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.     

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.     

Exploring the feasibility of green hydrogen production using excess energy from a country-scale 100% solar-wind renewable energy system

When planning large-scale 100% renewable energy systems (RES) for the year 2050, the system capacity is usually oversized for better supply-demand matching of electrical energy since solar and wind resources are highly intermittent. This causes excessive excess energy that is typically dissipated, curtailed, or sold directly. The public literature shows a lack of studies on the feasibility of using this excess for country-scale co-generation. This study presents the first investigation of utilizing this excess to generate green hydrogen gas. The concept is demonstrated for Jordan using three solar photovoltaic (PV), wind, and hybrid PV-wind RESs, all equipped with Lithium-Ion battery energy storage systems (ESSs), for hydrogen production using a polymer electrolyte membrane (PEM) system. The results show that the PV-based system has the highest demand-supply fraction (>99%). However, the wind-based system is more favorable economically, with installed RES, ESS, and PEM capacities of only 23.88 GW, 2542 GWh, and 20.66 GW. It also shows the highest hydrogen annual production rate (172.1 × 10³ tons) and the lowest hydrogen cost (1.082 USD/kg). The three systems were a better option than selling excess energy directly, where they ensure annual incomes up to 2.68 billion USD while having payback periods of as low as 1.78 years. Furthermore, the hydrogen cost does not exceed 2.03 USD/kg, which is significantly lower than the expected cost of hydrogen (3 USD/kg) produced using energy from fossil fuel-based systems in 2050.     

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.     

立柱加固型框架大楼的爆破拆除

采用定向控制爆破技术拆除立柱加固型7层框架大楼。为了彻底炸毁加固立柱,确保大楼顺利定向倾倒,通过多次爆破试验确定了炸药单耗、布孔参数和装药结构。为了控制大楼塌落时的触地震动,采取了秒差分区爆破、空中解体、铺垫缓冲层和开挖减震沟等技术措施。爆破过程中进行了震动监测。此外还介绍了起爆顺序、安全防护措施及爆破结果。     

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.     

Patterns in environmental priorities revealed through government open data portals

The ways in which environmental priorities are framed are varied and influenced by political forces. One technological advance--the proliferation of government open data portals (ODPs)--has the potential to improve governance through facilitating access to data. Yet it is also known that the data hosted on ODPs may simply reflect the goals and interests of multiple levels of political power. In this article, I use traditional statistical correlation and regression techniques along with newer natural language processing and machine learning algorithms to analyze the corpus of datasets hosted on government ODPs (total: 49,066) to extract patterns that relate scales of governance and political liberalism/conservatism to the priorities and meaning attached to environmental issues. I find that state-level and municipal-level ODPs host different categories of environmental datasets, with municipal-level ODPs generally hosting more datasets pertaining to services and amenities and state-level ODPs hosting more datasets pertaining to resource protection and extraction. Stronger trends were observed for the influences of political conservatism/liberalism among state-level ODPs than for municipal-level ODPs.