The role of a drug-loaded poly(lactic co-glycolic acid)(PLGA) copolymer stent in the treatment of ovarian cancer

Objectives:Cisplatin(CDDP)is a widely used and effective basic chemotherapeutic drug for the treatment of a variety of tumors,including ovarian cancer.However,adverse side effects and acquired drug resistance are observed in the clinical application of CDDP.Identifying a mode of administration that can alleviate side effects and reduce drug resistance has become a promising strategy to solve this problem.Methods:In this study,3 D printing technology was used to prepare a CDDP-poly(lactic-co-glycolic acid)(CDDP-PLGA)polymer compound stent,and its physicochemical properties and cytotoxicity were evaluated both in vitro and in vivo.Results:The CDDP-PLGA stent had a significant effect on cell proliferation and apoptosis and clearly decreased the size of subcutaneous tumors in nude mice,whereas the systemic side effects were mild compared with those of intraperitoneal CDDP injection.Compared with the control group,CDDP-PLGA significantly increased the mRNA and protein levels of p-glycoprotein(P<0.01;P<0.01)and decreased vascular endothelial growth factor mRNA(P<0.05)and protein levels(P<0.01),however,CDDP-PLGA significantly decreased the mR NA and protein levels of p-glycoprotein(P<0.01;P<0.01)and vascular endothelial growth factor(P<0.01;P<0.01),which are associated with chemoresistance,in subcutaneous tumor tissue.Immunohistochemistry assay results revealed that,in the CDDP-PLGA group,the staining of the proliferation-related genes Ki67 and PCNA were lightly,and the apoptosis-related gene caspase-3 stained deeply.Conclusions:PLGA biomaterials loaded with CDDP,as compared with the same amount of free CDDP,showed good efficacy in terms of cytotoxicity,as evidenced by changes in apoptosis.Continuous local CDDP release can decrease the systemic side effects of this drug and the occurrence of drug resistance and angiogenesis,and improve the therapeutic effect.This new approach may be an effective strategy for the local treatment of epithelial ovarian cancer.

A modified logarithmic spiral method for determining passive earth pressure

In this study, a modified logarithmic spiral method is proposed to determine the passive earth pressure and failure surface of cohesionless sloping backfill, with presence of wallesoil interface friction. The proposed method is based on a limit equilibrium analysis wherein the assumed profile of the backfill failure surface is a composite of logarithmic spiral and its tangent. If the wallesoil interface is smooth, a straight line does not need to be assumed for the failure surface. The geometry of the failure surface is determined using the Mohr circle analysis of the soil. The resultant passive earth thrust is computed considering equilibrium of moments. The passive earth pressure coefficients are calculated with varied values of soil internal friction angle and cohesion, wall friction angle and inclination angle, and sloping backfill angle. This method is verified with the finite element method(FEM) by comparing the horizontal passive earth pressure and failure surface. The results agree well with other solutions, particularly with those obtained by the FEM. The implementation of the present method is efficient. The logarithmic spiral theory is rigorous and self-explanatory for the geotechnical engineer.

基于手势交互和振动触觉反馈的沉浸式空间液桥实验系统

液桥操作是空间站遥科学实验的重要内容,为保证人与远程空间实验设备的同步交互操作需求,对交互操作精确性和实时性有严格要求。针对空间液桥实验中拉桥、清桥等典型操作的随动控制任务,为达到自然沉浸的交互式效果,研制了基于LeapMotion手势交互控制并融合振动触觉反馈的三维沉浸式液桥实验系统。提出了一种基于位置控制的手势识别算法与模糊控制算法,实验验证该算法记忆负荷小,识别准确率为97.68%。实验结果表明视触融合的交互性效果优于单一视觉反馈效果,将LeapMotion多手势识别、振动触觉反馈与三维沉浸显示有机融合,为空间遥科学实验提供了新型的自然交互方式。

Haptic display for virtual reality: progress and challenges

Immersion, interaction, and imagination are three features of virtual reality (VR). Existing VR systems possess fairly realistic visual and auditory feedbacks, and however, are poor with haptic feedback, by means of which human can perceive the physical world via abundant haptic properties. Haptic display is an interface aiming to enable bilateral signal communications between human and computer, and thus to greatly enhance the immersion and interaction of VR systems. This paper surveys the paradigm shift of haptic display occurred in the past 30 years, which is classified into three stages, including desktop haptics, surface haptics, and wearable haptics. The driving forces, key technologies and typical applications in each stage are critically reviewed. Toward the future high-fidelity VR interaction, research challenges are highlighted concerning handheld haptic device, multimodal haptic device, and high fidelity haptic rendering. In the end, the importance of understanding human haptic perception for designing effective haptic devices is addressed.

RePhine: An Integrative Method for Identification of Drug Response-related Transcriptional Regulators

Transcriptional regulators(TRs)participate in essential processes in cancer pathogenesis and are critical therapeutic targets.Identification of drug response-related TRs from cell line-based compound screening data is often challenging due to low m RNA abundance of TRs,protein modifications,and other confounders(CFs).In this study,we developed a regression-based pharmacogenomic and Ch IP-seq data integration method(Re Phine)to infer the impact of TRs on drug response through integrative analyses of pharmacogenomic and Ch IP-seq data.Re Phine was evaluated in simulation and pharmacogenomic data and was applied to pan-cancer datasets with the goal of biological discovery.In simulation data with added noises or CFs and in pharmacogenomic data,Re Phine demonstrated an improved performance in comparison with three commonly used methods(including Pearson correlation analysis,logistic regression model,and gene set enrichment analysis).Utilizing Re Phine and Cancer Cell Line Encyclopedia data,we observed that Re Phinederived TR signatures could effectively cluster drugs with different mechanisms of action.Re Phine predicted that loss-offunction of EZH2/PRC2 reduces cancer cell sensitivity toward the BRAF inhibitor PLX4720.Experimental validation confirmed that pharmacological EZH2 inhibition increases the resistance of cancer cells to PLX4720 treatment.Our results support that Re Phine is a useful tool for inferring drug response-related TRs and for potential therapeutic applications.The source code for Re Phine is freely available at https://github.com/coexps/Re Phine.