Amino acid and protein specificity of protein fatty acylation in C. elegans.

Protein lipidation plays critical roles in regulating protein function and localization. However, the chemical diversity and specificity of fatty acyl group utilization have not been investigated using untargeted approaches, and it is unclear to what extent structures and biosynthetic origins of S-acyl moieties differ from N- and O-fatty acylation. Here, we show that fatty acylation patterns in Caenorhabditis elegans differ markedly between different amino acid residues. Hydroxylamine capture revealed predominant cysteine S-acylation with 15-methylhexadecanoic acid (isoC17:0), a monomethyl branched-chain fatty acid (mmBCFA) derived from endogenous leucine catabolism. In contrast, enzymatic protein hydrolysis showed that N-terminal glycine was acylated almost exclusively with straight-chain myristic acid, whereas lysine was acylated preferentially with two different mmBCFAs and serine was acylated promiscuously with a broad range of fatty acids, including eicosapentaenoic acid. Global profiling of fatty acylated proteins using a set of click chemistry-capable alkyne probes for branched- and straight-chain fatty acids uncovered 1,013 S-acylated proteins and 510 hydroxylamine-resistant N- or O-acylated proteins. Subsets of S-acylated proteins were labeled almost exclusively by either a branched-chain or a straight-chain probe, demonstrating acylation specificity at the protein level. Acylation specificity was confirmed for selected examples, including the S-acyltransferase DHHC-10. Last, homology searches for the identified acylated proteins revealed a high degree of conservation of acylation site patterns across metazoa. Our results show that protein fatty acylation patterns integrate distinct branches of lipid metabolism in a residue- and protein-specific manner, providing a basis for mechanistic studies at both the amino acid and protein levels.

Regulation of a single inositol 1-phosphate synthase homeologue by HSFA6B contributes to fibre yield maintenance under drought conditions in upland cotton.

Drought stress substantially impacts crop physiology resulting in alteration of growth and productivity. Understanding the genetic and molecular crosstalk between stress responses and agronomically important traits such as fibre yield is particularly complicated in the allopolyploid species, upland cotton (Gossypium hirsutum), due to reduced sequence variability between A and D subgenomes. To better understand how drought stress impacts yield, the transcriptomes of 22 genetically and phenotypically diverse upland cotton accessions grown under well-watered and water-limited conditions in the Arizona low desert were sequenced. Gene co-expression analyses were performed, uncovering a group of stress response genes, in particular transcription factors GhDREB2A-A and GhHSFA6B-D, associated with improved yield under water-limited conditions in an ABA-independent manner. DNA affinity purification sequencing (DAP-seq), as well as public cistrome data from Arabidopsis, were used to identify targets of these two TFs. Among these targets were two lint yield-associated genes previously identified through genome-wide association studies (GWAS)-based approaches, GhABP-D and GhIPS1-A. Biochemical and phylogenetic approaches were used to determine that GhIPS1-A is positively regulated by GhHSFA6B-D, and that this regulatory mechanism is specific to Gossypium spp. containing the A (old world) genome. Finally, an SNP was identified within the GhHSFA6B-D binding site in GhIPS1-A that is positively associated with yield under water-limiting conditions. These data lay out a regulatory connection between abiotic stress and fibre yield in cotton that appears conserved in other systems such as Arabidopsis.

How does a small molecule bind at a cryptic binding site?

Protein-protein interactions (PPIs) are ubiquitous biomolecular processes that are central to virtually all aspects of cellular function. Identifying small molecules that modulate specific disease-related PPIs is a strategy with enormous promise for drug discovery. The design of drugs to disrupt PPIs is challenging, however, because many potential drug-binding sites at PPI interfaces are "cryptic": When unoccupied by a ligand, cryptic sites are often flat and featureless, and thus not readily recognizable in crystal structures, with the geometric and chemical characteristics of typical small-molecule binding sites only emerging upon ligand binding. The rational design of small molecules to inhibit specific PPIs would benefit from a better understanding of how such molecules bind at PPI interfaces. To this end, we have conducted unbiased, all-atom MD simulations of the binding of four small-molecule inhibitors (SP4206 and three SP4206 analogs) to interleukin 2 (IL2)-which performs its function by forming a PPI with its receptor-without incorporating any prior structural information about the ligands' binding. In multiple binding events, a small molecule settled into a stable binding pose at the PPI interface of IL2, resulting in a protein-small-molecule binding site and pose virtually identical to that observed in an existing crystal structure of the IL2-SP4206 complex. Binding of the small molecule stabilized the IL2 binding groove, which when the small molecule was not bound emerged only transiently and incompletely. Moreover, free energy perturbation (FEP) calculations successfully distinguished between the native and non-native IL2-small-molecule binding poses found in the simulations, suggesting that binding simulations in combination with FEP may provide an effective tool for identifying cryptic binding sites and determining the binding poses of small molecules designed to disrupt PPI interfaces by binding to such sites.

Rewiring of the protein-protein-metabolite interactome during the diauxic shift in yeast.

In budding yeast Saccharomyces cerevisiae, the switch from aerobic fermentation to respiratory growth is separated by a period of growth arrest, known as the diauxic shift, accompanied by a significant metabolic rewiring, including the derepression of gluconeogenesis and the establishment of mitochondrial respiration. Previous studies reported hundreds of proteins and tens of metabolites accumulating differentially across the diauxic shift transition. To assess the differences in the protein-protein (PPIs) and protein-metabolite interactions (PMIs) yeast samples harvested in the glucose-utilizing, fermentative phase, ethanol-utilizing and early stationary respiratory phases were analysed using isothermal shift assay (iTSA) and a co-fractionation mass spectrometry approach, PROMIS. Whereas iTSA monitors changes in protein stability and is informative towards protein interaction status, PROMIS uses co-elution to delineate putative PPIs and PMIs. The resulting dataset comprises 1627 proteins and 247 metabolites, hundreds of proteins and tens of metabolites characterized by differential thermal stability and/or fractionation profile, constituting a novel resource to be mined for the regulatory PPIs and PMIs. The examples discussed here include (i) dissociation of the core and regulatory particle of the proteasome in the early stationary phase, (ii) the differential binding of a co-factor pyridoxal phosphate to the enzymes of amino acid metabolism and (iii) the putative, phase-specific interactions between proline-containing dipeptides and enzymes of central carbon metabolism.

Autophagy complements metalloprotease FtsH6 in degrading plastid heat shock protein HSP21 during heat stress recovery.

Moderate and temporary heat stresses (HS) prime plants to tolerate, and survive, a subsequent severe HS. Such acquired thermotolerance can be maintained for several days under normal growth conditions, and create a HS memory. We recently demonstrated that plastid-localized small heat shock protein HSP21 is a key component of HS memory in Arabidopsis thaliana. A sustained high abundance of HSP21 during the HS recovery phase extends HS memory. The level of HSP21 is negatively controlled by plastid-localized metalloprotease FtsH6 during HS recovery. Here, we demonstrate that autophagy, a cellular recycling mechanism, exerts additional control over HSP21 degradation. Genetic and chemical disruption of both, metalloprotease activity and autophagy trigger superior HSP21 accumulation, thereby improving memory. Furthermore, we provide evidence that autophagy cargo receptor ATG8-INTERACTING PROTEIN1 (ATI1) is associated with HS memory. ATI1 bodies colocalize with both autophagosomes and HSP21, and their abundance and transport to the vacuole increase during HS recovery. Together, our results provide new insights into the control module for the regulation of HS memory, in which two distinct protein degradation pathways act in concert to degrade HSP21, thereby enabling cells to recover from the HS effect at the cost of reducing the HS memory.

Multifaceted regulatory function of tomato SlTAF1 in the response to salinity stress.

Salinity stress limits plant growth and has a major impact on agricultural productivity. Here, we identify NAC transcription factor SlTAF1 as a regulator of salt tolerance in cultivated tomato (Solanum lycopersicum). While overexpression of SlTAF1 improves salinity tolerance compared with wild-type, lowering SlTAF1 expression causes stronger salinity-induced damage. Under salt stress, shoots of SlTAF1 knockdown plants accumulate more toxic Na+ ions, while SlTAF1 overexpressors accumulate less ions, in accordance with an altered expression of the Na+ transporter genes SlHKT1;1 and SlHKT1;2. Furthermore, stomatal conductance and pore area are increased in SlTAF1 knockdown plants during salinity stress, but decreased in SlTAF1 overexpressors. We identified stress-related transcription factor, abscisic acid metabolism and defence-related genes as potential direct targets of SlTAF1, correlating it with reactive oxygen species scavenging capacity and changes in hormonal response. Salinity-induced changes in tricarboxylic acid cycle intermediates and amino acids are more pronounced in SlTAF1 knockdown than wild-type plants, but less so in SlTAF1 overexpressors. The osmoprotectant proline accumulates more in SlTAF1 overexpressors than knockdown plants. In summary, SlTAF1 controls the tomato's response to salinity stress by combating both osmotic stress and ion toxicity, highlighting this gene as a promising candidate for the future breeding of stress-tolerant crops.

Monopolar Radiofrequency Energy Delivered by a Conductive Endovascular Basket or Guidewire Leads to Thermal Occlusion in a Swine Model.

PURPOSE: To assess the feasibility of inducing vascular occlusion by application of radiofrequency (RF) energy via conductive endovascular wires or baskets. MATERIALS AND METHODS: A retrievable nitinol basket and stainless steel guidewire with a platinum tip were evaluated as conductors for endovascular application of RF energy. Tissue-mimicking thermochromic gel phantoms that change color with heating were cast with 2-, 5-, and 7-mm-diameter lumens and filled with 37 oC saline. After ablation, the phantoms were sectioned, and the thermal footprints were evaluated. Six castrated male domestic swine underwent endovascular ablation using the basket in iliac arteries and guidewires in renal arteries. Post-procedural angiography was performed, and postmortem arterial segments were resected for histopathologic analysis. RESULTS: In the phantom, the depth of thermal change in the 5- and 7-mm lumens averaged 6.3 and 6.0 mm along the basket, respectively, and in the 2- and 5-mm lumens, the depth of thermal change averaged 1.9 and 0.5 mm along the wire, respectively. In the swine, RF energy delivery led to angiographic occlusion at 12 of 13 sites. Thermal injury and occlusion were similar at the proximal, middle, and distal basket treatment zone, whereas injury and occlusion decreased from the proximal to the distal end of the 5-cm wire treatment zone. CONCLUSIONS: Endovascular delivery of RF energy via a conductive basket in medium-sized arteries or a guidewire in small arteries led to acute angiographic and histologic occlusion. The potential to induce stasis might be useful in settings where rapid occlusion is desirable.

Imaging in gynecological disease (20): clinical and ultrasound characteristics of adnexal torsion.

OBJECTIVES: To describe the clinical and ultrasound characteristics of adnexal torsion. METHODS: This was a retrospective study. From the operative records of the eight participating gynecological ultrasound centers, we identified patients with a surgically confirmed diagnosis of adnexal torsion, defined as surgical evidence of ovarian pedicle, paraovarian cyst and/or Fallopian tube twisted on its own axis, who had undergone preoperative ultrasound examination by an experienced examiner, between 2008 and 2018. Only cases with at least two available ultrasound images and/or videoclips (one grayscale and one with Doppler evaluation) were included. Clinical, ultrasound, surgical and histological information was retrieved from each patient's medical record and entered into an Excel file by the principal investigator at each center. In addition, two authors reviewed all available ultrasound images and videoclips of the twisted adnexa, with regard to the presence of four predefined ultrasound features reported to be characteristic of adnexal torsion: (1) ovarian stromal edema with or without peripherally displaced antral follicles, (2) the follicular ring sign, (3) the whirlpool sign and (4) absence of vascularization in the twisted organ. RESULTS: A total of 315 cases of adnexal torsion were identified. The median age of the patients was 30 (range, 1-88) years. Most patients were premenopausal (284/314; 90.4%) and presented with acute or subacute pelvic pain (305/315; 96.8%). The surgical approach was laparoscopic in 239/312 (76.6%) patients and conservative surgery (untwisting with or without excision of a lesion) was performed in 149/315 (47.3%) cases. According to the original ultrasound reports, the median largest diameter of the twisted organ was 83 (range, 30-349) mm. Free fluid in the pouch of Douglas was detected in 196/275 (71.3%) patients. Ovarian stromal edema with or without peripherally displaced antral follicles was reported in the original ultrasound report in 167/241 (69.3%) patients, the whirlpool sign in 178/226 (78.8%) patients, absent color Doppler signals in the twisted organ in 119/269 (44.2%) patients and the follicular ring sign in 51/134 (38.1%) patients. On retrospective review of images and videoclips, ovarian stromal edema with or without peripherally displaced antral follicles (201/254; 79.1%) and the whirlpool sign (139/153; 90.8%) were the most commonly detected features of adnexal torsion. CONCLUSION: Most patients with surgically confirmed adnexal torsion are of reproductive age and present with acute or subacute pain. Common ultrasound signs are an enlarged adnexa, the whirlpool sign, ovarian stromal edema with or without peripherally displaced antral follicles and free fluid in the pelvis. The follicular ring sign and absence of Doppler signals in the twisted organ are slightly less common signs. Recognizing ultrasound signs of adnexal torsion is important so that the correct treatment, i.e. surgery without delay, can be offered. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

A regulatory role of autophagy for resetting the memory of heat stress in plants.

As sessile life forms, plants are repeatedly confronted with adverse environmental conditions, which can impair development, growth, and reproduction. During evolution, plants have established mechanisms to orchestrate the delicate balance between growth and stress tolerance, to reset cellular biochemistry once stress vanishes, or to keep a molecular memory, which enables survival of a harsher stress that may arise later. Although there are several examples of memory in diverse plants species, the molecular machinery underlying the formation, duration, and resetting of stress memories is largely unknown so far. We report here that autophagy, a central self-degradative process, assists in resetting cellular memory of heat stress (HS) in Arabidopsis thaliana. Autophagy is induced by thermopriming (moderate HS) and, intriguingly, remains high long after stress termination. We demonstrate that autophagy mediates the specific degradation of heat shock proteins at later stages of the thermorecovery phase leading to the accumulation of protein aggregates after the second HS and a compromised heat tolerance. Autophagy mutants retain heat shock proteins longer than wild type and concomitantly display improved thermomemory. Our findings reveal a novel regulatory mechanism for HS memory in plants.

Mapping Drug Dose Distribution on CT Images Following Transarterial Chemoembolization with Radiopaque Drug-Eluting Beads in a Rabbit Tumor Model.

Purpose To correlate bead location and attenuation on CT images with the quantity and distribution of drug delivered to the liver following transarterial chemoembolization (TACE) with radiopaque drug-eluting beads (DEB) in a rabbit tumor model. Materials and Methods All procedures were performed with a protocol approved by the Institutional Animal Care and Use Committee. TACE was performed in rabbits (n = 4) bearing VX2 liver tumors by using radiopaque DEB (70-150 µm) loaded with doxorubicin (DOX). Livers were resected 1 hour after embolization, immediately frozen, and cut by using liver-specific three-dimensional-printed molds for colocalization of liver specimens and CT imaging. DOX penetration into tissue surrounding beads was evaluated with fluorescence microscopy. DOX levels in liver specimens were predicted by using statistical models correlating DOX content measured in tissue with bead volume and attenuation measured on CT images. Model predictions were then compared with actual measured DOX concentrations to assess the models' predictive power. Results Eluted DOX remained in close proximity (<600 µm) to beads in the liver 1 hour after TACE. Bead volume and attenuation measured on CT images demonstrated positive linear correlations (0.950 and 0.965, respectively) with DOX content in liver specimens. DOX content model predictions based on CT images were accurate compared with actual liver DOX levels at 1 hour. Conclusion CT may be used to estimate drug dose delivery and distribution in the liver following transarterial chemoembolization (TACE) with doxorubicin-loaded radiopaque drug-eluting beads (DEB). Although speculative, this informational map might be helpful in planning and understanding the spatial effects of TACE with DEB. © RSNA, 2018.

NAC transcription factor JUNGBRUNNEN1 enhances drought tolerance in tomato.

Water deficit (drought stress) massively restricts plant growth and the yield of crops; reducing the deleterious effects of drought is therefore of high agricultural relevance. Drought triggers diverse cellular processes including the inhibition of photosynthesis, the accumulation of cell-damaging reactive oxygen species and gene expression reprogramming, besides others. Transcription factors (TF) are central regulators of transcriptional reprogramming and expression of many TF genes is affected by drought, including members of the NAC family. Here, we identify the NAC factor JUNGBRUNNEN1 (JUB1) as a regulator of drought tolerance in tomato (Solanum lycopersicum). Expression of tomato JUB1 (SlJUB1) is enhanced by various abiotic stresses, including drought. Inhibiting SlJUB1 by virus-induced gene silencing drastically lowers drought tolerance concomitant with an increase in ion leakage, an elevation of hydrogen peroxide (H2 O2 ) levels and a decrease in the expression of various drought-responsive genes. In contrast, overexpression of AtJUB1 from Arabidopsis thaliana increases drought tolerance in tomato, alongside with a higher relative leaf water content during drought and reduced H2 O2 levels. AtJUB1 was previously shown to stimulate expression of DREB2A, a TF involved in drought responses, and of the DELLA genes GAI and RGL1. We show here that SlJUB1 similarly controls the expression of the tomato orthologs SlDREB1, SlDREB2 and SlDELLA. Furthermore, AtJUB1 directly binds to the promoters of SlDREB1, SlDREB2 and SlDELLA in tomato. Our study highlights JUB1 as a transcriptional regulator of drought tolerance and suggests considerable conservation of the abiotic stress-related gene regulatory networks controlled by this NAC factor between Arabidopsis and tomato.

Manipulation of a Senescence-Associated Gene Improves Fleshy Fruit Yield.

Senescence is the process that marks the end of a leaf's lifespan. As it progresses, the massive macromolecular catabolism dismantles the chloroplasts and, consequently, decreases the photosynthetic capacity of these organs. Thus, senescence manipulation is a strategy to improve plant yield by extending the leaf's photosynthetically active window of time. However, it remains to be addressed if this approach can improve fleshy fruit production and nutritional quality. One way to delay senescence initiation is by regulating key transcription factors (TFs) involved in triggering this process, such as the NAC TF ORESARA1 (ORE1). Here, three senescence-related NAC TFs from tomato (Solanum lycopersicum) were identified, namely SlORE1S02, SlORE1S03, and SlORE1S06. All three genes were shown to be responsive to senescence-inducing stimuli and posttranscriptionally regulated by the microRNA miR164 Moreover, the encoded proteins interacted physically with the chloroplast maintenance-related TF SlGLKs. This characterization led to the selection of a putative tomato ORE1 as target gene for RNA interference knockdown. Transgenic lines showed delayed senescence and enhanced carbon assimilation that, ultimately, increased the number of fruits and their total soluble solid content. Additionally, the fruit nutraceutical composition was enhanced. In conclusion, these data provide robust evidence that the manipulation of leaf senescence is an effective strategy for yield improvement in fleshy fruit-bearing species.

Epstein-Barr Virus-induced Gene 2 Mediates Allergen-induced Leukocyte Migration into Airways.

RATIONALE: Leukocyte recruitment to sites of allergic inflammation depends on the local production of priming cytokines, chemokines, and potentially other mediators. Previously, we showed that eosinophils (Eos) express numerous orphan G-protein-coupled receptors, including Epstein-Barr virus-induced gene 2 (EBI2). Despite its contribution to inflammatory diseases, the role of EBI2 in pulmonary eosinophilia is unknown. OBJECTIVES: To determine whether oxysterol ligands for EBI2 are increased in asthma exacerbation, and if or how they promote Eos pulmonary migration. METHODS: EBI2 ligands and pulmonary eosinophilia were measured in the bronchoalveolar lavage fluid from patients with mild asthma 48 hours after acute allergen challenge. In vitro, the ability of EBI2 ligands alone or in combination with IL-5 priming to induce the migration of human blood Eos was assessed. MEASUREMENTS AND MAIN RESULTS: EBI2 was constitutively and stably expressed in peripheral blood Eos. Eos treated with the EBI2 ligands showed significantly increased transwell migration that was enhanced by priming with physiologic doses of IL-5. Migration was suppressed by inhibitors of the prolyl isomerase Pin1 or extracellular signal-regulated kinases (ERK) 1/2 or by pertussis toxin. EBI2 signaling activated Pin1 isomerase activity through a cascade that was sensitive to ERK inhibitors and pertussis toxin. The concentration of EBI2 ligands was significantly increased in the bronchoalveolar lavage fluid 48 hours after segmental allergen challenge and strongly correlated with the increased numbers of Eos, lymphocytes, and neutrophils in the airways. CONCLUSIONS: Oxysterols are increased in inflamed airways after allergen challenge and, through G-protein subunit α, ERK, and Pin1 signaling, likely participate in the regulation of Eos migration into the lung in people with asthma.

Implementation of dynamic dual input multiple output logic gate via resonance in globally coupled Duffing oscillators.

We have used a system of globally coupled double-well Duffing oscillators under an enhanced resonance condition to design and implement Dual Input Multiple Output (DIMO) logic gates. In order to enhance the resonance, the first oscillator in the globally coupled system alone is excited by two forces out of which one acts as a driving force and the other will be either sub-harmonic or super-harmonic in nature. We report that for an appropriate coupling strength, the second force coherently drives and enhances not only the amplitude of the weak first force to all the coupled systems but also drives and propagates the digital signals if any given to the first system. We then numerically confirm the propagation of any digital signal or square wave without any attenuation under an enhanced resonance condition for an amplitude greater than a threshold value. Further, we extend this idea for computing various logical operations and succeed in designing theoretically DIMO logic gates such as AND/NAND, OR/NOR gates with globally coupled systems.

Design and implementation of dynamic logic gates and R-S flip-flop using quasiperiodically driven Murali-Lakshmanan-Chua circuit.

We report the propagation of a square wave signal in a quasi-periodically driven Murali-Lakshmanan-Chua (QPDMLC) circuit system. It is observed that signal propagation is possible only above a certain threshold strength of the square wave or digital signal and all the values above the threshold amplitude are termed as "region of signal propagation." Then, we extend this region of signal propagation to perform various logical operations like AND/NAND/OR/NOR and hence it is also designated as the "region of logical operation." Based on this region, we propose implementing the dynamic logic gates, namely, AND/NAND/OR/NOR, which can be decided by the asymmetrical input square waves without altering the system parameters. Further, we show that a single QPDMLC system will produce simultaneously two outputs which are complementary to each other. As a result, a single QPDMLC system yields either AND as well as NAND or OR as well as NOR gates simultaneously. Then, we combine the corresponding two QPDMLC systems in a cross-coupled way and report that its dynamics mimics that of fundamental R-S flip-flop circuit. All these phenomena have been explained with analytical solutions of the circuit equations characterizing the system and finally, the results are compared with the corresponding numerical and experimental analysis.

The disease-ameliorating function of autoregulatory CD8 T cells is mediated by targeting of encephalitogenic CD4 T cells in experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the CNS, and CD8 T cells are the predominant T cell population in MS lesions. Given that transfer of CNS-specific CD8 T cells results in an attenuated clinical demyelinating disease in C57BL/6 mice with immunization-induced experimental autoimmune encephalomyelitis (EAE), we investigated the cellular targets and mechanisms of autoreactive regulatory CD8 T cells. In this study we report that myelin oligodendrocyte glycoprotein peptide (MOG35-55)-induced CD8 T cells could also attenuate adoptively transferred, CD4 T cell-mediated EAE. Whereas CD8(-/-) mice exhibited more severe EAE associated with increased autoreactivity and inflammatory cytokine production by myelin-specific CD4 T cells, this was reversed by adoptive transfer of MOG-specific CD8 T cells. These autoregulatory CD8 T cells required in vivo MHC class Ia (K(b)D(b)) presentation. Interestingly, MOG-specific CD8 T cells could also suppress adoptively induced disease using wild-type MOG35-55-specific CD4 T cells transferred into K(b)D(b-/-) recipient mice, suggesting direct targeting of encephalitogenic CD4 T cells. In vivo trafficking analysis revealed that autoregulatory CD8 T cells are dependent on neuroinflammation for CNS infiltration, and their suppression/cytotoxicity of MOG-specific CD4 T cells is observed both in the periphery and in the CNS. These studies provide important insights into the mechanism of disease suppression mediated by autoreactive CD8 T cells in EAE.

Implication of novel thiazolo-thiophene derivative (MCD-KV-10) for management of asthma.

CONTEXT: Asthma is multifaceted disease where many targets contribute towards its development and progression. Among these, adenosine receptor subtypes play a major role. OBJECTIVE: MCD-KV-10, a novel thiazolo-thiophene was designed and evaluated pre-clinically for its implication in management of asthma. MATERIALS AND METHODS: This compound showed good affinity and selectivity towards A(2A)/A3 adenosine receptor (AR) subtypes. Furthermore, MCD-KV-10 was evaluated for in vitro lipoxygenase inhibition activity; in vivo mast cell stabilization potential and in vivo anti-asthmatic activity was done in ovalbumin-induced airway inflammation model in guinea pigs. RESULTS: The compound showed good (>57%) inhibition of lipoxygenase enzyme and also effectively protected mast cell degranulation (>63%). The compound showed good anti-asthmatic activity as inferred from the in vivo studies. DISCUSSION: These results indicate that MCD-KV-10 has an inhibitory effect on airway inflammation. CONCLUSION: Though, we have identified a potential candidate for management of asthma, further mechanistic studies are needed.

Efficacy of glycine powder air polishing in comparison with sodium bicarbonate air polishing and ultrasonic scaling - a double-blind clinico-histopathologic study.

BACKGROUND: Subgingival biofilm removal using glycine powder air polishing (GPAP) has antecedently been shown to be safe. The hypothesis that GPAP is efficacious during periodontal maintenance therapy and results in less gingival erosion than sodium bicarbonate air polishing (SBAP) or ultrasonic scaling was assessed. METHODS: Initial periodontal therapy was performed in each of the 22 chronic periodontitis patients having residual 5 mm probing depth in each quadrant and were randomly assigned to one of the following interventions: GPAP (test), SBAP (positive control), ultrasonic scaling (positive control) or no treatment. Clinical parameters were assessed, and gingival biopsies were taken immediately after instrumentation and sent for histological quantification. RESULTS: Significant improvement in plaque and gingival index scores were noted in glycine powder air-polishing and ultrasonic group. GPAP resulted in minor erosion of the gingival epithelium (score 1 & 2), whereas positive control specimens displayed moderate to severe erosions (score 3 & 4). Difference between GPAP and positive control was significant. (P < 0.05). CONCLUSION: GPAP results in clinically significant improvement in plaque and gingival index scores and histologically causes less gingival erosion than SBAP or ultrasonic instrumentation, further supporting the safety of this debridement technique in periodontal maintenance therapy.

Biocompatible neem gum-modified polyvinyl alcohol composite as dielectric material for flexible energy devices.

In our pursuit of a flexible energy storage solution, we have developed biocompatible (bc)-NG/PVA composite polymers by combining neem tree gum (NG) with polyvinyl alcohol (PVA). This innovative bio-inspired approach harnesses NG's unique properties for both the bio-electrolyte and bio-electrode components. The resulting bc-NG/PVA composites exhibit superior dielectric strength and versatility, surpassing traditional inorganic ceramic dielectrics in advanced electronics and pulsed power systems. Our study investigates the dielectric characteristics, conductivities, electric modulus, and impedance parameters of Pure PVA and NG-doped PVA composites. Adding 5 % NG to PVA significantly boosts its conductivity from 10-8 S cm-1 to 10-4 S cm-1, while the dielectric constant of PVA/5 % NG composite jumps to 104.5 compared to pure PVA. These improvements position the composite films of 5 % NG added PVA as promising materials for diverse applications. The heightened performance of these NG-blended PVA composite materials underscores their potential as a valuable resource for flexible energy storage solutions.

Two-phase simulation of entropy optimized mixed convection flow of two different shear-thinning nanomaterials in thermal and mass diffusion systems with Lorentz forces.

This research compares the momentum, thermal energy, mass diffusion and entropy generation of two shear thinning nanofluids in an angled micro-channel with mixed convection, nonlinear thermal radiation, temperature jump boundary condition and variable thermal conductivity effects. The [Formula: see text] approach was used to solve the Buongiorno nonlinear governing model. The effect of different parameters on the flow, energy, concentration, and entropy generating fields have been graphically illustrated and explained. The hyperbolic tangent nanoliquid has a better velocity than the Williamson nanofluid. The Williamson nanofluid has higher thermal energy and concentration than the hyperbolic tangent nanoliquid in the microchannel. The Grashof number, both thermal and solutal, increases the fluid flow rate throughout the flow system. The energy of the nanoliquid is reduced by the temperature jump condition, while the energy field of the nanoliquid is enhanced by the improving thermal conductivity value. The nanoliquids concentration rises as the Schmitt number rises. The irreversibility rate of the channel system is maximized by the variable thermal conductivity parameter.