Synthesis,crystallographic and spectroscopic studies,evaluation as antimicrobial and cytotoxic agents of a novel mixed-ligand nickel(II) complex

A new mononuclear mixed-ligand complex of Ni(II) has been synthesized and structurally characterized by single-crystal X-ray diffraction as [Ni(4-Cl-pydc)(apym)(H₂O)₂], where 4-Cl-pydc and apym are 4-chloropyridine-26-dicarboxylate and 2-aminopyrimidine, respectively. Spectroscopic studies such as FT-IR, UV-vis, ¹H-NMR, and thermal analysis (TGA/DTA) were carried out. The fluorescence properties were studied in solvents with different dipole moments. Antimicrobial activities of 4-chloropyridine-26-dicarboxylic acid (1), 2-aminopyrimidine (2), complex (3), and nickel(II) nitrate hexahydrate (4) were investigated by disk diffusion and broth microdilution methods against three Gram-positive bacteria, Staphylococcus aureus, Bacillus subtilis, Staphylococcus epidermidis and three Gram-negative bacteria, Escherichia coli, Pseudomonas aeruginosa, S. marcescens; also antifungal effect was evaluated on Aspergillus niger and Saccharomyces cerevisiae in vitro. The highest antibacterial activity of complex was observed nearly equal to gentamicin as a standard drug toward S. epidermids with IZD of 18 mm. The in vitro antiproliferative activity of 1–4 on H1299 (a human non-small cell lung carcinoma), HepG2 (a human liver hepatocellular carcinoma), and β-TC3 (a mouse beta pancreatic) cell lines was evaluated by MTT (3-(45-dimethylthiazol-2-yl)-25-diphenyl-2H-tetrazolium bromide) assay and, effect of complex on depolarization of mitochondrial membrane (MMP) of all three cell lines was measured by rhodamine 123. The highest cytotoxic effect of complex was exhibited toward H1299 cell line with IC₅₀ value equal to 10 μM.     

Polyphenol-Enriched Blueberry Preparation Controls Breast Cancer Stem Cells by Targeting FOXO1 and miR-145

Scientific evidence supports the early deregulation of epigenetic profiles during breast carcinogenesis. Research shows that cellular transformation, carcinogenesis, and stemness maintenance are regulated by epigenetic-specific changes that involve microRNAs (miRNAs). Dietary bioactive compounds such as blueberry polyphenols may modulate susceptibility to breast cancer by the modulation of CSC survival and self-renewal pathways through the epigenetic mechanism, including the regulation of miRNA expression. Therefore, the current study aimed to assay the effect of polyphenol enriched blueberry preparation (PEBP) or non-fermented blueberry juice (NBJ) on the modulation of miRNA signature and the target proteins associated with different clinical-pathological characteristics of breast cancer such as stemness, invasion, and chemoresistance using breast cancer cell lines. To this end, 4T1 and MB-MDM-231 cell lines were exposed to NBJ or PEBP for 24 h. miRNA profiling was performed in breast cancer cell cultures, and RT-qPCR was undertaken to assay the expression of target miRNA. The expression of target proteins was examined by Western blotting. Profiling of miRNA revealed that several miRNAs associated with different clinical-pathological characteristics were differentially expressed in cells treated with PEBP. The validation study showed significant downregulation of oncogenic miR-210 expression in both 4T1 and MDA-MB-231 cells exposed to PEBP. In addition, expression of tumor suppressor miR-145 was significantly increased in both cell lines treated with PEBP. Western blot analysis showed a significant increase in the relative expression of FOXO1 in 4T1 and MDA-MB-231 cells exposed to PEBP and in MDA-MB-231 cells exposed to NBJ. Furthermore, a significant decrease was observed in the relative expression of N-RAS in 4T1 and MDA-MB-231 cells exposed to PEBP and in MDA-MB-231 cells exposed to NBJ. Our data indicate a potential chemoprevention role of PEBP through the modulation of miRNA expression, particularly miR-210 and miR-145, and protection against breast cancer development and progression. Thus, PEBP may represent a source for novel chemopreventative agents against breast cancer.     

A note on the hidden conformal structure of non-extremal black holes

We study, following Bertini et al. [1], the hidden conformal symmetry of the massless Klein–Gordon equation in the background of the general, charged, spherically symmetric, static black-hole solution of a class of d  -dimensional Lagrangians which includes the relevant parts of the bosonic Lagrangian of any ungauged supergravity. We find that a hidden SL(2,R)$\mathit{SL}(2,\mathbb{R})$ symmetry appears at the near event- and Cauchy-horizon limits. We extend the two sl(2)$\mathfrak{sl}(2)$ algebras to two full Witt algebras (Virasoro algebras with vanishing central charges). We comment on the implications of the possible existence of an associated quantum conformal field theory.     

Noninvasive estimation of the ocular elastic modulus for age-related macular degeneration in the human eye using sequential ultrasound imaging

Introduction

Elastic modulus estimation may be an important clinical criterion, as it seems to affect such eye parameters as intraocular pressure, ocular pulsation, blood flow, effect of topical medications, and post-refractive surgery complications. The purpose of this study was to examine the differences in elasticity in the ocular axial length, posterior wall thickness (posterior pole), and retina-choroid thickness under normal and aged-related macular degeneration (AMD) conditions in the human eye by directly estimating the elastic modulus with sequential and noninvasive ultrasound image processing.

Materials and Methods

In this study, 25 healthy subjects and 20 patients with non-neovascular AMD participated in the experiment. The deformation of the ocular axial length, posterior wall thickness and retina-choroid complex thickness was captured using high-resolution ultrasonography before and after loading. The B-mode (20 MHz) and A-mode (8 MHz) frames were obtained and processed with an echo tracking technique. The elastic modulus was estimated using changes in ocular axial length, posterior wall thickness and retina-choroid complex thickness and with applied stress measurements.

Results

There was a significant difference (p < 0.05) in the ocular axial length elastic modulus between the AMD and healthy subjects (AMD patients: 95.165 ± 26.431 kPa, vs. healthy subjects: 49.539 ± 25.867 kPa). Moreover, there was a statistically significant difference (p < 0.05) in the posterior wall thickness elastic modulus between AMD patients and healthy subjects (AMD patients: 50.519 ± 12.295 kPa, vs. healthy subjects: 20.519 ± 11.827 kPa). However, no statistically significant difference (p-value > 0.05) was found in the retina-choroid complex elastic modulus between the two groups (AMD patients: 20.134 ± 3.898 kPa, vs. healthy subjects: 15.630 ± 4.250 kPa).

Conclusion

Although the results were obtained examining a relatively low number of patients, it would appear that noninvasive ultrasound estimation of the local elastic moduli of ocular axial length and posterior wall thickness is suited to aid in detection of the non-exudative AMD thus manifesting its potential as a screening tool in symptom-free individuals.     

On generalized m-th root finsler metrics

In this paper, we characterize locally dually flat generalized m-th root Finsler metrics. Then we find a condition under which a generalized m-th root metric is projectively related to a m-th root metric. Finally, we prove that if a generalized m-th root metric is conformal to a m-th root metric, then both of them reduce to Riemannian metrics.     

A Facile and Effective Procedure for Synthesis of Polyfunctionalized Bis (imidazolyl) Pyrrole/Imidazolyl Indole from Pyrrole/Indole with Arylglyoxals and N‐aryl amidines

Heterocyclic systems containing bis (imidazolyl) pyrrole or imidazolyl indole moieties were synthesized by heterocyclization of pyrrole or indole with arylglyoxal monohydrates and N‐aryl amidines in ethanol catalyzed by FeCl₃ at room temperature. The paper reports a facile, efficient, and environmentally friendly protocol for the synthesis of new products. Products were isolated by simple filtration, and their structures were established from their spectroscopic data.     

Methylenedioxy Piperamide-Derived Compound D5 Regulates Inflammatory Cytokine Secretion in a Culture of Human Glial Cells

Neuroinflammation is the cornerstone of most neuronal disorders, particularly neurodegenerative diseases. During the inflammatory process, various pro-inflammatory cytokines, chemokines, and enzymes—such as interleukin 1-β (IL1-β), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), inducible nitric oxide synthases (iNOS), inhibitory kappa kinase (IKK), and inducible nitric oxide (NO)—are over-expressed in response to every stimulus. Methods: In the present study, we focused on the anti-neuroinflammatory efficacy of (2E,4E)-N,5-bis(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienamide, encoded D5. We investigated the efficacy of D5 on the upstream and downstream products of inflammatory pathways in CHME3 and SVG cell lines corresponding to human microglia and astrocytes, respectively, using various in silico, in vitro, and in situ techniques. Results: The results showed that D5 significantly reduced the level of pro-inflammatory cytokines by up-regulating PPAR-γ expression and suppressing IKK-β, iNOS, NO production, and NF-κB activation in inflamed astrocytes (SVG) and microglia (CHME3) after 24 h of incubation. The data demonstrated remarkably higher efficacy of D5 compared to ASA (Aspirin) in reducing NF-κB-dependent neuroinflammation. Conclusions: We observed that the functional-group alteration had an extreme influence on the levels of druggability and the immunomodulatory properties of two analogs of piperamide, D5, and D4 ((2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-N-(4-(hydroxymethyl)phenyl)penta-2,4-dienamide)). The present study suggested D5 as a potential anti-neuroinflammatory agent for further in vitro, in vivo, and clinical investigations.     

Application of sequential aqueous steam treatments to the fractionation of softwood

The FIRST (Feedstock Impregnation and Rapid Steam Treatment) approach was used in this study to isolate extractives, hemicellulose, lignin, fibers, and cellulosic fines of softwood. With hydrolysis and fermentation of the hemicellulose and cellulosic fines fractions, this approach produces four co-products: extractives, cellulose, lignin, and ethanol. The first unit operation uses aqueous/alcohol to remove and recover the extractive rich fraction. The second unit operation uses steam treatment to destructure the matrix and solubilize a large fraction of the hemicelluloses. The third unit operation uses alkaline delignification to dissolve a lignin fraction. The fourth unit operation uses the refining process to separate fibers from cellulosic fines. The fibers are bleached. The yields of lignin and bleached cellulose were about 20.0 kg and 38.3 kg out of 100 kg initial dry pine, respectively. The recovered hemicelluloses were 23.3 kg (containing 16.1 kg hexoses and 5.0 kg pentoses) and the cellulose fines derived hexoses amounted to 3.4 kg out of 100 kg initial dry pine. When the two liquors containing the hemicellulose sugars and the cellulose fines-derived hexoses were fermented for ethanol production, an ethanol yield of 6.8 kg was obtained.     

Multigrid algorithms for high-order discontinuous Galerkin discretizations of the compressible Navier–Stokes equations

Multigrid algorithms are developed for systems arising from high-order discontinuous Galerkin discretizations of the compressible Navier–Stokes equations on unstructured meshes. The algorithms are based on coupling both p- and h-multigrid (ph-multigrid) methods which are used in nonlinear or linear forms, and either directly as solvers or as preconditioners to a Newton–Krylov method.The performance of the algorithms are examined in solving the laminar flow over an airfoil configuration. It is shown that the choice of the cycling strategy is crucial in achieving efficient and scalable solvers. For the multigrid solvers, while the order-independent convergence rate is obtained with a proper cycle type, the mesh-independent performance is achieved only if the coarsest problem is solved to a sufficient accuracy. On the other hand, the multigrid preconditioned Newton–GMRES solver appears to be insensitive to this condition and mesh-independent convergence is achieved under the desirable condition that the coarsest problem is solved using a fixed number of multigrid cycles regardless of the size of the problem.It is concluded that the Newton–GMRES solver with the multigrid preconditioning yields the most efficient and robust algorithm among those studied.