Electron microscopic findings in skin biopsies from patients with infantile osteopetrosis and neuronal storage disease

Infantile osteopetrosis with neuronal storage disease is a rare lysosomal storage disorder. It is an autosomal recessive disease that is associated with mutations in the OSTM1 and chloride channel ClCN-7genes. So far mutations in the OSTM1 gene have been identified in only 8 patients. To date, the clinical and morphological features of nine patients with infantile osteopetrosis with neuronal storage have been reported, but no ultrastructural findings of skin have been described in these patients. Skin biopsy is a cost-effective tool for the diagnosis of lysosomal storage disease. The purpose of this report is to define the ultrastructure of affected cells seen in skin biopsies of 2 boys whose mutation of OSTM1 has been characterized. The children presented in infancy with severe osteopetrosis and neurological deficiencies whose predominant symptoms were marked cerebral atrophy, decreased myelinization, and severe central nervous system involvement. Because of the difficulties in distinguishing this disorder from some lysosomal storage diseases such as mucopolysaccharidosis that have both neurological and skeletal abnormalities, the authors elected to examine skin biopsies from these children. Ultrastructural examination revealed the presence of swollen unmyelinated axons containing spheroids, reduced numbers of myelinated axons, and the presence of secondary lysosomes in Schwann cells containing lipofuscin. This study demonstrates that electron microscopy of skin biopsy is a useful diagnostic method to identify patients with clinical features of osteopetrosis with neuronal storage disease.     

Mixed Beverage of Fruits and Vegetables: Effect of Refrigerated Storage on Antioxidant Capacity and Acceptance

The aim of this work was to prepare a mixed beverage containing kale, ginger, coconut water, and orange, which is similar to the recipes found in the informal media, and to determine the effect of refrigerated storage on antioxidant, physical and chemical properties, ascorbic acid content, and sensory acceptance. The refrigeration of the mixed beverage for up to seven hours preserved the antioxidant properties, phenolic compounds, soluble solids, and titratable acidity but led to reduction of green color, pH, and ascorbic acid content. However, in the refrigeration for up to 25 hours, it was observed that antioxidant activity, color, pH, and ascorbic acid were not preserved. The beverage was considered appropriate by mean the sensory acceptance test, after microbiological analysis. The beverages refrigerated for 0, 13, and 25 hours were accepted, with maximum scores of 7 (10 cm scale), besides purchase intention above 3 on a 5-point scale.     

Effect of Storage Conditions and Activation on Growth Factor Concentration in Platelet-Rich Plasma

This study aimed to evaluate growth factor concentration in platelet-rich plasma (PRP) (leukocyte-rich PRP) based on storage temperature, duration of storage, and method of activation. PRP samples were stored at 24℃ (room temperature group), 4℃ (refrigerator group), and −70℃ (deep-freezer group). In each temperature, four aliquots were prepared based on the time of analysis (immediately, 1, 3, and 7 days after preparation). After storage, concentrations of platelet-derived growth factor-AA (PDGF-AA), transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and fibroblast growth factor-basic (FGF-B) were assessed with/without activation using Quantikine colorimetric sandwich immunoassay kits. PRP was activated with 10% Triton-X for PDGF-AA, VEGF, FGF-B, IGF-1 measurement and sonication for TGF-β1 measurement. Without activation, PDGF-AA concentration was highest on day 7 in the room temperature group. With activation, the concentration of PDGF-AA was constant over the observation period at all temperatures. Without activation, the TGF-β1 concentration remained negligible over the observation period at all temperatures. However, with activation, TGF-β1 gradually increased to its highest concentration on day 7 at all temperatures. Over the observation period, VEGF and IGF-1 concentrations were constant with and without activation at all temperatures. Without activation, FGF-B concentration increased, with the highest concentration observed on day 7 in the deep-freezer group. With activation, FGF-B concentration decreased after day 1 in the room temperature group. Growth factor concentration in PRP differed significantly based on storage temperature, duration of storage, and method of activation. Appropriate storage conditions and activation are important to optimize its effects on desired clinical outcomes. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:777-784, 2020     

Preparation and Characterization of Paraffin/Mesoporous Silica Shape-Stabilized Phase Change Materials for Building Thermal Insulation

The use of phase change materials (PCMs) is an attractive method for energy storage and utilization in building envelopes. Here, shape-stabilized phase change materials (SS-PCMs) were prepared via direct adsorption using mesoporous silica (MS) with different pore diameters as the support matrix. The leakage properties, microstructure, chemical structure, thermophysical properties, activation energy, thermal stability and thermal storage-release characteristics of paraffin and SS-PCMs were investigated. The results show that the maximum mass proportion of paraffin in SS-PCMs is 70% when the average pore diameter of mesoporous silica is 15 nm, and the phase change temperature and latent heat of the corresponding SS-PCM are 23.6 °C and 135.4 kJ/kg, respectively. No chemical reaction occurs between mesoporous silica and paraffin and the SS-PCMs exhibit high thermal stability. The high activation energy of the paraffin (70%)/MS1 SS-PCM verifies that the shape and thermal properties can be maintained stably during phase change conversions. The time required for SS-PCMs to complete the thermal storage and release process is reduced by up to 34.0% compared with that for pure paraffin, showing a decline in the thermal conductivity of SS-PCMs after the addition of mesoporous silica. Hence, the prepared paraffin/MS SS-PCMs, in particular paraffin (70%)/MS1 SS-PCM, can be used for storing thermal energy and regulating indoor temperature in buildings.     

Evolution of the Study of Phase Diagram of Binary and Ternary Mixtures Involving Fatty Acid Esters

Interest in phase change materials keeps on rising as thermal energy storage grows in popularity in the scientific community as a promising complement for renewable energies in the future. Extending the possibilities beyond pure compounds, the use of mixtures (especially eutectics) widens the range of suitable phase change materials (PCM) available in the market. However, a precise knowledge of the mixtures’ phase behavior is required, making phase diagrams the most appropriate tools to follow. The aim of this work is to collect and analyze published literature concerning the phase diagrams of fatty acid esters mixtures, which constitute promising candidates as PCM due to their attractive properties, such as high latent heat, chemical stability and the possibility of extracting them from vegetable and animal oils. The topic appears as a still open scientific field, where further studies need to be performed to complete, complement and perfect the currently available information.     

Short-Term Impact of AC Harmonics on Aging of NiMH Batteries for Grid Storage Applications

Batteries in energy storage systems are exposed to electrical noise, such as alternating current (AC) harmonics. While there have been many studies investigating whether Lithium-ion batteries are affected by AC harmonics, such studies on Nickel Metal Hydride (NiMH) batteries are scarce. In this study a 10 Ah, 12 V NiMH battery was tested with three different harmonic current frequency overlays during a single charge/discharge cycle: 50 Hz, 100 Hz, and 1000 Hz. No effect on battery internal temperature or gas pressure was found, indicating that NiMH battery aging is not affected by the tested harmonic AC frequencies. This can reduce the cost of energy storage systems, as no extra filters are needed to safeguard the batteries. Instead, the capacitive properties of the batteries give the possibility to use the battery bank itself as a high pass filter, further reducing system complexity and cost.     

Synthesis,Polymorphism and Thermal Decomposition Process of (n-C4H9)4NRE(BH4)4 for RE = Ho,Tm and Yb

In total, three novel organic derivatives of lanthanide borohydrides, n-But₄NRE(BH₄)₄ (TBAREB), RE = Ho, Tm, Yb, have been prepared utilizing mechanochemical synthesis and purified via solvent extraction. Studies by single crystal and powder X-ray diffraction (SC-XRD and PXRD) revealed that they crystalize in two polymorphic forms, α- and β-TBAREB, adopting monoclinic (P2₁/c) and orthorhombic (Pnna) unit cells, previously found in TBAYB and TBAScB, respectively. Thermal decomposition of these compounds has been investigated using thermogravimetric analysis and differential scanning calorimetry (TGA/DSC) measurements, along with the analysis of the gaseous products with mass spectrometry (MS) and with analysis of the solid decomposition products with PXRD. TBAHoB and TBAYbB melt around 75 °C, which renders them new ionic liquids with relatively low melting points among borohydrides.     

Platelets are efficient and protective depots for storage,distribution, and delivery of lysosomal enzyme in mice with Hurler Syndrome

Use of megakaryocytes/platelets for transgene expression may take advantage of their rapid turnover and protective storage in platelets and reduce the risk of activating oncogenes in hematopoietic stem and progenitor cells (HSCs). Here, we show that human megakaryocytic cells could overexpress the lysosomal enzyme, α-l-iduronidase (IDUA), which is deficient in patients with mucopolysaccharidosis type I (MPS I). Upon megakaryocytic differentiation, the amount of released enzyme increased rapidly and steadily by 30-fold. Using a murine MPS I model, we demonstrated that megakaryocyte/platelets were capable of producing, packaging, and storing large amounts of IDUA with proper catalytic activity, lysosomal trafficking, and receptor-mediated uptake. IDUA can be released directly into extracellular space or within microparticles during megakaryocyte maturation or platelet activation, while retaining the capacity for cross-correction in patient’s cells. Gene transfer into 1.7% of HSCs led to long-term normalization of plasma IDUA and preferential distribution of enzyme in liver and spleen with complete metabolic correction in MPS I mice. Detection of GFP (coexpressed with IDUA) in Kupffer cells and hepatocytes suggested liver delivery of platelet-derived IDUA possibly via the clearance pathway for senile platelets. These findings provide proof of concept that cells from megakaryocytic lineage and platelets are capable of generating and storing fully functional lysosomal enzymes and can also lead to efficient delivery of both the enzymes released into the circulation and those protected within platelets/microparticles. This study opens a door for use of the megakaryocytes/platelets as a depot for efficient production, delivery, and effective tissue distribution of lysosomal enzymes.The potential of therapeutic benefits from genetically modified hematopoietic stem cells (HSCs) has been supported in recent gene therapy clinical trials (1, 2). High transgene dosage or selective growth of genetically corrected HSCs appears to be necessary for achieving clinical efficacy. However, genotoxic risk caused by proviral integration-associated oncogenesis is directly concomitant with high numbers of integration events or clonal expansion (3, 4). New approaches are needed to balance the need for high transgene frequency while limiting the associated increased risk of oncogenesis.Platelets are anuclear, secretory particulate entities containing proteins stored in cytoplasmic granules that can be released upon activation (5). Healthy adults produce 2–5 × 10¹¹ platelets daily with a baseline activation rate of 1–5% (6). Use of megakaryocytes (MKs)/platelets for transgene expression may (i) take advantage of this immense cell mass and its rapid turnover (5–9 d); (ii) provide protective storage of the transgene product, which is essential for proteins sensitive to plasma pH; and (iii) continuously dispense proteins via degranulation from platelet activation at baseline (without detectable injury) and/or at sites of vascular injury. Highly efficient protein production and delivery could further reduce the need for high transgene frequency and the risk of activating oncogenes in HSCs and all their progeny. Although using platelets as a delivery system has been demonstrated for the expression of coagulation factors to treat inherited bleeding disorders in mice (7, 8), there has been no report of the feasibility of using MKs/platelets for the generation of nonhematologic proteins.Lysosomal storage diseases (LSDs) are a group of inherited disorders, often affecting multiple organs including the liver and spleen, with a cumulative incidence of 1 in 5,000–7,000 live births (9). Overexpressing lysosomal enzymes in platelets not only can provide the protection of pH-sensitive enzymes and continuous enzyme release via low physiological levels of platelet activation but may also offer the benefit of on-target delivery of platelet-derived enzymes to spleen and liver in the process of platelet clearance (10). However, maintaining proper posttranslational modifications for appropriate lysosomal trafficking and intercellular lysosomal enzyme transfer is essential for metabolic cross correction in treating these multiorgan diseases (11). It is not known whether lysosomal enzymes generated from the MK/platelet lineage would be fully functional and capable of correcting lysosomal deficits in diseased cells.In this study, we used a mouse model of Hurler syndrome, which is the severe form of mucopolysaccharidosis type I (MPS I), one of most common LSDs. It is caused by the deficiency of α-l-iduronidase (IDUA) and consequent accumulation of glycosaminoglycans (GAGs) (12, 13). We show that MKs are capable of producing large amounts of IDUA with proper catalytic function, lysosomal trafficking and receptor-mediated uptake, which could be sorted to and stored within platelets. The IDUA can be released directly into the extracellular space or within microparticles (MPs) during MK maturation or platelet activation, while retaining its ability to cross-correct cells derived from patients with MPS I.