Synthesis of Water-Dispersible Poly(dimethylsiloxane) and Its Potential Application in the Paper Coating Industry as an Alternative for PFAS-Coated Paper and Single-Use Plastics.

Polyethylene-, polyvinylidene chloride-, and per- and polyfluoroalkyl substance-coated paper generate microplastics or fluorochemicals in the environment. Here, we report an approach for the development of oil-resistant papers using an environmentally friendly, fluorine-free, water-dispersible poly(dimethylsiloxane) (PDMS) coating on kraft paper. Carboxylic-functionalized PDMS (PDMS-COOH) was synthesized and subsequently neutralized with ammonium bicarbonate to obtain a waterborne emulsion, which was then coated onto kraft paper. The water resistance of the coated paper was determined via Cobb60 measurements. The Cobb60 value was reduced to 2.70 ± 0.14 g/m2 as compared to 87.6 ± 5.1 g/m2 for uncoated paper, suggesting a remarkable improvement in water resistance. Similarly, oil resistance was found to be 12/12 on the kit test scale versus 0/12 for uncoated paper. In addition, the coated paper retained 70-90% of its inherent mechanical properties, and more importantly, the coated paper was recycled via pulp recovery using a standard protocol with a 91.1% yield.

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.

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.

Characterizations of biogenic selenium nanoparticles and their anti-biofilm potential against Streptococcus mutans ATCC 25175.

INTRODUCTION: S. mutans has been identified as the primary pathogenic bacterium in biofilm-mediated dental caries. The biogenic selenium nanoparticles (SeNPs) produced by L. plantarum KNF-5 were used in this study against S. mutans ATCC 25175. OBJECTIVES: The aims of this study were: (1) the biosynthesis of SeNPs by L. plantarum KNF-5, (2) the characterization of SeNPs, (3) the investigation of the inhibitory effect of biogenic SeNPs against S. mutans ATCC 25175, and (4) the determination of the anti-biofilm potential of SeNPS against S. mutans ATCC 25175. METHODOLOGY: 3 mL of the culture was added to 100 mL of MRS medium and incubated. After 4 h, Na2SeO3 solution (concentration 100 µg/mL) was added and incubated at 37 °C for 36 h. The color of the culture solution changed from brownish-yellow to reddish, indicating the formation of SeNPs. The characterization of SeNPs was confirmed by UV-Vis spectrophotometry, FTIR, SEM-EDS and a particle size analyzer. The antibacterial activity was determined by the disk diffusion method, the MIC by the micro-double dilution method, and the biofilm inhibitory potential by the crystal violet method and the MTT assay. The effect of SeNPs on S. mutans ATCC 25175 was determined using SEM and CLSM spectrometry techniques. The sulfate-anthrone method was used to analyze the effect of SeNPs on insoluble extracellular polysaccharides. The expression of genes in S. mutans ATCC 25175 was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). PREPARATION OF NANOPARTICLES: SeNPs produced by probiotic bacteria are considered a safe method. In this study, L. plantarum KNF-5 (probiotic strain) was used for the production of SeNPs. RESULTS: The biogenic SeNPs were spherical and coated with proteins and polysaccharides and had a diameter of about 270 nm. The MIC of the SeNPs against S. mutans ATCC 25175 was 3.125 mg/mL. Biofilm growth was also significantly suppressed at this concentration. The expression of genes responsible for biofilm formation (GtfB, GtfC, BrpA and GbpB,) was reduced when S. mutans ATCC 25175 was treated with SeNPs. CONCLUSION: It was concluded that the biogenic SeNPs produced by L. plantarum KNF-5 was highly effective to inhibit the growth of S. mutans ATCC 25175. NOVELTY STATEMENT: The application of biogenic SeNPs, a natural anti-biofilm agent against S. mutans ATCC 25175. In the future, this study will provide a new option for the prevention and treatment of dental caries.

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.

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.

A remote digital memory composite to detect cognitive impairment in memory clinic samples in unsupervised settings using mobile devices.

Remote monitoring of cognition holds the promise to facilitate case-finding in clinical care and the individual detection of cognitive impairment in clinical and research settings. In the context of Alzheimer's disease, this is particularly relevant for patients who seek medical advice due to memory problems. Here, we develop a remote digital memory composite (RDMC) score from an unsupervised remote cognitive assessment battery focused on episodic memory and long-term recall and assess its construct validity, retest reliability, and diagnostic accuracy when predicting MCI-grade impairment in a memory clinic sample and healthy controls. A total of 199 participants were recruited from three cohorts and included as healthy controls (n = 97), individuals with subjective cognitive decline (n = 59), or patients with mild cognitive impairment (n = 43). Participants performed cognitive assessments in a fully remote and unsupervised setting via a smartphone app. The derived RDMC score is significantly correlated with the PACC5 score across participants and demonstrates good retest reliability. Diagnostic accuracy for discriminating memory impairment from no impairment is high (cross-validated AUC = 0.83, 95% CI [0.66, 0.99]) with a sensitivity of 0.82 and a specificity of 0.72. Thus, unsupervised remote cognitive assessments implemented in the neotiv digital platform show good discrimination between cognitively impaired and unimpaired individuals, further demonstrating that it is feasible to complement the neuropsychological assessment of episodic memory with unsupervised and remote assessments on mobile devices. This contributes to recent efforts to implement remote assessment of episodic memory for case-finding and monitoring in large research studies and clinical care.

Cellular electrophysiological effects of the citrus flavonoid hesperetin in dog and rabbit cardiac ventricular preparations.

Recent experimental data shows that hesperetin, a citrus flavonoid, affects potassium channels and can prolong the QTc interval in humans. Therefore, in the present study we investigated the effects of hesperetin on various transmembrane ionic currents and on ventricular action potentials. Transmembrane current measurements and action potential recordings were performed by patch-clamp and the conventional microelectrode techniques in dog and rabbit ventricular preparations. At 10 µM concentration hesperetin did not, however, at 30 µM significantly decreased the amplitude of the IK1, Ito, IKr potassium currents. Hesperetin at 3-30 µM significantly and in a concentration-dependent manner reduced the amplitude of the IKs current. The drug significantly decreased the amplitudes of the INaL and ICaL currents at 30 µM. Hesperetin (10 and 30 µM) did not change the action potential duration in normal preparations, however, in preparations where the repolarization reserve had been previously attenuated by 100 nM dofetilide and 1 µg/ml veratrine, caused a moderate but significant prolongation of repolarization. These results suggest that hesperetin at close to relevant concentrations inhibits the IKs outward potassium current and thereby reduces repolarization reserve. This effect in certain specific situations may prolong the QT interval and consequently may enhance proarrhythmic risk.

Unraveling disparities: Probing gender, race, and geographic inequities in pulmonary heart disease mortality in the United States: An extensive longitudinal examination (1999-2020) leveraging CDC WONDER data.

This comprehensive study delves into the epidemiological landscape of Pulmonary Heart Disease (PHD) mortality in the United States from 1999 to 2020, leveraging the extensive CDC WONDER database. PHD encompasses conditions affecting the right side of the heart due to lung disorders or elevated pressure in the pulmonary arteries, including pulmonary hypertension, pulmonary embolism, and chronic thromboembolic pulmonary hypertension (CTEPH). Analyzing data from death certificates, demographic characteristics, and geographical segmentation, significant trends emerge. The age-adjusted mortality rates (AAMRs) for PHD-related deaths show a fluctuating pattern, initially decreasing from 1999 to 2006, followed by a steady increase until 2020. Male patients consistently exhibit higher AAMRs than females, with notable disparities observed among racial/ethnic groups and geographic regions. Non-hispanic (NH) Black or African American individuals, residents of specific states like Colorado and the District of Columbia, and those in the Midwest region demonstrate elevated AAMRs. Furthermore, nonmetropolitan areas consistently manifest higher AAMRs than metropolitan areas. These findings underscore the urgent need for intensified prevention and treatment strategies to address the rising mortality associated with PHD, particularly among vulnerable populations. Insights from this study offer valuable guidance for public health initiatives aimed at reducing PHD-related mortality and improving outcomes nationwide.

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.

Divergent responses of phosphorus solubilizing bacteria with P-laden biochar for enhancing nutrient recovery, growth, and yield of canola (Brassica napus L.).

The growing global population has led to a heightened need for food production, and this rise in agricultural activity is closely tied to the application of phosphorus-based fertilizers, which contributes to the depletion of rock phosphate (RP) reserves. Considering the limited P reserves, different approaches were conducted previously for P removal from waste streams, while the adsorption of ions is a novel strategy with more applicability. In this study, a comprehensive method was employed to recover phosphorus from wastewater by utilizing biochar engineered with minerals such as calcium, magnesium, and iron. Elemental analysis of the wastewater following a batch experiment indicated the efficiency of the engineered biochar as an adsorbent. Subsequently, the phosphorus-enriched biochar, hereinafter (PL-BCsb), obtained from the wastewater, underwent further analysis through FTIR, XRD, and nutritional assessments. The results revealed that the PL-BCsb contained four times higher (1.82%) P contents which further reused as a fertilizer supplementation for Brassica napus L growth. PL-BCsb showed citric acid (34.03%), Olsen solution (10.99%), and water soluble (1.74%) P desorption. Additionally, phosphorous solubilizing bacteria (PSB) were incorporated with PL-BCsb along two P fertilizer levels P45 (45 kg ha-1) and P90 (90 kg ha-1) for evaluation of phosphorus reuse efficiency. Integrated application of PL-BCsb with half of the suggested amount of P45 (45 kg ha-1) and PSB increased growth, production, physiological, biochemical, and nutritional qualities of canola by almost two folds when compared to control. Similarly, it also improved soil microbial biomass carbon up to four times, alkaline and acid phosphatases activities both by one and half times respectively as compared to control P (0). Furthermore, this investigation demonstrated that waste-to-fertilizer technology enhanced the phosphorus fertilizer use efficiency by 55-60% while reducing phosphorus losses into water streams by 90%. These results have significant implications for reducing eutrophication, making it a promising approach for mitigating environmental pollution and addressing climate change.

Impact of low light intensity on biomass partitioning and genetic diversity in a chickpea mapping population.

With recent climatic changes, the reduced access to solar radiation has become an emerging threat to chickpeas' drought tolerance capacity under rainfed conditions. This study was conducted to assess, and understand the effects of reduced light intensity and quality on plant morphology, root development, and identifying resistant sources from a Sonali/PBA Slasher mapping population. We evaluated 180 genotypes, including recombinant inbred lines (RILs), parents, and commercial checks, using a split-block design with natural and low light treatments. Low light conditions, created by covering one of the two benches inside two growth chambers with a mosquito net, reduced natural light availability by approximately 70%. Light measurements encompassed photosynthetic photon flux density, as well as red, and far-red light readings taken at various stages of the experiment. The data, collected from plumule emergence to anthesis initiation, encompassed various indices relevant to root, shoot, and carbon gain (biomass). Statistical analysis examined variance, treatment effects, heritability, correlations, and principal components (PCs). Results demonstrated significant reductions in root biomass, shoot biomass, root/shoot ratio, and plant total dry biomass under suboptimal light conditions by 52.8%, 28.2%, 36.3%, and 38.4%, respectively. Plants also exhibited delayed progress, taking 9.2% longer to produce their first floral buds, and 19.2% longer to commence anthesis, accompanied by a 33.4% increase in internodal lengths. A significant genotype-by-environment interaction highlighted differing genotypic responses, particularly in traits with high heritability (> 77.0%), such as days to anthesis, days to first floral bud, plant height, and nodes per plant. These traits showed significant associations with drought tolerance indicators, like root, shoot, and plant total dry biomass. Genetic diversity, as depicted in a genotype-by-trait biplot, revealed contributions to PC1 and PC2 coefficients, allowing discrimination of low-light-tolerant RILs, such as 1_52, 1_73, 1_64, 1_245, 1_103, 1_248, and 1_269, with valuable variations in traits of interest. These RILs could be used to breed desirable chickpea cultivars for sustainable production under water-limited conditions. This study concludes that low light stress disrupts the balance between root and shoot morphology, diverting photosynthates to vegetative structures at the expense of root development. Our findings contribute to a better understanding of biomass partitioning under limited-light conditions, and inform breeding strategies for improved drought tolerance in chickpeas.

Promising phytopharmacology, nutritional potential, health benefits, and traditional usage of Tribulus terrestris L. herb.

Traditional medicines are becoming more popular as people become more aware of the dangers of synthetic pharmaceuticals. Tribulus terrestris L., (Gokharu) an annual herbaceous plant, has been extensively utilized by herbalists for numerous medicinal purposes. T. terrestris has been studied for its multiple therapeutic effects, including immunomodulatory, aphrodisiac, anti-urolithic, absorption enhancer, cardioprotective, antidiabetic, anti-inflammatory, hypolipidemic, neuro-protective, anticancer, and analgesic properties. Saponins and flavonoids are two examples of beneficial substances that have recently been found in T. terrestris. These chemicals are very important for a variety of therapeutic effects. Numerous studies have shown that T. terrestris products and various parts may have antioxidant, anti-inflammatory, anti-cancer, anti-diabetic, testosterone-boosting, and liver protective effects. According to the published evidence, T. terrestris boosts testosterone secretion, regulates blood pressure, and protects the human body against injuries. The cardiovascular, reproductive, and urinary systems are all severely impacted. Due to its potent bioactive compounds, the literature evaluated from a wide range of sources including books, reports, PubMed, ScienceDirect, Wiley, Springer, and other databases demonstrated the extraordinary potential to treat numerous human and animal ailments. Our review is different from other published articles because we explored its importance for humans and especially in veterinary like poultry health. It could also be used as an aphrodisiac to treat different fertility-related disorders in human and animal science. More research into the pharmacodynamics of herbs like T. terrestris is needed so that it can be used in a wider variety of nutraceutical products for humans and poultry.

Study of selenium enrichment metabolomics in Bacillus subtilis BSN313 via transcriptome analysis.

In this study, the transcriptome analysis was practiced to identify potential genes of probiotic Bacillus subtilis BSN313 involved in selenium (Se) enrichment metabolism. The transcriptomic variation of the strain was deliberated in presence of three different sodium selenite concentrations (0, 3, and 20 µg/mL). The samples were taken at 1 and 13 h subsequent to inoculation of selenite and gene expression profiles in Se metabolism were analyzed through RNA sequencing. The gene expression levels of the pre log phase were lower than the stationary phase. It is because, the bacteria has maximum grown with high concentration of Se (enriched with organic Se), at stationary phase. Bacterial culture containing 3 µg/mL concentration of inorganic Se (sodium selenite) has shown highest gene expression as compared to no or high concentration of Se. This concentration (3 µg/mL) of sodium selenite (as Se) in the medium promoted the upregulation of thioredoxin reductase expression, whereas its higher Se concentration inhibited the formation of selenomethionine (SeMet). The result of 5 L bioreactor fermentation showed that SeMet was also detected in the fermentation supernatant as the growth entered in the late stationary phase and reached up to 857.3 ng/mL. The overall intracellular SeMet enriched content in BSN313 was extended up to 23.4 µg/g dry cell weight. The other two selenoamino acids (Se-AAs), methyl-selenocysteine, and selenocysteine were hardly detected in medium supernatant. From this study, it was concluded that SeMet was the highest content of organic Se byproduct biosynthesized by B. subtilis BSN313 strain in Se-enriched medium during stationary phase. Thus, B. subtilis BSN313 can be considered a commercial probiotic strain that can be used in the food and pharmaceutical industries. This is because it can meet the commercial demand for Se-AAs (SeMet) in both industries.

Bio-net dataset: AI-based diagnostic solutions using peripheral blood smear images.

Peripheral blood smear examination is one of the basic steps in the evaluation of different blood cells. It is a confirmatory step after an automated complete blood count analysis. Manual microscopy is time-consuming and requires professional laboratory expertise. Therefore, the turn-around time for peripheral smear in a health care center is approximately 3-4 hours. To avoid the traditional method of manual counting under the microscope a computerized automation of peripheral blood smear examination has been adopted, which is a challenging task in medical diagnostics. In recent times, deep learning techniques have overcome the challenges associated with human microscopic evaluation of peripheral smears and this has led to reduced cost and precise diagnosis. However, their application can be significantly improved by the availability of annotated datasets. This study presents a large customized annotated blood cell dataset (named the Bio-Net dataset from healthy individuals) and blood cell detection and counting in the peripheral blood smear images. A mini-version of the dataset for specialized WBC-based image processing tasks is also equipped to classify the healthy and mature WBCs in their respective classes. An object detection algorithm called You Only Look Once (YOLO) with a refashion disposition has been trained on the novel dataset to automatically detect and classify blood cells into RBCs, WBCs, and platelets and compare the results with other publicly available datasets to highlight the versatility. In short the introduction of the Bio-Net dataset and AI-powered detection and counting offers a significant potential for advancement in biomedical research for analyzing and understanding biological data.

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).

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).

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.

Control charts using half-normal and half-exponential power distributions using repetitive sampling.

This manuscript presents the development of an attribute control chart (ACC) designed to monitor the number of defective items in manufacturing processes. The charts are specifically tailored using time-truncated life test (TTLT) for two lifetime data distributions: the half-normal distribution (HND) and the half-exponential power distribution (HEPD) under a repetitive sampling scheme (RSS). To assess the effectiveness of the proposed control charts, both in-control (IC) and out-of-control (OOC) scenarios are considered by deriving the average run length (ARL). Various factors, including sample sizes, control coefficients, and truncated constants for shifted phases, are taken into account to evaluate the performance of the charts in terms of ARL. The behavior of ARLs is analyzed in the shifted process by introducing shifts in its parameters. The superiority of the HEPD-based chart is highlighted by comparing it with both the HND-based ACC and the ACC based on the Exponential distribution (ED) under TTLT using RSS. The results showcase the superior performance of the proposed HEPD-based chart, indicated by smaller ARL values. Additionally, the benefits of another proposed ACC using HND are compared with the ED-based ACC under RSS, further confirming the effectiveness of the HND-based approach through smaller ARLs Finally, the proposed control charts are evaluated through simulation testing and real-life implementation, emphasizing their practical applicability in real-world manufacturing settings.