Alkylation of phosphorothioated thrombin binding aptamers improves the selectivity of inhibition of tumor cell proliferation upon anticoagulation

Background: Recently, aptamers have been extensively researched for therapy and diagnostic applications. Thrombin-binding aptamer is a 15 nt deoxyribonucleic acid screened by SELEX, it can specifically bind to thrombin and inhibit blood coagulation. Since it is also endowed with excellent antitumor activity, the intrinsic anticoagulation advantage converted to a main potential side effect for its further application in antiproliferative therapy. Methods: Site-specific alkylation was conducted through nucleophilic reaction of phosphorothioated TBAs using bromide reagents. Circular dichroism (CD) spectroscopy and surface plasmon resonance (SPR) measurements were used to evaluate anticoagulation activity, and a CCK-8 assay was used to determine cell proliferation activity. Results: The CD spectra of the modified TBAs were weakened, and their affinity for thrombin was dramatically reduced, as reflected by the K-D values. On the other hand, their inhibition of A549 cells was retained. Conclusions: Incorporation of different alkyls apparently disrupted the binding of TBA to thrombin while maintaining the antitumor activity. General significance: A new modification strategy was established for the use of TBA as a more selective antitumor agent.National Natural Science Foundation of China [21332010, 21572013]; Ministry of Science and Technology of the People's Republic of China [2012CB720604]SCI(E)ARTICLE71864-1869186

Annealing novel nucleobase-lipids with oligonucleotides or plasmid DNA based on H-bonding or π-π interaction:Assemblies and transfections

Lipid derivatives of nucleoside analogs have been highlighted for their potential for effective gene delivery. A novel class of nucleobase-lipids are rationally designed and readily synthesized, comprising thymine/cytosine, an ester/amide linker and an oleyl lipid. The diversity of four nucleobase-lipids termed DXBAs (DOTA, DNTA, DOCA and DNCA) is investigated. Besides, DNCA is demonstrated to be an effective neutral transfection material for nucleic acid delivery, which enbles to bind to oligonucleotides via H-bonding and π-π stacking with reduced toxicity in vitro and in vivo. Several kinds of nucleic acid drugs including aptamer, ssRNA, antisense oligonucleotide, and plasmid DNAs can be delivered by DXBAs, especially DNCA. In particular, G4-aptamer AS1411 encapsulated by DNCA exhibits cellular uptake enhancement, lysosome degradation reduction, cell apoptosis promotion, cell cycle phase alteration in vitro and duration prolongation in vivo, resulting in significant anti-proliferative activity. Our results demonstrate that DNCA is a promising transfection agent for G4-aptamers and exhibites bright application prospects in the permeation improvement of single-stranded oligonucleotides or plasmid DNAs

Case Report: Septic arthritis in children caused by Streptococcus pyogenes–rational use of antibiotics

To investigate the clinical characteristics and treatment of septic arthritis caused by Streptococcus pyogenes(S. pyogenes) in children, we retrospectively analyzed the clinical data, laboratory results, treatments and outcomes of three pediatric cases of septic arthritis caused by S. pyogenes occurring from 2016–2018. The three cases of septic arthritis included 1 boy and 2 girls, aged from 2–7 years. Two patients experienced fever, and in all three cases, the affected joints showed redness, swelling, an increased local skin temperature, tenderness and restricted limb movement. At the first visit, all three cases showed a significantly increased white blood cell count [(27.68–32.02)×109/mL] and a significantly increased erythrocyte sedimentation rate (113–134 mm/h). The C-reactive protein level was significantly increased in two cases (67 mg/L, 147.7 mg/L) and normal in one case. The procalcitonin level was normal in 1 case, elevated in 1 case, and undetected in 1 case. S. pyogenes isolated from cases 1 and 2 were emm1/ST28 and from case 3 was emm12/ST36. All patients were treated by abscess incision and drainage, and S. pyogenes was cultured in the abscess puncture fluid. All patients were treated with intravenous antibiotics after admission, and all patients were cured and discharged. The patients were followed up for 2 months, and their condition was improved and stable. No sequelae such as heart and kidney damage were detected. In conclusion, for children with septic arthritis, early diagnosis and timely treatment with incision and drainage followed by culture of the abscess puncture fluid are important. Once S. pyogenes infection is confirmed, β-lactam antibiotics provide effective treatment, avoiding use of broad-spectrum antibiotics

Dysfunctional gut microbiota and relative co-abundance network in infantile eczema

Additional file 1. The representative sequences of OTUs in 33 infants

Research and Application of a New Method for Calculating Dynamic Reserves

 Reserves are the basis of oilfield development, and determination of reserves accurately has great significance for future adjustment of oil fields development. Due to distinct characteristics of offshore oilfield development, it is difficult to obtain dynamic reserves accurately using conventional methods. To overcome the limitations of existing methods, in this paper, a new model for calculating dynamic reserves is established through theoretical derivation with innovative introduction of relative permeability ratio and the quadratic power function of water saturation based on Buckley-Leveret function and frontal movement equation. The result shows that this approach is simple to use and with good applicability, and only needs typical oil field dynamic data. The results of the study facilitates better recalculation of oil field reserves and implementation of oilfield adjustment well. More importantly, it has laid out a new methodology for increasing oil production and exploration in Bohai oil field and provided theoretical foundation for subsequent oilfields’ efficient development

Recent Insights into Neutrophil Extracellular Traps in Cardiovascular Diseases

Neutrophils are primary effector cells of the innate immune system. Emerging evidence has consistently shown that activated neutrophils produce and release neutrophil extracellular traps (NETs) that play roles in immunity and non-infectious diseases. NETs are composed of DNA and proteins and serve as a structural platform for pathogen sequestration and degradation. In contrast to their protective role during pathogenic infection, NETs are pathologically involved in cardiovascular disease (CVD). In this review, we introduce the formation, release, and clearance of NETs and the regulatory mechanisms of NETs formation, followed by an overview of the clinical evidence for the involvement of NETs in CVD. Because atherosclerosis is a fundamental part of the pathogenesis of CVD, we chose to focus on the mechanisms by which NETs promote endothelial cell damage and collaborate with macrophages and platelets to accelerate plaque progression and thrombosis. Finally, we present options for clinical intervention to inhibit NETs production and release in the treatment of CVD. In conclusion, this review integrates the latest findings and provides new insights into NETs, which represent a novel biomarker and therapeutic target in clinical practice

Computational Study on the Catalytic Performance of Single-Atom Catalysts Anchored on g-CN for Electrochemical Oxidation of Formic Acid

The electrochemical formic acid oxidation reaction (FAOR) has attracted great attention due to its high volumetric energy density and high theoretical efficiency for future portable electronic applications, for which the development of highly efficient and low-cost electrocatalysts is of great significance. In this work, taking single-atom catalysts (SACs) supported on graphitic carbon nitrides (g-CN) as potential catalysts, their catalytic performance for the FAOR was systemically explored by means of density functional theory computations. Our results revealed that the strong hybridization with the unpaired lone electrons of N atoms in the g-CN substrate ensured the high stability of these anchored SACs and endowed them with excellent electrical conductivity. Based on the computed free energy changes of all possible elementary steps, we predicted that a highly efficient FAOR could be achieved on Ru/g-CN with a low limiting potential of −0.15 V along a direct pathway of HCOOH(aq) → HCOOH* → HCOO* → CO2* → CO2(g), in which the formation of HCOO* was identified as the potential-determining step, while the rate-determining step was located at the CO2* formation, with a moderate kinetic barrier of 0.89 eV. Remarkably, the moderate d-band center and polarized charge of the Ru active site caused the Ru/g-CN catalyst to exhibit an optimal binding strength with various reaction intermediates, explaining well its superior FAOR catalytic performance. Hence, the single Ru atom anchored on g-CN could be utilized as a promising SAC for the FAOR, which opens a new avenue to further develop novel catalysts for a sustainable FAOR in formic-acid-based fuel cells