Search

Objectives: This study validates the synergistic impact hypothesis of Morus alba phytocompounds on Mycobacterium via molecular docking and simulation. Methods: Phytocompounds (Petunidin-3-rutinoside, Beta-sitosterol, Ecdysterone, Quercetin-3′-glucoside, Quercitrin, Rutin, Scopolin) were tested against key metabolic proteins (MmpL3, DprE1, UgpABCE transporter, porins, OmpATb) of Mycobacterium. Additional proteins (CmaA2, oxidoreductase, FABH, Enoyl-ACP reductase, LpqN) were also included. Docked complexes were analyzed via MD trajectories (RMSD, RMSF, hydrogen bonds) over 100 ns. Results: Binding affinity of phytocompounds with 1UUN (Beta-sitosterol: −9.12692, Ecdysterrone:-12.11162 kcal/mol) and 2KGS (Beta-sitosterol: −6.93) reflects the easy entry of phytocompounds. Phytocompounds interact within cells, inhibiting metabolic pathways and microbial growth. Beta-sitosterol (−7.1 kcal/mol) affects the mycolic acid transfer. Beta-sitosterol (−11.21 kcal/mol) and Ecdysterrone (−9.15 kcal/mol) affect the ribose oxidase pathway. Both compounds also show affinity with UgpABCE transporter. During simulation studies, results showed that the average protein RMSD for the 6MNA-Beta-sitosterol, 6MNA-Scopolin, 4P8T-Beta-sitosterol, and 4P8T-Ecdysterone complexes were 1.87 Å, 2.28 Å, 2.34 Å, and 2.61 Å, respectively. The stability of each complex in dynamic states is ensured by low and steady RMSD variance. In addition, we have endeavored to prove the hypothesis of synergistic application by incorporating our latest findings into the data. Conclusions: Concept of synergistic impact of phytocompounds can be a promising source of treatment after proper lab validation.

Cotton is globally known for its high-priority cellulose-rich natural fiber. In addition to providing fiber for the textile industry, it is an important source material for edible oil, livestock feed, and fuel products. Global warming and the growing population are the major challenges to the world’s agriculture and the potential risks to food security. In this context, improving output traits in cotton is necessary to achieve sustainable cotton production. During the last few years, high throughput omics techniques have aided in identifying crucial genes associated with traits of cotton fiber, seed, and plant architecture which could be targeted with more precision and efficiency through the CIRPSR/Cas-mediated genome editing technique. The various CRISPR/Cas systems such as CRISPR/Cas9, CRISPR/nCas9, and CRISPR/Cas12a have been employed to edit cotton genes associated with a wide range of traits including fiber length, flowering, leaf colour, rooting, seed oil, plant architecture, gossypol content, somatic embryogenesis, and biotic and abiotic stresses tolerance, highlighting its effectiveness in editing the cotton genome. Thus, CRISPR/Cas-mediated genome editing has emerged as a technique of choice to tailor crop phenotypes for better yield potential and environmental resilience. The review covers a comprehensive analysis of cotton phenotypic traits and their improvement with the help of the latest genome editing tools to improve fiber, food, feed, and fuel-associated genes of cotton to ensure food security.

Abstract Cotton is one of the most important fiber crops that plays a vital role in the textile industry. Its production has been unstable over the years due to climate change induced biotic stresses such as insects, diseases, and weeds, as well as abiotic stresses including drought, salinity, heat, and cold. Traditional breeding methods have been used to breed climate resilient cotton, but it requires a considerable amount of time to enhance crop tolerance to insect pests and changing climatic conditions. A promising strategy for improving tolerance against these stresses is genetic engineering. This review article discusses the role of genetic engineering in cotton improvement. The essential concepts and techniques include genome editing via clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR-associated protein 9 (CRISPR-Cas9), overexpression of target genes, downregulation using RNA interference (RNAi), and virus-induced gene silencing (VIGS). Notably, the Agrobacterium-mediated transformation has made significant contributions to using these techniques for obtaining stable transgenic plants.

Abstract Background SRO (Similar to RCD1) genes family is largely recognized for their importance in the growth, development, and in responding to environmental stresses. However, genome-wide identification and functional characterization of SRO genes from cotton species have not been reported so far. Results A total of 36 SRO genes were identified from four cotton species. Phylogenetic analysis divided these genes into three groups with distinct structure. Syntenic and chromosomal distribution analysis indicated uneven distribution of GaSRO, GrSRO, GhSRO, and GbSRO genes on A2, D5 genomes, Gh-At, Gh-Dt, Gb-At, and Gb-Dt subgenomes, respectively. Gene duplication analysis revealed the presence of six duplicated gene pairs among GhSRO genes. In promoter analysis, several elements responsive to the growth, development and hormones were found in GhSRO genes, implying gene induction during cotton growth and development. Several miRNAs responsive to plant growth and abiotic stress were predicted to target 12 GhSRO genes. Organ-specific expression profiling demonstrated the roles of GhSRO genes in one or more tissues. In addition, specific expression pattern of some GhSRO genes during ovule development depicted their involvement in these developmental processes. Conclusion The data presented in this report laid a foundation for understanding the classification and functions of SRO genes in cotton.

ISoXD2 are well explored among versatile and outstanding class of pharmacophores for the preparation and discovery of drugs. Herein, the electronic absorption and emission spectra of ISoXD2 were investigated in three different solvents. The observed transition was attributed to π-π* with charge transfer character. Changes in the excited state and shift of the absorption and emission peaks to longer wavelengths are observed as a result of increasing solvent polarity, due to the interactions between the ISoXD2 molecule and the solvent molecules surrounding it. Changing the solvent confirms its solvatochromic effect. UV–vis and fluorescence analysis revealed that ISoXD2 binds to deoxyribonucleic acid (DNA) by intercalation mode, with a stoichiometric ratio of 1:1.5. Moreover, the fluorescence intensity of DNA bound to ethidium bromide (EB) in the presence of ISoXD2 was investigated. From this analysis, the Stern-Volmer quenching constant (Ksv), quenching rate constant (kq), binding constant (Kb) and binding sites number (n) were found to be 5.654 × 103 M−1, 2.827 × 1011 M−1 s−1, 3.81 × 104 M−1 and 1.225, respectively. The interaction between ISoXD2 and β-CD was investigated through absorption spectra analysis. Kb for this interaction was determined to be 4.9 × 104 M−1. The free radical-scavenging ability of the prepared ISoXD2, examined by DPPH and ABTS assays have shown a good antioxidant activity. Furthermore, modeling study was conducted to explore their plausible binding mechanism with ISoXD2 and to support the experimental results.

Abstract Excess salinity can affect the growth and development of all plants. Salinization jeopardizes agroecosystems, induces oxidative reactions in most cultivated plants and reduces biomass which affects crop yield. Some plants are affected more than others, depending upon their ability to endure the effects of salt stress. Cotton is moderately tolerant to salt stress among cultivated crops. The fundamental tenet of plant breeding is genetic heterogeneity in available germplasm for acquired characteristics. Variation for salinity tolerance enhancing parameters (morphological, physiological and biochemical) is a pre-requisite for the development of salt tolerant cotton germplasm followed by indirect selection or hybridization programs. There has been a limited success in the development of salt tolerant genotypes because this trait depends on several factors, and these factors as well as their interactions are not completely understood. However, advances in biochemical and molecular techniques have made it possible to explore the complexity of salt tolerance through transcriptomic profiling. The focus of this article is to discuss the issue of salt stress in crop plants, how it alters the physiology and morphology of the cotton crop, and breeding strategies for the development of salinity tolerance in cotton germplasm.

Abstract Background Cotton is a strategically important fibre crop for global textile industry. It profoundly impacts several countries' industrial and agricultural sectors. Sustainable cotton production is continuously threatened by the unpredictable changes in climate, specifically high temperatures. Breeding heat-tolerant, high-yielding cotton cultivars with wide adaptability to be grown in the regions with rising temperatures is one of the primary objectives of modern cotton breeding programmes. Therefore, the main objective of the current study is to figure out the effective breeding approach to imparting heat tolerance as well as the judicious utilization of commercially significant and stress-tolerant attributes in cotton breeding. Initially, the two most notable heat-susceptible (FH-115 and NIAB Kiran) and tolerant (IUB-13 and GH-Mubarak) cotton cultivars were spotted to develop filial and backcross populations to accomplish the preceding study objectives. The heat tolerant cultivars were screened on the basis of various morphological (seed cotton yield per plant, ginning turnout percentage), physiological (pollen viability, cell membrane thermostability) and biochemical (peroxidase activity, proline content, hydrogen peroxide content) parameters. Results The results clearly exhibited that heat stress consequently had a detrimental impact on every studied plant trait, as revealed by the ability of crossing and their backcross populations to tolerate high temperatures. However, when considering overall yield, biochemical, and physiological traits, the IUB-13 × FH-115 cross went over particularly well at both normal and high temperature conditions. Moreover, overall seed cotton yield per plant exhibited a positive correlation with both pollen viability and antioxidant levels (POD activity and proline content). Conclusions Selection from segregation population and criteria involving pollen viability and antioxidant levels concluded to be an effective strategy for the screening of heat-tolerant cotton germplasms. Therefore, understanding acquired from this study can assist breeders identifying traits that should be prioritized in order to develop climate resilient cotton cultivars.

Abstract Dalbergia sissoo Roxb. (Shisham) is a timber-producing species of economic, cultural, and medicinal importance in the Indian subcontinent. In the past few decades, Shisham's dieback disease caused by the fungus Botryodiplodia theobromae has become an evolving issue in the subcontinent endangering its survival. To gain insights into this issue, a standard transcriptome assembly was deployed to assess the response of D. sissoo at the transcriptomic level under the stress of B. theobromae infection. For RNA isolation, the control and infected leaf tissue samples were taken from 1-year-old greenhouse-grown D. sissoo plants after 20 days of stem-base spore inoculation. cDNA synthesis was performed from these freshly isolated RNA samples that were then sent for sequencing. About 18.14 Gb (Giga base) of data was generated using the BGISEQ-500 sequencing platform. In terms of Unigenes, 513,821 were identified after a combined assembly of all samples and then filtering the abundance. The total length of Unigenes, their average length, N50, and GC-content were 310,523,693 bp, 604 bp, 1,101 bp, and 39.95% respectively. The Unigenes were annotated using 7 functional databases i.e., 200,355 (NR: 38.99%), 164,973 (NT: 32.11%), 123,733 (Swissprot: 24.08%), 142,580 (KOG: 27.75%), 139,588 (KEGG: 27.17%), 99,752 (GO: 19.41%), and 137,281 (InterPro: 26.72%). Furthermore, the Transdecoder detected 115,762 CDS. In terms of SSR (Simple Sequence Repeat) markers, 62,863 of them were distributed on 51,508 Unigenes and on the predicted 4673 TF (Transcription Factor) coding Unigenes. A total of 16,018 up- and 19,530 down-regulated Differentially Expressed Genes (DEGs) were also identified. Moreover, the Plant Resistance Genes (PRGs) had a count of 9230. We are hopeful that in the future, these identified Unigenes, SSR markers, DEGs and PRGs will provide the prerequisites for managing Shisham dieback disease, its breeding, and in tree improvement programs.

Jamun plant displays enormous diversity throughout Pakistan, which necessitates its screening, evaluation, and validation to document elite genotypes having better traits for the benefit of the fruit industry and farmers. Surveys were made in natural Jamun habitats across Punjab, Pakistan, and genotypes were marked based on visual diversity of trees and fruits. In total, 60 Jamun genotypes were selected for characterization based on phenotypic and genetic markers. Phenotypic characters related to trees, leaf, and flower along with fruit qualitative traits were assessed in situ. Results revealed significant diversity with high (>25%) coefficient of variance values and the first two components of correspondence analysis exhibited 41.71% variation among genotypes. A strong association was observed among traits like upright tree and round fruit shape (0.74), bluish-colored fruit and pinkish pulp (0.85), and elliptic-shaped fruit with low fruit waxiness (−0.72). Leaves of phenotypically characterized plants were brought to Wheat Biotechnology Lab., University of Agriculture, Faisalabad, Pakistan, where Jamun genotypes were investigated genetically using Random Amplified Polymorphic DNA (RAPD) and Inter Simple Sequence Repeat (ISSR) markers. A total of 132 bands were scored, of which 108 were polymorphic, corresponding to almost 81% polymorphism among collected genotypes. High polymorphism information content values were observed against RAPD (0.389) and ISSR (0.457) markers. Genotypes were compared in relation to genetic markers, which exhibited that almost 86% of genetic variability was attributed to differences among accessions, while 14% of variation was due to differences between collections of different areas. Findings of this study confirmed wide phenotypic and genetic distinctness of Jamun in Pakistan that can aid breeders for marker-assisted selection and germplasm enhancement for future crop improvement programs.

In the development of novel antidiabetic agents, a novel series of isoxazolidine-isatin hybrids were designed, synthesized, and evaluated as dual α‐amylase and α-glucosidase inhibitors. The precise structures of the synthesized scaffolds were characterized using different spectroscopic techniques and elemental analysis. The obtained results were compared to those of the reference drug, acarbose (IC50 = 296.6 ± 0.825 μM for α‐amylase & IC50 = 780.4 ± 0.346 μM for α-glucosidase). Among the title compounds, 5d exhibited impressive α-amylase and α-glucosidase inhibitory activity with IC50 values of 30.39 ± 1.52 μM and 65.1 ± 3.11 μM, respectively, followed by 5h (IC50 = 46.65 ± 2.3 μM; IC50 = 85.16 ± 4.25 μM) and 5f (IC50 = 55.71 ± 2.78 μM; IC50 = 106.77 ± 5.31 μM). Mechanistic studies revealed that the most potent derivative 5d bearing the chloro substituent attached to the oxoindolin-3-ylidene core, and acarbose, are a competitive inhibitors of α-amylase and α-glucosidase, respectively. Structure activity relationship (SAR) was examined to guide further structural optimization of the most appropriate substituent(s). Moreover, drug-likeness qualities and ADMET prediction of the most active analogue, 5d was also performed. Subsequently, 5d was subjected to molecular docking and dynamic simulation during the progression of 120 ns analysis to check the essential ligand-receptor patterns, and to estimate its stability. In silico studies were found in good agreement with the in vitro enzymatic inhibitions results. In conclusion, we demonstrated that most potent compound 5d could be exploited as dual potential inhibitor of α-amylase and α-glucosidase for possible management of diabetes.

There are two main ways to discover or design small drug molecules. The first involves fine-tuning existing molecules or commercially successful drugs through quantitative structure-activity relationships and virtual screening. The second approach involves generating new molecules through de novo drug design or inverse quantitative structure-activity relationship. Both methods aim to get a drug molecule with the best pharmacokinetic and pharmacodynamic profiles. However, bringing a new drug to market is an expensive and time-consuming endeavor, with the average cost being estimated at around $2.5 billion. One of the biggest challenges is screening the vast number of potential drug candidates to find one that is both safe and effective. The development of artificial intelligence in recent years has been phenomenal, ushering in a revolution in many fields. The field of pharmaceutical sciences has also significantly benefited from multiple applications of artificial intelligence, especially drug discovery projects. Artificial intelligence models are finding use in molecular property prediction, molecule generation, virtual screening, synthesis planning, repurposing, among others. Lately, generative artificial intelligence has gained popularity across domains for its ability to generate entirely new data, such as images, sentences, audios, videos, novel chemical molecules, etc. Generative artificial intelligence has also delivered promising results in drug discovery and development. This review article delves into the fundamentals and framework of various generative artificial intelligence models in the context of drug discovery via de novo drug design approach. Various basic and advanced models have been discussed, along with their recent applications. The review also explores recent examples and advances in the generative artificial intelligence approach, as well as the challenges and ongoing efforts to fully harness the potential of generative artificial intelligence in generating novel drug molecules in a faster and more affordable manner. Some clinical-level assets generated form generative artificial intelligence have also been discussed in this review to show the ever-increasing application of artificial intelligence in drug discovery through commercial partnerships.

Abstract Background Drought is one of the limiting factors for quality and quantity of cotton lint in tropical and sub-tropical regions. Therefore, development of drought tolerant cotton genotypes have become indispensable. The identification of drought tolerant genotypes is pre-requisite to develop high yielding cultivars suitable for drought affected areas. Methods Forty upland cotton accessions were selected on the basis of their adaptability and yield. The collected germplasm accessions were evaluated at seedling stage on the basis of morphological, physiological and biochemical parameters. The experiment was conducted under controlled conditions in greenhouse where these genotypes were sown under different levels of drought stress by following factorial under completely randomized design. The data were collected at seedling stages for root and shoot lengths, relative leaf water content, excised leaf water losses, peroxidase content and hydrogen peroxide concentrations in leaf tissues. Results The biometrical analysis revealed that germplasm is significantly varied for recorded parameters, likewise interaction of genotypes and water stress was also significantly varied. The cotton germplasm was categorized in eight clusters based on response to water stress. The genotype Cyto-124 exhibited lowest H2O2 content under drought conditions, minimum excised leaf water loss under stress environment was exhibited by genotypes Ali Akber-802 and CEMB-33. Overall, on the basis of morphological and biochemical traits, SL-516 and Cyto-305 were found to be drought tolerant. Genotypes 1852 − 511, Stoneville 15–17 and Delta Pine-55 showed low values for root length, peroxidase activity and higher value for H2O2 contents. On the basis of these finding, these genotypes were declared as drought susceptible. Conclusion The categorization of cotton germplasm indicating the differential response of various parameters under the control and drought stress conditions. The recorded parameters particularly relative leaf water contents and biochemical assays could be utilized to screen large number of germplasm of cotton for water deficit conditions. Besides, the drought tolerant genotypes identified in this research can be utilized in cotton breeding programs for the development of improved cultivars.

Abstract Background Plant aquaporins are critical genetic players performing multiple biological functions, especially climate resilience and water-use efficiency. Their genomic diversity across genus Oryza is yet to be explored. Results This study identified 369 aquaporin-encoding genes from 11 cultivated and wild rice species and further categorized these into four major subfamilies, among which small basic intrinsic proteins are speculated to be ancestral to all land plant aquaporins. Evolutionarily conserved motifs in peptides of aquaporins participate in transmembrane transport of materials and their relatively complex gene structures provide an evolutionary playground for regulation of genome structure and transcription. Duplication and evolution analyses revealed higher genetic conservation among Oryza aquaporins and strong purifying selections are assisting in conserving the climate resilience associated functions. Promoter analysis highlighted enrichment of gene upstream regions with cis-acting regulatory elements involved in diverse biological processes, whereas miRNA target site prediction analysis unveiled substantial involvement of osa-miR2102-3p, osa-miR2927 and osa-miR5075 in post-transcriptional regulation of gene expression patterns. Moreover, expression patterns of japonica aquaporins were significantly perturbed in response to different treatment levels of six phytohormones and four abiotic stresses, suggesting their multifarious roles in plants survival under stressed environments. Furthermore, superior haplotypes of seven conserved orthologous aquaporins for higher thousand-grain weight are reported from a gold mine of 3,010 sequenced rice pangenomes. Conclusions This study unveils the complete genomic atlas of aquaporins across genus Oryza and provides a comprehensive genetic resource for genomics-assisted development of climate-resilient rice cultivars.

Abstract Very long-chain fatty acids (VLCFAs) possess more than twenty carbon atoms and are the major components of seed storage oil, wax, and lipids. FAE (Fatty Acid Elongation) like genes take part in the biosynthesis of VLCFAs, growth regulation, and stress responses, and are further comprised of KCS (Ketoacyl-CoA synthase) and ELO (Elongation Defective Elongase) sub-gene families. The comparative genome-wide analysis and mode of evolution of KCS and ELO gene families have not been investigated in tetraploid Brassica carinata and its diploid progenitors. In this study, 53 KCS genes were identified in B. carinata compared to 32 and 33 KCS genes in B. nigra and B. oleracea respectively, which suggests that polyploidization might has impacted the fatty acid elongation process during Brassica evolution. Polyploidization has also increased the number of ELO genes in B. carinata (17) over its progenitors B. nigra (7) and B. oleracea (6). Based on comparative phylogenetics, KCS, and ELO proteins can be classified into eight and four major groups, respectively. The approximate date of divergence for duplicated KCS and ELO genes varied from 0.03 to 3.20 million years ago (MYA). Gene structure analysis indicated that the maximum number of genes were intron-less and remained conserved during evolution. The neutral type of selection seemed to be predominant in both KCS and ELO genes evolution. String-based protein-protein interaction analysis suggested that bZIP53, a transcription factor might be involved in the activation of transcription of ELO/KCS genes. The presence of biotic and abiotic stress-related cis-regulatory elements in the promoter region suggests that both KCS and ELO genes might also play their role in stress tolerance. The expression analysis of both gene family members reflect their preferential seed-specific expression, especially during the mature embryo development stage. Furthermore, some KCS and ELO genes were found to be specifically expressed under heat stress, phosphorus starvation, and Xanthomonas campestris infection. The current study provides a basis to understand the evolution of both KCS and ELO genes in fatty acid elongation and their role in stress tolerance.

Abstract Background Fatty acid desaturases (FADs) are involved in regulating plant fatty acid composition by adding double bonds to growing hydrocarbon chain. Apart from regulating fatty acid composition FADs are of great importance, and are involved in stress responsiveness, plant development, and defense mechanisms. FADs have been extensively studied in crop plants, and are broadly classed into soluble and non-soluble fatty acids. However, FADs have not yet been characterized in Brassica carinata and its progenitors. Results Here we have performed comparative genome-wide identification of FADs and have identified 131 soluble and 28 non-soluble FADs in allotetraploid B. carinata and its diploid parents. Most soluble FAD proteins are predicted to be resided in endomembrane system, whereas FAB proteins were found to be localized in chloroplast. Phylogenetic analysis classed the soluble and non-soluble FAD proteins into seven and four clusters, respectively. Positive type of selection seemed to be dominant in both FADs suggesting the impact of evolution on these gene families. Upstream regions of both FADs were enriched in stress related cis-regulatory elements and among them ABRE type of elements were in abundance. Comparative transcriptomic data analysis output highlighted that FADs expression reduced gradually in mature seed and embryonic tissues. Moreover, under heat stress during seed and embryo development seven genes remained up-regulated regardless of external stress. Three FADs were only induced under elevated temperature whereas five genes were upregulated under Xanthomonas campestris stress suggesting their involvement in abiotic and biotic stress response. Conclusions The current study provides insights into the evolution of FADs and their role in B. carinata under stress conditions. Moreover, the functional characterization of stress-related genes would exploit their utilization in future breeding programs of B. carinata and its progenitors.

Tuberculosis, also known as TB, is a widespread bacterial infection that remains a significant global health issue. This study focuses on conducting a thorough investigation into the synthesis, evaluation of anti-Tb activity, molecular docking, and molecular dynamic simulation of substituted benzimidazole derivatives. A series of twelve substituted benzimidazole derivatives (1–12) were successfully synthesized, employing a scaffold consisting of electron-withdrawing and electron-donating groups. The newly synthesized compounds were defined by their FTIR, 1H NMR, and mass spectra. The microplate Alamar blue assay (MABA) was used to evaluate the antimycobacterial activity of the synthesized compound against Mycobacterium tuberculosis (Mtb). Compounds 7 (MIC = 0.8 g/mL) and 8 (MIC = 0.8 g/mL) demonstrated exceptional potential to inhibit M. tuberculosis compared to the standard drug (isoniazid). In addition, the synthesized compounds were docked with the Mtb KasA protein (PDB ID: 6P9K), and the results of molecular docking and molecular dynamic simulation confirmed the experimental results, as compounds 7 and 8 exhibited the highest binding energy of −7.36 and −7.17 kcal/mol, respectively. The simulation results such as the RMSD value, RMSF value, radius of gyration, and hydrogen bond analysis illustrated the optimum potential of compounds 7 and 8 to inhibit the M. tuberculosis strain. Hydrogen bond analysis suggested that compound 7 has greater stability and affinity towards the KasA protein compared to compound 8. Moreover, both compounds (7 and 8) were safe for acute inhalation and cutaneous sensitization. These two compounds have the potential to be potent M. tuberculosis​ inhibitors.

Abstract The inhibitory action of fifteen benzyloxy ortho/para-substituted chalcones (B1-B15) was evaluated against human monoamine oxidases (hMAOs). All the molecules inhibited hMAO-B isoform more potently than hMAO-A. Furthermore, the majority of the molecules showed strong inhibitory actions against hMAO-B at 10 μM level with residual activities of less than 50%. Compound B10 has an IC50 value of 0.067 μM, making it the most potent inhibitor of hMAO-B, trailed by compound B15 (IC50 = 0.12 μM). The thiophene substituent (B10) in the A-ring exhibited the strongest hMAO-B inhibition structurally, however, increased residue synthesis did not result in a rise in hMAO-B inhibition. In contrast, the benzyl group at the para position of the B-ring displayed more hMAO-B inhibition than the other positions. Compounds B10 and B15 had relatively high selectivity index (SI) values for hMAO-B (504.791 and 287.600, respectively). Ki values of B10 and B15 were 0.030 ± 0.001 and 0.033 ± 0.001 μM, respectively. The reversibility study showed that B10 and B15 were reversible inhibitors of hMAO-B. PAMPA assay manifested that the benzyloxy chalcones (B10 and B15) had a significant permeability and CNS bioavailability with Pe value higher than 4.0 × 10–6 cm/s. Both compounds were stabilized in protein–ligand complexes by the π-π stacking, which enabled them to bind to the hMAO-B enzyme's active site incredibly effectively. The hMAO-B was stabilized by B10- and B15-hMAO-B complexes, with binding energies of − 74.57 and − 87.72 kcal/mol, respectively. Using a genetic algorithm and multiple linear regression, the QSAR model was created. Based on the best 2D and 3D descriptor-based QSAR model, the following statistics were displayed: R2 = 0.9125, Q2 loo = 0.8347. These findings imply that B10 and B15 are effective, selective, and reversible hMAO-B inhibitors.

Abstract Chronic lymphocytic leukemia (CLL) is an incurable malignancy of B-cells. In this study, bioinformatics analyses were conducted to identify possible pathogenic roles of CK2α, which is a protein encoded by CSNK2A1, in the progression and aggressiveness of CLL. Furthermore, various computational tools were used to search for a competent inhibitor of CK2α from fungal metabolites that could be proposed for CLL therapy. In CLL patients, high-expression of CSNK2A1 was associated with early need for therapy (n = 130, p

Halogenated inhibitors showed robust, reversible, and selective monoamine oxidase-B (MAO-B) inhibitory efficacy in candidates that were derived from them. Our team has previously synthesized and assessed a panel of halogenated chalcones and coumarin for the study on MAO-B inhibition. The aim of this study was to build GA-MLR based QSAR models and predictive 3D Pharmacophore models, as well as to investigate the relationship between halogenated derivatives and MAO-B inhibitory activity. The robust statistical significance in the parameter (R2 = 0.78 and Q2 = 0.69) was demonstrated. Best Hypo1 contains one hydrophobic and two aromatic rings. The lead molecule for quantum mechanics was performed, and it was revealed that it would bind to proteins and provide stability. To determine the stability of the ligand-enzyme complex, a thorough molecular dynamics analysis of the lead compounds was accomplished.

Illicium verum, or star anise, has many uses ranging from culinary to religious. It has been used in the food industry since ancient times. The main purpose of this study was to determine the chemical composition, antibacterial, antibiofilm, and anti-quorum sensing activities of the essential oil (EO) obtained via hydro-distillation of the aerial parts of Illicium verum. Twenty-four components were identified representing 92.55% of the analyzed essential oil. (E)-anethole (83.68%), limonene (3.19%), and α-pinene (0.71%) were the main constituents of I. verum EO. The results show that the obtained EO was effective against eight bacterial strains to different degrees. Concerning the antibiofilm activity, trans-anethole was more effective against biofilm formation than the essential oil when tested using sub-inhibitory concentrations. The results of anti-swarming activity tested against P. aeruginosa PAO1 revealed that I. verum EO possesses more potent inhibitory effects on the swarming behavior of PAO1 when compared to trans-anethole, with the percentage reaching 38% at a concentration of 100 µg/mL. The ADME profiling of the identified phytocompounds confirmed their important pharmacokinetic and drug-likeness properties. The in silico study using a molecular docking approach revealed a high binding score between the identified compounds with known target enzymes involved in antibacterial and anti-quorum sensing (QS) activities. Overall, the obtained results suggest I. verum EO to be a potentially good antimicrobial agent to prevent food contamination with foodborne pathogenic bacteria.

Dalbergia sissoo is one of the most economically important trees in forestry, agroforestry, and horticulture. This tree species is severely threatened by dieback. Widespread dieback outbreaks and infestations have drastically destroyed billions of D. sissoo trees. Hence, we attempted to resolve the dieback etiology through phylogenomics associated with D. sissoo mortality. The Ceratocystis species was evaluated using morphologically investigated fungal isolates collected from dieback-affected tissue plants. Based on the symptomatology, we have differentiated dieback from Fusarium wilt and concluded that the Ceratocystis fimbriata sensu lato complex is causing shisham dieback in Pakistan. As the Ceratocystis species complex is a cryptic species complex, we used genomics and phylogenetic analysis for deciphering its evolutionary hierarchical order. The pathogen’s operational taxonomy was unlocked with the help of phylogenomics, and it was discovered that isolates from D. sissoo represent a species distinct from the other species in the C. fimbriata sensu lato species complex. The name Ceratocystis dalbergicans sp. nov. has been given to the fungus causing dieback disease in D. sissoo.

Abstract The introduction of genetically modified (GM) cotton in 1996 in the US and its worldwide spread later rejuvenated cotton production in many parts of the world. The evolution is continued since then and currently, the 3rd and fourth generation of same GM cotton is grown in many parts of the world. The GM cotton introduced in 1996 was simple Bt cotton that expressed a single Cry1Ac gene, the later generation carried multiple Cry genes along with the genes controlling herbicide tolerance. Current day GM cotton does not only give stable resistance against lepidopteran insects but also facilitates the farmers to spray broad-spectrum herbicides without harming the crop. The evolution of GM cotton is continued both on the basic and applied side and interventions have been introduced during the last decade. Earlier the cotton transformation was limited to Cocker strains which are getting possible in many other varieties, too. It is successful with both gene gun, and Agrobacterium and inplanta transformation has made it a routine activity. Apart from overexpression studies for various purposes including biotic, abiotic, and quality traits, RNAi and genome editing are explored vigorously. Through this review, we have tried to explore and discuss various interventions for improving transformation protocols, the applications of cotton transformation, and future strategies being developed to get maximum benefits from this technology during the last decade.

Consumption of water polluted by crude oil is a major environmental problem typical in exploration areas. Numerous health complications such as high blood pressure, myocardial infarction, and other heart complications are prevalent and ravaging. These have gradually become age-defiling disease conditions that are usually maintained with lifestyle changes and diet control. The effect of dietary supplementation with 10% and 20% roasted cashew nuts (RCN) on systolic blood pressure and angiotensin converting enzyme I (ACE I) activities in mixed petroleum fraction (MPF) induced toxicity was studied in male Wistar rats through the modulation of the renin-angiotensin system. The phytochemicals in RCN were quantified using the high performance liquid chromatography (HPLC) technique. To predict likely binding affinity and stability, computational methods such as molecular docking, ADME, and molecular dynamic simulation were used. Out of the seven phytochemicals identified, rutin, gallic acid, and quercetin had the greatest quantities. Similarly, rutin had the highest binding affinities with ACE I, -10.7 kcal/mol, followed by quercetin, at -9.1 kcal/mol. During the molecular dynamics simulation, all of the identified phytochemicals demonstrated good pharmacokinetic capabilities and remained stable at their respective binding sites. Subsequent in vivo validation studies revealed that RCN was able to attenuate the effect of MPF by significantly (p < 0.05) lowering the systolic blood pressure and ACE I activity in comparison to the reference medication, atenolol. We recommend that cashew nuts be explored as dietary snacks as well as a low-cost, easily available component of supplements for the treatment of high blood pressure.

The need for novel antiviral drug particularly for hepatitis B (HBV) and C (HCV) virus cannot be over emphasized hence, this work focuses on the stability and intermolecular interaction of three diazenylphenyl compounds; 5-((E)-(4-((E)-(3-hydroxy-nitrosonaphthalen-1-yl)diazinyl)phenyl)diazinyl)-3,8a-dihydroquinolin-8-ol, (Z)-4-(E-(4-(E)-(2,4-dihydroxyphenyl)phenyl)diazinyl-2-(hydroxyamino)-4a,8a-dihyroapthalen-1(2H)-one, and 4-((E)-(4-((E)-(2-hydroxy-3-nitrosophenyl)diazenyl)phenyl)diazenyl)-4a,8a-dihydronaphthalen-1(4H)-one depicted as A, B and C respectively. We have performed a comprehensive quantum computational study to ascertain the drug likeness of the titled molecules. Interestingly, Compound C was found to be the most stable compound compared to A and B. In the Density of state (DOS) studies, hydrogen was observed to have the highest peak in the antibonding region whereas carbon has the highest values at the bonding molecular orbitals. Compound C have the highest second order perturbation energies. The molecular dynamics simulation of the individual molecules indicate that compound B + 4MWF complex has the highest binding energy than other complexes and the RMSD values indicate that the targeted K7F, 6CWT, 4MWF and 5YAX proteins are more conformationally stable when bound with compound B. Antiviral property of the titled molecules was investigated by docking with the selected viral proteins. The studied compounds were observed to have the highest binding affinity compared to Telbivudine and Sofosbuvir which were used as standard drugs.

The chlorpyrifos-mineralizing rice root endophyte Enterobacter sp. HSTU-ASh6 strain was identified, which enormously enhanced the growth of tomato plant under epiphytic conditions. The strain solubilizes phosphate and grew in nitrogen-free Jensen’s medium. It secreted indole acetic acid (IAA; 4.8 mg/mL) and ACC deaminase (0.0076 μg/mL/h) and hydrolyzed chlorpyrifos phosphodiester bonds into 3,5,6-trichloro-2-pyridinol and diethyl methyl-monophosphate, which was confirmed by Gas Chromatography – Tandem Mass Spectrometry (GC–MS/MS) analysis. In vitro and in silico (ANI, DDH, housekeeping genes and whole genome phylogenetic tree, and genome comparison) analyses confirmed that the strain belonged to a new species of Enterobacter. The annotated genome of strain HSTU-ASh6 revealed a sets of nitrogen-fixing, siderophore, acdS, and IAA producing, stress tolerance, phosphate metabolizing, and pesticide-degrading genes. The 3D structure of 28 potential model proteins that can degrade pesticides was validated, and virtual screening using 105 different pesticides revealed that the proteins exhibit strong catalytic interaction with organophosphorus pesticides. Selected docked complexes such as α/β hydrolase–crotoxyphos, carboxylesterase–coumaphos, α/β hydrolase–cypermethrin, α/β hydrolase–diazinon, and amidohydrolase–chlorpyrifos meet their catalytic triads in visualization, which showed stability in molecular dynamics simulation up to 100 ns. The foliar application of Enterobacter sp. strain HSTU-ASh6 on tomato plants significantly improved their growth and development at vegetative and reproductive stages in fields, resulting in fresh weight and dry weight was 1.8–2.0-fold and 1.3–1.6-fold higher in where urea application was cut by 70%, respectively. Therefore, the newly discovered chlorpyrifos-degrading species Enterobacter sp. HSTU-ASh6 could be used as a smart biofertilizer component for sustainable tomato cultivation.

DNA-binding with one finger (Dof) transcription factors have been demonstrated to regulate various stresses and developmental processes in plants. Their identification and comparative evolutionary analyses in cultivated and wild species of genus oryza were yet to be explored. In this context, we report a comprehensive genomics atlas of DNA-binding with one finger (Dof) family genes in 13 diverse rice genomes (five cultivated and eight rice wild-relatives) through a genome-wide scanning approach. A galore of 238 Dof genes, identified across the genus Oryza, are categorized into seven distinct subgroups by comparative phylogenetic analysis with the model plant Arabidopsis. Conserved motifs and gene structure analyses unveiled the prevalence of species- and subgroups-specific structural and functional diversity that is expediating with the evolutionary period. Our results indicate that Dof genes might have undergone strong purifying selections and segmental duplications to expand their gene family members in corresponding Oryza genomes. We speculate that miR2927 potentially targets the Dof domain to regulate gene expression under different climatic conditions, which are supported by in-silico and wet-lab experiments-based expression profiles. In a nutshell, we report several superior haplotypes significantly associated with early flowering in a treasure trove of 3,010 sequenced rice accessions and have validated these haplotypes with two years of field evaluation-based flowering data of a representative subpanel. Finally, we have provided some insights on the resolution of Oryza species phylogeny discordance and divergence highlighting the mosaic evolutionary history of the genus Oryza. Overall, this study reports a complete genomic landscape of the Dof family in cultivated and wild Oryza species that could greatly facilitate in fast-track development of early maturing and climate-resilient rice cultivars through modern haplotype-led breeding.

In an attempt to rationalize the search for new potential anti-inflammatory and anti-infection agents, a new series of 1,4-and 1,5-disubstituted 1,2,3-triazoles linked benzoxazine conjugates have been synthesized via “Click Chemistry” reaction, were designed, synthesized and characterized by means of spectral and elemental data. The newly synthesized compounds have been assessed for their antimicrobial, antioxidant and anti-inflammatory potential. Results revealed that all synthesized compounds display superior activities to the standard drug against different bacterial strains especially S. aureus, M. luteus, and P. aeruginosa, with good to moderate activity towards the tested E. coli bacteria, in respect to the commercial antibiotic, tetracycline. Moreover, the antifungal activity was screened against C. albicans and C. krusei yeasts and results demonstrate potent activity as compared to the standard drug, ampicillin. The antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assays, whose results indicate that analogues 4a (IC50 1.88 ± 0.07 µM and 2.17 ± 0.02) followed by 4b (IC50 2.19 ± 0.09 µM and 2.38 ± 0.43 µM), 4d (IC50 2.30 ± 0.01 µM and 4.07 ± 0.57 µM), and 4f (2.98 ± 0.02 µM and 3.80 ± 0.01 µM), respectively, exhibited the strongest activity when compared to the standard reference, butylated hydroxytoluene (BHT) (3.52 ± 0.08 µM and 4.64 ± 0.11 µM). In addition, their anti-inflammatory activity was assessed using the xylene-induced ear edema standard technique and the results demonstrated the potency of 4a, 4b and 4d as excellent anti-inflammatory agents. Preliminary structure–activity relationship studies (SARs) provide those biological activities can be modulated by the presence of unsubstituted aromatic ring as well as the position of substituents on the phenyl moiety via electron withdrawing groups (EWGs) or electron donating groups (EDGs) effects. Docking studies on the most promising compounds 4a, 4b, and 4d into the active sites of S. aureus tyrosyl-tRNA synthetase, Candida albicans N-Myristoyltransferase, Human COX-2 enzyme, and Human Peroxiredoxin 5 revealed good binding profiles with the target proteins. The interaction's stability was further assessed using a conventional atomistic 100 ns dynamic simulation study. Hence, our results recommended the rationalized targets 4a, 4b and 4d, to be promising lead candidates for the discovery of novel dual anti-inflammatory and anti-infection agents.

Dalbergia sissoo is an important timber tree, and dieback disease poses a dire threat to it toward extinction. The genomic record of D. sissoo is not available yet on any database; that is why it is challenging to probe the genetic elements involved in stress resistance. Hence, we attempted to unlock the genetics involved in dieback resistance through probing the NBS-LRR family, linked with mostly disease resistance in plants. We analyzed the transcriptome of D. sissoo under dieback challenge through DOP-rtPCR analysis using degenerate primers from conserved regions of NBS domain-encoded gene sequences. The differentially expressed gene sequences were sequenced and in silico characterized for predicting the expressome that contributes resistance to D. sissoo against dieback. The molecular and bioinformatic analyses predicted the presence of motifs including ATP/GTP-binding site motif A (P-loop NTPase domain), GLPL domain, casein kinase II phosphorylation site, and N-myristoylation site that are the attributes of proteins encoded by disease resistance genes. The physicochemical characteristics of identified resistance gene analogs, subcellular localization, predicted protein fingerprints, in silico functional annotation, and predicted protein structure proved their role in disease and stress resistance.

Anethum graveolens L. has been known as an aromatic, medicinal, and culinary herb since ancient times. The main purpose of this study was to determine the chemical composition, antibacterial, antibiofilm, and anti-quorum sensing activities of the essential oil (EO) obtained by hydro-distillation of the aerial parts. Twelve components were identified, representing 92.55% of the analyzed essential oil. Limonene (48.05%), carvone (37.94%), cis-dihydrocarvone (3.5%), and trans-carvone (1.07%) were the main identified constituents. Results showed that the obtained EO was effective against eight bacterial strains at different degrees. Concerning the antibiofilm activity, limonene was more effective against biofilm formation than the essential oil when tested using sub-inhibitory concentrations. The results of anti-swarming activity tested against P. aeruginosa PAO1 revealed that A. graveolens induced more potent inhibitory effects in the swarming behavior of the PAO1 strain when compared to limonene, with a percentage reaching 33.33% at a concentration of 100 µg/mL. The ADME profiling of the identified phytocompounds confirms their important pharmacokinetic and drug-like properties. The in-silico study using molecular docking approaches reveals a high binding score between the identified compounds and known target enzymes involved in antibacterial and anti-quorum sensing (QS) activities. Overall, the obtained results highlight the possible use of A. graveolens EO to prevent food contamination with foodborne pathogenic bacteria.

With the advent of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated protein (Cas) mediated genome editing, crop improvement has progressed significantly in recent years. In this genome editing tool, CRISPR-associated Cas nucleases are restricted to their target of DNA by their preferred protospacer adjacent motifs (PAMs). A number of CRISPR-Cas variants have been developed e.g. CRISPR-Cas9, -Cas12a and -Cas12b, with different PAM requirements. In this mini-review, we briefly explain the components of the CRISPR-based genome editing tool for crop improvement. Moreover, we intend to highlight the information on the latest development and breakthrough in CRISPR technology, with a focus on a comparison of major variants (CRISPR-Cas9, -Cas12a, and -Cas12b) to the newly developed CRISPR-SpRY that have nearly PAM-less genome editing ability. Additionally, we briefly explain the application of CRISPR technology in the improvement of cultivated grasses with regard to biotic and abiotic stress tolerance as well as improving the quality and yield.

The seaweed industries generate considerable amounts of waste that must be appropriately managed. This biomass from marine waste is a rich source of high-value bioactive compounds. Thus, this waste can be adequately utilized by recovering the compounds for therapeutic purposes. Histone deacetylases (HDACs) are key epigenetic regulators established as one of the most promising targets for cancer chemotherapy. In the present study, our objective is to find the HDAC 2 inhibitor. We performed top-down in silico methodologies to identify potential HDAC 2 inhibitors by screening compounds from edible seaweed waste. One hundred ninety-three (n = 193) compounds from edible seaweeds were initially screened and filtered with drug-likeness properties using SwissADME. After that, the filtered compounds were followed to further evaluate their binding potential with HDAC 2 protein by using Glide high throughput virtual screening (HTVS), standard precision (SP), extra precision (XP), and quantum polarized ligand docking (QPLD). One compound with higher negative binding energy was selected, and to validate the binding mode and stability of the complex, molecular dynamics (MD) simulations using Desmond were performed. The complex-binding free energy calculation was performed using molecular mechanics-generalized born surface area (MM-GBSA) calculation. Post-MD simulation analyses such as PCA, DCCM, and free energy landscape were also evaluated. The quantum mechanical and electronic properties of the potential bioactive compounds were assessed using the density functional theory (DFT) study. These findings support the use of marine resources like edible seaweed waste for cancer drug development by using its bioactive compounds. The obtained results encourage further in vitro and in vivo research. Our in silico findings show that the compound has a high binding affinity for the catalytic site of the HDAC 2 protein and has drug-likeness properties, and can be utilized in drug development against cancer.

Russian olive (Elaeagnus angustifolia L., Elaeagnaceae) is a native multi-purpose medicinal shrub or tree of temperate Asian regions and an integral component of high altitude terraced agroforestry systems of Gilgit-Baltistan, northern Pakistan. The strong increase in deforestation, urbanisation, and the loss of ethnically-based medication practices in local communities are gradually leading to depletion of its stands and knowledge of its use. In view of these circumstances, this study was undertaken to characterise Russian olive accessions as a first step towards the conservation of this important wild plant genetic resource. Ninety-three fruits (including seeds) and leaves were sampled to determine morphological variability among accessions. In addition, the phenolic composition of fruit pulp of 40 fruits was determined. To assess the local importance of the species, 42 Russian olive collectors and traders were interviewed. Data were analysed using PCA followed by clustering. Fruit traits across groups were equally shared. Elevation enhanced fruit and seed dimensions especially length (r = 0.606 and 0.515, respectively) and weight (r = 0.618 and 0.695, respectively). Bioactive substances such as DPPH and flavonoids in the sampled fruits exceeded most values found in the literature by a factor of 100 and 30, respectively. The socio-economic household analysis highlighted that Russian olive harvest and trade are important additional income strategies. On average, about 90€ (ca. 16000 PKR) were earned annually per household ranging from about 35€ to about 205€ . Data yielded a mixed picture on morphological and biochemical diversity as well as the socio-economic background, but indicated that northern regions of Pakistan are an important centre for biodiversity of this species in Central Asia, which merits improved marketing.

MADS-box gene family members play multifarious roles in regulating the growth and development of crop plants and hold enormous promise for bolstering grain yield potential under changing global environments. Bread wheat (Triticum aestivum L.) is a key stable food crop around the globe. Until now, the available information concerning MADS-box genes in the wheat genome has been insufficient. Here, a comprehensive genome-wide analysis identified 300 high confidence MADS-box genes from the publicly available reference genome of wheat. Comparative phylogenetic analyses with Arabidopsis and rice MADS-box genes classified the wheat genes into 16 distinct subfamilies. Gene duplications were mainly identified in subfamilies containing unbalanced homeologs, pointing towards a potential mechanism for gene family expansion. Moreover, a more rapid evolution was inferred for M-type genes, as compared with MIKC-type genes, indicating their significance in understanding the evolutionary history of the wheat genome. We speculate that subfamily-specific distal telomeric duplications in unbalanced homeologs facilitate the rapid adaptation of wheat to changing environments. Furthermore, our in-silico expression data strongly proposed MADS-box genes as active guardians of plants against pathogen insurgency and harsh environmental conditions. In conclusion, we provide an entire complement of MADS-box genes identified in the wheat genome that could accelerate functional genomics efforts and possibly facilitate bridging gaps between genotype-to-phenotype relationships through fine-tuning of agronomically important traits.

Our investigation includes the synthesis of new naphthalene-bis-triazole-bis-quinolin-2(1H)-ones 4a–e and 7a–e via Cu-catalyzed [3 + 2] cycloadditions of 4-azidoquinolin-2(1H)-ones 3a–e with 1,5-/or 1,8-bis(prop-2-yn-1-yloxy)naphthalene (2) or (6). All structures of the obtained products have been confirmed with different spectroscopic analyses. Additionally, a mild and versatile method based on copper-catalyzed [3 + 2] cycloaddition (Meldal–Sharpless reaction) was developed to tether quinolinones to O-atoms of 1,5- or 1,8-dinaphthols. The triazolo linkers could be considered as anti and syn products, which are interesting precursors for functionalized epidermal growth factor receptor (EGFR) inhibitors with potential apoptotic antiproliferative action. The antiproliferative activities of the 4a–e and 7a–e were evaluated. Compounds 4a–e and 7a–e demonstrated strong antiproliferative activity against the four tested cancer cell lines, with mean GI50 ranging from 34 nM to 134 nM compared to the reference erlotinib, which had a GI50 of 33 nM. The most potent derivatives as antiproliferative agents, compounds 4a, 4b, and 7d, were investigated for their efficacy as EGFR inhibitors, with IC50 values ranging from 64 nM to 97 nM. Compounds 4a, 4b, and 7d demonstrated potent apoptotic effects via their effects on caspases 3, 8, 9, Cytochrome C, Bax, and Bcl2. Finally, docking studies show the relevance of the free amino group of the quinoline moiety for antiproliferative action via hydrogen bond formation with essential amino acids.

Thymus musilii Velen. is a rare plant species cultivated in the Ha’il region (Saudi Arabia) under greenhouse conditions. In this work, we described, for the first time, the phytochemical composition, antimicrobial, antioxidant, anti-quorum sensing, and anticancer activities of T. musilii methanolic extract using both experimental and computational approaches. The obtained results showed the identification of eight small-like peptides and eighteen phyto-compounds by using high-resolution liquid chromatography–mass spectrometry (HR-LCMS) dominated mainly by compounds belonging to isoprenoid, fatty acyl, flavonoid, and alkaloid classes. The tested extracts exhibited high antifungal and antibacterial activity with the mean diameter of growth inhibition zones ranging from 12.33 ± 0.57 mm (Pseudomonas aeruginosa ATCC 27853) to 29.33 ± 1.15 mm (Candida albicans ATCC 10231). Low minimal inhibitory concentrations were recorded for the tested micro-organisms ranging from 0.781 mg/mL to 12.5 mg/mL. While higher doses were necessary to completely kill all tested bacterial and fungal strains. Thyme extract was able to scavenge DPPH•, ABTS•+, β-carotene, and FRAP free radicals, and the IC50 values were 0.077 ± 0.0015 mg/mL, 0.040 ± 0.011 mg/mL, 0.287 ± 0.012 mg/mL, and 0.106 ± 0.007 mg/mL, respectively. The highest percentage of swarming and swimming inhibition was recorded at 100 µg/mL with 39.73 ± 1.5% and 25.18 ± 1%, respectively. The highest percentage of biofilm inhibition was recorded at 10 mg/mL for S. typhimurium ATCC 14028 (53.96 ± 4.21%) and L. monocytogenes ATCC 7644 (49.54 ± 4.5 mg/mL). The in silico docking study revealed that the observed antimicrobial, antioxidant, and anticancer activities of the constituent compounds of T. musilii are thermodynamically feasible, notably, such as those of the tripeptides (Asn-Met-His, His-Cys-Asn, and Phe-His-Gln), isoprenoids (10-Hydroxyloganin), and diterpene glycosides (4-Ketoretinoic acid glucuronide).

The regeneration of the high-yielding multilocular types has not been attempted, although successful regeneration and transformation in brassica have been done. Here, we report efficient regeneration and transformation protocols for two B. rapa genotypes; UAF11 and Toria. The B. rapa cv UAF11 is a multilocular, non-shattering, and high-yielding genotype, while Toria is the bilocular type. For UAF11 8 shoots and for Toria 7 shoots, explants were observed on MS supplemented with 3 mg/L BAP + 0.4 mg/L NAA + 0.01 mg/L GA3 + 5 mg/L AgNO3 + 0.75 mg/L Potassium Iodide (KI), MS salt supplemented with 1 mg/L IBA and 0.37 mg/L KI produced an equal number of roots (3) in UAF11 and Toria. For the establishment of transformation protocols, Agrobacterium-mediated floral dip transformation was attempted using different induction media, infection time, and flower stages. The induction medium III yielded a maximum of 7.2% transformants on half-opened flowers and 5.2% transformants on fully opened flowers in UAF11 and Toria, respectively, with 15 min of inoculation. This study would provide the basis for the improvement of tissue culture and transformation protocols in multilocular and bilocular Brassica genotypes.

Ducrosia flabellifolia Boiss. is a rare desert plant known to be a promising source of bioactive compounds. In this paper, we report for the first time the phytochemical composition and biological activities of D. flabellifolia hydroalcoholic extract by using liquid chromatography–electrospray tandem mass spectrometry (ESI-MS/MS) technique. The results obtained showed the richness of the tested extract in phenols, tannins, and flavonoids. Twenty-three phytoconstituents were identified, represented mainly by chlorogenic acid, followed by ferulic acid, caffeic acid, and sinapic acid. The tested hydroalcoholic extract was able to inhibit the growth of all tested bacteria and yeast on agar Petri dishes at 3 mg/disc with mean growth inhibition zone ranging from 8.00 ± 0.00 mm for Enterococcus cloacae (E. cloacae) to 36.33 ± 0.58 mm for Staphylococcus epidermidis. Minimal inhibitory concentration ranged from 12.5 mg/mL to 200 mg/mL and the hydroalcoholic extract from D. flabellifolia exhibited a bacteriostatic and fungistatic character. In addition, D. flabellifolia hydroalcoholic extract possessed a good ability to scavenge different free radicals as compared to standard molecules. Molecular docking studies on the identified phyto-compounds in bacterial, fungal, and human peroxiredoxin 5 receptors were performed to corroborate the in vitro results, which revealed good binding profiles on the examined protein targets. A standard atomistic 100 ns dynamic simulation investigation was used to further evaluate the interaction stability of the promising phytocompounds, and the results showed conformational stability in the binding cavity. The obtained results highlighted the medicinal use of D. flabellifolia as source of bioactive compounds, as antioxidant, antibacterial, and antifungal agent.

Abiotic stresses, such as drought, salinity, heat, cold, and heavy metals, are associated with global climate change and hamper plant growth and development, affecting crop yields and quality. However, the negative effects of abiotic stresses can be mitigated through exogenous treatments using small biomolecules. For example, the foliar application of melatonin provides the following: it protects the photosynthetic apparatus; it increases the antioxidant defenses, osmoprotectant, and soluble sugar levels; it prevents tissue damage and reduces electrolyte leakage; it improves reactive oxygen species (ROS) scavenging; and it increases biomass, maintains the redox and ion homeostasis, and improves gaseous exchange. Glutathione spray upregulates the glyoxalase system, reduces methylglyoxal (MG) toxicity and oxidative stress, decreases hydrogen peroxide and malondialdehyde accumulation, improves the defense mechanisms, tissue repairs, and nitrogen fixation, and upregulates the phytochelatins. The exogenous application of proline enhances growth and other physiological characteristics, upregulates osmoprotection, protects the integrity of the plasma lemma, reduces lipid peroxidation, increases photosynthetic pigments, phenolic acids, flavonoids, and amino acids, and enhances stress tolerance, carbon fixation, and leaf nitrogen content. The foliar application of glycine betaine improves growth, upregulates osmoprotection and osmoregulation, increases relative water content, net photosynthetic rate, and catalase activity, decreases photorespiration, ion leakage, and lipid peroxidation, protects the oxygen-evolving complex, and prevents chlorosis. Chemical priming has various important advantages over transgenic technology as it is typically more affordable for farmers and safe for plants, people, and animals, while being considered environmentally acceptable. Chemical priming helps to improve the quality and quantity of the yield. This review summarizes and discusses how exogenous melatonin, glutathione, proline, and glycine betaine can help crops combat abiotic stresses.

To combat emerging antimicrobial-resistant microbes, there is an urgent need to develop new antimicrobials with better therapeutic profiles. For this, a series of 13 new spiropyrrolidine derivatives were designed, synthesized, characterized and evaluated for their in vitro antimicrobial, antioxidant and antidiabetic potential. Antimicrobial results revealed that the designed compounds displayed good activity against clinical isolated strains, with 5d being the most potent (MIC 3.95 mM against Staphylococcus aureus ATCC 25923) compared to tetracycline (MIC 576.01 mM). The antioxidant activity was assessed by trapping DPPH, ABTS and FRAP assays. The results suggest remarkable antioxidant potential of all synthesized compounds, particularly 5c, exhibiting the strongest activity with IC50 of 3.26 ± 0.32 mM (DPPH), 7.03 ± 0.07 mM (ABTS) and 3.69 ± 0.72 mM (FRAP). Tested for their α-amylase inhibitory effect, the examined analogues display a variable degree of α-amylase activity with IC50 ranging between 0.55 ± 0.38 mM and 2.19 ± 0.23 mM compared to acarbose (IC50 1.19 ± 0.02 mM), with the most active compounds being 5d, followed by 5c and 5j, affording IC50 of 0.55 ± 0.38 mM, 0.92 ± 0.10 mM, and 0.95 ± 0.14 mM, respectively. Preliminary structure–activity relationships revealed the importance of such substituents in enhancing the activity. Furthermore, the ADME screening test was applied to optimize the physicochemical properties and determine their drug-like characteristics. Binding interactions and stability between ligands and active residues of the investigated enzymes were confirmed through molecular docking and dynamic simulation study. These findings provided guidance for further developing leading new spiropyrrolidine scaffolds with improved dual antimicrobial and antidiabetic activities.

Pathogenicity-associated genes are highly host-specific and contribute to host-specific virulence. We tailored the traditional Koch’s postulates with integrative omics by hypothesizing that the effector genes associated with host-pathogenicity are determinant markers for virulence, and developed Integrative Pathogenicity (IP) postulates for authenticated pathogenicity testing in plants. To set the criteria, we experimented on datepalm (Phoenix dactylifera) for the vascular wilt pathogen and confirmed the pathogen based on secreted in xylem genes (effectors genes) using genomic and transcriptomic approaches, and found it a reliable solution when pathogenicity is in question. The genic regions ITS, TEF1-α, and RPBII of Fusarium isolates were examined by phylogenetic analysis to unveil the validated operational taxonomy at the species level. The hierarchical tree generated through phylogenetic analysis declared the fungal pathogen as Fusarium oxysporum. Moreover, the Fusarium isolates were investigated at the subspecies level by probing the IGS, TEF1-α, and Pgx4 genic regions to detect the forma specialis of F. oxysporum that causes wilt in datepalm. The phylogram revealed a new forma specialis in F. oxysporum that causes vascular wilt in datepalm.

Abstract Background Climate change and particularly global warming has emerged as an alarming threat to the crop productivity of field crops and exerted drastic effects on the cropping patterns. Production of cotton has been dropped down to one million bales from 1.4 million bales since 2015 in Pakistan due to the increase in temperature at critical growth stages, i.e., flowering and boll formation. Keeping in view the importance of cotton in the country, this study was conducted to investigate the genetic effects conferring heat tolerance in six populations (P1, P2, F1, F2, BC1 and BC2) developed from cross-1 and cross-2, i.e., VH-282 × FH-142 and DNH-40 × VH-259. Results The results revealed that cross-1 performed better in heat stress as compared with cross-2 for majority of the traits recorded. Boll weight and ginning outturn (GOT) were highly effected under heat stress and had negative correlation with Relative cell injury (RCI). Boll weight, fiber length, fiber strength and fiber fineness were under the control of non-additive gene action, whereas RCI was controlled by additive gene effects. Lower values of genetic advance coupled with higher values of broad sense heritability for these traits except RCI confirmed the role of non-additive genetic effects. Duplicate types of epistasis were recorded for fiber strength in cross-1 in normal condition. However, complementary type of non-allelic interaction was recorded for fiber strength under normal condition, fiber fineness and RCI under heat stressed condition in cross-1. Likewise, boll weight, GOT and fiber length in populations derived from cross-2 in normal condition were also under the influence of complementary type of non-allelic interaction. Significant differences among values of mid parent and better parent heterosis for boll weight in both normal and heat stress condition provided the opportunity to cotton breeders for utilization of this germplasm for improvement of this trait through exploitation of heterosis breeding. Conclusion Cross-1 performed better in heat stress and could be utilized for development of heat tolerant cultivar. RCI was under the influence of additive gene action, so one can rely on this trait for screening of large number of accessions of cotton for heat stress. While other traits were predominantly controlled by non-additive gene action and selection based on these should be delayed in later generations.

Abstract A single nucleotide polymorphism is the simplest form of genetic variation among individuals and can induce minor changes in phenotypic, physiological and biochemical characteristics. This polymorphism induces various mutations that alter the sequence of a gene which can lead to observed changes in amino acids. Several assays have been developed for identification and validation of these markers. Each method has its own advantages and disadvantages but genotyping by sequencing is the most common and most widely used assay. These markers are also associated with several desirable traits like yield, fibre quality, boll size and genes respond to biotic and abiotic stresses in cotton. Changes in yield related traits are of interest to plant breeders. Numerous quantitative trait loci with novel functions have been identified in cotton by using these markers. This information can be used for crop improvement through molecular breeding approaches. In this review, we discuss the identification of these markers and their effects on gene function of economically important traits in cotton.

A major global health risk has been witnessed with the development of drug-resistant bacteria and multidrug-resistant pathogens linked to significant mortality. Coumarins are heterocyclic compounds belonging to the benzophenone class enriched in different plants. Coumarins and their derivatives have a wide range of biological activity, including antibacterial, anticoagulant, antioxidant, anti-inflammatory, antiviral, antitumour, and enzyme inhibitory effects. In the past few years, attempts have been reported towards the optimization, synthesis, and evaluation of novel coumarin analogues as antimicrobial agents. Several coumarin-based antibiotic hybrids have been developed, and the majority of them were reported to exhibit potential antibacterial effects. In the present work, studies reported from 2016 to 2020 about antimicrobial coumarin analogues are the focus. The diverse biological spectrum of coumarins can be attributed to their free radical scavenging abilities. In addition to various synthetic strategies developed, some of the structural features include a heterocyclic ring with electron-withdrawing/donating groups conjugated with the coumarin nucleus. The suggested structure−activity relationship (SAR) can provide insight into how coumarin hybrids can be rationally improved against multidrug-resistant bacteria. The present work demonstrates molecular insights for coumarin derivatives having antimicrobial properties from the recent past. The detailed SAR outcomes will benefit towards leading optimization during the discovery and development of novel antimicrobial therapeutics.

Abstract Background Rice is a drought susceptible crop. A symbiotic association between rice and mycorrhizal fungi could effectively protect the plant against sudden or frequent episodes of drought. Due to its extensive network of hyphae, the endophyte is able to deeply explore the soil and transfer water and minerals to the plant, some of them playing an important role in mitigating the effects of drought stress. Moreover, the endophyte could modify the expression of drought responsive genes and regulate antioxidants. Results Three rice genotypes, WC-297 (drought tolerant), Caawa (moderately drought tolerant) and IR-64 (drought susceptible) were inoculated with Piriformospora indica (P. indica), a dynamic endophyte. After 20 days of co-cultivation with the fungus, rice seedlings were subjected to 15% polyethylene glycol-6000 induced osmotic stress. P. indica improved the growth of rice seedlings. It alleviated the destructive effects of the applied osmotic stress. This symbiotic association increased seedling biomass, the uptake of phosphorus and zinc, which are functional elements for rice growth under drought stress. It boosted the chlorophyll fluorescence, increased the production of proline and improved the total antioxidant capacity in leaves. The association with the endophyte also up regulated the activity of the Pyrroline-5-carboxylate synthase (P5CS), which is critical for the synthesis of proline. Conclusion A mycorrhizal association between P. indica and rice seedlings provided a multifaceted protection to rice plants under osmotic stress (− 0.295 MPa).

Abiotic stress, particularly heat stress, affects various parts of the cotton plant and ultimately impacts the seed cotton yield. Different portions of a single cotton plant of a cultivar exhibit variable responses to stress during reproductive and vegetative phases. To test this hypothesis, physiological and morphological traits related to heat stress were observed for two flowering positions in 13 genotypes of upland cotton. These genotypes were sown in field conditions in triplicate following a randomized complete block design. Data were collected for pollen germination, pollen viability, cell membrane thermostability, chlorophyll content, boll weight, and boll retention for both the top and bottom branches of each genotype. The collected data were analyzed for the identification of variability within and between genotypes for these two flowering positions. Tukey’s test was applied to estimate the significance of differences between genotypes and positions within each genotype. Results showed that the two positions within the same plant statistically varied from each other. The bottom branches of the genotypes performed significantly better for all traits measured except boll weight. The genotype AA-933 performed best for pollen germination and boll retention, while CYTO-608 exhibited maximum pollen viability in both the bottom and top flower positions compared with other genotypes. Overall, MNH-1016 and CIM-602 showed better cell membrane thermostability and chlorophyll content, respectively. This intra-plant variability can be further exploited in breeding programs to enhance the stress tolerance capabilities of the resulting varieties.

Considering the current dramatic and fatal situation due to the high spreading of SARS-CoV-2 infection, there is an urgent unmet medical need to identify novel and effective approaches for prevention and treatment of Coronavirus disease (COVID 19) by re-evaluating and repurposing of known drugs. For this, tomatidine and patchouli alcohol have been selected as potential drugs for combating the virus. The hit compounds were subsequently docked into the active site and molecular docking analyses revealed that both drugs can bind the active site of SARS-CoV-2 3CLpro, PLpro, NSP15, COX-2 and PLA2 targets with a number of important binding interactions. To further validate the interactions of promising compound tomatidine, Molecular dynamics study of 100 ns was carried out towards 3CLpro, NSP15 and COX-2. This indicated that the protein-ligand complex was stable throughout the simulation period, and minimal backbone fluctuations have ensued in the system. Post dynamic MM-GBSA analysis of molecular dynamics data showed promising mean binding free energy 47.4633 ± 9.28, 51.8064 ± 8.91 and 54.8918 ± 7.55 kcal/mol, respectively. Likewise, in silico ADMET studies of the selected ligands showed excellent pharmacokinetic properties with good absorption, bioavailability and devoid of toxicity. Therefore, patchouli alcohol and especially, tomatidine may provide prospect treatment options against SARS-CoV-2 infection by potentially inhibiting virus duplication though more research is guaranteed and secured.