AuNP flares-capped mesoporous silica nanoplatform for MTH1 detection and inhibition

The human mutT homologue MTH1, a nucleotide pool sanitizing enzyme, represents a vulnerability factor and an attractive target for anticancer therapy. However, there is currently a lack of selective and effective platforms for the detection and inhibition of MTH1 in cells. Here, we demonstrate for the first time a gold nanoparticle (AuNP) flares-capped mesoporous silica nanoparticle (MSN) nanoplatform that is capable of detecting MTH1 mRNA and simultaneously suppressing MTH1 activity. The AuNP flares are made from AuNPs that are functionalized with a dense shell of MTH1 recognition sequences hybridized to short cyanine (Cy5)-labeled reporter sequences and employed to seal the pores of MSN to prevent the premature MTH1 inhibitors (S-crizotinib) release. Just like the pyrotechnic flares that produce brilliant light when activated, the resulting AuNP flares@MSN (S-crizotinib) undergo a significant burst of red fluorescence enhancement upon MTH1 mRNA binding. This hybridization event subsequently induces the opening of the pores and the release of S-crizotinib in an mRNA-dependent manner, leading to significant cytotoxicity in cancer cells and improved therapeutic response in mouse xenograft models. We anticipate that this nanoplatform may be an important step toward the development of MTH1-targeting theranostics and also be a useful tool for cancer phenotypic lethal anticancer therapy.     

Intranasal immunization with protective antigen of Bacillus anthracis induces a long-term immunological memory response

Although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. Here, we investigated whether intranasal immunization with recombinant protective antigen (rPA) of Bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. Intranasal immunization with rPA plus cholera toxin (CT) sustained PA-specific antibody responses for 6 months in lung, nasal washes, and vaginal washes as well as serum. A significant induction of PA-specific memory B cells was observed in spleen, cervical lymph nodes (CLNs) and lung after booster immunization. Furthermore, intranasal immunization with rPA plus CT remarkably generated effector memory CD4⁺ T cells in the lung. PA-specific CD4⁺ T cells preferentially increased the expression of Th1- and Th17-type cytokines in lung, but not in spleen or CLNs. Collectively, the intranasal immunization with rPA plus CT promoted immunologic memory responses in the mucosal and systemic compartments, providing long-term immunity.     

神经网络分析方法用于心脏病诊断的研究

神经网络可以很好的拟合任意的非线性函数。我们从 QRS波群的高频三维频谱中提取出一些定量的特征参数 ,用神经网络的方法对这些参数进行有监督的学习训练 ,最终能在由这些特征参数张成的 m维空间中构建出一个 m维的曲面来区分病人和健康人的 QRS波群高频三维频谱 ,从而使得训练后的网络能基于 QRS波群的高频三维频谱自行诊断出病人和健康人     

TANGO2全身敲除小鼠在生理条件下正常发育和繁殖

目的：利用运输和高尔基体组织蛋白2同系物(transport and Golgi organization protein 2 homolog,TANGO2)敲除小鼠阐明TANGO2在哺乳动物中的生理功能,探究TANGO2是否是导致DiGeorge综合征发生的候选基因。方法：制备TANGO2敲除小鼠模型,通过实时荧光定量PCR检测该小鼠模型的基因敲除效率。观察并记录野生型、杂合和纯合敲除小鼠的表型和生长繁育情况。通过组织解剖和组织学分析,观察野生型和敲除小鼠的心脏和大脑组织的形态结构。结果：TANGO2 mRNA在野生型小鼠的心脏和大脑中表达,而在敲除小鼠相应组织中的表达水平显著降低。TANGO2敲除小鼠发育正常,能够存活和繁殖,没有明显的表型异常。与野生型同窝仔相比,生存率没有显著差异。组织形态分析显示,新生敲除小鼠和6月龄敲除小鼠的心脏和大脑与野生型之间无明显差异。结论：TANGO2敲除小鼠能够正常发育和繁殖,并且缺乏人类中TANGO2相关疾病或DiGeorge综合征的相关表型。     

心脑疾病对同步十二导联心电图多重分形谱的影响

对心脑疾病人群的同步十二导联ECG(心电图)进行多重分形特性分析,发现不同导联的多重分形曲线互不重叠。计算其十二导联平均的多重分形奇异强度分布范围以及分布范围的十二个导联间的离散特性,发现不同人群中存在互为交叉而有明显不同的结果。用十二导联多重分形Δα的平均值Δα及其离散度δα(取Δα的标准差)两个参量来描述其多重分形谱特征。发现健康人与心脏病人Δα接近,但δα相差较大;健康人与脑损伤患者δα接近,但Δα相差较大。预示着多重分形特性受到神经自律和心脏组织结构的自谐特性的双重控制,特征参数Δα与神经控制相对应,δΔ与心脏组织结构自谐特性的各向异性相对应。     

基于估计补偿的医学显微图像拼接技术

图像拼接能很好地解决显微镜高倍镜成像时视野减小的问题.我们在分析显微成像系统对医学显微图像灰度分布影响的基础上,提出了一个系统对图像灰度分布的影响函数.结合系统影响函数和精确匹配下的相关性方程,得到一个以最小平方和形式误差函数为基础的方程组.利用奇异值分解得到系统对图像灰度分布的影响的估计值,然后用估计值来补偿系统的影响,得到图像的原始灰度,再进行拼接.这种方法能在不影响拼接速度的前提下消除医学显微图像中存在的拼接缝和拼接痕迹.