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.     

Machine learning algorithm selection for windage alteration fault diagnosis of mine ventilation system

Machine learning algorithms have been widely used in mine fault diagnosis. The correct selection of the suitable algorithms is the key factor that affects the fault diagnosis. However, the impact of machine learning algorithms on the prediction performance of mine fault diagnosis models has not been fully evaluated. In this study, the windage alteration faults (WAFs) diagnosis models, which are based on K-nearest neighbor algorithm (KNN), multi-layer perceptron (MLP), support vector machine (SVM), and decision tree (DT), are constructed. Furthermore, the applicability of these four algorithms in the WAFs diagnosis is explored by a T-type ventilation network simulation experiment and the field empirical application research of Jinchuan No. 2 mine. The accuracy of the fault location diagnosis for the four models in both networks was 100%. In the simulation experiment, the mean absolute percentage error (MAPE) between the predicted values and the real values of the fault volume of the four models was 0.59%, 97.26%, 123.61%, and 8.78%, respectively. The MAPE for the field empirical application was 3.94%, 52.40%, 25.25%, and 7.15%, respectively. The results of the comprehensive evaluation of the fault location and fault volume diagnosis tests showed that the KNN model is the most suitable algorithm for the WAFs diagnosis, whereas the prediction performance of the DT model was the second-best. This study realizes the intelligent diagnosis of WAFs, and provides technical support for the realization of intelligent ventilation.     

基于VMD和BSA-KELM的高陡边坡位移预测模型研究

边坡位移的时间序列曲线存在复杂的非线性特性,传统的预测模型精度不足以满足预测要求。为此提出了基于变分模态分解的鸟群优化-核极限学习机的预测模型,并用于河北省某水泥厂的边坡位移预测。该方法首先采用VMD把边坡位移序列分解为一系列的有限带宽的子序列,再对各子序列分别采用相空间重构并用核极限学习机预测,采用鸟群算法优化相空间重构的嵌入维度和KELM中惩罚系数和核参数三个数值,以取得最优预测模型。最后将各个子序列预测值叠加,得到边坡位移的最终预测值。结果表明：和KELM、BSA-KELM、EEMD-BSA-KELM模型相比,基于VMD的BSA-KELM预测精度更高,为边坡位移的预测提供一种有效的方法。     

Double emulsion (W/O/W) gel stabilised by polyglycerol polyricinoleate and calcium caseinate as mangiferin carrier: insights on formulation and stability properties

Mangiferin (MGF) is a phenolic compound isolated from mango, but its poor solubility significantly limits its use. In this study, MGF was embedded into the inner aqueous phase of W₁/O/W₂ emulsions. Firstly, the dissolution method of MGF was determined. MGF remained stable in solution with pH 13 at 30 min, and its solubility reached 10 mg mL⁻¹. When the pH of MGF solutions was adjusted from pH 13 to pH 6, MGF did not immediately crystallise, providing sufficient time to construct the MGF-loaded W₁/O/W₂ emulsions. Subsequently, the MGF-loaded W₁/O/W₂ emulsions were constructed using polyglycerol polyricinoleate (PGPR) and calcium caseinate (CAS). The formation and stability of the W₁/O/W₂ emulsions were investigated. The MGF-loaded W₁/O/W₂ emulsions stabilised with 1% PGPR and 1% – 3% CAS exhibited a low viscosity, limited loading capacity, and poor stability. Conversely, the MGF-loaded W₁/O/W₂ emulsions stabilised by 3%PGPR–3%CAS exhibited optimal loading capacity (encapsulation efficiency = 95.31% and loading efficiency = 0.91%) and stability, which was attributed to the fact that high viscosity and gel state retarded the migration of inner aqueous phase. These results indicated that the W₁/O/W₂ emulsions stabilised by PGPR and CAS may be a potential alternative for encapsulating mangiferin.     

Digital twin-based analysis of volumetric error mapping procedures

The evaluation of the volumetric accuracy of a machine tool is an open challenge in the industry, and a wide variety of technical solutions are available in the market and at research level. All solutions have advantages and disadvantages concerning which errors can be measured, the achievable uncertainty, the ease of implementation, possibility of machine integration and automation, the equipment cost and the machine occupation time, and it is not always straightforward which option to choose for each application. The need to ensure accuracy during the whole lifetime of the machine and the availability of monitoring systems developed following the Industry 4.0 trend are pushing the development of measurement systems that can be integrated in the machine to perform semi-automatic verification procedures that can be performed frequently by the machine user to monitor the condition of the machine. Calibrated artefact based calibration and verification solutions have an advantage in this field over laser based solutions in terms of cost and feasibility of machine integration, but they need to be optimized for each machine and customer requirements to achieve the required calibration uncertainty and minimize machine occupation time.This paper introduces a digital twin-based methodology to simulate all relevant effects in an artefact-based machine tool calibration procedure, from the machine itself with its expected error ranges, to the artefact geometry and uncertainty, artefact positions in the workspace, probe uncertainty, compensation model, etc. By parameterizing all relevant variables in the design of the calibration procedure, this simulation methodology can be used to analyse the effect of each design variable on the error mapping uncertainty, which is of great help in adapting the procedure to each specific machine and user requirements. The simulation methodology and the analysis possibilities are illustrated by applying it on a 3-axis milling machine tool.     

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。     

Designing optical glasses by machine learning coupled with a genetic algorithm

Engineering new glass compositions have experienced a sturdy tendency to move forward from (educated) trial-and-error to data- and simulation-driven strategies. In this work, we developed a computer program that combines data-driven predictive models (in this case, neural networks) with a genetic algorithm to design glass compositions with desired combinations of properties. First, we induced predictive models for the glass transition temperature (T_g) using a dataset of 45,302 compositions with 39 different chemical elements, and for the refractive index (n_d) using a dataset of 41,225 compositions with 38 different chemical elements. Then, we searched for relevant glass compositions using a genetic algorithm informed by a design trend of glasses having high n_d (1.7 or more) and low T_g (500 °C or less). Two candidate compositions suggested by the combined algorithms were selected and produced in the laboratory. These compositions are significantly different from those in the datasets used to induce the predictive models, showing that the used method is indeed capable of exploration. Both glasses met the constraints of the work, which supports the proposed framework. Therefore, this new tool can be immediately used for accelerating the design of new glasses. These results are a stepping stone in the pathway of machine learning-guided design of novel glasses.     

Combinations of Piperine with Hydroxypropyl-β-Cyclodextrin as a Multifunctional System

Piperine is an alkaloid that has extensive pharmacological activity and impacts other active substances bioavailability due to inhibition of CYP450 enzymes, stimulation of amino acid transporters and P-glycoprotein inhibition. Low solubility and the associated low bioavailability of piperine limit its potential. The combination of piperine with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) causes a significant increase in its solubility and, consequently, an increase in permeability through gastrointestinal tract membranes and the blood–brain barrier. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) were used to characterize interactions between piperine and HP-β-CD. The observed physicochemical changes should be combined with the process of piperine and CD system formation. Importantly, with an increase in solubility and permeability of piperine as a result of interaction with CD, it was proven to maintain its biological activity concerning the antioxidant potential (2,2-diphenyl-1-picryl-hydrazyl-hydrate assay), inhibition of enzymes essential for the inflammatory process and for neurodegenerative changes (hyaluronidase, acetylcholinesterase, butyrylcholinesterase).