Apoptosis Disorder,a Key Pathogenesis of HCMV-Related Diseases

Human cytomegalovirus (HCMV) belongs to the β-herpesvirus family, which is transmitted in almost every part of the world and is carried by more than 90% of the general population. Increasing evidence indicates that HCMV infection triggers numerous diseases by disrupting the normal physiological activity of host cells, particularly apoptosis. Apoptosis disorder plays a key role in the initiation and development of multiple diseases. However, the relationship and molecular mechanism of HCMV-related diseases and apoptosis have not yet been systematically summarized. This review aims to summarize the role of apoptosis in HCMV-related diseases and provide an insight into the molecular mechanism of apoptosis induced by HCMV infection. We summarize the literature on HCMV-related diseases and suggest novel strategies for HCMV treatment by regulating apoptosis.     

Virtual Screening of FDA-Approved Drugs against Triose Phosphate Isomerase from Entamoeba histolytica and Giardia lamblia Identifies Inhibitors of Their Trophozoite Growth Phase

Infectious diseases caused by intestinal protozoan, such as Entamoeba histolytica (E. histolytica) and Giardia lamblia (G. lamblia) are a worldwide public health issue. They affect more than 70 million people every year. They colonize intestines causing primarily diarrhea; nevertheless, these infections can lead to more serious complications. The treatment of choice, metronidazole, is in doubt due to adverse effects and resistance. Therefore, there is a need for new compounds against these parasites. In this work, a structure-based virtual screening of FDA-approved drugs was performed to identify compounds with antiprotozoal activity. The glycolytic enzyme triosephosphate isomerase, present in both E. histolytica and G. lamblia, was used as the drug target. The compounds with the best average docking score on both structures were selected for the in vitro evaluation. Three compounds, chlorhexidine, tolcapone, and imatinib, were capable of inhibit growth on G. lamblia trophozoites (0.05–4.935 μg/mL), while folic acid showed activity against E. histolytica (0.186 μg/mL) and G. lamblia (5.342 μg/mL).     

Computational-Driven Epitope Verification and Affinity Maturation of TLR4-Targeting Antibodies

Toll-like receptor (TLR) signaling plays a critical role in the induction and progression of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematous, experimental autoimmune encephalitis, type 1 diabetes mellitus and neurodegenerative diseases. Deciphering antigen recognition by antibodies provides insights and defines the mechanism of action into the progression of immune responses. Multiple strategies, including phage display and hybridoma technologies, have been used to enhance the affinity of antibodies for their respective epitopes. Here, we investigate the TLR4 antibody-binding epitope by computational-driven approach. We demonstrate that three important residues, i.e., Y328, N329, and K349 of TLR4 antibody binding epitope identified upon in silico mutagenesis, affect not only the interaction and binding affinity of antibody but also influence the structural integrity of TLR4. Furthermore, we predict a novel epitope at the TLR4-MD2 interface which can be targeted and explored for therapeutic antibodies and small molecules. This technique provides an in-depth insight into antibody–antigen interactions at the resolution and will be beneficial for the development of new monoclonal antibodies. Computational techniques, if coupled with experimental methods, will shorten the duration of rational design and development of antibody therapeutics.     

Molecular Genetics of Conjunctival Melanoma and Prognostic Value of TERT Promoter Mutation Analysis

The aim of this study was exploration of the genetic background of conjunctival melanoma (CM) and correlation with recurrent and metastatic disease. Twenty-eight CM from the Rotterdam Ocular Melanoma Study group were collected and DNA was isolated from the formalin-fixed paraffin embedded tissue. Targeted next-generation sequencing was performed using a panel covering GNAQ, GNA11, EIF1AX, BAP1, BRAF, NRAS, c-KIT, PTEN, SF3B1, and TERT genes. Recurrences and metastasis were present in eight (29%) and nine (32%) CM cases, respectively. TERT promoter mutations were most common (54%), but BRAF (46%), NRAS (21%), BAP1 (18%), PTEN (14%), c-KIT (7%), and SF3B1 (4%) mutations were also observed. No mutations in GNAQ, GNA11, and EIF1AX were found. None of the mutations was significantly associated with recurrent disease. Presence of a TERT promoter mutation was associated with metastatic disease (p-value = 0.008). Based on our molecular findings, CM comprises a separate entity within melanoma, although there are overlapping molecular features with uveal melanoma, such as the presence of BAP1 and SF3B1 mutations. This warrants careful interpretation of molecular data, in the light of clinical findings. About three quarter of CM contain drug-targetable mutations, and TERT promoter mutations are correlated to metastatic disease in CM.     

Dynamic “Molecular Portraits” of Biomembranes Drawn by Their Lateral Nanoscale Inhomogeneities

To date, it has been reliably shown that the lipid bilayer/water interface can be thoroughly characterized by a sophisticated so-called “dynamic molecular portrait”. The latter reflects a combination of time-dependent surface distributions of various physicochemical properties, inherent in both model lipid bilayers and natural multi-component cell membranes. One of the most important features of biomembranes is their mosaicity, which is expressed in the constant presence of lateral inhomogeneities, the sizes and lifetimes of which vary in a wide range—from 1 to 10³ nm and from 0.1 ns to milliseconds. In addition to the relatively well-studied macroscopic domains (so-called “rafts”), the analysis of micro- and nanoclusters (or domains) that form an instantaneous picture of the distribution of structural, dynamic, hydrophobic, electrical, etc., properties at the membrane-water interface is attracting increasing interest. This is because such nanodomains (NDs) have been proven to be crucial for the proper membrane functioning in cells. Therefore, an understanding with atomistic details the phenomena associated with NDs is required. The present mini-review describes the recent results of experimental and in silico studies of spontaneously formed NDs in lipid membranes. The main attention is paid to the methods of ND detection, characterization of their spatiotemporal parameters, the elucidation of the molecular mechanisms of their formation. Biological role of NDs in cell membranes is briefly discussed. Understanding such effects creates the basis for rational design of new prospective drugs, therapeutic approaches, and artificial membrane materials with specified properties.     

A Strategy of Liquid-Grafted Slippery Sponges with Simultaneously Enhanced Absorption and Desorption Performances for Crude Oil Spill Remediation

Crude oil spill accidents pose a worldwide environmental threat. Oleophilic and hydrophobic absorbents that can selectively absorb oil from water have shown promising application potential in oil spill remediation. Simultaneous optimization of the absorption and desorption speed of absorbents towards oil is highly desirable for their recyclable usage, but remains a great challenge, because these two properties are generally conflicting. Here, a facile and ingenious strategy is proposed to tackle the above challenge via surface modification of porous sponges with highly flexible linear polydimethylsiloxane (LPDMS) brushes. The LPDMS brushes feature liquid-like properties at room temperature owing to its extremely low glass transition temperature, and act as a covalently-grafted lubrication layer throughout the 3D network channels of the sponge, which can minimize contact angle hysteresis and reduce friction between oil and sponge channel. Compared to the prevalent cross-linked polydimethylsiloxane (CPDMS) modification strategy, sponges modified with LPDMS brushes not only shows significantly enhanced absorption speed, but also exhibits superior desorption dynamics towards viscous crude oils. The design strategy of slippery sponges with liquid-like molecules may open a new avenue for developing advanced absorbents with simultaneously enhanced absorption and desorption performances for liquid separation and purification applications.     

Efficient Linear dsDNA Tagging Using Deoxyuridine Excision**

Site-specific strategies for exchanging segments of dsDNA are important for DNA library construction and molecular tagging. Deoxyuridine (dU) excision is an approach for generating 3’ ssDNA overhangs in gene assembly and molecular cloning procedures. Unlike approaches that use a multi-base pair motif to specify a DNA cut site, dU excision requires only a dT→dU substitution. Consequently, excision sites can be embedded in biologically active DNA sequences by placing dU substitutions at non-perturbative positions. In this work, I describe a molecular tagging method that uses dU excision to exchange a segment of a dsDNA strand with a long synthetic oligonucleotide. The core workflow of this method, called deoxyUridine eXcision-tagging (dUX-tagging), is an efficient one-pot reaction: strategically positioned dU nucleotides are excised from dsDNA to generate a 3’ overhang so that additional sequence can be appended by annealing and ligating a tagging oligonucleotide. The tagged DNA is then processed by one of two procedures to fill the 5’ overhang and remove excess tagging oligo. To facilitate its widespread use, all dUX-tagging procedures exclusively use commercially available reagents. As a result, dUX-tagging is a concise and easily implemented approach for high-efficiency linear dsDNA tagging.     

铈基SCR脱硝催化剂研究进展

近年来铈（Ce）基脱硝催化剂成为低温脱硝领域的研究热点,按载体类型可分为金属氧化物催化剂、二氧化钛载体催化剂、分子筛载体催化剂、活性炭及氧化铝载体催化剂等。按催化剂种类分别介绍了掺杂改性、制备工艺、反应条件等对催化剂性能的影响,并阐述了可能的原因机理。目前,铈基催化剂大多处于实验室阶段,工业化应用尚存在问题,尤其作为低温脱硝催化剂,活性中心堵塞问题更加突出,并且催化剂成本较高。未来可从催化剂制备工艺入手解决催化剂成型问题,以实现工业应用。同时探讨催化剂中毒机理,进一步提升其抗中毒能力。另外,寻求适宜的材料与铈掺杂组合,达到高效脱硝和经济效益最大化。     

粗轧过程中轧制力和宽展的预测与分析

 板带轧制数学模型是实现自动控制的基础,高精度的数学模型是提升产品质量和市场竞争力的重要保障。在热连轧粗轧过程控制中,轧制力和宽展是关键参数,其模型精度不仅会影响粗轧轧制规程的设定,而且会影响最终热连轧带钢产品凸度。以矩形板坯热连轧粗轧过程为研究对象,针对轧制变形区建立了三维运动许可加权速度场,在此基础上充分考虑自然宽展效应,基于刚塑性材料的第一变分原理,采用可变上限积分法对塑性变形、剪切功率和摩擦功率进行积分获得变形区总功率泛函。利用Matlab优化工具箱对总功率泛函进行最小化,得到了轧制力、宽度分布的理论解。最后利用理论模型计算数据回归得到了板坯宽展及速度场中的加权系数模型。将基于所提出模型的轧制力和宽展预测值与现场实测值及部分有关学者所建立模型的预测值进行了对比,结果验证了所建立模型的准确性。研究得到的宽展模型和速度场加权系数表达式可以方便、灵活、快速地应用到粗轧现场中,为更高质量热连轧带钢产品的生产奠定了坚实基础。