| 1. |
- Hindy, George, et al.
(författare)
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Increased soluble urokinase plasminogen activator levels modulate monocyte function to promote atherosclerosis
- 2022
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 132:24, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- People with kidney disease are disproportionately affected by atherosclerosis for unclear reasons. Soluble urokinase plasminogen activator receptor (suPAR) is an immune-derived mediator of kidney disease, levels of which are strongly associated with cardiovascular outcomes. We assessed suPAR’s pathogenic involvement in atherosclerosis using epidemiologic, genetic, and experimental approaches. We found serum suPAR levels to be predictive of coronary artery calcification and cardiovascular events in 5,406 participants without known coronary disease. In a genome-wide association meta-analysis including over 25,000 individuals, we identified a missense variant in the plasminogen activator, urokinase receptor (PLAUR) gene (rs4760), confirmed experimentally to lead to higher suPAR levels. Mendelian randomization analysis in the UK Biobank using rs4760 indicated a causal association between genetically predicted suPAR levels and atherosclerotic phenotypes. In an experimental model of atherosclerosis, proprotein convertase subtilisin/kexin–9 (Pcsk9) transfection in mice overexpressing suPAR (suPARTg) led to substantially increased atherosclerotic plaques with necrotic cores and macrophage infiltration compared with those in WT mice, despite similar cholesterol levels. Prior to induction of atherosclerosis, aortas of suPARTg mice excreted higher levels of CCL2 and had higher monocyte counts compared with WT aortas. Aortic and circulating suPARTg monocytes exhibited a proinflammatory profile and enhanced chemotaxis. These findings characterize suPAR as a pathogenic factor for atherosclerosis acting at least partially through modulation of monocyte function.
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| 2. |
- Wei, Changli, et al.
(författare)
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Ab initio investigation on predissociation of the A2Σ+ state of the SeH radical induced by spin-orbit coupling
- 2023
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Ingår i: Journal of Quantitative Spectroscopy and Radiative Transfer. - : Elsevier. - 0022-4073 .- 1879-1352. ; 311
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Tidskriftsartikel (refereegranskat)abstract
- High-level ab initio calculations are performed to investigate potential energy curves (PECs) of seven low-lying Λ-S states associated with the two lowest dissociation limits of the SeH radical by utilizing the internally contracted multireference configuration interaction (icMRCI) method in combination with the aug-cc-pwCV5Z Gaussian basis set. The scalar relativistic effect (SR), the electronic core-valence (CV) correction, and Davidson (+Q) modification are included in our calculations. The fourteen Ω states generated from the seven Λ-S states are yielded when the spin-orbit coupling (SOC) effect is taken into account by using the Breit-Pauli operator. On the ground of the obtained PECs, the spectroscopic constants of the bound Λ-S and Ω states are evaluated, which reproduce pretty well the available experimental and theoretical values. By virtue of SOC matrix elements between the bound A2Σ+ state and repulsive 4Σ–(I), 2Σ–(I), or 4∏(I) states crossing with the A2Σ+ state PEC, the spin-orbit perturbations in the A2Σ+ rovibrational manifold in the crossing region and the A-state predissociation mechanism are analyzed. It is clearly exhibited that the avoided crossing phenomena between electronic states possessing the same Ω quantum number provide obvious spectroscopic effects in the transition dipole moments (TMDs) and Franck-Condon factors (FCFs) of the A2Σ+-X2Π transition. The radiative lifetimes of the A2Σ+ vibrational sublevels are determined. In addition, we finalized our study of the SeH molecule by optimizing its equilibrium ground state geometry in terms of a restricted coupled cluster approach including singles and doubles with perturbative triples account (RCCSD(T) method) plus CV, SR, and SOC corrections with extrapolating to complete basis set (CBS) limit.
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| 3. |
- Xu, Yingting, et al.
(författare)
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3-Pentanol glycosides from root nodules of the actinorhizal plant Alnus cremastogyne
- 2023
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Ingår i: Phytochemistry. - : Elsevier BV. - 0031-9422 .- 1873-3700. ; 207
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Tidskriftsartikel (refereegranskat)abstract
- Alnus cremastogyne Burkill (Betulaceae), an actinorhizal plant, can enter a mutualistic symbiosis with Frankia species that leads to the formation of nitrogen fixing root nodules. Some primary metabolites (carbohydrates, dicarboxylic acids, amino acids, citrulline and amides) involved in carbon and nitrogen metabolism in actinorhizal nodules have been identified, while specialized metabolites in A. cremastogyne root nodules are yet to be characterized. In this study, we isolated and identified three undescribed 3-pentanol glycosides, i.e., 3-pentyl α-l-arabinofuranosyl-(1′′→6′)-β-d-glucopyranoside, 3-pentyl α-l-rhamnopyranosyl-(1′′→6′)-β-d-glucopyranoside, and 3-pentyl 6′-(3-hydroxy3-methylglutaryl)-β-d-glucopyranoside, as well as seventeen known compounds from A. cremastogyne root nodules. 3-Pentanol glycosides are abundantly distributed in root nodules, while they are distributed in stems, roots, leaves and fruits at low/zero levels. A. cremastogyne plants treated by root nodule suspension emit 3-pentanol. This study enriches the knowledge about specialized metabolites in the actinorhizal host, and provides preliminarily information on the signal exchange in the actinorhizal symbiosis between A. cremastogyne and Frankia.
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