Postpolymerization modification of a hydroxy monolith precursor. Part II. Epoxy biphenyl modified poly (hydroxyethyl methacrylate‐co‐pentaerythritol triacrylate) monolithic capillary columns for reversed‐phase capillary electrochromatography based on π–π and hydrophobic interactions

In this second part of the series of investigations involving the postpolymerization modification of a hydroxy monolith (OHM) capillary column, the surface hydroxyl groups were reacted with epoxy biphenyl thus yielding the so‐called Biphenyl OHM capillary column. The modification involved the epoxy ring opening of the 2‐biphenylyl glycidyl ether catalyzed by BF₃ and its subsequent reaction with the hydroxyl groups on the OHM precursor surface. The Biphenyl OHM capillary column thus obtained exhibited the typical reversed phase behavior by primarily hydrophobic interactions vis‐à‐vis the homologous series of alkyl benzenes and in addition by π–π interactions toward nitroalkane homologous series via their π‐electron rich nitro groups. This dual retention mechanism was very distinctly observed with a set of PAH solutes in the sense that the k values of the PAH solutes were comparable to those obtained on a more non polar stationary phase, namely the Epoxy OHM C‐16 reported in the preceding article. Other aromatic solutes showed the dual retention mechanism on the Biphenyl OHM capillary including phenols, anilines derivatives, and phenoxy acid herbicides. The Biphenyl OHM capillary exhibited good reproducibility from run‐to‐run, day‐to‐day, and column‐to‐column.     

Affinity monolithic capillary columns for glycomics/proteomics: 1. Polymethacrylate monoliths with immobilized lectins for glycoprotein separation by affinity capillary electrochromatography and affinity nano-liquid chromatography in either a single column or columns coupled in series

In this report, microcolumn separation schemes involving monolithic capillary columns with immobilized lectins, and relevant to nanoglycomics/nanoproteomics were introduced. Positive and neutral monoliths based on poly(glycidyl methacrylate-co-ethylene dimethacrylate) were designed for achieving lectin affinity chromatography (LAC) by nano-LC and CEC. The positive monoliths (i.e., monoliths with cationic sites) afforded relatively high permeability in nano-LC but lack predictable EOF magnitude and direction, while neutral monoliths provided a good compromise between reasonable permeability in nano-LC and predictable EOF in CEC. Lectin affinity nano-LC permitted the enrichment of classes of different glycoproteins having similar N-glycans recognized by the immobilized lectin, whereas lectin affinity CEC provided the simultaneous capturing and separation of different glycoproteins due to differences in charge-to-mass ratio. Also, this investigation demonstrated for the first time the coupling of lectin capillary columns in series (i.e., tandem columns) for enhanced separation of glycoproteins by LAC using the CEC modality. Furthermore, in the coupled columns format, glycoforms of a given glycoprotein were readily separated.     

Analytical Expressions for the Mixed-Order Kinetics Parameters of TL Glow Peaks Based on the two Heating Rates Method

The two heating rates method (originally developed for first-order glow peaks) was used for the first time to evaluate the activation energy (E) from glow peaks obeying mixed-order (MO) kinetics. The derived expression for E has an insignificant additional term (on the scale of a few meV) when compared with the first-order case. Hence, the original expression for E using the two heating rates method can be used with excellent accuracy in the case of MO glow peaks. In addition, we derived a simple analytical expression for the MO parameter. The present procedure has the advantage that the MO parameter can now be evaluated using analytical expression instead of using the graphical representation between the geometrical factor and the MO parameter as given by the existing peak shape methods. The applicability of the derived expressions for real samples was demonstrated for the glow curve of Li₂B₄O₇:Mn single crystal. The obtained parameters compare very well with those obtained by glow curve fitting and with the available published data.     

Synthesis,characterization, dielectric and rectification properties of PANI/Nd2O3:Al2O3 nanocomposites

Polyaniline–Nd₂O₃:Al₂O₃ nanocomposites were prepared by in situ oxidative polymerization method using different weight percentages of oxide powders. The prepared nanocomposites were characterized by Fourier transform infrared spectroscopy and X‐ray diffraction for molecular and crystal structures. Scanning electron microscopy and transmission electron microscopy images show the tubular structure of polyaniline nanocomposite with embedded metal oxides. The electrical conductivity of the nanocomposites increases with increase in temperature as well as with concentration of Nd₂O₃:Al₂O₃ particles in polyaniline. This is because of the hopping of charge polarons and extended chain length of the nanocomposites as evidenced by the negative thermal coefficient (NTC) characteristic. A high NTC value of 2.67 was found in nanocomposites with 15 wt% of oxide particles. These nanocomposites show low dielectric constant and dielectric loss; the electrical conductivity is higher than 0.3 S/cm as confirmed by Cole–Cole plot that indicates a decrease in both grain resistance and bulk resistance of the nanocomposites. The current–voltage and capacitance–voltage measurements were also carried out. The carrier mobility μ values of pure polyaniline and nanocomposites were found to be 4.27 × 10^?3 and 1.45 × 10^–2 H.M^?1, respectively. A significant enhancement in carrier mobility was observed in comparison with the literature. Copyright © 2016 John Wiley & Sons, Ltd.     

Impedance study of polymethyl methacrylate composites/multi-walled carbon nanotubes (PMMA/MWCNTs)

The dielectric behavior of polymethyl methacrylate/multi-walled carbon nanocomposites (PMMA/MWCNTs) was investigated using impedance spectroscopy technique. The composites were prepared using melt mixing with MWCNTs loading ranging from 0.01 to 10 wt%. The experimental results showed that the measured impedance reflects the insulating behavior of the host material (PMMA) with no appreciable effects of the filler less than 8.5 wt%. However, for the sample containing 10 wt%, the calculated value of dc conductivity increases with increasing temperature from 2.0×10⁻⁶ (Ω m)⁻¹ to attain a value of 4.8×10⁻⁶ (Ω m)⁻¹ at 110 °C. The percolation threshold derived from the dielectric data was estimated to be higher than 8.5 wt% and lower than 10 wt%. A temperature dependent electrical relaxation phenomenon was only observed in the sample containing 10 wt% of MWCNTs. The frequency dependence of the ac conductivity data followed a power law.     

Screening an In-House Isoquinoline Alkaloids Library for New Blockers of Voltage-Gated Na+ Channels Using Voltage Sensor Fluorescent Probes: Hits and Biases

Voltage-gated Na⁺ (Na_V) channels are significant therapeutic targets for the treatment of cardiac and neurological disorders, thus promoting the search for novel Na_V channel ligands. With the objective of discovering new blockers of Na_V channel ligands, we screened an In-House vegetal alkaloid library using fluorescence cell-based assays. We screened 62 isoquinoline alkaloids (IA) for their ability to decrease the FRET signal of voltage sensor probes (VSP), which were induced by the activation of Na_V channels with batrachotoxin (BTX) in GH3b6 cells. This led to the selection of five IA: liriodenine, oxostephanine, thalmiculine, protopine, and bebeerine, inhibiting the BTX-induced VSP signal with micromolar IC₅₀. These five alkaloids were then assayed using the Na⁺ fluorescent probe ANG-2 and the patch-clamp technique. Only oxostephanine and liriodenine were able to inhibit the BTX-induced ANG-2 signal in HEK293-hNa_V1.3 cells. Indeed, liriodenine and oxostephanine decreased the effects of BTX on Na⁺ currents elicited by the hNa_V1.3 channel, suggesting that conformation change induced by BTX binding could induce a bias in fluorescent assays. However, among the five IA selected in the VSP assay, only bebeerine exhibited strong inhibitory effects against Na⁺ currents elicited by the hNav1.2 and hNav1.6 channels, with IC₅₀ values below 10 µM. So far, bebeerine is the first BBIQ to have been reported to block Na_V channels, with promising therapeutical applications.     

The Pathophysiology of Long COVID throughout the Renin-Angiotensin System

COVID-19 has expanded across the world since its discovery in Wuhan (China) and has had a significant impact on people’s lives and health. Long COVID is a term coined by the World Health Organization (WHO) to describe a variety of persistent symptoms after acute SARS-CoV-2 infection. Long COVID has been demonstrated to affect various SARS-CoV-2-infected persons, independently of the acute disease severity. The symptoms of long COVID, like acute COVID-19, consist in the set of damage to various organs and systems such as the respiratory, cardiovascular, neurological, endocrine, urinary, and immune systems. Fatigue, dyspnea, cardiac abnormalities, cognitive and attention impairments, sleep disturbances, post-traumatic stress disorder, muscle pain, concentration problems, and headache were all reported as symptoms of long COVID. At the molecular level, the renin-angiotensin system (RAS) is heavily involved in the pathogenesis of this illness, much as it is in the acute phase of the viral infection. In this review, we summarize the impact of long COVID on several organs and tissues, with a special focus on the significance of the RAS in the disease pathogenesis. Long COVID risk factors and potential therapy approaches are also explored.     

Capillary electrochromatography with monolithic stationary phases. II. Preparation of cationic stearyl-acrylate monoliths and their electrochromatographic characterization

A novel cationic monolithic stationary phase based on the co-polymerization of pentaerythritol diacrylate monostearate (PEDAS) with a selected quaternary amine acrylic monomer was designed for performing capillary electrochromatography at high flow velocity. While PEDAS functioned as both the ligand provider and the cross-linker, the quaternary amine acrylic monomer was introduced to control the magnitude of the electroosmotic flow (EOF). The fabrication of the cationic stearyl-acrylate monolith (designated as cationic C17 monolith) with controlled porosity was achieved by free radical polymerization using the initiator 2,2'-azobisisobutyronitrile in the presence of a ternary porogenic solvent composed of cyclohexanol, ethylene glycol and water. Four different quaternary amine acrylic monomers were investigated in order to find the optimum monomer for achieving maximum electroosmotic flow (EOF) velocity. Both photo- and thermally-initiated polymerization proved effective in producing the cationic C17 monolith, and the best monolith was achieved when [2-(acryloyloxy)ethyl]trimethyl ammonium methyl sulfate (AETA) was used as the quaternary amine acrylic monomer. Although the zeta potential of the resulting cationic C17 monolith is positive with respect to water, the magnitude and direction of the EOF was markedly affected by the nature of the electrolyte in the mobile phase. Consequently, anodal, zero or cathodal EOF was observed depending on the nature of the electrolyte, and this was attributed to the adsorption of the ionic components of the electrolyte on to the solid stationary phase, which is characterized by its amphiphilic nature consisting of C17 chains, ester functions, hydroxyl groups and quaternary amine moieties. Optimized PEDAS-AETA monoliths yielded columns with high separation efficiency and allowed rapid separations on the time scale of seconds to be achieved with short capillaries.