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.     

基于阶段注意力机制的电力线提取算法

电力系统维护是电力系统稳定运行的重要保障，应用智能算法的无人机电力巡检则为电力系统维护提供便捷。电力线提取是自主电力巡检以及保障飞行器低空飞行安全的关键技术，结合深度学习理论进行电力线提取是电力巡检的重要突破点。本文将深度学习方法用于电力线提取任务，结合电力线图像特点嵌入改进的图像输入策略和注意力模块，提出一种基于阶段注意力机制的电力线提取模型（SA-Unet）。本文提出的SA-Unet模型编码阶段采用阶段输入融合策略（Stage input fusion strategy， SIFS），充分利用图像的多尺度信息减少空间位置信息丢失。解码阶段通过嵌入阶段注意力模块（Stage attention module，SAM）聚焦电力线特征，从大量信息中快速筛选出高价值信息。实验结果表明，该方法在复杂背景的多场景中具有良好的性能。     

Trade-off study between risk and benefit in safety devices for hydrogen refueling stations using a dynamic physical model

As hydrogen refueling stations become increasingly common, it is clear that a high level of economic efficiency and safety is crucial to promoting their use. One way to reduce costs is to use a simple orifice instead of an excess flow valve, which Japanese safety regulations have identified as a safety device. However, there is concern about its effect on refueling time and on risk due to hydrogen leakage. To clarify the effect, we did a study of model-based refueling time evaluation and quantitative risk assessment for a typical refueling station. This study showed that an orifice is an effective alternative safety device. The increase in refueling time was less than 10%, based on simulations using a dynamic physical model of the station. Neither was there a significant difference in the risk between a configuration with excess flow valves and one with an orifice.     

2.3–21 GHz broadband and high linearity distributed low noise amplifier

This paper focuses on the design of a 2.3–21 GHz Distributed Low Noise Amplifier (LNA) with low noise figure (NF), high gain (S₂₁), and high linearity (IIP3) for broadband applications. This distributed amplifier (DA) includes S/C/X/Ku/K-band, which makes it very suitable for heterodyne receivers. The proposed DA uses a 0.18 μm GaAs pHEMT process (OMMIC ED02AH) in cascade architecture with lines adaptation and equalization of phase velocity techniques, to absorb their parasitic capacitances into the gate and drain transmission lines in order to achieve wide bandwidth and to enhance gain and linearity. The proposed broadband DA achieved an excellent gain in the flatness of 13.5 ± 0.2 dB, a low noise figure of 3.44 ± 1.12 dB, and a small group delay variation of ±19.721 ps over the range of 2.3–21 GHz. The input and output reflection coefficients S₁₁ and S₂₂ are less than −10 dB. The input compression point (P_1dB) and input third-order intercept point (IIP3) are −1.5 dBm and 11.5 dBm, respectively at 13 GHz. The dissipated power is 282 mW and the core layout size is 2.2 × 0.8 mm².     

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.     

CaDHN3, a Pepper (Capsicum annuum L.) Dehydrin Gene Enhances the Tolerance against Salt and Drought Stresses by Reducing ROS Accumulation

Dehydrins (DHNs) play an important role in abiotic stress tolerance in a large number of plants, but very little is known about the function of DHNs in pepper plants. Here, we isolated a Y₁SK₂-type DHN gene “CaDHN3” from pepper. To authenticate the function of CaDHN3 in salt and drought stresses, it was overexpressed in Arabidopsis and silenced in pepper through virus-induced gene silencing (VIGS). Sub-cellular localization showed that CaDHN3 was located in the nucleus and cell membrane. It was found that CaDHN3-overexpressed (OE) in Arabidopsis plants showed salt and drought tolerance phenotypic characteristics, i.e., increased the initial rooting length and germination rate, enhanced chlorophyll content, lowered the relative electrolyte leakage (REL) and malondialdehyde (MDA) content than the wild-type (WT) plants. Moreover, a substantial increase in the activities of antioxidant enzymes; including the superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), and lower hydrogen peroxide (H₂O₂) contents and higher O₂^•− contents in the transgenic Arabidopsis plants. Silencing of CaDHN3 in pepper decreased the salt- and drought-stress tolerance, through a higher REL and MDA content, and there was more accumulation of reactive oxygen species (ROS) in the CaDHN3-silenced pepper plants than the control plants. Based on the yeast two-hybrid (Y2H) screening and Bimolecular Fluorescence Complementation (BiFC) results, we found that CaDHN3 interacts with CaHIRD11 protein in the plasma membrane. Correspondingly, the expressions of four osmotic-related genes were significantly up-regulated in the CaDHN3-overexpressed lines. In brief, our results manifested that CaDHN3 may play an important role in regulating the relative osmotic stress responses in plants through the ROS signaling pathway. The results of this study will provide a basis for further analyses of the function of DHN genes in pepper.     

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.     

Energy conversion performances during biomass air gasification process under microwave irradiation

Biomass gasification technology under microwave irradiation is a new and novel method, and the energy conversion performances during the process play a guiding role in improving the energy conversion efficiencies and developing the gasification simulation models. In order to improve the energy utilization efficiency of microwave biomass gasification system, this study investigated and presented the energy conversion performances during biomass gasification process under microwave irradiation, and these were materialized through detailing (a) the energy conversion performance in the microwave heating stage, and (b) the energy conversion performance in the microwave assisted biomass gasification stage. Different forms of energies in the biomass microwave gasification process were calculated by the method given in this study based on the experimental data. The results showed that the useful energy (energy in silicon carbide (SiC), 18.73 kJ) accounted for 31.22% of the total energy input (electrical energy, 60.00 kJ) in the heating stage, and the useful energy (energy in the products, 758.55 kJ) accounted for 63.41% of the total energy input (electrical and biomass energy, 1196.28 kJ) in the gasification stage. During the whole biomass gasification process under microwave irradiation, the useful energy output (energy in the products, 758.55 kJ) accounted for 60.38% of the total energy input (electrical and biomass energy, 1256.28 kJ), and the energy in the gas (523.40 kJ) product played a dominate role in product energy (758.55 kJ). The energy loss mainly included the heat loss in the gas flow (89.20 kJ), magnetron loss (191.80 kJ) and microwave dissipation loss (198.00 kJ), which accounted for 7.10%, 15.27% and 15.76% of the total energy, respectively. The contents detailed in this study not only presented the energy conversion performances during microwave assisted gasification process but also supplied important data for developing gasification simulation models.     

基于FLAC3D的破碎围岩巷道支护效果分析

为了解破碎围岩分别采用锚杆支护、锚喷支护以及锚喷+锚索耦合三种支护方式下的支护效果,进而为破碎围岩巷道选择合理的支护方式提供参考。通过借助FLAC^3D软件建立数值模型,分析不同支护条件下的破碎围岩巷道位移量、应力分布以及塑性区的时空演化特征。结果表明,采用锚喷+锚索耦合支护时,可以较好的控制巷道围岩的位移量、减小应力集中效应、缩小塑性区的影响范围。     

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.