Molecular Mechanisms of Fetal Tendon Regeneration Versus Adult Fibrous Repair

Tendinopathies are painful, disabling conditions that afflict 25% of the adult human population. Filling an unmet need for realistic large-animal models, we here present an ovine model of tendon injury for the comparative study of adult scarring repair and fetal regeneration. Complete regeneration of the fetal tendon within 28 days is demonstrated, while adult tendon defects remained macroscopically and histologically evident five months post-injury. In addition to a comprehensive histological assessment, proteome analyses of secretomes were performed. Confirming histological data, a specific and pronounced inflammation accompanied by activation of neutrophils in adult tendon defects was observed, corroborated by the significant up-regulation of pro-inflammatory factors, neutrophil attracting chemokines, the release of potentially tissue-damaging antimicrobial and extracellular matrix-degrading enzymes, and a response to oxidative stress. In contrast, secreted proteins of injured fetal tendons included proteins initiating the resolution of inflammation or promoting functional extracellular matrix production. These results demonstrate the power and relevance of our novel ovine fetal tendon regeneration model, which thus promises to accelerate research in the field. First insights from the model already support our molecular understanding of successful fetal tendon healing processes and may guide improved therapeutic strategies.     

Ubiquitin-Specific Protease 29 Regulates Cdc25A-Mediated Tumorigenesis

Cell division cycle 25A (Cdc25A) is a dual-specificity phosphatase that is overexpressed in several cancer cells and promotes tumorigenesis. In normal cells, Cdc25A expression is regulated tightly, but the changes in expression patterns in cancer cells that lead to tumorigenesis are unknown. In this study, we showed that ubiquitin-specific protease 29 (USP29) stabilized Cdc25A protein expression in cancer cell lines by protecting it from ubiquitin-mediated proteasomal degradation. The presence of USP29 effectively blocked polyubiquitination of Cdc25A and extended its half-life. CRISPR-Cas9-mediated knockdown of USP29 in HeLa cells resulted in cell cycle arrest at the G0/G1 phase. We also showed that USP29 knockdown hampered Cdc25A-mediated cell proliferation, migration, and invasion of cancer cells in vitro. Moreover, NSG nude mice transplanted with USP29-depleted cells significantly reduced the size of the tumors, whereas the reconstitution of Cdc25A in USP29-depleted cells significantly increased the tumor size. Altogether, our results implied that USP29 promoted cell cycle progression and oncogenic transformation by regulating protein turnover of Cdc25A.     

负荷功率模型的最优特征选择研究

负荷功率呈现时空多样的变化特性,其影响因素众多,构建负荷功率模型的关键之一是确定模型的输入特征量。文中着重研究短期负荷功率模型的特征选择,旨在从历史负荷、气象、日期等众多特征中选出最优特征集。首先,采用最大信息系数、基于支持向量机的递归特征消除法和随机森林3种不同特征选择方法分别对输入特征集进行选择;然后,根据对比分析结果提出基于遗传算法的最优特征集搜索策略,选定XGBoost预测模型的误差指标作为适应性函数进行迭代优化搜索;最终,确定负荷功率模型的最优特征输入集。采用某地区220 kV变电站母线负荷数据进行算例分析,对比各方法所选特征集作为功率模型输入得到的负荷预测效果,验证了文中方法的有效性和准确性。     

Connexin 43 and Connexin 26 Involvement in the Ponatinib-Induced Cardiomyopathy: Sex-Related Differences in a Murine Model

Cardiac connexins (Cxs) are proteins responsible for proper heart function. They form gap junctions that mediate electrical and chemical signalling throughout the cardiac system, and thus enable a synchronized contraction. Connexins can also individually participate in many signal transduction pathways, interacting with intracellular proteins at various cellular compartments. Altered connexin expression and localization have been described in diseased myocardium and the aim of this study is to assess the involvement of Cx43, Cx26, and some related molecules in ponatinib-induced cardiac toxicity. Ponatinib is a new multi-tyrosine kinase inhibitor that has been successfully used against human malignancies, but its cardiotoxicity remains worrisome. Therefore, understanding its signaling mechanism is important to adopt potential anti cardiac damage strategies. Our experiments were performed on hearts from male and female mice treated with ponatinib and with ponatinib plus siRNA-Notch1 by using immunofluorescence, Western blotting, and proteomic analyses. The altered cardiac function and the change in Cxs expression observed in mice after ponatinib treatment, were results dependent on the Notch1 pathway and sex. Females showed a lower susceptibility to ponatinib than males. The downmodulation of cardiac Cx43, Cx26 and miR-122, high pS368-Cx43 phosphorylation, cell viability and survival activation could represent some of the female adaptative/compensatory reactions to ponatinib cardiotoxicity.     

Dynamic “Molecular Portraits” of Biomembranes Drawn by Their Lateral Nanoscale Inhomogeneities

To date, it has been reliably shown that the lipid bilayer/water interface can be thoroughly characterized by a sophisticated so-called “dynamic molecular portrait”. The latter reflects a combination of time-dependent surface distributions of various physicochemical properties, inherent in both model lipid bilayers and natural multi-component cell membranes. One of the most important features of biomembranes is their mosaicity, which is expressed in the constant presence of lateral inhomogeneities, the sizes and lifetimes of which vary in a wide range—from 1 to 10³ nm and from 0.1 ns to milliseconds. In addition to the relatively well-studied macroscopic domains (so-called “rafts”), the analysis of micro- and nanoclusters (or domains) that form an instantaneous picture of the distribution of structural, dynamic, hydrophobic, electrical, etc., properties at the membrane-water interface is attracting increasing interest. This is because such nanodomains (NDs) have been proven to be crucial for the proper membrane functioning in cells. Therefore, an understanding with atomistic details the phenomena associated with NDs is required. The present mini-review describes the recent results of experimental and in silico studies of spontaneously formed NDs in lipid membranes. The main attention is paid to the methods of ND detection, characterization of their spatiotemporal parameters, the elucidation of the molecular mechanisms of their formation. Biological role of NDs in cell membranes is briefly discussed. Understanding such effects creates the basis for rational design of new prospective drugs, therapeutic approaches, and artificial membrane materials with specified properties.     

How Cancer Cells Invade Bladder Epithelium and Form Tumors: The Mouse Bladder Tumor Model as a Model of Tumor Recurrence in Patients

Non-muscle-invasive bladder cancer is the most common form of bladder cancer. The main problem in managing bladder tumors is the high recurrence after the transurethral resection of bladder tumors (TURBT). Our study aimed to examine the fate of intravesically applied cancer cells as the implantation of cancer cells after TURBT is thought to be a cause of tumor recurrence. We established an orthotopic mouse bladder tumor model with MB49-GFP cancer cells and traced them during the first three days to define their location and contacts with normal urothelial cells. Data were obtained by Western blot, immunolabeling, and light and electron microscopy. We showed that within the first two hours, applied cancer cells adhered to the traumatized epithelium by cell projections containing α3β1 integrin on their tips. Cancer cells then migrated through the epithelium and on day 3, they reached the basal lamina or even penetrated it. In established bladder tumors, E-cadherin and desmoplakin 1/2 were shown as feasible immunohistochemical markers of tumor margins based on the immunolabeling of various junctional proteins. Altogether, these results for the first time illustrate cancer cell implantation in vivo mimicking cellular events of tumor recurrence in bladder cancer patients.     

六水氯化镁在六种多元醇中溶解度的测定和关联

六水氯化镁的溶解度是镁盐综合利用的重要基础数据。采用静态平衡法测定了六水氯化镁在1,2-丙二醇、1,3-丙二醇、1,3-丁二醇、一缩二乙二醇、二缩三乙二醇、一缩二丙二醇6种多元醇中的溶解度（278.15~328.15 K）。实验结果表明,六水氯化镁在6种多元醇中的溶解度均随着温度的升高而增大,其中在一缩二乙二醇中的溶解度最大,在二缩三乙二醇中的溶解度随着温度的变化较其他多元醇变化更为明显。使用Apelblat方程、λh方程、Van′t Hoff方程和多项式方程对溶解度数据进行了关联,结果良好,其中Apelblat方程和多项式方程拟合结果优于其他方程。利用Van′t Hoff方程计算了6种体系的溶解焓、溶解熵和吉布斯自由能。这些结果对镁盐的分离提取及镁基功能材料的制备具有重要的参考价值。     

微电网跟踪调度计划双层双时间尺度实时控制策略

为了提升微电网跟踪调度计划的能力,并降低分布式电源和负荷的功率波动对跟踪效果的影响,提出一种利用由超级电容和电池储能组成的混合储能系统跟踪调度计划的双层双时间尺度实时控制策略。上层基于模型预测控制方法建立日内滚动优化模型,结合分布式电源和负荷的超短期功率预测结果,综合考虑一段时域内的跟踪偏差及混合储能系统的功率和荷电状态对跟踪调度计划进行滚动优化;下层在上层优化结果的基础上,采用基于荷电状态的混合储能系统实时控制策略对超级电容和电池储能的实时功率进行协调分配,进一步降低分布式电源和负荷的实时功率波动对跟踪效果的影响。通过仿真算例对所提控制策略进行验证,结果表明:所提策略不但实现了良好的实时跟踪调度计划的控制效果,而且优化了超级电容和电池储能的荷电状态。     

考虑样本类别不平衡的电网故障事件智能识别方法

电网中不同设备的故障概率存在差异,影响智能诊断技术的准确性.为解决此问题,提出了一种基于代价敏感学习和模型自适应选择融合的电网故障事件智能识别方法.首先,利用Word2vec模型将预处理后的电网告警信息向量化,并搭建2个双向长短期记忆网络作为基础分类器;然后,设计代价敏感损失函数,将交叉熵损失函数与代价敏感损失函数分别应用于2个分类器中;最后,提出一种模型自适应选择融合法,融合上述分类器,得到故障事件识别结果.实际数据测试表明,所提方法能够有效降低故障事件识别中样本类别不平衡的影响.     

基于模型预测控制算法的多风储直流微电网分布式电压二次控制策略

针对含多组风储单元的直流微电网中蓄电池的电压优化控制问题,提出了一种基于模型预测控制算法的分布式电压二次控制策略.设计了一种多步长预测一致性模型作为电压预测模型,通过目标函数最小化求解预测系数,得到最优电压二次控制补偿量加入一次控制中,将传统一致性算法中比例积分控制器下的偏差调节问题转化为模型预测控制器下的电压跟踪问题进行求解,从而实现对直流母线电压动态响应的滚动优化.该方法有效解决了传统一致性算法下电压控制策略瞬态特性差和部分工况下存在控制误差等问题,并通过MATLAB/Simulink仿真平台搭建模型验证了不同工况下所提策略的有效性和优越性.