Microenvironment-Sensitive Fluorescent Ligand Binds Ascaris Telomere Antiparallel G-Quadruplex DNA with Blue-Shift and Enhanced Emission

The development of small molecules that can selectively target G-quadruplex (G4) DNAs has drawn considerable attention due to their unique physiological and pathological functions. However, only a few molecules have been found to selectively bind a particular G4 DNA structure. We have developed a fluorescence ligand Q1 , a molecular scaffold with a carbazole–pyridine core bridged by a phenylboronic acid side chain, that acts as a selective ascaris telomere antiparallel G4 DNA ASC20 ligand with about 18 nm blue-shifted and enhanced fluorescence intensity. Photophysical properties revealed that Q1 was sensitive to the microenvironment and gave the best selectivity to ASC20 with an equilibrium binding constant K_a=6.04×10⁵ M⁻¹. Time-resolved fluorescence studies also demonstrated that Q1 showed a longer fluorescence lifetime in the presence of ASC20. The binding characteristics of Q1 with ASC20 were shown in detail in a fluorescent intercalator displacement (FID) assay, a 2-Ap titration experiment and by molecular docking. Ligand Q1 could adopt an appropriate pose at terminal G-quartets of ASC20 through multiple interactions including π–π stacking between aromatic rings; this led to strong fluorescence enhancement. In addition, a co-staining image showed that Q1 is mainly distributed in the cytoplasm. Accordingly, this work provides insights for the development of ligands that selectively targeting a specific G4 DNA structure.     

煤系地层致密砂岩气甜点区地震逐级预测——以鄂尔多斯盆地东南缘下二叠统山西组2~3亚段为例

鄂尔多斯盆地东南部下二叠统山西组2~3亚段(以下简称山2~3亚段)为该盆地重要的天然气勘探目的层,但该亚段储层薄、厚度变化快、非均质性强,储层预测和勘探目标优选难度大。为了准确预测该亚段煤系地层致密砂岩气甜点区、提高天然气勘探成功率,针对该套储层的特征和预测难点,提出了90°相移技术识别河道外形、模型约束波阻抗反演刻画砂体厚度和子波衰减梯度属性识别含气砂体的地震逐级预测技术。研究结果表明:①山2~3亚段上覆5号煤地震强反射层,下伏储层地震反射能量弱,加之为稀疏二维地震测网、井控程度低,致使致密砂岩气甜点区预测难度大;②所提出的技术方法通过地震逐级预测约束,可以有效地刻画河道砂体分布并识别有效含气储层,提高了对勘探开发目标预测的精度;③基于该技术方法指导部署的勘探开发目标实钻效果好,地震预测结果横向分辨率高,真实地反映了河道及河道砂体的变化特征。结论认为,采用该方法可以有效地解决二维地震勘探区煤系地层强非均质性、薄储层致密砂岩气甜点区预测的地质难题。     

Application of adhesively bonded single lap joints for fracture assessment of adhesive materials

In this study, a method has been proposed to obtain the failure envelope of brittle adhesives using the experimental failure loads of precracked single lap joints (SLJs). The proposed technique is based on the principles of linear elastic fracture mechanics (LEFM), on J-integral relations, and on results of a numerical analysis. Compared to the previous approaches, the introduced experimental method has some advantages such as low manufacturing costs and simpler test procedure. The proposed method can also provide a wide range of mode mix ratios without the need of an additional apparatus. The fracture envelope obtained from the proposed method was then verified by performing some fracture tests including double cantilever beam (DCB), end-notched flexure (ENF), and single leg bending (SLB) specimens. Good correlation was seen between the fracture envelopes of the proposed method and the ones obtained from the fracture mechanics experiments.     

Ab initio calculations of the NO2 fission for CL-20 conformers

NO₂ fission is regarded to be the most important initial decomposition process of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20). In this study, four CL-20 conformers based on the ε-CL-20 were obtained after the optimization at m062x/cc-pvtz level, and the bond length, bond order and bond dissociation energy of the N-N bonds were examined to investigate the stability of these bonds. In addition, the rate constants and activation energy of the NO₂ fission were evaluated using the microcanonical variational transition state theory (μVT). The calculation results have shown that N-N bonds in the case of pseudo-equatorial and axial of nitro groups are the most stable and the least stable, respectively, by evaluating the bond length, bond order and minimum energy path (MEP). The NO₂ fission rate constants are affected by not only the stability of N-N bonds but also the repulsion forces from the other nitro groups, and the fission process for pseudo-equatorial positioning of nitro groups is easier to be accelerated due to the increase of the repulsion forces. The decomposition of CL-20 conformer may mainly originate from the fission of the pseudo-equatorial positioning of nitro groups, especially for CL-20 III conformer because of the significant low activation energy.     

时频非平稳地震动模型及结构随机振动应用

地震动具有显著的时域和频域非平稳性,传统的均匀调制地震动模型不能充分表征时频两域的非平稳性,并影响结构随机振动分析的精准度。为了克服上述不足,建立由多峰平滑包络和非平稳噪声信号点乘而成的非均匀调制地震动模型,该模型能够在时域上充分反映地震动的波动和衰减特性,同时其频谱特征也与真实信号相接近。在此基础上,建立同时以时间和频率为变量的非平稳地震动演变谱随机模型。分析结果表明,以上两种模型在时域和频域的合成精度上均优于均匀调制模型。针对以上地震动随机模型的形式和特点,对传统结构随机振动响应求解方法进行改进。通过算例证明,按照均匀调制模型计算结构随机响应不能充分获得结构时频域的非平稳特性且结果偏于不安全,而利用两种改进模型可以获得更精确的结构响应概率特征和更细致的非平稳性演变过程。     

Lamin-Related Congenital Muscular Dystrophy Alters Mechanical Signaling and Skeletal Muscle Growth

Laminopathies are a clinically heterogeneous group of disorders caused by mutations in the LMNA gene, which encodes the nuclear envelope proteins lamins A and C. The most frequent diseases associated with LMNA mutations are characterized by skeletal and cardiac involvement, and include autosomal dominant Emery–Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy type 1B, and LMNA-related congenital muscular dystrophy (LMNA-CMD). Although the exact pathophysiological mechanisms responsible for LMNA-CMD are not yet understood, severe contracture and muscle atrophy suggest that mutations may impair skeletal muscle growth. Using human muscle stem cells (MuSCs) carrying LMNA-CMD mutations, we observe impaired myogenic fusion with disorganized cadherin/β catenin adhesion complexes. We show that skeletal muscle from Lmna-CMD mice is unable to hypertrophy in response to functional overload, due to defective fusion of activated MuSCs, defective protein synthesis and defective remodeling of the neuromuscular junction. Moreover, stretched myotubes and overloaded muscle fibers with LMNA-CMD mutations display aberrant mechanical regulation of the yes-associated protein (YAP). We also observe defects in MuSC activation and YAP signaling in muscle biopsies from LMNA-CMD patients. These phenotypes are not recapitulated in closely related but less severe EDMD models. In conclusion, combining studies in vitro, in vivo, and patient samples, we find that LMNA-CMD mutations interfere with mechanosignaling pathways in skeletal muscle, implicating A-type lamins in the regulation of skeletal muscle growth.     

Cell-envelope proteinases from lactic acid bacteria: Biochemical features and biotechnological applications

Proteins displayed on the cell surface of lactic acid bacteria (LAB) perform diverse and important biochemical roles. Among these, the cell-envelope proteinases (CEPs) are one of the most widely studied and most exploited for biotechnological applications. CEPs are important players in the proteolytic system of LAB, because they are required by LAB to degrade proteins in the growth media into peptides and/or amino acids required for the nitrogen nutrition of LAB. The most important area of application of CEPs is therefore in protein hydrolysis, especially in dairy products. Also, the physical location of CEPs (i.e., being cell-envelope anchored) allows for relatively easy downstream processing (e.g., extraction) of CEPs. This review describes the biochemical features and organization of CEPs and how this fits them for the purpose of protein hydrolysis. It begins with a focus on the genetic organization and expression of CEPs. The catalytic behavior and cleavage specificities of CEPs from various LAB are also discussed. Following this, the extraction and purification of most CEPs reported to date is described. The industrial applications of CEPs in food technology, health promotion, as well as in the growing area of water purification are discussed. Techniques for improving the production and catalytic efficiency of CEPs are also given an important place in this review.     

高压下CL-20拉曼光谱和红外光谱相变研究

为了更好地认识和了解CL-20晶体结构演变规律和相变行为,利用金刚石对顶砧超高压实验技术,在0~50GPa下,研究了高压下ε-CL-20的原位拉曼光谱和红外光谱。结果表明,CL-20晶体在整个加压过程中存在两个相变,第一个相变发生在4.2~7.5GPa,认为是ε相到对称性更低的γ相转变,相变产生的原因是在压强的作用下,笼环外的硝基方向发生改变,电子云密度重置导致的分子构型转变;第二个相变发生在14.2~18.9GPa,属于γ相到ζ相的晶体结构转变;卸压后,拉曼和红外光谱恢复常压状态,表明CL-20晶体在研究压强范围内的相变过程是可逆的。     

复合曲流河道内的单河道识别

随着油气田开发程度的深入，复合河道砂体尺度的研究难以满足生产需求，需要开展单河道砂体边界的识别。埕海一区明化镇组曲流河河道频繁地决口、改道和侧向迁移，复合河道砂体较为发育。依据单河道砂体接触部位地震波形及振幅发生变化的特点，首先利用边缘检测属性突出岩性变化引起的振幅响应，识别出单河道的边界；再利用倾角方位属性能够反映地震波形的细微变化，预测单河道的侧向迁移方向；借助上述方法识别研究区单河道的边界，并且精确预测了单河道点坝砂体的具体位置。预测结果与钻井吻合程度较高，有效地指导了井网关系调整及剩余油挖潜，也为类似地区的单河道识别与划分提供了一种新的方法。     

How hydrogen-storage material affects the decomposition of nitramine explosive: CPMD investigations of LAB-doped CL20

As the most popular high-energy explosives, 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazatetracyclo [5.5.0.0.0] dodecane (Simplified as HNIW or CL20) attracts many attentions for improving its detonation appearance in the application. Here we introduce hydrogen-storage compounds into explosives to estimate the possible improved detonation performances by Car-Parrinello molecular dynamics (CPMD) simulation, where we construct lithium amidoborane (LAB) doped CL20 as the initial structure. Almost all the interactions between hydrogen and CL20 appear exothermic properties, which indicate LAB increases the enthalpies of detonation. The results suggest explosive mixed with hydrogen-storage material is possibly a new field of energetic compound.