-
Chemistry (Weinheim An Der Bergstrasse,... Feb 2024Macrocyclic and medium-sized ring ketones, lactones and lactams can all be made from common acryloyl imide starting materials through divergent, one-pot cascade...
Macrocyclic and medium-sized ring ketones, lactones and lactams can all be made from common acryloyl imide starting materials through divergent, one-pot cascade ring-expansion reactions. Following either conjugate addition with an amine or nitromethane, or osmium(VIII)-catalysed dihydoxylation, rearrangement through a four-atom ring expansion takes place spontaneously to form the ring expanded products. A second ring expansion can also be performed following a second iteration of imide formation and alkene functionalisation/ring expansion. In the dihydroxylation series, three- or four-atom ring expansion can be performed selectively, depending on whether the reaction is under kinetic or thermodynamic control.
PubMed: 37987097
DOI: 10.1002/chem.202303270 -
ACS Sensors Nov 2023Diabetes is a chronic disease caused by a decrease in insulin level or insulin resistance. Diabetes also has detrimental effects on the brain, which can lead to the...
Diabetes is a chronic disease caused by a decrease in insulin level or insulin resistance. Diabetes also has detrimental effects on the brain, which can lead to the injury of the blood-brain barrier and influence the glucose transport. In this study, we use in vivo electrochemical measurement to explore the glucose variation in the brain of early diabetic mice. The glucose level in mice brain is measured using a carbon fiber microelectrode modified with the osmium-derivatized polymer and glucose oxidase. The electrode shows an excellent electrochemical performance, antibiofouling ability, and high stability, which can work stably in the mice brain for 2 h. By monitoring the glucose level in the brain of normal and diabetic mice after injection of concentrated glucose solution into the abdominal cavity, it is found that the variation of cerebral glucose decreases by ∼2 fold for diabetic mice. It is proposed that diabetes can downregulate the activity of glucose transporter in the brain and finally inhibit the brain glucose uptake.
Topics: Mice; Animals; Glucose; Diabetes Mellitus, Experimental; Brain; Glucose Oxidase; Microelectrodes
PubMed: 37950693
DOI: 10.1021/acssensors.3c01165 -
Microscopy (Oxford, England) Jun 2024The two-dimensional observation of ultrathin sections from resin-embedded specimens provides an insufficient understanding of the three-dimensional (3D) morphological... (Review)
Review
The two-dimensional observation of ultrathin sections from resin-embedded specimens provides an insufficient understanding of the three-dimensional (3D) morphological information of membranous organelles. The osmium maceration method, developed by Professor Tanaka's group >40 years ago, is the only technique that allows direct observation of the 3D ultrastructure of membrane systems using scanning electron microscopy (SEM), without the need for any reconstruction process. With this method, the soluble cytoplasmic proteins are removed from the freeze-cracked surface of cells while preserving the integrity of membranous organelles, achieved by immersing tissues in a diluted osmium solution for several days. By employing the maceration method, researchers using SEM have revealed the 3D ultrastructure of organelles such as the Golgi apparatus, mitochondria and endoplasmic reticulum in various cell types. Recently, we have developed new SEM techniques based on the maceration method to explore further possibilities of this method. These include: (i) a rapid osmium maceration method that reduces the reaction duration of the procedure, (ii) a combination method that combines agarose embedding with osmium maceration to elucidate the 3D ultrastructure of organelles in free and cultured cells and (iii) a correlative immunofluorescence and SEM technique that combines cryosectioning with the osmium maceration method, enabling the correlation of the immunocytochemical localization of molecules with the 3D ultrastructure of organelles. In this paper, we review the novel osmium maceration methods described earlier and discuss their potential and future directions in the field of biology and biomedical research.
Topics: Microscopy, Electron, Scanning; Imaging, Three-Dimensional; Organelles; Animals; Osmium; Golgi Apparatus; Humans; Endoplasmic Reticulum
PubMed: 37930813
DOI: 10.1093/jmicro/dfad050 -
Chemical Science Nov 2023Photodynamic therapy (PDT) is a medical technique for the treatment of cancer. It is based on the use of non-toxic molecules, called photosensitizers (PSs), that become...
Photodynamic therapy (PDT) is a medical technique for the treatment of cancer. It is based on the use of non-toxic molecules, called photosensitizers (PSs), that become toxic when irradiated with light and produce reactive oxygen specious (ROS) such as singlet oxygen (O). This light-induced toxicity is rather selective since the physician only targets a specific area of the body, leading to minimal side effects. Yet, a strategy to improve further the selectivity of this medical technique is to confine the delivery of the PS to cancer cells only instead of spreading it randomly throughout the body prior to light irradiation. To address this problem, we present here novel sulfonamide-based monopodal and dipodal ruthenium and osmium polypyridyl complexes capable of targeting carbonic anhydrases (CAs) that are a major target in cancer therapy. CAs are overexpressed in the membrane or cytoplasm of various cancer cells. We therefore anticipated that the accumulation of our complexes in or outside the cell prior to irradiation would improve the selectivity of the PDT treatment. We show that our complexes have a high affinity for CAs, accumulate in cancer cells overexpressing CA cells and importantly kill cancer cells under both normoxic and hypoxic conditions upon irradiation at 540 nm. More importantly, Os(ii) compounds still exhibit some phototoxicity under 740 nm irradiation under normoxic conditions. To our knowledge, this is the first description of ruthenium/osmium-based PDT PSs that are CA inhibitors for the selective treatment of cancers.
PubMed: 37920359
DOI: 10.1039/d3sc03932c -
Asian Biomedicine : Research, Reviews... Oct 2023Hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome is generally considered to be a variant or complication of preeclampsia. It is a life-threatening...
BACKGROUND
Hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome is generally considered to be a variant or complication of preeclampsia. It is a life-threatening obstetric complication.
OBJECTIVES
To evaluate the immunohistochemistry and ultrastructural of syncytiotrophoblastand Hoffbauer cells in placental villi of patients with HELLP syndrome.
METHODS
Two groups of patients with a total of 50 full-term human placentas (n = 25 in each group) were assigned as the control (normotensive) and HELLP syndrome. Placental tissue samples were fixed in 10% neutral formalin and paraffin-embedding protocol was performed. We prepared 5 μm sections for histological and immunohistochemical staining. Sections were immunostained with Hoffbauer cell marker CD68. For transmission electron microscopy (TEM), placental tissue samples were fixed in 2.5% buffered glutaraldehyde and then, in 1% osmium tetroxide for routine ultrastructural examinations.
RESULTS
When the HELLP group fetal placental sections were examined, intracytoplasmic edema in syncytiotrophoblast, degenerative vacuoles, and degenerative findings on cell surface membranes were observed. Moreover, villous edema was remarkable. The number of CD68-positive Hoffbauer cells per villus control group sections was 0.23 ± 0.02 and the number of CD68-positive cells per villus in HELLP group placenta sections was 0.83 ± 0.12. The increase in the number of Hoffbauer cells per villus in the HELLP group was significant ( < 0.001). Compared with the control group, there was a significant increase in the number of Hoffbauer cells and syncytiotrophoblasts in the HELLP group, and degenerative changes were also observed in the ultrastructure of these cells.
CONCLUSIONS
Pathology of the HELLP syndrome is in relation to CD68-positive placental macrophages.
PubMed: 37899759
DOI: 10.2478/abm-2023-0065 -
Journal of Medical Imaging (Bellingham,... Sep 2023X-ray phase-contrast tomography (XPCT) is a non-destructive, three-dimensional imaging modality that provides higher contrast in soft tissue than absorption-based CT and...
PURPOSE
X-ray phase-contrast tomography (XPCT) is a non-destructive, three-dimensional imaging modality that provides higher contrast in soft tissue than absorption-based CT and allows one to cover the cytoarchitecture from the centi- and millimeter scale down to the nanoscale. To further increase contrast and resolution of XPCT, for example, in view of addressing connectivity issues in the central nervous system (CNS), metal staining is indispensable. However, currently used protocols, for example, based on osmium and/or uranium are less suited for XPCT, due to an excessive -ratio. In this work, we explore the suitability of different staining agents for XPCT. Particularly, neodymium(III)-acetate (NdAc), which has recently been proposed as a non-toxic, non-radioactive easy to use alternative contrast agent for uranyl acetate (UAc) in electron microscopy, is investigated. Due to its vertical proximity to UAc in the periodic table, similar chemical but better suited optical properties for phase contrast can be expected.
APPROACH
Differently stained whole eye samples of wild type mouse and tissues of the CNS are embedded into EPON epoxy resin and scanned using synchrotron as well as with laboratory radiation. Phase retrieval is performed on the projection images, followed by tomographic reconstruction, which enables a quantitative analysis based on the reconstructed electron densities. Segmentation techniques and rendering software is used to visualize structures of interest in the sample.
RESULTS
We show that staining neuronal samples with NdAc enhances contrast, in particular for laboratory scans, allowing high-resolution imaging of biological soft tissue in-house. For the example of murine retina, specifically rods and cones as well as the sclera and the Ganglion cell layer seem to be targeted by the stain. A comparison of electron density by the evaluation of histograms allowed to determine quantitative measures to describe the difference between the examined stains.
CONCLUSION
The results suggest NdAc to be an effective stain for XPCT, with a preferential binding to anionic groups, such as phosphate and carboxyl groups at cell surfaces, targeting certain layers of the retina with a stronger selectivity compared to other staining agents. Due to the advantageous X-ray optical properties, the stain seems particularly well-suited for phase contrast, with a comparably small number density and an overall superior image quality at laboratory sources.
PubMed: 37885921
DOI: 10.1117/1.JMI.10.5.056001 -
ACS Organic & Inorganic Au Oct 2023The influence of fluorinated substituents on the luminescent properties of rhenium-oxo, osmium-nitrido, and gold triarylcorroles was studied via a comparison of four...
The influence of fluorinated substituents on the luminescent properties of rhenium-oxo, osmium-nitrido, and gold triarylcorroles was studied via a comparison of four ligands: triphenylcorrole (TPC), tris(-trifluoromethylphenyl)corrole (TCFPC), tris{3,5-bis(trifluoromethyl)phenyl}corrole (T3,5-CFPC), and tris(pentafluorophenyl)corrole (TPFPC). For each metal series examined, fluorinated substituents were found to enhance the luminescent properties, with the phosphorescence quantum yields and triplet decay times increasing in the order TPC < TCFPC < T3,5-CFPC < TPFPC. Among the 11 complexes examined, the highest phosphorescence quantum yield, 2.2%, was recorded for Re[TPFPC](O).
PubMed: 37810408
DOI: 10.1021/acsorginorgau.3c00016 -
BioRxiv : the Preprint Server For... Sep 2023Mapping the complete synaptic connectivity of a mammalian brain would be transformative, revealing the pathways underlying perception, behavior, and memory. Serial...
Mapping the complete synaptic connectivity of a mammalian brain would be transformative, revealing the pathways underlying perception, behavior, and memory. Serial section electron microscopy, via membrane staining using osmium tetroxide, is ideal for visualizing cells and synaptic connections but, in whole brain samples, faces significant challenges related to chemical treatment and volume changes. These issues can adversely affect both the ultrastructural quality and macroscopic tissue integrity. By leveraging time-lapse X-ray imaging and brain proxies, we have developed a 12-step protocol, ODeCO, that effectively infiltrates osmium throughout an entire mouse brain while preserving ultrastructure without any cracks or fragmentation, a necessary prerequisite for constructing the first comprehensive mouse brain connectome.
PubMed: 37808722
DOI: 10.1101/2023.09.26.558265 -
BioRxiv : the Preprint Server For... Sep 2023Scanning electron microscopy (SEM) offers an unparalleled view of the membrane topography of mammalian cells by using a conventional osmium (OsO) and ethanol-based...
Scanning electron microscopy (SEM) offers an unparalleled view of the membrane topography of mammalian cells by using a conventional osmium (OsO) and ethanol-based tissue preparation. However, conventional SEM methods limit optimal resolution due to ethanol and lipid interactions and interfere with visualization of fluorescent reporter proteins. Therefore, SEM correlative light and electron microscopy (CLEM) has been hindered by the adverse effects of ethanol and OsO on retention of fluorescence signals. To overcome this technological gap in achieving high-resolution SEM and retain fluorescent reporter signals, we developed a freeze-drying method with gaseous nitrogen (FDGN). We demonstrate that FDGN preserves cyto-architecture to allow visualization of detailed membrane topography while retaining fluorescent signals and that FDGN processing can be used in conjunction with a variety of high-resolution imaging systems to enable collection and validation of unique, high-quality data from these approaches. In particular, we show that FDGN coupled with high resolution microscopy provided detailed insight into viral or tumor-derived extracellular vesicle (TEV)-host cell interactions and may aid in designing new approaches to intervene during viral infection or to harness TEVs as therapeutic agents.
PubMed: 37808646
DOI: 10.1101/2023.09.28.559906 -
Scientific Reports Oct 2023We have successfully synthesized three osmium-based hexagonal Laves compounds ROs (R = Sc, Y, Lu), and discussed their physical properties. LeBail refinement of pXRD...
We have successfully synthesized three osmium-based hexagonal Laves compounds ROs (R = Sc, Y, Lu), and discussed their physical properties. LeBail refinement of pXRD data confirms that all compounds crystallize in the hexagonal centrosymmetric MgZn-type structure (P6/mmc, No. 194). The refined lattice parameters are a = b = 5.1791(1) Å and c = 8.4841(2) Å for ScOs, a = b = 5.2571(3) Å and c = 8.6613(2) Å for LuOs and a = b = 5.3067(6) Å and c = 8.7904(1) Å for YOs. ROs Laves phases can be viewed as a stacking of kagome nets interleaved with triangular layers. Temperature-dependent magnetic susceptibility, resistivity and heat capacity measurements confirm bulk superconductivity at critical temperatures, T, of 5.36, 4.55, and 3.47 K for ScOs, YOs, and LuOs, respectively. We have shown that all investigated Laves compounds are weakly-coupled type-II superconductors. DFT calculations revealed that the band structure of ROs is intricate due to multiple interacting d orbitals of Os and R. Nonetheless, the kagome-derived bands maintain their overall shape, and the Fermi level crosses a number of bands that originate from the kagome flat bands, broadened by interlayer interaction. As a result, ROs can be classified as (breathing) kagome metal superconductors.
PubMed: 37794026
DOI: 10.1038/s41598-023-43621-w