N-Acetyl Cysteine,Selenium, and Ascorbic Acid Rescue Diabetic Cardiac Hypertrophy via Mitochondrial-Associated Redox Regulators

Metabolic disorders often lead to cardiac complications. Metabolic deregulations during diabetic conditions are linked to mitochondrial dysfunctions, which are the key contributing factors in cardiac hypertrophy. However, the underlying mechanisms involved in diabetes-induced cardiac hypertrophy are poorly understood. In the current study, we initially established a diabetic rat model by alloxan-administration, which was validated by peripheral glucose measurement. Diabetic rats displayed myocardial stiffness and fibrosis, changes in heart weight/body weight, heart weight/tibia length ratios, and enhanced size of myocytes, which altogether demonstrated the establishment of diabetic cardiac hypertrophy (DCH). Furthermore, we examined the expression of genes associated with mitochondrial signaling impairment. Our data show that the expression of PGC-1α, cytochrome c, MFN-2, and Drp-1 was deregulated. Mitochondrial-signaling impairment was further validated by redox-system dysregulation, which showed a significant increase in ROS and thiobarbituric acid reactive substances, both in serum and heart tissue, whereas the superoxide dismutase, catalase, and glutathione levels were decreased. Additionally, the expression levels of pro-apoptotic gene PUMA and stress marker GATA-4 genes were elevated, whereas ARC, PPARα, and Bcl-2 expression levels were decreased in the heart tissues of diabetic rats. Importantly, these alloxan-induced impairments were rescued by N-acetyl cysteine, ascorbic acid, and selenium treatment. This was demonstrated by the amelioration of myocardial stiffness, fibrosis, mitochondrial gene expression, lipid profile, restoration of myocyte size, reduced oxidative stress, and the activation of enzymes associated with antioxidant activities. Altogether, these data indicate that the improvement of mitochondrial dysfunction by protective agents such as N-acetyl cysteine, selenium, and ascorbic acid could rescue diabetes-associated cardiac complications, including DCH.     

Discovery of Potential Antiviral Compounds against Hendra Virus by Targeting Its Receptor-Binding Protein (G) Using Computational Approaches

Hendra virus (HeV) belongs to the paramyxoviridae family of viruses which is associated with the respiratory distress, neurological illness, and potential fatality of the affected individuals. So far, no competitive approved therapeutic substance is available for HeV. For that reason, the current research work was conducted to propose some novel compounds, by adopting a Computer Aided Drug Discovery approach, which could be used to combat HeV. The G attachment Glycoprotein (Ggp) of HeV was selected to achieve the primary objective of this study, as this protein makes the entry of HeV possible in the host cells. Briefly, a library of 6000 antiviral compounds was screened for potential drug-like properties, followed by the molecular docking of short-listed compounds with the Protein Data Bank (PDB) structure of Ggp. Docked complexes of top two hits, having maximum binding affinities with the active sites of Ggp, were further considered for molecular dynamic simulations of 200 ns to elucidate the results of molecular docking analysis. MD simulations and Molecular Mechanics Energies combined with the Generalized Born and Surface Area (MMGBSA) or Poisson–Boltzmann and Surface Area (MMPBSA) revealed that both docked complexes are stable in nature. Furthermore, the same methodology was used between lead compounds and HeV Ggp in complex with its functional receptor in human, Ephrin-B2. Surprisingly, no major differences were found in the results, which demonstrates that our identified compounds can also perform their action even when the Ggp is attached to the Ephrin-B2 ligand. Therefore, in light of all of these results, we strongly suggest that compounds (S)-5-(benzylcarbamoyl)-1-(2-(4-methyl-2-phenylpiperazin-1-yl)-2-oxoethyl)-6-oxo-3,6-dihydropyridin-1-ium-3-ide and 5-(cyclohexylcarbamoyl)-1-(2-((2-(3-fluorophenyl)-2-methylpropyl)amino)-2-oxoethyl)-6-oxo-3,6-dihydropyridin-1-ium-3-ide could be considered as potential therapeutic agents against HeV; however, further in vitro and in vivo experiments are required to validate this study.     

Multiple methoxy-substituted hole transporter for inverted perovskite solar cells

Inverted organic-inorganic hybrid perovskite solar cells(i-PSC)with low temperature processed interlayers and weak hysteresis behaviors have shown great potential for commercialization[1-5].However,their relatively lower power conversion efficiency(PCE)and inferior reproducibility than conventional PSCs limit further developments.These problems are largely determined by the hole transporting layer(HTL)and the quality of the upper perovskite film[6-8];in particular,the latter is considerably influenced by the surface property of the underlying HTL.     

Open-air green-light-driven ATRP enabled by dual photoredox/copper catalysis

Photoinduced atom transfer radical polymerization (photo-ATRP) has risen to the forefront of modern polymer chemistry as a powerful tool giving access to well-defined materials with complex architecture. However, most photo-ATRP systems can only generate radicals under biocidal UV light and are oxygen-sensitive, hindering their practical use in the synthesis of polymer biohybrids. Herein, inspired by the photoinduced electron transfer-reversible addition–fragmentation chain transfer (PET-RAFT) polymerization, we demonstrate a dual photoredox/copper catalysis that allows open-air ATRP under green light irradiation. Eosin Y was used as an organic photoredox catalyst (PC) in combination with a copper complex (X–Cu^II/L). The role of PC was to trigger and drive the polymerization, while X–Cu^II/L acted as a deactivator, providing a well-controlled polymerization. The excited PC was oxidatively quenched by X–Cu^II/L, generating Cu^I/L activator and PC˙⁺. The ATRP ligand (L) used in excess then reduced the PC˙⁺, closing the photocatalytic cycle. The continuous reduction of X–Cu^II/L back to Cu^I/L by excited PC provided high oxygen tolerance. As a result, a well-controlled and rapid ATRP could proceed even in an open vessel despite continuous oxygen diffusion. This method allowed the synthesis of polymers with narrow molecular weight distributions and controlled molecular weights using Cu catalyst and PC at ppm levels in both aqueous and organic media. A detailed comparison of photo-ATRP with PET-RAFT polymerization revealed the superiority of dual photoredox/copper catalysis under biologically relevant conditions. The kinetic studies and fluorescence measurements indicated that in the absence of the X–Cu^II/L complex, green light irradiation caused faster photobleaching of eosin Y, leading to inhibition of PET-RAFT polymerization. Importantly, PET-RAFT polymerizations showed significantly higher dispersity values (1.14 ≤ Đ ≤ 4.01) in contrast to photo-ATRP (1.15 ≤ Đ ≤ 1.22) under identical conditions.

Fully oxygen-tolerant photoinduced atom transfer radical polymerization (photo-ATRP) allowed the synthesis of well-defined polymers using a Cu catalyst and eosin Y at ppm levels in both aqueous and organic media.     

Oligomer Sensor Nanoarchitectonics for “Turn-On” Fluorescence Detection of Cholesterol at the Nanomolar Level

Sensitive and rapid monitoring of cholesterol levels in the human body are highly desirable as they are directly related to the diagnosis of cardiovascular diseases. By using the nanoarchitectonic approach, a novel fluorescent conjugated oligofluorene (OFP-CD) functionalized with β-cyclodextrin (β-CD) was assembled for “Turn-On” fluorescence sensing of cholesterol. The appended β-CD units in OFP-CD enabled the forming of host-guest complexes with dabsyl chloride moieties in water, resulting in fluorescence quenching of the oligofluorene through intermolecular energy transfer. In the presence of cholesterol molecules, a more favorable host-guest complex with stoichiometry 1 cholesterol: 2 β-CD units was formed, replacing dabsyl chloride in β-CD’s cavities. This process resulted in fluorescence recovery of OFP-CD, owing to disruption of energy transfer. The potential of this nanoarchitectonic system for “Turn-On” sensing of cholesterol was extensively studied by fluorescence spectroscopy. The high selectivity of the sensor for cholesterol was demonstrated using biologically relevant interfering compounds, such as carbohydrates, amino acids, metal ions, and anions. The detection limit (LOD value) was as low as 68 nM, affirming the high sensitivity of the current system.     

Recent synthetic strategies toward the synthesis of spirocyclic compounds comprising six-membered carbocyclic/heterocyclic ring systems

Molecular Diversity - Spirocyclic compounds fascinate the synthetic chemists due to their privileged ring system and efficacy in drug discovery. Many natural compounds comprise spirocyclic moiety...     

Spin density polarization effects in the presence of Coriolis force on ion acoustic waves in quantum plasma

Ion acoustic solitary waves in a quantum plasma, which is slowly rotating around an axis at an angle θ with the direction of magnetic field, are investigated. Quantum hydrodynamic model is under consideration with the effects of rotations which are included via Coriolis force. Fermions are degenerate and have different spin density states, that is, up and down characterized via parameter α. Linear analysis is performed by applying Fourier transformation to derive dispersion relation. For nonlinear analysis, we apply reductive perturbation method to derive Korteweg de Vries equation (KdV). The effects of variations of Coriolis force, spin polarization, and quantum parameter on characteristics of solitary structure are discussed. These results are applicable to astrophysical and laboratory plasmas.     

Toward a modeling study of thermal conductivity of nanofluids using LSSVM strategy

Journal of Thermal Analysis and Calorimetry - In the present study, a comprehensive model based on least square support vector machine algorithm (LSSVM) was developed to estimate thermal...