Designing amorphous formulations of polyphenols with naringin by spray-drying for enhanced solubility and permeability

Naringin (NAR), a major flavanone (FVA) glycoside, is a component of food mainly obtained from grapefruit. We used NAR as a food additive to improve the solubility and permeability of hydrophobic polyphenols used as supplements in the food industry. The spray-dried particles (SDPs) of NAR alone show an amorphous state with a glass transition temperature (T_g) at 93.2 °C. SDPs of hydrophobic polyphenols, such as flavone (FVO), quercetin (QCT), naringenin (NRG), and resveratrol (RVT) were prepared by adding varying amounts of NAR. All SDPs of hydrophobic polyphenols with added NAR were in an amorphous state with a single T_g, but SDPs of hydrophobic polyphenols without added NAR showed diffraction peaks derived from each crystal. The SDPs with NAR could keep an amorphous state after storage at a high humidity condition for one month, except for SDPs of RVT/NAR. SDPs with NAR enhanced the solubility of hydrophobic polyphenols, especially NRG solubility, which was enhanced more than 9 times compared to NRG crystal. The enhanced solubility resulted in the increased membrane permeability of NRG. The antioxidant effect of the hydrophobic NRG was also enhanced by the synergetic effect of NAR. The findings demonstrated that NAR could be used as a food additive to enhance the solubility and membrane permeability of hydrophobic polyphenols.     

Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics.     

WSN低功耗低时延路径式协同计算方法

针对云计算应用于无线传感器网络(Wireless Sensor Network,WSN)时延敏感型业务时存在的高传输时延问题,提出了一种WSN低功耗低时延路径式协同计算方法。该方法基于一种云雾网络架构开展研究,该架构利用汇聚节点组成雾计算层;在数据传输过程中基于雾计算层的计算能力分步骤完成任务计算,降低任务处理时延;由于汇聚节点计算能力较弱,时延降低将导致能耗增加,WSN工作寿命减短,为此提出能耗约束下的任务映射策略,并利用离散二进制粒子群优化(Binary Particle Swarm Optimization,BPSO)算法解决能耗约束下的时延优化问题。仿真结果表明,在相同的能耗约束下,对比其他算法,基于BPSO算法得出的映射方案能有效降低业务处理时延,满足时延敏感型业务的需求。     

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。     

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.     

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.     

Total Site Hydrogen Integration with fresh hydrogen of multiple quality and waste hydrogen recovery in refineries

This paper proposes a novel method combining Pinch Methodology and waste hydrogen recovery, aiming to minimise fresh hydrogen consumption and waste hydrogen discharge. The method of multiple-level resource Pinch Analysis is extended to the level of Total Site Hydrogen Integration by considering fresh hydrogen sources with various quality. Waste hydrogen after Total Site Integration is further regenerated. The technical feasibility and economy of the various purification approaches are considered, demonstrated with a case study of a refinery hydrogen network in a petrochemical industrial park. The results showed that fresh hydrogen usage and waste hydrogen discharge could be reduced by 21.3% and 67.6%. The hydrogen recovery ratio is 95.2%. It has significant economic benefits and a short payback period for Total Site Hydrogen Integration with waste hydrogen purification. The proposed method facilitates the reuse of waste hydrogen before the purification process that incurs an additional environmental footprint. In line with the Circular Economy principles, hydrogen resource is retained in the system as long as possible before discharge.