Severe central nervous system demyelination in Sanfilippo disease.

Introduction: Chronic progressive neuroinflammation is a hallmark of neurological lysosomal storage diseases, including mucopolysaccharidosis III (MPS III or Sanfilippo disease). Since neuroinflammation is linked to white matter tract pathology, we analyzed axonal myelination and white matter density in the mouse model of MPS IIIC HgsnatP304L and post-mortem brain samples of MPS III patients. Methods: Brain and spinal cord tissues of human MPS III patients, 6-month-old HgsnatP304L mice and age- and sex-matching wild type mice were analyzed by immunofluorescence to assess levels of myelin-associated proteins, primary and secondary storage materials, and levels of microgliosis. Corpus callosum (CC) region was studied by transmission electron microscopy to analyze axon myelination and morphology of oligodendrocytes and microglia. Mouse brains were analyzed ex vivo by high-filed MRI using Diffusion Basis Spectrum Imaging in Python-Diffusion tensor imaging algorithms. Results: Analyses of CC and spinal cord tissues by immunohistochemistry revealed substantially reduced levels of myelin-associated proteins including Myelin Basic Protein, Myelin Associated Glycoprotein, and Myelin Oligodendrocyte Glycoprotein. Furthermore, ultrastructural analyses revealed disruption of myelin sheath organization and reduced myelin thickness in the brains of MPS IIIC mice and human MPS IIIC patients compared to healthy controls. Oligodendrocytes (OLs) in the CC of MPS IIIC mice were scarce, while examination of the remaining cells revealed numerous enlarged lysosomes containing heparan sulfate, GM3 ganglioside or "zebra bodies" consistent with accumulation of lipids and myelin fragments. In addition, OLs contained swollen mitochondria with largely dissolved cristae, resembling those previously identified in the dysfunctional neurons of MPS IIIC mice. Ex vivo Diffusion Basis Spectrum Imaging revealed compelling signs of demyelination (26% increase in radial diffusivity) and tissue loss (76% increase in hindered diffusivity) in CC of MPS IIIC mice. Discussion: Our findings demonstrate an important role for white matter injury in the pathophysiology of MPS III. This study also defines specific parameters and brain regions for MRI analysis and suggests that it may become a crucial non-invasive method to evaluate disease progression and therapeutic response.

Non-invasive in vivo MRI detects long-term microstructural brain alterations related to learning and memory impairments in a model of inflammation-induced white matter injury.

Magnetic resonance imaging (MRI) is currently under investigation as a non-invasive tool to monitor neurodevelopmental trajectories and predict risk of cognitive deficits following white matter injury (WMI) in very preterm infants. In the present study, we evaluated the capacity of multimodal MRI (high-resolution T2-weighted imaging and diffusion tensor imaging)to assess changes following WMI and their relationship to learning and memory performance in Wistar rats as it has been demonstrated for preterm infants. Multimodal MRI performed at P31-P32 shown that animals exposed to neonatal LPS could be classified into two groups: minimal and overt injury. Animals with overt injury had significantly enlarged ventricles, hippocampal atrophy, diffusivity changes in hippocampal white and gray matter, in the striatum and the cortex. Following neonatal LPS exposure, animals presented learning and memory impairments as shown at the fear conditioning test at P36-P38. The severity of learning and memory deficits was related to increased mean diffusivity in the hippocampal region. In conclusion, non-invasive multimodal MRI (volumetric and DTI) assessed and classified the extent of injury at long-term following neonatal LPS exposure. Microstructural changes in the hippocampus at DTI were associated to learning and memory impairments. This further highlights the utility of multimodal MRI as a non-invasive quantitative biomarker following perinatal inflammation.

Separation and recovery of arsenic from As, Cu, and Zn rich leaching liquor using a reduction-crystallization approach.

As, Cu, and Zn rich leaching liquor is generated in the leaching process of copper dust, which contains various metals with high recovery value. Herein, an approach for the direct separation and recovery of arsenic from As, Cu, and Zn rich leaching liquor was proposed. The approach includes two steps, namely SO2 reduction and arsenic crystallization. The factors affecting the reduction of As(v) to As(iii) were investigated, including the pH, SO2 dosage, and reduction temperature. In the crystallization stage, the impacts of sulfuric acid consumption and temperature on the crystallization of arsenic (As2O3) were studied. The results show that the optimal H+ concentration, temperature, and SO2 input for the arsenic reduction were 3.95 mol L-1, 45 °C, and 1.14 L g-1 As(v), respectively. While the optimal temperature and sulfuric acid dosage in As recovery process were 5 °C and 0.1 L L-1 leaching liquor, respectively. Under these conditions, the As2O3 recovery percentage reached 96.53%, and the losses of Cu and Zn were only 3.12% and 0.75%, respectively. The precipitate contained 96.72% of As2O3, 0.83% of Cu, and 0.13% Zn. Compared with the traditional technologies, this new method can improve the recovery efficiency of As2O3 and reduce the loss percentage of other valuable metals (Cu and Zn).

Improving thermo-optic properties of smart windows via coupling to radiative coolers.

In this work we first solve the radiative heat transfer problem in one dimension to perform a comparative analysis of the time-averaged performance of the partially transparent radiative windows and radiative coolers. In doing so, we clearly distinguish the design goals for the partially transparent windows and radiative coolers and provide optimal choice for the material parameters to realize these goals. Thus, radiative coolers are normally non-transparent in the visible, and the main goal is to design a cooler with the temperature of its dark side as low as possible relative to that of the atmosphere. For the radiative windows, however, their surfaces are necessarily partially transparent in the visible. In the cooling mode, the main question is rather about the maximal visible light transmission through the window at which the temperature on the window somber side does not exceed that of the atmosphere. We then demonstrate that transmission of the visible light through smart windows can be significantly increased (by as much as a factor of 2) without additional heating of the windows. This is accomplished via coupling the windows to the radiative coolers using transparent cooling liquid that flows inside of the window and radiative cooler structures. We also demonstrate that efficient heat exchange between radiative coolers and smart windows can be realized using small coolant velocities (sub-1 mm/s for ${\sim}{1}\;{\rm m}$∼1m large windows) or even using a purely passive gravitationally driven coolant flows between a hot smart window and a cold radiative cooler mounted on top of the window with only a minimal temperature differential (sub-1K) between the two. We believe that our simple models complemented with an in-depth comparative analysis of the standalone and coupled smart windows and radiative coolers can be of interest to a broad scientific community pursuing research in these disciplines.

Improving thermo-optic properties of smart windows via coupling to radiative coolers: publisher's note.

This publisher's note amends several equations and one formula in Appl. Opt.59, D210 (2020).APOPAI0003-693510.1364/AO.382050.