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.     

Charge source and the charging mechanism of the contact electrification of polymer powder

The charge sources, as well as the charging mechanism of the contact electrification (CE) of polymers, are still debatable. Since CE is accompanied by destruction, it is considered that “hard contacting” via ball milling can induce covalent bond scission and produce naked-activated-charge sources. Regarding “soft contacting” via nano-scale sliding, which does not induce covalent bond scission, a frontier-electron, “f-electron,” of the naked-activated-charge source is crucial to electron transfer among the naked-activated-charge sources. Here, we configure naked-activated-charge-source models, naked-activated-mechano-anion, and naked-activated-mechano-cation, which are produced by mechanical energy induced heterogeneous covalent bond scission, as well as naked-activated-mechano-radicals that are produced by homogeneous covalent bond scission. Regarding “soft contacting” among naked-activated-charge sources in a vacuum, f-electron can be transferred from a donor to an acceptor if the energy level of the donor is higher than that of the acceptor. The net amount of the normalized transferred-f-electrons is obtained by adopting settings in which the average energy level of the naked-activated-charge sources (as the donors) is higher than that of the sources employed as acceptors. Thus, the surfaces comprising the donors and acceptors will exhibit positive and negative net surface charges, respectively. We conclude that net surface charges depend on the average energy level of naked-activated-charge sources. Further, we observe that the alignment of polyethylene (PE)-polyvinyl chloride (PVC)-polytetrafluoroethylene (PTFE) to the average energy level is identical to that of the triboelectric series.     

深孔爆破成井技术在三道庄钼矿的试验与应用研究

洛钼集团矿山公司三道庄矿区由于历史原因,露天开采境界地下内存在的采空区已危及矿山公司的正常安全生产,阻碍了洛钼集团可持续发展。为解决这一重大问题,经过充分调研和多方论证,认为深孔一次爆破成井技术是解决此类采空区难题唯一的经济上合理、技术可行、安全可靠的手段与途径。深孔爆破成井实现与采空区顶板的贯通,使采空区边岩稳定,顶岩暴露面积缩小,确保了采空区的稳定;保证了台阶正常推进。     

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.     

Automatic design for shop scheduling strategies based on hyper-heuristics: A systematic review

Against the background of smart manufacturing and Industry 4.0, how to achieve real-time scheduling has become a problem to be solved. In this regard, automatic design for shop scheduling based on hyper-heuristics has been widely studied, and a number of reviews and scheduling algorithms have been presented. Few studies, however, have specifically discussed the technical points involved in algorithm development. This study, therefore, constructs a general framework for automatic design for shop scheduling strategies based on hyper-heuristics, and various state-of-the-art technical points in the development process are summarized. First, we summarize the existing types of shop scheduling strategies and classify them using a new classification method. Second, we summarize an automatic design algorithm for shop scheduling. Then, we investigate surrogate-assisted methods that are popular in the current algorithm field. Finally, current problems and challenges are discussed, and potential directions for future research are proposed.     

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.     

An economic investigation of the wind-hydrogen projects: A case study

Hydrogen as an energy carrier can play a significant role in reducing environmental emissions if it is produced from renewable energy resources. This research aims to assess hydrogen production from wind energy considering environmental, economic, and technical aspect for the East Azerbaijan province of Iran. The economic assessment is performed by calculation of payback period, levelized cost of hydrogen, and levelized cost of electricity. Since uncertainty in the power output of wind turbines may affect the payback period, all calculations are performed for four different turbine degradation rates. While it is common in the literature to choose the wind turbine based on a single criterion, this study implements Multi-Criteria Decision-Making (MCDM) techniques for this purpose. The results of Step-wise Weight Assessment Ratio Analysis illustrates that economic issue is the most important criterion for this research. The results of Weighted Aggregated Sum Product Assessment shows that Vestas V52 is the most suitable wind turbine for Ahar and Sarab cities, while Eovent EVA120 H-Darrieus is a better choice for other stations. The most suitable location for wind power generation is found to be Ahar, where it is estimated to annually generate 2914.8 kWh of electricity at the price of 0.045 $/kWh, and 47.2 tons of hydrogen at the price of 1.38 $/kg, which result in 583 tons of CO₂ emission reduction.     

Piezoelectric properties and microstructure of ceramicrete-based piezoelectric composites

Inorganic piezoelectric ceramic composite is the potential sensing element for long-term structural health monitoring due to its excellent durability and compatibility. In this study, a Ceramicrete-based piezoelectric composite is proposed preliminarily, in which the magnesium potassium phosphate cement is used as the matrix and the lead zirconate titanate particle is utilized as the functional phase. Piezoelectric properties test and microstructure analysis are performed to evaluate the testing samples. Results show that the piezoelectric performance of the composite increase with the increase of piezoelectric ceramic particle size. The value of the piezoelectric strain factor (d₃₃) can reach 83.8 pC/N, while the corresponding piezoelectric voltage factor (g₃₃) is 50.1 × 10^-3 V•m/N at the 50th day after polarization. Microstructure analysis illustrates that the interfacial transition zone (ITZ) between the matrix and the particles is dense. Moreover, the influence of aging on the composite is attributed to the continuous hydration after polarization. It indicates that the composites have a higher piezoelectric performance, which can be regarded as a promising sensing element material.