The intermolecular interactions and structural features in crystals of seven halogenated N‐benzylideneanilines (Schiff bases), all of which exhibit remarkable flexibility, were examined to identify ...the common packing features that are the raison d’être for the observed elasticity. The following two features, in part related, were identified as essential to obtain elastic organic crystals: 1) A multitude of weak and dispersive interactions, including halogen bonds, which may act as structural buffers for deformation through easy rupture and reformation during bending; and 2) corrugated packing patterns that would get interlocked and, in the process, prevent long‐range sliding of molecular planes.
Slinky springs: Elastic organic crystals may be designed by selecting molecules that are likely to adopt isotropic packing with weak and only moderately polar interactions. The restorative ability of halogen bonds upon application of stress is particularly relevant in this context and is used in this family of Schiff bases.
The increased prevalence of diabetes and associated complications presents a major health risk worldwide, and requires an efficient management protocol. Type-1 and type-2 diabetes have several common ...pathophysiological denominators including hyperglycemia, elevated oxidative stress, increased inflammation and apoptosis. These pathological factors are implicated in the progression and worsening of the disease, and the related cardiometabolic complications associated with it. Despite the advancement in management of type-1 and type-2 diabetes, the high incidence of diabetes and related complications calls for novel therapeutic strategies. Recent findings suggest that the pharmacological modulation of the microsomal heme oxygenase (HO) system may be an important therapeutic avenue to explore. The HO system and related products such as carbon monoxide, bilirubin, biliverdin, biliverdin reductase and ferritin have been shown to abate inflammation, oxidative stress, and apoptosis and reduce hyperglycemia. In addition, the HO system also enhances insulin sensitivity and increase pancreatic beta cell insulin production in experimental models of type-1 and type-2 diabetes. This review is an effort to provide evidence of the regulatory and cytoprotective role of the HO system in type-1 and type-2 diabetes, and will highlight the multifaceted mechanisms implicated in the anti-diabetic effects of the HO system.
Ibuprofen, an inhibitor of prostanoid biosynthesis, is a common pharmacological agent used for the management of pain, inflammation and fever. However, the chronic use of ibuprofen at high doses is ...associated with increased risk for cardiovascular, renal, gastrointestinal and liver injuries. The underlying mechanisms of ibuprofen-mediated effects on liver remain unclear. To determine the mechanisms and signaling pathways affected by ibuprofen (100 mg/kg/day for seven days), we performed proteomic profiling of male mice liver with quantitative liquid chromatography tandem mass spectrometry (LC-MS/MS) using ten-plex tandem mass tag (TMT) labeling. More than 300 proteins were significantly altered between the control and ibuprofen-treated groups. The data suggests that several major pathways including (1) energy metabolism, (2) protein degradation, (3) fatty acid metabolism and (4) antioxidant system are altered in livers from ibuprofen treated mice. Independent validation of protein changes in energy metabolism and the antioxidant system was carried out by Western blotting and showed sex-related differences. Proteasome and immunoproteasome activity/expression assays showed ibuprofen induced gender-specific proteasome and immunoproteasome dysfunction in liver. The study observed multifactorial gender-specific ibuprofen-mediated effects on mice liver and suggests that males and females are affected differently by ibuprofen.
In the context of processing of molecular solids, especially pharmaceuticals, hardness is an important property that often determines the manufacturing steps employed. Through nanoindentation studies ...on a series of omeprazole polymorphs, in which the proportions of the 5- and 6-methoxy tautomers vary systematically, we demonstrate that solid-solution strengthening can be effectively employed to engineer the hardness of organic solids. High hardness can be attained by increasing lattice resistance to shear sliding of molecular layers during plastic deformation.
We demonstrate the synthesis of polysiloxane-modified inorganic-oxide nanoparticles comprising a TiO2-based pigment (Ti-Pure R-706), which undergo drastic wettability reversal from a hydrophilic wet ...state to a hydrophobic state upon drying. Furthermore, the dry hydrophobic pigment particles can be reversibly converted back to a hydrophilic form by the application of high shear aqueous milling. Our synthetic approach involves first condensing the cross-linking monomer CH3Si(OH)3 onto the surface of Ti-Pure R-706 at pH 9.5 ± 0.2 in an aqueous suspension. After drying this surface-modified material in the presence of a polyanionic dispersant so as to preserve the primary particle size via dynamic light scattering, it is trimethylsilyl-capped with (CH3)3SiOH, which consumes some residual Si-OH functionalities, and washed to remove all dispersant and excess reagents. Transmission electron microscopy demonstrates a ∼6 nm polysiloxane coating uniformly surrounding the surface of the pigment particle. A 70 wt % (37 vol %) concentrated aqueous slurry of the hydrophobically modified pigment particles prepared in the absence of dispersant exhibits rheological characteristics that are nearly the same as an aqueous dispersion of native unmodified hydrophilic Ti-Pure R-706 comprising an optimal amount of the organic anionic dispersant. It is also possible to synthesize dispersions without the use of an added surfactant and/or dispersant at even higher solid concentrations of up to 75 wt % (43 vol %) in water, conditions at which even the hydrophilic native Ti-Pure R-706 oxide pigment yields a gel-like paste in the absence of a dispersant. Films prepared by drying an aqueous suspension of these pigment particles exhibited a hydrophobic contact angle of ∼125°. When acrylic-based waterborne coatings were prepared comprising these surface-modified Ti Pure R-706 pigments, they showed excellent corrosion protection of a mild steel substrate. These data point to a wettability reversal in which the particles change from hydrophobic to hydrophilic upon high-shear aqueous milling and vice versa upon drying. 29Si CP/MAS NMR spectroscopy highlights the importance of flexibility of the polysiloxane coating for achieving this wettability reversal, a result that emphasizes the importance of surface reconstruction.
Curcumin and sulfathiazole exist as three and five polymorphs, respectively. We correlate solubility and mechanical properties in these polymorphic systems. It is seen that hardness (H) is inversely ...proportional to the solubility of a polymorph. H of the polymorphs is explained on the basis of slip planes in the crystal structure, the Schmid factor (m), and the relative orientation of molecules with respect to the nanoindenter direction. Effectively, H is a useful parameter (compared to melting point, T m , and density, ρ) that correlates well with the solubility of a polymorph. Such a correlation is helpful in systems like curcumin and sulfathiazole in which the Gibbs free energy of the polymorphs are close to one another. To summarize, a softer polymorph is more soluble.
Immunoassays such as ELISAs and Western blotting have been the common choice for protein validation studies for the past several decades. Technical advancements and modifications are continuously ...being developed to enhance the detection sensitivity of these procedures. Among them, Streptavidin‐containing poly‐horseradish peroxidase (PolyHRP) based detection strategies have been shown to improve signals in ELISA. The use of commercially available Streptavidin and antibodies conjugated with many HRPs (PolyHRPs) to potentially enhance the detection sensitivity in Western blotting has not been previously investigated in a comprehensive manner. The use of PolyHRP‐secondary antibody instead of HRP‐secondary antibody increased the Western blotting sensitivity up to 85% depending on the primary antibody used. The use of a biotinylated secondary antibody and commercially available Streptavidin‐conjugated with HRP or PolyHRP all resulted in increased sensitivity with respect to antigen detection. Utilizing a biotinylated secondary antibody and Streptavidin‐conjugated PolyHRP resulted in as much as a 110‐fold increase in Western blotting sensitivity over traditional Western blotting methods. Quantification of troponin I in rat heart lysates showed that the traditional Western blotting method only detected troponin I in ≥2 μg of lysate while Streptavidin‐conjugated PolyHRP20 detected troponin I in ≥50 ng of lysate. A modified blocking procedure is also described that eliminated the interference caused by the endogenous biotinylated proteins. These results suggest that Streptavidin‐conjugated PolyHRP and PolyHRP secondary antibodies are likely to be commonly utilized for Western blots in the future.
Abstract
The Indian Environmental Radiation Monitoring Network continuously monitors, throughout India, the absorbed dose rate in air due to outdoor natural gamma radiation, by using Geiger–Mueller ...detector-based standalone environmental radiation monitors. The network consists of 546 monitors spread across 91 monitoring locations distributed all over the country. In this paper, the countrywide long-term monitoring results are summarised. The measured mean dose rate of the monitoring locations followed a log-normal distribution and ranged from 50 to 535 nGy.h−1 with a median value of 91 nGy.h−1. Due to outdoor natural gamma radiation, the average annual effective dose was estimated to be 0.11 mSv.y−1.
Diabetic retinopathy remains one of the most debilitating chronic complications, but despite extensive research in the field, the exact mechanism(s) responsible for how retina is damaged in diabetes ...remains ambiguous. Many metabolic pathways have been implicated in its development, and genes associated with these pathways are altered. Diabetic environment also facilitates epigenetics modifications, which can alter the gene expression without permanent changes in DNA sequence. The role of epigenetics in diabetic retinopathy is now an emerging area, and recent work has shown that genes encoding mitochondrial superoxide dismutase (Sod2) and matrix metalloproteinase-9 (MMP-9) are epigenetically modified, activates of epigenetic modification enzymes, histone lysine demethylase 1 (LSD1), and DNA methyltransferase are increased, and the micro RNAs responsible for regulating nuclear transcriptional factor and VEGF are upregulated. With the growing evidence of epigenetic modifications in diabetic retinopathy, better understanding of these modifications has potential to identify novel targets to inhibit this devastating disease. Fortunately, the inhibitors and mimics targeted towards histone modification, DNA methylation, and miRNAs are now being tried for cancer and other chronic diseases, and better understanding of the role of epigenetics in diabetic retinopathy will open the door for their possible use in combating this blinding disease.
A systematic mapping of natural absorbed dose rate was carried out to assess the existing exposure situation in India. The mammoth nationwide survey covered the entire terrestrial region of the ...country comprising of 45127 sampling grids (grid size 36 km2) with more than 100,000 data points. The data was processed using Geographic Information System. This study is based on established national and international approaches to provide linkage with conventional geochemical mapping of soil. Majority (93%) of the absorbed dose rate data was collected using handheld radiation survey meters and remaining were measured using environmental Thermo Luminescent Dosimeters. The mean absorbed dose rate of the entire country including several mineralized regions, was found to be 96 ± 21 nGy/h. The median, Geometric Mean and Geometric Standard Deviation values of absorbed dose rate were 94, 94 and 1.2 nGy/h, respectively. Among the High Background Radiation Areas of the country, absorbed dose rate varied from 700 to 9562 nGy/h in Karunagappally area of Kollam district, Kerala. The absorbed dose rate in the present nationwide study is comparable with the global database.
•Mapping of gamma radiation levels carried out to assess existing exposure situation.•Nationwide survey comprised of more than 100,000 data points processed using GIS.•Mean absorbed gamma dose rate was 96 ± 21 nGy/h with median of 94 nGy/h.•Highest background radiation of 9562 nGy/h was in Karunagappally, Kerala.•This national dose rate map will help scientific community and decision makers.
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