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- Boorsma, CE, et al.
(author)
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A Potent Tartrate Resistant Acid Phosphatase Inhibitor to Study the Function of TRAP in Alveolar Macrophages
- 2017
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 12570-
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Journal article (peer-reviewed)abstract
- The enzyme tartrate resistant acid phosphatase (TRAP, two isoforms 5a and 5b) is highly expressed in alveolar macrophages, but its function there is unclear and potent selective inhibitors of TRAP are required to assess functional aspects of the protein. We found higher TRAP activity/expression in lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma compared to controls and more TRAP activity in lungs of mice with experimental COPD or asthma. Stimuli related to asthma and/or COPD were tested for their capacity to induce TRAP. Receptor activator of NF-κb ligand (RANKL) and Xanthine/Xanthine Oxidase induced TRAP mRNA expression in mouse macrophages, but only RANKL also induced TRAP activity in mouse lung slices. Several Au(III) coordination compounds were tested for their ability to inhibit TRAP activity and [Au(4,4′-dimethoxy-2,2′-bipyridine)Cl2][PF6] (AubipyOMe) was found to be the most potent inhibitor of TRAP5a and 5b activity reported to date (IC50 1.3 and 1.8 μM respectively). AubipyOMe also inhibited TRAP activity in murine macrophage and human lung tissue extracts. In a functional assay with physiological TRAP substrate osteopontin, AubipyOMe inhibited mouse macrophage migration over osteopontin-coated membranes. In conclusion, higher TRAP expression/activity are associated with COPD and asthma and TRAP is involved in regulating macrophage migration.
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- Chen, Hao, et al.
(author)
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Surface-Directed Structural Transition of Amyloidogenic Aggregates and the Resulting Neurotoxicity
- 2020
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In: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 5:6, s. 2856-2864
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Journal article (peer-reviewed)abstract
- The transition of amyloidogenic species into ordered structures (i.e., prefibrillar oligomers, protofibrils, mature fibrils, and amyloidogenic aggregates) is closely associated with many neurodegenerative disease pathologies. It is increasingly appreciated that the liquid-solid interface contributes to peptide aggregation under physiological conditions. However, much remains to be explored on the molecular mechanism of surface-directed amyloid formation. We herein demonstrate that physical environmental conditions (i.e., negatively charged surface) affect amyloid formation. Nontoxic amyloid aggregates quickly develop into intertwisting fibrils on a negatively charged mica surface. These fibrillar structures show significant cytotoxicity on both neuroblastoma cell-lines (SH-SY5Y) and primary neural stem cells. Our results suggest an alternative amyloid development pathway, following which A beta peptides form large amyloidogenic aggregates upon stimulation, and later transit into neurotoxic fibrillar structures while being trapped and aligned by a negatively charged surface. Conceivably, the interplay between chemical and physical environmental conditions plays important roles in the development of neurodegenerative diseases.
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| 4. |
- Cheng, Jie, et al.
(author)
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Guanidimidazole-quanternized and cross-linked alkaline polymer electrolyte membrane for fuel cell application
- 2016
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In: Journal of Membrane Science. - : Elsevier BV. - 0376-7388 .- 1873-3123. ; 501, s. 100-108
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Journal article (peer-reviewed)abstract
- A modified imidazole, namely guanidimidazole (GIm) was designed and synthesized as a novel quaternizing- and cross-linking agent for alkaline polymer electrolyte membrane fabrication. The resulting membrane was more alkali tolerant and swelling resistant than that quaternized purely by 1-methylimidazole owing to the enhanced resonance and cross-linking ability of GIm, the former confirmed by a LUMO (lowest unoccupied molecular orbital) energy calculation. The membrane also showed good ionic conductivity, mechanical strength and thermal stability. A H2/O2 fuel cell using the synthesized membrane showed a peak power density of 39 mW cm−2 at 50 °C. This work preliminarily demonstrates the beneficial effect of imidazole modification by both experimental and computational investigation; it provides a new cation design strategy that may potentially achieve simultaneous improvement of alkali-stability and swelling resistance of alkaline electrolyte membranes.
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| 8. |
- Ruilope, LM, et al.
(author)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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In: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Journal article (peer-reviewed)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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- Yao, Houze, et al.
(author)
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Janus-interface engineering boosting solar steam towards high-efficiency water collection
- 2021
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In: Energy & Environmental Science. - : Royal Society of Chemistry (RSC). - 1754-5692 .- 1754-5706. ; :10
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Journal article (peer-reviewed)abstract
- Solar powered clean water production has been considered a favorable way to address the problem of the global water shortage. Recently, the interfacial solar-steam generation system has greatly improved water evaporation by localizing the solar energy at an advanced solar-thermal conversion material interface. However, the specific water productivity (SWP) is still far away from a satisfactory level due to the strong mutual interference between the incident sunlight and the generated water vapor, which causes a huge loss in energy and in turn restrains the final efficiency in water evaporation and collection. SWP is the water collection per solar radiation area per hour, which reflects the actual solar efficiency for water production and a key concern in desalination. Herein, we report a rational Janus-interface solar-steam generator (J-SSG), which separates the water evaporation and the solar-thermal conversion on the two sides of the film generator. This J-SSG demonstrates a water evaporation rate of up to 2.21 kg m(-2) h(-1) under 1 sun in a large area of 100 cm(2). More importantly, a record high SWP of 1.95 kg m(-2) h(-1) is realized in a simple system, and the SWP efficiency corresponding to the ratio of SWP to evaporation rate is as high as 88%. In an outdoor test (Beijing, solar energy similar to 15 MJ m(-2) day(-1)), 10 L purified water per square meter have been easily achieved. This Janus-interface engineering of the solar-steam generator provides a novel strategy and solution for solar powered water production of practical significance.
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