Self-Targeted Co-Delivery of an Antibiotic and a Cancer-Chemotherapeutic from Synthetic Liposomes for the Treatment of Infected Tumors

Intra-tumor bacteria promote tumor growth and inactivate cancer-chemotherapeutics, causing poor treatment prognoses. Combined administration of cancer-chemotherapeutics and antibiotics may disturb the oral and intestinal microflora in critically-ill patients. To establish intra-tumor co-delivery of cancer-chemotherapeutics and antibiotics, gemcitabine and ciprofloxacin are loaded in so-called “self-targeting”, highly blood-compatible, synthetic DCPA-H₂O liposomes equipped with complexed water for pH-responsiveness. Liposomal pH-responsiveness can be maintained by in-shell loading of gemcitabine and in-core loading of ciprofloxacin. These dual-loaded liposomes are stealthily transported in the blood circulation to accumulate in the acidic environment of an infected tumor. Upon tumor self-targeting, liposomes are fused with tumor cells and infecting bacteria and are disassembled to simultaneously release gemcitabine and ciprofloxacin. Treatment of mice with these self-targeting liposomes yields significantly higher responses of Escherichia coli infected tumors with respect to both infection and tumor volume than gemcitabine and ciprofloxacin co-delivered from non-self-targeting liposomes or free gemcitabine with or without ciprofloxacin in solution.     

A Metal-Organic Framework Incorporating Eight Different Size Rare-Earth Metal Elements: Toward Multifunctionality À La Carte

Multi-metallic multivariate (MTV) rare earth (RE) metal−organic frameworks (MOFs) are of interest for the development of multifunctional materials, however examples with more than three RE cations are rare and obstructed by compositional segregation during synthesis. Herein, this work demonstrates the synthesis of a multi-metallic MTV RE MOF incorporating two, four, six, or eight different RE ions with different sizes and in nearly equimolar amounts and no compositional segregation. The MOFs are formed by a combination of RE cations (La, Ce, Eu, Gd, Tb, Dy, Y, and Yb) and a 1,7-di(4-carboxyphenyl)-1,7-dicarba-closo-dodecaborane (mCB-L) linker. The steric bulkiness and acidity of mCB-L is crucial for the incorporation of different size RE ions into the MOF structure. Demonstration of the incorporation of all RE cations is performed via compositional and structural characterization. The more complex MTV MOF, including all eight RE ions (mCB-8RE), are also characterized using optical, thermal, and magnetic techniques. Element-selective X-ray absorption spectroscopy and X-ray Magnetic Circular Dichroism measurements allow us to characterize spectroscopically each of the eight RE ions and determine their magnetic moments. This work paves the way for the investigation of MTV MOFs with the possibility to combine RE ions à la carte for diverse applications.     

基于Kullback-Leibler距离的闭环系统传感器微小故障诊断

在闭环控制系统中,当故障幅值较小时,由故障带来的影响会被控制量所掩盖.因此,闭环系统中的微小故障诊断实现更为复杂.本文针对闭环系统中的传感器故障,提出了基于Kullback-Leibler(KL)距离的微小故障在线检测与估计方法.本文首先介绍了KL距离的定义及其在多变量故障检测中的应用,然后提出了结合KL距离与快速移动窗口主成分分析(MWPCA)的在线微小故障检测与估计模型.在高斯分布的假设下,利用系统输入输出残差构造MWPCA的数据矩阵,然后通过在线更新数据矩阵主成分的均值与方差实现KL距离的在线更新,最终实现闭环系统中传感器的在线故障检测与估计.仿真实验表明,该方法能有效实现具有低故障—噪声比(FNR)特性的微小故障诊断.