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.     

Influence of Al3+ doping for V5+ on the structural,optical, thermal and electrical properties of V2-xAlxO5-δ (x=0–0.20) ceramics

This paper reports an investigation on the structure-properties correlation of trivalent metal oxide (Al₂O₃)-doped V₂O₅ ceramics synthesized by the melt-quench technique. XRD patterns confirmed a single orthorhombic V₂O₅ phase formation with increasing strain on the doping of Al₂O₃ in place of V₂O₅ in the samples estimated by Williamson-Hall analysis. FTIR and Raman investigations revealed a structural change as [VO₅] polyhedra converts into [VO₄] polyhedra on the doping of Al₂O₃ into V₂O₅. The optical band gap was found in a wide semiconductor range as confirmed by UV–visible spectroscopy analysis. The thermal and conductivity behavior of the prepared samples were studied using thermal gravimetric analysis (TGA) and impedance analyzer, respectively. All the prepared ceramics exhibit good DC conductivity (0.22–0.36 Sm^-1) at 400 ?C. These materials can be considered for intermediate temperature solid oxide fuel cell (IT-SOFC)/battery applications due to their good conductivity and good thermal stability.     

Electrochemical Quantification of Neurotransmitters in Single Live Cell Vesicles Shows Exocytosis is Predominantly Partial

Exocytosis plays an essential role in the communication between cells in the nervous system. Understanding the regulation of neurotransmitter release during exocytosis and the amount of neurotransmitter content that is stored in vesicles is of importance, as it provides fundamental insights to understand how the brain works and how neurons elicit a certain behavior. In this minireview, we summarize recent progress in amperometric measurements for monitoring exocytosis in single cells and electrochemical cytometry measurements of vesicular neurotransmitter content in individual vesicles. Important steps have increased our understanding of the different mechanisms of exocytosis. Increasing evidence is firmly establishing that partial release is the primary mechanism of release in multiple cell types.     

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.     

Magnetic porous nano-carbon catalysts supported silver nanoparticles derived from chitin and their application in catalytic reduction reactions

The exploitation of recycled carbonaceous catalysts from renewable biomass resources such as chitin is a crucial issue for the development of the sustainable society. In this article, the chitin-based N and O doped carbon microspheres (ChC) were fabricated by a simple dissolution, sol–gel transformation, and the carbonization methods. Subsequently, the novel magnetic Ag-Fe₃O₄@chitin-based carbon microspheres catalyst (MChC) was successfully constructed through the in situ redox reaction. The as-prepared MChC possessed rich micropores with high-surface area, and a narrow size distribution (50–120 μm). The Ag-Fe₃O₄ nanoparticles were immobilized through the interaction with C, N, and O atoms in the pores of MChC. The reduction of 4-nitrophenol was applied to evaluate the catalytic activity of MChC. 4-Nitrophenol (4-NP) could be fully reduced to 4-aminophenol (4-AP) in 5 min with the catalyst MChC-45. Moreover, MChC could be collected in solution with an external magnet in 8 s and remained relatively high-catalytic activity after 10 cycle times. This work provided novel ideas for the fabrication of doped carbon material from biomass and promoted its utilization in nanocatalytic applications.     

OBE-CDIO理念下“集成电路版图分析与设计”课程教学改革与探索

针对目前集成电路版图分析与设计课程存在教学方法老化、教学模式形式化等问题,本文以OBE-CDIO教育理念为指导,对”集成电路版图分析与设计”课程的课程教学模式、课程设计、项目式教学方式和课程考核方式等方面的改革进行有益的探索与实践。将工程教学认证中对学生的专业毕业要求作为制定教学目标的依据,将BB网络平台、ISO9001等现代化教学资源和质量标准融入课堂教学,采用OBE-CDIO能力教学理念指导课程设计,实现教学环节与考核环节的科学化与多元化,通过引入课程思政激发学生学习热情,树立社会主义核心价值观,全面地培养学生的综合版图分析与设计能力和素养。     

Synthesis of thermoresponsive copolymer/silica-coated magnetite nanoparticle composite and its application for heavy metal ion recovery

To enhance chemical stability and suppress of aggregation of magnetite nanoparticles (MNPs), which are used as a support for thermoresponsive copolymer immobilization, silica coating of the MNPs is applied via the electrooxidation method. Although the resulting silica coated-MNPs also formed aggregates, the size distribution of the aggregate shifted to smaller size range. Because of that, the surface area available for copolymer immobilization increased approximately 6.7 times at maximum as compared with that of the uncoated MNPs. It contributed to the increase of the amount of the immobilized copolymer on the silica-coated MNPs, which is approximately four times larger than that on the uncoated MNPs. Fe₃O₄ dissolution test confirmed enhancement of chemical stability of MNPs. The thermoresponsive copolymer immobilized on the silica-coated MNPs shows the ability to recycle Cu(II) ion from Cu(II) containing solution by changing temperature with significantly shorter time than those in other thermoresponsive adsorbents in gel form.     

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.