Atrophy of dorsal root ganglia (DRG) and thinning of dorsal roots (DR) are hallmarks of Friedreich's ataxia (FRDA). Many previous authors also emphasized the selective vulnerability of larger neurons in DRG and thicker myelinated DR axons. This report is based on a systematic reexamination of DRG, DR and ventral roots (VR) in 19 genetically confirmed cases of FRDA by immunocytochemistry and single- and double-label immunofluorescence with antibodies to specific proteins of myelin, neurons and axons; S-100alpha as a marker of satellite and Schwann cells; laminin; and the iron-responsive proteins ferritin, mitochondrial ferritin, and ferroportin. Confocal images of axons and myelin allowed the quantitative analysis of fiber density and size, and the extent of DR and VR myelination. A novel technology, high-definition X-ray fluorescence (HDXRF) of polyethylene glycol-embedded fixed tissue, was used to "map" iron in DRG. Unfixed frozen tissue of DRG in three cases was available for the chemical assay of total iron. Proliferation of S-100alpha-positive satellite cells accompanied neuronal destruction in DRG of all FRDA cases. Double-label visualization of peripheral nerve myelin protein 22 and phosphorylated neurofilament protein confirmed the known loss of large myelinated DR fibers, but quantitative fiber counts per unit area did not change. The ratio of myelinated to neurofilament-positive fibers in DR rose significantly from 0.55 to 0.66. In VR of FRDA patients, fiber counts and degree of myelination did not differ from normal. Pooled histograms of axonal perimeters disclosed a shift to thinner fibers in DR, but also a modest excess of smaller axons in VR. Schwann cell cytoplasm in DR of FRDA was depleted while laminin reaction product remained prominent. Numerous small axons clustered around fewer Schwann cells. Ferritin in normal DRG localized to satellite cells, and proliferation of these cells in FRDA caused wide rims of reaction product about degenerating nerve cells. Mitochondrial ferritin was not detectable. Ferroportin was present in the cytoplasm of normal satellite cells and neurons, and in large axons of DR and VR. In FRDA, some DRG neurons lost their cytoplasmic ferroportin immunoreactivity, whereas the cytoplasm of satellite cells remained ferroportin positive. Ferroportin in DR axons disappeared in parallel with atrophy of large fibers. HDXRF of DRG detected regional and diffuse increases in iron fluorescence that matched ferritin expression in satellite cells. The observations support the conclusions that satellite cells and DRG neurons are affected by iron dysmetabolism; and that regeneration and inappropriate myelination of small axons in DR are characteristic of the disease.
Chronic or intermittent extravasations of blood into the subarachnoid space, and dissemination of heme by circulating cerebrospinal fluid, are the only established causes of superficial siderosis of the central nervous system (CNS). We studied the autopsy tissues of nine patients by iron histochemistry, immunocytochemistry, single- and double-label immunofluorescence, electron microscopy of ferritin, and high-definition X-ray fluorescence. In one case, frozen brain tissue was available for quantitative assay of total iron and ferritin. Siderotic tissues showed extensive deposits of iron and ferritin, and infiltration of the cerebellar cortex was especially severe. In addition to perivascular collections of hemosiderin-laden macrophages, affected tissues displayed iron-positive anuclear foamy structures in the neuropil that resembled axonal spheroids. They were especially abundant in eighth cranial nerves and spinal cord. Double-label immunofluorescence of the foamy structures showed co-localization of neurofilament protein and ferritin but comparable merged images of myelin-basic protein and ferritin, and ultrastructural visualization of ferritin, did not allow the conclusion that axonopathy was simply due to dilatation and rupture of fibers. Heme-oxygenase-1 (HO-1) immunoreactivity persisted in macrophages of siderotic cerebellar folia. Siderosis caused a large increase in total CNS iron but high-definition X-ray fluorescence of embedded tissue blocks excluded the accumulation of other metals. Holoferritin levels greatly exceeded the degree of iron accumulation. The susceptibility of the cerebellar cortex is likely due to Bergmann glia that serve as conduits for heme; and the abundance of microglia. Both cell types biosynthesize HO-1 and ferritin in response to heme. The eighth cranial nerves are susceptible because they consist of CNS axons, myelin, and neuroglial tissue along their subarachnoid course. The persistence of HO-1 protein implies continuous exposure of CNS to free heme or an excessively sensitive transcriptional response of the HO-1 gene. The conversion of heme iron to hemosiderin probably involves both translational and transcriptional activation of ferritin biosynthesis.
N-doped TiO2nanotube arrays were prepared by electrochemical anodization in glycerol electrolyte, followed by electrochemical deposition in NH4Cl solution. An orthogonal experiment was used to optimize the doping conditions. Electrolyte concentration, reaction voltage, and reaction time were the main factors to influence the N-doping effect which was the determinant of the visible range photoresponse. The optimal N-doping conditions were determined as follows: reaction voltage is 3 V, reaction time is 2 h, and electrolyte concentration is 0.5 M. The maximal photocurrent enhanced ratio was 30% under white-light irradiation. About 58% improvement of photocatalytic efficiency was achieved in the Rhodamine B degradation experiment by N doping. The kinetic constant of the N-doped TNT arrays sample was almost twice higher than that of the undoped sample. Further analysis by X-ray photoelectron spectroscopy supported that electrochemical deposition is a simple and efficient method for N doping into TiO2nanotube arrays.
Summary Determination of the microdistribution of trace elements in bone at low concentrations has previously been performed with proton induced X-ray emission (PIXE), high-energy synchrotron source X-ray fluorescence (XRF) and laser ablation - inductively coupled plasma mass spectrometry (LA-ICP-MS). Several commercial benchtop XRF systems with micrometer-scale resolution are currently available. While providing convenient, non-destructive mapping capability, they appear to lack the sensitivity required for detection of trace elements in biological tissues such as bone. We investigated the application of a prototype benchtop XRF system for the measurement of strontium and lead at physiological levels in bone. Detection of several elements of interest, including Sr and Pb was achieved with an experimental set up based on focused monochromatic microbeam X-ray fluorescence (Mµ-XRF) instrumentation with a low power source (45 W molybdenum tube) coupled to doubly curved crystal (DCC) optics. A cross-section of bone about 5 mm × 8 mm size was mapped with 80-µm resolution showing heterogeneous distribution of Sr and Pb. The data showed that Mµ-XRF coupled to DCC is powerful method for measurement of the spatial distribution of trace elements in bone.
Introduction Early in the epidemic of corona virus disease 2019, the Chinese government recruited a proportion of healthcare workers to support the designated hospital (Huoshenshan Hospital) in Wuhan, China. The majority of front-line medical staff suffered from adverse effects, but their real health status during COVID-19 epidemic was still unknown. The aim of the study was to explore the latent relationship of the physical and mental health of front-line medical staff during this special period. Methods A total of 115 military medical staff were recruited between February 17th and February 29th, 2020 and asked to complete questionnaires assessing socio-demographic and clinical characteristics, self-reported sleep status, fatigue, resilience and anxiety. Results 55 medical staff worked within Intensive Care and 60 worked in Non-intensive Care, the two groups were significantly different in general fatigue, physical fatigue and tenacity (P<0.05). Gender, duration working in Wuhan, current perceived stress level and health status had significant differences in fatigue scores (P<0.05), the current perceived health status (P<0.05) impacted on the resilience and anxiety of participants. The structural equation modeling analysis revealed resilience were negatively associated with fatigue (β=-0.52, P <0.01) and anxiety (β=-0.24, P <0.01), and fatigue had direct association with the physical burden (β=0.65, P <0.01); Fatigue mediated the relationship between resilience and anxiety (β=-0.305, P =0.039) as well as resilience and physical burden (β=-0.276, P =0.02). Conclusion During an explosive pandemic, motivating the effect of protective resilience and taking tailored interventions against fatigue are promising ways to protect the physical and mental health of the front-line medical staff.
Monochromatic imaging can provide better contrast and resolution than conventional broadband radiography. In broadband systems, low energy photons do not contribute to the image, but are merely absorbed, while high energy photons produce scattering that degrades the image. By tuning to the optimal energy, one can eliminate undesirable lower and higher energies. Monochromatization is achieved by diffraction from a single crystal. A crystal oriented to diffract at a particular energy, in this case the characteristic line energy, diffracts only those photons within a narrow range of angles. The resultant beam from a divergent source is nearly parallel, but not very intense. To increase the intensity, collimation was performed with polycapillary x-ray optics, which can collect radiation from a divergent source and redirect it into a quasi parallel beam. Contrast and resolution measurements were performed with diffracting crystals with both high and low angular acceptance. Testing was first done at 8 keV with an intense copper rotating anode x-ray source, then 17.5 keV measurements were made with a low power molybdenum source. At 8 keV, subject contrast was a factor of five higher than for the polychromatic case. At 17.5 keV, monochromatic contrast was two times greater than the conventional polychromatic contrast. The subject contrasts measured at both energies were in good agreement with theory. An additional factor of two increase in contrast, for a total gain of four, is expected at 17.5 keV from the removal of scatter. Scatter might be simply removed using an air gap, which does not degrade resolution with a parallel beam.
A process is described for the synthesis of kilogram quantities of homochiral 4-silyloxycyclopentenone (R)-1, a key intermediate useful for the synthesis of a plurality of prostaglandin analogue drugs. Cyclopentenone (R)-1 was synthesized in 14 isolated steps from furfural. Key steps in the synthesis include a Wittig reaction, Piancatelli rearrangement, and an enzymatic resolution featuring in situ recycling of the undesired enantiomer furnishing the desired homochiral alcohol in ≥99.5% ee. As a retort to the unsatisfactory coformation of about 8% at best of the trans-olefin in the Wittig reaction, a change to the order of several steps and the identification of a recrystallisable, amine salt derivative, 2, allowed the unwanted isomer to be controlled to as low as 0.2%.
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