Magnetically Guidable Proteinaceous Adhesive Microbots for Targeted Locoregional Therapeutics Delivery in the Highly Dynamic Environment of the Esophagus

The esophagus is a tubular-shaped muscular organ where swallowed fluids and muscular contractions constitute a highly dynamic environment. The turbulent, coordinated processes that occur through the oropharyngeal conduit can often compromise targeted administration of therapeutic drugs to a lesion, significantly reducing therapeutic efficacy. Here, magnetically guidable drug vehicles capable of strongly adhering to target sites using a bioengineered mussel adhesive protein (MAP) to achieve localized delivery of therapeutic drugs against the hydrodynamic physiological conditions are proposed. A suite of highly uniform microparticles embedded with iron oxide (IO) nanoparticles (MAP@IO MPs) is microfluidically fabricated using the genipin-mediated covalent cross-linking of bioengineered MAP. The MAP@IO MPs are successfully targeted to a specific region and prolongedly retained in the tubular-structured passageway. In particular, orally administered MAP@IO MPs are effectively captured in the esophagus in vivo in a magnetically guidable manner. Moreover, doxorubicin (DOX)-loaded MAP@IO MPs exhibit a sustainable DOX release profile, effective anticancer therapeutic activity, and excellent biocompatibility. Thus, the magnetically guidable locomotion and robust underwater adhesive properties of the proteinaceous soft microbots can provide an intelligent modular approach for targeted locoregional therapeutics delivery to a specific lesion site in dynamic fluid-associated tubular organs such as the esophagus.     

Unsupervised Segmentation of Stereoscopic Video Objects: Constrained Segmentation Fusion Versus Greedy Active Contours

In this paper, we present a novel memory access reduction scheme (MARS) for two-dimension fast cosine transform (2-D FCT). It targets programmable DSPs with high memory-access latency. It reduces the number of memory accesses by: 1) reducing the number of weighting factors and 2) combining butterflies in vector-radix 2-D FCT pruning diagram from two stages to one stage with an efficient structure. Hardware platform based on general purpose processor is used to verify the effectiveness of the proposed method for vector-radix 2-D FCT pruning implementation. Experimental results validate the benefits of the proposed method with reduced memory access, less clock cycle and fewer memory space compared with the conventional implementation.     

二甲基二氯硅烷水解反应器研究进展

基于对甲基氯硅烷单体生产中水解反应特点的分析,论述了国内外几种水解反应器的结构特点,着重介绍了几种水解反应器在工业应用过程中存在的优缺点,并对水解反应器未来的发展方向进行了展望。     

区域导航对流层延迟误差修正模型研究

本文研究了电波大气折射理论，分析了传播误差因素，阐述了区域导航信号的传播路径与 GNSS 卫星导航的不同，论述了对流层延迟对区域导航信号测量精度的影响，设计了满足区域导航系统应用需求的对流层延迟误差修正模型，并通过仿真研究，验证了所设计区域导航对流层延迟误差修正模型的可行性，并给出了该模型在远距离低仰角和近距离高仰角下的误差修正能力。     

Expression of RCAS1 Correlates with Urothelial Bladder Cancer Malignancy

RCAS1 is a protein that participates in regulation of the tumor microenvironment and its immune responses, all in order to evade the immune system. The aim of this study was to analyze RCAS1 expression in urothelial bladder cancer cells (and in fibroblasts and macrophages of the tumor stroma) and its relationship with the histological pattern of malignancy. Eighty-three postcystectomy patients were enrolled. We analyzed the histological maturity (grade), progress (pT stage), tissue invasion type (TIT), nonclassic differentiation number (NDN), and the ability to metastasize (pN). The expression of RCAS1 protein was analyzed by immunohistochemistry. Indicators of histological malignancy were observed solely in association with the RCAS1 expression in cells in the border parts (BPs) of the tumor. Histological malignancy of the tumor, indicated by the pT and pN, and metastasis-free survival time, correlated significantly with RCAS1 expression in tumor neoplastic cells, whereas malignancy determined by grade, TIT, and NDN correlated with RCAS1 expression in fibroblasts and macrophages in the tumor microenvironment. These findings suggest that the increased RCAS1 expression depends on its cellular source and that RCAS1 expression itself is a component of various signaling pathways. The immune escape occurs within the tumor BPs, where the increase in the RCAS1 expression occurs within tumor cells and stromal cells in its microenvironment. We conclude that the histological pattern of tumor malignancy, indicated by grade, TIT, NDN, pT, and pN is a morphological indicator of immune escape.     

Sperm metabolism is altered during storage by female insects: evidence from two-photon autofluorescence lifetime measurements in bedbugs

We explore the possibility of characterizing sperm cells without the need to stain them using spectral and fluorescence lifetime analyses after multi-photon excitation in an insect model. The autofluorescence emission spectrum of sperm of the common bedbug, Cimex lectularius, was consistent with the presence of flavins and NAD(P)H. The mean fluorescence lifetimes showed smaller variation in sperm extracted from the male (tau m, τ_m = 1.54–1.84 ns) than in that extracted from the female sperm storage organ (tau m, τ_m = 1.26–2.00 ns). The fluorescence lifetime histograms revealed four peaks. These peaks (0.18, 0.92, 2.50 and 3.80 ns) suggest the presence of NAD(P)H and flavins and show that sperm metabolism can be characterized using fluorescence lifetime imaging. The difference in fluorescence lifetime variation between the sexes is consistent with the notion that female animals alter the metabolism of sperm cells during storage. It is not consistent, however, with the idea that sperm metabolism represents a sexually selected character that provides females with information about the male genotype.     

Adventitial Tertiary Lymphoid Organs as Potential Source of MicroRNA Biomarkers for Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with marked changes in the cellular composition of the aortic wall. This study aims to identify microRNA (miRNA) expression in aneurysmal inflammatory cells isolated by laser microdissection from human tissue samples. The distribution of inflammatory cells (neutrophils, B and T lymphocytes, mast cells) was evaluated in human AAA biopsies. We observed in half of the samples that adventitial tertiary lymphoid organs (ATLOs) with a thickness from 0.5 to 2 mm were located exclusively in the adventitia. Out of the 850 miRNA that were screened by microarray in isolated ATLOs (n = 2), 164 miRNAs were detected in ATLOs. The three miRNAs (miR-15a-3p, miR-30a-5p and miR-489-3p) with the highest expression levels were chosen and their expression quantified by RT-PCR in isolated ATLOs (n = 4), M1 (n = 2) and M2 macrophages (n = 2) and entire aneurysmal biopsies (n = 3). Except for the miR-30a-5p, a similar modulation was found in ATLOs and the two subtypes of macrophages. The modulated miRNAs were then evaluated in the plasma of AAA patients for their potential as AAA biomarkers. Our data emphasize the potential of miR-15a-3p and miR-30a-5p as biomarkers of AAA but also as triggers of ATLO evolution. Further investigations will be required to evaluate their targets in order to better understand AAA pathophysiology.     

烧结时间对含铅玻璃制备微晶玻璃析晶及性能的影响

以铅玻璃与粉煤灰为原料，通过协同熔炼制备了微晶玻璃。通过XRD和SEM等手段研究了不同烧结时间下微晶玻璃的物相组成及显微结构，测定了微晶玻璃的密度、吸水率、维氏硬度和化学抗性。结果表明: 延长烧结时间对含铅玻璃加入量为40%(FG40)、50%(FG50)样品的晶相类型和晶化程度有影响，而对含铅玻璃加入量为60%(FG60)、70%(FG70)和80%(FG80)样品的影响较小。随着烧结时间延长，样品晶化程度提高，晶体长大，玻璃相减少。适宜的含铅玻璃加入量为50%~70%，对应的FG50、FG60、FG70样品最佳烧结时间分别为4 h、3 h、3 h。     

Histone Methylation Marks on Circulating Nucleosomes as Novel Blood-Based Biomarker in Colorectal Cancer

Circulating nucleic acids (CNAs) are under investigation as a liquid biopsy in cancer as potential non-invasive biomarkers, as stable structure in circulation nucleosomes could be valuable sources for detection of cancer-specific alterations in histone modifications. Our interest is in histone methylation marks with a focus on colorectal cancer, one of the leading cancers respective the incidence and mortality. Our previous work included the analysis of trimethylations of lysine 9 on histone 3 (H3K9me3) and of lysine 20 on histone 4 (H4K20me3) by chromatin immuno- precipitation-related PCR in circulating nucleosomes. Here we asked whether global immunologic measurement of histone marks in circulation could be a suitable approach to show their potential as biomarkers. In addition to H3K9me3 and H4K20me3 we also measured H3K27me3 in plasma samples from CRC patients (n = 63) and cancer free individuals (n = 40) by ELISA-based methylation assays. Our results show that of three marks, the amounts of H3K27me3 (p = 0.04) and H4K20me3 (p < 0.001) were significantly lower in CRC patients than in healthy controls. For H3K9me3 similar amounts were measured in both groups. Areas under the curve (AUC) in receiver operating characteristic (ROC) curves indicating the power of CRC detection were 0.620 for H3K27me3, 0.715 for H4K20me3 and 0.769 for the combination of both markers. In conclusion, findings of this preliminary study reveal the potential of blood-based detection of CRC by quantification of histone methylation marks and the additive effect of the marker combination.     

复杂膨胀性围岩条件下交岔点支护技术研究

针对复杂膨胀性围岩条件下交岔点高应力集中区围岩稳定性控制和支护技术难题，通过对交岔点围岩变形表现形式、交岔点围岩变形机理的研究分析，提出了交岔点支护难点及重点。基于围岩控制理论分析，提出了“有限让压的柔性支护+全断面封闭抗压的刚性支护技术”，前期柔性支护采用“高强、高预应力锚杆+锚索+喷浆”联合支护有限度控制围岩变形，允许围岩在可控范围内释放围岩应力|后期通过架设异形支架与支撑架组成的联合支护体并喷射混凝土对交岔点围岩进行全断面封闭抗压支护，有效控制巷道交岔点围岩的变形。确保了交岔点围岩变形的整体可控性、稳定性，达到了预期支护效果。