Reduction of In-Stent Restenosis Risk on Nickel-Free Stainless Steel by Regulating Cell Apoptosis and Cell Cycle

High nitrogen nickel-free austenitic stainless steel (HNNF SS) is one of the biomaterials developed recently for circumventing the in-stent restenosis (ISR) in coronary stent applications. To understand the ISR-resistance mechanism, we have conducted a comparative study of cellular and molecular responses of human umbilical vein endothelial cells (HUVECs) to HNNF SS and 316L SS (nickel-containing austenitic 316L stainless steel) which is the stent material used currently. CCK-8 analysis and flow cytometric analysis were used to assess the cellular responses (proliferation, apoptosis, and cell cycle), and quantitative real-time PCR (qRT-PCR) was used to analyze the gene expression profile of HUVECs exposed to HNNF SS and 316L SS, respectively. Flow cytometry analysis revealed that 316L SS could activate the cellular apoptosis more efficiently and initiate an earlier entry into the S-phase of cell cycle than HNNF SS. At the molecular level, qRT-PCR results showed that the genes regulating cell apoptosis and autophagy were overexpressed on 316L SS. Further examination indicated that nickel released from 316L SS triggered the cell apoptosis via Fas-Caspase8-Caspase3 exogenous pathway. These molecular mechanisms of HUVECs present a good model for elucidating the observed cellular responses. The findings in this study furnish valuable information for understanding the mechanism of ISR-resistance on the cellular and molecular basis as well as for developing new biomedical materials for stent applications.     

1991-2010年宁夏水稻病虫害发生特征与经济损失分析

水稻病虫害发生种类繁多、暴发频繁,是威胁宁夏水稻稳产、高产的重要因素,但对其变化趋势与实际危害损失不清楚.基于宁夏水稻统计数据、稻田覆盖类型遥感数据和水稻产量数据,分析1991年至2010年宁夏水稻病虫害发生特征与经济损失情况.结果表明:1991年到2010年期间,宁夏水稻病害、虫害年均发生面积分别为5.3万hm2和2.0万hm2,其年均防治面积分别为8.4万hm2和1.6万hm2;水稻病害的发生程度下降了23.10％,防治程度上升了77.30％.20年间宁夏水稻虫害的发生面积、发生程度、防治面积和防治程度均显著增加.防治水稻病害、虫害后,分别挽回稻谷为2.67万吨、0.28万吨,其挽回损失量在20年期间分别增加了55.15％、2775.0％,表明水稻病虫害防治意义重大.由于气候变化等诸多因子,导致1991年到2010年宁夏水稻病害、虫害年均造成的实际稻谷损失量分别为0.71万吨与0.13万吨,水稻病害实际损失量在0值附件波动、虫害呈现波动增加趋势,说明水稻病害防控效果好、虫害的防控还有提升的空间.从全区各市县分布来看,水稻病虫害主要分布在宁夏的银北地区.为有效地防止或减少病虫害对水稻产量的损失,应加强农田景观变化和气候变化等对水稻病虫害发生与灾变的风险评估和监测预警,开展区域性水稻病虫害综合治理研究,并建立相应的防控新对策与技术体系.     

Integration: An Effective Strategy to Develop Multifunctional Energy Storage Devices

Energy storage devices are arousing increasing interest due to their key role in next‐generation electronics. Integration is widely explored as a general and effective strategy aiming at high performances. Recent progress in integrating a variety of functions into electrochemical energy storage devices is carefully described. Through integration at the level of materials: flexible, stretchable, responsive, and self‐healing devices are discussed to highlight the state‐of‐the‐art multi‐functional electronics. Through the integration at the level of devices, the incorporation of photovoltaic and piezoelectric devices is detailed to reflect the advances in self‐powering electronics. Integrated energy storage devices are presented for wearable applications to indicate a new growth direction. The main challenges and important directions are summarized to offer some useful clues for future development.     

Monoacylglycerol lipase promotes progression of hepatocellular carcinoma via NF-κB-mediated epithelial-mesenchymal transition

Background

Monoacylglycerol lipase (MAGL), a critical lipolytic enzyme, has emerged as a key regulator of tumor progression, yet its biological function and clinical significance in hepatocellular carcinoma (HCC) is still unknown.

Methods

In this study, we used a tissue microarray containing samples from 170 HCC patients to evaluate the expression of MAGL and its correlation with other clinicopathologic characteristics. In addition, we investigated the regulating effects of MAGL on various HCC lines. Finally, we identified the NF-κB signaling pathway participated in MAGL-mediated epithelial-mesenchymal transition (EMT) using HCC cell lines with different metastatic potentials.

Results

The expression of MAGL was significantly higher in HCC tumors than in matched peritumor tissues. Specifically, high MAGL expression was found in tumors with larger tumor size, microvascular invasion, poor differentiation, or advanced TNM stage. In addition, the clinical prognosis for the MAGL^high group was markedly poorer than that for the MAGL^low group in the 1-, 3-, and 5-year overall survival times and recurrence rates of HCC patients. MAGL expression was an independent prognostic factor for both survival and recurrence after curative resection. Furthermore, the upregulation of MAGL in HCC cells promoted cell growth and invasiveness abilities, and accompanied by EMT. In contrast, downregulation of MAGL obviously inhibited these characteristics. Moreover, further investigations verified that MAGL facilitates HCC progression via NF-κB-mediated EMT process.

Conclusions

Our findings demonstrate MAGL could promote HCC progression by the induction of EMT and suggest a potential therapeutic target, as well as a biomarker for prognosis, in patients with HCC.

     

A bispecific antibody effectively neutralizes all four serotypes of dengue virus by simultaneous blocking virus attachment and fusion

Although dengue virus (DENV) infection severely threatens the health of humans, no specific antiviral drugs are currently approved for clinical use against DENV infection. Attachment and fusion are 2 critical steps for the flavivirus infection, and the corresponding functional epitopes are located at E protein domain III (E-DIII) and domain II (E-DII), respectively. Here, we constructed a bispecific antibody (DVD-1A1D-2A10) based on the 2 well-characterized anti-DENV monoclonal antibodies 1A1D-2 (1A1D) and 2A10G6 (2A10). The 1A1D antibody binds E-DIII and can block the virus attaching to the cell surface, while the 2A10 antibody binds E-DII and is able to prevent the virus from fusing with the endosomal membrane. Our data showed that DVD-1A1D-2A10 retained the antigen-binding activity of both parental antibodies. Importantly, it was demonstrated to be significantly more effective at neutralizing DENV than its parental antibodies both in vitro and in vivo, even better than the combination of them. To eliminate the potential antibody-dependent enhancement (ADE) effect, this bispecific antibody was successfully engineered to prevent Fc-γ-R interaction. Overall, we generated a bispecific anti-DENV antibody targeting both attachment and fusion stages, and this bispecific antibody broadly neutralized all 4 serotypes of DENV without risk of ADE, suggesting that it has great potential as a novel antiviral strategy against DENV.