Hymenaea courbaril resin-mediated gold nanoparticles as catalysts in organic dyes degradation and sensors in pharmaceutical pollutants.

In this study, green synthesis of gold nanoparticles (AuNPs) using aqueous extract from Hymenaea courbaril resin (HCR) is reported. The successful formation, functional group involvement, size, and morphology of the subject H. courbaril resin mediated gold nanoparticles (HCRAuNPs) were confirmed by Ultra Violet-Visible (UV-vis) spectroscopy, Fourier-Transform Infrared spectroscopy (FTIR), and Transmission Electron Microscopy (TEM) techniques. Stable and high yield of HCRAuNPs was formed in 1:15 (aqueous solution: salt solution) reacted in sunlight as indicated by the visual colour change and appearance of surface Plasmon resonance (SPR) at 560 nm. From the FT-IR results, the phenolic hydroxyl (-OH) functional group was found to be involved in synthesis and stabilization of nanoparticles. The TEM analysis showed that the particles are highly dispersed and spherical in shape with average size of 17.5 nm. The synthesized HCRAuNPs showed significant degradation potential against organic dyes, including methylene blue (MB, 85 %), methyl orange (MO, 90 %), congo red (CR, 83 %), and para nitrophenol (PNP, 76 %) up to 180 min. The nanoparticles also demonstrated the effective detection of pharmaceutical pollutants, including amoxicillin, levofloxacin, and azithromycin in aqueous environment as observable changes in color and UV-Vis spectral graph.

Network pharmacology and molecular docking: combined computational approaches to explore the antihypertensive potential of Fabaceae species.

Hypertension is a major global public health issue, affecting quarter of adults worldwide. Numerous synthetic drugs are available for treating hypertension; however, they often come with a higher risk of side effects and long-term therapy. Modern formulations with active phytoconstituents are gaining popularity, addressing some of these issues. This study aims to discover novel antihypertensive compounds in Cassia fistula, Senna alexandrina, and Cassia occidentalis from family Fabaceae and understand their interaction mechanism with hypertension targeted genes, using network pharmacology and molecular docking. Total 414 compounds were identified; initial screening was conducted based on their pharmacokinetic and ADMET properties, with a particular emphasis on adherence to Lipinski's rules. 6 compounds, namely Germichrysone, Benzeneacetic acid, Flavan-3-ol, 5,7,3',4'-Tetrahydroxy-6, 8-dimethoxyflavon, Dihydrokaempferol, and Epiafzelechin, were identified as effective agents. Most of the compounds found non-toxic against various indicators with greater bioactivity score. 161 common targets were obtained against these compounds and hypertension followed by compound-target network construction and protein-protein interaction, which showed their role in diverse biological system. Top hub genes identified were TLR4, MMP9, MAPK14, AKT1, VEGFA and HSP90AA1 with their respective associates. Higher binding affinities was found with three compounds Dihydrokaempferol, Flavan-3-ol and Germichrysone, -7.1, -9.0 and -8.0 kcal/mol, respectively. The MD simulation results validate the structural flexibility of two complexes Flavan-MMP9 and Germich-TLR4 based on no. of hydrogen bonds, root mean square deviations and interaction energies. This study concluded that C. fistula (Dihydrokaempferol, Flavan-3-ol) and C. occidentalis (Germichrysone) have potential therapeutic active constituents to treat hypertension and in future novel drug formulation.

Synthesis, molecular docking evaluation for LOX and COX-2 inhibition and determination of in-vivo analgesic potentials of aurone derivatives.

In the current study, seven (7) aurone derivatives (ADs) were synthesized and employed to in-vitro LOX and COX-2 assays, in-vivo models of acetic acid-induced mice writhing, formalin-induced mice paw licking and tail immersion test to evaluate their analgesic potential at the doses of 10 mg and 20 mg/kg body weight. Molecular docking was performed to know the active binding site at both LOX and COX-2 as compared to standard drugs. Among the ADs, 2-(3,4-dimethoxybenzylidene)benzofuran-3(2H)-one (WE-4)possessed optimal LOX and COX-2 inhibitory strength (IC50=0.30 µM and 0.22 µM) as compared to standard (ZileutonIC50 = 0.08 µM, CelecoxibIC50 = 0.05 µM). Similarly in various pain models compound WE-4 showed significantly (p < 0.05) highest percent analgesic potency as compared to control at a dose of 20 mg/kg i.e. 77.60 % analgesic effect in acetic acid model, 49.97 % (in Phase-1) and 70.93 % (inPhase-2) analgesic effect in formalin pain model and 74.71 % analgesic response in tail immersion model. By the administration of Naloxone, the tail flicking latencies were reversed (antagonized) in all treatments. The WE-4 (at 10 mg/kg and 20 mg/kg) was antagonized after 90 min from 11.23 ± 0.93 and 13.41 ± 1.21 to 5.30 ± 0.48 and 4.80 ± 0.61 respectively as compared to standard Tramadol (from 17.74 ± 1.33 to 3.70 ± 0.48), showing the opiodergic receptor involvement. The molecular docking study of ADs revealed that WE-4 had a higher affinity for LOX and COX-2 with docking scores of -4.324 and -5.843 respectively. As a whole, among the tested ADs, compound WE-4 demonstrated excellent analgesic effects that may have been caused by inhibiting the LOX and COX-2 pathways.

Nanozyme-based sensing of dopamine using cobalt-doped hydroxyapatite nanocomposite from waste bones.

Dopamine is one of the most important neurotransmitters and plays a crucial role in various neurological, renal, and cardiovascular systems. However, the abnormal levels of dopamine mainly point to Parkinson's, Alzheimer's, cardiovascular diseases, etc. Hydroxyapatite (HAp), owing to its catalytic nature, nanoporous structure, easy synthesis, and biocompatibility, is a promising matrix material. These characteristics make HAp a material of choice for doping metals such as cobalt. The synthesized cobalt-doped hydroxyapatite (Co-HAp) was used as a colorimetric sensing platform for dopamine. The successful synthesis of the platform was confirmed by characterization with FTIR, SEM, EDX, XRD, TGA, etc. The platform demonstrated intrinsic peroxidase-like activity in the presence of H2O2, resulting in the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). The proposed sensor detected dopamine in a linear range of 0.9-35 µM, a limit of detection of 0.51 µM, limit of quantification of 1.7 µM, and an R2 of 0.993. The optimization of the proposed sensor was done with different parameters, such as the amount of mimic enzyme, H2O2, pH, TMB concentration, and time. The proposed sensor showed the best response at 5 mg of the mimic enzyme, pH 5, 12 mM TMB, and 8 mM H2O2, with a short response time of only 2 min. The fabricated platform was successfully applied to detect dopamine in physiological solutions.

A novel variant in the FLNB gene associated with spondylocarpotarsal synostosis syndrome.

OBJECTIVES: Genetic disorders involved in skeleton system arise due to the disturbance in skeletal development, growth and homeostasis. Filamin B is an actin binding protein which is large dimeric protein which cross link actin cytoskeleton filaments into dynamic structure. A single nucleotide changes in the FLNB gene causes spondylocarpotarsal synostosis syndrome, a rare bone disorder due to which the fusion of carpels and tarsals synostosis occurred along with fused vertebrae. In the current study we investigated a family residing in north-western areas of Pakistan. METHODS: The whole exome sequencing of proband was performed followed by Sanger sequencing of all family members of the subject to validate the variant segregation within the family. Bioinformatics tools were utilized to assess the pathogenicity of the variant. RESULTS: Whole Exome Sequencing revealed a novel variant (NM_001457: c.209C>T and p.Pro70Leu) in the FLNB gene which was homozygous missense mutation in the FLNB gene. The variant was further validated and visualized by Sanger sequencing and protein structure studies respectively as mentioned before. CONCLUSIONS: The findings have highlighted the importance of the molecular diagnosis in SCT (spondylocarpotarsal synostosis syndrome) for genetic risk counselling in consanguineous families.

Modulation in serum and hematological parameters as a prognostic indicator of COVID-19 infection in hypertension, diabetes mellitus, and different cardiovascular diseases.

SARS-CoV-2 infection affects and modulates serum as well as hematological parameters. However, whether it modifies these parameters in the existing disease conditions, which help in the erection of specific treatments for the disease, is under investigation. Here, we aimed to determine whether serum and hematological parameters alteration in various diseases, diabetes mellitus (DM), hypertension (HTN), ischemic heart disease (IHD) and myocardial infarction (MI) conditions correlate and signal SARS-CoV-2 infection, which could be used as a rapid diagnosis tool for SARS-CoV-2 infection in disease conditions. To assess the projected goals, we collected blood samples of 1,113 male and female patients with solo and multiple disease conditions of DM/HTN/IHD/MI with severe COVID-19, followed by biochemical analysis, including COVID-19 virus detection by RT-qPCR. Furthermore, blood was collected from age-matched disease and healthy individuals 502 and 660 and considered as negative control. In our results, we examined higher levels of serum parameters, including D-dimer, ferritin, hs-CRP, and LDH, as well as hematological parameters, including TLC in sole and multiple diseases (DM/HTN/IHD/MI) conditions compared to the control subjects. Besides, the hematological parameters, including Hb, RBC, and platelet levels, decreased in the patients. In addition, we found declined levels of leukocyte count (%), lymphocyte (%), monocyte (%), and eosinophil (%), and elevated level of neutrophil levels (%) in all the disease patients infected with SARS-CoV-2. Besides, NLR and NMR ratios were also statistically significantly (p < 0.05) high in the patients with solo and multiple disease conditions of DM/HTN/IHD/MI infected with the SARS-CoV-2 virus. In conclusion, rapid alteration of sera and hematological parameters are associated with SARS-CoV-2 infections, which could help signal COVID-19 in respective disease patients. Moreover, our results may help to improve the clinical management for the rapid diagnosis of COVID-19 concurrent with respective diseases.

Blending cold-pressed peanut oil with omega-3 fatty acids from walnut oil: Analytical profiling and prediction of nutritive attributes and oxidative stability.

This study aimed to explore the possibility of enriching cold-pressed Virginia (VIO) and Valencia (VAO) peanut oils with omega-3 fatty acids (FAs) from walnut oil (WO) to produce blended oils with improved nutritional value. The oxidative stability of pure and blended oils was examined under accelerated conditions (60 °C) for 28 days. The FA and tocopherol profiles, as well as nutritional quality indices, were determined. As the proportion of WO increased in the blends, the levels of linoleic and α-linolenic essential FAs increased, while oleic acid content decreased. Furthermore, γ- and δ-tocopherol levels rose, whereas α-tocopherol declined. Among the studied blends, VIO:WO blends, especially at a (70:30) ratio, were nutritionally favorable with a balanced FA profile. During storage, notable changes were observed in tocopherol levels, along with subtle alterations in the FA profile of the blended oils. Hence, the oxidative stability of pure VIO and VAO decreased with WO incorporation.

Rice seeds biofortification using biogenic iron oxide nanoparticles synthesized by using Glycyrrhiza glabra: a study on growth and yield improvement.

Iron, a crucial micronutrient, is an integral element of biotic vitality. The scarcity of iron in the soil creates agronomic challenges and has a detrimental impact on crop vigour and chlorophyll formation. Utilizing iron oxide nanoparticles (IONPs) via nanopriming emerges as an innovative method to enhance agricultural efficiency and crop health. The objective of this study was to synthesize biogenic IONPs from Glycyrrhiza glabra (G. glabra) plant extract using green chemistry and to evaluate their nanopriming effects on rice seed iron levels and growth. The synthesized IONPs were analyzed using UV-Vis spectroscopy, Fourier-transform infrared spectroscopy (FTIR), Scanning electron microscope (SEM), Transmission electron microscopy (TEM), and Energy-dispersive X-ray (EDX) techniques. The UV-Vis peak at 280 nm revealed the formation of IONPs. SEM and TEM showed that the nanoparticles were spherical and had an average diameter of 23.8 nm. Nanopriming resulted in a substantial enhancement in growth, as seen by a 9.25% and 22.8% increase in shoot lengths for the 50 ppm and 100 ppm treatments, respectively. The yield metrics showed a positive correlation with the concentrations of IONPs. The 1000-grain weight and spike length observed a maximum increase of 193.75% and 97.73%, respectively, at the highest concentration of IONPs. The study indicates that G. glabra synthesized IONPs as a nanopriming agent significantly increased rice seeds' growth and iron content. This suggests that there is a relationship between the dosage of IONPs and their potential for improving agricultural biofortification.

Nutritional and bioactive properties and antioxidant potential of Amaranthus tricolor, A. lividus, A viridis, and A. spinosus leafy vegetables.

Climate change results in continuous warming of the planet, threatening sustainable crop production around the world. Amaranth is an abiotic stress-tolerant, climate-resilient, C4 leafy orphan vegetable that has grown rapidly with great divergence and potential usage. The C4 photosynthesis allows amaranth to be grown as a sustainable future food crop across the world. Most amaranth species grow as weeds in many parts of the world, however, a few amaranth species can be also found in cultivated form. Weed species can be used as a folk medicine to relieve pain or reduce fever thanks to their antipyretic and analgesic properties. In this study, nutritional value, bioactive pigments, bioactive compounds content, and radical scavenging potential (RSP) of four weedy and cultivated (WC) amaranth species were evaluated. The highest dry matter, carbohydrate content, ash, content of iron, copper, sodium, boron, molybdenum, zinc, ß-carotene and carotenoids, vitamin C, total polyphenols (TP), RSP (DPPH), and RSP (ABTS+) was determined in Amaranthus viridis (AV). On the other hand, A. spinosus (AS) was found to have the highest content of protein, fat, dietary fiber, manganese, molybdenum, and total flavonoids (TF). In A. tricolor (AT) species the highest total chlorophyll, chlorophyll a and b, betaxanthin, betacyanin, and betalain content was determined. A. lividus (AL) was evaluated as the highest source of energy. AV and AT accessions are underutilized but promising vegetables due to their bioactive phytochemicals and antioxidants.

Bio synthesis, comprehensive characterization, and multifaceted therapeutic applications of BSA-Resveratrol coated platinum nanoparticles.

This study examines the manufacturing, characterization, and biological evaluation of platinum nanoparticles, which were synthesized by Enterobacter cloacae and coated with Bovine Serum Albumin (BSA) and Resveratrol (RSV). The formation of PtNPs was confirmed with the change of color from dark yellow to black, which was due to the bioreduction of platinum chloride by E. cloacae. BSA and RSV functionalization enhanced these nanoparticles' biocompatibility and therapeutic potential. TGA, SEM, XRD, and FTIR were employed for characterization, where PtNPs and drug conjugation-related functional groups were studied by FTIR. XRD confirmed the crystalline nature of PtNPs and Pt-BSA-RSV NPs, while TGA and SEM showed thermal stability and post-drug coating morphological changes. Designed composite was also found to be biocompatible in nature in hemolytic testing, indicating their potential in Biomedical applications. After confirmation of PtNPs based nanocaompsite synthesis, they were examined for anti-bacterial, anti-oxidant, anti-inflammatory, and anti-cancer properties. Pt-BSA-RSV NPs showed higher concentration-dependent DPPH scavenging activity, which measured antioxidant capability. Enzyme inhibition tests demonstrated considerable anti-inflammatory activity against COX-2 and 15-LOX enzymes. In in vitro anticancer studies, Pt-BSA-RSV NPs effectively killed human ovarian cancer cells. This phenomenon was demonstrated to be facilitated by the acidic environment of cancer, as the drug release assay confirmed the release of RSV from the NP formulation in the acidic environment. Finally, Molecular docking also demonstrated that RSV has strong potential as an anti-oxidant, antibacterial, anti-inflammatory, and anticancer agent. Overall, in silico and in vitro investigations in the current study showed good medicinal applications for designed nanocomposites, however, further in-vivo experiments must be conducted to validate our findings.

Ethnobotanical assessment of antidiabetic medicinal plants in District Karak, Pakistan.

BACKGROUND: Diabetes is a leading health disorder and is responsible for high mortality rates across the globe. Multiple treatment protocols are being applied to overcome this morbidity and mortality including plant-based traditional medicines. This study was designed to investigate the ethnomedicinal status of plant species used to treat diabetes in District Karak, Pakistan. MATERIALS AND METHODS: A semi-structured survey was created to collect data about traditionally used medicinal plants for diabetes and other ailments. The convenience sampling method was applied for the selection of informants. The collected data was evaluated through quantitative tools like frequency of citation (FC), relative frequency of citation (RFC), informant consensus factor (FIC), fidelity level (FL), and use value (UV). RESULTS: A total of 346 local informants were selected for this research. Out of them, 135 participants were men and 211 participants were women. Overall 38 plant species belonging to 29 plant families were used to treat diabetes. The most dominant plant family was Oleaceae having 11 species. Powder form (19%) was the most recommended mode of preparation for plant-based ethnomedicines. Leaves (68%) were the most frequently used parts followed by fruit (47%). The highest RFC was recorded for Apteranthes tuberculata (0.147). The maximum FL was reported for Apteranthes tuberculata (94.4) and Zygophyllum indicum (94.11) for diabetes, skin, and wounds. Similarly, the highest UV of (1) each was found for Brassica rapa, Melia azedarach, and Calotropis procera. Based on documented data, the reported ailments were grouped into 7 categories. The ICF values range between 0.89 (diabetes) to 0.33 (Cardiovascular disorders). CONCLUSION: The study includes a variety of antidiabetic medicinal plants, which are used by the locals in various herbal preparations. The species Apteranthes tuberculata has been reported to be the most frequently used medicinal plant against diabetes. Therefore, it is recommended that such plants be further investigated in-vitro and in-vivo to determine their anti-diabetic effects.

Insights into measles virus: Serological surveillance and molecular characterization.

BACKGROUND: Measles has been a significant public health concern in Pakistan, especially in the Khyber Pakhtunkhwa (KPK) province, where sporadic and silent epidemics continue to challenge existing control measures. This study aimed to estimate the prevalence and investigate the molecular epidemiology of the measles virus (MeV) in KPK and explore the vaccination status among the suspected individuals. METHODS: A cross-sectional study was conducted between February and October 2021. A total of 336 suspected measles cases from the study population were analyzed for IgM antibodies using Enzyme-Linked Immunosorbent Assay (ELISA). Throat swabs were randomly collected from a subset of positive cases for molecular analysis. Phylogenetic analysis of MeV isolates was performed using the neighbor-joining method. The vaccination status of individuals was also recorded. RESULTS: Among the suspected participants, 61.0% (205/336) were ELISA positive for IgM antibodies, with a higher prevalence in males (64.17%) compared to females (57.04%). The majority of cases (36.0%) were observed in infants and toddlers, consistent with previous reports. The majority of IgM-positive cases (71.7%) had not received any dose of measles vaccine, highlighting gaps in vaccine coverage and the need for improved immunization programs. Genetic analysis revealed that all MeV isolates belonged to the B3 genotype, with minor genetic variations from previously reported variants in the region. CONCLUSION: This study provides valuable insights into the genetic epidemiology of the MeV in KPK, Pakistan. The high incidence of measles infection among unvaccinated individuals highlights the urgency of raising awareness about vaccine importance and strengthening routine immunization programs.

Potassium augments growth, yield, nutrient content, and drought tolerance in mung bean (Vigna radiata L. Wilczek.).

Uneven rainfall and high temperature cause drought in tropical and subtropical regions which is a major challenge to cultivating summer mung bean. Potassium (K), a major essential nutrient of plants can alleviate water stress (WS) tolerance in plants. A field trial was executed under a rainout shelter with additional K fertilization including recommended K fertilizer (RKF) for relieving the harmful impact of drought in response to water use efficiency (WUE), growth, yield attributes, nutrient content, and yield of mung bean at the Regional Agricultural Research Station, BARI, Ishwardi, Pabna in two successive summer season of 2018 and 2019. Drought-tolerant genotype BMX-08010-2 (G1) and drought-susceptible cultivar BARI Mung-1 (G2) were grown by applying seven K fertilizer levels (KL) using a split-plot design with three replications, where mung bean genotypes were allotted in the main plots, and KL were assigned randomly in the sub-plots. A considerable variation was observed in the measured variables. Depending on the different applied KL and seed yield of mung bean, the water use efficiency (WUE) varied from 4.73 to 8.14 kg ha-1 mm-1. The treatment applying 125% more K with RKF (KL7) under WS gave the maximum WUE (8.14 kg ha-1 mm-1) obtaining a seed yield of 1093.60 kg ha-1. The treatment receiving only RKF under WS (KL2) provided the minimum WUE (4.73 kg ha-1 mm-1) attaining a seed yield of 825.17 kg ha-1. Results showed that various characteristics including nutrients (N, P, K, and S) content in stover and seed, total dry matter (TDM) in different growth stages, leaf area index (LAI), crop growth rate (CGR), root volume (RV), root density (RD), plant height, pod plant-1, pod length, seeds pod-1, seed weight, and seed yield in all pickings increased with increasing K levels, particularly noted with KL7. The highest grain yield (32.52%) was also obtained from KL7 compared to lower K with RKF. Overall, yield varied from 1410.37 kg ha-1 using 281 mm water (KL1; well-watered condition with RKF) to 825.17 kg ha-1 using 175 mm water (KL2). The results exhibited that the application of additional K improves the performance of all traits under WS conditions. Therefore, mung beans cultivating under WS requires additional K to diminish the negative effect of drought, and adequate use of K contributes to accomplishing sustainable productivity.

Nanowarriors from Mentha: Unleashing Nature's Antimicrobial Arsenal with Cerium Oxide Nanoparticles.

Medicinal plant-based cerium oxide nanoparticles (CeO2NPs) possessed excellent antimicrobial properties against multiple strains of Gram-positive and Gram-negative bacteria. The CeO2NPs are popular because their electropositive charged surface causes oxidation of plasma membrane and facilitates the penetration of CeO2NPs inside the pathogen body. In the present research work, CeO2NPs stabilized with Mentha leaf extract; as a result, nanoparticles surface-bonded with various functional groups of phytochemicals which enhanced the therapeutic potential of CeO2NPs. The inhibition percentage of CeO2NPs was evaluated against eight pathogenic Gram-positive bacteria Staphylococcus aureus and Streptococcus epidermidis; Gram-negative bacteria Escherichia coli, Stenotrophomonas maltophilia, Comamonas sp., Halobacterium sp., and Klebsiella pneumoniae; and plant bacteria Xanthomonas sp. The antifungal properties of CeO2NPs were evaluated against three pathogenic fungal species Bipolaris sorokiniana, Aspergillus flavus, and Fusarium oxysporum via the streak plate method. The antimicrobial inhibitory activity of CeO2NPs was good to excellent. The current research work clearly shows that three different medicinal plants Mentha royleana, Mentha longifolia, and Mentha arvensis based CeO2NPs, variation in nanoparticle sizes, and surface-to-volume ratio of green CeO2NPs are three factors responsible to generate and provoke antimicrobial activities of CeO2NPs against human pathogenic bacteria and plant infecting fungi. The results show that CeO2NPs possessed good antimicrobial properties and are effective to use for pharmaceutical applications and as a food preservative because of low toxicity, organic coating, and acceptable antimicrobial properties. This study showed a rapid and well-organized method to prepare stable phytochemical-coated CeO2NPs with three different plants M. royleana, M. longifolia, and M. arvensis with remarkable antibacterial and antifungal characteristics.

Analysis of Primary and Secondary Metabolites, Physical Properties, Antioxidant and Antidiabetic Activities, and Chemical Composition of Rosmarinus officinalis Essential Oils under Differential Water Stress Conditions.

This study investigated the effects of varying water stress levels on Rosmarinus officinalis essential oils (EO). Three samples (S1, S2, and S3) were cultivated under different stress levels (40, 60, and 80%). Increased water stress led to changes in primary and secondary metabolites, EO contents, and physical properties. Antioxidant activity varied, with S2 exhibiting the highest IC50 value. In terms of antidiabetic activity, S2 showed robust α-amylase inhibition, while S3 displayed a commendable influence. For α-galactosidase inhibition, S3 had a moderate effect, and S2 stood out with increased efficacy. Gas chromatography-mass spectrometry analysis revealed stress-induced changes in major compounds. The study enhances the understanding of plant responses to water stress, with potential applications in antioxidant therapy and diabetes management. The findings emphasize the importance of sustainable water management for optimizing the EO quality in its various uses.

Identification of Novel Quinolone and Quinazoline Alkaloids as Phosphodiesterase 10A Inhibitors for Parkinson's Disease through a Computational Approach.

Phosphodiesterases (PDEs) are vital in signal transduction, specifically by hydrolyzing cAMP and cGMP. Within the PDE family, PDE10A is notable for its prominence in the striatum and its regulatory function over neurotransmitters in medium-spiny neurons. Given the dopamine deficiency in Parkinson's disease (PD) that affects striatal pathways, PDE10A inhibitors could offer therapeutic benefits by modulating D1 and D2 receptor signaling. This study was motivated by the successful history of quinazoline/quinazoline scaffolds in the inhibition of PDE10A. This study involved detailed in silico evaluations through docking followed by pharmacological, pharmacophoric, and pharmacokinetic analyses, prioritizing central nervous system (CNS)-active drug criteria. Seven cyclic peptides, those featuring the quinazoline/quinazoline moiety at both termini, exhibited notably enhanced docking scores compared to those of the remaining alkaloids within the screened library. We identified 7 quinolines and 1 quinazoline including Lepadin G, Aspernigerin, CJ-13536, Aurachin A, 2-Undecyl-4(1H)-quinolone, Huajiaosimuline 3-Prenyl-4-prenyloxyquinolin-2-one, and Isaindigotone that followed the standard CNS active drug criteria. The dominant quinoline ring in our study and its related quinazoline were central to our evaluations; therefore, the pharmacophoric features of these scaffolds were highlighted. The top alkaloids met all CNS-active drug properties; while nonmutagenic and without PAINS alerts, many indicated potential hepatotoxicity. Among the compounds, Huajiaosimuline was particularly significant due to its alignment with lead-likeness and CNS-active criteria. Aspernigerin demonstrated its affinity for numerous dopamine receptors, which signifies its potential to alter dopaminergic neurotransmission that is directly related to PD. Interestingly, the majority of these alkaloids had biological targets primarily associated with G protein-coupled receptors, critical in PD pathophysiology. They exhibit superior excretion parameters and toxicity end-points compared to the standard. Notably, selected alkaloids demonstrated stability in the binding pocket of PDE10A according to the molecular dynamic simulation results. Our findings emphasize the potential of these alkaloids as PDE10A inhibitors. Further experimental studies may be necessary to confirm their actual potency in inhibiting PDE10A before exploring their therapeutic potential in PD.

Antifungal efficacy of chitosan extracted from shrimp shell on strawberry (Fragaria × ananassa) postharvest spoilage fungi.

The strong demand for biological materials in the food industry places chitosan at the forefront of other biopolymers. The present study aims to evaluate the antifungal properties of chitosan extracted from shrimp shell waste (Parapenaeus longirostris) against post-harvest strawberry (Fragaria × ananassa) spoilage fungi. The physicochemical characteristics (DD, Mw, and solubility) of extracted chitosan were determined. In addition, functional characteristics were studied by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The antifungal effect of chitosan on mycelial growth and spore germination of Aspergillus niger, Botrytis cinerea, Fusarium oxysporum, and Rhizopus stolonifer was evaluated. Yield, degree of deacetylation, molecular weight, and solubility were 21.86%, 83.50%, 180 kDa, and 80.10%, respectively. A degree of deacetylation of 81.27% was calculated from the FTIR spectrum and a crystallinity index of 79.83% was determined from the X-ray diffraction pattern. SEM images of extracted chitosan showed a combination of fibrous and porous structure. At 3% chitosan, mycelial growth inhibition rates of A. niger, B. cinerea, F. oxysporum, and R. stolonifer ranged from 81.37% to 92.70%. At the same chitosan concentration, the percentages of spore germination inhibition of the isolated fungi ranged from 65.47% to 71.48%. The antifungal activity was highly dose-dependent. As a natural polymer, chitosan offers a convincing alternative to synthetic antimicrobials for the post-harvest preservation of strawberries. Its potential lies in its ability to inhibit the growth of spoilage fungi.

Potential role of Citrus bergamia flower essential oil against oral pathogens.

BACKGROUND: Oral bacterial infections are difficult to treat due to emergence of resistance against antibiotic therapy. Essential oils are considered emerging alternate therapy against bacterial infections and biofilms. We investigated Citrus bergemia flower essential oil against oral pathogens. METHODS: The essential oil was analsyed using Gas Chromatography(GC-MS), in silico investigations, antioxidant, antimicrobial, antibiofilm and antiquorum sensing assays. RESULTS: Gas Chromatography analysis confirmed presence of 17 compounds including 1,6-Octadien-3-ol,3,7-dimethyl, 48.17%), l-limonene (22.03%) and p-menth-1-ol, 8-ol (7.31%) as major components. In silico analysis showed compliance of all tested major components with Lipinski's rule, Bioavailability and antimicrobial activity using PASS (prediction of activity spectrum of substances). Molecular docking with transcriptional regulators 3QP5, 5OE3, 4B2O and 3Q3D revealed strong interaction of all tested compounds except 1,6-Octadien-3-ol,3,7-dimethyl. All tested compounds presented significant inhibition of DPPH (2,2-diphenyl-1-picrylhydrazyl) (IC50 0.65 mg/mL), H2O2 (hydrogen peroxide) (63.5%) and high FRAP (ferrous reducing antioxidant power) value (239.01 µg). In antimicrobial screening a significant activity (MIC 0.125 mg/mL) against Bacillus paramycoides and Bacillus chungangensis was observed. Likewise a strong antibiofilm (52.1 - 69.5%) and anti-QS (quorum sensing) (4-16 mm) activity was recorded in a dose dependent manner. CONCLUSION: It was therefore concluded that C. bergemia essential oil posess strong antioxidant, antimicrobial and antibiofilm activities against tested oral pathogens.

Strength Characteristics and Rheological Behavior of a High Level of Fly Ash in the Production of Concrete.

This study investigates the valorization of coal fly ash (FA-C) generated by the Jerada thermal power plant, aiming to address the pressing need for sustainable construction practices and reduced greenhouse gas emissions in the concrete industry. It is widely used as a pozzolanic material. The key objective is to harness the potential of FA-C as a supplementary material in concrete production, which not only reduces costs but also contributes to environmental sustainability. To achieve this objective, various concrete mixtures were formulated, with FA-C serving as a partial substitute for cement at percentages ranging from 15 to 50%. According to ASTM standards, compressive strength tests were conducted on standard-sized cylinders at 7 and 28 days. The results revealed that the blend containing 15% FA-C exhibited the highest compressive strength, indicating its effectiveness as a concrete additive. Furthermore, this study delves into the rheological properties of concrete mixes, an essential aspect of successful concrete processing. It was observed that a higher replacement level of FA-C significantly improved the rheology, leading to reduced water demand and a linear decrease in plastic viscosity over time. The rheological parameters stabilized after a certain period, demonstrating the controllability of concrete flow behavior with FA-C. The investigation also employed three analytical methods-Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM)-to comprehensively analyze both raw materials and processed samples. FTIR analysis highlighted the minimal impact of FA particles on hydration product formation, emphasizing the role of FA-C in enhancing the concrete's strength. XRD analysis confirmed the presence of an amorphous phase crucial for FA's reactivity. SEM observations revealed that concrete with 15% FA-C exhibited a more uniform microstructure with aluminosilicate gel, while 50% FA-C mixes showed increased porosity and nonhomogeneity due to unreacted FA particles.

Design and synthesis of novel dihydropyridine- and benzylideneimine-based tyrosinase inhibitors.

Tyrosinase (TYR) inhibitors are very significant as they inhibit enzyme tyrosinase activity, and its inhibition is vital for skin care, anticancer medication, and antibrowning of fruits and vegetables. This work presents a novel and economical route for the preparation of new synthetic tyrosinase inhibitors using amlodipine (4). The novel conjugates 6 (a-o) were designed, synthesized, and characterized by spectroscopic analyses, including Fourier transform infrared and low- and high-resolution mass spectroscopy. The purified compound 4 was refluxed with various aldehydes and ketones 5 (a-o) for 5-8 h in methanol at 60°C-90°C. This research modified the drug in a step-by-step manner to develop therapeutic properties as a tyrosinase inhibitor. The structures of synthesized ligands 6 (a-o) were established based on spectral and analytical data. The synthesized compounds 6 (a-o) were screened against tyrosinase enzyme. Kojic acid was taken as standard. All the prepared compounds 6 (a-o) have good inhibition potential against the enzyme tyrosinase. Compounds 6o, 6b, 6f, and 6k depicted excellent antityrosinase activity. Compound 6k, with an IC50 value of 5.34 ± 0.58 µM, is as potent as the standard kojic acid (IC50 6.04 ± 0.11 µM), standing out among all synthesized compounds 6 (a-o). The in silico studies of the conjugates 6 (a-o) were evaluated via PatchDock. Compound 6k showed a binding affinity score of 8,999 and an atomic contact energy (ACE) value of -219.66 kcal/mol. The structure-activity relationship illustrated that the presence of dihydropyridine nuclei and some activating groups at the ortho and para positions of the benzylideneimine moiety is the main factor for good tyrosinase activity. The compound 6k could be used as a lead compound for drug modification as a tyrosinase inhibitor for skin care, anticancer medication, and antibrowning for fruits and vegetables.