Application of connectivity index of cubic fuzzy graphs for identification of danger zones of tsunami threat.

Fuzzy graphs are very important when we are trying to understand and study complex systems with uncertain and not exact information. Among different types of fuzzy graphs, cubic fuzzy graphs are special due to their ability to represent the membership degree of both vertices and edges using intervals and fuzzy numbers, respectively. To figure out how things are connected in cubic fuzzy graphs, we need to know about cubic α-strong, cubic ß-strong and cubic δ-weak edges. These concepts better help in making decisions, solving problems and analyzing things like transportation, social networks and communication systems. The applicability of connectivity and comprehension of cubic fuzzy graphs have urged us to discuss connectivity in the domain of cubic fuzzy graphs. In this paper, the terms partial cubic α-strong and partial cubic δ-weak edges are introduced for cubic fuzzy graphs. The bounds and exact expression of connectivity index for several cubic fuzzy graphs are estimated. The average connectivity index for cubic fuzzy graphs is also defined and some results pertaining to these concepts are proved in this paper. The results demonstrate that removing some vertices or edges may cause a change in the value of connectivity index or average connectivity index, but the change will not necessarily be related to both values. This paper also defines the concepts of partial cubic connectivity enhancing node and partial cubic connectivity reducing node and some related results are proved. Furthermore, the concepts of cubic α-strong, cubic ß- strong, cubic δ-weak edge, partial cubic α-strong and partial cubic δ-weak edges are utilized to identify areas most affected by a tsunami resulting from an earthquake. Finally, the research findings are compared with the existing methods to demonstrate their suitability and creativity.

Synthesis, biochemical and computational evaluations of novel bis-acylhydrazones of 2,2'-(1,1'-biphenyl)-4,4'-diylbis(oxy))di(acetohydrazide) as dual cholinesterase inhibitors.

A series of twenty-seven bis(acylhydrazones) were successfully synthesized with high yields through a multistep process, which entailed the esterification of hydroxyl groups, hydrazination with an excess of hydrazine hydrate, and subsequent reactions with various carbonyl moieties (aldehydes). In the final stage of synthesis, different chemical species including aromatic, heterocyclic, and aliphatic compounds were integrated into the framework. The resulting compounds were characterized using several spectroscopic techniques (1H NMR, 13C NMR, and mass spectrometry). Their anticholinesterase activities were assessed in vitro by examining their interactions with two cholinesterase enzymes: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among the synthesized hits, compounds 3, 5, 6, 9-12, and 14 exhibited good to moderate inhibition of AChE. Specifically, 10 (IC50 = 26.3 ± 0.4 µM) and 11 (IC50 = 28.4 ± 0.5 µM) showed good inhibitory activity against AChE, while 9, 12, 3, and 6 exhibited significant inhibition potential against AChE with IC50 values ranging from 35.2 ± 1.1 µM to 64.4 ± 0.3 µM. On the other hand, 5 (IC50 = 22.0 ± 1.1 µM) and 27 (IC50 = 31.3 ± 1.3 µM) displayed significant, and 19 (IC50 = 92.6 ± 0.4 µM) showed moderate inhibitory potential for BChE. Notably, 5 and 27 exhibited dual inhibition of AChE and BChE, with greater potency than the standard drug galantamine. The binding patterns of these molecules within the binding cavities of AChE and BChE were anticipated by molecular docking which showed good correlation with our in vitro findings. Further structural optimization of these molecules may yield more potent AChE and BChE inhibitors.

De novo design of anti-variant COVID-19 vaccine.

Recent studies highlight the effectiveness of hybrid Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) vaccines combining wild-type nucleocapsid and Spike proteins. We have further enhanced this strategy by incorporating delta and omicron variants' spike protein mutations. Both delta and omicron mark the shifts in viral transmissibility and severity in unvaccinated and vaccinated patients. So their mutations are highly crucial for future viral variants also. Omicron is particularly adept at immune evasion by mutating spike epitopes. The rapid adaptations of Omicron and sub-variants to spike-based vaccines and simultaneous transmissibility underline the urgency for new vaccines in the continuous battle against SARS-CoV-2. Therefore, we have added three persistent T-cell-stimulating nucleocapsid peptides similar to homologous sequences from seasonal Human Coronaviruses (HuCoV) and an envelope peptide that elicits a strong T-cell immune response. These peptides are clustered in the hybrid spike's cytoplasmic region with non-immunogenic linkers, enabling systematic arrangement. AlphaFold (Artificial intelligence-based model building) analysis suggests omitting the transmembrane domain enhances these cytoplasmic epitopes' folding efficiency which can ensure persistent immunity for CD4+ structural epitopes. Further molecular dynamics simulations validate the compact conformation of the modeled structures and a flexible C-terminus region. Overall, the structures show stability and less conformational fluctuation throughout the simulation. Also, the AlphaFold predicted structural epitopes maintained their folds during simulation to ensure the specificity of CD4+ T-cell response after vaccination. Our proposed approach may provide options for incorporating diverse anti-viral T-cell peptides, similar to HuCoV, into linker regions. This versatility can be promising to address outbreaks and challenges posed by various viruses for effective management in this era of innovative vaccines.

Oleuropein: Chemistry, extraction techniques and nutraceutical perspectives-An update.

Olive family (Oleaceae) contains several species among which Olea europaea L. is mostly used for production of olive oils. Various parts of olive tree are rich source of diverse bioactive compounds such as Apigenin, elenolic acid, Hydroxytyrosol, Ligstroside, Oleoside, Oleuropein, Oleuropein aglycone, Tyrosol, etc. Among these, oleuropein, a secoiridoid is predominantly found in olive leaves and young olive fruits of different species of Oleaceae family. Scientists have adopted numerous extraction methods (conventional & latest) to increase the yield of oleuropein. Among these techniques, maceration, soxhlet, microwave-assisted, ultrasonication, and supercritical fluid methods are most commonly employed for extraction of oleuropein. Evidently, this review emphasizes on various in-vitro and in-vivo studies focusing on nutraceutical properties of oleuropein. Available literature highlights the pharmaceutical potential of oleuropein against various diseases such as obesity, diabetes, cardiovascular complications, neurodegenerative diseases, cancer, inflammation, microbial infections, and oxidation. This review will benefit the scientific community as it narrates comprehensive literature regarding absorption, metabolism, bioavailability, extraction techniques, and nutraceutical perspectives associated with oleuropein.

Industrially Important Fungal Carotenoids: Advancements in Biotechnological Production and Extraction.

Carotenoids are lipid-soluble compounds that are present in nature, including plants and microorganisms such as fungi, certain bacteria, and algae. In fungi, they are widely present in almost all taxonomic classifications. Fungal carotenoids have gained special attention due to their biochemistry and the genetics of their synthetic pathway. The antioxidant potential of carotenoids may help fungi survive longer in their natural environment. Carotenoids may be produced in greater quantities using biotechnological methods than by chemical synthesis or plant extraction. The initial focus of this review is on industrially important carotenoids in the most advanced fungal and yeast strains, with a brief description of their taxonomic classification. Biotechnology has long been regarded as the most suitable alternative way of producing natural pigment from microbes due to their immense capacity to accumulate these pigments. So, this review mainly presents the recent progress in the genetic modification of native and non-native producers to modify the carotenoid biosynthetic pathway for enhanced carotenoid production, as well as factors affecting carotenoid biosynthesis in fungal strains and yeast, and proposes various extraction methods to obtain high yields of carotenoids in an attempt to find suitable greener extraction methods. Finally, a brief description of the challenges regarding the commercialization of these fungal carotenoids and the solution is also given.

Mucor circinelloides: a model organism for oleaginous fungi and its potential applications in bioactive lipid production.

Microbial oils have gained massive attention because of their significant role in industrial applications. Currently plants and animals are the chief sources of medically and nutritionally important fatty acids. However, the ever-increasing global demand for polyunsaturated fatty acids (PUFAs) cannot be met by the existing sources. Therefore microbes, especially fungi, represent an important alternative source of microbial oils being investigated. Mucor circinelloides-an oleaginous filamentous fungus, came to the forefront because of its high efficiency in synthesizing and accumulating lipids, like γ-linolenic acid (GLA) in high quantity. Recently, mycelium of M. circinelloides has acquired substantial attraction towards it as it has been suggested as a convenient raw material source for the generation of biodiesel via lipid transformation. Although M. circinelloides accumulates lipids naturally, metabolic engineering is found to be important for substantial increase in their yields. Both modifications of existing pathways and re-formation of biosynthetic pathways in M. circinelloides have shown the potential to improve lipid levels. In this review, recent advances in various important metabolic aspects of M. circinelloides have been discussed. Furthermore, the potential applications of M. circinelloides in the fields of antioxidants, nutraceuticals, bioremediation, ethanol production, and carotenoids like beta carotene and astaxanthin having significant nutritional value are also deliberated.

Case report: A novel de novo loss of function variant in the DNA-binding domain of TBX2 causes severe osteochondrodysplasia.

Background: T-box family members are transcription factors characterized by highly conserved residues corresponding to the DNA-binding domain known as the T-box. TBX2 has been implicated in several developmental processes, such as coordinating cell fate, patterning, and morphogenesis of a wide range of tissues and organs, including lungs, limbs, heart, kidneys, craniofacial structures, and mammary glands. Methods: In the present study, we have clinically and genetically characterized a proband showing a severe form of chondrodysplasia with developmental delay. Whole-exome sequencing (WES), Sanger sequencing, and 3D protein modeling were performed in the present investigation. Results: Whole-exome sequencing revealed a novel nonsense variant (c.529A>T; p.Lys177*; NM_005994.4) in TBX2. 3D-TBX2 protein modeling revealed a substantial reduction of the mutated protein, which might lead to a loss of function (LOF) or nonsense-mediated decay (NMD). Conclusion: This study has not only expanded the mutation spectrum in the gene TBX2 but also facilitated the diagnosis and genetic counseling of related features in affected families.

Genetic Modification of Mucor circinelloides for Canthaxanthin Production by Heterologous Expression of ß-carotene Ketolase Gene.

Canthaxanthin is a reddish-orange xanthophyll with strong antioxidant activity and higher bioavailability than carotenes, primarily used in food, cosmetics, aquaculture, and pharmaceutical industries. The spiking market for natural canthaxanthin promoted researchers toward genetic engineering of heterologous hosts for canthaxanthin production. Mucor circinelloides is a dimorphic fungus that produces ß-carotene as the major carotenoid and is considered as a model organism for carotenogenic studies. In this study, canthaxanthin-producing M. circinelloides strain was developed by integrating the codon-optimized ß-carotene ketolase gene (bkt) of the Haematococcus pluvialis into the genome of the fungus under the control of strong promoter zrt1. First, a basic plasmid was constructed to disrupt crgA gene, a negative regulator of carotene biosynthesis resulted in substantial ß-carotene production, which served as the building block for canthaxanthin by further enzymatic reaction of the ketolase enzyme. The genetically engineered strain produced a significant amount (576 ± 28 µg/g) of canthaxanthin, which is the highest amount reported in Mucor to date. Moreover, the cell dry weight of the recombinant strain was also determined, producing up to more than 9.0 g/L, after 96 h. The mRNA expression level of bkt in the overexpressing strain was analyzed by RT-qPCR, which increased by 5.3-, 4.1-, and 3-folds at 24, 48, and 72 h, respectively, compared with the control strain. The canthaxanthin-producing M. circinelloides strain obtained in this study provided a basis for further improving the biotechnological production of canthaxanthin and suggested a useful approach for the construction of more valuable carotenoids, such as astaxanthin.

Comparative Analysis of Different Isolated Oleaginous Mucoromycota Fungi for Their γ-Linolenic Acid and Carotenoid Production.

γ-Linolenic acid (GLA) and carotenoids have attracted much interest due to their nutraceutical and pharmaceutical importance. Mucoromycota, typical oleaginous filamentous fungi, are known for their production of valuable essential fatty acids and carotenoids. In the present study, 81 fungal strains were isolated from different Egyptian localities, out of which 11 Mucoromycota were selected for further GLA and carotenoid investigation. Comparative analysis of total lipids by GC of selected isolates showed that GLA content was the highest in Rhizomucor pusillus AUMC 11616.A, Mucor circinelloides AUMC 6696.A, and M. hiemalis AUMC 6031 that represented 0.213, 0.211, and 0.20% of CDW, respectively. Carotenoid analysis of selected isolates by spectrophotometer demonstrated that the highest yield of total carotenoids (640 µg/g) was exhibited by M. hiemalis AUMC 6031 and M. hiemalis AUMC 6695, and these isolates were found to have a similar carotenoid profile with, ß-carotene (65%), zeaxanthin (34%), astaxanthin, and canthaxanthin (5%) of total carotenoids. The total fatty acids of all tested isolates showed moderate antimicrobial activity against Staphylococcus aureus and Salmonella Typhi, and Penicillium chrysogenum. To the best of our knowledge, this is the first report on the highest yield of total lipid accumulation (51.74% CDW) by a new oleaginous fungal isolate R. pusillus AUMC 11616.A. A new scope for a further study on this strain will be established to optimize and improve its total lipids with high GLA production. So, R. pusillus AUMC 11616.A might be a potential candidate for industrial application.

Redirecting Metabolic Flux towards the Mevalonate Pathway for Enhanced ß-Carotene Production in M. circinelloides CBS 277.49.

Carotenoids produced by microbial sources are of industrial and medicinal importance due to their antioxidant and anticancer properties. In the current study, optimization of ß-carotene production in M. circinelloides strain 277.49 was achieved using response surface methodology (RSM). Cerulenin and ketoconazole were used to inhibit fatty acids and the sterol biosynthesis pathway, respectively, in order to enhance ß-carotene production by diverting metabolic pool towards the mevalonate pathway. All three variables used in screening experiments were found to be significant for the production of ß-carotene. The synergistic effect of the C/N ratio, cerulenin, and ketoconazole was further evaluated and optimized for superior ß-carotene production using central composite design of RSM. Our results found that the synergistic combination of C/N ratios, cerulenin, and ketoconazole at different concentrations affected the ß-carotene productions significantly. The optimal production medium (std. order 11) composed of C/N 25, 10 µg/mL cerulenin, and 150 mg/L ketoconazole, producing maximum ß-carotene of 4.26 mg/L (0.43 mg/g) which was 157% greater in comparison to unoptimized medium (1.68 mg/L, 0.17 mg/g). So, it was concluded that metabolic flux had been successfully redirected towards the mevalonate pathway for enhanced ß-carotene production in CBS 277.49.

Sources, Extraction and Biomedical Properties of Polysaccharides.

In the recent era, bioactive compounds from plants have received great attention because of their vital health-related activities, such as antimicrobial activity, antioxidant activity, anticoagulant activity, anti-diabetic activity, UV protection, antiviral activity, hypoglycemia, etc. Previous studies have already shown that polysaccharides found in plants are not likely to be toxic. Based on these inspirational comments, most research focused on the isolation, identification, and bioactivities of polysaccharides. A large number of biologically active polysaccharides have been isolated with varying structural and biological activities. In this review, a comprehensive summary is provided of the recent developments in the physical and chemical properties as well as biological activities of polysaccharides from a number of important natural sources, such as wheat bran, orange peel, barely, fungi, algae, lichen, etc. This review also focused on biomedical applications of polysaccharides. The contents presented in this review will be useful as a reference for future research as well as for the extraction and application of these bioactive polysaccharides as a therapeutic agent.

Antioxidant Potential and the Characterization of Arachis hypogaea Roots.

Arachis hypogaea roots are used as traditional Chinese medicine to treat different ailments, and the present study involves the exploration and comparison of phenolic profile and antioxidant activities (ABTS+ and DPPH assay) of A. hypogaea root extract in different solvents. 70% aqueous acetone and 70% aqueous ethanol were proved to be the best solvents to recover total phenolic compounds, with a yield of 42.59 ± 1.96 and 41.34 ± 0.92 mg/g dry weight of extract, respectively. ABTS+ radical scavenging activity was the highest in 70% aqueous ethanol, while the absolute methanol extract showed the highest DPPH radical scavenging activity (29.50 ± 2.19 µg/mL). Furthermore, phytochemical profiling of 70% acetone extract of A. hypogaea roots was performed by LC-ESI-TOF-MS analysis which in turn indicated the presence of diverse compounds in the A. hypogaea root extract, namely, quinones, stilbenoids, and flavones and flavonoid glucosides.

Farm to Consumer: Factors Affecting the Organoleptic Characteristics of Coffee. II: Postharvest Processing Factors.

The production and consumption of coffee are increasing despite the roadblocks to its agriculture and global trade. The unique, refreshing, and stimulating final cupping quality of coffee is the only reason for this rising production and consumption. Coffee quality is a multifaceted trait and is inevitably influenced by the way it is successively processed after harvesting. Reportedly, 60% of the quality attributes of coffee are governed by postharvest processing. The current review elaborates and establishes for the first time the relationship between different methods of postharvest processing of coffee and its varying organoleptic and sensory quality attributes. In view of the proven significance of each processing step, this review has been subdivided into three sections, secondary processing, primary processing, and postprocessing variables. Secondary processing addresses the immediate processing steps on the farm after harvest and storage before roasting. The primary processing section adheres specifically to roasting, grinding and brewing/extraction, topics which have been technically addressed more than any others in the literature and by industry. The postprocessing attribute section deals generally with interaction of the consumer with products of different visual appearance. Finally, there are still some bottlenecks which need to be addressed, not only to completely understand the relationship of varying postharvest processing methods with varying in-cup quality attributes, but also to devise the next generation of coffee processing technologies.

Comparison of characteristics of femtosecond laser-assisted anterior capsulotomy versus manual continuous curvilinear capsulorrhexis: A meta-analysis of 5-year results.

OBJECTIVE: To perform a meta-analysis on the precision and safety of femtosecond laser-assisted anterior capsulotomy versus conventional manual continuous curvilinear capsulorrhexis. METHODS: This meta-analysis was conducted from February 2010 to November 2014. Literature search on PubMed, Google Scholar, ExcerptaMedica database and Cochrane Library was done to identify randomised controlled trials and case-control studies. SPSS 20 was used for data analysis. RESULTS: Of the 10 articles included, there were 3(30%) randomised controlled trials and 7(70%) non-randomised controlled trials. The meta-analysis was based on a total of 2,882eyes. Of them, 1,498(51.97%) underwent femtosecond laser-assisted capsulotomy and 1,384(48.02%) underwent manual continuous curvilinear capsulorrhexis. The diameter of the capsulotomy and the rates of anterior capsule tear showed no statistical difference between the femtosecond laser group and the manual capsulorrhexis group (p=0.29 and p=0.68). In terms of circularity of capsulotomy, femtosecond laser group had a more significant advantage than the manual capsulorrhexis group (p<0.001). CONCLUSIONS: Femtosecond laser performed capsulotomy with more precision and higher reliability than the manual continuous curvilinear capsulorrhexis.