A Novel LRRK2 Variant p.G2294R in the WD40 Domain Identified in Familial Parkinson’s Disease Affects LRRK2 Protein Levels

Leucine-rich repeat kinase 2 (LRRK2) is a major causative gene of late-onset familial Parkinson’s disease (PD). The suppression of kinase activity is believed to confer neuroprotection, as most pathogenic variants of LRRK2 associated with PD exhibit increased kinase activity. We herein report a novel LRRK2 variant—p.G2294R—located in the WD40 domain, detected through targeted gene-panel screening in a patient with familial PD. The proband showed late-onset Parkinsonism with dysautonomia and a good response to levodopa, without cognitive decline or psychosis. Cultured cell experiments revealed that p.G2294R is highly destabilized at the protein level. The LRRK2 p.G2294R protein expression was upregulated in the patient’s peripheral blood lymphocytes. However, macrophages differentiated from the same peripheral blood showed decreased LRRK2 protein levels. Moreover, our experiment indicated reduced phagocytic activity in the pathogenic yeasts and α-synuclein fibrils. This PD case presents an example wherein the decrease in LRRK2 activity did not act in a neuroprotective manner. Further investigations are needed in order to elucidate the relationship between LRRK2 expression in the central nervous system and the pathogenesis caused by altered LRRK2 activity.     

Phosphorylated chitosan/poly(vinyl alcohol) based proton exchange membranes modified with propylammonium nitrate ionic liquid and silica filler for fuel cell applications

In our previous work, phosphorylated chitosan was modified through polymer blending with poly(vinyl alcohol) (PVA) polymer to produce N-methylene phosphonic chitosan/poly(vinyl alcohol) (NMPC/PVA) composite membranes. The aim of this work is to further investigate the effects of a propylammonium nitrate (PAN) ionic liquid and/or silicon dioxide (SiO₂) filler on the morphology and physical properties of NMPC/PVA composite membranes. The temperature-dependent ionic conductivity of the composite membranes with various ionic liquid and filler compositions was studied by varying the loading of PAN ionic liquid and SiO₂-PAN filler in the range of 5–20 wt%. As the loading of PAN ionic liquid increased in the NMPC/PVA membrane matrix, the ionic conductivity value also increased with the highest value of 0.53 × 10^?3 S cm^?1 at 25 °C and increased to 1.54 × 10^?3 S cm^?1 at 100 °C with 20 wt% PAN. The NMPC/PVA-PAN (20 wt%) composite membrane also exhibited the highest water uptake and ion exchange capacity, with values of 60.5% and 0.60 mequiv g^?1, respectively. In addition, in the single-cell performance test, the NMPC/PVA-PAN (20 wt%) composite membrane displayed a maximum power density, which was increased by approximately 14% compared to the NMPC/PVA composite membrane with 5 wt% SiO₂-PAN. This work demonstrated that modified NMPC/PVA composite membranes with ionic liquid PAN and/or SiO₂ filler showed enhanced performance compared with unmodified NMPC/PVA composite membranes for proton exchange membrane fuel cells.     

Numerical study on methane/air combustion characteristics in a heat-recirculating micro combustor embedded with porous media

Micro-combustor is a portable power device that can provide energy efficiently, heat recirculating is considered to be an important factor affecting the combustion process. For enhancing the heat recirculating and improving the combustion stability, we proposed a heat-recirculating micro-combustor embedded with porous media, and the numerical simulation was carried out by CFD software. In this paper, the effect of porous media materials, thickness and inlet conditions (equivalence ratio, inlet velocity) on the temperature distribution and exhaust species in the micro combustor are investigated. The results showed that compared with the micro combustor without embedded porous media (MCNPM), micro-combustor embedded with porous media (MCEPM) can improve the temperature uniformity distribution in the radial direction and strengthen the preheating capacity. However, it is found that the embedding thickness of porous media should be reasonably arranged. Setting the thickness of porous media to 15 mm, the combustor can obtain excellent comprehensive capacity of steady combustion and heat recirculating. Compared the thermal performance of Al₂O₃, SiC, and ZrO₂ porous media materials, indicating that SiC due to its strong thermal conductivity, its combustion stabilization and heat recirculating capacity are obviously better than that of Al₂O₃ and ZrO₂. With the porous media embedded in the micro combustor, the combustion has a tempering limit of more than 10 m/s, and the flame is blown out of the porous media area over 100 m/s. The reasonable equivalence ratio of CH₄/air combustion should be controlled within the range of 0.1–0.5, and “super-enthalpy combustion” can be realized.     

Thermo-economic investigation on the hydrogen production through the stored solar energy in a salinity gradient solar pond: A comparative study by employing APC and ORC with zeotropic mixture

In this paper, a salinity gradient solar pond (SGSP) is used to harness the solar energy for hydrogen production through two cycles. The first cycle includes an absorption power cycle (APC), a proton exchange membrane (PEM) electrolyzer, and a thermoelectric generator (TEG) unit; in the second one, an organic Rankine cycle (ORC) with the zeotropic mixture is used instead of APC. The cycles are analyzed through the thermoeconomic vantage point to discover the effect of key decision variables on the cycles’ performance. Finally, NSGA-II is used to optimize both cycles. The results indicate that employing ORC with zeotropic mixture leads to a better performance in comparison to utilizing APC. For the base mode, unit cost product (UCP), exergy, and energy efficiency when APC is employed are 59.9 $/GJ, 23.73%, and 3.84%, respectively. These amounts are 47.27 $/GJ, 29.48%, and 5.86% if ORC with the zeotropic mixture is utilized. The APC and ORC generators have the highest exergy destruction rate which is equal to 6.18 and 10.91 kW. In both cycles, the highest investment cost is related to the turbine and is 0.8275 $/h and 0.976 $/h for the first and second cycles, respectively. In the optimum state the energy efficiency, exergy efficiency, UCP, and H₂ production rate of the system enhances 42.44%, 27.54%,15.95%, and 38.24% when ORC with the zeotropic mixture is used. The maximum H₂ production is 0.47 kg/h, and is obtained when the mass fraction of R142b, LCZ temperature, pumps pressure ratio, generator bubble point temperature are 0.603, 364.35 K, 2.12, 337.67 K, respectively.     

MicroRNAs,Parkinson’s Disease,and Diabetes Mellitus

Parkinson’s disease (PD) is a neurodegenerative disorder that affects 1% of the population over the age of 60. Diabetes Mellitus (DM) is a metabolic disorder that affects approximately 25% of adults over the age of 60. Recent studies showed that DM increases the risk of developing PD. The link between DM and PD has been discussed in the literature in relation to different mechanisms including mitochondrial dysfunction, oxidative stress, and protein aggregation. In this paper, we review the common microRNA (miRNA) biomarkers of both diseases. miRNAs play an important role in cell differentiation, development, the regulation of the cell cycle, and apoptosis. They are also involved in the pathology of many diseases. miRNAs can mediate the insulin pathway and glucose absorption. miRNAs can also regulate PD-related genes. Therefore, exploring the common miRNA biomarkers of both PD and DM can shed a light on how these two diseases are correlated, and targeting miRNAs is a potential therapeutic opportunity for both diseases.     

Blends of Bio-Based Poly(Limonene Carbonate) with Commodity Polymers

In this study, blends of the bio-based poly(limonene carbonate) (PLimC) with different commodity polymers are investigated in order to explore the potential of PLimC toward generating more sustainable polymer materials by reducing the amount of petro- or food-based polymers. PLimC is employed as minority component in the blends. Next to the morphology and thermal properties of the blends the impact of PLimC on the mechanical properties of the matrix polymers is studied. The interplay of incompatibility and zero-shear melt viscosity contrast determines the blend morphology, leading for all blends to a dispersed droplet morphology for PLimC. Blends with polymers of similar structure to PLimC (i.e., aliphatic/aromatic polyester) show the best performance with respect to mechanical properties, whereas blends with polystyrene or poly(methyl methacrylate) are too brittle and polyamide 12 blends show very low elongations at break. In blends with Ecoflex (poly(butylene adipate-co-terephthalate)) and Arnitel EM400 (copoly(ether ester)) with poly(butylene terephthalate) hard and polytetrahydrofuran soft segments) a threefold increase in E-modulus can be achieved, while keeping the elongation at break at reasonable high values of ≈200%, making these blends highly interesting for applications.     

Revealing the high sensitivity in the metal toinsulator transition properties of the pulsed laser deposited VO2 thin films

Vanadium dioxide (VO₂) is known as a typical 3d-orbital transition metal oxide exhibiting the metal-to-insulator-transition (MIT) property near room temperature. However, their electronic applications have been challenged by the quality and uniformity of VO₂ thin films. In this work, we demonstrate the high sensitivity in the valence charge of vanadium and the MIT properties of the VO₂ thin films to the deposition temperature. This observation indicates the necessity to eliminate the inhomogeneity in the temperature distribution of substrate during the vacuum-deposition process of VO₂. In addition, a high thermoelectric power factor (PF, e.g., exceeding 1 μWcm⁻¹K⁻²) was achieved in the metallic phase of the VO₂ thin films and this value is comparable to typical organic or oxide thermoelectric materials. We believe this high PF enriches the potential functionality in thermoelectric energy conversions beyond the existing electronic applications of the current vacuum-grown VO₂ thin films.     

Effect of heat loss on the syngas production by fuel-rich combustion in a divergent two-layer burner

The effect of heat loss on the syngas production from partial combustion of fuel-rich in a divergent two-layer burner is numerically studied using two-dimensional model with detailed kinetics GRI-Mech 1.2. Both the radiation and wall heat losses to the surrounding are considered in the computations. It is shown that two types heat losses have different effects on the syngas production. The radiation heat loss has significant effect on the syngas temperature and the syngas temperature is dropped as radiation heat loss is increased, but it has neglected effect on the reforming efficiency and methane conversion efficiency. The wall heat loss has a comprehensive effect on the syngas production. The wall heat loss not only reduces the conversion efficiency, but also significantly decreases the syngas temperature. The effect of wall heat loss becomes weak as the equivalence is increased. The reforming efficiency drops from 0.440 to 0.424 for equivalence ratio of 2 and mixture velocity of 0.17 m/s for the predictions between adiabatic wall and non-adiabatic conditions.     

Preparation and Evaluation of a Self-Nanoemulsifying Drug Delivery System Loaded with Heparin Phospholipid Complex

A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin in n-octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation.