Conformational Studies on Muonic Free Radicals

Abstract Not Provided

Comment on "Which is greater: eπe^{\pi} or πe\pi^{e}? An unorthodox physical solution to a classic puzzle"

In a recent Note (Am. J. Phys. 92:397, 2024; arXiv:2309.10826), Vallejo and Bove provide a physical argument based nominally on the second law of thermodynamics as a way of resolving the mathematical question appearing in the title. A remarkable aspect of their argument is that it does not depend on the numerical value of $\pi$, because $e^{x} \ge x^{e}$ for all positive $x$, with equality occurring only when $x = e$. Moreover, their argument does not depend on the validity of the second law but is rather a limited proof of it for this particular case.Comment: 5 pages, 1 figure, accepted for publication by Am. J. Phys., comment on arXiv:2309.1082

4-Chloro-N-(3-methoxy­phen­yl)­benz­amide

The title benzamide derivative, C14H12ClNO2, crystallizes with two independent mol­ecules in the asymmetric unit. Both are close to being planar, with dihedral angles between the two benzene rings of 11.92 (6) and 12.80 (7)°. In the crystal structure, N—H⋯O hydrogen bonds link mol­ecules into chains along a. These inter­actions are augmented by C—H⋯O hydrogen bonds to form two-dimensional layers in the ac plane. Additional C—H⋯O inter­actions result in a three-dimensional network consisting of undulating rows along c. The crystal studied was an inversion twin with a 0.59 (3):0.41 (3) domain ratio

2-Fluoro-N-o-tolyl­benzamide

In the title compound, C14H12FNO, the ortho-F atom and corresponding H atom on the fluoro­benzene ring are disordered over two positions with occupancies of 0.856 (4) and 0.144 (4). The amide unit is planar with a maximum deviation of 0.0057 (16) Å and the amide plane makes dihedral angles of 38.27 (11)° with the fluoro­benzene ring plane and 37.53 (10)° with the tolyl ring. The two benzene rings are inclined at an angle of 4.17 (15)°. In the crystal structure, chains form along b through N—H⋯O hydrogen bonds augmented by C—H⋯π inter­actions. Additional inter­molecular C—H⋯O and C—H⋯F hydrogen bonds further stabilize the structure, forming layers in the ac plane

2-Fluoro-N-(4-methoxy­phen­yl)benzamide

In the title compound, C14H12FNO2, the fluoro­benzene and methoxy­benzene rings are inclined at 27.06 (7) and 23.86 (7)°, respectively, to the amide portion of the mol­ecule and at 3.46 (9)° to one another. The meth­oxy substituent lies close to the methoxy­benzene ring plane, with a maximum deviation of 0.152 (3) Å for the methyl C atom. In the crystal structure, inter­molecular N—H⋯O hydrogen bonds link mol­ecules into rows along a. Weak C—H⋯O and C—H⋯F inter­actions further stabilize the packing, forming corrugated sheets in the bc plane

N-Cyclo­hexyl-2-fluoro­benzamide

In the title compound, C13H16FNO, the fluoro­benzene ring plane and the plane through the amide unit are inclined at a dihedral angle of 29.92 (7)°. The cyclo­hexane ring adopts a chair conformation. In the crystal structure, N—H⋯O hydrogen bonds, augmented by weak C—H⋯O inter­actions, link the mol­ecules into transverse chains along a. These chains are linked into zigzag columns down a by C—H⋯F hydrogen bonds and C—H⋯π inter­actions

1-(2-Chloro-5-nitro­phen­yl)-3-(2,2-di­methyl­propion­yl)thio­urea

With the exception of the C atoms of two of the methyl groups of the tert-butyl substituent, all of the non-H atoms of the title compound, C12H14ClN3O3S, lie on a mirror plane. The 2-chloro-5-nitro­phenyl and 2,2-dimethyl­propionyl substituents are, respectively, cis and trans relative to the thio­carbonyl S atom across the two C—N bonds. Intra­molecular N—H⋯O and C—H⋯S hydrogen bonds form S(6) ring motifs, also in the mirror plane. Despite the presence of two N—H subsituents, no inter­molecular hydrogen bonds are observed in the crystal structure. Weak π–π contacts [centroid–centroid distances of 4.2903 (17) Å] involving adjacent aromatic rings link the mol­ecules in a head-to-tail fashion above and below the mol­ecular plane

Mitochondrial dysfunction and mitophagy blockade contribute to renal osteodystrophy in chronic kidney disease-mineral bone disorder

Chronic kidney disease–mineral and bone disorder (CKD-MBD) presents with extra-skeletal calcification and renal osteodystrophy (ROD). The origins of ROD likely lie with elevated uremic toxins and/or an altered hormonal profile but the cellular events responsible remain unclear. Here, we report that stalled mitophagy contributes to mitochondrial dysfunction in bones of a CKD-MBD mouse model, and also human CKD-MBD patients. RNA-seq analysis exposed an altered expression of genes associated with mitophagy and mitochondrial function in tibia of CKD-MBD mice. The accumulation of damaged osteocyte mitochondria and the expression of mitophagy regulators, p62/SQSTM1, ATG7 and LC3 was inconsistent with functional mitophagy, and in mito-QC reporter mice with CKD-MBD, there was a 2.3-fold increase in osteocyte mitolysosomes. Altered expression of mitophagy regulators in human CKD-MBD bones was also observed. To determine if uremic toxins were possibly responsible for these observations, indoxyl sulfate treatment of osteoblasts revealed mitochondria with distorted morphology and whose membrane potential and oxidative phosphorylation were decreased, and oxygen-free radical production increased. The altered p62/SQSTM1 and LC3-II expression was consistent with impaired mitophagy machinery and the effects of indoxyl sulfate were reversible by rapamycin. In conclusion, mitolysosome accumulation from impaired clearance of damaged mitochondria may contribute to the skeletal complications, characteristic of ROD. Targeting mitochondria and the mitophagy process may therefore offer novel routes for intervention to preserve bone health in patients with ROD. Such approaches would be timely as our current armamentarium of anti-fracture medications has not been developed for, or adequately studied in, patients with severe CKD-MBD

Osteocalcin Regulates Arterial Calcification via Altered Wnt Signalling and Glucose Metabolism

Arterial calcification is an important hallmark of cardiovascular disease and shares many similarities with skeletal mineralisation. The bone-specific protein osteocalcin (OCN) is an established marker of vascular smooth muscle cell (VSMC) osteochondrogenic trans-differentiation and a known regulator of glucose metabolism. However, the role of OCN in controlling arterial calcification is unclear. We hypothesised that OCN regulates calcification in VSMCs and sought to identify the underpinning signalling pathways. Immunohistochemistry revealed OCN co-localisation with VSMC calcification in human calcified carotid artery plaques. Additionally, 3 mM phosphate treatment stimulated OCN mRNA expression in cultured VSMCs (1.72 fold; p &lt; 0.001). Phosphate-induced calcification was blunted in VSMCs derived from OCN null mice (Ocn-/- ) compared to cells derived from Wild-Type (WT) mice (0.37 fold, p &lt; 0.001). Ocn-/- VSMCs showed reduced mRNA expression of the osteogenic marker Runx2 (0.51 fold, p &lt; 0.01) and the sodium-dependent phosphate transporter, PiT1 (0.70 fold, p &lt; 0.001), with an increase in the calcification inhibitor Mgp (1.42 fold, p &lt; 0.05) compared to WT. Ocn-/- VSMCs also showed reduced mRNA expression of Axin2 (0.13 fold; p &lt; 0.001) and Cyclin D (0.71 fold; p &lt; 0.01), markers of Wnt signalling. CHIR99021 (GSK3β inhibitor) treatment increased calcium deposition in WT and Ocn-/- VSMCs (1 μM; p &lt; 0.001). Ocn-/- VSMCs however calcified less than WT cells (1 μM; 0.27 fold; p &lt; 0.001). Ocn-/- VSMCs showed reduced mRNA expression of Glut1 (0.78 fold p &lt; 0.001), Hex1 (0.77 fold p &lt; 0.01) and Pdk4 (0.47 fold p &lt; 0.001). This was accompanied by reduced glucose uptake (0.38 fold, p &lt; 0.05). Subsequent mitochondrial function assessment revealed increased ATP-linked respiration (1.29 fold, p &lt; 0.05), spare respiratory capacity (1.59 fold, p &lt; 0.01) and maximal respiration (1.52 fold, p &lt; 0.001) in Ocn-/- versus WT VSMCs. Together these data suggest that OCN plays a crucial role in arterial calcification mediated by Wnt/β-catenin signalling through reduced maximal respiration. Mitochondrial dynamics may therefore represent a novel therapeutic target for clinical intervention. This article is protected by copyright. All rights reserved.</p