Intelligent Drug Delivery by Peptide-Based Dual-Function Micelles

To endow the polymeric prodrug with smart properties through a safe and simple method, matrix metalloproteinase (MMPs) responsive peptide GPLGVRGDG was introduced into the block copolymer to prepare TPGS₃₃₅₀-GPLGVRGDG-DOX&DOX micelles, where TPGS₃₃₅₀ is D-α-tocopheryl polyethylene glycol 3350 succinate. During the doxorubicin delivery, the cleavage of the peptide chain triggers de-PEGylation, and the remaining VRGDG sequence was retained on the surface of the micelles, which can act as a ligand to facilitate cell uptake. Moreover, the cytotoxicity of TPGS₃₃₅₀-GPLGVRGDG-DOX&DOX micelles against 4T1 cells was significantly improved, compared with TPGS₃₃₅₀-GPLGVRG-DOX&DOX micelles and TPGS₃₃₅₀-DOX&DOX micelles. During in vivo studies, TPGS₃₃₅₀-GPLGVRGDG-DOX&DOX micelles exhibited good anticancer efficacy with long circulation in the body and more efficient accumulation at the tumor site. Therefore, TPGS₃₃₅₀-GPLGVRGDG-DOX&DOX micelles have improved antitumor activity and reduced toxic side effects. This work opens new potential for exploring the strategy of drug delivery in clinical applications.     

Identification and Functional Analysis of Key Autophosphorylation Residues of Arabidopsis Senescence Associated Receptor-like Kinase

Reversible protein phosphorylation mediated by protein kinases and phosphatases plays important roles in the regulation of leaf senescence. We previously reported that the senescence-associated leucine-rich repeat receptor-like kinase AtSARK autophosphorylates on both serine/threonine and tyrosine residues and functions as a positive regulator of Arabidopsis leaf senescence; the senescence-suppressed protein phosphatase SSPP interacts with and dephosphorylates the cytoplasmic domain of AtSARK, thereby negatively regulating leaf senescence. Here, 27 autophosphorylation residues of AtSARK were revealed by mass spectrometry analysis, and six of them, including two Ser, two Thr, and two Tyr residues, were further found to be important for the biological functions of AtSARK. All site-directed mutations of these six residues that resulted in decreased autophosphorylation level of AtSARK could significantly inhibit AtSARK-induced leaf senescence. In addition, mutations mimicking the dephosphorylation form of Ser384 (S384A) or the phosphorylation form of Tyr413 (Y413E) substantially reduced the interaction between AtSARK and SSPP. All results suggest that autophosphorylation of AtSARK is essential for its functions in promoting leaf senescence. The possible roles of S384 and Y413 residues in fine-tuning the interaction between AtSARK and SSPP are discussed herein.     

采用长工作距离物镜的低噪声相移数字全息显微研究

在数字全息显微技术中,为了提高测量精度,提出了一种利用长工作距离物镜的相移数字全息显微的测量装置和方法。该装置采用LED作为照明光源,可以有效地抑制相位噪声,提高了重建精度。通过在长工作距离物镜和样品之间加入分光棱镜的方法,构建了一种准物参共路的迈克尔逊干涉仪。该装置结构简单,调整方便,在部分相干光照明时,容易实现干涉。重建时,采用盲相移干涉技术,结合两步盲相移算法,重建出物体的表面相位分布。实验中,分别采用LED照明和He-Ne激光照明,测量了一个反射式USAF1951分辨率板的高度分布。结果表明,两者的测量结果相互吻合,但是LED照明时的噪声与激光照明时相比降低了70%。此外,为了进一步验证装置的有效性,使用该装置对刻于硅基底的微纳矩形台阶进行测量,测量结果与标称值具有良好的一致性,表明该装置在微结构的形貌测量方面有广阔的应用前景。     

基于热流场仿真的井状通路暖气垫的结构优化

路面结冰易于导致交通事故的发生,因此提出一种路面暖气垫融冰法。为了获得最佳的融冰效果,以固定体积暖气垫为研究对象,将暖气垫工作表面的融冰速率和融冰均匀度作为评估指标,以暖气垫长度、厚度和通路间距为优化参数,通过热流场仿真分析,采用均匀设计响应面法得到优化目标与结构参数间的函数关系,运用遗传算法进行多目标优化得到非劣解集,采用理想点法TOPSIS从中选出最优解,得出结论:当通路直径取20 mm时,最佳参数组合为通路间距48 mm、暖气垫厚度68 mm,横向边长可根据工程应用确定。     

Changes in the Expression and Functional Activities of C-X-C Motif Chemokine Ligand 13 (CXCL13) in Hyperplastic Prostate

Background: C-X-C motif chemokine ligand 13 (CXCL13), a member of the CXC subtype in chemokine superfamily, affects numerous biological processes of various types of cells and the progress of a great number of clinical diseases. The purpose of the current study was to reveal the internal mechanism between CXCL13 and benign prostatic hyperplasia (BPH). Methods: Human serum, prostate tissues and human prostate cell lines (BPH-1, WPMY-1) were utilized. The effect of recombinant human CXCL13 (rHuCXCL13) protein and the influences of the knockdown/overexpression of CXCL13 on two cell lines were studied. Rescue experiments by anti-CXCR5 were also conducted. In vivo, rHuCXCL13 was injected into the ventral prostate of rats. Additionally, a tissue microarray of hyperplastic prostate tissues was constructed to analyze the correlations between CXCL13 and clinical parameters. Results: CXCL13 was highly expressed in the prostate tissues and upregulated in the BPH group. It was observed that CXCL13 modulated cell proliferation, apoptosis, and the epithelial–mesenchymal transition (EMT) through CXCR5 via AKT and the ERK1/2 pathway in BPH-1, while it contributed to inflammation and fibrosis through CXCR5 via the STAT3 pathway in WPMY-1. In vivo, rHuCXCL13 induced the development of rat BPH. Additionally, CXCL13 was positively correlated with the prostate volume and total prostate specific antigen. Conclusions: Our novel data demonstrated that CXCL13 modulated cell proliferation, cell cycle, the EMT of epithelial cells, and induced the fibrosis of prostatic stromal cells via a variety of inflammatory factors, suggesting that CXCL13 might be rediscovered as a potential therapeutic target for the treatment of BPH.     

超高分辨力微型光谱仪的光学系统设计

由于光谱仪的尺寸限制,微型光谱仪在满足一定光谱范围时,其分辨力往往难以小于0.1 nm。而一些特殊应用场合要求光谱仪不仅具有微小的尺寸,还要求具有极高的光谱分辨力。本文基于Zemax光学设计软件,通过选择合适的初始结构参数与评价函数,自动优化准直镜、聚焦镜、柱透镜、光栅,以及CCD间倾角和距离,设计出光谱分辨力高达0.05 nm,尺寸为90 mm×130 mm×40 mm的Czerny-Turner结构微型光谱仪。在此基础上优化出8个光栅倾斜角度,使微型光谱仪光谱分辨力在优于0.05 nm的同时,波段范围达到了820 nm~980 nm。所设计的光谱仪具有超高的光谱分辨力、微小的外形尺寸与适中的光谱范围等特点。     

pTrace: 一种面向可控云计算的DDoS攻击源控制技术

当前,越来越多的分布式拒绝服务(distributed denial of service, DDoS)攻击的攻击源迁移至云中,给云计算的可控性及整个网络空间的安全带来了严重挑战.然而关于有效控制云中该类攻击源的研究还比较缺乏.为此设计了一种面向可控云计算的DDoS攻击源控制系统pTrace,该系统包括入口流量过滤inFilter和恶意进程溯源mpTrace两部分.其中,inFilter过滤伪造源地址信息的数据包;mpTrace先识别攻击流及其源地址信息,依据源地址信息追溯并管控发送攻击流的恶意进程.在Openstack和Xen环境下实现了pTrace的原型系统,分析及实验表明,inFilter可以有效地防止含有虚假源地址信息的DDoS攻击包流出云外;当攻击流速率约为正常流量的2.5倍时,mpTrace即可正确识别攻击流信息,并可在ms级的时间内正确追溯攻击流量发送进程.该方法有效控制了位于云中的DDoS攻击源,减小了对云内傀儡租户及云外攻击目标的影响.