Functionalized Reduced Graphene Oxide as a Versatile Tool for Cancer Therapy

Cancer is one of the deadliest diseases in human history with extremely poor prognosis. Although many traditional therapeutic modalities—such as surgery, chemotherapy, and radiation therapy—have proved to be successful in inhibiting the growth of tumor cells, their side effects may vastly limited the actual benefits and patient acceptance. In this context, a nanomedicine approach for cancer therapy using functionalized nanomaterial has been gaining ground recently. Considering the ability to carry various anticancer drugs and to act as a photothermal agent, the use of carbon-based nanomaterials for cancer therapy has advanced rapidly. Within those nanomaterials, reduced graphene oxide (rGO), a graphene family 2D carbon nanomaterial, emerged as a good candidate for cancer photothermal therapy due to its excellent photothermal conversion in the near infrared range, large specific surface area for drug loading, as well as functional groups for functionalization with molecules such as photosensitizers, siRNA, ligands, etc. By unique design, multifunctional nanosystems could be designed based on rGO, which are endowed with promising temperature/pH-dependent drug/gene delivery abilities for multimodal cancer therapy. This could be further augmented by additional advantages offered by functionalized rGO, such as high biocompatibility, targeted delivery, and enhanced photothermal effects. Herewith, we first provide an overview of the most effective reducing agents for rGO synthesis via chemical reduction. This was followed by in-depth review of application of functionalized rGO in different cancer treatment modalities such as chemotherapy, photothermal therapy and/or photodynamic therapy, gene therapy, chemotherapy/phototherapy, and photothermal/immunotherapy.     

Prediction of Functional Consequences of Missense Mutations in ANO4 Gene

The anoctamin (TMEM16) family of transmembrane protein consists of ten members in vertebrates, which act as Ca²⁺-dependent ion channels and/or Ca²⁺-dependent scramblases. ANO4 which is primarily expressed in the CNS and certain endocrine glands, has been associated with various neuronal disorders. Therefore, we focused our study on prioritizing missense mutations that are assumed to alter the structure and stability of ANO4 protein. We employed a wide array of evolution and structure based in silico prediction methods to identify potentially deleterious missense mutations in the ANO4 gene. Identified pathogenic mutations were then mapped to the modeled human ANO4 structure and the effects of missense mutations were studied on the atomic level using molecular dynamics simulations. Our data show that the G80A and A500T mutations significantly alter the stability of the mutant proteins, thus providing new perspective on the role of missense mutations in ANO4 gene. Results obtained in this study may help to identify disease associated mutations which affect ANO4 protein structure and function and might facilitate future functional characterization of ANO4.     

基于断电后残余电压的感应电机定子故障诊断

为了提高感应电机定子绕组故障诊断的准确性,提出了一种基于Hilbert-Huang变换(HHT)的故障诊断新方法.选取断电后零序电压的基波分量作为定子故障特征,可有效避免电源不平衡和负荷波动的影响,直接反映电机定子的不对称度.利用Hilbert-Huang变换中经验模态分解(EMD)方法对断电后的零序电压进行了分解,提取出基波分量,通过计算其均方根值可以诊断出电机定子绕组故障.在一台4 kW的感应电机上进行的实验证明了该方法的可行性和有效性.     

基于家族基因的网格信任模型

针对现有基于PKI (Public Key Infrastructure)的网格信任系统的不足,证书主体信息不明确, 认证过程复杂等缺陷提出了一种新颖的基于家族基因的网格信任模型。该模型解决了传统信任模型存在的问题,如采用将用户的全部身份信息放在用户的基因里方法解决了证书主体信息的不明确,用基因检测解决了认证过程的复杂,用基因指派解决了访问控制的繁琐,并且给出了网格家族、家族基因、基因指派、基因鉴别和信任等概念,并建立了模型的形式化描述,理论分析和实验结果表明这种模型是网格信任领域一种较好的解决方案。     

Development of Covalent Chitosan-Polyethylenimine Derivatives as Gene Delivery Vehicle: Synthesis,Characterization, and Evaluation

There is an increasing interest in cationic polymers as important constituents of non-viral gene delivery vectors. In the present study, we developed a versatile synthetic route for the production of covalent polymeric conjugates consisting of water-soluble depolymerized chitosan (dCS; M_W 6–9 kDa) and low molecular weight polyethylenimine (PEI; 2.5 kDa linear, 1.8 kDa branched). dCS-PEI derivatives were evaluated based on their physicochemical properties, including purity, covalent bonding, solubility in aqueous media, ability for DNA condensation, and colloidal stability of the resulting polyplexes. They were complexed with non-integrating DNA vectors coding for reporter genes by simple admixing and assessed in vitro using liver-derived HuH-7 cells for their transfection efficiency and cytotoxicity. Using a rational screening cascade, a lead compound was selected (dCS-Suc-LPEI-14) displaying the best balance of biocompatibility, cytotoxicity, and transfection efficiency. Scale-up and in vivo evaluation in wild-type mice allowed for a direct comparison with a commercially available non-viral delivery vector (in vivo-jetPEI). Hepatic expression of the reporter gene luciferase resulted in liver-specific bioluminescence, upon intrabiliary infusion of the chitosan-based polyplexes, which exceeded the signal of the in vivo jetPEI reference formulation by a factor of 10. We conclude that the novel chitosan-derivative dCS-Suc-LPEI-14 shows promise and potential as an efficient polymeric conjugate for non-viral in vivo gene therapy.