppressed O adsorption and thus promoted stability. It is believed that this novel atomic-level distance modulation strategy of catalytic sites and the reversed hydrogen adsorption-distance relationship can shew new insights for optimal design of highly efficient catalysts.
PubMed: 37395826
DOI: 10.1007/s40820-023-01142-1 -
Heliyon Jun 2023In-resin CLEM (Correlative Light and Electron Microscopy) of Epon-embedded cells involves correlating fluorescence microscopy with electron microscopy in the same...
In-resin CLEM (Correlative Light and Electron Microscopy) of Epon-embedded cells involves correlating fluorescence microscopy with electron microscopy in the same Epon-embedded ultrathin section. This method offers the advantage of high positional accuracy compared to standard CLEM. However, it requires the expression of recombinant proteins. In order to detect the localization of endogenous target(s) and their localized ultrastructures of Epon-embedded samples using in-resin CLEM, we investigated whether immunological and affinity-labeling using fluorescent dyes applied to in-resin CLEM of Epon-embedded cells. The orange fluorescent (λ ∼550 nm) and far-red (λ ∼650 nm) fluorescent dyes examined maintained a sufficient level of fluorescent intensity after staining with osmium tetroxide and subsequent dehydration treatment with ethanol. Immunological in-resin CLEM of mitochondria and the Golgi apparatus was achieved using anti-TOM20, anti-GM130 antibodies, and fluorescent dyes. Two-color in-resin CLEM revealed that wheat germ agglutinin-puncta showed the ultrastructures of multivesicular body-like structures. Finally, taking the advantage of high positional accuracy, volume in-resin CLEM of mitochondria in the semi-thin section (2 μm thick) of Epon-embedded cells was performed by focused ion beam scanning electron microscopy. These results suggested that the application of immunological reaction and affinity-labeling with fluorescent dyes to in-resin CLEM of Epon-embedded cells is suitable for analyzing the localization of endogenous targets and their ultrastructures by scanning and transmission electron microscopy.
PubMed: 37389060
DOI: 10.1016/j.heliyon.2023.e17394 -
Biosensors May 2023The inclusion of online, in situ biosensors in microfluidic cell cultures is important to monitor and characterize a physiologically mimicking environment. This work...
The inclusion of online, in situ biosensors in microfluidic cell cultures is important to monitor and characterize a physiologically mimicking environment. This work presents the performance of second-generation electrochemical enzymatic biosensors to detect glucose in cell culture media. Glutaraldehyde and ethylene glycol diglycidyl ether (EGDGE) were tested as cross-linkers to immobilize glucose oxidase and an osmium-modified redox polymer on the surface of carbon electrodes. Tests employing screen printed electrodes showed adequate performance in a Roswell Park Memorial Institute (RPMI-1640) media spiked with fetal bovine serum (FBS). Comparable first-generation sensors were shown to be heavily affected by complex biological media. This difference is explained in terms of the respective charge transfer mechanisms. Under the tested conditions, electron hopping between Os redox centers was less vulnerable than HO diffusion to biofouling by the substances present in the cell culture matrix. By employing pencil leads as electrodes, the incorporation of these electrodes in a polydimethylsiloxane (PDMS) microfluidic channel was achieved simply and at a low cost. Under flow conditions, electrodes fabricated using EGDGE presented the best performance with a limit of detection of 0.5 mM, a linear range up to 10 mM, and a sensitivity of 4.69 μA mM cm.
Topics: Glucose; Microfluidics; Polymers; Hydrogen Peroxide; Glucose Oxidase; Biosensing Techniques; Oxidation-Reduction; Electrodes; Cell Culture Techniques, Three Dimensional; Electrochemical Techniques; Enzymes, Immobilized
PubMed: 37366947
DOI: 10.3390/bios13060582 -
Journal of Clinical Medicine Jun 2023Ex vivo hypothermic machine perfusion (HMP) is a strategy for controlling ischemia-reperfusion injury in donation after circulatory death (DCD) liver transplantation....
Ex vivo hypothermic machine perfusion (HMP) is a strategy for controlling ischemia-reperfusion injury in donation after circulatory death (DCD) liver transplantation. The pH of blood increases with a decrease in temperature and water dissociation, leading to a decrease in [H]. This study aimed to verify the optimal pH of HMP for DCD livers. Rat livers were retrieved 30 min post-cardiac arrest and subjected to 3-h cold storage (CS) in UW solution (CS group) or HMP with UW-gluconate solution (machine perfusion [MP] group) of pH 7.4 (original), 7.6, 7.8, and 8.0 (MP-pH 7.6, 7.8, 8.0 groups, respectively) at 7-10 °C. The livers were subjected to normothermic perfusion to simulate reperfusion after HMP. All HMP groups showed greater graft protection compared to the CS group due to the lower levels of liver enzymes in the former. The MP-pH 7.8 group showed significant protection, evidenced by bile production, diminished tissue injury, and reduced flavin mononucleotide leakage, and further analysis by scanning electron microscopy revealed a well-preserved structure of the mitochondrial cristae. Therefore, the optimum pH of 7.8 enhanced the protective effect of HMP by preserving the structure and function of the mitochondria, leading to reduced reperfusion injury in the DCD liver.
PubMed: 37298042
DOI: 10.3390/jcm12113845 -
Science Advances Jun 2023The activation of inert C─H bonds by transition metals is of considerable industrial and academic interest, but important gaps remain in our understanding of this...
The activation of inert C─H bonds by transition metals is of considerable industrial and academic interest, but important gaps remain in our understanding of this reaction. We report the first experimental determination of the structure of the simplest hydrocarbon, methane, when bound as a ligand to a homogenous transition metal species. We find that methane binds to the metal center in this system through a single M···H-C bridge; changes in the coupling constants indicate clearly that the structure of the methane ligand is significantly perturbed relative to the free molecule. These results are relevant to the development of better C─H functionalization catalysts.
Topics: Osmium; Methane; Ligands; Metals
PubMed: 37294762
DOI: 10.1126/sciadv.adg8130 -
Bioelectrochemistry (Amsterdam,... Oct 2023We investigated the bioelectrochemical properties of an FAD-dependent glucose dehydrogenase from Trichoderma virens (TvGDH) and its electrochemical behaviour when...
We investigated the bioelectrochemical properties of an FAD-dependent glucose dehydrogenase from Trichoderma virens (TvGDH) and its electrochemical behaviour when immobilized on a graphite electrode. TvGDH was recently shown to have an unusual substrate spectrum and to prefer maltose over glucose as substrate, and hence could be of interest as recognition element in a maltose sensor. In this study, we determined the redox potential of TvGDH, which is -0.268 ± 0.007 V vs. SHE, and advantageously low to be used with many redox mediators or redox polymers. The enzyme was entrapped in, and wired by an osmium redox polymer (poly(1-vinylimidazole-co-allylamine)-{[Os(2,2'-bipyridine)Cl]Cl}) with formal redox potential of +0.275 V vs. Ag|AgCl via poly(ethylene glycol) diglycidyl ether crosslinking onto a graphite electrode. When the TvGDH-based biosensor was tested with maltose it showed a sensitivity of 1.7 μA mMcm, a linear range of 0.5-15 mM, and a detection limit of 0.45 mM. Furthermore, it gave the lowest apparent Michaelis-Menten constant (K) of 19.2 ± 1.5 mM towards maltose when compared to other sugars. The biosensor is also able to detect other saccharides including glucose, maltotriose and galactose, these however also interfere with maltose sensing.
Topics: Glucose 1-Dehydrogenase; Hypocrea; Graphite; Maltose; Glucose; Biosensing Techniques; Electrodes; Oxidation-Reduction; Polymers; Enzymes, Immobilized
PubMed: 37269684
DOI: 10.1016/j.bioelechem.2023.108480 -
International Journal of Molecular... May 2023Multiple sclerosis (MS) is the chronic inflammatory demyelinating disease of the CNS. Relapsing-remitting MS (RRMS) is the most common type of MS. However, the...
Involvement of Degenerating 21.5 kDa Isoform of Myelin Basic Protein in the Pathogenesis of the Relapse in Murine Relapsing-Remitting Experimental Autoimmune Encephalomyelitis and MS Autopsied Brain.
Multiple sclerosis (MS) is the chronic inflammatory demyelinating disease of the CNS. Relapsing-remitting MS (RRMS) is the most common type of MS. However, the mechanisms of relapse and remission in MS have not been fully understood. While SJL mice immunized with proteolipid protein (PLP) develop relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE), we have recently observed that some of these mice were resistant to the active induction of relapsing EAE after initial clinical and histological symptoms of EAE with a severity similar to the relapsing EAE mice. To clarify the mechanism of relapsing, we examined myelin morphology during PLP-induced RR-EAE in the SJL mice. While RR-EAE mice showed an increased EAE severity (relapse) with CNS inflammation, demyelination with abnormal myelin morphology in the spinal cord, the resistant mice exhibited a milder EAE phenotype with diminished relapse. Compared with the RR-EAE mice, the resistant mice showed less CNS inflammation, demyelination, and abnormalities of the myelin structure. In addition, scanning electron microscopic (SEM) analysis with the osmium-maceration method displayed ultrastructural abnormalities of the myelin structure in the white matter of the RR-EAE spinal cord, but not in that of the resistant mice. While the intensity of myelin staining was reduced in the relapsing EAE spinal cord, immunohistochemistry and immunoblot analysis revealed that the 21.5 kDa isoform of degenerating myelin basic protein (MBP) was specifically induced in the relapsing EAE spinal cord. Taken together, the neuroinflammation-induced degenerating 21 kDa isoform of MBP sheds light on the development of abnormal myelin on the relapse of MS pathogenesis.
Topics: Mice; Animals; Encephalomyelitis, Autoimmune, Experimental; Myelin Basic Protein; Myelin Proteolipid Protein; Neoplasm Recurrence, Local; Spinal Cord; Multiple Sclerosis; Mice, Inbred Strains; Chronic Disease; Inflammation; Brain; Protein Isoforms
PubMed: 37175866
DOI: 10.3390/ijms24098160