Selective Delivery of Doxorubicin to EGFR+ Cancer Cells by Cetuximab–DNA Conjugates

Doxorubicin is a hydrophobic anticancer drug that has poor selectivity, due to the lack of active targeting capability. Here, learning lessons from the success of antibody–drug conjugates, we have designed a new doxorubicin delivery system without conjugating doxorubicin to antibody directly. In this setup, cetuximab, an antibody that targets the epidermal growth factor receptor (EGFR) in cancer cells, was conjugated to a single-stranded DNA with a carefully designed sequence in a site-selective manner by using the DNA-templated protein conjugation (DTPC) method. The DNA duplex in the conjugates serves as a carrier of doxorubicin through noncovalent intercalation, and cetuximab functions as the targeting agent; this could drastically decrease systemic toxicity and potentially avoid under- or overdosing. The size of conjugates loaded with doxorubicin was about 8.77 or 16.61 nm when characterized by dynamic light scattering and atomic force microscopy, respectively. In vitro cytotoxicity and selective cancer cell killing was investigated against two EGFR⁺ cell lines (KB and MDA-MB-231) and one EGFR⁻ cell line (NIH-3T3). Cytotoxicity and flow cytometry data showed that doxorubicin loaded in cetuximab–DNA conjugates was more potent in terms of cell cytotoxicity than free doxorubicin in EGFR-overexpressed cell lines, thus suggesting that the conjugates were more selectively and easily taken up into cells, followed by rapid release of doxorubicin from the system into the cytoplasm from endosomes.     

Environmental Enrichment Enhances Cav 2.1 Channel-Mediated Presynaptic Plasticity in Hypoxic–Ischemic Encephalopathy

Hypoxic–ischemic encephalopathy (HIE) is a devastating neonatal brain condition caused by lack of oxygen and limited blood flow. Environmental enrichment (EE) is a classic paradigm with a complex stimulation of physical, cognitive, and social components. EE can exert neuroplasticity and neuroprotective effects in immature brains. However, the exact mechanism of EE on the chronic condition of HIE remains unclear. HIE was induced by a permanent ligation of the right carotid artery, followed by an 8% O₂ hypoxic condition for 1 h. At 6 weeks of age, HIE mice were randomly assigned to either standard cages or EE cages. In the behavioral assessments, EE mice showed significantly improved motor performances in rotarod tests, ladder walking tests, and hanging wire tests, compared with HIE control mice. EE mice also significantly enhanced cognitive performances in Y-maze tests. Particularly, EE mice showed a significant increase in Ca_v 2.1 (P/Q type) and presynaptic proteins by molecular assessments, and a significant increase of Ca_v 2.1 in histological assessments of the cerebral cortex and hippocampus. These results indicate that EE can upregulate the expression of the Ca_v 2.1 channel and presynaptic proteins related to the synaptic vesicle cycle and neurotransmitter release, which may be responsible for motor and cognitive improvements in HIE.     

Synthesis and characterization of polycrystalline Mo2BC ceramic

Single-phase polycrystalline Mo₂BC ceramic bulks were synthesized successfully from molybdenum, boron, and graphite powders using the spark plasma sintering method. Herein, it was established that the synthesis temperature of the Mo₂BC ceramic could be as low as 1300 °C. Transmission electron microscopy (TEM) characterization confirmed that the crystal structure of the Mo₂BC ceramic was comparable to that of the MoAlB ceramic. The Vickers hardness of the Mo₂BC ceramic was measured to be 18.1 GPa. Additionally, the compressive strength, flexural strength, and fracture toughness were determined to be 1.74 GPa, 457.72 MPa, and 3.26 MPa· m^1/2, respectively. The Mo₂BC bulk exhibited typical brittle features, in which intergranular and transgranular fractures were the main failure modes.     

WSN低功耗低时延路径式协同计算方法

针对云计算应用于无线传感器网络(Wireless Sensor Network,WSN)时延敏感型业务时存在的高传输时延问题,提出了一种WSN低功耗低时延路径式协同计算方法。该方法基于一种云雾网络架构开展研究,该架构利用汇聚节点组成雾计算层;在数据传输过程中基于雾计算层的计算能力分步骤完成任务计算,降低任务处理时延;由于汇聚节点计算能力较弱,时延降低将导致能耗增加,WSN工作寿命减短,为此提出能耗约束下的任务映射策略,并利用离散二进制粒子群优化(Binary Particle Swarm Optimization,BPSO)算法解决能耗约束下的时延优化问题。仿真结果表明,在相同的能耗约束下,对比其他算法,基于BPSO算法得出的映射方案能有效降低业务处理时延,满足时延敏感型业务的需求。     

An adaptive failure boundary approximation method for reliability analysis and its applications

Engineering with Computers - In practical engineering problems, accurate reliability assessment often is computationally expensive with time-consuming numerical models or simulation models. How to...     

包钢120t转炉滑板挡渣技术的改进

文章介绍了包钢120 t转炉滑板挡渣与红外下渣检测技术改进及实际应用情况,并与目前常用挡渣方式进行对比分析,结果表明:改进后挡渣成功率达到99％以上,下渣量控制在80 mm以内,钢水回磷平均控制在0.001％以内,提高了钢水的洁净度,为生产高附加值的钢种和降低生产成本奠定了基础.     

A new As3Mo8V4/PANi/rGO composite for high performance supercapacitor electrode

Herein, [As₂^IIIAs^VMo₈^VIV₄^IVO₄₀]₂[Cu^ICu₂^II(pz)₄]₂·9H₂O/polyaniline/reduced graphene oxide (pz = pyrazine, abbreviated to As₃Mo₈V₄/PANi/rGO) composite is first assembled, characterized and systematically explored for its supercapacitor performance. As₃Mo₈V₄/PANi/rGO composite shows a exceptional specific capacitance (2351 F g^?1 at 1 A g^?1) and outstanding cyclic stability (96.9% after 5000 cycles). The symmetric supercapacitor exhibits high specific capacitance of 1295 F g^?1 at 1 A g^?1 and excellent energy density of 88.1 Wh kg^-1 at power density of 349.6 W kg^-1, while maintaining a notable capacitance retention of 85.7% after 5000 cycles at 2 A g^-1. The above results confirm the potential application of As₃Mo₈V₄/PANi/rGO composite in energy storage devices.     

新型限力输出保护功能柔性夹钳的设计与参数评估

柔性夹钳因具有微/纳精密操作能力, 常应用于微操作系统中, 但因抓爪无法提供恒定输出力或恒力范围小, 容易造成操作对象的损伤或脱落。根据放大模块与常力模块串联的结构形式, 设计了一种具有常力特性的柔性夹钳。基于伪刚体法, 建立放大模块中桥式机构与杠杆机构的刚度和放大率数学模型, 通过对倾斜导向梁进行分析, 得到常力模块的力-位移关系式, 计算出恒定输出力为42.5 N, 输出范围为370 μm。最后, 结合不同柔顺梁的结构参数, 运用MATLAB仿真探究了各关键参数对常力特性的影响。研究结果可为常力柔性夹钳的构型设计和分析提供一定的理论支撑。