Identification and Engineering of Aptamers for Theranostic Application in Human Health and Disorders

An aptamer is a short sequence of synthetic oligonucleotides which bind to their cognate target, specifically while maintaining similar or higher sensitivity compared to an antibody. The in-vitro selection of an aptamer, applying a conjoining approach of chemistry and molecular biology, is referred as Systematic Evolution of Ligands by Exponential enrichment (SELEX). These initial products of SELEX are further modified chemically in an attempt to make them stable in biofluid, avoiding nuclease digestion and renal clearance. While the modification is incorporated, enough care should be taken to maintain its sensitivity and specificity. These modifications and several improvisations have widened the window frame of aptamer applications that are currently not only restricted to in-vitro systems, but have also been used in molecular imaging for disease pathology and treatment. In the food industry, it has been used as sensor for detection of different diseases and fungal infections. In this review, we have discussed a brief history of its journey, along with applications where its role as a therapeutic plus diagnostic (theranostic) tool has been demonstrated. We have also highlighted the potential aptamer-mediated strategies for molecular targeting of COVID-19. Finally, the review focused on its future prospective in immunotherapy, as well as in identification of novel biomarkers in stem cells and also in single cell proteomics (scProteomics) to study intra or inter-tumor heterogeneity at the protein level. Small size, chemical synthesis, low batch variation, cost effectiveness, long shelf life and low immunogenicity provide advantages to the aptamer over the antibody. These physical and chemical properties of aptamers render them as a strong biomedical tool for theranostic purposes over the existing ones. The significance of aptamers in human health was the key finding of this review.     

重组人肠道病毒71型病毒样颗粒疫苗外源DNA残留量检测方法的建立

目的建立重组人肠道病毒71型(enterovirus 71,EV71)病毒样颗粒(virus-like particles,VLPs)疫苗原液中昆虫细胞宿主DNA残留的地高辛探针杂交检测方法。方法抽提昆虫细胞sf9基因组DNA,经分子筛纯化后作为阳性对照品;分别以1 000~5 000 bp和100~1 000 bp的基因组DNA超声随机小片段为模板,制备地高辛探针,与阳性对照进行杂交试验。同时验证方法的检测范围、灵敏度和特异性,并采用该方法对3批重组EV71 VLPs疫苗原液中宿主DNA残留量进行测定。结果纯化后DNA样品浓度为47. 5 ng/μL,A260/A280值为1. 86,可作为阳性对照。以100~1 000 bp DNA超声随机小片段作为模板,探针标记效率更高,杂交显色更清晰。该法检测范围为10 pg^10 ng,灵敏度达1 pg,特异性强。3批重组EV71 VLPs疫苗原液中每人份剂量的宿主细胞DNA残留均<50 pg。结论本实验建立的方法特异性强,灵敏度高,可用于重组EV71 VLPs疫苗制备过程中的原液检定及质量控制。     

水厂废水处理投加PAM的分析选择

水厂废水需要寻求高效、无毒、经济的絮凝剂改善污泥水质 ,本文通过实验 ,对多种型号聚丙烯酰胺 (PAM )絮凝剂进行测试 ,对比分析 ,选择了合适型号的絮凝剂     

2-苯基吲哚衍生物的结构表达及其与雌激素受体相对亲和力的估计与预测

根据原子类型分类,采用分子电性距离矢量,对2 苯基吲哚衍生物完成了参数化表达,并依据定量结构活性关系,结合雌激素受体的相对亲和力,建立了多元线性回归模型,取得良好的效果,当样本数分别为36和32时,多参数模型相关系数分别达0 926和0 944。采用逐步回归对变量进行选择后,所建立的少参数模型其相关系数分别为0 926和0 940。采用留一法交互检验的结果分别为RCV=0 872和RCV=0 826。结果表明所建立的模型具有良好的稳定性和预测能力。     

合成R134和R134a的新工艺

以一氯二氟甲烷（Ｒ２２）为原料,裂解成含四氟乙烯Ｃ２Ｆ４混合气,以钯为催化剂加氢合成１,１,２,２ 四氟乙烷（Ｒ１３４）,以铬为催化剂经异构化制得１,１,１,２ 四氟乙烷（Ｒ１３４ａ）。自行设计和制作了中试合成装置,加氢的最佳工艺条件是：反应温度为８０℃,Ｖ（Ｃ２Ｆ４）∶Ｖ（Ｈ２）＝１∶２～１∶４,气体流速２．５０～３．５０ｍ／ｍｉｎ,Ｃ２Ｈ４的转化率为８０％左右;异构化的最佳工艺条件是：温度３００℃,异构化后的混合物中Ｒ１３４ａ的体积分数达７２．６％。     

Microstructure and phase evolution of micronized ceramic colorants from a pilot plant for inks production

The advent of inkjet printing as digital decoration of ceramic materials has irreversibly modified the industrial decoration technology, imposing companies to change the colorant production process. The inkjet application requires micronized particles in the ultrafine particle size range (smaller than 1 μm). Particles size reduction of ceramic colorants is performed by a high-energy comminution process in wet-operated bead mills, affecting colorants properties. Since a deep knowledge of milling-induced microstructural changes is still lacking, the micronization effects on a set of five industrial ceramic colorants are thoughtfully investigated in this work by simulating the industrial process at a pilot plant. Particle size distribution and energy consumption are monitored during the comminution process. The compositional (including crystallite size and microstrain analysis of the main phases) and morphological variation of four ceramic pigments (yellow zircon, brown spinel, pink malayaite, and green eskolaite) and one dye (blue olivine) is investigated by XRPD (Rietveld method) and SEM analyses. The analytical approach combined with a physical/semiempirical modelling of the colorants elastic features versus the energy demand for particle reduction has yielded details on the nature of the micronization-induced microstructural changes in ceramic colorants. Specifically, the comminution efficiency as well as the crystalline phase stability are related to the intrinsic properties of each colorant. Brittle breakage rather than plastic deformation on comminution are also system dependent. When an euhedral to subhedral crystal habit is maintained a brittle fracture is preserved throughout the comminution progress, while the formation of flake-like particles and particle agglomeration are strong evidences of plastic deformation. The last evidence deals with the material elastic features. Materials with high bulk modulus convert the grinding energy to lattice defects that lead to particle breakage by brittle fractures, while materials with lower bulk modulus convert/dissipate part of the supplied energy in plastic deformations, drastically decreasing the comminution process efficiency.     

Analysis and Experimentation of a New Half-Bridge High-Frequency Resonant Inverter for DBD Type Ozonizer

The peak voltage across the dielectric barrier discharge (DBD) type ozonizer is a key factor for ozone synthesis, and it is hard to be kept stable in widely used high-frequency resonant inverters within the entire working range. The soft switching conditions of power switches in these resonant inverters cannot always be satisfied within the entire working range, too. To address the two questions, a new half-bridge high-frequency resonant inverter is proposed in the paper, and the expressions that accurately describe the behavior of the inverter are derived by analyzing different operating modes. The simulation and experimental results show that the peak voltage across DBD type ozonizer is kept stable, moreover, zero current switching of power switches is realized within the entire working range.     

Application of Advanced Non-Linear Spectral Decomposition and Regression Methods for Spectroscopic Analysis of Targeted and Non-Targeted Irradiation Effects in an In-Vitro Model

Irradiation of the tumour site during treatment for cancer with external-beam ionising radiation results in a complex and dynamic series of effects in both the tumour itself and the normal tissue which surrounds it. The development of a spectral model of the effect of each exposure and interaction mode between these tissues would enable label free assessment of the effect of radiotherapeutic treatment in practice. In this study Fourier transform Infrared microspectroscopic imaging was employed to analyse an in-vitro model of radiotherapeutic treatment for prostate cancer, in which a normal cell line (PNT1A) was exposed to low-dose X-ray radiation from the scattered treatment beam, and also to irradiated cell culture medium (ICCM) from a cancer cell line exposed to a treatment relevant dose (2 Gy). Various exposure modes were studied and reference was made to previously acquired data on cellular survival and DNA double strand break damage. Spectral analysis with manifold methods, linear spectral fitting, non-linear classification and non-linear regression approaches were found to accurately segregate spectra on irradiation type and provide a comprehensive set of spectral markers which differentiate on irradiation mode and cell fate. The study demonstrates that high dose irradiation, low-dose scatter irradiation and radiation-induced bystander exposure (RIBE) signalling each produce differential effects on the cell which are observable through spectroscopic analysis.     

Rationale for a Combination Therapy with the STAT5 Inhibitor AC-4-130 and the MCL1 Inhibitor S63845 in the Treatment of FLT3-Mutated or TET2-Mutated Acute Myeloid Leukemia

The FMS-like tyrosine kinase 3 (FLT3) gene is mutated in one-third of patients with de novo acute myeloid leukemia (AML). Mutated FLT3 variants are constitutively active kinases signaling via AKT kinase, MAP kinases, and STAT5. FLT3 inhibitors have been approved for the treatment of FLT3-mutated AML. However, treatment response to FLT3 inhibitors may be short-lived, and resistance may emerge. Compounds targeting STAT5 may enhance and prolong effects of FLT3 inhibitors in this subset of patients with FLT3-mutated AML. Here STAT5-inhibitor AC-4-130, FLT3 inhibitor midostaurin (PKC412), BMI-1 inhibitor PTC596, MEK-inhibitor trametinib, MCL1-inhibitor {"type":"entrez-nucleotide","attrs":{"text":"S63845","term_id":"400540","term_text":"S63845"}}S63845, and BCL-2 inhibitor venetoclax were assessed as single agents and in combination for their ability to induce apoptosis and cell death in leukemic cells grown in the absence or presence of bone marrow stroma. Synergistic effects on cell viability were detected in both FLT3-mutated and FLT3-wild-type AML cells treated with AC-4-130 in combination with the MCL1 inhibitor {"type":"entrez-nucleotide","attrs":{"text":"S63845","term_id":"400540","term_text":"S63845"}}S63845. AML patient samples with a strong response to AC-4-130 and {"type":"entrez-nucleotide","attrs":{"text":"S63845","term_id":"400540","term_text":"S63845"}}S63845 combination treatment were characterized by mutated FLT3 or mutated TET2 genes. Susceptibility of AML cells to AC-4-130, PTC596, trametinib, PKC412, and venetoclax was altered in the presence of HS-5 stroma. Only the MCL1 inhibitor {"type":"entrez-nucleotide","attrs":{"text":"S63845","term_id":"400540","term_text":"S63845"}}S63845 induced cell death with equal efficacy in the absence or presence of bone marrow stroma. The combination of the STAT5-inhibitor AC-4-130 and the MCL1 inhibitor {"type":"entrez-nucleotide","attrs":{"text":"S63845","term_id":"400540","term_text":"S63845"}}S63845 may be an effective treatment targeting FLT3-mutated or TET2-mutated AML.     

Relation of glass transition temperature to the hydrogen bonding degree and energy in poly(N-vinyl pyrrolidone) blends with hydroxyl-containing plasticizers: 3. Analysis of two glass transition temperatures featured for PVP solutions in liquid poly(ethylene glycol)

The phase behaviour of poly(N-vinyl pyrrolidone)-poly(ethylene glycol) (PVP-PEG) blends has been examined in the entire composition range using Temperature Modulated Differential Scanning Calorimetry (TM-DSC) and conventional DSC techniques. Despite the unlimited solubility of PVP in oligomers of ethylene glycol, the PVP-PEG system under consideration demonstrates two distinct and mutually consistent glass transition temperatures (T_g) within a certain concentration region. The dissolution of PVP in oligomeric PEG has been shown earlier (by FTIR spectroscopy) to be due to hydrogen bonding between carbonyl groups in PVP repeat units and complementary hydroxyl end-groups of PEG chains. Forming two H-bonds through both terminal OH-groups, PEG acts as a reversible crosslinker of PVP macromolecules. To characterise the hydrogen bonded complex formation between PVP (M_w=10⁶) and PEG (M_w=400) we employed an approach described in the first two papers of this series that is based on the modified Fox equation. We evaluated the fraction of crosslinked PVP units and PEG chains participating to the complex formation, the H-bonded network density, the equilibrium constant of complex formation, etc. Based on the established molecular details of self-organisation in PVP-PEG solutions, we propose a three-stage mechanism of PVP-PEG H-bonded complex formation/breakdown with increase of PEG content. The two observed T_gs are assigned to a coexisting PVP-PEG network (formed via multiple hydrogen bonding between a PEG and PVP) and a homogeneous PVP-PEG blend (involving a single hydrogen bond formation only). Based on the strong influence of coexisting regions on each other and the absence of signs of phase separation (evidenced by Optical Wedge Microinterferometry) we conclude that the PVP-PEG blend is fully miscible on a molecular scale.