Ecofriendly Synthesis of DHPMs using Copper-based Nano catalysts and Evaluation of Antibacterial Activity

A new catalytic approach has been developed under microwave irradiation for the multicomponent reaction (MCR) of aromatic aldehydes, urea/thiourea and ethylacetoacetate to give corresponding dihydropyrimidinones (DHPMs) by using CuFe2O4/CuO-CeO2 nanoparticles (NPs) as heterogeneous and recyclable catalysts. 3, 4-Dihydropyrimidin-2(1H) ones/thiones are synthesized in higher yields (80-95 %) and short reaction time (8−10 minutes) at 245 Watts. It is applicable for both types of aromatic aldehydes containing EWS as well as EDS. Further, the synthesized compounds were evaluated for antibacterial activity against E. coli, B. subtilis, B. megaterium, and P. vulgaris. Among the compounds tested, ethyl-6-methyl-2-oxo-4-(4-chlorophenyl)-1,2,3,4-tetrahydropyrimidin-5-carboxylate, 4c showed response against B. subtilis, B. megaterium, and P. vulgaris and ethyl-6-methyl-2-oxo-4-(4-fluorophenyl)-1,2,3,4-tetrahydropyrimidin-5-carboxylate, 4h showed –ve response against E. coli, B. subtilis, B. megaterium, and P. vulgaris

Molecular cloning of HSP17 gene (sHSP) and their differential expression under exogenous putrescine and heat shock in wheat (Triticum aestivum)

Polyamines (PAs) are low molecular weight ubiquitous nitrogenous compounds found in all the living  organisms, which have been implicated in the expression of various stress-proteins against the abiotic  stresses. Small heat shock proteins (sHSPs) are of particular importance in the thermotolerance and have  been reported to act as molecular chaperones preventing denaturation or aggregation of the target proteins. Here, we report cloning of a small HSP of ~573 bp from C-306 cultivar of wheat (Triticum aestivum L), having open reading frame of 162 amino acids. In silico analysis showed the presence of an alpha crystalline domain (ACD), the signature domain for small HSPs. Consensus localization prediction (ConLoc) provides 98%  consensus prediction of HSP17 in the nucleus. Quantitative real time polymerase chain reaction (qRT-PCR) analysis of HSP17 gene showed maximum (34 fold) transcript in C-306 and minimum (1.5 fold) in HD2329  cultivars of wheat in response to differential treatment of putrescine (1.5 to 2.5 mM + heat shock of 42°C for 2 h). Putrescine seems to enhance the transcript levels against the heat shock much more pronounced in  thermotolerant than in the susceptible cultivars.Key words: Triticum aestivum, heat stress, small heat shock protein, putrescine, HSP17, polyamine, domain, cloning

Mechanism of action of hydrogen peroxide in wheat thermotolerance - interaction between antioxidant isoenzymes, proline and cell membrane

Terminal heat stress causes an array of physiological, biochemical and morphological changes in plants, which affect plant growth and development. It has very severe effect on the pollen viability and seed setting in wheat. In the present investigation, an altered expression of H2O2 (0.9 μg/g in C-306 and 0.75 μg/g in HD2329) was observed with the highest accumulation at seed hardening stage and against heat shock (HS) of 42°C for 2 h. With the increase in H2O2 accumulation, an increase in the number of isoenzymes of superoxide dismutase and catalase were observed with high activities under differential heat shock. A decrease in the proline accumulation was observed under differential heat shock. Exogenous application of H2O2 (10 mmole/L) leads to increase in the accumulation of intracellular H2O2 and further an increase in the number of isoenzymes of superoxide dismutase (SOD) and catalase (CAT) was observed. The tolerant cultivar was more responsive to exogenous application of H2O2 compared to susceptible cultivar. The percentage decrease in cell membrane stability under differential heat shock was low in H2O2 treated plants compared to non-treated. The results from this study suggest a potential role for H2O2 in regulating the activity of antioxidant enzymes and accumulation of proline inside cells and in turn influence the cell membrane stability under heat stress. All the defense associated genes were observed to be very responsive to intracellular H2O2, which gives inference that H2O2 has regulatory role to play in controlling the expression and activities of these proteins under abiotic stresses.Key words: Antioxidant enzymes, wheat, heat stress, H2O2, proline, catalase, superoxide dismutase, cell membrane stability, reactive oxygen species

Potential of Synthetic and Natural Compounds as Novel Histone Deacetylase Inhibitors for the Treatment of Hematological Malignancies

Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are enzymes that remove or add acetyl groups to lysine residues of histones, respectively. Histone deacetylation causes DNA to more snugly encircle histones and decreases gene expression, whereas acetylation has the opposite effect. Through these small alterations in chemical structure, HATs and HDACs regulate DNA expression. Recent research indicates histone deacetylase inhibitors (HDACis) may be used to treat malignancies, including leukemia, B-cell lymphoma, virus-associated tumors, and multiple myeloma. These data suggest that HDACis may boost the production of immune-related molecules, resulting in the growth of CD8-positive T-cells and the recognition of nonreactive tumor cells by the immune system, thereby diminishing tumor immunity. The argument for employing epigenetic drugs in the treatment of acute myeloid leukemia (AML) patients is supported by evidence that both epigenetic changes and mutations in the epigenetic machinery contribute to AML etiology. Although hypomethylating drugs have been licensed for use in AML, additional epigenetic inhibitors, such as HDACis, are now being tested in humans. Preclinical studies evaluating the efficacy of HDACis against AML have shown the ability of specific agents, such as anobinostat, vorinostat, and tricostatin A, to induce growth arrest, apoptosis, autophagy and cell death. However, these inhibitors do not seem to be successful as monotherapies, but instead achieve results when used in conjunction with other medications. In this article, we discuss the mounting evidence that HDACis promote extensive histone acetylation, as well as substantial increases in reactive oxygen species and DNA damage in hematological malignant cells. We also evaluate the potential of various natural product-based HDACis as therapeutic agents to combat hematological malignancies

Anisotropic thermal transport using xSThM studies in 2D-3D heterostructures and composites

Thermal conductivity is a crucial parameter defining the thermal transport as well as thermophysical properties of materials in thermoelectric, manufacturing and processing applications of materials where heat transport plays a major role. To address a current challenge of measuring these properties locally, in the areas of few tens or hundreds nanometres, we used a novel approach of cross-sectional scanning thermal microrcopy, or SThM, (xSThM). In this method, we first create a fine low angle wedge of the studied material via precision Ar ion cross-sectional polishing [1] and then measure a thermal conductance via SThM with each measurement point providing thermal conductance of the material with different thickness. Furthermore, an analytical model is then used to extract not only anisotropic values of thermal conductivity but also determines the effect of interfacial thermal resistance between the substrate and complex structured materials (heterostructure and composite structures). This technique thus facilitates a direct measurement of thermal conductance as a function of thickness in 2D-3D based heterostructures (Sb2Te3/MoS2) and composites structures (Sb2Te3/AgSbTe2). The thickness and number of layers of MoS2 was optimized to achieve extremely lower values of thermal conductivity (0.7 0.1 Wm-1K-1) along with higher values of power factor ((4.97 0.39) ×10-3 Wm-1K-2) leading to high values of ZT of 2.08 0.37 at room temperature. Similarly, the concentration of Ag in Sb2Te3/AgSbTe2 is optimized for highest values of ZT. A major enhancement in the value of TE performance was observed due to the effective majority carriers filtering and phonon scattering at the potential barrier present due to multiple interfaces. The current methodology provides an efficient tool for quantifying the thermal transport in thin films and 2D materials, and hence is useful in establishing the thermal transport in such complex structures. References: [1] Jean Spièce, Charalambos Evangeli, Alex J. Robson, Alexandros El Sachat, Linda Haenel, M. Isabel Alonso,○ Miquel Garriga,○ Benjamin J. Robinson, Michael Oehme, Jörg Schulz, Francesc Alzina, Clivia Sotomayor Torres, Oleg V. Kolosov, Nanoscale, 24, 10829 (2021)

Tuning thermoelectric properties of Sb2_2Te3_3-AgSbTe2_2 nanocomposite thin film -- synergy of band engineering and heat transport modulation

The present study demonstrates a large enhancement in the Seebeck coefficient and ultralow thermal conductivity (TE) in Sb$_2$Te$_3$-AgSbTe$_2$ nanocomposite thin film. The addition of Ag leads to the in-situ formation of AgSbTe$_2$ secondary phase nanoaggregates in the Sb$_2$Te$_3$ matrix during the growth resulting in a large Seebeck coefficient and reduction of the thermal conductivity. A series of samples with different amounts of minor AgSbTe$_2$ phases are prepared to optimize the TE performance of Sb$_2$Te$_3$ thin films. Based on the experimental and theoretical evidence, it is concluded that a small concentration of Ag promotes the band flattening and induces a sharp resonate-like state deep inside the valence band of Sb$_2$Te$_3$, concurrently modifying the density of states (DOS) of the composite sample. In addition, the electrical potential barrier introduced by the band offset between the host TE matrix and the secondary phases promotes strong energy-dependent carrier scattering in the composite sample, which is also responsible for enhanced TE performance. A contemporary approach based on scanning thermal microscopy is performed to experimentally obtain thermal conductivity values of both the in-plane and cross-plane directions, showing a reduced in-plane thermal conductivity value by ~ 58% upon incorporating the AgSbTe$_2$ phase in the Sb$_2$Te$_3$ matrix. Benefitting from the synergistic manipulation of electrical and thermal transport, a large ZT value of 2.2 is achieved at 375 K. The present study indicates the importance of a combined effect of band structure modification and energy-dependent charge carrier scattering along with reduced thermal conductivity for enhancing TE properties

Mixed type second-order symmetric duality under F-convexity

We introduce a pair of second order mixed symmetric dual problems. Weak, strong and converse duality theorems for this pair are established under $F-$convexity assumptions

The Role of Drug–Polymer Hydrogen Bonding Interactions on the Molecular Mobility and Physical Stability of Nifedipine Solid Dispersions

We investigated the influence of drug–polymer hydrogen bonding interactions on molecular mobility and the physical stability in solid dispersions of nifedipine with each of the polymers polyvinylpyrrolidone (PVP), hydroxypropylmethyl cellulose (HPMCAS), and poly­(acrylic acid) (PAA). The drug–polymer interactions were monitored by FT-IR spectroscopy, the molecular mobility was characterized using broadband dielectric spectroscopy, and the crystallization kinetics was evaluated by powder X-ray diffractometry. The strength of drug–polymer hydrogen bonding, the structural relaxation time, and the crystallization kinetics were rank ordered as PVP > HPMCAS > PAA. At a fixed polymer concentration, the fraction of the drug bonded to the polymer was the highest with PVP. Addition of 20% w/w polymer resulted in ∼65-fold increase in the relaxation time in the PVP dispersion and only ∼5-fold increase in HPMCAS dispersion. In the PAA dispersions, there was no evidence of drug–polymer interactions and the polymer addition did not influence the relaxation time. Thus, the strongest drug–polymer hydrogen bonding interactions in PVP solid dispersions translated to the longest structural relaxation times and the highest resistance to drug crystallization

Influence of Molecular Mobility on the Physical Stability of Amorphous Pharmaceuticals in the Supercooled and Glassy States

We investigated the correlation between molecular mobility and physical stability in three model systems, including griseofulvin, nifedipine, and nifedipine–polyvinyl­pyrrolidone dispersion, and identified the specific mobility mode responsible for instability. The molecular mobility in the glassy as well as the supercooled liquid states of the model systems were comprehensively characterized using dynamic dielectric spectroscopy. Crystallization kinetics was monitored by powder X-ray diffractometry using either a laboratory (in the supercooled state) or a synchrotron (glassy) X-ray source. Structural (α-) relaxation appeared to be the mobility responsible for the observed physical instability at temperatures above <i>T</i>_g. Although the direct measurement of the structural relaxation time below <i>T</i>_g was not experimentally feasible, dielectric measurements in the supercooled state were used to provide an estimate of the α-relaxation times as a function of temperature in glassy pharmaceuticals. Again, there was a strong correlation between the α-relaxation and physical instability (crystallization) in the glassy state but not with any secondary relaxations. These results suggest that structural relaxation is a major contributor to physical instability both above and below <i>T</i>_g in these model systems

The Role of Polymer Concentration on the Molecular Mobility and Physical Stability of Nifedipine Solid Dispersions

We investigated the influence of polymer concentration (2.5–20% w/w) on the molecular mobility and the physical stability in solid dispersions of nifedipine (NIF) with polyvinylpyrrolidone (PVP). With an increase in polymer concentration, the α-relaxation times measured by broadband dielectric spectroscopy were longer, which reflects a decrease in molecular mobility. In the supercooled state, at a given temperature (between 55 and 75 °C), the relaxation time increased linearly as a function of polymer concentration (2.5–20% w/w). The temperature dependence of the relaxation time indicated that the fragility of the dispersion, and by extension the mechanism by which the polymer influences the relaxation time, was independent of polymer concentration. The time for NIF crystallization also increased as a function of polymer concentration. Therefore, by using molecular mobility as a predictor, a model was built to predict NIF crystallization from the dispersions in the supercooled state. The predicted crystallization times were in excellent agreement with the experimental data