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Journal of Medical Imaging (Bellingham,... Sep 2023Assessing the complex three-dimensional (3D) structure of the cochlea is crucial to understanding the fundamental aspects of signal transduction in the inner ear and is...
PURPOSE
Assessing the complex three-dimensional (3D) structure of the cochlea is crucial to understanding the fundamental aspects of signal transduction in the inner ear and is a prerequisite for the development of novel cochlear implants. X-ray phase-contrast computed tomography offers destruction-free 3D imaging with little sample preparation, thus preserving the delicate structure of the cochlea. The use of heavy metal stains enables higher contrast and resolution and facilitates segmentation of the cochlea.
APPROACH
For μ-CT of small animal and human cochlea, we explore the heavy metal osmium tetroxide (OTO) as a radiocontrast agent and delineate laboratory from synchrotron CT. We investigate how phase retrieval can be used to improve the image quality of the reconstructions, both for stained and unstained specimens.
RESULTS
Image contrast for soft tissue in an aqueous solution is insufficient under the in-house conditions, whereas the OTO stain increases contrast for lipid-rich tissue components, such as the myelin sheaths in nervous tissue, enabling contrast-based rendering of the different components of the auditory nervous system. The overall morphology of the cochlea with the three scalae and membranes is very well represented. Further, the image quality of the reconstructions improves significantly when a phase retrieval scheme is used, which is also suitable for non-ideal laboratory settings. With highly brilliant synchrotron radiation (SR), we achieve high contrast for unstained whole cochleae at the cellular level.
CONCLUSIONS
The OTO stain is suitable for 3D imaging of small animal and human cochlea with laboratory , and relevant pathologies, such as a loss of sensory cells and neurons, can be visualized. With SR and optimized phase retrieval, the cellular level can be reached even for unstained samples in aqueous solution, as demonstrated by the high visibility of single hair cells and spiral ganglion neurons.
PubMed: 37753271
DOI: 10.1117/1.JMI.10.5.053501 -
Chemistry, An Asian Journal Dec 2023The versatile coordinating nature of N,S bidentate ligands is of great importance in medicinal chemistry imparting stability and enhancing biological properties of the...
The versatile coordinating nature of N,S bidentate ligands is of great importance in medicinal chemistry imparting stability and enhancing biological properties of the metal complexes. Phenylthiocarbamide-based N,S donor Schiff bases converted into Ru /Os (cymene) complexes and characterized by spectroscopic techniques and elemental analysis. The hydrolytic stability of metal complexes to undergo metal-halide ligand exchange reaction was confirmed both by the DFT and NMR experimentation. The ONIOM (QM/MM) study confirmed the histone protein targeting nature of aqua/hydroxido complex 2 aH with an excellent binding energy of -103.19 kcal/mol. The antiproliferative activity against a panel of cancer cells A549, MCF-7, PC-3, and HepG2 revealed that ruthenium complexes 1 a-3 a were more cytotoxic than osmium complexes and their respective ligands 1-3 as well. Among these ruthenium cymene complex bearing sulfonamide moiety 2 a proved a strong cytotoxic agent and showed excellent correlation of cellular accumulation, lipophilicity, and drug-likeness to the anticancer activity. Moreover, the favorable physiochemical properties such as bioavailability and gastrointestinal absorption of ligand 2 also supported the development of Ru complex 2 a as an orally active anticancer metallodrug.
Topics: Coordination Complexes; Cymenes; Ligands; Ruthenium; Schiff Bases; Antineoplastic Agents; Cell Line, Tumor
PubMed: 37737043
DOI: 10.1002/asia.202300804 -
Endocrine Jan 2024Accumulation of bone marrow adipose tissue (BMAT) is always seen in osteoporosis induced by estrogen deficiency. Herein, we aimed to investigate the mechanisms and...
BACKGROUND
Accumulation of bone marrow adipose tissue (BMAT) is always seen in osteoporosis induced by estrogen deficiency. Herein, we aimed to investigate the mechanisms and consequences of this phenomenon by establishing a mouse model of osteoporosis caused by ovariectomy (OVX)-mimicked estrogen deficiency.
METHODS
Micro-CT, osmium tetroxide staining, and histological analyses were performed to examine the changes in bone microstructure, BMAT and white adipose tissue (WAT) in OVX mice compared to sham mice. The osteogenesis and adipogenesis of primary bone marrow stromal cells (BMSCs) isolated from sham and OVX mice were compared in vitro. The molecular phenotypes of BMAT and WAT were determined and compared by quantitative PCR (qPCR). Bone marrow adipocyte-conditioned medium (BMA CM) was prepared from sham or OVX mice for coculture assays, and BMSCs or bone marrow monocytes/macrophages (BMMs) were isolated and subjected to osteoblast and osteoclast differentiation, respectively. Cell staining and qPCR were used to assess the effects of BMAT on bone metabolism.
RESULTS
OVX-induced estrogen deficiency induced reductions in both cortical and trabecular bone mass along with an expansion of BMAT volume. At the cellular level, loss of estrogen inhibited BMSC osteogenesis and promoted BMSC adipogenesis, whereas addition of estradiol exerted the opposite effects. In response to estrogen deficiency, despite the common proinflammatory molecular phenotype observed in both fat depots, BMAT, unlike WAT, unexpectedly exhibited an increase in adipocyte differentiation and lipolytic activity as well as the maintenance of insulin sensitivity. Importantly, BMAT, but not WAT, presented increased mRNA levels of both BMP receptor inhibitors (Grem1, Chrdl1) and Rankl following OVX. In addition, treatment with BMA CM, especially from OVX mice, suppressed the osteoblast differentiation of BMSCs while favoring the osteoclast differentiation of BMMs.
CONCLUSION
Our study illustrates that OVX-induced estrogen deficiency results in bone loss and BMAT expansion by triggering imbalance between the osteogenesis and adipogenesis of BMSCs. Furthermore, expanded BMAT, unlike typical WAT, may negatively regulate bone homeostasis through paracrine inhibition of osteoblast-mediated bone formation and promotion of osteoclast-mediated bone resorption.
Topics: Female; Mice; Animals; Humans; Bone Marrow; Adipose Tissue; Osteoporosis; Osteogenesis; Cell Differentiation; Estrogens; Ovariectomy; Eye Proteins; Nerve Tissue Proteins
PubMed: 37682419
DOI: 10.1007/s12020-023-03504-6 -
Dalton Transactions (Cambridge, England... Sep 2023Optically active -symmetric bis(aminophenols) based on ()-2,2'-diaminobinaphthyl (BiniqH) and (,)-2,3-butanediyldianthranilate (BdanH) have been prepared by condensation...
Optically active -symmetric bis(aminophenols) based on ()-2,2'-diaminobinaphthyl (BiniqH) and (,)-2,3-butanediyldianthranilate (BdanH) have been prepared by condensation of the diamines with 3,5-di--butylcatechol. Group 10 bis(iminosemiquinone) complexes ()-(Biniq)M (M = Pd, Pt) and (,,)-(Bdan)Pd have been prepared by oxidatively metalating the corresponding ligands. In ()-(Biniq)M, the axis passes through the approximate square plane of the bis(iminosemiquinone)metal core, while in (,,)-(Bdan)Pd the axis is perpendicular to this plane. In the latter compound, the (,)-butanediyl strap binds selectively over one enantioface of the metal complex in a conformation where the methyl groups are to one another. Osmium oxo complexes with the intrinsically chiral OsO(amidophenoxide) chromophore are obtained by metalation of OsO(OCHCHO) with (,)-BdanH. Both the (,,) and (,,) diastereomers can be observed, with metalation in refluxing toluene selectively giving the latter isomer. The electronic structures of the complexes are illuminated by the circular dichroism spectra, in conjuction with the optical spectra and TDDFT calculations.
PubMed: 37668189
DOI: 10.1039/d3dt02436a -
Dalton Transactions (Cambridge, England... Sep 2023The transition metal frustrated Lewis pair compounds [(Cym)M(κS,P,N-HL1)][SbF] (Cym = η--MeCHiPr; H2L1 = -(-tolyl)-'-(2-diphenylphosphanoethyl)thiourea; M = Ru (5), Os...
The transition metal frustrated Lewis pair compounds [(Cym)M(κS,P,N-HL1)][SbF] (Cym = η--MeCHiPr; H2L1 = -(-tolyl)-'-(2-diphenylphosphanoethyl)thiourea; M = Ru (5), Os (6)) have been prepared from the corresponding dimer [{(Cym)MCl}(μ-Cl)] and H2L1 by successive chloride abstraction with NaSbF and AgSbF and NH deprotonation with NaHCO. Complexes 5 and 6 and the previously reported phosphano-guanidino compounds [(Cym)M(κP,N,N'-HL2)][SbF] [H2L2 = ,'-bis(-tolyl)-''-(2-diphenylphosphanoethyl) guanidine; M = Ru (7), Os (8)] and pyridinyl-guanidino compounds [(Cym)M(κN,N',N''-HL3)][SbF] [H2L3 = ,'-bis(-tolyl)-''-(2-pyridinylmethyl) guanidine; M = Ru (9), Os (10)] heterolytically activate H in a reversible manner affording the hydrido complexes [(Cym)MH(H2L)][SbF] (H2L = H2L1; M = Ru (11), Os (12); H2L = H2L2; M = Ru (13), Os (14); H2L = H2L3; M = Ru (15), Os (16)). DFT calculations carried out on the hydrogenation of complex 7 support an FLP mechanism for the process. Heating 9 and 10 in methanol yields the orthometalated complexes [(Cym)M(κN,N',C-H2L3-H)][SbF] (M = Ru (17), Os (18)). The phosphano-guanidino complex 7 activates deuterated water in a reversible fashion, resulting in the gradual deuteration of the three cymene methyl protons through sequential C(sp)-H bond activation. From DFT calculations, a metal-ligand cooperative reversible mechanism that involves the O-H bond activation and the formation of an intermediate methylene cyclohexenyl complex has been proposed. Complexes 5-10 catalyse the hydrogenation of the CC double bond of styrene and a range of acrylates, the CO bond of acetophenone and the CN bond of -benzylideneaniline and quinoline. The CC double bond of methyl acrylate adds to catalyst 9, affording complex 19 in which a new ligand exhibiting a κN,N',C coordination mode has been incorporated.
PubMed: 37665066
DOI: 10.1039/d3dt02339g -
Heliyon Sep 2023Cochlear implants (CIs) allow individuals with profound hearing loss to understand speech and perceive sounds. However, not all patients obtain the full benefits that...
Cochlear implants (CIs) allow individuals with profound hearing loss to understand speech and perceive sounds. However, not all patients obtain the full benefits that CIs can provide and the cause of this disparity is not fully understood. One possible factor for the variability in outcomes after cochlear implantation, is the development of fibrotic scar tissue around the implanted electrode. It has been hypothesised that limiting the extent of fibrosis after implantation may improve overall CI function, and longevity of the device. Currently, histology is often used to quantify the extent of intracochlear tissue growth after implantation however this method is labour intensive, time-consuming, often involves significant user bias, and causes physical distortion of the fibrosis. Therefore, this study aimed to evaluate x-ray micro computed tomography (μCT) as a method to measure the amount and distribution of fibrosis in a guinea pig model of cochlear implantation. Adult guinea pigs were implanted with an inactive electrode, and cochleae harvested eight weeks later (n = 7) and analysed using μCT, to quantify the extent of tissue reaction, followed by histological analysis to confirm that the tissue was indeed fibrotic. Cochleae harvested from an additional six animals following implantation were analysed by μCT, before and after contrast staining with osmium tetroxide (OsO), to enhance the visualisation of soft tissues within the cochlea, including the tissue reaction. Independent analysis by two observers showed that the quantification method was robust and provided additional information on the distribution of the response within the cochlea. Histological analysis revealed that μCT visualised dense collagenous material and new bone formation but did not capture loose, areolar fibrotic tissue. Treatment with OsO significantly enhanced the visible tissue reaction detected using μCT. Overall, μCT is an alternative and reliable method that can be used to quantify the extent of the CI-induced intracochlear tissue response and will be a useful tool for the assessment of novel anti-fibrotic treatments.
PubMed: 37662829
DOI: 10.1016/j.heliyon.2023.e19343 -
Microscopy Research and Technique Dec 2023Midthermic machine perfusion (MMP) of post-circulatory arrest donor liver grafts has the advantage of preserving the functional ultrastructure of hepatocytes in donor...
Midthermic machine perfusion (MMP) of post-circulatory arrest donor liver grafts has the advantage of preserving the functional ultrastructure of hepatocytes in donor grafts. It was reported that oxygenation during MMP reduces portal venous resistance and increases bile production. The MMP with hemoglobin-based oxygen vesicles (HbV) keeps the lower aspartate aminotransferase level (an indicator of liver injury) and maintains the functional ultrastructure of mitochondria in the hepatocytes. To evaluated differences of ultrastructural damages in donor livers between the MMP with and without HbV, porcine liver grafts after 60 min of warm ischemia were perfused at 22°C for 4 h with or without HbV, and a part of liver grafts were analyzed by transmission electron microscopy (TEM) and osmium-maceration scanning electron microscopy (OM-SEM). The remaining grafts were perfused with autologous blood at 38°C for 2 h in an isolated liver reperfusion model (IRM) that mimics the inside of the body after transplantation, and then analyzed by TEM and OM-SEM. Hepatocytes after MMP had small round mitochondria with rod-shaped cristae and reticulovesicular rough endoplasmic reticulum (rER) in both HbV(+) and HbV(-) livers. After IRM of HbV(+) livers, the well-developed lamellar rER was often found in hepatocytes. Liver sinusoidal endothelial cells (LSECs) after MMP contained some large vacuolar structures containing amorphous garbage in the cytoplasm, and their size along with appearance frequency were smaller and lower, respectively, in HbV(+) livers than HbV(-). Oxygenation during the MMP by using HbV suppressed the ultrastructural damages in donor livers, in particular for the LSECs. RESEARCH HIGHLIGHTS: Liver sinusoidal endothelial cells after midthermic machine perfusion had large vacuolar organelles with amorphous garbage. Oxygenation during the perfusion made them less and smaller, ultrastructurally supporting its utility.
Topics: Swine; Animals; Humans; Liver Transplantation; Oxygen; Endothelial Cells; Organ Preservation; Perfusion; Living Donors; Liver; Death; Hemoglobins
PubMed: 37656974
DOI: 10.1002/jemt.24405 -
Open Research Europe 2022Precious metal nanoparticles are key for a range of applications ranging from catalysis and sensing to medicine. While gold (Au), silver (Ag), platinum (Pt), palladium... (Review)
Review
Precious metal nanoparticles are key for a range of applications ranging from catalysis and sensing to medicine. While gold (Au), silver (Ag), platinum (Pt), palladium (Pd) or ruthenium (Ru) nanoparticles have been widely studied, other precious metals are less investigated. Osmium (Os) is one of the least studied of the precious metals. However, Os nanoparticles are interesting materials since they present unique features compared to other precious metals and Os nanomaterials have been reported to be useful for a range of applications, catalysis or sensing for instance. With the increasing availability of advanced characterization techniques, investigating the properties of relatively small Os nanoparticles and clusters has become easier and it can be expected that our knowledge on Os nanomaterials will increase in the coming years. This review aims to give an overview on Os and Os oxide materials syntheses and applications.
PubMed: 37645302
DOI: 10.12688/openreseurope.14595.2 -
Applied Radiation and Isotopes :... Nov 2023Tungsten, tantalum and osmium are important alloying elements in the nuclear technology research and development, particularly in nuclear fission/fusion power plant...
Tungsten, tantalum and osmium are important alloying elements in the nuclear technology research and development, particularly in nuclear fission/fusion power plant material applications. So, data results of the cross sections and emission spectra of neutron-induced reactions are required to predict nuclear responses in these elements. However, the cross sections measurements of (n,2n) reactions on tungsten, tantalum and osmium isotopes are rather limited in the literature. In this case, theoretical approaches are often used for obtaining the cross section data. In this article, theoretical (n,2n) cross sections on W, Ta and Os target nuclei are calculated up to 20 MeV energy, using the simulation codes TALYS 1.95, ALICE/ASH and CEM03.01. Further, the empirical (n,2n) systematics based on the statistical model have been used for predicting the cross section data at ∼14 MeV incident neutrons. The present results from the empirical systematics and model-based calculations are also compared with the literature experimental data, and JENDL-5.0, ENDF/B-VIII, JEFF3.3 and TENDL-2021 libraries. This paper can provide a contribution to complete description of the (n,2n) reactions considering the lack of experimental cross section data.
PubMed: 37639970
DOI: 10.1016/j.apradiso.2023.110999 -
Internal Medicine (Tokyo, Japan) 2023A 32-year-old man was admitted for the evaluation of proteinuria (5.69 g/day). A light microscopic examination showed markedly dilated glomerular capillary loops with...
A 32-year-old man was admitted for the evaluation of proteinuria (5.69 g/day). A light microscopic examination showed markedly dilated glomerular capillary loops with vacuolated areas in many glomeruli, and vacuolated areas were seen on peritubular capillaries in the tubulointerstitium. When electron microscopy specimens prepared by pre-fixation with glutaraldehyde and post-fixation with osmium tetroxide were used for oil red staining, the deposition was confirmed on the affected areas. A genetic analysis of apoE showed that the lipoprotein glomerulopathy was due to apoE-Sendai (Arg145Pro, p.R163P) heterozygosity, which was found in not only the patient but also his mother and twin brother.
Topics: Male; Humans; Adult; Apolipoproteins E; Kidney Diseases; Kidney Glomerulus; Proteinuria; Heterozygote
PubMed: 37532513
DOI: 10.2169/internalmedicine.0834-22