Botanicals against some important nematodal diseases: Ascariasis and hookworm infections.

Ascariasis and intestinal parasitic nematodes are the leading cause of mass mortality infecting many people across the globe. In light of the various deleterious side effects of modern chemical-based allopathic drugs, our preferences have currently shifted towards the use of traditional plant-based drugs or botanicals for treating diseases. The defensive propensities in the botanicals against parasites have probably evolved during their co-habitation with parasites, humans and plants in nature and hence their combative interference in one another's defensive mechanisms has occurred naturally ultimately being very effective in treating diseases. This article broadly outlines the utility of plant-based compounds or botanicals prepared from various medicinal herbs that have the potential to be developed as effective therapies against the important parasites causing ascariasis and intestinal hookworm infections leading to ascariasis & infections and thereby human mortality, wherein allopathic treatments are less effective and causes enormous side-effects.

Abiotic and biotic stress alleviating effects of the medicinal and aromatic plant-derived product on striped catfish Pangasianodonhypophthalmus.

Intensification of aquaculture production leads to abiotic and biotic stresses, which are further induced by the impact of climate change. Thus, it is important to explore a combined strategy to alleviate multiple stresses in fish. In the present investigation, the removal of nitrogenous metabolites from aquaponics water was studied using products derived from five different locally available medicinal and aromatic plants (MAPs) namely banana stem (Musa Accuminata), Aloe vera, Mint (Minata sepicata), Indian beech/Pongameoil-tree/Karanj (Pongamia pinnatum), and Coat Button/Mexican daisy/Dagadipala (Tridax procrumbens) in the batch experiment for 24 h. A reduction of 91-94% in the ammonia level and 75-80% removal of nitrite-N in the treatments with products derived from mint, banana stem, and aloe vera has been observed. Mint product was also found to be bactericidal against fish pathogenic bacteria. Based on this dual function of mint, further study was conducted under wet-lab conditions to evaluate the possible protective role of the mint-based product in dry powder form against abiotic stresses caused by nitrogenous toxicants for 24 h and 45 days multiple stresses caused by nitrogenous toxicants in freshwater stocked with eight fingerlings of Pangasianodon hypophthalmus of the initial weight of 8 ± 0.5g for 24 h and 8.82 ± 0.75g for 45 days. The results revealed that mint-derived plant product has better anti-stress properties in terms of their bioremediation effectiveness in lowering ammonia and nitrite. Mint also improved the fish growth performance with better physiological responses and anti-oxidative status and reduced the cellular metabolic stress in fish reared under ammonia, as further indicated by reduced oxidative stress parameters, and tissue biochemical indices. Overall, mint showed its main properties as a growth promoter, and immune enhancer, where this medicinal plant product acts as a bioremediation and antibacterial agent to the host immune system. This has potential applications in the environmental and health management of aquaculture.

Eco-Oriented Formulation and Stabilization of Oil-Colloidal Biodelivery Systems Based on GC-MS/MS-Profiled Phytochemicals from Wild Tomato for Long-Term Retention and Penetration on Applied Surfaces for Effective Crop Protection.

Vegetable oils as hydrophobic reserves in oil dispersions (OD) provide a practical approach to halt bioactive degradation for user and environment-efficient pest management. Using biodegradable soybean oil (57%), castor oil ethoxylate (5%), calcium dodecyl benzenesulfonates as nonionic and an-ionic surfactants, bentonite (2%), and fumed silica as rheology modifiers, we created an oil-colloidal biodelivery sytem (30%) of tomato extract with homogenization. The quality-influencing parameters, such as particle size (4.5 µm), dispersibility (97%), viscosity (61 cps), and thermal stability (2 years), have been optimized in accordance with specifications. Vegetable oil was chosen for its improved bioactive stability, high smoke point (257 °C), coformulant compatibility, and as a green build-in-adjuvant by improving spreadability (20-30%), retention and penetration (20-40%). In in vitro testing, it efficiently controlled aphids with 90.5% mortalities and 68.7-71.2% under field-conditions without producing phytotoxicity. Wild tomato-derived phytochemicals can be a safe and efficient alternative to chemical pesticides when combined wisely with vegetable oils.

Breeding and adoption of biofortified crops and their nutritional impact on human health.

Micronutrient malnutrition has affected over two billion people worldwide and continues to be a health risk. A growing human population, poverty, and the prevalence of low dietary diversity are jointly responsible for malnutrition, particularly in developing nations. Inadequate bioavailability of key micronutrients, such as iron (Fe), zinc (Zn), and vitamin A, can be improved through agronomic and/or genetic interventions. The Consultative Group on International Agricultural Research prioritizes developing biofortified food crops that are rich in minerals and vitamins through the HarvestPlus initiative on biofortification. The objective of this review is to provide an overview of biofortified food crops along with evidence supporting their acceptability and adoption. Between 2004 and 2019, 242 biofortified varieties belonging to 11 major crops were released in 30 countries across Asia, Africa, and Latin America. These conventionally bred biofortified crops include Fe-enriched beans, pearl millet, and cowpea; Zn-enriched rice, wheat, and maize; both Fe- and Zn-enriched lentil and sorghum; and varieties with improved vitamin A in orange-fleshed sweet potato, maize, cassava, and banana/plantain. In addition to ongoing efforts, breeding innovations, such as speed breeding and CRISPR-based gene editing technologies, will be necessary for the next decade to reach two billion people with biofortified crops.

Meta-QTLs, ortho-MetaQTLs and candidate genes for grain Fe and Zn contents in wheat (Triticum aestivum L.).

Majority of cereals are deficient in essential micronutrients including grain iron (GFe) and grain zinc (GZn), which are therefore the subject of research involving biofortification. In the present study, 11 meta-QTLs (MQTLs) including nine novel MQTLs for GFe and GZn contents were identified in wheat. Eight of these 11 MQTLs controlled both GFe and GZn. The confidence intervals of the MQTLs were narrower (0.51-15.75 cM) relative to those of the corresponding QTLs (0.6 to 55.1 cM). Two ortho-MQTLs involving three cereals (wheat, rice and maize) were also identified. Results of MQTLs were also compared with the results of earlier genome wide association studies (GWAS). As many as 101 candidate genes (CGs) underlying MQTLs were also identified. Twelve of these CGs were prioritized; these CGs encoded proteins with important domains (zinc finger, RING/FYVE/PHD type, flavin adenine dinucleotide linked oxidase, etc.) that are involved in metal ion binding, heme binding, iron binding, etc. qRT-PCR analysis was conducted for four of these 12 prioritized CGs using genotypes which have differed for GFe and GZn. Significant differential expression in these genotypes was observed at 14 and 28 days after anthesis. The MQTLs/CGs identified in the present study may be utilized in marker-assisted selection (MAS) for improvement of GFe/GZn contents and also for understanding the molecular basis of GFe/GZn homeostasis in wheat. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01149-9.

Phenolic and flavonoid contents and antioxidant activity of an endophytic fungus Nigrospora sphaerica (EHL2), inhabiting the medicinal plant Euphorbia hirta (dudhi) L.

Since endophytic fungi are pivotal sources of various bioactive natural compounds, the present study is aimed to investigate the antioxidant compounds of the endophytic fungus Nigrospora sphaerica isolated from a pantropical weed, Euphorbia hirta L. The fungus was fermented in four different media and each filtered broth was sequentially extracted in various solvents. Crude extracts collected from different solvents were subjected to phytochemical analysis and antioxidant activity. The total phenolic content (TPC) and total flavonoid content (TFC) were maximal in ethyl acetate crude extract (EtOAcE) of endophyte fermented in potato dextrose broth (PDB) medium (77.74 ± 0.046mgGAE/g and 230.59 ± 2.0 mgRE/g) with the highest 96.80% antioxidant activity. However, TPC and TFC were absent in hexane extract of Czapek Dox broth (CDB) medium exhibiting the lowest 4.63 ± 2.75% activity. The EtOAcE (PDB) showed a positive correlation between TFC and antiradical activity (R2 = 0.762; P < 0.05), whereas a high positive correlation was noticed between TPC and antioxidant activity (R2 = 0.989; P < 0.05). Furthermore, to determine the antioxidant activity, EtOAcE (PDB) was subjected to TLC bioautography-based partial purification, while GC/MS analysis of the partial purified extract was done to confirm the presence of phenolics along with antioxidant compounds that resulted in the detection of 2,4-Di-tert-butylphenol (13.83%), a phenolic compound accountable for the antioxidant potential. Conclusively, N. sphaerica is a potential candidate for natural antioxidant.

Managing arsenic (V) toxicity by phosphate supplementation in rice seedlings: modulations in AsA-GSH cycle and other antioxidant enzymes.

The toxic and non-essential metalloid arsenic (As) is ubiquitous in the environment with its absorption from the soil into the plants' roots posing detrimental effects on the crop plants and hence the food availability and food security are also threatened. The present study was intended to reduce the As-induced toxicity in rice seedlings (Oryza sativa L.) by phosphate (PO43-). For this, three concentrations of potassium phosphate (KH2PO4), 50, 100 and 150 µM were supplemented along with 50 µM As exposure to hydroponically grown 7-day-old rice seedlings. Supplementation of PO43- significantly recovered arsenic-induced diminutions in growth parameters and photosynthetic pigment contents which were due to the significant increase in superoxide radical (SOR, O2•¯) and hydrogen peroxide (H2O2). Supplementation of 50 µM PO43- could significantly increase the activity of APX (ascorbate peroxidase) and GR (glutathione reductase) while 100 µM PO43- could increase the activity of DHAR (dehydroascorbate reductase) and monodehydroascorbate reductase (MDHAR). As the amount of PO43- was increased, the ratio of AsA/DHA (reduced to oxidized ascorbate) and GSH/GSSG (reduced to oxidized glutathione) was increased significantly due to increase in the reduced form of the non-enzymes i.e. AsA and GSH. The activity of SOD (superoxide dismutase) and GPX (guaiacol peroxidase) decreased significantly after a substantive increase in their activities due to As stress while the CAT (catalase) activity further enhanced after the supplementation of 50 and 100 µM PO43-. Thus, the As-induced oxidative stress in the rice seedlings was managed by concerted modulations in the activities of SOD, GPX, CAT and AsA-GSH cycle enzymes and metabolites.

Impregnation of pectin-cedarwood essential oil nanocapsules onto mini cotton bag improves larvicidal performances.

The use pesticide is one of the indispensable means to combat mosquito borne diseases. However, the repeated use of synthetic pesticides has induced resistance in the vector pest along with undesirable impact on the environment. The biodegradability, non-persistent and user's safety are the root cause to prefer plant-derived pesticides to synthetic ones. The botanical based pesticides tend to degrade rapidly under the influence of several environmental factors. For the feasible application as pesticides, the plant products are formulated either as liquid or as purely solid. Despite well-established formulation technology in pesticide delivery, their handling trouble is being ignored. There is difficulty in liquid formulation of pesticide products, as they are prone to splashing and spillage, resulting in contamination, wastage and direct exposure to skin; whereas a solid formulation tends to produce dust. In the present work, cedarwood (Cedrus deodara) essential oil embedded pectin nanocapsules were produced. The nanocapsules were characterized according to their morphology, size, encapsulation efficiency and thermal stability. Furthermore, the nanocapsules were impregnated onto mini cotton tea bags to be employed as RTU (ready to use) formulation for treating the breeding sites of mosquitoes. The larvicidal activity of the bags treated with pectin-cedar wood nanocapsules was assessed against malaria vector, Anopheles culicifacies and 98% mortality was recorded till 4 weeks, this suggests its potential and hassle free applications in controlling mosquito vector.

Harnessing the Phytotherapeutic Treasure Troves of the Ancient Medicinal Plant Azadirachta indica (Neem) and Associated Endophytic Microorganisms.

Azadirachta indica, commonly known as neem, is an evergreen tree of the tropics and sub-tropics native to the Indian subcontinent with demonstrated ethnomedicinal value and importance in agriculture as well as in the pharmaceutical industry. This ancient medicinal tree, often called the "wonder tree", is regarded as a chemical factory of diverse and complex compounds with a plethora of structural scaffolds that is very difficult to mimic by chemical synthesis. Such multifaceted chemical diversity leads to a fantastic repertoire of functional traits, encompassing a wide variety of biological activity and unique modes of action against specific and generalist pathogens and pests. Until now, more than 400 compounds have been isolated from different parts of neem including important bioactive secondary metabolites such as azadirachtin, nimbidin, nimbin, nimbolide, gedunin, and many more. In addition to its insecticidal property, the plant is also known for antimicrobial, antimalarial, antiviral, anti-inflammatory, analgesic, antipyretic, hypoglycaemic, antiulcer, antifertility, anticarcinogenic, hepatoprotective, antioxidant, anxiolytic, molluscicidal, acaricidal, and antifilarial properties. Notwithstanding the chemical and biological virtuosity of neem, it has also been extensively explored for associated microorganisms, especially a class of mutualists called endophytic microorganisms (or endophytes). More than 30 compounds, including neem "mimetic" compounds, have been reported from endophytes harbored in the neem trees in different ecological niches. In this review, we provide an informative and in-depth overview of the topic that can serve as a point of reference for an understanding of the functions and applications of a medicinal plant such as neem, including associated endophytes, within the overall theme of phytopathology. Our review further exemplifies the already-noted current surge of interest in plant and microbial natural products for implications both within the ecological and clinical settings, for a more secure and sustainable future.

Binding of the periplakin linker requires vimentin acidic residues D176 and E187.

Plakin proteins form connections that link the cell membrane to the intermediate filament cytoskeleton. Their interactions are mediated by a highly conserved linker domain through an unresolved mechanism. Here analysis of the human periplakin linker domain structure reveals a bi-lobed module transected by an electropositive groove. Key basic residues within the periplakin groove are vital for co-localization with vimentin in human cells and compromise direct binding which also requires acidic residues D176 and E187 in vimentin. We propose a model whereby basic periplakin linker domain residues recognize acidic vimentin side chains and form a complementary binding groove. The model is shared amongst diverse linker domains and can be used to investigate the effects of pathogenic mutations in the desmoplakin linker associated with arrhythmogenic right ventricular cardiomyopathy. Linker modules either act solely or collaborate with adjacent plakin repeat domains to create strong and adaptable tethering within epithelia and cardiac muscle.

Naphthalene-triazolopyrimidine hybrid compounds as potential multifunctional anti-Alzheimer's agents.

In an attempt to construct potential anti-Alzheimer's agents Naphthalene-triazolopyrimidine hybrids were synthesized and screened in vitro against the two cholinesterases (ChE)s, amyloid ß aggregation and for antioxidation activity. Single-crystal X-ray crystallography was utilized for crystal structure determination of one of the compounds. In vitro study of compounds revealed that most of the compounds are capable of inhibiting acetylcholinesterase and Butyrylcholinesterase activity. Particularly, the compounds 4e and 4d exhibited IC50 values ranging from 8.6 to 14 nM against AChE lower than the standard drug Donepezil (IC50 49 nM). Best result was found for compound 4e with IC50 of 8.6 nM (for AChE) and 150 nM (for BuChE). Selectivity upto that of Donepezil and even more was observed for 4a, 4c and 4h. Investigation by electron microscopy, transmission electron microscopy and ThT fluorescence assay unveils the fact that synthesized hybrids exhibit amyloid ß self-aggregation inhibition. The compounds 4i and 4j revealed highest inhibitory potential, 85.46% and 72.77% at 50 µM respectively; above the standard Aß disaggregating agent, Curcumin. Their antioxidation profile was also analyzed. Studies from DPPH free radical scavenging assay and ORAC assay depicts molecules to possess low antioxidation profile. Results suggest that triazolopyrimidines are potential candidate for Acetylcholinesterase (AChE), Butyrylcholinesterase (BuChE), and amyloid ß aggregation inhibition. In silico ADMET profiling indicates drug-like properties with a very low toxic influence. Such synthesized compounds provide a strong vision for further development of potential anti-Alzheimer's agents.

Effect of dose reduction of supplemental zinc for childhood diarrhoea: study protocol for a double-masked, randomised controlled trial in India and Tanzania.

BACKGROUND: Diarrhoea-associated mortality and morbidity are highest in infants and young children in low-income and middle-income countries (LMICs). Zinc supplementation during acute diarrhoea has been shown to reduce the duration of illness and the risk of persistent diarrhoea. However, vomiting with zinc supplementation is a common side effect that may interfere with compliance and programmatic scale-up, and may be related to the dose prescribed. METHODS/DESIGN: The Zinc Therapeutic Dose Trial (ZTDT) is a two-centre (Tanzania and India), three-arm randomised, double-blind controlled non-inferiority trial. Children 6-59 months of age with acute diarrhoea are eligible to participate. Enrolled children (1500 per arm; 4500 total) will be randomly allocated to receive 5, 10 or 20 mg of zinc sulfate daily for 14 days and will be followed up for 60 days after enrolment. All children will receive WHO/Unicef Integrated Management of Childhood Illness standard of care (oral or intravenous rehydration and zinc as indicated and feeding advice). The primary efficacy outcomes of the trial are the percentage of subjects with diarrhoea duration >5 days, the mean total number of loose or watery stools after enrolment and the proportion of children vomiting within 30 min of zinc administration. DISCUSSION: The ZTDT trial will determine the optimal dose of therapeutic zinc supplements for treatment of acute diarrhoea in children aged 6-59 months in two LMICs. The results of the trial are likely to be generalisable to childhood acute diarrhoea in similar resource-limited settings and may influence global policy about zinc supplementation dosage during acute diarrhoea. TRIAL REGISTRATION NUMBER: NCT03078842. TRIAL STATUS: Enrolment began in January 2017 and follow-up is estimated to be completed by April 2019. As of 1 February 2019, 742 children are still contributing data to the ZTDT study.

A multifunctional therapeutic approach: Synthesis, biological evaluation, crystal structure and molecular docking of diversified 1H-pyrazolo[3,4-b]pyridine derivatives against Alzheimer's disease.

2-(piperazin-1-yl)N-(1H-pyrazolo[3,4-b]pyridin-3-yl)acetamides are described as a new class of selective and potent acetylcholinesterase (AChE) inhibitors and amyloid ß aggregation inhibitors. Formation of synthesized compounds (P1P9) was justified via H1 NMR, C13 NMR, mass spectra and single crystal X-Ray diffraction study. All compounds were evaluated for their acetylcholinesterase and butyrylcholinesterase inhibitory activity, inhibition of self-mediated Aß aggregation and Cu(II)-mediated Aß aggregation. Also, docking study carried out was in concordance with in vitro results. The most potent molecule amongst the derivatives exhibited excellent anti-AChE activity (IC50 = 4.8 nM). Kinetic study of P3 suggested it to be a mixed type inhibitor. In vitro study revealed that all the compounds are capable of inhibiting self-induced ß-amyloid (Aß) aggregation with the highest inhibition percentage to be 81.65%. Potency of P1 and P3 to inhibit self-induced Aß1-42 aggregation was ascertained by TEM analysis. Compounds were also evaluated for their Aß disaggregation, antioxidation, metal-chelation activity.

Exploration of immunomodulatory and protective effect of Withania somnifera on trace metal oxide (zinc oxide nanoparticles) induced toxicity in Balb/c mice.

The current study was undertaken to investigate the immunomodulatory and protective effects of Withania somnifera (WS) extract and Withaferin A (WA) supplementation on zinc oxide nanoparticles mediated toxicity in Balb/c mice. The animals were exposed to ZnO NPs along with WS and WA for 28 days and various parameters like body weight, organ coefficient, cytotoxicity, nitric oxide (NO), total serum protein, phagocytosis, and the gene expression levels of TLR6 and ARG genes were determined. In vivo study showed that, dose-dependent reduction in phagocytosis, an increase in the levels of NO production along with up-regulation of TLR6, arginase gene was significant (P < 0.05) when ZnO NPs were given. However toxicity of ZnO NP was reduced in presence of WS and WA with decreased TLR6 over expression and restoration of phagocytic activities. Our results provided a valuable insight into the underlying mechanism for the protective effects of WS. Mechanism of toxicity induced by Zinc oxide nanoparticles ZnO NPs and immunomodulatory protective effects of Withania somnifera extract (WS) and Withaferin A (WA), in Balb/c mice modal of peritoneal macrophages. Red arrows: effect of ZnO NPs independently leads to ROS production which attenuated the phagocytosis of yeast by macrophages through, up-regulation of TLR6 and down-regulation of arginase gene expression. Green arrows: co-treatment, Impact of Withania somnifera extract with zinc oxide nanoparticles (WS + ZnO NPs), Withaferin A along with zinc oxide nanoparticles (WA + ZnO NPs)-enhance phagocytic activity by counteracting mechanism of ZnO NPs toxicity. Black arrows: increasing or decreasing effects. Per oral (P.O).

Efficacy of high zinc biofortified wheat in improvement of micronutrient status, and prevention of morbidity among preschool children and women - a double masked, randomized, controlled trial.

BACKGROUND: Biofortification of staple food crops with zinc (Zn) can be one of the cost-effective and sustainable strategies to combat zinc deficiency and prevent morbidity among the target population. Agronomic approaches such as application of Zn fertilizers to soil and/or foliar spray seem to be a practical tool for Zn biofortification of wheat. However, there is a need to evaluate its efficacy from randomized controlled trials. This study aimed to evaluate the efficacy of zinc biofortified wheat flour on zinc status and its impact on morbidity among children aged 4-6 years and non-pregnant non lactating woman of child bearing age (WCBA) in Delhi, India. METHODS: In a community based, double-masked randomized controlled trial, 6005 participants (WCBA and child pairs) were enrolled and randomly allocated to receive either high zinc biofortified wheat flour (HZn, 30 ppm zinc daily) or low zinc biofortified wheat flour (LZn, 20 ppm zinc daily) for 6 months (WCBA @ 360 g/day and children @ 120 g/day). Baseline and endline blood samples were obtained for assessing hematological markers; zinc status and data on compliance and morbidity were collected. RESULTS: Compliance rates were high; ~ 88% of the WCBAs in both the groups consumed 50% or more of recommended amount of biofortfied wheat flour during the follow up. Similarly 86.9% children in HZn and 87.5% in LZn consumed 50% or more of recommended wheat flour intake. There was no significant difference in mean zinc levels between the groups at end study. This observation might be due to a marginal difference in zinc content (10 ppm) between the HZn and LZn wheat flour, and a short intervention period. However a positive impact of bio-fortification on self-reported morbidity was observed. Compared to children in LZn group, children in HZn group had 17% (95% CI: 6 to 31%, p = 0.05) and 40% (95% CI: 16 to 57%; p = 0.0019) reduction in days with pneumonia and vomiting respectively. WCBA in the HZn group also showed a statistically significant 9% fewer days with fever compared to LZn group. CONCLUSIONS: Biofortified wheat flour had a good compliance among children and WCBAs. Significant improvement on some of the self-reported morbidity indicators suggests that evaluating longer-term effects of biofortification with higher grain zinc content would be more appropriate. TRIAL REGISTRATION: http://ctri.nic.in/Clinicaltrials/ , CTRI/2014/04/004527, Registered April 7, 2014.

Detection of pesticides in popular medicinal herbs: a modified QuEChERS and gas chromatography-mass spectrometry based approach.

Although a lot of work has been conducted in the pesticide residues analysis in food matrices but the quality determination (with respect to major contaminants such as pesticide residues) in medicinal plant matrices has a long way to go. Hence a study was conducted to determine pesticide residues in four medicinal herbs, which are highly traded commodities in international market. Samples were extracted and cleaned up by modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) approach and analyzed by gas chromatograph-mass spectrometer (GC-MS). The method was subjected to thorough validation procedure in-terms of accuracy, precision, limits of quantification (LOQ), matrix effect, linearity and uncertainty analysis. The mean recoveries for most of the pesticides were in the range of 70-120% with RSD <20% and measurement uncertainties were less than 20% for all the compounds at spiking level of 0.5 mg kg-1 in all the matrices. The limits of quantification (LOQ) ranged from 0.01 to 0.069 mg kg-1. The proposed method was successfully applied to determine pesticide residues in 52 commercial market samples obtained from different locations in India.

Validation of a QuEChERS-based gas chromatographic method for analysis of pesticide residues in Cassia angustifolia (senna).

A simple multi-residue method based on modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) approach was established for the determination of 17 organochlorine (OC), 15 organophosphorous (OP) and 7 synthetic pyrethroid (SP) pesticides in an economically important medicinal plant of India, Senna (Cassia angustifolia), by gas chromatography coupled to electron capture and flame thermionic detectors (GC/ECD/FTD) and confirmation of residues was done on gas chromatograph coupled with mass spectrometry (GC-MS). The developed method was validated by testing the following parameters: linearity, limit of detection (LOD), limit of quantification (LOQ), matrix effect, accuracy-precision and measurement uncertainty; the validation study clearly demonstrated the suitability of the method for its intended application. All pesticides showed good linearity in the range 0.01-1.0 µg mL(-1) for OCs and OPs and 0.05-2.5 µg mL(-1) for SPs with correlation coefficients higher than 0.98. The method gave good recoveries for most of the pesticides (70-120%) with intra-day and inter-day precision < 20% in most of the cases. The limits of detection varied from 0.003 to 0.03 mg kg(-1), and the LOQs were determined as 0.01-0.049 mg kg(-1). The expanded uncertainties were <30%, which was distinctively less than a maximum default value of ±50%. The proposed method was successfully applied to determine pesticide residues in 12 commercial market samples obtained from different locations in India.

Synthesis and screening of triazolopyrimidine scaffold as multi-functional agents for Alzheimer's disease therapies.

In present study a series of triazolopyrimidine-quinoline and cyanopyridine-quinoline hybrids were designed, synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs). Molecular docking and scoring was utilized for the design of inhibitors. The molecules were synthesized via an easily accessible, convergent synthetic route. Three triazolopyrimidine based compounds showed nanomolar activity towards acetylcholinesterase. Among them, Ethyl 6-fluoro-4-(4-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)piperazin-1-yl)quinoline-3-carboxylate (10d), strongly inhibited AChE with IC50 value of 42 nM. Furthermore compound 10d was identified as most promising compound with 12 fold selectivity against butyrylcholinesterase (BuChE). This compound displayed a composed multitargeted profile with promising inhibition of self-induced and AChE - induced Aß aggregation and antioxidant activity.

Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans.

Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy.