Endothelial Dysfunction in Primary Aldosteronism Chen, Zheng-Wei; Tsai, Cheng-Hsuan; Pan, Chien-Ting ...
International journal of molecular sciences,
10/2019, Letnik:
20, Številka:
20
Journal Article
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Primary aldosteronism (PA) is characterized by excess production of aldosterone from the adrenal glands and is the most common and treatable cause of secondary hypertension. Aldosterone is a ...mineralocorticoid hormone that participates in the regulation of electrolyte balance, blood pressure, and tissue remodeling. The excess of aldosterone caused by PA results in an increase in cardiovascular and cerebrovascular complications, including coronary artery disease, myocardial infarction, stroke, transient ischemic attack, and even arrhythmia and heart failure. Endothelial dysfunction is a well-established fundamental cause of cardiovascular diseases and also a predictor of worse clinical outcomes. Accumulating evidence indicates that aldosterone plays an important role in the initiation and progression of endothelial dysfunction. Several mechanisms have been shown to contribute to aldosterone-induced endothelial dysfunction, including aldosterone-mediated vascular tone dysfunction, aldosterone- and endothelium-mediated vascular inflammation, aldosterone-related atherosclerosis, and vascular remodeling. These mechanisms are activated by aldosterone through genomic and nongenomic pathways in mineralocorticoid receptor-dependent and independent manners. In addition, other cells have also been shown to participate in these mechanisms. The complex interactions among endothelium, inflammatory cells, vascular smooth muscle cells and fibroblasts are crucial for aldosterone-mediated endothelial dysregulation. In this review, we discuss the association between aldosterone and endothelial function and the complex mechanisms from a molecular aspect. Furthermore, we also review current clinical research of endothelial dysfunction in patients with PA.
G-quadruplex (G4) structures formed by guanine-rich nucleic acids are implicated in essential physiological and pathological processes and serve as important drug targets. The genome-wide detection ...of G4s in living cells is important for exploring the functional role of G4s but has not yet been achieved due to the lack of a suitable G4 probe. Here we report an artificial 6.7 kDa G4 probe (G4P) protein that binds G4s with high affinity and specificity. We used it to capture G4s in living human, mouse, and chicken cells with the ChIP-Seq technique, yielding genome-wide landscape as well as details on the positions, frequencies, and sequence identities of G4 formation in these cells. Our results indicate that transcription is accompanied by a robust formation of G4s in genes. In human cells, we detected up to >123 000 G4P peaks, of which >1/3 had a fold increase of ≥5 and were present in >60% promoters and ∼70% genes. Being much smaller than a scFv antibody (27 kDa) or even a nanobody (12-15 kDa), we expect that the G4P may find diverse applications in biology, medicine, and molecular devices as a G4 affinity agent.
Ni‐rich cathode materials are considered promising candidates for next‐generation lithium‐ion batteries because of their high energy density and low cost. However, interphase failure at the surface ...of Ni‐rich cathodes negatively impacts cycling performance, making it challenging to meet the requirements of long‐term applications. In this study, a strategy is developed to improve interphase properties through introduction of a nucleophilic reaction‐based additive, using an appropriate amount of the inducer lithium isopropoxide (LIP) in the commercial electrolyte to achieve long‐term cycling stability of Li||LiNi0.83Co0.11Mn0.06O2 (NCM83) cells. This strategy enables Li||NCM83 cells to maintain a capacity of 148.7 mAh g−1 with a retention of 83.3 % even after 500 cycles. This outstanding cycling stability is attributed to a robust cathode‐electrolyte interphase (CEI) constructed on NCM83 surface LIP‐induce ring‐opening polymerization of ethylene carbonate (EC). As a result, the organic‐inorganic components of the CEI effectively constrain gas evolution and the corresponding phase transformation behavior. Furthermore, the CEI also suppresses microcrack formation and eventually sustains the Ni valence and coordination environment at high voltage.
Ready, willing, and stable: Interphase stability issues affect the commercialization of Ni‐rich cathode materials. In this study, interphase engineering improves the interphase stability of LiNi0.83Co0.11Mn0.06O2 in lithium‐ion batteries. A robust cathode‐electrolyte interphase is constructed by a nucleophilic reaction in the commercial electrolyte and the cathode achieves long‐term cycling stability in a Li||NCM83 cell.
Patients with kidney failure commonly require dialysis to remove nitrogenous wastes and to reduce burden to the kidney. Here, we show that a bacterial cocktail orally delivered in animals with kidney ...injury can metabolize blood nitrogenous waste products before they diffuse through the intestinal mucosal barrier. The microbial cocktail consists of three strains of bacteria isolated from faecal microbiota that metabolize urea and creatinine into amino acids, and is encapsulated in calcium alginate microspheres coated with a polydopamine layer that is selectively permeable to small-molecule nitrogenous wastes. In murine models of acute kidney injury and chronic kidney failure, and in porcine kidney failure models, the encapsulated microbial cocktail significantly reduced urea and creatinine concentrations in blood, and did not lead to any adverse effects.
Person reidentification, which matches person images of the same identity across nonoverlapping camera views, becomes an important component for cross-camera-view activity analysis. Most (if not all) ...person reidentification algorithms are designed based on appearance features. However, appearance features are not stable across nonoverlapping camera views under dramatic lighting change, and those algorithms assume that two cross-view images of the same person can be well represented either by exploring robust and invariant features or by learning matching distance. Such an assumption ignores the nature that images are captured under different camera views with different camera characteristics and environments, and thus, mostly there exists large discrepancy between the extracted features under different views. To solve this problem, we formulate an asymmetric distance model for learning camera-specific projections to transform the unmatched features of each view into a common space where discriminative features across view space are extracted. A cross-view consistency regularization is further introduced to model the correlation between view-specific feature transformations of different camera views, which reflects their nature relations and plays a significant role in avoiding overfitting. A kernel cross-view discriminant component analysis is also presented. Extensive experiments have been conducted to show that asymmetric distance modeling is important for person reidentification, which matches the concerns on cross-disjoint-view matching, reporting superior performance compared with related distance learning methods on six publically available data sets.
Concomitant atrial fibrillation and end-stage renal disease is common and associated with an unfavorable prognosis. Although oral anticoagulants have been well established to prevent thromboembolism, ...the applicability in patients under long-term dialysis remains debatable. The study aimed to determine the efficacy and safety of anticoagulation in the dialysis-dependent population.
An updated network meta-analysis based on MEDLINE, EMBASE, and the Cochrane Library was performed. Studies published up to December 2022 were included. Direct oral anticoagulants (DOACs, dabigatran, rivaroxaban, apixaban 2.5/5 mg twice daily), vitamin K antagonists (VKAs), and no anticoagulation were compared on safety and efficacy outcomes. The outcomes of interest were major bleeding, thromboembolism, and all-cause death. A total of 42 studies, including 3 randomized controlled trials, with 185 864 subjects were pooled. VKAs were associated with a significantly higher risk of major bleeding than either no anticoagulation (hazard ratio HR, 1.47; 95% CI, 1.34-1.61) or DOACs (DOACs versus VKAs; HR, 0.74 95% CI, 0.64-0.84). For the prevention of thromboembolism, the efficacies of VKAs, DOACs, and no anticoagulation were equivalent. Nevertheless, dabigatran and rivaroxaban were associated with fewer embolic events. There were no differences in all-cause death with the administration of VKAs, DOACs, or no anticoagulation.
For dialysis-dependent populations, dabigatran and rivaroxaban were associated with better efficacy, while dabigatran and apixaban demonstrated better safety. No anticoagulation was a noninferior alterative, and VKAs were associated with the worst outcomes.
In bioreactor landfills, leachate recirculation system can significantly promote moisture distribution, thereby enhancing the biodegradation of municipal solid waste (MSW). However, it increases pore ...pressure inside landfills, which can greatly affect slope stability. In this study, a three-dimensional numerical model is established to study the landfill slope stability under leachate recirculation through Vertical Wells (VWs). A leachate flow model is adopted to describe the migration of leachate, and the distribution of pore pressure is then used to calculate the Factor of Safety (FS) using strength reduction method. A large number of simulations are conducted using the proposed model to investigate the influences of injection pressure, hydraulic and mechanical properties, slope gradient, VW location and group-well configuration on slope stability. Large injection pressure or anisotropy of MSW is adverse to the slope stability. FS changes almost linearly with the variation of friction angle and cohesion. The horizontal distance between the VWs and the slope surface (d) and well spacing (D) are two important factors for slope stability. Design charts of the minimum safe distance (ds) and the minimum safe well spacing (Ds) are proposed considering various conditions. Finally, a design method of leachate recirculation system using VWs is proposed considering both recirculation efficiency and slope stability. The proposed model can well accommodate practical landfills with leachate recirculation system using VWs. The method and the results are promising to be used as a reference in engineering practice.
•A 3D model for analyzing slope stability of landfills considering leachate recirculation using vertical wells is developed.•Large injection pressure or anisotropy of MSW is adverse to the slope stability.•Factor of safety changes almost linearly with the variation of friction angle and cohesion.•Design charts of the minimum safe distance (ds) and the minimum safe well spacing (Ds) are proposed.•A design method of leachate recirculation system using VWs is proposed.
Lanthanide‐doped upconversion nanoparticles (UCNPs) have shown great promise in bioapplications. Exploring new host materials to realize efficient upconversion luminescence (UCL) output is a goal of ...general concern. Herein, we develop a unique strategy for the synthesis of novel LiLuF4:Ln3+ core/shell UCNPs with typically high absolute upconversion quantum yields of 5.0 % and 7.6 % for Er3+ and Tm3+, respectively. Based on our customized UCL biodetection system, we demonstrate for the first time the application of LiLuF4:Ln3+ core/shell UCNPs as sensitive UCL bioprobes for the detection of an important disease marker β subunit of human chorionic gonadotropin (β‐hCG) with a detection limit of 3.8 ng mL−1, which is comparable to the β‐hCG level in the serum of normal humans. Furthermore, we use these UCNPs in proof‐of‐concept computed tomography imaging and UCL imaging of cancer cells, thus revealing the great potential of LiLuF4:Ln3+ UCNPs as efficient nano‐bioprobes in disease diagnosis.
A small but sensitive biosensor: Successive injection of shell precursors enabled the synthesis of novel and highly emissive LiLuF4:Ln3+ core/shell upconversion nanoparticles that were effective as sensitive upconversion luminescent probes for the detection of β‐hCG (an important disease marker). The nanoprobes were also used successfully in proof‐of‐concept computed tomography and upconversion luminescence dual‐mode bioimaging.
Applications of persistent luminescence phosphors as night or dark‐light vision materials in many technological fields have fueled up a growing demand for rational control over the emission profiles ...of the phosphors. This, however, remains a daunting challenge. Now a unique strategy is reported to fine‐tune the persistent luminescence by using all‐inorganic CsPbX3 (X=Cl, Br, and I) perovskite quantum dots (PeQDs) as efficient light‐conversion materials. Full‐spectrum persistent luminescence with wavelengths covering the entire visible spectral region is achieved through tailoring of the PeQD band gap, in parallel with narrow bandwidth of PeQDs and highly synchronized afterglow decay owing to the single energy storage source. These findings break through the limitations of traditional afterglow phosphors, thereby opening up opportunities for persistent luminescence materials for applications such as a white‐emitting persistent light source and dark‐light multicolor displays.
A unique and versatile strategy is proposed to fine‐tune the persistent luminescence over the entire visible spectral region with narrow bandwidth and highly synchronized afterglow decay. It uses a CaAl2O4:Eu2+,Nd3+ (CAO) afterglow phosphor as the single energy storage source and all‐inorganic CsPbX3 (X=Cl, Br, and I) perovskite quantum dots (PeQDs) as efficient light conversion materials.
A simple and efficient one‐pot oxidation synthesis of N‐1‐piperidonyl amides was successfully developed through the double oxidation of hydrazides (involving hydrazonium formation, azodioxy‐carbonyl ...compounds generation, and α‐carbon oxidation) by using meta‐chloroperbenzoic acid (mCPBA). The convenient oxidation method was also extended to Rimonabant analogue. The lactam oxidized Rimonabant analogue was first successfully synthesized for demonstrating the construction and characterized by NMR spectroscopic methods and the single‐crystal X‐ray diffraction study (ORTEP).
N‐1‐Piperidonyl amides were firstly oxidized by mCPBA from N‐1‐piperidinyl amides. The new developed method was also extended to Rimonabant analogue, N‐(piperidin‐1‐yl)‐1H‐1,2,4‐triazole‐3‐carboxamide, and N‐(azepan‐1‐yl)benzamide, especially for Rimonabant analogue. This work presented a significant advancement in the synthesis of oxidized N‐1‐piperidonyl amides that had important implications for the further development of potential drugs and the study of the oxidized metabolite.
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