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Single-point mutations in the Kirsten rat sarcoma (KRAS) viral proto-oncogene are the most common cause of human cancer. In humans, oncogenic KRAS mutations are responsible for about 30% of lung, pancreatic, and colon cancers. One of the predominant mutant KRAS G12D variants is responsible for pancreatic cancer and is an attractive drug target. At the time of writing, no Food and Drug Administration (FDA) approved drugs are available for the KRAS G12D mutant. So, there is a need to develop an effective drug for KRAS G12D. The process of finding new drugs is expensive and time-consuming. On the other hand, in silico drug designing methodologies are cost-effective and less time-consuming. Herein, we employed machine learning algorithms such as K-nearest neighbor (KNN), support vector machine (SVM), and random forest (RF) for the identification of new inhibitors against the KRAS G12D mutant. A total of 82 hits were predicted as active against the KRAS G12D mutant. The active hits were docked into the active site of the KRAS G12D mutant. Furthermore, to evaluate the stability of the compounds with a good docking score, the top two complexes and the standard complex (MRTX-1133) were subjected to 200 ns MD simulation. The top two hits revealed high stability as compared to the standard compound. The binding energy of the top two hits was good as compared to the standard compound. Our identified hits have the potential to inhibit the KRAS G12D mutation and can help combat cancer. To the best of our knowledge, this is the first study in which machine-learning-based virtual screening, molecular docking, and molecular dynamics simulation were carried out for the identification of new promising inhibitors for the KRAS G12D mutant.
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Heavy metal pollution threatens plant growth and development as well as ecological stability. Here, we synthesize current research on the interplay between plants and their microbial symbionts under heavy metal stress, highlighting the mechanisms employed by microbes to enhance plant tolerance and resilience. Several key strategies such as bioavailability alteration, chelation, detoxification, induced systemic tolerance, horizontal gene transfer, and methylation and demethylation, are examined, alongside the genetic and molecular basis governing these plant-microbe interactions. However, the complexity of plant-microbe interactions, coupled with our limited understanding of the associated mechanisms, presents challenges in their practical application. Thus, this review underscores the necessity of a more detailed understanding of how plants and microbes interact and the importance of using a combined approach from different scientific fields to maximize the benefits of these microbial processes. By advancing our knowledge of plant-microbe synergies in the metabolism of heavy metals, we can develop more effective bioremediation strategies to combat the contamination of soil by heavy metals.
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Interacciones de Hierba-Droga , Metales Pesados , Metales Pesados/toxicidad , Procesamiento Proteico-Postraduccional , SueloRESUMEN
Biogenic nanoparticle (NP), derived from plant sources, is gaining prominence as a viable, cost-effective, sustainable, and biocompatible alternative for mitigating the extensive environmental impact of arsenic on the interplay between plant-soil system. Herein, the impact of green synthesized zinc oxide nanoparticles (ZnONPs) was assessed on Catharanthus roseus root system-associated enzymes and their possible impact on microbiome niches (rhizocompartments) and overall plant performance under arsenic (As) gradients. The application of ZnONPs at different concentrations successfully modified the arsenic uptake in various plant parts, with the root arsenic levels increasing 1.5 and 1.4-fold after 25 and 50 days, respectively, at medium concentration compared to the control. Moreover, ZnONPs gradients regulated the various soil enzyme activities. Notably, urease and catalase activities showed an increase when exposed to low concentrations of ZnONPs, whereas saccharase and acid phosphatase displayed the opposite pattern, showing increased activities under medium concentration which possibly in turn influence the plant root system associated microflora. The use of nonmetric multidimensional scaling ordination revealed a significant differentiation (with a significance level of p < 0.05) in the structure of both bacterial and fungal communities under different treatment conditions across root associated niches. Bacterial and fungal phyla level analysis showed that Proteobacteria and Basidiomycota displayed a significant increase in relative abundance under medium ZnONPs concentration, as opposed to low and high concentrations, respectively. Similarly, in depth genera level analysis revealed that Burkholderia, Halomonas, Thelephora and Sebacina exhibited a notably high relative abundance in both the rhizosphere and rhizoplane (the former refers to the soil region influenced by root exudates, while the latter is the root surface itself) under medium concentrations of ZnONPs, respectively. These adjustments to the plant root-associated microcosm likely play a role in protecting the plant from oxidative stress by regulating the plant's antioxidant system and overall biomass.
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Arsénico , Raíces de Plantas , Microbiología del Suelo , Contaminantes del Suelo , Contaminantes del Suelo/metabolismo , Arsénico/metabolismo , Arsénico/química , Raíces de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Catharanthus/metabolismo , Catharanthus/efectos de los fármacos , Tecnología Química Verde , Nanopartículas del Metal/química , Microbiota/efectos de los fármacos , Bacterias/metabolismo , Bacterias/efectos de los fármacos , RizosferaRESUMEN
The elimination of hazardous industrial pollutants from aqueous solutions is an emerging area of scientific research and a worldwide problem. An efficient catalyst, Ag-CuO was synthesized for the degradation of methylene blue, the chemical sensing of ammonia. A simple novel synthetic method was reported in which new plant material Capparis decidua was used for the reduction and stabilization of the synthesized nanocatalyst. A Varying amount of Ag was doped into CuO to optimize the best catalyst that met the required objectives. Through this, the Ag-CuO nanocomposite was characterized by XRD, SEM, HR-TEM, EDX, and FTIR techniques. The mechanism of increased catalytic activity with Ag doping involves the formation of charge sink and suppression of drop back probability of charge from conduction to valance band. Herein, 2.7 mol % Ag-CuO exhibited better catalytic activities and it was used through subsequent catalytic experiments. The experimental conditions such as pH, catalyst dose, analyte initial concentration, and contact time were optimized. The as-synthesized nanocomposite demonstrates an excellent degradation efficacy of MB which is 97% at pH 9. More interestingly, the as-synthesized catalyst was successfully applied for the chemical sensing of ammonia even at very low concentrations. The lower limit of detection (LLOD) also called analytic sensitivity was calculated for ammonia sensing and found to be 1.37 ppm.
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Nylon-6,6 microplastics (NMPs) in aquatic systems have emerged as potential contaminants to the global environment and have garnered immense consideration over the years. Unfortunately, there is currently no efficient method available to eliminate NMPs from sewage. This study aims to address this issue by isolating Brucella intermedia ZL-06, a bacterium capable of producing a bacterial polysaccharide-based flocculant (PBF). The PBF generated from this bacterium shows promising efficacy in effectively flocculating NMPs. Subsequently, the precipitated flocs (NMPs + PBF) were utilized as sustainable feedstock for synthesizing PBF. The study yielded 6.91 g/L PBF under optimum conditions. Genome sequencing analysis was conducted to study the mechanisms of PBF synthesis and nylon-6,6 degradation. The PBF exhibited impressive flocculating capacity of 90.1 mg/g of PBF when applied to 0.01 mm NMPs, aided by the presence of Ca2+. FTIR and XPS analysis showed the presence of hydroxyl, carboxyl, and amine groups in PBF. The flocculation performance of PBF conformed to Langmuir isotherm and pseudo-first-order adsorption kinetics model. These findings present a promising approach for reducing the production costs of PBF by utilizing NMPs as sustainable nutrient sources.
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Brucella , Caprolactama/análogos & derivados , Microplásticos , Polímeros , Plásticos , Aguas del Alcantarillado/microbiología , FloculaciónRESUMEN
Illicium verum, or star anise, has many uses ranging from culinary to religious. It has been used in the food industry since ancient times. The main purpose of this study was to determine the chemical composition, antibacterial, antibiofilm, and anti-quorum sensing activities of the essential oil (EO) obtained via hydro-distillation of the aerial parts of Illicium verum. Twenty-four components were identified representing 92.55% of the analyzed essential oil. (E)-anethole (83.68%), limonene (3.19%), and α-pinene (0.71%) were the main constituents of I. verum EO. The results show that the obtained EO was effective against eight bacterial strains to different degrees. Concerning the antibiofilm activity, trans-anethole was more effective against biofilm formation than the essential oil when tested using sub-inhibitory concentrations. The results of anti-swarming activity tested against P. aeruginosa PAO1 revealed that I. verum EO possesses more potent inhibitory effects on the swarming behavior of PAO1 when compared to trans-anethole, with the percentage reaching 38% at a concentration of 100 µg/mL. The ADME profiling of the identified phytocompounds confirmed their important pharmacokinetic and drug-likeness properties. The in silico study using a molecular docking approach revealed a high binding score between the identified compounds with known target enzymes involved in antibacterial and anti-quorum sensing (QS) activities. Overall, the obtained results suggest I. verum EO to be a potentially good antimicrobial agent to prevent food contamination with foodborne pathogenic bacteria.
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Illicium , Aceites Volátiles , Aceites Volátiles/farmacología , Aceites Volátiles/química , Percepción de Quorum , Illicium/química , Simulación del Acoplamiento Molecular , Biopelículas , Antibacterianos/farmacología , Antibacterianos/química , Bacterias , Pseudomonas aeruginosaRESUMEN
Benzene, a potent carcinogen, is known to cause acute myeloid leukaemia. While chemotherapy is commonly used for cancer treatment, its side effects have prompted scientists to explore natural products that can mitigate the haematotoxic effects induced by chemicals. One area of interest is nano-theragnostics, which aims to enhance the therapeutic potential of natural products. This study aimed to enhance the effects of methanolic extracts from Ocimum basilicum, Rosemarinus officinalis, and Thymus vulgaris by loading them onto silica nanobeads (SNBs) for targeted delivery to mitigate the benzene-induced haematotoxic effects. The SNBs, 48 nm in diameter, were prepared using a chemical method and were then loaded with the plant extracts. The plant-extract-loaded SNBs were then coated with carboxymethyl cellulose (CMC). The modified SNBs were characterized using various techniques such as scanning electron microscopy (SEM), X-ray diffraction (XRD), UV-visible spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. The developed plant-extract-loaded and CMC-modified SNBs were administered intravenously to benzene-exposed rats, and haematological and histopathological profiling was conducted. Rats exposed to benzene showed increased liver and spleen weight, which was mitigated by the plant-extract-loaded SNBs. The differential white blood cell (WBC) count was higher in rats with benzene-induced haematotoxicity, but this count decreased significantly in rats treated with plant-extract-loaded SNBs. Additionally, blast cells observed in benzene-exposed rats were not found in rats treated with plant-extract-loaded SNBs. The SNBs facilitated targeted drug delivery of the three selected medicinal herbs at low doses. These results suggest that SNBs have promising potential as targeted drug delivery agents to mitigate haematotoxic effects induced by benzene in rats.
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Anethum graveolens L. has been known as an aromatic, medicinal, and culinary herb since ancient times. The main purpose of this study was to determine the chemical composition, antibacterial, antibiofilm, and anti-quorum sensing activities of the essential oil (EO) obtained by hydro-distillation of the aerial parts. Twelve components were identified, representing 92.55% of the analyzed essential oil. Limonene (48.05%), carvone (37.94%), cis-dihydrocarvone (3.5%), and trans-carvone (1.07%) were the main identified constituents. Results showed that the obtained EO was effective against eight bacterial strains at different degrees. Concerning the antibiofilm activity, limonene was more effective against biofilm formation than the essential oil when tested using sub-inhibitory concentrations. The results of anti-swarming activity tested against P. aeruginosa PAO1 revealed that A. graveolens induced more potent inhibitory effects in the swarming behavior of the PAO1 strain when compared to limonene, with a percentage reaching 33.33% at a concentration of 100 µg/mL. The ADME profiling of the identified phytocompounds confirms their important pharmacokinetic and drug-like properties. The in-silico study using molecular docking approaches reveals a high binding score between the identified compounds and known target enzymes involved in antibacterial and anti-quorum sensing (QS) activities. Overall, the obtained results highlight the possible use of A. graveolens EO to prevent food contamination with foodborne pathogenic bacteria.
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Staphylococcus aureus (S. aureus) is a ubiquitous pathogen responsible for several severe infections. This study aimed to investigate the adhesive properties and antibiotic resistance among clinical S. aureus isolated from Hail Hospital Province, Kingdom of Saudi Arabia (KSA), using molecular approaches. This study was conducted according to the ethical committee at Hail's guidelines on twenty-four S. aureus isolates. A polymerase chain reaction (PCR) was performed to identify genes encoding the ß-lactamase resistance (blaZ), methicillin resistance (mecA), fluoroquinolone resistance (norA), nitric oxide reductase (norB), fibronectin (fnbA and fnbB), clumping factor (clfA) and intracellular adhesion factors (icaA and icaD). This qualitative study tested adhesion based on exopolysaccharide production on Congo red agar (CRA) medium and biofilm formation on polystyrene by S. aureus strains. Among 24 isolates, the cna and blaz were the most prevalent (70.8%), followed by norB (54.1%), clfA (50.0%), norA (41.6%), mecA and fnbB (37.5%) and fnbA (33.3%). The presence of icaA/icaD genes was demonstrated in almost all tested strains in comparison to the reference strain, S. aureus ATCC 43300. The phenotypic study of adhesion showed that all tested strains had moderate biofilm-forming capacity on polystyrene and represented different morphotypes on a CRA medium. Five strains among the twenty-four harbored the four genes of resistance to antibiotics (mecA, norA, norB and blaz). Considering the genes of adhesion (cna, clfA, fnbA and fnbB), these genes were present in 25% of the tested isolates. Regarding the adhesive properties, the clinical isolates of S. aureus formed biofilm on polystyrene, and only one strain (S17) produced exopolysaccharides on Congo red agar. All these results contribute to an understanding that the pathogenesis of clinical S. aureus isolates is due to their antibiotic resistance and adhesion to medical material.
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In the present study, sequencing of TORC1 prompter region explored three SNPs at loci g.80G>T, g.93A>T, and g.1253G>A. The SNP1 produced GG, GT and TT, SNP2 AA, AT and TT, and SNP3 produced GG, GA and AA genotypes. Allelic and genotypic frequencies analysis exhibited that SNP1 is within Hardy-Weinberg equilibrium (HWE). All three SNPs were found highly polymorphic as PIC value (0.25 < PIC < 0.50). At loci g.80G>T the cattle with genotype GG showed significantly (P <0.01) larger body length (BL), Wither height (WH), Hip height (HH), Rump length (RL), Hip width (HW), Chest depth (CD), and Chest circumference (CC). The genotype AA at g.93A>T showed significantly (P< 0.01 and 0.05) Larger body length (BL), Wither height (WH), Hip height, Rump length (RL), Hip width (HW), Chest depth (CD), and Chest circumference (CC). Interestingly, the carcass quality parameters such as Ultrasound loin area (ULA) and Intramuscular fat percentage (IF%) was highest in genotype GG at loci g.1253G>A. These findings conclude that genotype GG at loci g.80 G>T and AA at loci g.93A>T could be used as genetic markers for body measurement and genotype GG at loci g.1253G>A for carcass quality traits of TORC1 gene in Qinchuan beef cattle.
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Pesos y Medidas Corporales , Polimorfismo de Nucleótido Simple , Bovinos/genética , Animales , Fenotipo , Genotipo , Polimorfismo de Nucleótido Simple/genética , Marcadores Genéticos , Frecuencia de los Genes , CarneRESUMEN
Fungal infections caused by Candida species have attracted great interest due to their resistance to commercial antifungal agents. Essential oils from aromatic and medicinal plants have many bioactive compounds that are known for their important biological activities, mainly their antimicrobial effects. In the present study, we aimed to evaluate the antifungal ability of Elettaria cardamomum essential oil (EO) against different clinical Candida isolates. Then, we investigated the anti-phospholipase, anti-protease, and anti-biofilm activity of E. cardamomum EO against the selected isolates. Twenty-four Candida strains (clinical and reference) were tested for virulence factors such as biofilm formation, protease, and phospholipase activity. The minimum inhibitory (MIC) and fungicidal (MFC) concentrations of E. cardamomum were determined, and their effects were tested against all Candida strains. Our results revealed that E. cardamomum EO was rich in α-terpinyl acetate (56.5%), limonene (12.6%), and mentha-2.4(8)-diene (7.65%). The tested EO showed activity against all tested Candida strains in their planktonic form and against exoenzymes and biofilm production. Based on our findings, we promote the use of E. cardamomum EO as a treatment against clinical Candida isolates active on the virulence factors of this fungus.
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Essential oils from aromatic and medicinal plants have many bioactive compounds known for their important biological activities mainly their antibacterial effects. Here we evaluated qualitatively and quantitatively the biofilm formation capability of pathogenic bacterial strains (n = 8). Then, we investigated the antibacterial, antibiofilm, antiquorum-sensing, and antiswarming efficacy of Origanum vulgare essential oil (EO) and terpinene-4-ol. Our results revealed that EO exhibited a more potent inhibitory effect against the tested strains. While the terpinene-4-ol was found to be more effective against developed Staphylococcus aureus biofilm. Regarding the anti quorum-sensing activity, we noticed that O. vulgare displayed better inhibition percentages in violacein production even at a low concentration (MIC/4). Additionally, this EO showed better inhibition of Pseudomonas aeruginosa PAO1 migration in comparison with the terpinene-4-ol. Our findings revealed that using pure O. vulgare EO demonstrated better competitive effects against pathogenic bacteria with a different mode of action when compared to the terpinene-4-ol. Hence, exploration and development of efficient anti-infection agents from natural resources such as full EOs represent promising tools in anti-infective therapy.
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Terpolymerizations of newly synthesized ethylene (E), vinylcyclohexene (VCH), and 1-hexene were carried out with symmetrical metallocene catalysts rac-Me2Si(2-Me-4-Ph-Ind)2ZrCl2 (catalyst A) and rac-Et(Ind)2ZrCl2 (catalyst B). X-ray diffractometry (XRD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), high-temperature gel permeation chromatography (GPC), and nuclear magnetic resonance (NMR) spectroscopy were used to evaluate the behavior and microstructure of the polymers. The activity of catalyst B was 1.49 × 106 gm/mmolMt·h), with a T m of 73.45 (°C) and ΔH m of 43.19 (J/g), while catalyst A produced first higher 1-hexene, 19.6 mol %, and VCH contents with a narrow molecular weight distribution (MWD). In previous reports, ethylene propylene monomer dienes (EPDM) had a low content and were used for dielectric and insulating properties with nanomaterials. Second, this paper presents a kind of elastomeric polymers based on E/1-hexene and VCH with a high dielectric constant (k = 6-4) and mechanical properties. In addition, low dielectric loss suggests the suitable application potential of these polymeric materials for the fabrications of capacitors. Also, this work reveals that these polymers can be a better candidate for high-voltage electrical insulation due to their enhanced dielectric, mechanical, and thermal characteristics. To examine the insulating property, the interface characteristics of the polymer were evaluated using electrochemical impedance spectroscopy (EIS) with a frequency range of 1 × 105-0.01 Hz and an amplitude of 5.0 mV. EIS is an effective method to investigate the polymers' interfacial electron transfer characteristics. The EIS Nyquist plot showed high Warburg impedance features in the low-frequency domain with straight lines without a semicircle, suggesting that the property of the polymer owing to the high electrical resistance and poor conductivity for ionic kinetics in the electrolyte may have surpassed that of the semicircle. Although the slope of low frequencies in polymers holding potent exoelectrogenic bacteria (Shewanella oneidensis MR-1) as a charge carrier in the electrolyte could significantly reduce the Warburg resistance, it still could not improve the conductivity, which demonstrated that the external charge supply could not alter the insulating property in the used polymers.
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This study is aimed at understanding the serious foaming problems during microalgal cultivation in industrial raceway ponds by studying the dynamic foam properties in Arthrospira platensis cultivation. A. platensis was cultivated in a 4 L bowl bioreactor for 4 days, during which the foam height above the algal solution increased from 0 to 30 mm with a bubble diameter of 1.8 mm, and biomass yield reached 1.5 g/L. The algal solution surface tension decreased from 55 to 45 mN/m, which favored the adsorption of microalgae on the bubble to generate more stable foams. This resulted in increased foam stability (FS) from 1 to 10 s, foam capacity (FC) from 0.3 to 1.2, foam expansion (FE) from 15 to 43, and foam maximum density (FMD) from 0.02 to 0.07. These results show a decrease in CO2 flow rate and operation temperature when using the Foamscan instrument, which minimized the foaming phenomenon in algal solutions to a significantly lower and acceptable level.