The Protective Effect of Zebularine,an Inhibitor of DNA Methyltransferase,on Renal Tubulointerstitial Inflammation and Fibrosis

Renal fibrosis, the final pathway of chronic kidney disease, is caused by genetic and epigenetic mechanisms. Although DNA methylation has drawn attention as a developing mechanism of renal fibrosis, its contribution to renal fibrosis has not been clarified. To address this issue, the effect of zebularine, a DNA methyltransferase inhibitor, on renal inflammation and fibrosis in the murine unilateral ureteral obstruction (UUO) model was analyzed. Zebularine significantly attenuated renal tubulointerstitial fibrosis and inflammation. Zebularine decreased trichrome, α-smooth muscle actin, collagen IV, and transforming growth factor-β1 staining by 56.2%. 21.3%, 30.3%, and 29.9%, respectively, at 3 days, and by 54.6%, 41.9%, 45.9%, and 61.7%, respectively, at 7 days after UUO. Zebularine downregulated mRNA expression levels of matrix metalloproteinase (MMP)-2, MMP-9, fibronectin, and Snail1 by 48.6%. 71.4%, 31.8%, and 42.4%, respectively, at 7 days after UUO. Zebularine also suppressed the activation of nuclear factor-κB (NF-κB) and the expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, by 69.8%, 74.9%, and 69.6%, respectively, in obstructed kidneys. Furthermore, inhibiting DNA methyltransferase buttressed the nuclear expression of nuclear factor (erythroid-derived 2)-like factor 2, which upregulated downstream effectors such as catalase (1.838-fold increase at 7 days, p < 0.01), superoxide dismutase 1 (1.494-fold increase at 7 days, p < 0.05), and NAD(P)H: quinone oxidoreduate-1 (1.376-fold increase at 7 days, p < 0.05) in obstructed kidneys. Collectively, these findings suggest that inhibiting DNA methylation restores the disrupted balance between pro-inflammatory and anti-inflammatory pathways to alleviate renal inflammation and fibrosis. Therefore, these results highlight the possibility of DNA methyltransferases as therapeutic targets for treating renal inflammation and fibrosis.     

High-Intensity Focused Ultrasound Induces Adipogenesis via Control of Cilia in Adipose-Derived Stem Cells in Subcutaneous Adipose Tissue

During skin aging, the volume of subcutaneous adipose tissue (sWAT) and the adipogenesis potential of adipose-derived stem cells (ASCs) decrease. It is known that the shortening of cilia length by pro-inflammatory cytokines is related to the decreased adipogenic differentiation of ASCs via increase in Wnt5a/β-catenin. High-intensity focused ultrasound (HIFU) is known to upregulate heat shock proteins (HSP), which decrease levels of pro-inflammatory cytokines. In this study, we evaluated whether HIFU modulates the cilia of ASCs by upregulating HSP70 and decreasing inflammatory cytokines. HIFU was applied at 0.2 J to rat skin, which was harvested at 1, 3, 7, and 28 days. All results for HIFU-applied animals were compared with control animals that were not treated. HIFU increased expression of HSP70 and decreased expression of NF-κB, IL-6, and TNF-α in sWAT. HIFU decreased the expression of cilia disassembly-related factors (AurA and HDAC9) in ASCs. Furthermore, HIFU increased the expression of cilia assembly-related factors (KIF3A and IFT88), decreased that of WNT5A/β-catenin, and increased that of the adipogenesis markers PPARγ and CEBPα in sWAT. HIFU increased the number of adipocytes in the sWAT and the thickness of sWAT. In conclusion, HIFU could selectively increase sWAT levels by modulating the cilia of ASCs and be used for skin rejuvenation.     

Thermistor behavior of PEDOT:PSS thin film

The temperature-dependent resistance changing characteristics (thermistor behaviors) of a poly(3,4-ethylenedioxythophene):poly(4-styrenesulfonate) (PEDOT:PSS) thin film are investigated in the 30–100 °C range using Greek-cross and bar patterns. The PEDOT:PSS film was spin-coated onto a Si wafer passivated with a SiO₂ layer, and a conventional dry etching technique was used to pattern the PEDOT:PSS film in conjunction with a nitride etch mask layer. Cr/Au was used for the electrode material. It was found that the characteristic temperature (T₀) and resistivity of the PEDOT:PSS film have an inversely proportional relationship with the number of coatings and the number of interfaces between multiply coated PEDOT:PSS layers. It was also found that as the number of coatings and the number of the interfaces increase, lower temperature-dependent resistance changes are observed. The temperature coefficient of resistance (TCR) value of 60 nm thick PEDOT:PSS film was slightly larger than or comparable to that of a conventional metal (Au or Pt) thermistor. The possibility of utilizing the PEDOT:PSS thin film in thermistor applications is discussed.     

Application of solid phase-microextraction (SPME) and electronic nose techniques to differentiate volatiles of sesame oils prepared with diverse roasting conditions

Headspace volatiles of sesame oil (SO) from sesame seeds roasted at 9 different conditions were analyzed by a combination of solid phase microextraction (SPME)-gas chromatography/mass spectrometry (GC/MS), electronic nose/metal oxide sensors (MOS), and electronic nose/MS. As roasting temperature increased from 213 to 247 °C, total headspace volatiles and pyrazines increased significantly (P < 0.05). Pyrazines were major volatiles in SO and furans, thiazoles, aldehydes, and alcohols were also detected. Roasting temperature was more discrimination factor than roasting time for the volatiles in SO through the principal component analysis (PCA) of SPME-GC/MS, electronic nose/MOS, and electronic nose/MS. Electronic nose/MS showed that ion fragment 52, 76, 53, and 51 amu played important roles in discriminating volatiles in SO from roasted sesame seeds, which are the major ion fragments from pyrazines, furans, and furfurals. SO roasted at 213, 230, and 247 °C were clearly differentiated from each other on the base of volatile distribution by SPME-GC/MS, electronic nose/MOS, and electronic nose/MS analyses. Practical Application: The results of this study are ready to apply for the discriminating samples using a combinational analysis of volatiles. Not only vegetable oils prepared from roasting process but also any food sample possessing volatiles could be targets for the SPME-GC/MS and electronic nose assays. Contents and types of pyrazines in sesame seed oil could be used as markers to track down the degree of roasting and oxidation during oil preparation.     

The effect of chemical treatment on reduction of aflatoxins and ochratoxin A in black and white pepper during washing

The effect of 18 different chemicals, which included acidic compounds (sulfuric acid, chloridric acid, phosphoric acid, benzoic acid, citric acid, acetic acid), alkaline compounds (ammonia, sodium bicarbonate, sodium hydroxide, potassium hydroxide, calcium hydroxide), salts (acetate ammonium, sodium bisulfite, sodium hydrosulfite, sodium chloride, sodium sulfate) and oxidising agents (hydrogen peroxide, sodium hypochlorite), on the reduction of aflatoxins B(1), B(2), G(1) and G(2) and ochratoxin A (OTA) was investigated in black and white pepper. OTA and aflatoxins were determined using HPLC after immunoaffinity column clean-up. Almost all of the applied chemicals showed a significant degree of reduction on mycotoxins (p < 0.05). The lowest and highest reduction of aflatoxin B(1), which is the most dangerous aflatoxin, was 20.5% ± 2.7% using benzoic acid and 54.5% ± 2.7% using sodium hydroxide. There was no significant difference between black and white peppers (p < 0.05).     

关于Filon算法的一点注记

本文对谐波分析中数值积分的Filon公式提出了一点改进,改进后的算法在微机上得到实现,经实算表明,计算结果满足工程精度要求。     

A systematic approach for model refinement considering blind and recognized uncertainties in engineered product development

In recent years, virtual testing has played an increasingly important role in the design and evaluation of engineered products. However, it is challenging to build the highly accurate computational models for virtual testing. Blind and recognized uncertainties are often unintentionally incorporated. These uncertainties consequently decrease the predictive capability of the models. To this end, this paper proposes a systematic approach for model refinement that minimizes the impact of unrecognized blind and recognized epistemic uncertainties in computational modeling. The approach consists of three steps: model invalidity analysis (MIA), development of an invalidity reasoning tree (IRT), and invalidity sensitivity analysis (ISA). First, in the MIA, possible causes that lead to discrepancies between the experimental and simulation responses are identified through brainstorming. Next, the IRT is built using the affinity diagram. It sequentially lists and screens potential candidate issues for model refinement at the stages of conceptual, mathematical, and computational modeling. Finally, the ISA quantifies the effect of incorporating updates in the model to address potential candidate issues with the goal of reducing the impact of the blind and recognized uncertainties. The most critical candidates are determined by using a weighted decision matrix. To demonstrate the effectiveness of the proposed approach, a case study examining a smartphone liquid crystal display fracture is presented.     

Moment-Based Angular Difference Estimation Between Two Tomographic Projections in 2D and 3D

This paper introduces a new method for estimating the angular difference between two tomographic projections belonging to a set of projections taken at unknown directions in 2D and 3D. Our method relies on the projection neighbor selection in projection moment space, the calculation of the angular differences between these neighboring projections using moment properties and a projection moment neighborhood graph. The accuracy and the robustness of our method are shown on a test database including fifty 2D and 3D gray-level images at different resolutions and with different levels of noise.     

Advancements in Dry Powder Delivery to the Lung

The dry powder inhaler (DPI) has become widely known as a very attractive platform for drug delivery. Many patients have traditionally used DPIs to treat asthma and chronic obstructive pulmonary disease. Recently, the development of new DPIs for delivering therapeutic proteins such as insulin has been accelerated by patient demands, and innovative research. The current market for DPIs has over 20 devices presently in use, and many devices under development for delivering a variety of therapeutic agents. DPIs are recognized as suitable alternatives to pressurized metered dose inhalers for some patients, but the performance of DPI devices may vary according to a given patient's physiological condition. This variation can be associated with the necessary powder dispersion mechanism of each device. As such, much interest has focused on the development of efficient powder dispersion mechanisms, as this effectively minimizes the influence of interpatient variability. This article reviews DPI devices currently available, advantages of newly developed devices, outlines some requirements for future device design.