COX-2 Is Downregulated in Human Stenotic Aortic Valves and Its Inhibition Promotes Dystrophic Calcification

Calcific aortic valve disease (CAVD) is the result of maladaptive fibrocalcific processes leading to a progressive thickening and stiffening of aortic valve (AV) leaflets. CAVD is the most common cause of aortic stenosis (AS). At present, there is no effective pharmacotherapy in reducing CAVD progression; when CAVD becomes symptomatic it can only be treated with valve replacement. Inflammation has a key role in AV pathological remodeling; hence, anti-inflammatory therapy has been proposed as a strategy to prevent CAVD. Cyclooxygenase 2 (COX-2) is a key mediator of the inflammation and it is the target of widely used anti-inflammatory drugs. COX-2-inhibitor celecoxib was initially shown to reduce AV calcification in a murine model. However, in contrast to these findings, a recent retrospective clinical analysis found an association between AS and celecoxib use. In the present study, we investigated whether variations in COX-2 expression levels in human AVs may be linked to CAVD. We extracted total RNA from surgically explanted AVs from patients without CAVD or with CAVD. We found that COX-2 mRNA was higher in non-calcific AVs compared to calcific AVs (0.013 ± 0.002 vs. 0.006 ± 0.0004; p < 0.0001). Moreover, we isolated human aortic valve interstitial cells (AVICs) from AVs and found that COX-2 expression is decreased in AVICs from calcific valves compared to AVICs from non-calcific AVs. Furthermore, we observed that COX-2 inhibition with celecoxib induces AVICs trans-differentiation towards a myofibroblast phenotype, and increases the levels of TGF-β-induced apoptosis, both processes able to promote the formation of calcific nodules. We conclude that reduced COX-2 expression is a characteristic of human AVICs prone to calcification and that COX-2 inhibition may promote aortic valve calcification. Our findings support the notion that celecoxib may facilitate CAVD progression.     

Dislocations in carbon nanotube walls

We present a novel interpretation of defected tubes based on a dislocation model. A scroll (a sheet rolled without closure) is considered as an axial edge dislocation in a multiwall nanotube (MWNT). Screw dislocation type defects separate scroll from nested-tubes within the same nanotube. The glide of the screw dislocation causes the transformation between these two forms. In some cases, the mechanism of formation of an MWNT could, therefore, start with the formation of a scroll which, by gliding of a screw dislocation, is transformed into the more stable MWNT We compare the structure and energetics of prismatic screw and edge dislocations in graphite and carbon nanotubes. We present calculations for the Peierls barrier of the first kind for graphite and we discuss this result for glide motion of screw dislocations in nanotubes. There is no evidence for stable sp3 atoms in any of the studied nanostructures.     

Modeling cellular lysis in skeletal muscle due to electric shock

High-voltage electrical trauma frequently results in injury patterns that cannot be completely attributed to Joule heating. An electrical-injury model describing cellular lysis damage caused by supraphysiological electric fields is introduced, and used to evaluate the effects of high-voltage electric shock on the skeletal muscle of a human upper limb in a configuration that simulates hand-to-hand contact. A novel multiresolution admittance method, capable of efficiently handling large computational models while maintaining excellent accuracy, was used to perform the numerical computations. Values for the computed current through the arm and the upper limb impedance are reported.     

Reconciling deep learning and first-principle modelling for the investigation of transport phenomena in chemical engineering

The use of machine learning in chemical engineering has the potential to greatly improve the design and analysis of complex systems. However, there are also risks associated with its adoption, such as the potential for bias in algorithms and the need for careful oversight to ensure the safety and reliability of machine learning-powered systems. This paper explores the opportunities and risks of using machine learning in chemical engineering and provides a perspective on how it may be integrated into engineering practices in a responsible and effective manner. We generated the text of this abstract with GPT-3, OpenAI's large-scale language-generation model. Upon generating the draft, we ensured that the language was to our liking, and we take ultimate responsibility for the content of this publication.     

Lattice Discrete Particle Model (LDPM) for failure behavior of concrete. II: Calibration and validation

The Lattice Discrete Particle Model (LDPM) formulated in the preceding Part I of this study is calibrated and validated in the present Part II. Calibration and validation is performed by comparing the results of numerical simulations with experimental data gathered from the literature. Simulated experiments include uniaxial and multiaxial compression, tensile fracture, shear strength, and cycling compression tests.     

Bio-template route for facile fabrication of Cd(OH)2@yeast hybrid microspheres and their subsequent conversion to mesoporous CdO hollow microspheres

Cadmium oxide (CdO) microspheres with a porous hollow microstructure were prepared by a facile yeast mediated bio-template route. The yeast provides a solid scaffold for the deposition of cadmium hydroxide (Cd(OH)₂) from cadmium acetate and sodium hydroxide solutions to form the hybrid Cd(OH)₂@yeast precursor. Thermal conversions of this at above 500 °C in air have produced hollow CdO microspheres. The products were characterized by scanning electron microscopy (SEM), energy dispersive spectrometry (EDS), X-ray diffraction (XRD), Fourier transformed infrared spectroscopy (FT-IR), thermal gravimetric and differential thermal analysis (TGA-DTA), and Brunauer-Emmett-Teller (BET) surface analysis respectively. The obtained CdO microspheres have uniform size (length = 2.6 ± 0.4 μm; width = 2.0 ± 0.2 μm) and a well defined, continuous, mesoporous hollow microstructure. The shell is about 250-280 nm in thickness. The mechanism of formation of Cd(OH)₂@yeast precursor and its conversion to CdO hollow microspheres is discussed. In comparison with traditional template-directed method, the present strategy represents a general, economical and environmentally benign route for the formation of metal oxide hollow microspheres. These materials have potential applications in different fields such as encapsulation, drug delivery, efficient catalysis, battery materials and photonic crystals. The method presented can be extended to the synthesis of other inorganic hollow microstructures of different sizes and shapes by pre-selecting suitable bio-templates.     

Casein proteolysis in human milk: tracing the pattern of casein breakdown and the formation of potential bioactive peptides

The protein and peptide fraction of human milk samples collected from mothers of pre- and full-term infants in the first week after parturition was analysed by use of liquid chromatography-mass spectrometry and tandem mass spectrometry. By characterising the peptide sequence, we defined the pathway of casein hydrolysis which leads to the formation of small peptides through intermediate oligopeptides. It was found that the action of a plasmin-like enzyme acting on specific lysine residues is the primary step in casein degradation. This is followed by endopeptidases and/or exopeptidases mediated cleavage of the oligopeptides which, in turn, produces a multiplicity of short peptides differing by one or more amino acid residues. In this process, a series of potentially bioactive peptides (opioid, phosphopeptides) and their precursors are produced.     

Sonochemical Synthesis and Structural Characterization and DFT Calculations of a Novel Nano Flower Pb(II) Coordination Compound [Pb(phen)2(4-abs)2]n

Nano-structures of a new coordination polymer of divalent Pb with the ligands 1,10-phenanthroline (phen) and 4-aminobenzene sulfonic acid (4-abs), [Pb(phen)₂(4-abs)₂]_n (1), were synthesized by a sonochemical method that produced a coordination polymer of nanometer size. The new nano-structure was characterized by scanning electron microscopy, X-ray powder diffraction and IR spectroscopy and elemental analysis. Compound 1 was structurally characterized by single crystal X-ray diffraction and showed that the coordination number of the Pb(II) ions is six; i.e. (PbN₄O₂). Compound 1 also has a stereochemically active lone pair of electrons and a hemi-directed coordination sphere. The chains interact with each other through π–π stacking to create a 3D framework. The structure of 1 was optimized by density functional theory calculations. The calculated structural parameters and IR spectra of 1 are consistent with the crystal structure.     

Ozonation kinetics of cork-processing water in a bubble column reactor

The oxidative degradation of organic pollutants present in cork-processing water at natural pH (6.45) was studied in a bubble column ozonation reactor. A steady reduction in both chemical oxygen demand (COD) and total organic carbon (TOC) was observed under the action of ozone alone and the feasibility of deep mineralisation (organic matter removal more than 90% in 120 min under the following experimental conditions: liquid volume 9L; superficial gas velocity 6.8x10(-3) m s(-1); ozone partial pressure 1.31 kPa; initial COD 328 mg L(-1); initial TOC 127 mg L(-1)) was demonstrated. The monitoring of pH, redox potential (ORP) and the mean oxidation number of carbon (MOC) was correlated with the oxidation and mineralisation of the organic species in the water. The ozonation of cork-processing water in the bubble column was analysed in terms of a mole balance coupled with ozonation kinetics modelled by the two-film theory of mass transfer and chemical reaction. Under the experimental conditions used, and in contrast with the literature, it was determined that the reaction follows a fast kinetic regime at the beginning of the oxidation process, shifting to the moderate and the slow kinetic regimes at later stages of the oxidation reaction. The dynamic change of the rate coefficient estimated by the model was correlated to changes in the water composition.