Potential beneficial effects of masupirdine (SUVN-502) on agitation/aggression and psychosis in patients with moderate Alzheimer's disease: Exploratory post hoc analyses.

OBJECTIVES: The effects of masupirdine on the neuropsychiatric symptoms were explored. METHODS: Masupirdine (SUVN-502) was evaluated for its effects on cognition in patients with moderate AD. The prespecified primary outcome showed no drug-placebo difference. Post hoc analyses of domains of the 12-item neuropsychiatric inventory scale were carried out. RESULTS: In a subgroup of patients (placebo, n = 57; masupirdine 50 mg, n = 53; masupirdine 100 mg, n = 48) with baseline agitation/aggression symptoms ≥1, a statistically significant reduction in agitation/aggression scores was observed in masupirdine 50 mg (95% confidence interval (CI), -1.9 to -0.5, p < 0.001) and masupirdine 100 mg (95% CI, -1.7 to -0.3, p = 0.007) treated arms at Week 13 in comparison to placebo and the effect was sustained for trial duration of 26 weeks in the masupirdine 50 mg treatment arm (95% CI, -2.3 to -0.8, p < 0.001). Similar observations were noted in the subgroup of patients (placebo, n = 29; masupirdine 50 mg, n = 30; masupirdine 100 mg, n = 21) with baseline agitation/aggression symptoms ≥3. In the subgroup of patients (placebo, n = 28; masupirdine 50 mg, n = 28; masupirdine 100 mg, n = 28) who had baseline psychosis symptoms and/or symptom emergence, a significant reduction in psychosis scores was observed in the masupirdine 50 mg (Week 4: 95% CI, -2.8 to -1.4, p < 0.001; Week 13: 95% CI, -3.3 to -1.3, p < 0.001) and masupirdine 100 mg (Week 4: 95% CI, -1.4 to 0, p = 0.046; Week 13: 95% CI, -1.9 to 0.1, p = 0.073) treatment arms in comparison to placebo. CONCLUSION: Further research is warranted to explore the potential beneficial effects of masupirdine on NPS.

Short-term toxicity study of 1-aminobenzotraizole, a CYP inhibitor, in Wistar rats.

1-Aminobenzotriazole (ABT) is a pan-specific, mechanism-based inhibitor of CYP P450 enzymes, often used as co-treatment to investigate the metabolism-dependent toxicity of drugs or chemicals. To assess the confounding effects of ABT in such kind of mechanistic studies, a repeated dose toxicity study with ABT following 7 days oral administration at 0, 25, 50 and 100 mg/kg/day was performed in Wistar rats (5 rats/sex/group). Wistar rat is selected as a model being one of the well characterized rodent species, widely used for toxicity and toxicokinetics studies. The standard parameters of general toxicity study viz. clinical signs, body weight, feed consumption, clinical, gross and histopathology were evaluated. The ABT was tolerated up to the highest tested dose of 100 mg/kg/day. No clinical signs, mortality or effect on feed consumption at any dose. Slight increase in body weight gain was noted in ABT treated females. Increased reticulocyte, and decreased triglycerides, BUN, A/G ratio and plasma potassium; increased weight of liver, kidneys, adrenals and thyroid was noted in ABT treated animals. Microscopically, hypertrophic findings were noted in liver, thyroid, adrenal glands, pituitary and uterus. Some of these changes were observed at as low as 25 mg/kg/day, therefore, NOEL could not be established. Based on this study, it is concluded that ABT is tolerable up to 100 mg/kg/day with some variations in clinical pathology, organ weight and histopathology; these changes should be considered during the assessment of any mechanistic study with ABT. Findings of this manuscript were presented at 58th meeting of the Society of Toxicology, Baltimore, 11 March 2019.

Emerging warriors against salinity in plants: Nitric oxide and hydrogen sulphide.

The agriculture sector is vulnerable to various environmental stresses, which significantly affect plant growth, performance, and development. Abiotic stresses, such as salinity and drought, cause severe losses in crop productivity worldwide. Soil salinity is a major stress suppressing plant development through osmotic stress accompanied by ion toxicity, nutritional imbalance, and oxidative stress. Various defense mechanisms like osmolytes accumulations, activation of stress-induced genes, and transcription factors, production of plant growth hormones, accumulation of antioxidants, and redox defense system in plants are responsible for combating salt stress. Nitric oxide (NO) and hydrogen sulphide (H2 S) have emerged as novel bioactive gaseous signaling molecules that positively impact seed germination, homeostasis, plant metabolism, growth, and development, and are involved in several plant acclimation responses to impart stress tolerance in plants. NO and H2 S trigger cell signaling by activating a cascade of biochemical events that result in plant tolerance to environmental stresses. NO- and H2 S-mediated signaling networks, interactions, and crosstalks facilitate stress tolerance in plants. Research on the roles and mechanisms of NO and H2 S as challengers of salinity is entering an exponential exploration era. The present review focuses on the current knowledge of the mechanisms of stress tolerance in plants and the role of NO and H2 S in adaptive plant responses to salt stress and provides an overview of the signaling mechanisms and interplay of NO and H2 S in the regulation of growth and development as well as modulation of defense responses in plants and their long term priming effects for imparting salinity tolerance in plants.

Nitric oxide and hydrogen sulfide crosstalk during heavy metal stress in plants.

Gases such as ethylene, hydrogen peroxide (H2 O2 ), nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2 S) have been recognized as vital signaling molecules in plants and animals. Of these gasotransmitters, NO and H2 S have recently gained momentum mainly because of their involvement in numerous cellular processes. It is therefore important to study their various attributes including their biosynthetic and signaling pathways. The present review provides an insight into various routes for the biosynthesis of NO and H2 S as well as their signaling role in plant cells under different conditions, more particularly under heavy metal stress. Their beneficial roles in the plant's protection against abiotic and biotic stresses as well as their adverse effects have been addressed. This review describes how H2 S and NO, being very small-sized molecules, can quickly pass through the cell membranes and trigger a multitude of responses to various factors, notably to various stress conditions such as drought, heat, osmotic, heavy metal and multiple biotic stresses. The versatile interactions between H2 S and NO involved in the different molecular pathways have been discussed. In addition to the signaling role of H2 S and NO, their direct role in posttranslational modifications is also considered. The information provided here will be helpful to better understand the multifaceted roles of H2 S and NO in plants, particularly under stress conditions.

Assessment of toxicity and tolerability of a combination vehicle; 5% Pharmasolve, 45% Propylene glycol and 50% Polyethylene glycol 400 in rats following repeated intravenous administration.

The selection of a suitable vehicle for administration of NCEs in non-clinical studies is always a challenge for poorly soluble compounds. Challenge is increased if the dose formulation is intended for intravenous (i.v.) administration where isotonic, biologically compatible pH and solution form is an absolute requirement. Vehicle toxicity and tolerability data are not readily available for a number of combination vehicles therefore, an i.v. tolerability studies was planned in rats with 5% v/v Pharmasolve (NMP), 45% v/v Propylene glycol (PG) and 50% v/v Polyethylene glycol (PEG) 400 combination, at dose volume of 0.5, 1, 2 and 5 mL/kg body weight for 28 days. The vehicle combination was administered via lateral tail vein and effects on clinical signs, body weights, feed consumption, clinical pathology and histopathology were evaluated. Clinical signs of toxicity like tremors, convulsions and death were noticed at 5 mL/kg during the course of the study. At 2 mL/kg, injection site injury without systemic toxicity was noticed. In conclusion, 1 mL/kg of a combination vehicle of 5% NMP, 45% PG and 55% PEG 400 can be administered intravenously once-a-day up to 28 days without any discomfort or injury to rats.

Alteration in Taste Perception among Young Children during the use of Removable Orthodontic Appliance Therapy.

BACKGROUND: The sense of smell is very influential in the taste of foods. If the smell pleases us, we anticipate the taste of the food with a great deal of relish. If our sense of smell is impaired, so is our taste. The effect of appliance on taste perceptions has always had a controversial subject. MATERIALS AND METHODS: The present study was designed to analyze the change in taste perception in children using removable orthodontic appliances. All the selected volunteers were given different taste stimuli and were asked to score as per their perception. The verbal score was calculated based on the correct and incorrect taste stimuli given to them. Visual analog scale was used to assess intensity and hedonic (palatability) estimation of the volunteers. RESULTS: The volunteers from both study and control groups scored different values for taste stimuli. The majority of stimuli were estimated correctly by both groups. There was no statistically significant difference between the study and control groups. CONCLUSION: In different testing sessions, the scoring of the volunteers was nearly constant, indicating that an appliance does not play a major role in the alteration of taste stimuli. CLINICAL SIGNIFICANCE: The appliance brings about transient change in taste perception, we should educate the patient before delivering the appliance about the transient change in taste perception and encourage full-time wear of the appliance, including during meals, without fear of affecting taste sensations.

Assessment of the Effect of Orthodontic Treatment on the Periodontal Health of Endodontically Restored Tooth.

Intorduction: Patients usually undergo orthodontic treatment for achieving ideal interocclusal relationship between the dental tissue and bony tissue along with improving the speech, mastication, and facial esthetic appearance. Literature quotes paucity in the studies evaluating the effect of orthodontic treatment on the periodontal health of endodontically treated teeth. Hence, we planned the present study to assess the effect of orthodontic treatment on the periodontal health of endodonti-cally restored tooth. MATERIALS AND METHODS: The present study included assessment of 80 patients who underwent orthodontic treatment. All the patients were divided broadly into two study groups: groups I and II. Group I included patients with the absence of endodontically treated teeth, while group II included patients which maxillary central incisors were resorted endodontically. Examination of the periodontal health of the patients was done using the community periodontal index of treatment need (CPITN) around the selected teeth. All the values were recorded during the preorthodontic time, postorthodontic time, and after the first 6 months of starting of the orthodontic treatment. All the results were recorded separately and analyzed. RESULTS: In the groups I and II, 28 and 25 patients respectively, had score of 1, while 10 patients in group I and 12 patients in group II had score of 2. Nonsignificant results were obtained while comparing the CPITN score in between the two study groups when measured at the pre-, intra-, and postortho time. CONCLUSION: In patients undergoing orthodontic treatment, having endodontically resorted teeth, no difference exists in relation to the periodontal health. CLINICAL SIGNIFICANCE: Orthodontic treatment can be safely carried in patients with endodontically restored teeth.

Mutagenicity and clastogenicity evaluation of metaphenoxy benzyl chloride by ames and micronucleus assays.

Metaphenoxy Benzyl Chloride (3-PBC; CAS # 53874-66-1) is a commonly used intermediate in organic synthesis and is a widely used chemical building block. There is likelihood of human contact with 3-PBC in the process of organic or pesticide synthesis and even through as impurity in the product. Further, this chemical has been reported to be found in water reservoirs causing a threat to aqueous flaura and fauna. Genotoxic alert has been suspected for the chemical 3-PBC based on its structure hence, the impetus of present work was to assess the mutagenic potential of 3-PBC using Ames bacterial reverse-mutation assay and in vitro micronucleus assay. 3-PBC was tested for mutagenic potential at six different concentrations, with 0.05 (without metabolic activation) and 0.50 (with metabolic activation) µL/plate as the highest concentrations, followed by five lower concentrations with 2-fold spacing. In clastogenic evaluation, 3-PBC was tested at concentrations ranged from 0.31 to 4.88 µL/mL to assess micronucleus induction in mammalian cells viz. Chinese Hamster Ovarian-K1 cells (CHO-K1 cells). In the Ames assay, 3-PBC did not show mutagenicity in all five tester strains of Salmonella typhimurium viz. TA98, TA100, TA102, TA1535 and TA1537 both in the presence and absence of a metabolic activation system and found to be nonclastogenic when evaluated in "CHO-K1 cells".

Green Synthesis and Characterization of Ginger-Derived Silver Nanoparticles and Evaluation of Their Antioxidant, Antibacterial, and Anticancer Activities.

The efficacy, targeting ability, and biocompatibility of plant-based nanoparticles can be exploited in fields such as agriculture and medicine. This study highlights the use of plant-based ginger nanoparticles as an effective and promising strategy against cancer and for the treatment and prevention of bacterial infections and related disorders. Ginger is a well-known spice with significant medicinal value due to its phytochemical constituents including gingerols, shogaols, zingerones, and paradols. The silver nanoparticles (AgNPs) derived from ginger extracts could be an important non-toxic and eco-friendly nanomaterial for widespread use in medicine. In this study, AgNPs were biosynthesized using an ethanolic extract of ginger rhizome and their phytochemical, antioxidant, antibacterial, and cytotoxic properties were evaluated. UV-visible spectral analysis confirmed the formation of spherical AgNPs. FTIR analysis revealed that the NPs were associated with various functional biomolecules that were associated with the NPs during stabilization. The particle size and SEM analyses revealed that the AgNPs were in the size range of 80-100 nm, with a polydispersity index (PDI) of 0.510, and a zeta potential of -17.1 mV. The purity and crystalline nature of the AgNPs were confirmed by X-ray diffraction analysis. The simple and repeatable phyto-fabrication method reported here may be used for scaling up for large-scale production of ginger-derived NPs. A phytochemical analysis of the ginger extract revealed the presence of alkaloids, glycosides, flavonoids, phenolics, tannins, saponins, and terpenoids, which can serve as active biocatalysts and natural stabilizers of metallic NPs. The ginger extracts at low concentrations demonstrated promising cytotoxicity against Vero cell lines with a 50% reduction in cell viability at 0.6-6 µg/mL. When evaluated for biological activity, the AgNPs exhibited significant antioxidant and antibacterial activity on several Gram-positive and Gram-negative bacterial species, including Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, and Staphylococcus aureus. This suggests that the AgNPs may be used against multi-drug-resistant bacteria. Ginger-derived AgNPs have a considerable potential for use in the development of broad-spectrum antimicrobial and anticancer medications, and an optimistic perspective for their use in medicine and pharmaceutical industry.

Hits and misses with animal models of narcolepsy and the implications for drug discovery.

INTRODUCTION: Narcolepsy is a chronic and rare neurological disorder characterized by disordered sleep. Based on animal models and further research in humans, the dysfunctional orexin system was identified as a contributing factor to the pathophysiology of narcolepsy. Animal models played a larger role in the discovery of some of the pharmacological agents with established benefit/risk profiles. AREAS COVERED: In this review, the authors examine the phenotypes observed in animal models of narcolepsy and the characteristics of clinically used pharmacological agents in these animal models. Additionally, the authors compare the effects of clinically used pharmacological agents on the phenotypes in animal models with those observed in narcolepsy patients. EXPERT OPINION: Research in canine and mouse models have linked narcolepsy to the O×R2mutation and orexin deficiency, leading to new diagnostic criteria and a drug development focus. Advancements in pharmacological therapies have significantly improved narcolepsy management, with insights from both clinical experience and from animal models having led to new treatments such as low sodium oxybate and solriamfetol. However, challenges persist in addressing symptoms beyond excessive daytime sleepiness and cataplexy, highlighting the need for further research, including the development of diurnal animal models to enhance understanding and treatment options for narcolepsy.

Bioequivalence, food effect and comparative pharmacokinetics of SUVN-1105, a novel granule formulation of abiraterone acetate, to Zytiga in healthy male subjects.

PURPOSE: SUVN-1105 is a novel formulation of abiraterone acetate which was developed to demonstrate improved bioavailability, compared to Zytiga and Yonsa, and to reduce the dose and eliminate the food effect. A Phase 1 study was conducted to assess the bioequivalence, food effect, and comparative pharmacokinetics of SUVN-1105 to Zytiga in healthy male subjects. METHODS: The study comprised of 2 segments. Segment 1 was a single-center, 4-period crossover, open-label, fixed treatment sequence, single-dose study to evaluate the safety and pharmacokinetics of SUVN-1105 (N = 12 subjects per period). Segment 2 was a single-center, open-label, single-dose, randomized, 4-period, 4-treatment, 4-sequence crossover study to evaluate bioequivalence and comparative pharmacokinetics of SUVN-1105 against Zytiga (N = 44) under overnight fasted, modified fasted, and fed conditions. RESULTS: Abiraterone exposures appeared to increase proportionately with SUVN-1105 dose (200 mg vs. 250 mg) in Segment 1. In Segment 2, abiraterone exposures of 250 mg SUVN-1105 in the fasted or fed conditions were higher than those of Zytiga 1000 mg in the overnight fasted conditions. Abiraterone exposures of 250 mg SUVN-1105 decreased in the fed conditions (64% and 29% decrease in Cmax and AUC, respectively) compared to overnight fasted conditions. CONCLUSIONS: The abiraterone exposures of 250 mg SUVN-1105 in the fasted or fed conditions fall within the abiraterone exposures of 1000 mg Zytiga in fasted and modified fasted conditions. Single doses of SUVN-1105 were safe and well-tolerated in healthy males both in the fasted and fed conditions.

Alleviating Drought Stress in Brassica juncea (L.) Czern & Coss. by Foliar Application of Biostimulants-Orthosilicic Acid and Seaweed Extract.

Agricultural productivity is negatively impacted by drought stress. Brassica is an important oilseed crop, and its productivity is often limited by drought. Biostimulants are known for their role in plant growth promotion, increased yields, and tolerance to environmental stresses. Silicon in its soluble form of orthosilicic acid (OSA) has been established to alleviate deteriorative effects of drought. Seaweed extract (SWE) also positively influence plant survival and provide dehydration tolerance under stressed environments. The present study was conducted to evaluate the efficacy of OSA and SWE on mitigating adverse effects of drought stress on Brassica genotype RH-725. Foliar application of OSA (2 ml/L and 4 ml/L) and SWE of Ascophyllum nodosum (3 ml/L and 4 ml/L) in vegetative stages in Brassica variety RH 725 under irrigated and rainfed condition revealed an increase in photosynthetic rate, stomatal conductance, transpirational rate, relative water content, water potential, osmotic potential, chlorophyll fluorescence, chlorophyll stability index, total soluble sugars, total protein content, and antioxidant enzyme activity; and a decrease in canopy temperature depression, proline, glycine-betaine, H2O2, and MDA content. Application of 2 ml/L OSA and 3 ml/L SWE at vegetative stage presented superior morpho-physiological and biochemical characteristics and higher yields. The findings of the present study will contribute to developing a sustainable cropping system by harnessing the benefits of OSA and seaweed extract as stress mitigators.

Survival mechanisms of chickpea (Cicer arietinum) under saline conditions.

Salinity is a significant abiotic stress that is steadily increasing in intensity globally. Salinity is caused by various factors such as use of poor-quality water for irrigation, poor drainage systems, and increasing spate of drought that concentrates salt solutions in the soil; salinity is responsible for substantial agricultural losses worldwide. Chickpea (Cicer arietinum) is one of the crops most sensitive to salinity stress. Salinity restricts chickpea growth and production by interfering with various physiological and metabolic processes, downregulating genes linked to growth, and upregulating genes encoding intermediates of the tolerance and avoidance mechanisms. Salinity, which also leads to osmotic stress, disturbs the ionic equilibrium of plants. Survival under salinity stress is a primary concern for the plant. Therefore, plants adopt tolerance strategies such as the SOS pathway, antioxidative defense mechanisms, and several other biochemical mechanisms. Simultaneously, affected plants exhibit mechanisms like ion compartmentalization and salt exclusion. In this review, we highlight the impact of salinity in chickpea, strategies employed by the plant to tolerate and avoid salinity, and agricultural strategies for dealing with salinity. With the increasing spate of salinity spurred by natural events and anthropogenic agricultural activities, it is pertinent to explore and exploit the underpinning mechanisms for salinity tolerance to develop mitigation and adaptation strategies in globally important food crops such as chickpea.

The nematicidal potential of novel fungus, Trichoderma asperellum FbMi6 against Meloidogyne incognita.

One of the most damaging pests in vegetable crops is the root-knot nematode (Meloidogyne incognita) worldwide. The continuous use of nematicide is costly and has unintended consequences for human and environmental health. To minimize nematicides, eco-friendly integrated nematode management is required. Trichoderma, an antagonistic fungus has been explored to control root-knot nematode. The fungal bio-control strain FbMi6 was identified as Trichoderma asperellum (accession no. MT529846.1). T. asperellum FbMi6 showed substantial nematicidal activity in the laboratory, with egg hatch suppression (96.6%) and juvenile mortality (90.3%) of M. incognita. T. asperellum FbMi6 was examined under pot and field  conditions (after neem cake enrichment), both alone and in combination, and compared with controls. Application of T. asperellum FbMi6 enriched neem cake (1-ton ha-1) increased (28.3%) the okra yield and decreased (57.1%) nematode population as compared with control. T. asperellum FbMi6 enriched neem cake had higher polyphenol content (resistance enhancer) in okra compared with inoculated check.

Unlocking the Potential of Nano-Enabled Precision Agriculture for Efficient and Sustainable Farming.

Nanotechnology has attracted remarkable attention due to its unique features and potential uses in multiple domains. Nanotechnology is a novel strategy to boost production from agriculture along with superior efficiency, ecological security, biological safety, and monetary security. Modern farming processes increasingly rely on environmentally sustainable techniques, providing substitutes for conventional fertilizers and pesticides. The drawbacks inherent in traditional agriculture can be addressed with the implementation of nanotechnology. Nanotechnology can uplift the global economy, so it becomes essential to explore the application of nanoparticles in agriculture. In-depth descriptions of the microbial synthesis of nanoparticles, the site and mode of action of nanoparticles in living cells and plants, the synthesis of nano-fertilizers and their effects on nutrient enhancement, the alleviation of abiotic stresses and plant diseases, and the interplay of nanoparticles with the metabolic processes of both plants and microbes are featured in this review. The antimicrobial activity, ROS-induced toxicity to cells, genetic damage, and growth promotion of plants are among the most often described mechanisms of operation of nanoparticles. The size, shape, and dosage of nanoparticles determine their ability to respond. Nevertheless, the mode of action of nano-enabled agri-chemicals has not been fully elucidated. The information provided in our review paper serves as an essential viewpoint when assessing the constraints and potential applications of employing nanomaterials in place of traditional fertilizers.

Progress in Investigational Agents Targeting Serotonin-6 Receptors for the Treatment of Brain Disorders.

Serotonin (5-HT) plays an important role in the regulation of several basic functions of the central and peripheral nervous system. Among the 5-HT receptors, serotonin-6 (5-HT6) receptor has been an area of substantial research. 5-HT6 receptor is a G-protein-coupled receptor mediating its effects through diverse signaling pathways. Exceptional features of the receptors fueling drug discovery efforts include unique localization and specific distribution in the brain regions having a role in learning, memory, mood, and behavior, and the affinity of several clinically used psychotropic agents. Although non-clinical data suggest that both agonist and antagonist may have similar behavioral effects, most of the agents that entered clinical evaluation were antagonists. Schizophrenia was the initial target; more recently, cognitive deficits associated with Alzheimer's disease (AD) or other neurological disorders has been the target for clinically evaluated 5-HT6 receptor antagonists. Several 5-HT6 receptor antagonists (idalopirdine, intepirdine and latrepirdine) showed efficacy in alleviating cognitive deficits associated with AD in the proof-of-concept clinical studies; however, the outcomes of the subsequent phase 3 studies were largely disappointing. The observations from both non-clinical and clinical studies suggest that 5-HT6 receptor antagonists may have a role in the management of neuropsychiatric symptoms in dementia. Masupirdine, a selective 5-HT6 receptor antagonist, reduced agitation/aggression-like behaviors in animal models, and a post hoc analysis of a phase 2 trial suggested potential beneficial effects on agitation/aggression and psychosis in AD. This agent will be assessed in additional trials, and the outcome of the trials will inform the use of 5-HT6 receptor antagonists in the treatment of agitation in dementia of the Alzheimer's type.

Nanoscale CuO charge and morphology control Fusarium suppression and nutrient biofortification in field-grown tomato and watermelon.

Limited data exist on how surface charge and morphology impact the effectiveness of nanoscale copper oxide (CuO) as an agricultural amendment under field conditions. This study investigated the impact of these factors on tomatoes and watermelons following foliar treatment with CuO nanosheets (NS-) or nanospikes (NP+ and NP-) exhibiting positive or negative surface charge. Results showed plant species-dependent benefits. Notably, tomatoes infected with Fusarium oxysporum had significantly reduced disease progression when treated with NS-. Watermelons benefited similarly from NP+. Although disease suppression was significant and trends indicated increased yield, the yield effects weren't statistically significant. However, several nanoscale treatments significantly enhanced the fruit's nutritional value, and this nano-enabled biofortification was a function of particle charge and morphology. Negatively charged nanospikes significantly increased the Fe content of healthy watermelon and tomato (20-28 %) and Ca in healthy tomato (66 %), compared to their positively charged counterpart. Negatively charged nanospikes also outperformed negatively charged nanosheets, leading to significant increases in the content of S and Mg in infected watermelon (37-38 %), Fe in healthy watermelon (58 %), and Ca (42 %) in healthy tomato. These findings highlight the potential of tuning nanoscale CuO chemistry for disease suppression and enhanced food quality under field conditions.

Mutagenicity and clastogenicity evaluation of tacrine by Ames and micronucleus assays.

Tacrine was evaluated for its mutagenic and clastogenic activities using the Ames bacterial reverse-mutation assay and the rodent bone marrow micronucleus assay. Tacrine was tested for mutagenic potential at six different concentrations, with 1,250 µg/plate as the highest concentration, followed by five lower concentrations with 2-fold spacing. In clastogenic evaluation, tacrine was administered orally to Wistar rats for 2 days at 5, 10, and 20 mg/kg body weights to assess micronucleus induction in bone marrow erythrocytes. In the Ames assay, tacrine showed nonmutagenicity in four tester strains of Salmonella typhimurium viz. TA98, TA100, TA102, and TA1535, but it was found to be mutagenic in the TA1537 tester strain, both in the presence and absence of a metabolic activation system. Tacrine was found to be nonclastogenic on bone marrow cells of rats at all doses tested and was found to be mutagenic in only the TA1537 strain of Salmonella.

Amelioration Effect of Salicylic Acid Under Salt Stress in Sorghum bicolor L.

Salinity is a major abiotic stress, limiting plant growth and agriculture productivity worldwide. Salicylic acid is known to alleviate the negative effects of salinity. The present study demonstrated the impact of SA on sorghum, a moderately salt-tolerant crop, grown for food, fodder, fiber, and fuel. A screen house experiment was conducted using sorghum genotypes Haryana Jowar HJ 513 and HJ 541 under 4 salt levels (0, 5.0, 7.5, and 10.0 dS m-1 NaCl) and 3 SA (0, 25, and 50 mg dm-3) levels with 12 combinations. The leaves were assayed for electrolyte leakage percentage (ELP), i.e., 88.7 % in HJ 541 and 87.2 % in HJ 513, and osmolyte content. Proline content, total soluble carbohydrate content, and glycine betaine content increased considerably. Photosynthetic rate, transpiration rate, and stomatal conductance declined at higher salt levels. The specific enzymatic activities of SOD, CAT, and POX increased 41.1 %, 122.0 %, and 72.8 %, respectively, in HJ 513 under salt stress. Combinations of salt treatment and SA decreased ELP and enhanced osmolyte concentration, rates of gaseous exchange attributes, and also the antioxidant enzymatic activity in salt-stressed leaves. The study established that the specific activity of antioxidative enzymes is enhanced further by addition of SA which may protect the cells from oxidative damage under salt stress, thus mitigating salt stress and enhancing the yield of sorghum. SA can ameliorate the salt stress in plants by affecting the metabolic or physiological frameworks. SA application is an effective management strategy towards mitigating salt stress in order to meet agricultural production and sustainability.

Pinpointing Genomic Regions and Candidate Genes Associated with Seed Oil and Protein Content in Soybean through an Integrative Transcriptomic and QTL Meta-Analysis.

Soybean with enriched nutrients has emerged as a prominent source of edible oil and protein. In the present study, a meta-analysis was performed by integrating quantitative trait loci (QTLs) information, region-specific association and transcriptomic analysis. Analysis of about a thousand QTLs previously identified in soybean helped to pinpoint 14 meta-QTLs for oil and 16 meta-QTLs for protein content. Similarly, region-specific association analysis using whole genome re-sequenced data was performed for the most promising meta-QTL on chromosomes 6 and 20. Only 94 out of 468 genes related to fatty acid and protein metabolic pathways identified within the meta-QTL region were found to be expressed in seeds. Allele mining and haplotyping of these selected genes were performed using whole genome resequencing data. Interestingly, a significant haplotypic association of some genes with oil and protein content was observed, for instance, in the case of FAD2-1B gene, an average seed oil content of 20.22% for haplotype 1 compared to 15.52% for haplotype 5 was observed. In addition, the mutation S86F in the FAD2-1B gene produces a destabilizing effect of (ΔΔG Stability) -0.31 kcal/mol. Transcriptomic analysis revealed the tissue-specific expression of candidate genes. Based on their higher expression in seed developmental stages, genes such as sugar transporter, fatty acid desaturase (FAD), lipid transporter, major facilitator protein and amino acid transporter can be targeted for functional validation. The approach and information generated in the present study will be helpful in the map-based cloning of regulatory genes, as well as for marker-assisted breeding in soybean.