Novel Dual COX-2/5-LOX Inhibitory Activity by Chalcone Derivatives: A Safe and Efficacious Anti-Inflammatory Agent.

BACKGROUND: Non-communicable diseases are chronic systemic inflammation in humans that occurs because of enhanced inflammatory mediators of the arachidonic acid cas-cade. We aimed to explore whether the lead chalcone compounds could exhibit anti-inflam-matory activity via dual blockage of COX-2/5-LOX enzymes and their regulatory mechanism. METHODS: RAW 264.7 macrophages were collected from NCC, Pune, for in-vitro experiments. The IC50 values of chalcone compounds C45 and C64 were calculated. RAW 264.7 macro-phages were treated with C45 and C64 (10%, 5%, 2.5%, 0.125%, and 0.0625% concentration). The cell viability was carried out with an MTT assay. The COX-1, COX-2, 5-LOX, PGE2, and LTB4 levels were detected by ELISA-based kits. The in-vivo evaluation was carried out in Male Wistar rats (250-300 g, 7-8 weeks old) with acute and chronic anti-inflammatory models and histopathological studies on the stomach, liver, and kidney. RESULTS: The present study described the in-vitro and in-vivo biological evaluation of dual COX-2/5-LOX inhibitors in chalcone derivatives (C45 and C64) compounds showed the most effective COX-2 and 5-LOX inhibition with IC50 values 0.092 and 0.136µM respectively. Simultaneously, compound C64 showed comparable selectivity towards COX-2 with a Selec-tivity Index (SI) of 68.43 compared to etoricoxib, with an SI of 89.32. In-vivo carrageenan-induced rat paw oedema activity, the compound C64 showed a significant reduction in oedema with 78.28% compared to indomethacin with 88.07% inhibition. Furthermore, cotton pellet-induced granuloma activity revealed that compound C64 significantly reduced 32.85% com-pared with standard 40.13% granuloma inhibition. CONCLUSION: The chalcone compound C64, (E)-1-(4-Amino-2-hydroxyphenyl)-3-(3,4,5-tri-methoxyphenyl)-prop-2-en-1-one was proved to be a potent and novel Dual COX-2/5-LOX inhibitor with improved gastric safety profiling.

Breed and timepoint-based analysis of chicken harderian gland transcriptome during Newcastle disease virus challenge.

Introduction: Newcastle disease is a highly infectious disease caused by the Newcastle Disease Virus (NDV) and has a devastating financial impact on the global chicken industry. It was previously established that Leghorn and Fayoumi breeds of chicken exhibit variable resistance against NDV infection. The harderian gland is the less studied tissue of the chicken, known to play an essential role in the immune response. Methods: Our previous study, we reported differential gene expression and long noncoding RNAs (lncRNAs) between challenged and non-challenged chickens in the Harderian gland transcriptomic data. Now, we report the analysis of the same data studying the differential expression patterns between Leghorn and Fayoumi and between different timepoints during disease. First, the pipeline FHSpipe was used for identification of lncRNAs, followed by differential expression analysis by edgeR (GLM), functional annotation by OmicsBox, co-expression analysis using WGCNA and finally validation of selected lncRNAs and co-expressing genes using qRT-PCR. Results: Here, we observed that Leghorn showed a higher number of upregulated immune-related genes than Fayoumi in timepoint-based analysis, especially during the initial stages. Surprisingly, Fayoumi, being comparatively resistant, showed little difference between challenged and non-challenged conditions and different time points of the challenge. The breed-based analysis, which compared Leghorn with Fayoumi in both challenged and non-challenged conditions separately, identified several immune-related genes and positive co-expressing cis lncRNAs to be upregulated in Fayoumi when compared to Leghorn in both challenged and non-challenged conditions. Discussion: The current study shows that Leghorn, being comparatively more susceptible to NDV than Fayoumi, showed several immune-related genes and positive co-expressing cis lncRNAs upregulated in challenged Leghorn when compared to non-challenged Leghorn and also in different timepoints during challenge. While, breed-based analysis showed that there were more upregulated immune genes and positive cis-lncRNAs in Fayoumi than Leghorn. This result clearly shows that the differences in the expression of genes annotated with immune-related GO terms and pathways, i.e., immune-related genes and the co-expressing cis-lncRNAs between Leghorn and Fayoumi, and their role in the presence of differences in the resistance of Leghorn and Fayoumi chicken against NDV. Conclusion: These immune-genes and cis-lncRNAs could play a role in Fayoumi being comparatively more resistant to NDV than Leghorn. Our study elucidated the importance of lncRNAs during the host defense against NDV infection, paving the way for future research on the mechanisms governing the genetic improvement of chicken breeds.

Experimental and Theoretical Investigations of MAPbX3 -Based Perovskites (X=Cl, Br, I) for Photovoltaic Applications.

This work mainly focuses on synthesizing and evaluating the efficiency of methylammonium lead halide-based perovskite (MAPbX3 ; X=Cl, Br, I) solar cells. We used the colloidal Hot-injection method (HIM) to synthesize MAPbX3 (X=Cl, Br, I) perovskites using the specific precursors and organic solvents under ambient conditions. We studied the structural, morphological and optical properties of MAPbX3 perovskites using XRD, FESEM, TEM, UV-Vis, PL and TRPL (time-resolved photoluminescence) characterization techniques. The particle size and morphology of these perovskites vary with respect to the halide variation. The MAPbI3 perovskite possesses a low band gap and low carrier lifetime but delivers the highest PCE among other halide perovskite samples, making it a promising candidate for solar cell technology. To further enrich the investigations, the conversion efficiency of the MAPbX3 perovskites has been evaluated through extensive device simulations. Here, the optical constants, band gap energy and carrier lifetime of MAPbX3 were used for simulating three different perovskite solar cells, namely I, Cl or Br halide-based perovskite solar cells. MAPbI3 , MAPbBr3 and MAPbCl3 absorber layer-based devices showed ~13.7 %, 6.9 % and 5.0 % conversion efficiency. The correlation between the experimental and SCAPS simulation data for HIM-synthesized MAPBX3 -based perovskites has been reported for the first time.

Experimental analysis of methylammonium and Formamidinium-based halide perovskite properties for optoelectronic applications.

Nowadays, the toxicity of lead in metal-halide perovskites is the most precarious obstruction in the commercialization of perovskite-based optoelectronic devices. However, Pb-free metal halide perovskites as environment-friendly materials because of their exceptional properties, such as band-gap tunability, narrow emission spectra, low toxicity and easy solution-processability, are potential candidates for optoelectronic applications. Recently, literature reported the poor structural stability and low-emission intensity of Bi-based perovskite NCs. Still, this paper focuses on the fabrication of Formamidinium (FA)-based Bi mixed halide and Methylammonium(MA)-based Bi-pure halide perovskites using Ligand-Assisted Reprecipitation Technique (LARP) technique. XRD diffraction patterns of FA-based perovskites were slightly broad, signifying the nanocrystalline form and limited size of perovskite nanocrystals. While the XRD diffraction patterns of MA3Bi2X9 (X = Cl/Br/I) perovskites were narrow, signifying the amorphous nature and larger size of perovskite nanocrystals. The peak positions were varied in MA-based bismuth halide perovskites with respect to the halide variation from Br to Cl to I ions. The optical study shows the variation in band gap and average lifetime with respect to halide variation leading to enhanced optical properties for device applications. The band-gap of FA3Bi2BrxCl1-x & FA3Bi2IxCl1-x perovskites was calculated to be around 3.7 & 3.8 eV, respectively, while in MA-halide perovskites the band-gap was calculated to be 2.8 eV, 3.1 eV & 3.4 eV with respect to halide variation from I to Cl to Br in perovskite samples using Tauc's plot respectively. Moreover, simulation is carried out using the SCAPS-1D software to study the various parameters in MA & FA-based Bi-pure or mixed halide perovskites. Here, we discussed the variation in efficiency with respect to the thickness variation from 100 to 500 nm for MA3Bi2I9 halide perovskites. These MA3Bi2I9 halide perovskites show minimum efficiency of 4.65 % at 100 nm thickness, while the perovskite sample exhibits maximum efficiency of 10.32 % at 500 nm thickness. Thus, the results stated that the thickness of absorber layers directly affects the device characteristics for optoelectronic applications.

Integrated analysis of genes and long non-coding RNAs in trachea transcriptome to decipher the host response during Newcastle disease challenge in different breeds of chicken.

Newcastle disease is a highly infectious economically devastating disease caused by Newcastle disease Virus in Chicken (Gallus gallus). Leghorn and Fayoumi are two breeds which show differential resistance patterns towards NDV. This study aims to identify the differentially expressed genes and lncRNAs during NDV challenge which could play a potential role in this differential resistance pattern. A total of 552 genes and 1580 lncRNAs were found to be differentially expressing. Of them, 52 genes were annotated with both Immune related pathways and Gene ontologies. We found that most of these genes were upregulated in Leghorn between normal and challenged chicken but several were down regulated between different timepoints after NDV challenge, while Fayoumi showed no such downregulation. We also observed that higher number of positively correlating lncRNAs was found to be downregulated along with these genes. This shows that although Leghorn is showing higher number of differentially expressed genes in challenged than in non-challenged, most of them were downregulated during the disease between different timepoints. With this we hypothesize that the downregulation of immune related genes and co-expressing lncRNAs could play a significant role behind the Leghorn being comparatively susceptible breed than Fayoumi. The computational pipeline is available at https://github.com/Venky2804/FHSpipe.

Symbiotic Antimicrobial Effects of Cellulose-Based Bio-Nanocomposite for Disease Management of Agricultural Crops.

In the present work, a bionanocomposite for plant crop protection was prepared by non-toxic biocompatible & biodegradable nanomaterials (Cellulose & TiO2 ) to utilize its synergistic effects against antimicrobial pathogens. The commercially available microcrystalline cellulose has been reduced to a nanometric scale regime using acid hydrolysis, while the standard TiO2 nano-powder of particle size ~20 nm has been used to prepare their nanocomposite (NC). The antibacterial studies via agar well diffusion method demonstrated that after 72 h of incubation, parent nanomaterials Ncell and TiO2 were not showing any activity against phytopathogens X. campestris pv. campestris, and Clavibacter while the nanocomposite's NC's were still effective depicting both bacteriostatic and bactericidal actions. However, the bacterial growth of biocontrol P. fluorescence was not affected by Ncell, TiO2 NPs and NC after 72 h of incubation. The antifungal testing results via poison food agar assay method suggest that the nanocomposite, along with Ncell and TiO2 NPs, exhibited strong inhibition of fungal growth of Phytophthora Spp at 0.125 mg/ml concentration while for F. graminearum, similar effect was observed at 0.25 mg/ml concentration. The nanocomposite has proved its potential by exhibiting longer & stronger synergistic effects against plant pathogens as a good antimicrobial agent for protection of agricultural crops.

Recent Progress in Selective COX-2 Inhibitor Formulations and Therapeutic Applications - A Patent Review (2012-2022).

INTRODUCTION: Cyclooxygenase (COX), in literature, known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme that is responsible for the formation of prostanoids, including thromboxane and prostaglandins from arachidonic acid. COX-1 does housekeeping activity, whereas COX- 2 induces inflammation. Continuous rise in COX-2 gives birth to chronic pain-associated disorders, i.e., arthritis, cardiovascular complications, macular degeneration, cancer, and neurodegenerative disorders. Despite their potent anti-inflammatory effects, the detrimental effects of COX-2 inhibitors coexist in healthy tissues. Non-preferential NSAIDs cause gastrointestinal discomfort, whereas selective COX-2 inhibitors exert higher cardiovascular risk and renal impairment on chronic use. METHODS: This review paper covers key patents published between 2012-2022 on NSAIDs and coxibs, highlighting their importance, mechanism of action, and patents related to formulation and drug combination. So far, several drug combinations with NSAIDS have been used in clinical trials to treat chronic pain besides combating the side effects. CONCLUSION: Emphasis has been given on the formulation, drug combination, administration routesmodification, and alternative routes, i.e., parenteral, topical, and ocular DEPOT, improving its riskbenefit ratio of NSAIDs to improvise their therapeutic availability and minimize the adverse effects. Considering the wide area of research on COX-2 and ongoing studies, and future scope of view for the better use of the NSAIDs in treating debilitating disease-associated algesia.

Surface engineering of colloidal quaternary chalcogenide Cu2ZnSnS4 nanocrystals: a potential low-cost photocatalyst for water remediation.

Colloidal route synthesis of quaternary compound CZTS (Cu2ZnSnS4) has been anticipated with an inimitable combination of coordinating ligands and solvents using the hot injection technique. CZTS is recognized as one of the worthiest materials for photo-voltaic/catalytic applications due to its exclusive properties (viz., non-toxic, economical, direct bandgap, high absorbance coefficient, etc.). This paper demonstrates the formation of crystalline, single-phased, monodispersed, and electrically passivated CZTS nanoparticles using a distinctive combination of ligands viz. oleic acid (OA)-trioctylphosphine (TOP) and butylamine (BA)-trioctylphosphine (TOP). Detailed optical, structural, and electrochemical studies were done for all CZTS nanoparticles, and the most efficient composition was found using ligands butylamine and TOP. CZTS nanocrystals were rendered hydrophilic via surface-ligand engineering, which was used for photocatalysis studies of organic pollutants. Malachite green (MG) and rhodamine 6G (Rh) for water remediation have great commercial prospects. The unique selling proposition of this work is the rapid synthesis time (~ 45 min) of colloidal CZTS nanocrystals, cost-effective ligand-exchange process, and negligible material wastage (~ 200 µl per 10 ml of pollutant) during photocatalytic experiments.

Visible-light driven noble metal (Au, Ag) permeated multicomponent Cu2ZnSnS4 nanocrystals: A potential low-cost photocatalyst for textile effluents and heavy metal removal.

An exemplary vision to understand the fundamental role of metal-doped multi-components system such as Au/Ag doped CZTS (Cu2ZnSnS4) nanocrystals encourages the non-vacuum approach for the best performing photocatalyst. Hydrophilic nanoparticles (Au/Ag and CZTS) are allowed to amalgamate under NTP atmosphere, eradicating the prerequisite for high-end equipment. The potential of Au and Ag-doped CZTS nanoparticles was speculated using various optical and structural characterizations. The absorption range of CZTS nanoparticles lies in the visible range, while Au/Ag doping slightly red-shifts the absorption range, considered the desirable state for photocatalysis. The synthesized nanoparticles are highly monodispersed with ∼15-35 nm particle size for Ag, Au, and CZTS. Photocatalysis is a discernible scheme for treating wastewater containing dyes, textile effluents, chemicals, and heavy metals. Here, we strive to use these ex-situ synthesized nanomaterials as photocatalysts, where the real textile waste (collected from industrial outlets), dyes, and heavy metal (chromium (VI)) have been photo-reduced after scrutinizing the finest combination of Ag or Au doped CZTS. Au-CZTS shows superior catalytic activity with an efficiency of 99.7% with a rate constant of 0.2 min-1 (while Ag-CZTS shows 90% efficiency with a rate constant of 0.07 min-1); hence, used for real textile waste and heavy metal (Chromium VI) photo-reduction. The maximum efficiency achieved for textile-1, textile-2, and Cr (VI) reductions is 80%, 70%, and 97%, respectively. The nanocrystals are highly stable and recyclable, tested for 15 repeated cycles. These studies pave the way for developing cost-effective, environmentally-friendly, durable, and selective semiconductor-metal (Au/Ag) hybrid heterostructures as visible-light-driven photocatalysts for wastewater remediation.

Phytochemistry and Polypharmacological Potential of Colebrookea oppositifolia Smith.

BACKGROUND: Colebrookea oppositifolia Smith. is a valuable traditional therapeutic plant belonging to the family Lamiaceae. It is a dense and wool-like shrub that is mostly found in subtropical regions of some countries of Asia, such as China and India. It has been widely used for the mitigation of nervous system disorders like epilepsy. The active constituents of the plant have exhibited antioxidant, anti-microbial, and antifungal properties, which are considered due to the presence of polyphenols and flavonoids as chief chemical constituents. Flavonoids like quercetin, landenein, chrysin, and 5, 6, 7-trimethoxy flavones cause protein denaturation of the microbial cell wall. OBJECTIVES: To comprehend and assemble the fragmented pieces of evidence presented on the traditional uses, botany, phytochemistry, and pharmacology of the plant to reconnoiter its therapeutic perspective and forthcoming research opportunities. METHODS: The available information on Colebrookea oppositifolia has been established by electronically searching peer-reviewed literature from PubMed, Google Scholar, Springer, Scopus, Web of Science, and Science Direct over the earlier few years. RESULTS: The plant has been greatly used for the preparation of many herbal medicines which are used for treating traumatic injuries, fever, rheumatoid arthritis, headache, and gastric problems. From the aerial parts of the plant, a phenylethanoid glycoside named acteoside has been isolated and evaluated for its therapeutic potential viz. immunomodulatory, neuroprotective, hepatoprotective, analgesic, anti-tumour, antispasmodic, antioxidant, antibacterial, free radical scavenger, and improving sexual function. Acteoside showed neuroprotective activities against Aß-peptide, which is neurotoxic and causes apoptosis. The petroleum ether extract of the plant leaves offers many active compounds like sitosterol, n-triacontane, hydroxydotriacontyl ferulate, acetyl alcohol, and 3,7,4,2-tetramethoxyflavones which have shown hepatoprotective potential. CONCLUSION: The plant should be evaluated further for the estimation of some other health benefits. The consequences of restricted pharmacological screening and reported phytomolecules of Colebrookea oppositifolia Smith. advocate that there is still an exigent requisite for in-depth pharmacological studies of the plant.

Identification and differential expression of long non-coding RNAs and their association with XIST gene during early embryonic developmental stages of Bos taurus.

X-chromosomes inactivation (XCI) is a phenomenon that aims to equalize the dosage of X-linked gene products between XY males and XX females in mammals. XIST gene is the master regulator of X chromosome inactivation during early embryonic developmental stages of Bos taurus. Biological molecule such as lncRNA plays significant role in the control of XCI, by RNA-based regulatory mechanisms and are non-coding regions of the genome. In our study, using in-silico transcriptome data analysis approach, we analysed RNA-seq data of E35, E39 and E43 samples from bovine genital ridges of early embryonic stages, and identified lncRNA transcripts. More than 7 lakh lncRNA transcripts were identified. Further, our study identified DE-lncRNAs and genes between male and female and studied their co-expression. More than four thousand differentially expressed lncRNAs identified. The co-expression and RT-PCR study in the result showed that there exists an association between the XIST and DE-lncRNAs in early embryonic gonads of bovine at E35. In this study, the association between DE-lncRNAs and XIST gene indicates, the potentially important role of DE-lncRNAs during embryo development in bovine. In conclusion, this study shows there exist an interplay between genes and lncRNAs at transcriptome level of bovine during early embryonic days.

In silico prediction of the animal susceptibility and virtual screening of natural compounds against SARS-CoV-2: Molecular dynamics simulation based analysis.

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. It has six open reading frames (orf1ab, orf3a, orf6, orf7a, orf8, and orf10), a spike protein, a membrane protein, an envelope small membrane protein, and a nucleocapsid protein, out of which, orf1ab is the largest ORF coding different important non-structural proteins. In this study, an effort was made to evaluate the susceptibility of different animals against SARS-CoV-2 by analyzing the interactions of Spike and ACE2 proteins of the animals and propose a list of potential natural compounds binding to orf1ab of SARS-CoV-2. Here, we analyzed structural interactions between spike proteins of SARS-CoV-2 and the ACE2 receptor of 16 different hosts. A simulation for 50 ns was performed on these complexes. Based on post-simulation analysis, Chelonia mydas was found to have a more stable complex, while Bubalus bubalis, Aquila chrysaetos chrysaetos, Crocodylus porosus, and Loxodonta africana were found to have the least stable complexes with more fluctuations than all other organisms. Apart from that, we performed domain assignment of orf1ab of SARS-CoV-2 and identified 14 distinct domains. Out of these, Domain 3 (DNA/RNA polymerases) was selected as a target, as it showed no similarities with host proteomes and was validated in silico. Then, the top 10 molecules were selected from the virtual screening of ∼1.8 lakh molecules from the ZINC database, based on binding energy, and validated for ADME and toxicological properties. Three molecules were selected and analyzed further. The structural analysis showed that these molecules were residing within the pocket of the receptor. Finally, a simulation for 200 ns was performed on complexes with three selected molecules. Based on post-simulation analysis (RMSD, RMSF, Rg, SASA, and energies), the molecule ZINC000103666966 was found as the most suitable inhibitory compound against Domain 3. As this is an in silico prediction, further experimental studies could unravel the potential of the proposed molecule against SARS-CoV-2.

Development, Characterization and In Vitro Antimicrobial Evaluation of Novel Flavonoids Entrapped Micellar Topical Formulations of Neomycin Sulfate.

Flavonoids are the secondary metabolites widely used in pharmaceutical industries due to their several health benefits. Quercetin and rutin, well known flavonoids possesses various pharmacological properties but the constraints of poor aqueous solubility and impermeability across cell membranes restricts their use in formulation development. Moreover, the rising problem of antimicrobial resistance has also caused a serious threat to human life, thus demanding the urgent need of developing more effective antimicrobial formulations. In view of this, the present research work is focused on utilizing the most feasible flavonoid-surfactant concentrations obtained from the already reported physico-chemical analysis in developing an improved neomycin topical formulation through drug combinatorial approach. The formulations were subjected for assessment of physical parameters such as determination of pH, viscosity and spreadability. The drug release profile of the formulations was studied through different mathematical models. After evaluation of all the parameters, two best formulations (NQ-T2 [HE] and NR-T1 [HE]) were selected for antimicrobial evaluation studies against different bacterial and fungal clinical isolates. Among the two formulations, NQ-T2 [HE] showed excellent antibacterial activity against the bacterial strains while NR-T1 [HE] also exhibited promising results when compared with the standard formulations. Overall, this study represents a possible solution to enhance the antimicrobial efficacy of neomycin formulations by combining them with flavonoids through micelles assisted drug combination approach.

Activation of Microbiota Sensing - Free Fatty Acid Receptor 2 Signaling Ameliorates Amyloid-ß Induced Neurotoxicity by Modulating Proteolysis-Senescence Axis.

Multiple emerging evidence indicates that the gut microbiota contributes to the pathology of Alzheimer's disease (AD)-a debilitating public health problem in older adults. However, strategies to beneficially modulate gut microbiota and its sensing signaling pathways remain largely unknown. Here, we screened, validated, and established the agonists of free fatty acid receptor 2 (FFAR2) signaling, which senses beneficial signals from short chain fatty acids (SCFAs) produced by microbiota. The abundance of SCFAs, is often low in the gut of older adults with AD. We demonstrated that inhibition of FFAR2 signaling increases amyloid-beta (Aß) stimulated neuronal toxicity. Thus, we screened FFAR2 agonists using an in-silico library of more than 144,000 natural compounds and selected 15 of them based on binding with FFAR2-agonist active sites. Fenchol (a natural compound commonly present in basil) was recognized as a potential FFAR2 stimulator in neuronal cells and demonstrated protective effects against Aß-stimulated neurodegeneration in an FFAR2-dependent manner. In addition, Fenchol reduced AD-like phenotypes, such as Aß-accumulation, and impaired chemotaxis behavior in Caenorhabditis (C.) elegans and mice models, by increasing Aß-clearance via the promotion of proteolysis and reduced senescence in neuronal cells. These results suggest that the inhibition of FFAR2 signaling promotes Aß-induced neurodegeneration, while the activation of FFAR2 by Fenchol ameliorates these abnormalities by promoting proteolytic Aß-clearance and reducing cellular senescence. Thus, stimulation of FFAR2 signaling by Fenchol as a natural compound can be a therapeutic approach to ameliorate AD pathology.

Transcriptomic analysis to infer key molecular players involved during host response to NDV challenge in Gallus gallus (Leghorn & Fayoumi).

Long non-coding RNAs (lncRNAs) are the transcripts of length longer than 200 nucleotides. They are involved in the regulation of various biological activities. Leghorn and Fayoumi breeds of Gallus gallus were known to be having differential resistance against Newcastle Disease Virus (NDV) infection. Differentially expressed genes which were thought to be involved in this pattern of resistance were already studied. Here we report the analysis of the transcriptomic data of Harderian gland of Gallus gallus for studying the lncRNAs involved in regulation of these genes. Using bioinformatics approaches, a total of 37,411 lncRNAs were extracted and 359 lncRNAs were differentially expressing. Functional annotation using co-expression analysis revealed the involvement of lncRNAs in the regulation of various pathways. We also identified 1232 quantitative trait loci (QTLs) associated with the genes interacting with lncRNA. Additionally, we identified the role of lncRNAs as putative micro RNA precursors, and the interaction of differentially expressed Genes with transcription factors and micro RNAs. Our study revealed the role of lncRNAs during host response against NDV infection which would facilitate future experiments in unravelling regulatory mechanisms of development in the genetic improvement of the susceptible breeds of Gallus gallus.

SARS-CoV-2 Spike Glycoprotein and ACE2 Interaction Reveals Modulation of Viral Entry in Wild and Domestic Animals.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral pathogen causing life-threatening diseases in humans. Interaction between the spike protein of SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2) is a potential factor in the infectivity of a host. In this study, the interaction of SARS-CoV-2 spike protein with its receptor, ACE2, in different hosts was evaluated to predict the probability of viral entry. Phylogeny and alignment comparison of the ACE2 sequences did not lead to any meaningful conclusion on viral entry in different hosts. The binding ability between ACE2 and the spike protein was assessed to delineate several spike binding parameters of ACE2. A significant difference between the known infected and uninfected species was observed for six parameters. However, these parameters did not specifically categorize the Orders into infected or uninfected. Finally, a logistic regression model constructed using spike binding parameters of ACE2, revealed that in the mammalian class, most of the species of Carnivores, Artiodactyls, Perissodactyls, Pholidota, and Primates had a high probability of viral entry. However, among the Proboscidea, African elephants had a low probability of viral entry. Among rodents, hamsters were highly probable for viral entry with rats and mice having a medium to low probability. Rabbits have a high probability of viral entry. In Birds, ducks have a very low probability, while chickens seemed to have medium probability and turkey showed the highest probability of viral entry. The findings prompt us to closely follow certain species of animals for determining pathogenic insult by SARS-CoV-2 and for determining their ability to act as a carrier and/or disseminator.

Quantifying and addressing the prevalence and bias of study designs in the environmental and social sciences.

Building trust in science and evidence-based decision-making depends heavily on the credibility of studies and their findings. Researchers employ many different study designs that vary in their risk of bias to evaluate the true effect of interventions or impacts. Here, we empirically quantify, on a large scale, the prevalence of different study designs and the magnitude of bias in their estimates. Randomised designs and controlled observational designs with pre-intervention sampling were used by just 23% of intervention studies in biodiversity conservation, and 36% of intervention studies in social science. We demonstrate, through pairwise within-study comparisons across 49 environmental datasets, that these types of designs usually give less biased estimates than simpler observational designs. We propose a model-based approach to combine study estimates that may suffer from different levels of study design bias, discuss the implications for evidence synthesis, and how to facilitate the use of more credible study designs.

Oral Disintegrating Tablets - An Updated Patent Perspective.

Current Development in drug delivery system has been employed with an endeavour to enhance the bioavailability of the drug, mask its taste, induce the rapid onset of action and improve patient compliance. An alternative approach to the conventional dosage form is being employed to triumph over all these issues named as Orodispersible system. Over the past three decades, this novel dosage form has gained considerable attention as compared to other conventional solid dosage forms such as tablets and capsules. ODTs dissolve or disintegrate within a few seconds or a minute when put on the tongue, without the need for water. ODT has an advantageous effect on paediatrics and geriatrics patients with dysphagia. Over the last decade, widespread advances in the formulation of ODTs have been executed in academia and industry that resulted in the emergence of a large number of patents. Products developed from ODT mechanics launched in the market in the 1980s have grown bit by bit in demand and their products are rapidly escalating. Expanding in the technology forum based on industrialization, these systems include the use of lyophilization, cotton candy, sublimation, melt extrusion and direct compression in addition to the conventional wet granulation processes and patent techniques. The present study focused on non-patent and patent citations concerning ODT along with active ingredients, techniques used and results of the innovations.

SARS-CoV-2 transcriptome analysis and molecular cataloguing of immunodominant epitopes for multi-epitope based vaccine design.

Genomics-led researches are engaged in tracing virus expression pattern, and induced immune responses in human to develop effective vaccine against COVID-19. In this study, targeted expression profiling and differential gene expression analysis of major histocompatibility complexes and innate immune system genes were performed through SARS-CoV-2 infected RNA-seq data of human cell line, and virus transcriptome was generated for T-and B-cell epitope prediction. Docking studies of epitopes with MHC and B-cell receptors were performed to identify potential T-and B-cell epitopes. Transcriptome analysis revealed the specific multiple allele expressions in cell line, genes for elicited induce immune response, and virus gene expression. Proposed T- and B-cell epitopes have high potential to elicit equivalent immune responses caused by SARS-CoV-2 infection which can be useful to provide links between elicited immune response and virus gene expression. This study will facilitate in vitro and in vivo vaccine related research studies in disease control.

Comparative transcriptomics reveals candidate transcription factors involved in costunolide biosynthesis in medicinal plant-Saussurea lappa.

Costunolides, an important sesquiterpene lactone (STL) isolated from Saussurea lappa, are the major pharmaceutical ingredient of various drug formulations. Identification of the genes and transcriptional regulation of costunolide biosynthesis pathway in S. lappa will propose alternatives for engineering enhanced metabolite biosynthesis in plant. Here, we aimed to unravel the transcription factors (TFs) regulating the costunolide biosynthesis. Comparative transcriptome analysis of root and leaf tissues and transcripts were annotated using various in silico tools. Putative transcription factors were identified using PlantTFDB and TF- gene co-expression network was generated followed by clustering using module based analysis to observe their coordinated behaviour. The module 1 was found to be significant based on its enrichment with major pathway genes. Further, promoter cloning determined the cis acting elements in costunolide synthase (SlCOS1) gene which catalyses the final key step of costunolide biosynthesis. Bioinformatics tools were employed to predict the cis regulatory elements, leading to the identification of MYB family of TFs as an interacting partner of SlCOS1 gene. The present study is the pioneer attempt for TF prediction and elucidation of their regulatory role in costunolide synthesis. This will help in future metabolic engineering of the pharmaceutically important STLs and their yield improvement.