低压静电场辅助冷冻对竹笋品质的影响

为研究低压静电场辅助冷冻对竹笋冻结特性的影响，以冻结曲线、硬度、水分损失率、水分迁移、冰晶形态和组织微观结构为指标，探究低压静电场辅助冷冻（－35 ℃）和普通冷冻（－35 ℃）条件下竹笋品质的变化规律。结果表明：低压静电场辅助冷冻提高了冻结效率，改变了冰晶形态及分布，减轻了组织微观结构破损程度，改善了解冻汁液流失情况。与静电板间距10、20、30、40 cm处的冷冻竹笋解冻后水分损失率分别为14.16%、12.58%、9.73%、10.44%，显著低于对照组（21.01%）（P＜0.05），硬度分别为461.19、507.48、496.65 g和455.31 g，显著高于对照组（350.70 g）（P＜0.05）。低场核磁共振分析结果表明，在低压静电场辅助冷冻下竹笋解冻后汁液流失减少，扫描电子显微镜观察结果显示，竹笋纤维排列整齐，组织微观结构保持较好。低压静电场辅助冷冻可有效改善竹笋品质，可为利用低压静电场进行果蔬的冷冻贮藏和冷链运输提供参考。     

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.     

基于气相色谱-离子迁移色谱分析不同贮藏方式对洋葱浆馕风味的影响

采用气相色谱-离子迁移谱（gas chromatography-ion mobility spectrometry，GC-IMS）对洋葱浆馕6 种不同贮藏条件下挥发性物质进行分析，包括低温贮藏、室温贮藏、真空贮藏、脱氧贮藏、保鲜剂贮藏和保鲜剂结合脱氧贮藏。研究表明：在洋葱浆馕中共鉴定出66 种挥发性风味物质，其中包括醇类9 种、酮类4 种、醛类18 种、酯类4 种、呋喃衍生物3 种，酸类1 种和未能识别的化合物27 种。随着贮藏时间的延长，低温贮藏和真空贮藏洋葱浆馕在贮藏期内醛类挥发性有机物基本不变，其他处理组的醛类挥发性有机物在贮藏期内变化呈降低的趋势。结合主成分分析和欧氏距离可以发现低温贮藏和其他贮藏方式的第0天挥发性物质种类和浓度较为接近，主成分分析图中点的位置也相聚在一起，说明低温贮藏馕的挥发性物质变化不明显。该研究建立不同贮藏方式洋葱浆馕挥发性气味指纹图谱，可视化出洋葱浆馕挥发性成分轮廓，为洋葱浆馕贮藏期间风味变化规律提供信息。     

Effect of fiber-reinforcement on the mechanical behavior of sand approaching the critical state

Several types of ground improvement methods that employ fiber-reinforcement have been developed in recent years. A series of consolidated drained triaxial compression tests has been conducted here to examine the effect of short fibers on the mechanical properties of Toyoura sand. Sand with 0%, 0.2%, 0.4%, and 1% fiber contents, prepared to yield random distribution, was sheared under several confining pressures and controlled via their initial relative densities. The test results showed that the maximum and residual deviatoric stresses increased, whereas the volumetric expansion decreased with an increase in fiber content. Although the stress ratio η (=q/p′) and specific volume changed depending on the fiber content and confining pressure with shear progression, they each reached the same values for a definite fiber content at the end of shearing, independent of initial relative density. In other words, the unique critical state line can be found for a definite fiber content. Moreover, the greater the fiber content, the larger the slope of the critical state line at the end of shearing. Additionally, as the length of fibers shortened with the same percentage of fiber inclusions in sand, the deviatoric stress and the stress ratio decreased, approaching the shear-strain-volumetric response of unreinforced sand.     

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.     

Meta-Analysis of Methamphetamine Modulation on Amyloid Precursor Protein through HMGB1 in Alzheimer’s Disease

The deposition of amyloid-beta (Aβ) through the cleavage of amyloid-beta precursor protein (APP) is a biomarker of Alzheimer’s disease (AD). This study used QIAGEN Ingenuity Pathway Analysis (IPA) to conduct meta-analysis on the molecular mechanisms by which methamphetamine (METH) impacts AD through modulating the expression of APP. All the molecules affected by METH and APP were collected from the QIAGEN Knowledge Base (QKB); 78 overlapping molecules were identified. Upon simulation of METH exposure using the “Molecule Activity Predictor” feature, eight molecules were found to be affected by METH and exhibited activation relationships on APP expression at a confidence of p = 0.000453 (Z-score = 3.51, two-tailed). Core Analysis of these eight molecules identified High Mobility Group Box protein 1 (HMGB1) signaling pathway among the top 5 canonical pathways with most overlap with the 8-molecule dataset. Simulated METH exposure increased APP expression through HMGB1 at a confidence of p < 0.00001 (Z-score = 7.64, two-tailed). HMGB1 is a pathogenic hallmark in AD progression. It not only increases the production of inflammatory mediators, but also mediates the disruption of the blood-brain barrier. Our analyses suggest the involvement of HMGB1 signaling pathway in METH-induced modulation of APP as a potential casual factor of AD.     

Neoagarooligosaccharide Protects against Hepatic Fibrosis via Inhibition of TGF-β/Smad Signaling Pathway

Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by β-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, α-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-β-treated LX-2 cells. Furthermore, downstream of TGF-β, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl₄)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl₄-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-β/Smad signaling pathway.     

纳米药物非临床药代动力学的研究策略及关注要点

随着纳米技术的迅速发展，纳米药物的研发已成为目前药物创新的发展方向之一。纳米药物具有基于纳米结构的尺度效应，其药代动力学特征与普通药物相比存在明显差异，其药代动力学研究与普通药物相比也有其特殊性。本文着重探讨纳米药物的非临床药代动力学的研究策略及关注要点，包括受试物、体内/外试验、生物样本分析、数据评价分析等，期望为研发者提供参考。