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.     

菱铁矿直接还原-低阶煤提质一体化扩大试验

摘要：菱铁矿作为中国重要的铁矿资源，因具有“贫、细、杂”的特点，常规选矿工艺无法对其进行有效分选；此外，中国低阶煤通常被用作低级燃料直接燃烧使用，导致大气污染严重。因此，开发复杂难选铁矿石及低阶煤资源高效清洁利用新技术，将具有重要现实意义。以难选的低品位菱铁矿和难利用低阶煤为对象，开展菱铁矿直接还原与低阶煤提质一体化扩大试验研究。以神府烟煤为还原剂，在直接还原温度为1050℃，时间为120min，C/Fe质量比为250，脱硫剂配比为6%，干式磁选磁场强度为015 T，一段磨矿细度小于0074mm占50%左右，湿式磁选磁场强度为008 T，二段磨矿细度小于0074mm占90%左右，磁选磁场强度为0043 T的条件下，可获得直接还原铁（DRI）粉铁品位9103%、铁总回收率8133%的良好指标；同时每吨DRI固定碳质量分数为7611%的半焦产品产出率为1340kg，其质量达到工业及民用燃料兰炭Ⅰ级品标准。在煤基直接还原工艺中一步成功实现低阶煤半焦化提质和铁矿直接还原，不仅可制备电炉炼钢原料，还可以生产新型的清洁燃料半焦。     

基于并行跟踪检测框架与深度学习的目标跟踪算法

在空地协同背景下，地面目标的移动导致其在无人机视角下外观会发生较大变化，传统算法很难满足此类场景的应用要求。针对这一问题，提出基于并行跟踪和检测（PTAD）框架与深度学习的目标检测与跟踪算法。首先，将基于卷积神经网络（CNN）的目标检测算法SSD作为PTAD的检测子处理关键帧获取目标信息并提供给跟踪子；其次，检测子与跟踪子并行处理图像帧并计算检测与跟踪结果框的重叠度及跟踪结果的置信度；最后，根据跟踪子与检测子的跟踪或检测状态来判断是否对跟踪子或检测子进行更新，并对图像帧中的目标进行实时跟踪。在无人机视角下的视频序列上开展实验研究和对比分析，结果表明所提算法的性能高于PTAD框架下最优算法，而且实时性提高了13%，验证了此算法的有效性。     

电站锅炉空气预热器跳闸分析与处理

某厂空气预热器因蓄热元件损坏严重,存在很大安全隐患.运行中出现了空气预热器卡涩跳闸,排烟温度大幅升高,严重威胁锅炉安全运行.分析了空气预热器卡涩跳闸原因,并提出防范措施.     

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.