Exploring the extrachromosomal plasmid rDNA of Naegleria fowleri AY27 genotype II: A human brain-eating amoeba via high-throughput sequencing.

Naegleria fowleri, also known as brain-earing amoeba, causes severe and rapidly fatal CNS infection in humans called primary amebic meningoencephalitis (PAM). The DNA from the N. fowleri clinical isolate was sequenced for circular extrachromosomal ribosomal DNA (CERE - rDNA). The CERE contains 18 S, 5.8 S, and 28 S ribosomal subunits separated by internal transcribed spacers, 5 open reading frames (ORFs), and mostly repeat elements comprising 7268 bp out of 15,786 bp (46%). A wide variety of variations and recombination events were observed. Finally, the ORFs that comprised only 4 hypothetical proteins were modeled and screened against Zinc drug-like compounds. Two compounds [ZINC77564275 (ethyl 2-(((4-isopropyl-4 H-1,2,4-triazol-3-yl) methyl) (methyl)amino) oxazole-4-carboxylate) and ZINC15022129 (5-(2-methoxyphenoxy)-[2,2'-bipyrimidine]-4,6(1 H,5 H)-dione)] were finalized as potential druggable compounds based on ADME toxicity analysis. We propose that the compounds showing the least toxicity would be potential drug candidates after laboratory experimental validation is performed.

Molecular identification of Proteus mirabilis, Vibrio species leading to CRISPR-Cas9 modification of tcpA and UreC genes causing cholera and UTI.

Heavy metal accumulation increases rapidly in the environment due to anthropogenic activities and industrialization. The leather and surgical industry produces many contaminants containing heavy metals. Cadmium, a prominent contaminant, is linked to severe health risks, notably kidney and liver damage, especially among individuals exposed to contaminated wastewater. This study aims to leverage the natural cadmium resistance mechanisms in bacteria for bioaccumulation purposes. The industrial wastewater samples, characterized by an alarming cadmium concentration of 29.6 ppm, 52 ppm, and 76.4 ppm-far exceeding the recommended limit of 0.003 ppm-were subjected to screening for cadmium-resistant bacteria using cadmium-supplemented media with CdCl2. 16S rRNA characterization identified Vibrio cholerae and Proteus mirabilis as cadmium-resistant bacteria in the collected samples. Subsequently, the cadmium resistance-associated cadA gene was successfully amplified in Vibrio species and Proteus mirabilis, revealing a product size of 623 bp. Further analysis of the identified bacteria included the examination of virulent genes, specifically the tcpA gene (472 bp) associated with cholera and the UreC gene (317 bp) linked to urinary tract infections. To enhance the bioaccumulation of cadmium, the study proposes the potential suppression of virulent gene expression through in-silico gene-editing tools such as CRISPR-Cas9. A total of 27 gRNAs were generated for UreC, with five selected for expression. Similarly, 42 gRNA sequences were generated for tcpA, with eight chosen for expression analysis. The selected gRNAs were integrated into the lentiCRISPR v2 expression vector. This strategic approach aims to facilitate precise gene editing of disease-causing genes (tcpA and UreC) within the bacterial genome. In conclusion, this study underscores the potential utility of Vibrio species and Proteus mirabilis as effective candidates for the removal of cadmium from industrial wastewater, offering insights for future environmental remediation strategies.

Fabrication and characterization of pullulan/tapioca starch-based antibacterial films incorporated with Litsea cubeba essential oil for meat preservation.

Active packaging is a novel technology that utilizes active materials to interact with products and the environment, improving food shelf life. The purpose of this work was to fabricate a multifunctional film using Litsea cubeba essential oil (LC-EO) (1 %, 3 %, 5 %, and 7 %) as the active ingredient and pullulan(P)/tapioca starch (TS) as the carrier material. Adding essential oil improves the films properties, such as barrier ability, anti-oxidant, and antibacterial activity. However, tensile strength (TS) and elongation at break (EAB) were slightly reduced from 28.94 MPa to 11.29 MPa and 15.36 % to 12.19 %. The developed PTS3% films showed the best performance in mechanical properties, especially EAB (14.26 %), WVP (3.26 %) and OP (3.13 %), respectively. The inhibitory zone diameters in the agar-well diffusion test were 18.59 mm for Staphylococcus aureus and 17.32 mm for Escherichia coli. Further study was conducted to compare the preservation effects of film with low-density polyethylene bag (LDPE) on chilled beef. Remarkably, PTS3% film decreased the bacterial population in beef meat while maintaining the pH, color, texture, and TBARS levels within an acceptable range for ten days of storage at 4 °C rather than in a low-density polyethylene bag. The outcomes indicated the potential of PTS3% films in food packaging applications.

Comparative analysis among the degradation potential of enzymes obtained from Escherichia coli against the toxicity of sulfur dyes through molecular docking.

The common bacterium Escherichia coli has demonstrated potential in the field of biodegradation. E. coli is naturally capable of biodegradation because it carries a variety of enzymes that are essential for the breakdown of different substances. The degradation process is effectively catalyzed by these enzymes. The collaborative effects of E. coli's aryl sulfotransferase, alkanesulfonate moonoxygenase, and azoreductase enzymes on the breakdown of sulfur dyes from industrial effluents are investigated in this work. ExPASY ProtParam was used to confirm the stability of the enzyme, showing an instability index less than 40. We determined the maximum binding affinities of these enzymes with sulfur dye pollutants - 1-naphthalenesulfonic acid, sulfogene, sulfur green 3, sulfur red 6, sulfur red 1, sulfur yellow 2, thianthrene, thiazone, and thional - using comparative molecular docking. Significantly, the highest binding affinity was shown by monooxygenase (-12.1), whereas aryl sulfotransferase and azoreductase demonstrated significant energies of -11.8 and -11.4, respectively. The interactions between proteins and ligands in the docked complexes were examined. To evaluate their combined effects, co-expression analysis of genes and enzyme bioengineering were carried out. Using aryl sulfotransferase, alkanesulfonate monooxygenase, and azoreductase, this study investigates the enzymatic degradation of sulfur dye pollutants, thereby promoting environmentally friendly and effective sulfur dye pollutant management.

Lacticaseibacillusparacasei BNCC345679 revolutionizes DSS-induced colitis and modulates gut microbiota.

The gut microbiota plays an important role in the disease progression of inflammatory bowel disease. Although probiotics are effective against IBD, not many studies have investigated their effects on gut microbiota composition and immunomodulation in mouse colitis models. Our study aimed at the therapeutic effects of Lacticaseibacillus paracasei BNCC345679 for the first time and explored its impact on gut microbiome dysbiosis, inflammatory cytokines, related miRNAs, VCAM-1, oxidative stress, intestinal integrity, and mucus barrier. We found that oral intervention of L. paracasei BNCC345679 affects recovering beneficial microbial taxa, including lactobacillus spp. and akkermansia spp., followed by improved body weight, DAI score, and inflammatory cytokines. L. paracasei BNCC345679 mitigated oxidative stress and increased the expression of intestinal integrity proteins MUC2 and ZO-1. These results suggested that L. paracasei BNCC345679 has the capacity to reduce DSS-induced colitis and has the potential as a supplement for the mitigation of IBD.

Investigating the anti-cancer compounds from Calliandra harrisii for precision medicine in pancreatic cancer via in-silico drug design and GC-MS analysis.

Pancreatic cancer is a fatal illness caused by mutations in multiple genes. Pancreatic cancer damages the organ that helps in digestion, resulting in symptoms including fatigue, bloating, and nausea. The use of medicinal plants has been crucial in the treatment of numerous disorders. The medicinal plant Calliandra Harrisi has been widely exploited for its possibilities in biology and medicine. The current study aimed to assess the biopotential of biologically active substances against pancreatic cancer. The GC-MS data of these phytochemicals from Calliandra Harrisi were further subjected to computational approaches with pancreatic cancer genes to evaluate their potential as therapeutic candidates. Molecular docking analysis revealed that N-[Carboxymethyl] maleamic acid is the leading molecule responsible for protein denaturation inhibition, having the highest binding affinity of 6.8 kJ/mol among all other compounds with KRAS inflammatory proteins. Furthermore, ADMET analysis and Lipinski's rule validation were also performed revealing its higher absorption in the gastrointestinal tract. The results of the hepatotoxicity test demonstrated that phytochemicals are non-toxic, safe to use, and do not cause necrosis, fibrosis, or vacuolar degeneration even at excessive levels. Calliandra Harrisi has phytoconstituents that have a variety of pharmacological uses in consideration.

In vitro enzymatic, in silico ADME and molecular docking based analysis for the identification of novel bis-indole containing triazine-thiazole hybrids derivatives as promising urease inhibitors.

The current study details a sequence of sequential reactions for synthesizing bis-indole-based triazine bearing thiazole derivatives. Several steps were involved in the synthesis of bis-indole-based triazine bearing thiazole derivative. The synthetic reactions were monitored via thin-layer chromatography (TLC). Synthesized compounds were characterized using various spectroscopic techniques, including 1H NMR, 13C NMR, and HR-EIMS. The inhibitory activity against urease enzyme of these synthesized compounds was compared with that of thiourea, a standard drug (IC50 = 9.30 ± 0.20 µM). A range of inhibitory potencies were observed for the synthesized compounds, ranging from moderate to excellent, as follows (IC50 = 5.10 ± 0.40 µM to 29.80 ± 0.20 µM). Analyzing the structure-activity relationship (SAR) provided insight into the results, showing that different substituents had different effects on aromatic rings. Several compounds displayed outstanding inhibitory properties (among those tested were 1, 2, 4, 5, and 6 with IC50 = 6.30 ± 0.80, 5.10 ± 0.40, 5.90 ± 0.50, 8.20 ± 0.10, 8.90 ± 0.60 µM, respectively). Anti-urease evaluation of all the synthesized derivatives was conducted in which the selected compounds have shown remarkable potency compared with the standard drug thiourea (IC50 = 9.30 ± 0.20 µM). Molecular docking analysis was carried out for investigating the better binding sites and distance of the derivatives. Moreover, the drug-like properties were explored by the ADME attributes of the synthesized analogs.

Whole Genome Analysis of Tibetan Kefir-Derived Lactiplantibacillus Plantarum 12-3 Elucidates Its Genomic Architecture, Antimicrobial and Drug Resistance, Potential Probiotic Functionality and Safety.

BACKGROUND: Lactiplantibacillus plantarum 12-3 holds great promise as a probiotic bacterial strain, yet its full potential remains untapped. This study aimed to better understand this potential therapeutic strain by exploring its genomic landscape, genetic diversity, CRISPR-Cas mechanism, genotype, and mechanistic perspectives for probiotic functionality and safety applications. METHODS: L. plantarum 12-3 was isolated from Tibetan kefir grains and, subsequently, Illumina and Single Molecule Real-Time (SMRT) technologies were used to extract and sequence genomic DNA from this organism. After performing pan-genomic and phylogenetic analysis, Average Nucleotide Identity (ANI) was used to confirm the taxonomic identity of the strain. Antibiotic resistance gene analysis was conducted using the Comprehensive Antibiotic Resistance Database (CARD). Antimicrobial susceptibility testing, and virulence gene identification were also included in our genomic analysis to evaluate food safety. Prophage, genomic islands, insertion sequences, and CRISPR-Cas sequence analyses were also carried out to gain insight into genetic components and defensive mechanisms within the bacterial genome. RESULTS: The 3.4 Mb genome of L. plantarum 12-3, was assembled with 99.1% completeness and low contamination. A total of 3234 genes with normal length and intergenic spacing were found using gene prediction tools. Pan-genomic studies demonstrated gene diversity and provided functional annotation, whereas phylogenetic analysis verified taxonomic identity. Our food safety study revealed a profile of antibiotic resistance that is favorable for use as a probiotic. Analysis of insertional sequences, genomic islands, and prophage within the genome provided information regarding genetic components and their possible effects on evolution. CONCLUSIONS: Pivotal genetic elements uncovered in this study play a crucial role in bacterial defense mechanisms and offer intriguing prospects for future genome engineering efforts. Moreover, our findings suggest further in vitro and in vivo studies are warranted to validate the functional attributes and probiotic potential of L. plantarum 12-3. Expanding the scope of the research to encompass a broader range of L. plantarum 12-3 strains and comparative analyses with other probiotic species would enhance our understanding of this organism's genetic diversity and functional properties.

Genotypic Profiling, Functional Analysis, Cholesterol-Lowering Ability, and Angiotensin I-Converting Enzyme (ACE) Inhibitory Activity of Probiotic Lactiplantibacillus plantarum K25 via Different Approaches.

Due to its alleged health advantages, several uses in biotechnology and food safety, the well-known probiotic strain Lactiplantibacillus plantarum K25 has drawn interest. This in-depth investigation explores the genetic diversity, makeup, and security characteristics of the microbial genome of L. plantarum K25, providing insightful knowledge about its genotypic profile and functional characteristics. Utilizing cutting-edge bioinformatics techniques like comparative genomics, pan-genomics, and genotypic profiling was carried out to reveal the strain's multidimensional potential in various fields. The results not only add to our understanding of the genetic makeup of L. plantarum K25 but also show off its acceptability in various fields, notably in biotechnology and food safety. The explanation of evolutionary links, which highlights L. plantarum K25's aptitude as a probiotic, is one notable finding from this research. Its safety profile, which is emphasized by the absence of genes linked to antibiotic resistance, is crucial and supports its status as a promising probiotic option.

Pharmacological evaluation and phytochemical profiling of butanol extract of L. edodes with in- silico virtual screening.

L. edodes (L. edodes) is the most consumed mushroom in the world and has been well known for its therapeutic potential as an edible and medicinal candidate, it contains dietary fibers, vitamins, proteins, minerals, and carbohydrates. In the current study butanolic extract of mushroom was used to form semisolid butanol extract. The current study aimed to explore biometabolites that might have biological activities in n-butanol extract of L. edodes using FT-IR and GC-MS and LC-MS. The synergistic properties of bioactive compounds were futher assessed by performing different biological assays such as antioxidant, anti-inflammatory and antidiabetic. FTIR spectra showed different functional groups including amide N-H group, Alkane (C-H stretching), and (C = C stretching) groups at different spectrum peaks in the range of 500 cm-1 to 5000 cm-1 respectively. GC-MS profiling of n-butanol extract depicted 34 potent biomolecules among those dimethyl; Morphine, 2TMS derivative; Benzoic acid, methyl ester 1-(2-methoxy-1-methylethoxy)-2-propanol were spotted at highest range. Results indicate that L. edodes n-butanol extract showed a maximum anti-inflammatory potential 91.4% at 300 mg/mL. Antioxidant activity was observed by measuring free radical scavenging activity which is 64.6% at optimized concentration along with good antidiabetic activity. In-silico study executed the biopotential of active ingredient morphine which proved the best docking score (- 7.0 kJ/mol) against aldose reductase. The in-silico drug design analysis was performed on biometabolites detected through GC-MS that might be a potential target for sulfatase-2 to treat ruminated arthritis. Morphine binds more strongly (- 7.9 kJ/mol) than other bioactive constituents indicated. QSAR and ADMET analysis shown that morphine is a good candidates against ruminated arthritis. The current study showed that L. edodes might be used as potent drug molecules to cure multiple ailments. As mushrooms have high bioactivity, they can be used against different diseases and to develop antibacterial drugs based on the current situation in the world in which drug resistance is going to increase due to misuse of antibiotics so new and noval biological active compounds are needed to overcome the situation.

Revolutionizing and identifying novel drug targets in Citrobacter koseri via subtractive proteomics and development of a multi-epitope vaccine using reverse vaccinology and immuno-informatics.

Citrobacter koseri is a gram-negative rod that has been linked to infections in people with significant comorbidities and immunocompromised immune systems. It is most commonly known to cause urinary tract infections. Thus, the development of an efficacious C. koseri vaccine is imperative, as the pathogen has acquired resistance to current antibiotics. Subtractive proteomics was employed during this research to identify potential antigenic proteins to design an effective vaccine against C. koseri. The pipeline identified two antigenic proteins as potential vaccine targets: DP-3-O-acyl-N-acetylglucosamine deacetylase and Arabinose 5-phosphate isomerase. B and T cell epitopes from the specific proteins were forecasted employing several immunoinformatic and bioinformatics resources. A vaccine was created using a combination of seven cytotoxic T cell lymphocytes (CTL), five helper T cell lymphocyte (HTL), and seven linear B cell lymphocyte (LBL) epitopes. An adjuvant (ß-defensin) was added to the vaccine to enhance immunological responses. The created vaccine was stable for use in humans, highly antigenic, and non-allergenic. The vaccine's molecular and interactions binding affinity with the human immunological receptor TLR3 were studied using MMGBSA, molecular dynamics (MD) simulations, and molecular docking analyses. E. coli (strain-K12) plasmid vector pET-28a (+) was used to examine the ability of the vaccine to be expressed. The vaccine shows great promise in terms of developing protective immunity against diseases, based on the results of these computer experiments. However, in vitro and animal research are required to validate our findings.Communicated by Ramaswamy H. Sarma.

Optimal Enzyme-Assisted Extraction of Phenolics from Leaves of Pongamia pinnata via Response Surface Methodology and Artificial Neural Networking.

This research work seeks to evaluate the impact of selected enzyme complexes on the optimised release of phenolics from leaves of Pongamia pinnata. After preliminary solvent extraction, the P. pinnata leaf extract was subjected to enzymatic treatment, using enzyme cocktails such as kemzyme dry-plus, natuzyme, and zympex-014. It was noticed that zympex-014 had a greater extract yield (28.0%) than kemzyme dry-plus (17.0%) and natuzyme (18.0%). Based on the better outcomes, zympex-014-based extract values were subsequently applied to several RSM parameters. The selected model is suggested to be significant by the F value (12.50) and R2 value (0.9669). The applicability of the ANN model was shown by how closely the projected values from the ANN were to the experimental values. In terms of total phenolic contents (18.61 mg GAE/g), total flavonoid contents (12.56 mg CE/g), and DPPH test (IC50) (6.5 g/mL), antioxidant activities also shown significant findings. SEM analysis also revealed that the cell walls were damaged during enzymatic hydrolysis, as opposed to non-hydrolysed material. Using GC-MS, five potent phenolic compounds were identified in P. pinnata extract. According to the findings of this study, the recovery of phenolic bioactives and subsequent increase in the antioxidant capacity of P. pinnata leaf extract were both positively impacted by the optimisation approaches suggested, including the use of zympex-014.

Changes of physicochemical and functional properties of processed cheese made with natural cheddar and mozzarella cheeses during refrigerated storage.

The present study aimed to investigate changes of physicochemical and functional properties of the processed cheeses (PCs) made with Cheddar (PC1), Mozzarella (PC2) and both of them at a ratio of 1:1 (PC3) during storage at 4 °C for 4 months. The results showed that the type of natural cheese used affected the composition of PCs with lower fat content in PC2 due to the lower fat content of Mozzarella cheese used. PC2 with lower fat content showed decreased meltability and oil leakage compared with PC1 and PC3. The stretchability of all the samples significantly (P < 0.05) decreased during storage, and PC1 showed lower stretchability. This was confirmed by increased protein hydrolysis of all the samples during the storage with a higher level of proteolysis in PC1, leading to decreased stretchability of PCs. Further low-field nuclear magnetic resonance analysis indicated more entrapped water in cheese due to moisture migration into the cheese matrix that might squeeze the fat globules to aggregate, causing more fat leakage during later stages of storage. This was evidenced by microstructural analysis showing different extents of increase in fat particle sizes and decrease in free serum in all the PC samples over the storage time. Therefore, the present study provides further understanding of the mechanism of quality change of PC during refrigerated storage as affected by proteolytic properties and composition of natural cheese used.

Physicochemical, microbiological and metabolomics changes in yogurt supplemented with lactosucrose.

Lactosucrose (LS) is a known prebiotic that has gained recognition for its low caloric content and various health benefits. However, its potential in food applications remains largely unexplored. In this study the effects of adding LS to milk at concentrations (0 %, 2 %, 5 % and 8 % w/v) for yogurt production, and the relevant changes in yogurt texture, microbial composition and metabolomics were investigated. Our findings revealed that LS played a role in promoting the formation of a structured gel during fermentation, resulting in increased elasticity and viscosity while reducing fluidity. Additionally incorporating high doses of LS into yogurt led to reduced post-acidification, enhanced survival of starter bacteria, improved water retention capacity and overall texture throughout a refrigerated storage period of 21 days. Notably higher concentrations of LS (8 % w/v) exhibited effects on enhancing yogurt quality. Furthermore, untargeted metabolomics analysis using UPLC Q TOF MS/MS revealed 45 differentially expressed metabolites, including up-regulated L-arginine, L-proline and L-glutamic acid along with the down-regulated glutathione, L-tyrosine, L-phenylalanyl and L-proline. These differential metabolites were primarily associated with amino acid metabolism such as thiamine metabolism, nicotinic acid salt and nicotinamide metabolism, and pyrimidine metabolism. As a result, the inclusion of LS in yogurt had an impact on the production of various beneficial metabolites in yogurt, highlighting the importance of combining prebiotic LS with probiotics to obtain desired physiological benefits of yogurt.

An Aedes-Anopheles Vaccine Candidate Supplemented with BCG Epitopes Against the Aedes and Anopheles Genera to Overcome Hypersensitivity to Mosquito Bites.

BACKGROUND: Skeeter syndrome is a severe local allergic response to mosquito bites that is accompanied by considerable inflammation and, in some cases, a systemic response like fever. People with the syndrome develop serious allergies, ranging from rashes to anaphylaxis or shock. The few available studies on mosquito venom immunotherapy have utilized whole-body preparations and small sample sizes. Still, owing to their little success, vaccination remains a promising alternative as well as a permanent solution for infections like Skeeter's. METHODS: This study, therefore, illustrated the construction of an epitope-based vaccine candidate against Skeeter Syndrome using established immunoinformatic techniques. We selected three species of mosquitoes, Anopheles melas, Anopheles funestus, and Aedes aegypti, to derive salivary antigens usually found in mosquito bites. Our construct was also supplemented with bacterial epitopes known to elicit a strong TH1 response and suppress TH2 stimulation that is predicted to reduce hypersensitivity against the bites. RESULTS: A quality factor of 98.9496, instability index of 38.55, aliphatic index of 79.42, solubility of 0.934747, and GRAVY score of -0.02 indicated the structural (tertiary and secondary) stability, thermostability, solubility, and hydrophilicity of the construct, respectively. The designed Aedes-Anopheles vaccine (AAV) candidate was predicted to be flexible and less prone to deformability with an eigenvalue of 1.5911e-9 and perfected the human immune response against Skeeter (hypersensitivity) and many mosquito-associated diseases as we noted the production of 30,000 Th1 cells per mm3 with little (insignificant production of Th2 cells. The designed vaccine also revealed stable interactions with the pattern recognition receptors of the host. The TLR2/vaccine complex interacted with a free energy of - 1069.2 kcal/mol with 26 interactions, whereas the NLRP3/vaccine complex interacted with a free energy of - 1081.2 kcal/mol with 16 molecular interactions. CONCLUSION: Although being a pure in-silico study, the in-depth analysis performed herein speaks volumes of the potency of the designed vaccine candidate predicting that the proposition can withstand rigorous in-vitro and in-vivo clinical trials and may proceed to become the first preventative immunotherapy against mosquito bite allergy.

Elucidating the role of diet in maintaining gut health to reduce the risk of obesity, cardiovascular and other age-related inflammatory diseases: recent challenges and future recommendations.

A healthy balanced diet is crucial in protecting the immune system against infections and diseases. Poor diets, such as the Western diet, contribute to the development of metabolic diseases, hypertension, and obesity. Microbiota, primarily composed of different microorganisms and residing in the gastrointestinal tract (GIT), also play a significant role in maintaining gut health. Polyphenols and probiotics found in fruits, vegetables, whole grains, legumes, nuts, and seeds promote gut health and support the growth of beneficial bacteria. Different types of diets, their categories, and their impact on health are also mentioned. The relationship between diet, gut health, and the risk of developing obesity, cardiovascular diseases, and inflammatory diseases is discussed in this review article. The rationale behind the review concludes future recommendations for maintaining gut health and reducing the occurrence of obesity, cardiometabolic diseases, and other inflammatory diseases. There is also the need for standardized research methods, long-term studies, and translating scientific knowledge into practical dietary recommendations.

Development and immunological evaluation of an mRNA-based vaccine targeting Naegleria fowleri for the treatment of primary amoebic meningoencephalitis.

More than 95% of patients fall victim to primary amoebic meningoencephalitis (PAM), a fatal disease attacking the central nervous system. Naegleria fowleri, a brain-eating microorganism, is PAM's most well-known pathogenic ameboflagellate. Despite the use of antibiotics, the fatality rate continues to rise as no clinical trials have been conducted against this disease. To address this, we mined the UniProt database for pathogenic proteins and selected assumed epitopes to create an mRNA-based vaccine. We identified thirty B-cell and T-cell epitopes for the vaccine candidate. These epitopes, secretion boosters, subcellular trafficking structures, and linkers were used to construct the vaccine candidate. Through predictive modeling and confirmation via the Ramachandran plot (with a quality factor of 92.22), we assessed secondary and 3D structures. The adjuvant RpfE was incorporated to enhance the vaccine construct's immunogenicity (GRAVY index: 0.394, instability index: 38.99, antigenicity: 0.8). The theoretical model of immunological simulations indicated favorable responses from both innate and adaptive immune cells, with memory cells expected to remain active for up to 350 days post-vaccination, while the antigen was eliminated from the body within 24 h. Notably, strong interactions were observed between the vaccine construct and TLR-4 (- 11.9 kcal/mol) and TLR-3 (- 18.2 kcal/mol).

The natural breakthrough: phytochemicals as potent therapeutic agents against spinocerebellar ataxia type 3.

There is no FDA-approved drug for neurological disorders like spinocerebellar ataxia type 3. CAG repeats mutation in the ATXN3 gene, causing spinocerebellar ataxia type 3 disease. Symptoms include sleep cycle disturbance, neurophysiological abnormalities, autonomic dysfunctions, and depression. This research focuses on drug discovery against ATXN3 using phytochemicals of different plants. Three phytochemical compounds (flavonoids, diterpenoids, and alkaloids) were used as potential drug candidates and screened against the ATXN3 protein. The 3D structure of ATXN3 protein and phytochemicals were retrieved and validation of the protein was 98.1% Rama favored. The protein binding sites were identified for the interaction by CASTp. ADMET was utilized for the pre-clinical analysis, including solubility, permeability, drug likeliness and toxicity, and chamanetin passed all the ADMET properties to become a lead drug candidate. Boiled egg analysis attested that the ligand could cross the gastrointestinal tract. Pharmacophore analysis showed that chamanetin has many hydrogen acceptors and donors which can form interaction bonds with the receptor proteins. Chamanetin passed all the screening analyses, having good absorption, no violation of Lipinski's rule, nontoxic properties, and good pharmacophore properties. Chamanetin was one of the lead compounds with a - 7.2 kcal/mol binding affinity after screening the phytochemicals. The stimulation of ATXN3 showed stability after 20 ns of interaction in an overall 50 ns MD simulation. Chamanetin (Flavonoid) was predicted to be highly active against ATXN3 with good drug-like properties. In-silico active drug against ATXN3 from a plant source and good pharmacokinetics parameters would be excellent drug therapy for SC3, such as flavonoids (Chamanetin).

Biodegradation of PVCs through in-vitro identification of Bacillus albus and computational pathway analysis of ABH enzyme.

Microplastics pose significant challenges to ecosystems and organisms. They can be ingested by marine and terrestrial species, leading to potential health risks and ecological disruptions. This study aims to address the urgent need for effective remediation strategies by focusing on the biodegradation of microplastics, specifically polyvinyl chloride (PVC) derivatives, using the bacterial strain Bacillus albus. The study provides a comprehensive background on the accumulation of noxious substances in the environment and the importance of harnessing biodegradation as an eco-friendly method for pollutant elimination. The specific objective is to investigate the enzymatic capabilities of Bacillus albus, particularly the alpha/beta hydrolases (ABH), in degrading microplastics. To achieve this, in-silico studies were conducted, including analysis of the ABH protein sequence and its interaction with potential inhibitors targeting PVC derivatives. Docking scores of - 7.2 kcal/mol were obtained to evaluate the efficacy of the interactions. The study demonstrates the promising bioremediation prospects of Bacillus albus for microplastics, highlighting its potential as a key player in addressing microplastic pollution. The findings underscore the urgent need for further experimental validation and practical implementation of Bacillus albus in environmental remediation strategies.

Biological Significance of EphB4 Expression in Cancer.

Eph receptors and their Eph receptor-interacting (ephrin) ligands comprise a vital cell communication system with several functions. In cancer cells, there was evidence of bilateral Eph receptor signaling with both tumor-suppressing and tumor-promoting actions. As a member of the Eph receptor family, EphB4 has been linked to tumor angiogenesis, growth, and metastasis, which makes it a viable and desirable target for drug development in therapeutic applications. Many investigations have been conducted over the last decade to elucidate the structure and function of EphB4 in association with its ligand ephrinB2 for its involvement in tumorigenesis. Although several EphB4-targeting drugs have been investigated, and some selective inhibitors have been evaluated in clinical trials. This article addresses the structure and function of the EphB4 receptor, analyses its possibility as an anticancer therapeutic target, and summarises knowledge of EphB4 kinase inhibitors. To summarise, EphB4 is a difficult but potential treatment option for cancers.