Tetrahydroisoquinolines: New Inhibitors of Neutrophil Extracellular Trap (NET) Formation

Neutrophils are short‐lived leukocytes that migrate to sites of infection as part of the acute immune response, where they phagocytose, degranulate, and form neutrophil extracellular traps (NETs). During NET formation, the nuclear lobules of neutrophils disappear and the chromatin expands and, accessorized with neutrophilic granule proteins, is expelled. NETs can be pathogenic in, for example, sepsis, cancer, and autoimmune and cardiovascular diseases. Therefore, the identification of inhibitors of NET formation is of great interest. Screening of a focused library of natural‐product‐inspired compounds by using a previously validated phenotypic NET assay identified a group of tetrahydroisoquinolines as new NET formation inhibitors. This compound class opens up new avenues for the study of cellular death through NET formation (NETosis) at different stages, and might inspire new medicinal chemistry programs aimed at NET‐dependent diseases.     

Mycoplasma bovis MBOV_RS02825 Encodes a Secretory Nuclease Associated with Cytotoxicity

This study aimed to determine the activity of one Mycoplasma bovis nuclease encoded by MBOV_RS02825 and its association with cytotoxicity. The bioinformatics analysis predicted that it encodes a Ca²⁺-dependent nuclease based on existence of enzymatic sites in a TNASE_3 domain derived from a Staphylococcus aureus thermonuclease (SNc). We cloned and purified the recombinant MbovNase (rMbovNase), and demonstrated its nuclease activity by digesting bovine macrophage linear DNA and RNA, and closed circular plasmid DNA in the presence of 10 mM Ca²⁺ at 22–65 °C. In addition, this MbovNase was localized in membrane and rMbovNase able to degrade DNA matrix of neutrophil extracellular traps (NETs). When incubated with macrophages, rMbovNase bound to and invaded the cells localizing to both the cytoplasm and nuclei. These cells experienced apoptosis and the viability was significantly reduced. The apoptosis was confirmed by activated expression of phosphorylated NF-κB p65 and Bax, and inhibition of Iκβα and Bcl-2. In contrast, rMbovNase^Δ181–342 without TNASE_3 domain exhibited deficiency in all the biological functions. Furthermore, rMbovNase was also demonstrated to be secreted. In conclusion, it is a first report that MbovNase is an active nuclease, both secretory and membrane protein with ability to degrade NETs and induce apoptosis.     

Interface trap effect on the transient characteristics of a photovoltaic InSb infrared detector

The transient characteristics can be significantly affected by the interface trap. In order to reveal the intrinsic mechanism and provide some references for the design of detectors, the interface trap effect on the transient characteristics of a back-illuminated photovoltaic InSb infrared detector is studied with two-dimensional simulations. The relationships between interface traps and some key physical parameters, such as the hole concentration, the recombination rate and the electric field, are analyzed to reveal the intrinsic mechanisms of the influence of the interface traps on the transient characteristics. Studies show that with the increase of the interface trap density, the recombination rate and the electric field near the interface increase, the hole concentration decreases, and the “black holes” in current density distribution appear and move forward to the pn junction. And the transient photoresponse decreases with the increase of the interface trap density.     

Quantified NOx adsorption on Pt/K/gamma-Al2O3 and the effects of CO2 and H2O

A multi-component NO_x-trap catalyst consisting of Pt and K supported on γ-Al₂O₃ was studied at 250 °C to determine the roles of the individual catalyst components, to identify the adsorbing species during the lean capture cycle, and to assess the effects of H₂O and CO₂ on NO_x storage. The Al₂O₃ support was shown to have NO_x trapping capability with and without Pt present (at 250 °C Pt/Al₂O₃ adsorbs 2.3 μmols NO_x/m²). NO_x is primarily trapped on Al₂O₃ in the form of nitrates with monodentate, chelating and bridged forms apparent in Diffuse Reflectance mid-Infrared Fourier Transform Spectroscopy (DRIFTS) analysis. The addition of K to the catalyst increases the adsorption capacity to 6.2 μmols NO_x/m², and the primary storage form on K is a free nitrate ion. Quantitative DRIFTS analysis shows that 12% of the nitrates on a Pt/K/Al₂O₃ catalyst are coordinated on the Al₂O₃ support at saturation.

When 5% CO₂ was included in a feed stream with 300 ppm NO and 12% O₂, the amount of K-based nitrate storage decreased by 45% after 1 h on stream due to the competition of adsorbed free nitrates with carboxylates for adsorption sites. When 5% H₂O was included in a feed stream with 300 ppm NO and 12% O₂, the amount of K-based nitrate storage decreased by only 16% after 1 h, but the Al₂O₃-based nitrates decreased by 92%. Interestingly, with both 5% CO₂ and 5% H₂O in the feed, the total storage only decreased by 11%, as the hydroxyl groups generated on Al₂O₃ destabilized the K–CO₂ bond; specifically, H₂O mitigates the NO_x storage capacity losses associated with carboxylate competition.     

Quantification of the in situ DRIFT spectra of Pt/K/γ-A12O3 NOx adsorber catalysts

A method to quantify DRIFT spectral features associated with the in situ adsorption of gases on a NO_x adsorber catalyst, Pt/K/Al₂O₃, is described. To implement this method, the multicomponent catalyst is analysed with DRIFT and chemisorption to determine that under operating conditions the surface comprised a Pt phase, a pure γ-Al₂O₃ phase with associated hydroxyl groups at the surface, and an alkalized-Al₂O₃ phase where the surface –OH groups are replaced by –OK groups. Both DRIFTS and chemisorption experiments show that 93–97% of the potassium exists in this form. The phases have a fractional surface area of 1.1% for the 1.7 nm-sized Pt, 34% for pure Al₂O₃ and 65% for the alkalized-Al₂O₃. NO₂ and CO₂ chemisorption at 250 °C is implemented to determine the saturation uptake value, which is observed with DRIFTS at 250 °C. Pt/Al₂O₃ adsorbs 0.087 μmol CO₂/m²and 2.0 μmol NO₂/m², and Pt/K/Al₂O₃ adsorbs 2.0 μmol CO₂/m²and 6.4 μmol NO₂/m². This method can be implemented to quantitatively monitor the formation of carboxylates and nitrates on Pt/K/Al₂O₃ during both lean and rich periods of the NO_x adsorber catalyst cycle.     

Neutrophil Extracellular Traps and Their Implications in Cardiovascular and Inflammatory Disease

Neutrophils are primary effector cells of innate immunity and fight infection by phagocytosis and degranulation. Activated neutrophils also release neutrophil extracellular traps (NETs) in response to a variety of stimuli. These NETs are net-like complexes composed of cell-free DNA, histones and neutrophil granule proteins. Besides the evolutionarily conserved mechanism to capture and eliminate pathogens, NETs are also associated with pathophysiological processes of various diseases. Here, we elucidate the mechanisms of NET formation and their different implications in disease. We focused on autoinflammatory and cardiovascular disorders as the leading cause of death. Neutrophil extracellular traps are not only present in various cardiovascular diseases but play an essential role in atherosclerotic plaque formation, arterial and venous thrombosis, as well as in the development and progression of abdominal aortic aneurysms. Furthermore, NETosis can be considered as a source of autoantigens and maintains an inflammatory milieu promoting autoimmune diseases. Indeed, there is further need for research into the balance between NET induction, inhibition, and degradation in order to pharmacologically target NETs and their compounds without impairing the patient’s immune defense. This review may be of interest to both basic scientists and clinicians to stimulate translational research and innovative clinical approaches.     

Dynamic Changes in the Ability to Release Neutrophil ExtraCellular Traps in the Course of Childhood Acute Leukemias

Acute leukemias, the most common cancers in children, are characterized by excessive proliferation of malignant progenitor cells. As a consequence of impaired blood cell production, leukemia patients are susceptible to infectious complications—a major cause of non-relapse mortality. Neutrophil extracellular traps (NETs) are involved in various pathologies, from autoimmunity to cancer. Although aberrant NETs formation may be partially responsible for immune defects observed in acute leukemia, still little is known on the NET release in the course of leukemia. Here, we present the first comprehensive evaluation of NETs formation by neutrophils isolated from children with acute leukemia in different stages of the disease and treatment stimulated in vitro with phorbol 12-myristate 13-acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine (fMLP), and calcium ionophore (CI). NETs release was measured using quantitative fluorescent method and visualized microscopically. In this setting, NETs release was significantly impaired in leukemic children both at the diagnosis and during the treatment, and full restoration of neutrophil function was achieved only after successful completion of the leukemia treatment. We suggest that neutrophil function impairment may result from both disease- and treatment-related factors. In this context, deficient innate immune response observed in acute leukemia patients may be present regardless of neutrophil count and contribute to secondary immunodeficiency observed in this population.     

Photoluminescence enhancement and atmosphere-dependent photovoltaic performance in CdS nanorod arrays/MEH-PPV hybrid

Performance improvement of CdS nanorod arrays (NRA)/poly[2-methoxy-5-(2′-ethylhexyloxy)-1,4-phenylene vinylene] (MEH-PPV) hybrid solar cells (HSCs) during the storage in ambient atmosphere has been demonstrated. An unusual photoluminescence (PL) enhancement was observed after MEH-PPV hybridizing with CdS NRA due to the abundance of S-vacancy-induced interface electron traps in CdS NRA, which was confirmed by temperature-dependent PL and charge transport analysis. By investigating on the time-resolved photoluminescence (TRPL) and current-voltage characteristics, we demonstrated that the performance improvement of CdS NRA/MEH-PPV HSCs was contributed to the co-effects of interface electron trap-oxygen interaction and MEH-PPV-oxygen interaction, and the contribution ratio between these two interactions was varied over time in air.     

吐哈盆地小草湖次凹天然气成藏条件及勘探方向分析

吐哈盆地台北凹陷小草湖次凹发育多套烃源岩,油源条件好,天然气资源丰富,勘探潜力巨大;该次凹陷中侏罗统发育3套储盖组合,天然气藏类型主要为J2s―J2q的构造―岩性复合型气藏和J2x―J1的深盆气藏,成藏期为燕山期和喜山期2期。认为古构造背景和构造―岩性复合型圈闭发育是小草湖次凹天然气成藏的主控因素,进凹寻找连片分布的岩性气藏是该区下一步天然气勘探的方向。     

Quantifying and characterizing contemporary riparian sedimentation

Fluvial processes of erosion, sediment transport and deposition determine the changing form and sedimentary structure of naturally adjusting riparian zones. Riparian sediment storage has both scientific and management importance in relation to: (i) the quantities of sediment that are involved; (ii) the quality of the sediment; and (iii) the dispersal of biological materials, notably the vegetation propagules that are transported and deposited in association with the sediment. After discussing the significance of riparian sedimentation processes, this paper reviews methods for quantifying contemporary sediment deposition within water bodies and their margins. Methods for investigating contemporary riparian sedimentation are given particular emphasis, and the extent to which different methods provide comparable estimates and have been used to support the analysis of different physical and chemical properties of the sediment are outlined. The importance of the following are stressed: (i) selecting a sampling method that is suited to the sedimentation environment; (ii) incorporating careful cross‐calibration if measurements from different methods are to be combined; and (iii) replicating measurements to give more robust estimates if small traps are employed. It is concluded that artificial turf mats provide a useful design of sediment trap across a range of environmental conditions because: (i) their surface roughness reduces problems of sediment removal by flood waters or rainfall; (ii) their pliability permits installation on irregular surfaces; (iii) they can be securely attached to the ground with metal pins to resist high shear stresses from river flows; (iv) they are robust and light and so easily manipulated in the field and laboratory; (v) it is possible to fully recover the deposited sediment to accurately determine the amount of sediment deposited and to support a range of other analyses. Results are presented to illustrate how artificial turf mats can be used to estimate the quantity and quality of deposited sediment and to explore the associated deposition of viable seeds. This provides one example of the important hydroecological role of riparian sedimentation processes and of the potential for the development of innovative, interdisciplinary research on riparian sediment dynamics. Copyright © 2003 John Wiley & Sons, Ltd.