Liquid-solid coexistence via the metadynamics approach

The metadynamics method, recently proposed by Laio and Parrinello as a general tool to map multidimensional free-energy landscapes [A. Laio and M. Parrinello, Proc. Natl. Acad. Sci. U.S.A. 99, 12562 (2002)], has been exploited with the aim of illustrating the properties of generalized thermodynamic potentials across a discontinuous phase transition. Virtues and limitations of the method are discussed in the exemplifying case of the freezing of a Lennard-Jones fluid in two dimensions.     

Effects of Visible‐Light Irradiation of Protoporphyrin IX on the Self‐Assembly of Tubulin Heterodimers

The formation and the effects of laser irradiation of the complex formed by protoporphyrin IX (PPIX) and tubulin was investigated. We have used tubulin as a model protein to investigate whether docked photoactive ligands can affect the structure and function of polypeptides upon exposure to visible light. We observed that laser irradiation in the Soret band prompts bleaching of the PPIX, which is accompanied by a sharp decrease in the intensity and average fluorescence lifetime of the protein (dominated by the four tryptophan residues of the tubulin monomer). The kinetics indicate non‐trivial effects and suggest that the photosensitization of the PPIX bound to tubulin prompts structural alterations of the protein. These modifications were also observed through changes in the energy transfer between Trp residues and PPIX. The results suggest that laser irradiation produces localized partial unfolding of tubulin and that the changes prompt modification of the formation of microtubules in vitro. Measurements of singlet oxygen formation were inconclusive in determining whether the changes are prompted by reactive oxygen species or other excited state mechanisms.     

l-Arginine Improves Solubility and ANTI SARS-CoV-2 Mpro Activity of Rutin but Not the Antiviral Activity in Cells

The COVID-19 pandemic outbreak prompts an urgent need for efficient therapeutics, and repurposing of known drugs has been extensively used in an attempt to get to anti-SARS-CoV-2 agents in the shortest possible time. The glycoside rutin shows manifold pharmacological activities and, despite its use being limited by its poor solubility in water, it is the active principle of many pharmaceutical preparations. We herein report our in silico and experimental investigations of rutin as a SARS-CoV-2 Mpro inhibitor and of its water solubility improvement obtained by mixing it with l-arginine. Tests of the rutin/l-arginine mixture in a cellular model of SARS-CoV-2 infection highlighted that the mixture still suffers from unfavorable pharmacokinetic properties, but nonetheless, the results of this study suggest that rutin might be a good starting point for hit optimization.     

Enhancement of electrochemical properties of Ca<Subscript>3</Subscript>Co<Subscript>4</Subscript>O<Subscript>9</Subscript> as anode materials for lithium-ion batteries by transition metal doping

Misfit-layered calcium cobaltites (Ca₃Co₄O₉, Ca₃Co_3.9Fe_0.1O₉, and Ca₃Co_3.9Mn_0.1O₉), as anode materials for lithium-ion batteries, were synthesized by a simple hydro-decomposition method. All synthesized samples do not show any impurity phase. They exhibited plate-like particle with the particle size of 1–2 μm. The specific capacities of doped samples showed higher electrochemical performance compared to the undoped sample. After charge/discharge of 50 cycles, the specific capacities of Ca₃Co₄O₉, Ca₃Co_3.9Fe_0.1O₉, and Ca₃Co_3.9Mn_0.1O₉ were 343, 562, and 581 mAh g^?1, respectively. The doped samples showed an increase of over 60% compared to the undoped sample. The cyclic voltammetry profile of the doped samples showed the enhanced reactivity corresponding to their improved electrochemical performance. The capacity improvement of doped samples resulted from the metal oxide/Li conversion reactions, volume change, and high reactivity.     

Nanostructures and magnetic properties of cobalt ferrite (CoFe2O4) fabricated by electrospinning

This paper describes the fabrication of cobalt ferrite (CoFe₂O₄) nanostructures (in the form of nanofibers and nanoparticles) by the electrospinning method using a solution that contained poly(vinyl pyrrolidone) (PVP) and cheap Co and Fe nitrates as metal sources. The as-spun and calcined CoFe₂O₄/PVP composite samples were characterized by TG-DTA, X-ray diffraction, FT-IR, SEM and TEM, respectively. After calcination of the as-spun CoFe₂O₄/PVP composite nanofibers (fiber size of 320±48 nm in diameter) at 500, 600, and 800°C in air for 3 h with different heating rates of 5 or 20°C/min, either NiFe₂O₄ nanofibers of ∼10−200 nm in diameter or nanoparticles with particle sizes of ∼50−400 nm having a well-developed spinel structure were successfully obtained. The crystal structure and morphology of the nanofibers were influenced by the calcination temperature and heating rate. A faster heating rate allowed for a rapid removal of the PVP matrix and resulted in a complete change from fibrous structure to particle in the calcined CoFe₂O₄/PVP composite nanofibers. Room temperature magnetization results showed a ferromagnetic behavior of the calcined CoFe₂O₄/PVP composite nanofibers, having their hysteresis loops in the field range of ± 4500 and 3000 Oe for the samples calcined respectively with heating rates of 5 and 20°C/min. The values of the specific magnetization (M _s) at 10 kOe, remnant magnetization (M _r), M _r/M _s ratio, and coercive forces (H _c) are obtained from hysteresis loops. It was found that the values of M _s, M _r, M _r/M _s, and H _c depended strongly on morphology of the CoFe₂O₄ nanostructures.     

Nanocrystalline hydroxyapatite powders by a chitosan–polymer complex solution route: Synthesis and characterization

Nanocrystalline hydroxyapatite (HAp) powders were successfully synthesized by a simple method using chitosan–polymer complex solution. To obtain HAp nanopowders, the prepared precursor was calcined in air at 400–800 °C for 2 h. The phase composition of the calcined samples was studied by X-ray diffraction (XRD) technique. The XRD results confirmed the formation of HAp phase with a small trace of monotite phase. With increasing calcination temperature, the crystallinity of the HAp increased, showing the hexagonal structure of HAp with the lattice parameter a in a range of 0.94030–0.94308 nm and c of 0.68817–0.68948 nm. The particle sizes of the powder were found to be 55.02–73.36 nm as evaluated by the XRD line broadening method. The chemical composition of the calcined powders was characterized by FTIR spectroscopy. The peaks of the phosphate carbonate and hydroxyl vibration modes were observed in the FTIR spectra for all the calcined powders. TEM investigation revealed that the prepared HAP samples consisted of rod-like nanoparticles having the particle size in the range of 100–300 nm. The corresponding selected-area electron diffraction (SAED) analysis further confirmed the formation of hexagonal structure of HAp.     

Covering by discrete and closed discrete sets

Say that a cardinal number κ is small relative to the space X if κ<Δ(X), where Δ(X) is the least cardinality of a non-empty open set in X. We prove that no Baire metric space can be covered by a small number of discrete sets, and give some generalizations. We show a ZFC example of a regular Baire σ-space and a consistent example of a normal Baire Moore space which can be covered by a small number of discrete sets. We finish with some remarks on linearly ordered spaces.     

Activating hybrid modular interfaces in synthetic polyketide synthases by cassette replacement of ketosynthase domains

Unnatural combinations of polyketide synthase modules often fail to make a polyketide product. The causes of these failures are likely complex and are not yet amenable to rational correction. One possible explanation is the inability of the ketosynthase (KS) domain to extend the ketide donated to it by the upstream module. We therefore addressed the problem by exchanging KS domains of the acceptor module in a combinatorial fashion and coexpressing these chimeric modules with ketide-donor modules that naturally interact with the transplanted KS. This approach was remarkably successful in activating previously unproductive bimodular combinations, and the results augur well for the ongoing development of molecular tools to design and produce novel polyketides.