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Chickpeas (Cicer arietinum L.) are used as a good source of proteins and energy in the diets of various organisms including humans and animals. Chickpea straws can serve as an alternative option for forage for different ruminants. This research mainly focussed on screening the effects of adding beneficial chickpea seed endophytes on increasing the nutritional properties of the different edible parts of chickpea plants. Two efficient chickpea seed endophytes (Enterobacter sp. strain BHUJPCS-2 and BHUJPCS-8) were selected and applied to the chickpea seeds before sowing in the experiment conducted on clay pots. Chickpea seeds treated with both endophytes showed improved plant growth and biomass accumulation. Notably, improvements in the uptake of mineral nutrients were found in the foliage, pericarp, and seed of the chickpea plants. Additionally, nutritional properties such as total phenolics (0.47, 0.25, and 0.55 folds), total protein (0.04, 0.21, and 0.18 folds), carbohydrate content (0.31, 0.32, and 0.31 folds), and total flavonoid content (0.45, 027, and 0.8 folds) were increased in different parts (foliage, pericarp, and seed) of the chickpea plants compared to the control plants. The seed endophyte-treated plants showed a significant increase in mineral accumulation and improvement in nutrition in the different edible parts of chickpea plants. The results showed that the seed endophyte-mediated increase in dietary and nutrient value of the different parts (pericarp, foliage, and seeds) of chickpea are consumed by humans, whereas the other parts (pericarp and foliage) are used as alternative options for forage and chaff in livestock diets and may have direct effects on their nutritional conditions.

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Rice is a major dietary element for about two billion people worldwide and it faces numerous biotic and abiotic stress for its cultivation. Rice blast disease caused by Magnaporthe oryzae reduce up to 30 % rice yield. Overuse of synthetic chemicals raises concerns about health and environment; so, there is an urgent need to explore innovative sustainable strategies for crop productivity. The main aim of this study is to explore the impact of bacterial volatiles (BVCs) on seedling growth and defense mechanisms of rice under in-vitro condition. On the basis of plant growth promoting properties, six bacterial strains were selected out of ninety-one isolated strains for this study; Pantoea dispersa BHUJPVR01, Enterobacter cloacae BHUJPVR02, Enterobacter sp. BHUJPVR12, Priestia aryabhattai BHUJPVR13, Pseudomonas sp. BHUJPVWRO5 and Staphylococcus sp. BHUJPVWLE7. Through the emission of bacterial volatiles compounds (BVCs), Enterobacter sp., P. dispersa and P. aryabhattai significantly reduces the growth of rice blast fungus Magnaporthe oryzae by 69.20 %, 66.15 % and 62.31 % respectively. Treatment of rice seedlings with BVCs exhibited significant enhancement in defence enzyme levels, including guaiacol peroxidase, polyphenol oxidase, total polyphenols, and total flavonoids by a maximum of up to 24 %, 48 %, 116 % and 80 %, respectively. Furthermore, BVCs effectively promote shoot height, root height, and root counts of rice. All BVCs treated plant showed a significant increase in shoot height. P. dispersa treated plants showed the highest increase of 60 % shoot and 110 % root length, respectively. Root counts increased up to 30% in plants treated with E. cloacae and Staphylococcus sp. The BVCs can be used as a sustainable approach for enhancing plant growth attributes, productivity and defence mechanism of rice plant under biotic and abiotic stresses.

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As a result of current therapeutic interventions and the progressive nature of diseases, a variety of side effects have emerged, prompting patients to seek alternative treatment. The role of medicinal plants in such situations has been advantageous due to their manifestation through various cellular and molecular mechanisms. Inhibition of monoamine oxidase enzyme is suspected to be a highly effective treatment for various neurological illnesses like Alzheimer's disease, Parkinson's disease, depression, social phobia, and panic disorders. The study of phytochemicals and plant extracts used as a traditional source of medication revealed that they possess vast potential for monoamine oxidase inhibition. The purpose of this review is to highlight the potential of plant extracts and their chemicals to inhibit monoamine oxidase enzymes. This communication mentions a number of potential plant species and phytoconstituents as monoamine oxidase inhibitors which can be further developed for the treatment of various neurological disorders.

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In recent years, the PDE1B enzyme has become a desirable drug target for the treatment of psychological and neurological disorders, particularly schizophrenia disorder, due to the expression of PDE1B in brain regions involved in volitional behaviour, learning and memory. Although several inhibitors of PDE1 have been identified using different methods, none of these inhibitors has reached the market yet. Thus, searching for novel PDE1B inhibitors is considered a major scientific challenge. In this study, pharmacophore-based screening, ensemble docking and molecular dynamics simulations have been performed to identify a lead inhibitor of PDE1B with a new chemical scaffold. Five PDE1B crystal structures have been utilised in the docking study to improve the possibility of identifying an active compound compared to the use of a single crystal structure. Finally, the structure-activity- relationship was studied, and the structure of the lead molecule was modified to design novel inhibitors with a high affinity for PDE1B. As a result, two novel compounds have been designed that exhibited a higher affinity to PDE1B compared to the lead compound and the other designed compounds.

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The rhizosphere microbes play a key role in plant nutrition and health. However, the interaction of beneficial microbes and Vigna unguiculata (lobia) production remains poorly understood. Thus, we aimed to isolate and characterize the soil microbes from the rhizosphere and develop novel microbial consortia for enhancing lobia production. Fifty bacterial strains were isolated from the rhizosphere soil samples of lobia. Finally, five effective strains (e.g., Pseudomonas sp. IESDJP-V1 and Pseudomonas sp. IESDJP-V2, Serratia marcescens IESDJP-V3, Bacillus cereus IESDJP-V4, Ochrobactrum sp. IESDJP-V5) were identified and molecularly characterized by 16 S rDNA gene amplification. All selected strains showed positive plant growth promoting (PGP) properties in broth culture. Based on morphological, biochemical, and plant growth promoting activities, five effective isolated strains and two collected strains (Azospirillum brasilense MTCC-4037 and Paenibacillus polymyxa BHUPSB17) were selected. The pot trials were conducted with seed inoculations of lobia (Vigna unguiculata) var. Kashi Kanchan with thirty treatments and three replications. The treatment combination T3 (Pseudomonas sp. IESDJP-V2), T14 (Pseudomonas sp. IESDJP-V2 + A. brasilense), T26 (Pseudomonas sp. IESDJP-V1+ B. cereus IESDJP-V4 + P. polymyxa) and T27 (IESDJP-V1+ IESDJP-V5+ A. brasilense) were recorded for enhancing plant growth attributes, yield, nutritional content like protein, total sugar, flavonoid and soil properties as compared to control and others. The effective treatments T3 (Pseudomonas sp.), T14 (Pseudomonas sp. IESDJP-V2 + A. brasilense), T26 (Pseudomonas sp. IESDJP-V1+ B. cereus IESDJP-V4 + P. polymyxa) and T27 (IESDJP-V1+ IESDJP-V5+ A. brasilense) recorded as potential PGPR consortium for lobia production. The treatment of single (Pseudomonas sp.), duel (IESDJP-V2 + A. brasilense) and triple combination (IESDJP-V1+ IESDJP-V4 + P. polymyxa) and (IESDJP-V1+ IESDJP-V5+ A. brasilense) can be further used for developing effective indigenous consortium for lobia production under sustainable farming practices. These PGPR bio-inoculant will be cost-effective, environment-friendly and socially acceptable.

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CNS disorders are indications with a very high unmet medical needs, relatively smaller number of available drugs, and a subpar satisfaction level among patients and caregiver. Discovery of CNS drugs is extremely expensive affair with its own unique challenges leading to extremely high attrition rates and low efficiency. With explosion of data in information age, there is hardly any aspect of life that has not been touched by data driven technologies such as artificial intelligence (AI) and machine learning (ML). Drug discovery is no exception, emergence of big data via genomic, proteomic, biological, and chemical technologies has driven pharmaceutical giants to collaborate with AI oriented companies to revolutionise drug discovery, with the goal of increasing the efficiency of the process. In recent years many examples of innovative applications of AI and ML techniques in CNS drug discovery has been reported. Research on therapeutics for diseases such as schizophrenia, Alzheimer's and Parkinsonism has been provided with a new direction and thrust from these developments. AI and ML has been applied to both ligand-based and structure-based drug discovery and design of CNS therapeutics. In this review, we have summarised the general aspects of AI and ML from the perspective of drug discovery followed by a comprehensive coverage of the recent developments in the applications of AI/ML techniques in CNS drug discovery.

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Phosphodiesterase 1B (PDE1B) and PDE10A are dual-specificity PDEs that hydrolyse both cyclic adenosine monophosphate and cyclic guanosine monophosphate, and are highly expressed in the striatum. Several reports have suggested that PDE10A inhibitors may present a promising approach for the treatment of positive symptoms of schizophrenia, whereas PDE1B inhibitors may present a novel mechanism to modulate cognitive deficits. Previously, we have reported a novel dual inhibitor of PDE1B and PDE10A, compound 2 [(3-fluorophenyl)(2-methyl-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)methanone] which has shown inhibitory activity for human recombinant PDE1B and PDE10A in vitro. In the present study, the safety profile of compound 2 has been evaluated in rats in the acute oral toxicity study, as well as; the antipsychotic-like effects in the rat model of schizophrenia. Compound 2 was tolerated up to 1 g/kg when administered at a single oral dose. Additionally, compound 2 has strongly suppressed ketamine-induced hyperlocomotion, which presented a model for the positive symptoms of schizophrenia. It has also shown an ability to attenuate social isolation induced by chronic administration of ketamine and enhanced recognition memory of rats ​in the novel object recognition test. Altogether, our results suggest that compound 2 represents a promising therapy for the treatment of the three symptomatic domains of schizophrenia.

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(1) Insulin resistance, a symptom of type 2 diabetes mellitus (T2DM), is caused by the inactivation of the insulin signaling pathway, which includes IRS-PI3K-IRS-1-PKC-AKT2 and GLUT4. Metformin (biguanide) and glimepiride (sulfonylurea) are both drugs that are derivatives of urea, and they are widely used as first-line drugs for the treatment of type 2 diabetes mellitus. Palmatine has been previously reported to possess antidiabetic and antioxidant properties. (2) The current study compared palmatine to metformin and glimepiride in a type 2 diabetes model for ADME and insulin resistance via the PI3K/Akt/GLUT4 signaling pathway: in vitro, in vivo, ex vivo, and in silico molecular docking. (3) Methods: Differentiated L6 skeletal muscle cells and soleus muscle tissue were incubated in standard tissue culture media supplemented with high insulin and high glucose as a cellular model of insulin resistance, whilst streptozotocin (STZ)-induced Sprague Dawley rats were used as the diabetic model. The cells/tissue/animals were treated with palmatine, while glimepiride and metformin were used as standard drugs. The differential gene expression of PI3K, IRS-1, PKC-α, AKT2, and GLUT4 was evaluated using qPCR. (4) Results: The results revealed that the genes IRS-PI3K-IRS-1-PKC-AKT2 were significantly down-regulated, whilst PKC-α was upregulated significantly in both insulin-resistant cells and tissue animals. Interestingly, palmatine-treated cells/tissue/animals were able to reverse these effects. (5) Conclusions: Palmatine appears to have rejuvenated the impaired insulin signaling pathway through upregulation of the gene expression of IRS-1, PI3K, AKT2, and GLUT4 and downregulation of PKC-expression, according to in vitro, in vivo, and ex vivo studies.

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Over the last two decades, computational technologies have played a crucial role in antiviral drug development. Whenever a virus spreads and becomes a threat to global health, it brings along the challenge of developing new therapeutics and prophylactics. Computational drug and vaccine discovery has evolved quickly over the years. Some interesting examples of computational drug discovery are anti-AIDS drugs, where HIV protease and reverse transcriptase have been targeted by agents developed using computational methods. Various computational methods that have been applied to anti-viral research include ligand-based methods that rely on known active compounds, i.e., pharmacophore modeling, machine learning or classical QSAR; structure-based methods that rely on an experimentally determined 3D structure of the targets, i.e., molecular docking and molecular dynamics and methods for the development of vaccines such as reverse vaccinology; structural vaccinology and vaccine epitope prediction. This review summarizes these approaches to battle viral diseases and underscores their importance for anti-viral research. We discuss the role of computational methods in developing small molecules and vaccines against human immunodeficiency virus, yellow fever, human papilloma virus, SARS-CoV-2, and other viruses. Various computational tools available for the abovementioned purposes have been listed and described. A discussion on applying artificial intelligence-based methods for antiviral drug discovery has also been included.

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Benign prostatic hyperplasia (BPH) is a common disease that affects elderly men with various complications. This study evaluates the effects of an Iranian traditional herbal medicine "Atrifil and Oshagh gum" on BPH in male Wistar rats. Atrifil is a combination of three medicinal plants: Emblica officinalis Gaertn, Terminalia chebula Retz, and Terminalia bellerica Retz" extracts, and Oshagh gum is Dorema ammoniacum D. Dono gum. In this study, 30 male Wistar rats were divided into five groups: normal control, disease, finasteride, and extract with 300 and 600 mg/kg groups. The extract is a combination of hydroalcoholic Atrifil extract and Oshagh gum. All groups received intramuscular testosterone enanthate to induce BPH except the normal control group. On the twenty-eighth day, prostate glands were separated. Histopathological changes were observed. Furthermore, the prostate-specific antigen (PSA) and prostate weights were measured. The binding propensities of finasteride, equol, and flavonoids present in this extract such as quercetin, rutin, and kaempferol for 5α-reductase, estrogen receptor alpha and beta, and estrogen-related receptor gamma were assessed using in silico docking approach. Histopathological evaluation, biochemical parameter, and PSA level results indicated significant inhibition of accruing and progression of BPH in groups treated with 600 mg/kg extract (p < 0.01). Furthermore, molecular docking showed that rutin had a high affinity to bind the receptors 5α-reductase, estrogen receptor beta, and estrogen-related receptor gamma even more than finasteride, and on average, quercetin had a higher affinity to all these receptors. In the end, it can be concluded that Atrifil and Oshagh gum is effective in preventing BPH.

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Plant hormones play an important role in growth, defence and plants productivity and there are several studies on their effects on plants. However, their role in humans and animals is limitedly studied. Recent studies suggest that plant hormone also works in mammalian systems, and have the potential to reduce human diseases such as cancer, diabetes, and also improve cell growth. Plant hormones such as indole-3-acetic acid (IAA) works as an antitumor, anti-cancer agent, gibberellins help in apoptosis, abscisic acid (ABA) as antidepressant compounds and regulation of glucose homeostasis whereas cytokinin works as an anti-ageing compound. The main aim of this review is to explore and correlate the relation of plant hormones and their important roles in animals, microbes and plants, and their interrelationships, emphasizing mainly human health. The most important and well-known plant hormones e.g., IAA, gibberellins, ABA, cytokinin and ethylene have been selected in this review to explore their effects on humans and animals.

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The main aim of the present work was to explore culturable bacteria and to develop potential microbial consortium as bio-inoculants for enhancing plant productivity, nutritional content, and soil health. For this study, we selected two bacterial strains e.g., Enterobacter hormaechei (BHUJPCS-15) and Brevundimonas naejangsanensis (BHUJPVCRS-1) based on plant growth-promoting activities We developed a consortium of both strains and estimated plant growth promotion (PGP) activity which recorded significant better production of Indole-3-acetic acid (IAA) (61.53 µg/ml), siderophore (12.66%), ammonia (98.66 µg/ml), phosphate solubilisation (942.64 µg/ml), potassium solubilisation, and antagonistic activity against Fusarium sp. than individual bacterial strains. Bacterial consortium (E. hormaechei + B. naejangsanensis) treatment significantly enhanced plant growth attributes, grain yields, nutritional content in plant and seed, followed by E. hormaechei as compared to control. Seed treated with consortium recorded a significant increase in available N P K, enzymes and microbial communities in soils. Microbiome analysis revealed that the dominance of bacterial group and its functional properties is directly correlated with plant growth attributes, nutrient content, soil N P K, and enzyme activity. The relative abundance of bacterial phyla Proteobacteria (98%) was dominantly recorded in all treatments. The microbiome of seed and soil, treated with consortium (E. hormaechei + B. naejangsanensis) showed high amount of diversity of bacterial phyla Verrucomicrobia, Firmicutes, Bacteroidetes, Acidobacteria, Chloroflexi, and Proteobacteria than E. hormaechei (Firmicutes, Bacteroidetes, Chloroflexi and Proteobacteria) and control (Firmicutes, Bacteroidetes and Proteobacteria). In soil, root and shoot, E. hormaechei treatment enriched ligninolytic, nitrogen fixation, cellulolytic, nitrate ammonification among other pathways. The main finding is that the consortium treated seed of chickpea recorded significant enhancement of plant growth attributes, productivity, nutritional content, and soil health as well as microbial colonization in soil and seed part.

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Phosphodiesterase10A (PDE10A) is a potential therapeutic target for the treatment of several neurodegenerative disorders. Thus, extensive efforts of medicinal chemists have been directed toward developing potent PDE10A inhibitors with minimal side effects. However, PDE10A inhibitors are not approved as a treatment for neurodegenerative disorders, possibly due to the lack of research in this area. Therefore, the discovery of novel and diverse scaffolds targeting PDE10A is required. In this study, we described the identification of a new PDE10A inhibitor by structure-based virtual screening combining pharmacophore modelling, molecular docking, molecular dynamics simulations, and biological evaluation. Zinc42657360 with a cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-one scaffold from the zinc database exhibited a significant inhibitory activity of 1.60 µM against PDE10A. The modelling studies demonstrated that Zinc42657360 is involved in three hydrogen bonds with ASN226, THR187 and ASP228, and two aromatic interactions with TYR78 and PHE283, besides the common interactions with the P-clamp residues PHE283 and ILE246. The novel scaffold of Zinc42657360 can be used for the rational design of PDE10A inhibitors with improved affinity.

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Abstract Existing medications i.e. the antipsychotic drugs are known to be effective in treating only the positive symptoms of schizophrenia, while being ineffective on negative and cognitive symptoms of the disease. In addition, these medications cause extrapyramidal symptoms, forcing many patients towards natural medicine in the hope of minimizing the unwanted adverse effects. Nardostachys jatamansi is a medicinal plant that has been traditionally prescribed for various types of brain disorders. The active constituents of the plant have beneficial effects on the negative and cognitive symptoms of schizophrenia. This study was designed to identify the active constituents of Nardostachys jatamansi with the highest binding affinities for the key macromolecular drug targets involved in the pathophysiology of schizophrenia and thereby elucidate the possible mechanism of action. These targets are dopamine receptors, Gamma-aminobutyric acid receptors, N-methyl-D-aspartate receptors and Phosphodiesterase 10A. The results of molecular docking showed that, β-sitosterol, chlorogenic acid, oleanic acid and ursolic acid, displayed high binding affinity toward all the macromolecular drug targets. Ligands with steroid backbone and pentacyclic triterpene structure have been found to possess high binding affinity toward the dopamine receptor and phosphodiesterase 10A. While ligands with carbonyl group form stronger binding interactions with the N-methyl-D-aspartate receptor.

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AIM: The aim of the present study was to apply pharmacophore based virtual screening to a natural product database to identify potential PDE1B inhibitor lead compounds for neurodegenerative and neuropsychiatric disorders. BACKGROUND: Neurodegenerative and neuropsychiatric disorders are a major health burden globally. The existing therapies do not provide optimal relief and are associated with substantial adverse effects. This has resulted in a huge unmet medical need for newer and more effective therapies for these disorders. Phosphodiesterase (PDEs) enzymes have been identified as potential targets of drugs for neurodegenerative and neuropsychiatric disorders, and one of the subtypes, i.e., PDE1B, accounts for more than 90 % of total brain PDE activity associated with learning and memory process, making it an interesting drug target for the treatment of neurodegenerative disorders. OBJECTIVES: The present study has been conducted to identify potential PDE1B inhibitor lead compounds from the natural product database. METHODS: Ligand-based pharmacophore models were generated and validated; they were then employed for virtual screening of Universal Natural Products Database (UNPD) followed by docking with PDE1B to identify the best hit compound. RESULTS: Virtual screening led to the identification of 85 compounds which were then docked into the active site of PDE1B. Out of the 85 compounds, six showed a higher affinity for PDE1B than the standard PDE1B inhibitors. The top scoring compound was identified as Cedreprenone. CONCLUSION: Virtual screening of UNPD using Ligand based pharmacophore led to the identification of Cedreprenone, a potential new natural PDE1B inhibitor lead compound.

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BACKGROUND: The expression of hERG K+ channels is observed in various cancer cells including epithelial, neuronal, leukemic, and connective tissue. The role of hERG potassium channels in regulating the growth and death of cancer cells include cell proliferation, survival, secretion of proangiogenic factors, invasiveness, and metastasis. METHODS: In the reported study, an attempt has been made to investigate some non-cancer hERG blockers as potential cancer therapeutics using a computational drug repurposing strategy. Preliminary investigation for hERG blockers/non-blockers has identified 26 potential clinically approved compounds for further studies using molecular modeling. RESULTS: The interactions at the binding pockets have been investigated along with the prioritization based on the binding score. Some of the identified potential hERG inhibitors, i.e., Bromocriptine, Darglitazone, and Troglitazone, have been investigated to derive the mechanism of cancer inhibition. CONCLUSIONS: The proposed mechanism for anti-cancer properties via hERG blocking for some of the potential compounds is required to be explored using other experimental methodologies. The drug repurposing approach applied to investigate anti-cancer therapeutics may direct to provide a therapeutic solution to late-stage cancer and benefit a significant population of patients.

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Inhibition of phosphodiesterase 4 (PDE4) is a promising therapeutic approach for the treatment of inflammatory pulmonary disorders, i.e. asthma and chronic obstructive pulmonary disease. However, the treatment with non-selective PDE4 inhibitors is associated with side effects such as nausea and vomiting. Among the subtypes of PDE4 inhibited by these inhibitors, PDE4B is expressed in immune, inflammatory and airway smooth muscle cells, whereas, PDE4D is expressed in the area postrema and nucleus of the solitary tract. Thus, PDE4D inhibition is responsible for the emetic response. In this regard, a selective PDE4B inhibitor is expected to be a potential drug candidate for the treatment of inflammatory pulmonary disorders. Therefore, a shared feature pharmacophore model was developed and used as a query for the virtual screening of Maybridge and SPECS databases. A number of filters were applied to ensure only compounds with drug-like properties were selected. Accordingly, nine compounds have been identified as final hits, where HTS04529 showed the highest affinity and selectivity for PDE4B over PDE4D in molecular docking. The docked complexes of HTS04529 with PDE4B and PDE4D were subjected to molecular dynamics simulations for 100ns to assess their binding stability. The results showed that HTS04529 was bound tightly to PDE4B and formed a more stable complex with it than with PDE4D.

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Salinity stress is one of the major abiotic stresses threatening sustainable crop production worldwide. The extent of salinity affected area is expected to cover about 50% of total agricultural land by 2050. Salinity stress produces various detrimental effects on plants' physiological, biochemical, and molecular features and reduces productivity. The poor plant growth under salinity stress is due to reduced nutrient mobilization, hormonal imbalance, and formation of reactive oxygen species (ROS), ionic toxicity, and osmotic stress. Additionally, salinity also modulates physicochemical properties and reduces the microbial diversity of soil and thus decreases soil health. On the other hand, the demand for crop production is expected to increase in coming decades owing to the increasing global population. Conventional agricultural practices and improved salt-tolerant crop varieties will not be sufficient to achieve the yields desired in the near future. Plants harbor diverse microbes in their rhizosphere, and these have the potential to cope with the salinity stress. These salinity-tolerant plant growth-promoting bacteria (PGPB) assist the plants in withstanding saline conditions. These plant-associated microbes produce different compounds such as 1-aminocyclopropane-1-carboxylate (ACC) deaminase, indole-3-acetic acid (IAA), antioxidants, extracellular polymeric substance (EPS), and volatile organic compounds (VOC). Additionally, the naturally associated microbiome of plants has the potential to protect the host through stress avoidance, tolerance, and resistance strategies. Recent developments in microbiome research have shown ways in which novel microbe-assisted technologies can enhance plant salt tolerance and enable higher crop production under saline conditions. This focused review article presents the global scenario of salinity stress and discusses research highlights regarding PGPB and the microbiome as a biological tool for mitigation of salinity stress in plants.

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Schizophrenia is a severe mental disorder that affects more than 1% of the population worldwide. Dopamine system dysfunction and alterations in glutamatergic neurotransmission are strongly implicated in the aetiology of schizophrenia. To date, antipsychotic drugs are the only available treatment for the symptoms of schizophrenia. These medications, which act as D2-receptor antagonist, adequately address the positive symptoms of the disease, but they fail to improve the negative symptoms and cognitive impairment. In schizophrenia, cognitive impairment is a core feature of the disorder. Therefore, the treatment of cognitive impairment and the other symptoms related to schizophrenia remains a significant unmet medical need. Currently, phosphodiesterases (PDEs) are considered the best drug target for the treatment of schizophrenia since many PDE subfamilies are abundant in the brain regions that are relevant to cognition. Thus, this review aims to illustrate the mechanism of PDEs in treating the symptoms of schizophrenia and summarises the encouraging results of PDE inhibitors as anti-schizophrenic drugs in preclinical and clinical studies.

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Orally disintegrating tablet (ODT) is a friendly dosage form that requires no access to water and serves as a solution to non-compliance. There are many co-processed adjuvants available in the market. However, there is no single product possesses all the ideal characteristics such as good compressibility, fast disintegration and good palatability for ODT application. The aim of this research was to produce a xylitol-starch base co-processed adjuvant which is suitable for ODT application. Two processing methods namely wet granulation and freeze drying were used to compare the characteristics of co-processed adjuvant comprising of xylitol, starch and crospovidone XL-10 mixed at various ratios. The co-processed excipients were compressed into ODT and physically characterized for powder flow, particle size, hardness, thickness, weight, friability, in-vitro disintegration time and in-situ disintegration time, lubricant sensitivity, dilution potential, Fourier transform infrared spectroscopy, scanning electronic microscopy and x-ray diffraction analysis. Formulation F6 was selected as the optimum formulation due to the fastest in-vitro (135.33±11.52 s) and in-situ disintegration time (88.67±13.56s) among all the formulations (p<0.05). Increase in starch component decreases disintegration time of ODT. The powder flow fell under the category of fair flow. Generally, it was observed that freeze drying method produced smaller particle size granules compared to wet granulation method. ODT produced from freeze drying method had shorter disintegration time compared to ODT from wet granulation batch. In conclusion, a novel co-processed excipient comprised of xylitol, starch and crospovidone XL-10, produced using freeze drying method with fast disintegration time, good compressibility and palatability was developed and characterized. The co-processed excipient is suitable for ODT application.

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