PD‐1 Blockade for Improving the Antitumor Efficiency of Polymer–Doxorubicin Nanoprodrug

Chemotherapy is well recognized to induce immune responses during some chemotherapeutic drugs‐mediated tumor eradication. Here, a strategy involving blocking programmed cell death protein 1 (PD‐1) to enhance the chemotherapeutic effect of a doxorubicin nanoprodrug HA‐Psi‐DOX is proposed and the synergetic mechanism between them is further studied. The nanoprodrugs are fabricated by conjugating doxorubicin (DOX) to an anionic polymer hyaluronic acid (HA) via a tumor overexpressed matrix metalloproteinase sensitive peptide (CPLGLAGG) for tumor targeting and enzyme‐activated drug release. Once accumulated at the tumor site, the nanoprodrug can be activated to release antitumor drug by tumor overexpressed MMP‐2. It is found that HA‐Psi‐DOX nanoparticles can kill tumor cells effectively and initiate an antitumor immune response, leading to the upregulation of interferon‐γ. This cytokine promotes the expression of programmed cell death protein‐ligand 1 (PD‐L1) on tumor cells, which will cause immunosuppression after interacting with PD‐1 on the surface of lymphocytes. The results suggest that the therapeutic efficiency of HA‐Psi‐DOX nanoparticles is significantly improved when combined with checkpoint inhibitors anti‐PD‐1 antibody (α‐PD1) due to the neutralization of immunosuppression by blocking the interaction between PD‐L1 and PD‐1. This therapeutic system by combining chemotherapy and immunotherapy further increases the link between conventional tumor therapies and immunotherapy.     

Highly Uniform Resistive Switching Properties of Solution‐Processed Silver‐Embedded Gelatin Thin Film

The silver‐embedded gelatin (AgG) thin film produced by the solution method of metal salts dissolved in gelatin is presented. Its simple fabrication method ensures the uniform distribution of Ag dots. Memory devices based on AgG exhibit good device performance, such as the ON/OFF ratio in excess of 10⁵ and the coefficient of variation in less of 50%. To further investigate the position of filament formation and the role of each element, current sensing atomic force microscopy (CSAFM) analysis as well as elemental line profiles across the two different conditions in the LRS and HRS are analyzed. The conductive and nonconductive regions in the current map of the CSAFM image show that the conductive filaments occur in the AgG layer around Ag dots. The migration of oxygen ions and the redox reaction of carbon are demonstrated to be the driving mechanism for the resistive switching of AgG memory devices. The results show that dissolving metal salts in gelatin is an effective way to achieve high‐performance organic–electronic applications.     

Synthesis of Branched DNA Scaffolded Super‐Nanoclusters with Enhanced Antibacterial Performance

Metal nanoclusters (NCs) possess unique optical properties, and exhibit a wide variety of potential applications. DNA with robust molecular programmability is demonstrated as an ideal scaffold to regulate the formation of NCs, offering a rational approach to precisely tune the spatial structures of NCs. Herein, the first use of branched DNA as scaffold to regulate the formation of silver nanoclusters (super‐AgNC) is reported, in which the spatial structures are precisely designed and constructed. Super‐AgNC with tunable shapes and arm‐lengths including Y‐, X‐, and (Y–X)‐ shaped super‐AgNC is achieved. The molecular structures and optical properties of super‐AgNCs are systemically studied. As a proof of application, remarkably, super‐AgNCs exhibit superior antibacterial performance. In addition, super‐AgNCs show excellent biocompatibility with three types of tissue cells including 293T (human embryonic kidney cells), SMCs (vascular smooth muscle cells), and GLC‐82 (lung adenocarcinoma cells). These performances enable the super‐AgNCs adaptable in a variety of applications such as biosensing, bioimaging, and antibacterial agents.     

UV resonance Raman-selective amide vibrational enhancement: quantitative methodology for determining protein secondary structure

We have directly determined the amide band resonance Raman spectra of the "average" pure alpha-helix, beta-sheet, and unordered secondary structures by exciting within the amide pi-->pi* transitions at 206.5 nm. The Raman spectra are dominated by the amide bands of the peptide backbone. We have empirically determined the average pure alpha-helix, beta-sheet, and unordered resonance Raman spectra from the amide resonance Raman spectra of 13 proteins with well-known X-ray crystal structures. We demonstrate that we can simultaneously utilize the amide I, II, and III bands and the Calpha-H amide bending vibrations of these average secondary structure spectra to directly determine protein secondary structure. The UV Raman method appears to be complementary, and in some cases superior, to the existing methods, such as CD, VCD, and absorption spectroscopy. In addition, the spectra are immune to the light-scattering artifacts that plague CD, VCD, and IR absorption measurements. Thus, it will be possible to examine proteins in micelles and other scattering media.     

岩体结构的可靠性设计

考虑岩体性质的空间变异性和随机性,本文讨论了基于可靠度理论的岩体结构的可靠性设计。分析了岩体结构的可靠性设计的研究现状,提出了面临的问题和相应的措施。     

一次风反切系统的数值模拟和多相流动特性分析

四角切圆燃烧锅炉,存在着稳燃和结渣的矛盾,一次风微反切技术已在多台锅炉上得到应用,较好地解决了这对矛盾并能在一定程度上降低ＮＯｘ的排放量。本文把湍流理论和多相流动理论应用于炉内空气动力场的计算机数值模拟,用投影法编制的计算软件对６００ＭＷ锅炉炉内流动进行了计算,得出了一次风反切系统中炉内速度场、实际切圆、颗粒运动轨迹等结果,与冷炉和冷模试验基本吻合,对一次风反切系统的设计和调试具有参考价值。     

Retardation of human drug-resistant HL-60 cell in G1 phase and induction of sensitive cell to apoptosis by cyclosporine A

To further study the relationship between resistance to apoptosis and drug resistance in harringtonine-resistant HL-60 cells (HR20), cyclosporine A (CsA) 20, 10 micrograms.ml-1 was shown to induce the sensitive HL-60 cells to apoptosis, showing a typical DNA "ladder" band. But the same concentrations of CsA retarded the HR20 cells in G1 phase and could not induce the cells to apoptosis. The cellular daunorubicin accumulation increased when HR20 cells were treated with low concentration of CsA and the reversal of drug resistance by CsA was unrelated to the retardation of cell cycle progression. High phosphorylation of about 50 kDa protein occured when HR20 cells were treated with CsA 10 micrograms.ml-1. The results domonstrate that cyclosporine A retarded the harringtonine-resistant HL-60 cells in G1 phase but induced HL-60 cells to apoptosis, and the retardation was unrelated to drug resistance.     

新型军械装备损坏程度评估方法研究

根据新型军械装备损坏程度具有不确定性的特点,提出了基于D-S证据理论的新型军械装备损坏程度评估方法,并求出了新型军械装备损坏程度区分.通过对典型新型军械装备损坏程度的评估,验证了该方法的有效性和实用性.     

基于Snort的边界数据包安全性检测

无论是蠕虫病毒、木马或是其他的网络攻击行为,无不向目标网络发送恶意数据包,以达到恶意攻击的目的.网络监控成为检测来自外部网络的数据包安全性的重要手段,Snort作为防火墙的补充广泛应用于网络内部,监控网络流量、数据包安全等.将Snort IDS部署在网络边界,基于CVE漏洞库建立本地Snort特征库,以检测所有通过边界的数据包,保护内网安全.     

基于地理位置改进的动态源路由协议

本文对DSR协议进行局部改进,提出有限半径内的洪泛与半径区域间依靠最短地理位置来选择最优下一跳中转节点的机制。改进后的协议减少了路由发现过程的开销和端到端分组传输的平均时延,更适合实时业务需求。