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Tomato (Solanum lycopersicum L.) is the second most important cultivated crop next to potato, worldwide. Tomato serves as an important source of antioxidants in human diet. Alternaria solani and Fusarium oxysporum cause early blight and vascular wilt of tomato, respectively, resulting in severe crop losses. The foremost objective of the present study was to generate transgenic tomato plants with rolB gene and evaluate its effect on plant morphology, nutritional contents, yield and resistance against fungal infection. Tomato cv. Rio Grande was transformed via Agrobacterium tumefaciens harbouring rolB gene of Agrobacterium rhizogenes. rolB. Biochemical analyses showed considerable improvement in nutritional quality of transgenic tomato fruits as indicated by 62% increase in lycopene content, 225% in ascorbic acid content, 58% in total phenolics and 26% in free radical scavenging activity. Furthermore, rolB gene significantly improved the defence response of leaves of transgenic plants against two pathogenic fungal strains A. solani and F. oxysporum. Contrarily, transformed plants exhibited altered morphology and reduced fruit yield. In conclusion, rolB gene from A. rhizogenes can be used to generate transgenic tomato with increased nutritional contents of fruits as well as improved foliar tolerance against fungal pathogens. [ABSTRACT FROM AUTHOR]

Context: Natural products are a very productive source of leads for the development of medicines. Six Pakistani plants were chosen for study based on ethnobotanical data. Objective: Exploration of important medicinal plants of Pakistan for cancer treatment. Materials and methods: The crude extracts of the six plants and their fractions were tested for inhibition of nuclear factor κB (NFκB), aromatase, and nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells, induction of quinone reductase 1 (QR1), agonism of retinoid X receptor, and growth inhibition with MCF-7, LU-1 and MDA-MB-231 cancer cells. Results: Two samples of Withania coagulans (Stocks) Dunal (Solanaceae) demonstrated inhibition of TNF-α induced activity of NFκB with IC50 values of 2.6 and 4.3 µg/mL, respectively. Two fractions from W. coagulans and Euphorbia wallichii Hook F. (Euphorbiaceae) aerial parts inhibited aromatase with IC50 values of 17.0 and 17.7 µg/mL, respectively. A total of 13 samples (five from E. wallichii, one from Acer oblongifolium Hort. ex Dippel (Aceraceae), one from Aster thomsonii C. B. Clarke (Asteraceae) and six from W. coagulans aerial parts with fruits) inhibited NO production with IC50 values ranging from 1.3 to 15.6 µg/mL. Fourteen samples demonstrated induction of QR1 with CD ranging from 1.0 to 20.6 µg/mL, and a total of eight extracts and fractions inhibited the proliferation of cancer cells in culture with IC50 values ranging from 1.2 to 7.8 µg/mL. Discussion and conclusion: Selected plants can be a valuable source of chemopreventive and anticancer products. W. coagulans aerial parts showed the strongest activity. [ABSTRACT FROM AUTHOR]

Background: Rickets is recognized for centuries and is due to defective mineralization of the growth plate in growing children. Nutritional vitamin D deficiency rickets remains the most prevalent cause worldwide. This study was carried out with the objectives to assess the prevalence, clinical presentation and predisposing factors of rickets in children of Swat District. Material & Methods: This cross-sectional descriptive study was conducted in Department of Child health, Saidu Teaching Hospital, Swat from December 2009 to December 2010. Children presenting with signs and symptoms of rickets from newborns to fifteen years of age were included in the study. Patients with hepatic and renal diseases or on anticonvulsant medicines were excluded from the study. Provisional diagnosis was made after taking detailed history including predisposing factors and a through examination and the findings were entered to pre planed proforma. Results: Fifty children with rickets were included. These patients presented as recurrent lower respiratory infections in 30(60%), delay in motor mile stone in 12(24%), convulsions in 10(20%) and recurrent diarrhea in 8(16%) children. On clinical examination skeletal changes were present in 45(90%) and radiological signs 40(80%) children. In all cases healing took place after vitamin D supplementation. The main predisposing factors were lack of awareness about sun exposure, malnourishment and antenatal factors. Conclusion: Rickets is common in district swat presenting with different signs and symptoms predisposing the childhood population to different illnesses and skeletal deformities. [ABSTRACT FROM AUTHOR]

Over the last two decades, radiologists have been using multi-view images to detect tumors. Computer Tomography (CT) imaging is considered as one of the reliable imaging techniques. Many medical-image-processing techniques have been developed to diagnoses lung cancer at early or later stages through CT images; however, it is still a big challenge to improve the accuracy and sensitivity of the algorithms. In this paper, we propose an algorithm based on image fusion for lung segmentation to optimize lung cancer diagnosis. The image fusion technique was developed through Laplacian Pyramid (LP) decomposition along with Adaptive Sparse Representation (ASR). The suggested fusion technique fragments medical images into different sizes using the LP. After that, the LP is used to fuse the four decomposed layers. For the evaluation purposes of the proposed technique, the Lungs Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI) was used. The results showed that the Dice Similarity Coefficient (DSC) index of our proposed method was 0.9929, which is better than recently published results. Furthermore, the values of other evaluation parameters such as the sensitivity, specificity, and accuracy were 89%, 98% and 99%, respectively, which are also competitive with the recently published results. [ABSTRACT FROM AUTHOR]

The current study was intended to explore the phytochemical profiling and therapeutic activities of Putranjiva roxburghii Wall. Crude extracts of different plant parts were subjected to the determination of antioxidant, antimicrobial, antidiabetic, cytotoxic, and protein kinase inhibitory potential by using solvents of varying polarity ranges. Maximum phenolic content was notified in distilled water extracts of the stem (DW-S) and leaf (DW-L) while the highest flavonoid content was obtained in ethyl acetate leaf (EA-L) extract. HPLC-DAD analysis confirmed the presence of various polyphenols, quantified in the range of 0.02 ± 0.36 to 2.05 ± 0.18 μg/mg extract. Maximum DPPH scavenging activity was expressed by methanolic extract of the stem (MeOH-S). The highest antioxidant capacity and reducing power was shown by MeOH-S and leaf methanolic extract (MeOH-L), respectively. Proficient antibacterial activity was shown by EA-L extract against Bacillus subtilis and Escherichia coli. Remarkable α-amylase and α-glucosidase inhibition potential was expressed by ethyl acetate fruit (EA-F) and n-Hexane leaf (nH-L) extracts, respectively. In case of brine shrimp lethality assay, 41.67% of the extracts (LC50 < 50 µg/mL) were considered as extremely cytotoxic. The test extracts also showed mild antifungal and protein kinase inhibition activities. The present study explores the therapeutic potential of P. roxburghii and calls for subsequent studies to isolate new bioactive leads through bioactivity-guided isolation. [ABSTRACT FROM AUTHOR]

Wheat is a staple crop of Pakistan that covers almost 40% of the cultivated land and contributes almost 3% in the overall Gross Domestic Product (GDP) of Pakistan. However, due to increasing seasonal variation, it was observed that wheat is majorly affected by rust disease, particularly in rain-fed areas. Rust is considered the most harmful fungal disease for wheat, which can cause reductions of 20–30% in wheat yield. Its capability to spread rapidly over time has made its management most challenging, becoming a major threat to food security. In order to counter this threat, precise detection of wheat rust and its infection types is important for minimizing yield losses. For this purpose, we have proposed a framework for classifying wheat yellow rust infection types using machine learning techniques. First, an image dataset of different yellow rust infections was collected using mobile cameras. Six Gray Level Co-occurrence Matrix (GLCM) texture features and four Local Binary Patterns (LBP) texture features were extracted from grayscale images of the collected dataset. In order to classify wheat yellow rust disease into its three classes (healthy, resistant, and susceptible), Decision Tree, Random Forest, Light Gradient Boosting Machine (LightGBM), Extreme Gradient Boosting (XGBoost), and CatBoost were used with (i) GLCM, (ii) LBP, and (iii) combined GLCM-LBP texture features. The results indicate that CatBoost outperformed on GLCM texture features with an accuracy of 92.30%. This accuracy can be further improved by scaling up the dataset and applying deep learning models. The development of the proposed study could be useful for the agricultural community for the early detection of wheat yellow rust infection and assist in taking remedial measures to contain crop yield. [ABSTRACT FROM AUTHOR]

Heteroleptic triorganobismuth (V) complexes of general formula, R3Bi(OOCR')2 (1–7), where R = C6H5 (1–3), p‐CH3C6H4 (4–7) and R' = 3,5‐Cl2C6H3 (1, 5); 3,4,5‐(OCH3)3C6H2 (2, 6); 3‐CH3C6H4 (3,7); 2‐OH‐3‐OCH3C6H3 (4) have been synthesized and fully characterized by FT‐IR, 1H &13C NMR spectroscopy, single crystal X‐ray crystallography and elemental analysis. The molecular geometry observed for the compounds is predominantly distorted trigonal bipyramidal, the fact which was subsequently authenticated through X‐ray analyses for (1–4). All the synthesized compounds have been bio‐assayed for antileishmanial (Leishmania tropica KWH23) and Jack beans urease inhibitory activity, and human Lymphocytes were used to measure the general toxicity. Of these, (4) proved to be highly effective against the target species (Leishmania tropica KWH23), while being non‐toxic towards the mammalian cells at levels below 0.74 μgmL−1, making it highly promising drug candidate. The high activities for (2, 4, and 6) against Jack beans Urease as compared to the reference standard demonstrate their significance in searching of therapeutic agents in future programs. The significant binding score of (2&4) against H. pylori in molecular docking studies further revealed their importance in future drug discovery processes. [ABSTRACT FROM AUTHOR]

The original publication of this paper contains a mistake. [ABSTRACT FROM AUTHOR]

In this paper, a modified form of the Proportional Integral Derivative (PID) controller known as the Integral- Proportional Derivative (I-PD) controller is developed for Automatic Generation Control (AGC) of the two-area multi-source Interconnected Power System (IPS). Fitness Dependent Optimizer (FDO) algorithm is employed for the optimization of proposed controller with various performance criteria including Integral of Absolute Error (IAE), Integral of Time multiplied Absolute Error (ITAE), Integral of Time multiplied Square Error (ITSE), and Integral Square Error (ISE). The effectiveness of the proposed approach has been assessed on a two-area network with individual source including gas, hydro and reheat thermal unit and then collectively with all three sources. Further, to validate the efficacy of the proposed FDO based PID and I-PD controllers, comprehensive comparative performance is carried and compared with other controllers including Differential Evolution based PID (DE-PID) controller and Teaching Learning Based Optimization (TLBO) hybridized with Local Unimodal Sampling (LUS-PID) controller. The comparison of outcomes reveal that the proposed FDO based I-PD (FDO-I-PD) controller provides a significant improvement in respect of Overshoot (Osh), Settling time (Ts), and Undershoot (Ush). The robustness of an I-PD controller is also verified by varying parameter of the system and load variation. [ABSTRACT FROM AUTHOR]

The peach fruit fly, Bactrocera zonata (Saunders) (Diptera: Tephritidae), is a pest of economic importance, endemic to South and South‐East Asia. It is highly invasive and due to its quarantine pest status, it interferes with horticultural trade. Males of many Bactrocera species are strongly attracted to methyl eugenol (ME) [1,2‐dimethoxy‐4‐(2‐propenyl) benzene], a phenylpropanoid compound naturally occurring in many plant species. Feeding on ME is also reported to enhance male mating success in several Bactrocera species. Such an effect can increase the effectiveness of the sterile insect technique (SIT). The current study was designed to identify the sexual maturity age of males of B. zonata, the relation between male age and attraction to ME, and the effect of ME on male mating success. The results showed that males initiated their mating at 8 days of age and attained the highest mating success at 16 days of age. The percentage of immature males responding to ME increased with age and the maximum response was observed during the age of sexual maturity. Methyl eugenol treatment at sexual maturity significantly enhanced male mating success over untreated males. The males treated with ME at a sexually immature age (5 days old) achieved significantly higher mating success after reaching sexual maturity. These findings suggested that B. zonata males can be treated with ME at the age of 5 days in sterile‐male 'holding and release' facilities and thereafter released in the field, where they are expected to achieve higher mating success after attaining sexual maturity. The results are discussed as a valid approach for enhancing the effectiveness of SIT application against B. zonata. [ABSTRACT FROM AUTHOR]

Objective: Berberis lycium is an indigenous plant of Pakistan that is known for its medicinal properties. In the current study, we investigated the anti-Alzheimer's effect of berberine isolated from Berberis lycium. Methods: Root extract of B. lycium was subjected to acetylcholinesterase inhibition assay and column chromatography for bioassays guided isolation of a compound. The neuroprotective and memory improving effects of isolated compound were evaluated by aluminium chloride induced Alzheimer's disease rat model, elevated plus maze (EPM) and Morris water maze (MWM) tests., Levels of dopamine and serotonin in rats brains were determined using HPLC. Moreover, western blot and docking were performed to determine interaction between berberine and β-secretase. Results: During fractionation, ethyl acetate and methanol (3:7) fraction was collected from solvent mixture of ethyl acetate and methanol. This fraction showed the highest anti-acetylcholinesterase activity and was alkaloid positive. The results of TLC and HPLC analysis indicated the presence of the isolated compound as berberine. Additionally, the confirmation of isolated compound as berberine was carried out using FTIR and NMR analysis. In vivo EPM and MWM tests showed improved memory patterns after berberine treatment in Alzheimer's disease model. The levels of dopamine, serotonin and activity of antioxidant enzymes were significantly (p<0.05) enhanced in brain tissue homogenates of berberine treated group. This was supported by decreased expression of β-secretase in berberine treated rat brain homogenates and good binding affinity of berberine with β-secretase in docking studies. Binding energies for interaction of β-secretase with berberine and drug Rivastigmine is -7.0 kcal/mol and -5.8 kcal/mol respectively representing the strong interactions. The results of docked complex of secretase with berberine and Rivastigmine was carried out using Gromacs which showed significant stability of complex in terms of RMSD and radius of gyration. Overall, the study presents berberine as a potential drug against Alzheimer's disease by providing evidence of its effects in improving memory, neurotransmitter levels and reducing β-secretase expression in the Alzheimer's disease model. [ABSTRACT FROM AUTHOR]

Bidentate Schiff bases (I1–I9) are synthesized by condensation between substituted anilines, benzothiazoles, and 2-hydroxy aromatic aldehydes. The Zn(II) derivatives (1–9) are prepared by reacting the respective ligand and zinc acetate dihydrate in a 2:1 mole ratio in dry methanol using triethylamine as a base. They are characterized by FTIR, NMR, and single-crystal XRD techniques. The XRD data confirmed distorted tetrahedral molecular geometry for 6; the intermolecular interactions are investigated comprehensively by 3-D Hirschfeld surface analysis and 2-D fingerprint plots. The DFT studies for the compounds are conducted for geometrical and energy optimization by applying 3-21 G* and 6-311++G (d, p)/B3LYP basis sets. Molecular docking data show that ligands possess GOLD scores in the range 51.5–46.7, whereas 2 and 3 have shown good fitness score of 57.7 and 53.3, respectively, with a maximum score of 60.2 for 7. The antibacterial data for 7 shows zone of inhibition as 17.3 mm against Staphylococcus aureus and 16.3 mm against Staphylococcus epidermidis, whereas 2 exhibits maximum value of 15.6 mm against gram negative bacteria Escherichia coli. The maximum and comparable alpha amylase inhibition potential of 12.6 and 12.3% are found for 8 and 3, respectively. [ABSTRACT FROM AUTHOR]

Search for biologically active nanoparticles is prerequisite for biomedical applications. CuO nanoparticles synthesized by co -precipitation method are capped by polyethylene-glycol (PEG) and polyvinyl-pyrrolidone (PVP) on the surface by simple adsorption. Physical and chemical properties carried out by SEM, XRD and FTIR confirm nanometer in size and efficient capping of PVP and PEG on CuO NPs. Biological assays reveal higher activities of CuO-PEG and CuO-PVP as compared to the uncapped CuO nanoparticles. CuO-PEG shows better antitumor activity against Streptomyces as compared with CuO-PVP and CuO NPs. Both the capped NPs are significantly active for α-amylase inhibition assay. CuO-PVP demonstrates significantly better activity against bacterial strains followed by CuO-PEG and uncapped CuO. PVP coated CuO NPs also shows strong DPPH based free radical scavenging activity, total reducing power potential, total antioxidative potential and also carries flavonoid and phenolics properties determines to querecetin and gallic acid equivalence, respectively. It can be concluded that PVP and PEG capped CuO NPs are more capable to be used in biomedical applications as drug and diagnostic carrier molecules. [ABSTRACT FROM AUTHOR]

People of all ages experience injuries, whether mild or severe. The most available option to treat wounds as an alternative to allopathic care in both urban and rural populations is traditional medicine, which is mostly target inflammation. Bergenia ciliata (Haw.) Sternb rhizome and leaf powder are used in Ayurveda and local communities for various ailments including healing of wounds and burns. Owing to this property it is traditionally known as "Zakham-e-hayat" (wound healer). In the present study, we compared biological activity and wound healing potential of B. ciliata rhizome (R) extract and bergenin, a glycoside isolated from B. ciliata. Reverse-phase high performance liquid chromatography (RP-HPLC) was performed to analyze polyphenols and bergenin in B. ciliata R extract. Samples were subjected to in vitro antioxidant assays including free radical scavenging, ferric chloride reducing power and total antioxidant capacity. Micro-broth dilution method, brine shrimp lethality assay and isolated RBC hemolysis assay were conducted to assess in vitro antibacterial and cytotoxic activities. Moreover, in vivo wound healing potential was determined by an excision wound model in mice. RP-HPLC showed significant content of polyphenols and bergenin (6.05 ± 0.12 μg/mg) in B. ciliata R extract. Crude extract possesses higher overall antioxidant and antibacterial capacities than bergenin due to presence of multiple phytoconstituents in extract. Both samples showed low hemolytic activity indicating their safe profile. Furthermore, mice treated with B. ciliata R extract depicted substantial decrease in wound area (99.3%; p < 0.05) as compared to bergenin, which showed 88.8% of wound closure after 12 days of treatment. Additionally, both treatments reduced epithelization duration by 1.6- and 1.4-fold in B. ciliata R extract (12.0 ± 0.6 days) and bergenin (14.2 ± 0.8 days) treated mice, respectively. This was supported by histopathological examination that showed greater epithelization, fibroblast proliferation, collagen synthesis, and revascularization in mice treated with B. ciliata R. Concisely, it is evident that B. ciliata R contains phytoconstituents in addition to bergenin, which potentiated wound healing activity of the extract. Hence, B. ciliata R is good source of compounds for treating wounds. [Display omitted] • Bergenia ciliata rhizome has potent antioxidant activity. • Bergenia ciliata rhizome and bergenin can inhibit bacterial growth in vitro. • Wound healing capacity of Bergenia ciliata rhizome is higher than bergenin. • Biological effects of Bergenia ciliata are attributed to bergenin and polyphenols. [ABSTRACT FROM AUTHOR]

The pentacyclic triterpenoids (PTs) of plant origin are reputed to restrain prostate cancer (PCa) cell proliferation. This study aims to assess 3-epifriedelinol (EFD) isolated from aerial part of Ipomoea batatas against PCa and its potential mechanism, in vitro and in vivo. Molecular docking affirms good binding affinity of the compound with target proteins exhibiting binding energy of −7.9 Kcal/mol with BAX, −8.1 Kcal/mol (BCL-2), −1.9 Kcal/mol (NF-κB) and −8.5 Kcal/mol with P53. In the MTT assay, EFD treatment (3–50 µM) showed a significant (p < 0.05 and p < 0.01) dose and time dependent drop in the proliferative graph of DU145 and PC3, and an upsurge in apoptotic cell population. EFD displayed substantial IC50 against DU145 (32.32 ± 3.72 µM) and PC3 (35.22 ± 3.47 µM). According to Western blots, EFD administration significantly enhanced the cleavage of caspases and PARP, elevated BAX and P53 and decreased BCL-2 and NF-κB expression, thereby triggering apoptosis in PCa cells. When male Sprague Dawley rats were intoxicated with Bisphenol A (BPA), an apparent increase in prostate mass (0.478 ± 0.08 g) in comparison to control (0.385 ± 0.03 g) indicates prostatitis. Multidose treatment of EFD (10 mg/kg) significantly reduced prostate size (0.404 ± 0.05 g). EFD exhibited substantial curative potential in vivo, as hematological, hormonal and histopathological parameters have been significantly improved. Reduced peroxidation (TBARS), and suppression of inflammatory markers i.e., NO, IL-6 and TNF-α, signposts substantial antiinflammatory potential of the compound. Overall, EFD has shown better binding affinity with target molecules, acceptable ADMET profile, potent antiproliferative and apoptotic nature and significant reduction in inflamed prostate mass of rats. The present study demonstrates acceptable physicochemical and pharmacokinetic properties of the compound with excellent drugable nature, hence EFD in the form of standardized formulation can be developed as primary or adjuvant therapy against PCa and toxins-induced gonadotoxicity. [ABSTRACT FROM AUTHOR]

The current study aimed to determine the safety and efficacy of Coag-A through in vivo analysis in CFA induced mice model. Treatment of CFA induced arthritis in mice with Coagulansin-A (10 mg/kg i.p. daily for 28 days), a withanolide obtained from Withania coagulans, as well as standard drug treatment with Dexamethasone (5 mg/kg i.p) was provided. The effect of Coag-A on body weight, relative organ weight, hematology, serum biochemistry, survival rate, oxidative stress markers, and antioxidant enzymes was evaluated. The liver and kidney histopathology were also assessed to ascertain its safety profile. Treatment of arthritic mice with Coag-A considerably improved body weight, relative organ weight of liver, kidney, and spleen, ameliorated hematology and serum biochemistry, and increased survival and antioxidant potential. Coag-A was found to be safer with fewer adverse effects showing hepato-protective, nephroprotective, and anti-inflammatory effect. It also significantly (p < 0.001) improved histopathology of CFA-induced mice when compared with Dexa. In conclusion, compared to dexamethasone, Coag-A has demonstrated a greater therapeutic benefit and fewer side effects in the treatment of arthritis against the CFA-induced model. [Display omitted] • Coagulansin-A shows promising anti-inflammatory and anti-arthritic effects. • Coagulansin-A exhibits good antioxidant potential. • Coagulansin-A shows excellent hepatoprotective and nephroprotective potential. • Coagulansin-A has a great safety profile. [ABSTRACT FROM AUTHOR]

Organotin (IV) compounds are a focus of research for potential use in cancer chemotherapy. Here, we established anticancer profile of dibutyltin (IV) carboxylate derivatives in prostate cancer (PCa) model. We determined cytotoxicity of a library of dibutyltin (IV) carboxylate derivatives and observed that dibutylstannanediyl (2 Z ,2′ Z)-bis(4-(benzylamino)-4-oxobut-2-enoate (Ch-620; 10 μM) was minimally toxic to normal fibroblasts. Ch-620 (1–1.25 μM) inhibited proliferation of PCa and melanoma cells on short- and long-term exposures with induction of cell cycle arrest. Ch-620 treatment increased population of apoptotic cells, as assessed by flow cytometry, and activated caspase 3. Proteomics showed activation of PPARα, with repression of SMAD4 and integrin β5 (ITGB5) in Ch-620-treated PCa cells. Further analysis demonstrated that Ch-620 resulted in phosphorylation of p38 MAPK, upregulation of PPARα and decreased expression of SMAD4 and ITGB5 with reduced migration of PCa cells. In vivo studies in PC3M grafted athymic nude mice showed that Ch-620 (5 μg/week; 7 weeks) treatment reduced tumor growth as opposed to untreated controls. Immunoblot analysis of tumors demonstrated upregulated p-p38 MAPK and PPARα, followed by a decline in SMAD4 and ITGB5. Immunohistochemistry reinforced these results with increased caspase 3 and p-p38 MAPK and diminished Ki67 staining in Ch-620 treated animals. Taken together, our data indicate that Ch-620 inhibited proliferation of PCa through modulation of MAPK/PPARα/SMAD4 signaling. Organotin (IV) carboxylate compounds; specifically Ch-620 can be a potential anticancer agent for the treatment of PCa subject to detailed pre-clinical and clinical investigations. This unlocks prospects for the development of new tin-based drugs in cancer therapeutics. • Dibutyltin (IV) compound Ch-620 inhibited growth of prostate cancer cells in vitro. • p38 MAPK/PPARα/SMAD4 signaling was modulated by Ch-620 in prostate cancer. • Ch-620 impeded migration of prostate cancer cells by targeting ITGB5. • Tumor growth was inhibited by Ch-620 in PC3M implanted athymic nude mice. [ABSTRACT FROM AUTHOR]

Honey is a nutrient-rich natural substance prepared by honeybees from the nectars of flowers. Various factors including botanical composition of the bee diet, geographical locations and environmental features affect the biochemical properties of honey, including its composition in biomolecules. In the present study melissopalynological techniques were applied to identify the honeybee (Apis mellifera) flora using light microscopy. Phenolic and flavonoid contents in honey samples were analyzed via Folin-Ciocalteu and colorometric methods. Total reducing power, alpha-amylase and mineral contents were calculated by Phull's method, and atomic absorption spectroscopy (AAS). Acacia nilotica (Ghawandi village), Cynodon dactylon (Jathanbanda), Saccharum spontaneum (Paniala), and Ziziphus jujuba (Kot Kashmir) were identified as the predominant plant species in four unifloral honey samples. In terms of biochemical properties, total phenolic contents ranged from 0.27 ± 0.094 to 1.76 ± 0.02 µg/mL while total flavonoid contents varied from 0.80 ± 0.1 to 1.23 ± 0.102 µg/mL. One of the applications of this investigation is that the pollen profile of honey samples here determined is useful for the identification of bee floral diet diversity and the geographical origin of honey. Moreover, the biochemical properties will be helpful to clarify the medicinal properties of honey samples. In addition to this, the biochemical profile of honey samples is the basis for further pharmacological analysis. [ABSTRACT FROM AUTHOR]

The use of the green approach for nanoparticle synthesis yielded noticeable concern due to its eco-friendliness, cost-effectiveness, and reduced production of toxic chemicals. The current study was designed to formulate Zinc oxide nanoparticles (ZnO NPs) by using Fagonia cretica extracts, evaluating its phytochemical content, and different biological activities. Four different solvents; methanol (MeOH), n-Hexane (n–H), aqueous (Aq), and ethyl acetate (EA), had been utilized in the extracting method. ZnO NPs were successfully synthesized and characterized by UV–vis spectroscopy and scanning electron microscopy (SEM). The UV–vis spectra showed absorbance peaks between 350–400 nm range and SEM analysis revealed spherical morphology with particle sizes ranging from 65–80 nm. In phytochemical analysis, crude extracts exhibited the highest phytochemical content as they contain enriched secondary metabolites. n-hexane extract showed the highest phenolic contents while aqueous extracts showed the highest flavonoid content. Maximum free radicle scavenging activity was observed in NPs synthesized from ethyl-acetate extract with an IC50 value of 35.10 µg/ml. Significant antibacterial activity was exhibited by NPs polar solvents against K. pneumonae, E. coli, and B. subtilis. Polar solvents showed considerable antifungal potential against A. flavus and F. solani. NPs synthesized from nH extract showed potential cytotoxic activity with an LC50 value of 42.41 µg/ml against brine shrimps. A noteworthy antidiabetic activity was exhibited by nanoparticles synthesized from methanol extract i.e., 52.61 ± 0.36%. Significant bald zones were observed in nanoparticles synthesized from methanol extract rendering protein kinase inhibition. The present study highlights the significance of F. indica as a natural source for synthesizing functional nanoparticles with substantial antioxidant, antimicrobial, cytotoxic, protein kinase inhibitory, and antidiabetic properties. [ABSTRACT FROM AUTHOR]

A series of 18 biologically active C5‐arylated‐2‐isobutylthiazole derivatives that were synthesized by Pd‐NHC complexes [Pd(μ‐Cl)Cl (NHC)]2, NHC = SIXyl, 2), (LCl2Pd‐NHC, L = PPh3, 3), (LCl2Pd‐NHC, L = Py, 4), (LCl2Pd‐NHC, L = 3‐CHO‐Py, 5) catalyzed C‐H bond activation reactions. The catalytic activity of Pd‐NHC complexes was examined on the C‐H bond activation reaction of 2‐isobutylthiazole. All Pd‐NHC complexes were characterized by 1H nuclear magnetic resonance specroscopy (NMR), 13C NMR, fouirer transform infrared spektroscopy (FTIR), quadrupole‐time of flying‐liquit cromotagraphy/mass spektroscopy (Q‐TOF‐LC/MS), gas chromatography–mass spectrometry (GCMS), and melting point detection technique. The physicochemical properties, pharmacokinetics, and drug‐likeness were calculated by SwissADME. PkCSM database was used to calculate toxicities profile. All the products (6a–6s) were additionally assessed in vitro for their antidiabetic potential using α‐amylase and α‐glucosidase inhibitory activities. The protein kinase activity was performed to evaluate their anticancer activities. All the compounds possess drug‐like characters as they followed Lipinski's rule of five (RO5). Almost all the compounds showed no to fewer toxicities. In addition, other than the compounds, that is, 6a, 6b, 6c, 6m, 6n, 6p, and 6s, the rest of the compounds showed good α‐glucosidase inhibitory potential (IC50 7.17 ± 0.201 to 74.08 ± 0.244 μg/ml) when compared with acarbose standard (IC50 16.59 ± 0.135 μg/ml). All compounds had moderate to good inhibitory potential against the α‐amylase enzyme, with IC50 values ranging from 12.00 ± 0.289 to 76.15 ± 0.477 μg/ml. Eleven analogs (6e, 6f, 6g, 6h, 6j, 6k, 6l, 6n, 6o, 6p, and 6r) showed good to moderate activity. Seven analogs (6a, 6b, 6c, 6d, 6i, 6m, and 6s) showed no α‐amylase inhibitory activity. The protein kinase inhibition potential was determined for the first time, and the compounds 6d, 6e, 6f, 6h, 6k, 6p, and 6r depicted activity with the zone of inhibition in the range of 9 ± 1.3 to 19 ± 1.5 mm. The ligands and active site binding interactions of α‐glucosidase, α‐amylase, and protein kinase enzymes were also studied using molecular modeling. [ABSTRACT FROM AUTHOR]

• Zeugodacus tau and Z. signata may be sibling species due to similar host preference. • The host preference can be a marker for species delimitation. • Machine learning tools predict host preference better than statistical methods. Detecting the host preference of highly polyphagous and economically significant pest species of fruit flies (Diptera; Tephritidae) is important for identifying their species status, their management in orchards and the international trade of fruits and vegetables. In the current study, three fruit fly species Zeugodacus tau, Z. signata, and Z. cucrbitae , (Diptera: Tephritidae) were evaluated for their oviposition preference among three host fruits: pumpkin, cucumber, and bitter gourd. The investigation was conducted under choice conditions in the laboratory. Fruit fly species and host fruits were used as input/predictive variables whereas, oviposition preference, number of pupae, weight of pupae, adult emergence, and sex ratio were used as output/response variables to test the host preference through an Artificial Neural Network ANN/machine learning (ML) algorithms. ANN-based on a Multi-Layer Perceptron (MLP) model and decision tree-based Random Forest (RF) models were employed. Results revealed that Z. tau preferred pumpkin > cucumber > bitter gourd in order, Z. cucurbitae preferred bitter gourd > pumpkin > cucumber in order and Z. signata also preferred pumpkin but followed by bitter gourd and cucumber for oviposition. The specific host preferences observed in both Z. tau and Z. signata suggest that they may not be distinct species but rather closely related siblings. These findings highlight host preference as a marker for species delimitation. Moreover, the machine learning (ML) tools, provide better prediction in identifying host preference than statistical methods. These results are discussed in the context of the importance of studying host preferences for fruit flies' species delimitation, their management, and international trade of fruits and vegetables. [ABSTRACT FROM AUTHOR]

The validation of underexplored traditional plant remedies represents a reservoir of novel leads for drug discovery. In line with this, in vitro total phenolics and flavonoids content, multimode antioxidants, antimicrobial, cytotoxicity, and protein kinase inhibition assays were conducted on C. ambrosioides seed extracts in addition to RP-HPLC. Methanol extract exhibited highest total phenolics (64.6 ± 0.6 μ g gallic acid equivalent/mg) and flavonoids (50.9 ± 0.5 μ g quercetin equivalent/mg) content. RP-HPLC quantified rutin (1.98 μg/mg) in methanol extract whereas quercetin (0.322 μg/mg) and kaempferol (2.86 μg/mg) in methanol-distilled water extract. Methanol extract exhibited highest ascorbic acid equivalent (AAE) free radical (DPPH) scavenging (IC50 of 110.7 ± 5 μ g / ml), total antioxidant capacity (110.6 ± 2.2 μ g AAE/mg), and total reducing power (94.30 ± 0.46 μ g AAE/mg). Highest antibacterial activity against K. pneumonia (14 ± 1.61 mm ZOI) and antifungal activity against F. solani (17 ± 1.38 mm ZOI) were shown by n-hexane and chloroform extracts, respectively. Ethyl acetate extract exhibited highest brine shrimps cytotoxicity (LC50 of 125 μg/ml). A noteworthy protein kinase inhibitory potential was shown by ethanol extract with a 20 ± 1.27 mm bald zone. Therapeutic potential of medicinal plants can be completely explored by using multiple solvent system. This study makes C. ambrosioides, a resourceful prospect for the bioactivity-guided isolation of lead compounds. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the most common cancer in men, accounting for approximately 10% of all new cases in the United States. Plant-derived bioactive compounds, such as pentacyclic triterpenoids (PTs), have the ability to inhibit PCa cell proliferation. We isolated and characterized nummularic acid (NA), a potent PT, as a major chemical constituent of Ipomoea batatas, a medicinal food plant used in ethnomedicine for centuries. In the current study, in vitro antiproliferative potential against PCa cells (DU145 and PC3) via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay; Western blot protein expression analysis; absorption, distribution, metabolism, excretion (ADME); pharmacokinetic prediction studies; and bisphenol A (BPA)-induced prostate inhibition in Sprague Dawley rats were conducted to gauge the anti-cancer ability of NA. Significant (p < 0.05 and p < 0.01) time- and dose-dependent reductions in proliferation of PCa cells, reduced migration, invasion, and increased apoptotic cell population were recorded after NA treatment (3–50 µM). After 72 h of treatment, NA displayed significant IC50 of 21.18 ± 3.43 µM against DU145 and 24.21 ± 3.38 µM against PC3 cells in comparison to the controls cabazitaxel (9.56 ± 1.45 µM and 12.78 ± 2.67 µM) and doxorubicin (10.98 ± 2.71 µM and 15.97 ± 2.77 µM). Further deep mechanistic studies reveal that NA treatment considerably increased the cleavage of caspases and downstream PARP, upregulated BAX and P53, and downregulated BCL-2 and NF-κB, inducing apoptosis in PCa cells. Pharmacokinetic and ADME characterization indicate that NA has a favorable physicochemical nature, with high gastrointestinal absorption, low blood–brain barrier permeability, no hepatotoxicity, and cytochrome inhibition. BPA-induced perturbations of prostate glands in Sprague Dawley rats show a potential increase (0.478 ± 0.28 g) in prostate weight compared to the control (0.385 ± 0.13 g). Multi-dose treatment with NA (10 mg/kg) significantly reduced the prostate size (0.409 ± 0.21 g) in comparison to the control. NA-treated groups exhibited substantial restoration of hematological and histological parameters, reinstatement of serum hormones, and suppression of inflammatory markers. This multifaceted analysis suggests that NA, as a novel small molecule with a strong pharmacokinetic and pharmacological profile, has the potential to induce apoptosis and death in PCa cells. [ABSTRACT FROM AUTHOR]

The ethyl 2-[2-(2-nitrobenzylidene)hydrazinyl]thiazole-4-carboxylate (1), a thiazole ester, was synthesized by refluxing 1-(2-nitrobenzylidene)thiosemicarbazide and ethyl bromopyruvate. The compound is characterized by spectrometric, spectroscopic and single crystal (SC-XRD) techniques. Non-covalent interactions that are responsible for crystal packing are explored by Hirshfeld surface analysis. All theoretical calculations were performed by DFT quantum chemical methods using 6-311G(d,p) and cc-pVTZ basis sets and compared. Theoretical harmonic frequencies of ethyl 2-[2-(2-nitrobenzylidene)hydrazinyl]thiazole-4-carboxylate (1) were optimized. Confirmation of hydrogen bonding sites was analyzed by molecular electrostatic potential (MEP) and Mulliken population analysis. The vibrational frequencies of characteristic functional groups and chemical shifts were found in good agreement with experimental assignments. Frontier molecular orbital (FMO) revealed relatively small HOMO–LUMO (highest occupied molecular orbital-lowest unoccupied molecular orbital) gape, which speaks off the nearly planar geometry and extended conjugation, as compared to the substituents with no conjugation possible. It has also been observed that –NO2 substituent plays a vital role for this relatively small HOMO–LUMO gape and overall electronic properties when compared with similar thiazole carboxylates (2–6, Table 6). Ethyl 2-[2-(2-nitrobenzylidene)hydrazinyl]thiazole-4-carboxylate (1) was also evaluated for its anti-oxidant and anti-microbial activities. [ABSTRACT FROM AUTHOR]

Background. Inflammation is a frequent phenomenon in the pathogenesis of hepatic disorders leading to fibrosis and cirrhosis. Phytopharmaceuticals developed from traditional medicine can provide effective therapeutic alternatives to conventional medications. Datura stramonium (DS) has reported traditional uses in inflammatory diseases. In this study, we have tried to validate its potential as a source of anti-inflammatory agents. Methods. Powdered leaf part of DS was extracted using ethyl acetate (EA) to provide the extract (DSL-EA). Lymphocyte and macrophage viability and acute toxicity assays established the safety profile, while nitric oxide (NO) scavenging assay estimated the in vitro anti-inflammatory potential. Noninvasive anti-inflammatory, antidepressant, and antinociceptive activities were monitored using BALB/c mice using low and high doses (150 and 250 mg/kg). Major inflammatory studies were performed on Sprague-Dawley male rats using CCl4-induced liver injury model. Disease induction was initiated by intraperitoneal injections of CCl4 (1 mL/kg of 30% CCl4 in olive oil). The rats were divided into six groups. The anti-inflammatory potential of DSL-EA in low and high doses (150 and 300 mg/kg, respectively) was assessed through hematological, biochemical, liver antioxidant defense, oxidative stress markers, and histological studies as well as the expression of Nrf2 and iNOS. Results. DSL-EA exhibited prominent in vitro NO scavenging (IC50: 7.625 ± 0.51 μg/mL) and in vivo anti-inflammatory activity in paw and anal edema models. In CCl4 model, hematological investigations revealed vasotonic effects. Liver functionality was significantly (P < 0.001 − 0.05) improved in DSL-EA-treated rats. The activity level of endogenous antioxidant enzymes in liver tissues was improved in a manner identical to silymarin. The extract reduced the percent concentration of oxidative stress markers in liver tissues. Furthermore, DSL-EA displayed restorative effects on histological parameters (H and E and Masson's trichrome staining). Immunohistochemistry studies showed marked decline in Nrf2 expression, while overexpression of iNOS was also observed in disease control rats. The damage was distinctly reversed by the extract. [ABSTRACT FROM AUTHOR]

In a quest to discover new formulations for the treatment of various parasitic diseases, a series of heteroleptic triorganobismuth(V) biscarboxylates of type [BiR3(O2CR′)2], where R=C6H5 for 1–4 and p-CH3C6H4 for 5–8, were synthesized, characterized and evaluated for their biological potential against L. tropica. All the synthesized complexes were fully characterized by elemental analysis, FT-IR, multinuclear (1H and 13C) NMR spectroscopy and X-ray crystallography. The crystal structures for [BiPh3(O2CC6H4(o-Br))2] (1), [BiPh3(O2CC2H2C6H4)2] (2), [BiPh3(O2CC6H4(m-NO2))2] (3) and [BiPh3(O2CC6H4(2-OH,3-CH3))2] (4) were determined and found to have a distorted pentagonal bipyramidal molecular geometry with seven coordinated bismuth center for 1–3 and for 4 distorted octahedral geometry, respectively. All the synthesized complexes demonstrated a moderate to significant activity against leishmania parasites. A broad analytical approach was followed to testify the stability for (1–8) in solid state as well as in solution and in leishmanial culture M199, ensuring them to be stable enough to exert a significant antileishmanial effect with promising results. Cytotoxicity profile suggests that tris(tolyl) derivatives show lower toxicity against isolated lymphocytes with higher antileishmanial potential. Molecular docking studies were carried out to reveal the binding modes for (1–8) targeting the active site of trypanothione reductase (TR) (PDB ID: 4APN) and Trypanothione Synthetase-Amidase structure (PDB ID 2vob). [ABSTRACT FROM AUTHOR]

Wheat yellow rust is a common agricultural disease that affects the crop every year across the world. The disease not only negatively impacts the quality of the yield but the quantity as well, which results in adverse impact on economy and food supply. It is highly desired to develop methods for fast and accurate detection of yellow rust in wheat crop; however, high-resolution images are not always available which hinders the ability of trained models in detection tasks. The approach presented in this study harnesses the power of super-resolution generative adversarial networks (SRGAN) for upsampling the images before using them to train deep learning models for the detection of wheat yellow rust. After preprocessing the data for noise removal, SRGANs are used for upsampling the images to increase their resolution which helps convolutional neural network (CNN) in learning high-quality features during training. This study empirically shows that SRGANs can be used effectively to improve the quality of images and produce significantly better results when compared with models trained using low-resolution images. This is evident from the results obtained on upsampled images, i.e., 83% of overall test accuracy, which are substantially better than the overall test accuracy achieved for low-resolution images, i.e., 75%. The proposed approach can be used in other real-world scenarios where images are of low resolution due to the unavailability of high-resolution camera in edge devices. [ABSTRACT FROM AUTHOR]

The present research paper reports a convenient synthesis of novel 4-(benzylideneamino)-5-pentadecyl-2H-1,2,4-triazol-3(4H)-ones and their in vitro antioxidant assay. The synthesized azomethine-triazole hybrids are characterized using FT-IR, multi nuclear NMR and elemental analysis (CHN). Oxidative potential of the synthesized derivatives is assessed by performing various in vitro antioxidant and α-amylase assays. The best antioxidant potential was displayed by 4d followed by 4a, 4e and 4i. Molecular docking simulations revealed that the tested azomethine-triazole 4a showed strong binding inside the active-site gorges of the α-amylase. A striking agreement was obtained as the best-docked poses showed important binding features mostly based on interactions due to triazolone moiety of the azomethine linkage. The docking computations coupled with the experimental findings ascertained that the compound 4a can serve as a potential scaffold for the development of a novel class of α-amylase inhibitors. [ABSTRACT FROM AUTHOR]

Graphical abstract A series of new triorganotin(IV) complexes of Schiff base ligands as benzylidene benzohydrazide and their hydrazone analogues have been synthesized. Then they were complexed with organotin(IV) moiety with general formula [R' 3 SnL] where L = C 4 H 3 O-CONH-N CH-R, R = C 6 H 5 O(I a), C 4 H 5 O(I b), C 6 H 3 Cl 2 (I c) and R' = –CH 3 (1 – 3), –CH 2 Ph(4 – 6), –Ph(7 – 9). The complexes (1 – 9) have been fully characterized by IR, NMR(1H, 13C and 119Sn) spectroscopy, combined with CHN and melting point determinations. Highlights • New substituted hydrazones have been synthesized. • Hydrazones, then, complexed with triorganotin(IV) moieties to get target compounds. • All compounds characterized by advanced analytical techniques. • These compounds were preliminary bio-assayed and found encouraging results. Abstract A series of Schiff base ligands as benzylidene benzohydrazide and their hydrazone analogues (I a -I c) have been synthesized and then complexed with organotin(IV) moiety having general formula [R' 3 SnL] to get the target compounds (1 – 9) , where L = C 4 H 3 OCONHN CHR, R = C 6 H 5 O(I a), C 4 H 5 O(I b), C 6 H 3 Cl 2 (I c) and R' = –CH 3 (1 – 3), –CH 2 Ph(4 – 6), –Ph(7 – 9). They were fully characterized using FT-IR, NMR(1H, 13C and 119Sn) spectroscopy, along with elemental analysis and melting point. One of the precursor (I b) has been analyzed by single crystal XRD to further authenticate the structure. The 119Sn NMR data suggest the molecular geometry of organotin derivatives as distorted pentagonal bipyramidal. They were also evaluated for their antibacterial, antifungal, α-amylase inhibition, DPPH, total reducing power and total antioxidant activities. Triaryltin(IV) derivatives show good antibacterial and antifungal activity. Whereas the data for antidiabetic activity demonstrated that the compounds may serve as moderately effective alpha amylase inhibitor. [ABSTRACT FROM AUTHOR]

• Pd(II)-NHC complexes used as catalysts in direct C H arylation reaction of caffeine. • The C8-(hetero)aryl xanthines were obtained in good to excellent yields. • Different C8-(hetero)aryl xanthines which are important to biological applications were synthesised for the first time. • Molecular docking, antioxidant, antifungal, antibacterial and enzyme inhibitory evaluations of 8-(hetero)aryl xanthines were examined. A series of 8-(hetero)aryl caffeine was synthesized by the C H bond activation reaction using Pd-NHCs complexes as a catalyst. 8-(hetero)aryl caffeine derivatives were screened for their antioxidant, antimicrobial, and enzyme inhibitory activities and in-silico studies. The 4a, 4b, 4e, 4f, 4 g, 4i, and 4n showed significant total antioxidant capacity (TAC) of 64.03, 50.87, 70.02, 98.14, 71.81, 45.48, and 44.28 µg AAE/mg, respectively. The 4a, 4b, 4d, 4e, 6 h, 4i, 4j, 4k, and 4l were found active against Staphylococcus aureus at a minimum inhibitory concentration of 25, 12.5, 12.5, 12.5, 12.5, 6.25, 6.25, 6.25, and 6.25 µg/ml, respectively. Some derivatives displayed activity against Escherichia coli, Bacillus subtilus, Klebsiella pneumonae, and Pseudomonas aeruginosa. A good activity was exhibited against Alternaria solani among five fungal strains. All the compounds (4a–4n) showed excellent protein kinase inhibitory activity except 4e, 4 g, and 4n. Additionally, 8-(hetero)aryl caffeine derivatives showed α-amylase inhibition potential (IC50 = 1.49 ± 0.317 to 7.44 ± 0.156 μg/ml) compared to standard acarbose (IC50 = 4.34 ± 0.333 μg/ml). The 4b, 4d, 4j, 4 m, and 4n compounds displayed good α-glucosidase inhibitory potential. Molecular modeling was done for protein kinase, α-amylase, and α-glucosidase. The results of these activities proved the caffeine derivatives to be bioactive. [Display omitted] [ABSTRACT FROM AUTHOR]

Present work describes the in vitro antibacterial evaluation of some new amino acid conjugated antimicrobial drugs. Structural modification was attempted on the three existing antimicrobial pharmaceuticals namely trimethoprim, metronidazole, isoniazid. Twenty one compounds from seven series of conjugates of these drugs were synthesized by coupling with some selected Boc-protected amino acids. The effect of structural features and lipophilicity on the antibacterial activity was investigated. The synthesized compounds were evaluated against five standard American type culture collection (ATCC) i.e. Staphylococcus aureus , Bacillus subtilis, Escherichia coli , Pseudomonas aeruginosa and Salmonella typhi strains of bacteria. Our results identified a close relationship between the lipophilicity and the activity. Triazine skeleton proved beneficial for the increase in hydrophobicity and potency. Compounds with greater hydrophobicity have shown excellent activities against Gram-negative strains of bacteria than Gram-positive. 4-amino unsubstituted trimethoprim-triazine derivative 7b have shown superior activity with MIC = 3.4 μM (2 μg/mL) for S. aureus and 1.1 μM (0.66 μg/mL) for E. coli . The synthesized compounds were also evaluated for their urease inhibition study. Microbial urease from Bacillus pasteurii was chosen for this study. Triazine derivative 7a showed excellent inhibition with IC 50  = 6.23 ± 0.09 μM. Docking studies on the crystal structure of B. pasteurii urease (PDB ID 4UBP ) were carried out. [ABSTRACT FROM AUTHOR]

Diabetic neuropathic pain is one of the microvascular complications of diabetes mellitus characterized by symmetrical pain and sensory abnormalities. A steroidal lactone isolated from the datura innoxa plant, withametelin (WMT), exhibited significant neuroprotective, anti-inflammatory, antioxidant, and anticancer properties. The current study aimed to investigate anti-neuropathic pain activity and the molecular mechanism of WMT against streptozotocin (STZ)-induced diabetic neuropathy. Rats were given a single injection of STZ (60 mg/kg, intraperitoneally (i.p.)) for induction of diabetes on the first day of the study. After the onset of diabetic neuropathy, pregabalin (10 mg/kg, i.p.) and WMT (0.1 and 1 mg/kg, i.p.) treatments were started from day 14 up to day 42. It was found that STZ-induced neuropathic pain behaviors were markedly reduced by WMT. It inhibited the STZ-associated histopathological changes and genotoxicity in the sciatic nerve and spinal cord. Additionally, Fourier transforms infrared (FTIR) spectroscopy results revealed that STZ-induced alterations in the biochemical components of the sciatic nerve's myelin sheath were inhibited by WMT. In the spinal cord, it markedly reduced the immunoreactivity of mitogen-activated protein kinases (MAPKs) signaling components such as p38 - MAPK, c-Jun N-terminal kinase (JNK), extracellular-signal-regulated-kinase (ERK), and activator-protein 1 (AP-1). It also reduced the expression levels of nuclear factor-kappa-B (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). The production of inflammatory cytokines was considerably reduced by WMT. This study provides convincing evidence that WMT treatment attenuated STZ-induced diabetic neuropathic pain by inhibition of MAPK/NF-κB signaling. [Display omitted] • Withametelin alleviated STZ-induced neuropathic pain behaviors. • Withametelin restored STZ-associated histopathological changes. • Withametelin suppressed the STZ-induced inflammatory cytokines. • Withametelin reduced the immunoreactivity of MAPK/NF-kB signaling proteins. [ABSTRACT FROM AUTHOR]

1,3,4-Oxadiazoles are important class of heterocyclic compounds, with diverse biological applications. In this study, the synthesis of three different 1,3,4-oxadiazoles bearing pentadecyl moiety is reported. All compounds were synthesized with significant (70–82%) yields, characterized by using different spectroanalytical techniques such as UV–vis., FT-IR, NMR ( 1 H and 13 C), and finally structures were confirmed unequivocally by single crystal X-ray diffraction analysis. Quantum chemical studies by using GAUSSIAN software at DFT/B3LYP/6-31G (d, p) level of theory have been exercised to compare and validate the spectroscopic and X-ray results. Frontier molecular orbitals (FMOs) analysis of all compounds was performed by utilizing optimized geometries and gave the idea about kinetic stability and reactivity. Molecular electrostatic potential (MEP) analysis indicated the regions for electrophilic as well as nucleophilic attack. Compounds were also screened to check their antibacterial and antifungal potential. [ABSTRACT FROM AUTHOR]

• Synthesis of arylidenehydrazinylthiazole carbohydrazides with varying electonic properties of the aryidene group • Structures were analyzed through different spectroscopic techniques. • The experimental results show good agreement with theoretical results. • NLO and electronic properties were also studied. Hydrazide scaffold is very significant in medicinal and synthetic chemistry. Hydrazides lead to heterocyclic pharmacophores exhibiting substantial physicochemical properties. Synthesis of 2-(2-(arylidene)hydrazinyl)thiazole-4-carbohydrazides (BHTC1-BHTC6) (48–69%), was accomplished through multistep sequence, incorporating variable electronic properties in the arylidene moiety. The structures of the accomplished synthetic design were established via FT-IR, HRMS, 1H and 13CNMR. The α -Amylase study of all new compounds showed percentage inhibition values within the range of 17.78±0.023 to 31.00±0.19 at 50 µg/mL as compared to acarbose (85.56±0.56, at 50 µg/mL). However, the synthesized compounds also exhibited moderate to good protein kinase inhibition as well. The computational analyses were also accomplished for BHTC1-BHTC6 at M06 functional with a 6–31G(d,p) basis set. To elucidate the stability and ICT of the compounds, NBO and FMO analyses were conducted. The synthesized compound BHTC6 displayed the lowest bandgap value, i.e., 4.355 eV among BHTC1-BHTC5. The global reactivity parameters were correlated with their bandgap data and BHTC6 was concluded to express a high value of softness and a low hardness value among entitled compounds. Moreover, UV–Vis analysis indicates that BHTC6 is the most bathochromically shifted among all designed compounds, possessing λ max of 381.534 nm. The aforementioned results reveal that these compounds may prove significant in developing better enzyme inhibitors or antimicrobial agents. [Display omitted] [ABSTRACT FROM AUTHOR]

This study aimed to investigate the anti-neuropathic pain activity and its underlying molecular mechanism of Ajugarin-I (Aju-I) in a rat model of diabetic neuropathic pain. The rats were given a single injection of 60 mg/kg of streptozotocin (STZ) intraperitoneally (i.p.) to induce diabetic neuropathic pain. After two weeks, rats were given Aju-I (1 and 5 mg/kg/day) i.p. for four consecutive weeks. The results demonstrated that in diabetic rats, treatment with Aju-I decreased STZ-induced hyperglycemia. It reduced the pain hypersensitivity (mechanical, thermal, and cold nociception) caused by STZ. It effectively restored STZ-associated pathological changes in the pancreas. In the sciatic nerve and spinal cord, it attenuated STZ-associated histopathological alterations and DNA damage. It suppressed oxidative stress by increasing the expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2), thioredoxin (Trx), and heme oxygenase (HO-1), but decreasing the immunoreactivity of Kelch-like ECH-associated protein 1 (Keap1). Additionally, TRPV1 (transient receptor potential vanilloid 1) and TRPM8 (transient receptor potential melastatin 8) expression levels were considerably reduced by Aju-I treatment. It enhanced antioxidant levels and suppressed inflammatory cytokines production. Taken together, this research suggests that Aju-I treatment reduces pain behaviors in the STZ model of diabetic neuropathy via modulating Nrf2/Keap-1/HO-1 signaling and TRPV1/TRPM8 nociceptors. [Display omitted] • Ajugarin-I attenuated the STZ-induced diabetic neuropathic pain. • Ajugarin-I reversed the histopathological alterations caused by STZ. • Ajugarin-I increased the expression levels of Nrf2/HO-1/Trx. • Ajugarin-I suppressed TRPV1/TRPM8 nociceptors. [ABSTRACT FROM AUTHOR]

The olive fly Bactrocera oleae (Rossi) is the key pest for olive cultivation worldwide. Substantial effort has been invested in the development of the sterile insect technique (SIT) to control this pest. One of the limitations to develop SIT technology for olive fruit fly is the low ability of wild females to lay eggs in other medium than olive fruits, and their slow adaptation to oviposition in artificial substrates. In the present study, fruit grapes were used as an alternative egg collection medium to harvest eggs and young larvae from freshly colonized wild strains originating from France, Italy, Spain and Croatia. The larvae were allowed to develop into the fruits until the second instar, before they were extracted out and further reared on a standard artificial diet. Furthermore, F1 to F4 female flies were alternatively offered wax bottles to oviposit. Finally, the performance of hybrid strains created from crosses between wild and long colonised flies was assessed. The results showed that females of all 4 wild strains readily oviposited eggs in grapes and from the F2 generation onward, females from all strains were adapted to laying eggs in wax bottles. No difference was observed in eggs and pupae production among all strains tested. The findings are discussed for their implications on SIT application against olive fruit fly. [ABSTRACT FROM AUTHOR]

Withaferin A (WA) is a pivotal withanolide that has conquered a conspicuous place in research, owning to its multidimensional biological properties. It is an abundant constituent in Withania somnifera Dunal. (Ashwagandha, WS) that is one of the prehistoric pivotal remedies in Ayurveda. This article reviews the literature about the pharmacological profile of WA with special emphasis on its anticancer aspect. We reviewed research publications concerning WA through four databases and provided a descriptive analysis of literature without statistical or qualitative analysis. WA has been found as an effective remedy with multifaceted mechanisms and a broad spectrum of pharmacological profiles. It has anticancer, anti-inflammatory, antiherpetic, antifibrotic, antiplatelet, profibrinolytic, immunosuppressive, antipigmentation, antileishmanial, and healing potentials. Evidence for wide pharmacological actions of WA has been established by both in vivo and in vitro studies. Further, the scientific literature accentuates the role of WA harboring a variable therapeutic spectrum for integrative cancer chemoprevention and cure. WA is a modern drug from traditional medicine that is necessary to be advanced to clinical trials for advocating its utility as a commercial drug. [ABSTRACT FROM AUTHOR]

Solubility of phytoconstituents depends on the polarity of the extraction medium used, which might result in the different pharmacological responses of extracts. In line with this, ethnomedicinally important food plant (i.e., Caralluma tuberculata extracts) have been made in fourteen distinct solvent systems that were then analyzed phytochemically via total phenolic amount estimation, total flavonoid amount estimation, and HPLC detection and quantification of the selected polyphenols. Test extracts were then subjected to a battery of in vitro assays i.e., antioxidants (DDPH scavenging, antioxidant capacity, and reducing power estimation), antimicrobial (antibacterial, antifungal, and antileishmanial), cytotoxic (brine shrimps, THP-1 human leukemia cell lines and normal lymphocytes), and protein kinase inhibition assays. Maximum phenolic and flavonoid contents were computed in distilled water–acetone and acetone extracts (i.e., 16 ± 1 μg/mg extract and 8 ± 0.4/mg extract, respectively). HPLC-DAD quantified rutin (0.58 µg/mg extract) and gallic acid (0.4 µg/mg extract) in methanol–ethyl acetate and methanol extracts, respectively. Water–acetone extract exhibited the highest DPPH scavenging of 36 ± 1%. Total reducing potential of 76.0 ± 1 μg/mg extract was shown by ethanol chloroform while maximum total antioxidant capacity was depicted by the acetone extract (92.21 ± 0.70 μg/mg extract). Maximal antifungal effect against Mucor sp., antileishmanial, brine shrimp cytotoxicity, THP-1 cell line cytotoxicity, and protein kinase inhibitory activities were shown by ethyl acetate-methanol (MIC: 50 µg/disc), n-hexane (IC50: 120.8 ± 3.7 µg/mL), ethyl acetate (LD50: 29.94 ± 1.6 µg/mL), distilled water–acetone (IC50: 118 ± 3.4 µg/mL) and methanol–chloroform (ZOI: 19 ± 1 mm) extracts, respectively. Our findings show the dependency of phytochemicals and bioactivities on the polarity of the extraction solvent and our preliminary screening suggests the C. tuberculata extract formulations to be tested and used in different ailments, however, detailed studies remain necessary for corroboration with our results. [ABSTRACT FROM AUTHOR]

A worldwide increase in the incidence of fungal infections, emergence of new fungal strains, and antifungal resistance to commercially available antibiotics indicate the need to investigate new treatment options for fungal diseases. Therefore, the interest in exploring the antifungal activity of medicinal plants has now been increased to discover phyto-therapeutics in replacement to conventional antifungal drugs. The study was conducted to explore and identify the mechanism of action of antifungal agents of edible plants, including Cinnamomum zeylanicum, Cinnamomum tamala, Amomum subulatum, Trigonella foenumgraecum, Mentha piperita, Coriandrum sativum, Lactuca sativa, and Brassica oleraceae var. italica. The antifungal potential was assessed via the disc diffusion method and, subsequently, the extracts were assessed for phytochemicals and total antioxidant activity. Potent polyphenols were detected using high-performance liquid chromatography (HPLC) and antifungal mechanism of action was evaluated in silico. Cinnamomum zeylanicum exhibited antifungal activity against all the tested strains while all plant extracts showed antifungal activity against Fusarium solani. Rutin, kaempferol, and quercetin were identified as common polyphenols. In silico studies showed that rutin displayed the greatest affinity with binding pocket of fungal 14-alpha demethylase and nucleoside diphosphokinase with the binding affinity (Kd, −9.4 and −8.9, respectively), as compared to terbinafine. Results indicated that Cinnamomum zeylanicum and Cinnamomum tamala exert their antifungal effect possibly due to kaempferol and rutin, respectively, or possibly by inhibition of nucleoside diphosphokinase (NDK) and 14-alpha demethylase (CYP51), while Amomum subulatum and Trigonella foenum graecum might exhibit antifungal potential due to quercetin. Overall, the study demonstrates that plant-derived products have a high potential to control fungal infections. [ABSTRACT FROM AUTHOR]

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system (CNS) that remains incurable. Withametelin (WMT), a phytosterol, showed diverse biological activities isolated from the leaves of Datura innoxa. In the present study, we used an in vitro model of HT22 and BV - 2 cell lines and an in vivo murine model of MS, experimental autoimmune encephalomyelitis (EAE), to explore the antioxidant and anti neuroinflammatory potential of WMT. The results showed that pretreatment with WMT markedly inhibited H 2 O 2 - induced cytotoxicity and oxidative stress in a dose-dependent manner. Correspondingly, WMT post-immunization treatment significantly attenuated EAE-induced clinical score, weight loss, neuropathic pain behaviors, and motor dysfunction. It markedly lowers EAE-induced elevated circulating leucocytes, spinal deformity, and splenomegaly. It strikingly inhibited the Evans blue and FITC extravasation in the brain. It remarkably reversed the EAE-induced histopathological alteration of the brain, spinal cord, eye, and optic nerve. It significantly intensified the antioxidant defense mechanism by improving the expression level of nuclear factor-erythroid-related factor-2 (Nrf2), heme-oxygenase-1 (HO-1) but reducing the expression level of the Kelch-like-ECH-associated-protein-1 (keap-1), inducible-nitric-oxide-synthase (iNOS) in the CNS. Likewise, it markedly suppressed neuroinflammation by reducing the expression level of toll-like-receptor 4 (TLR4), nuclear-factor-kappa-B (NF-κB), activator-protein-1 (AP-1) but increased the expression level IkB-α in the CNS. Furthermore, molecular dynamics simulations and MMPBSA binding free energies were determined to validate the dynamic stability of complexes and shed light on the atomic level intermolecular interaction energies. Taken together, this study showed that WMT has significant neuroprotective potential in EAE via modulation of Nrf2 mediated-oxidative stress and NF-κB mediated inflammation. [Display omitted] • Withametelin ameliorated EAE-associated clinical symptoms. • Withametelin reversed EAE-associated histopathological alteration in the CNS. • Withametelin suppressed the BBB permeability, oxidative stress & neuroinflammation. • Withametelin inhibited the apoptosis, protein, and myelin damage in the EAE mice. • Withametelin modulates the expression of TLR4/IκB-α/NF-κB/AP-1 & Nrf2/Keap-1/HO-1/iNOS/Bcl-2. [ABSTRACT FROM AUTHOR]

Exploration of leads with therapeutic potential in inflammatory disorders is worth pursuing. In line with this, the isolated natural compound daturaolone from Datura innoxia Mill. was evaluated for its anti-inflammatory potential using in silico, in vitro and in vivo models. Daturaolone follows Lipinski's drug-likeliness rule with a score of 0.33. Absorption, distribution, metabolism, excretion and toxicity prediction show strong plasma protein binding; gastrointestinal absorption (Caco-2 cells permeability = 34.6 nm/s); no blood–brain barrier penetration; CYP1A2, CYP2C19 and CYP3A4 metabolism; a major metabolic reaction, being aliphatic hydroxylation; no hERG inhibition; and non-carcinogenicity. Predicted molecular targets were mainly inflammatory mediators. Molecular docking depicted H-bonding interaction with nuclear factor kappa beta subunit (NF-κB), cyclooxygenase-2, 5-lipoxygenase, phospholipase A2, serotonin transporter, dopamine receptor D1 and 5-hydroxy tryptamine. Its cytotoxicity (IC50) value in normal lymphocytes was >20 µg/mL as compared to cancer cells (Huh7.5; 17.32 ± 1.43 µg/mL). Daturaolone significantly inhibited NF-κB and nitric oxide production with IC50 values of 1.2 ± 0.8 and 4.51 ± 0.92 µg/mL, respectively. It significantly reduced inflammatory paw edema (81.73 ± 3.16%), heat-induced pain (89.47 ± 9.01% antinociception) and stress-induced depression (68 ± 9.22 s immobility time in tail suspension test). This work suggests a possible anti-inflammatory role of daturaolone; however, detailed mechanistic studies are still necessary to corroborate and extrapolate the findings. [ABSTRACT FROM AUTHOR]

Automatic Generation Control (AGC) delivers a high quality electrical energy to energy consumers using efficient and intelligent control systems ensuring nominal operating frequency and organized tie-line power deviation. Subsequently, for the AGC analysis of a two-area interconnected hydro-gas-thermal-wind generating unit, a novel Fractional Order Integral-Tilt Derivative (FOI-TD) controller is proposed that is fine-tuned by a powerful meta-heuristic optimization technique referred as Improved-Fitness Dependent Optimizer (I-FDO) algorithm. For more realistic analysis, various constraints, such as Boiler Dynamics (BD), Time Delay (TD), Generation Rate Constraint (GRC), and Governor Dead Zone (GDZ) having non-linear features are incorporated in the specified system model. Moreover, a comparative analysis of I-FDO algorithm is performed with state-of-the-art approaches, such as FDO, teaching learning based optimization, and particle swarm optimization algorithms. Further, the proposed I-FDO tuned controller is compared with Fractional Order Tilt Integral Derivative (FOTID), PID, and Integral-Tilt Derivative (I-TD) controllers. The performance analysis demonstrates that proposed FOI-TD controller provides better performance and show strong robustness by changing system parameters and load condition in the range of  ± 50%, compared to other controllers. [ABSTRACT FROM AUTHOR]

The present study aims to determine the neuroprotective effect of Bergenin against spatial memory deficit associated with neurodegeneration. Preliminarily, the protective effect of Bergenin was observed against H2O2-induced oxidative stress in HT-22 and PC-12 cells. Further studies were performed in 5xFAD Tg mouse model by administering Bergenin (1, 30 and 60 mg/kg; orally), whereas Bergenin (60 mg/kg) significantly attenuated the memory deficit observed in the Y-maze and Morris water maze (MWM) test. Fourier transform-infrared (FT-IR) spectroscopy displayed restoration of lipids, proteins and their derivatives compared to the 5xFAD Tg mice group. The differential scanning calorimeter (DSC) suggested an absence of amyloid beta (Aβ) aggregation in Bergenin-treated mice. The immunohistochemistry (IHC) analysis suggested the neuroprotective effect of Bergenin by increasing Reelin signaling (Reelin/Dab-1) and attenuated Aβ (1–42) aggregation in hippocampal regions of mouse brains. Furthermore, IHC and western blot results suggested antioxidant (Keap-1/Nrf-2/HO-1), anti-inflammatory (TLR-4/NF-kB) and anti-apoptotic (Bcl-2/Bax/Caspase-3) effect of Bergenin. Moreover, a decrease in Annexin V/PI-stained hippocampal cells suggested its effect against neurodegeneration. The histopathological changes were reversed significantly by Bergenin. In addition, a remarkable increase in antioxidant level with suppression of pro-inflammatory cytokines, oxidative stress and nitric oxide production were observed in specific regions of the mouse brains. [ABSTRACT FROM AUTHOR]

• · Eight new bioactive bismuth(III) hydrazones were synthesized and fully characterized, besides the solvent molecule, DMSO, contribute to their structural motifs. • X-ray structure for 1 revealed a distinctive seven coordinated Bi(III) center, assuming pentagonal bipyramidal molecular geometry. • · The compounds 6, 7 and 8 exhibited significant antidiabetic activity. • · Molecular docking study revealed significant activity of 2 against Human pancreatic alpha amylase with the highest GOLD fitness score. • · The docking data for (1) described its active role against H. pylori urease having the highest GOLD fitness score. Eight new bismuth(III) complexes (1-8) of substituted hydrazones having general formula; [Bi(RCONHNCHC 5 H 4 N)Cl x ] and [Bi(RCONHNCHC 9 H 6 N)Cl x ], where R = C 10 H 7 O (1, and 8) , C 4 H 3 S (2) , C 6 H 5 O (3, and 6), C 7 H 7 (4), C 5 H 4 N (5, and 7), x = 2 or 3 have been prepared. The substituted hydrazones (I 1 -I 8) were synthesized by reacting the stoichiometric amounts of the respective hydrazides such as p-toluic hydrazide, 4-hydroxybenzhydrazide, thiophene-2-carboxylic acid hydrazide, 3-hydroxy-2-naphthoic acid hydrazide, Isonicotic acid hydrazide and appropriate aromatic aldehydes like pridine-2-carboxaldehyde and quinoline-2-carboxyaldehyde. These hydrazones (ligands),then complexed to Bi(III) species to yield the target compounds. They were characterized by FTIR, and NMR spectroscopy to find out an explicit evidence about their structural motifs. The X-ray data for (1 & I 6) further validate the chemical structures of the synthesized compounds. The molecular geometry for (1) is predominately distorted pentagonal bipyramidal where hepta-coordinated Bi(III) center is attached to the nitrogens of pyridine and of azomethine moieties along with the carbonyl oxygen, two chloro and two oxygens of the (two) DMSO molecules. The bond lengths for Bi(1)-O(1), Bi(1)-N(1) and Bi(1)-N(2) are 2.323(5), 2.539(6), 2.390(5) oA respectively indicating Bi(1)-O(1) as the strongest linkage to the metal center. The H-bonding, present in (1), contributed an extra stability to the structure. The synthesized compounds were initially screened for their possible antimicrobial, alpha-amylase, and protein kinase inhibition, some (1,2,6,8) exhibit significant activity. The experimental results are further endorsed by molecular docking studies against helicobacter pylori urease (1E9Y), epidermal growth factor receptor tyrosine kinase (1M17) and human pancreatic alpha amylase (5U3A) inhibition activity. The significant ligand-receptor interactions, observed at the binding pocket of the selected drug targets, further revealed the enzyme inhibition potential of the compounds and highlighting their possible roles as therapeutic agents in future drug discovery processes. [ABSTRACT FROM AUTHOR]