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Helicobacter pylori is one of the most prevalent bacteria, infecting more than 40% of the world’s population. Rising antibiotic resistance has created an urgent need for the discovery of novel therapeutic agents. One of the potent drug targets for H. pylori is shikimic acid pathway, which synthesizes chorismate, an essential precursor for various aromatic compounds necessary for the survival of microorganisms. This pathway is absent in humans but its inhibition is lethal to microorganisms. In this study, shikimate kinase, which catalyzes the fifth step of the shikimic acid pathway, was targeted as a receptor. Potential inhibitors were sourced from the North African Natural Product Database (NANPDB) and the East African Natural Product Database (EANPDB). The natural products were investigated using computational tools. Molecular docking was used to screen the natural products and molecular dynamics simulation was used to assess the dynamic stability of docked protein-ligand complexes. The docking protocol was validated by heavy-atom superimposition of the docked shikimate 3-phosphate onto its co-crystallized conformation. Out of approximately 6500 compounds, six compounds with binding energy ranging from −8.73 to −10.57 kcal/mol were selected from molecular docking. Selected compounds showed stability during 200 ns molecular dynamics simulation. These compounds displayed strong prospects for experimental investigation of possible antibiotics against H. pylori .

Zinc (Zn) is an essential micronutrient for plants and animals. Unfortunately, deficiency of Zn in humans has increased on a global scale. The main reason of this micronutrient deficiency is dietary intakes of food with low Zn levels. Adoption of biofortification approaches would result in Zn enrichment of target tissue to a considerable extent. However, there is a basic need to understand Zn absorption mechanisms in plants prior to exploitation of such practical approaches. Zn absorption is a complex physiological trait which is mainly governed by Zn transporters and metal chelators of plant system. Plant growth stage, edaphic factors, season etc. also influence Zn efficiency of particular species. Molecular studies in Zn hyperaccumulators have already demonstrated the participation of specific Zn transporters, vacuolar sequestration and detoxification mechanisms in maintenance of Zn homeostasis. These have been described in detail in present review and provide opportunities for utilization in biofortification programmes. However, issues such as lesser bioavailability of Zn in target organ, uptake of toxic divalent cations (Cd, Ni, Pb, As etc.) along with Zn, sink activity and dilution in Zn concentration in response to sink number etc. in biofortified crops need further investigation. In order to design novel strategy in biofortification programmes, future researches should focus on physiological performance and yield penalties in concerned crop, metabolic load in term of organic acid production and crosstalk of Zn with other mineral nutrients under low and high Zn conditions.

The increasing heavy metal contamination in agricultural soils has become a serious concern across the globe. The present study envisages developing microbial inoculant approach for agriculture in Zn contaminated soils. Potential zinc tolerant bacteria (ZTB) were isolated from zinc (Zn) contaminated soils of southern Rajasthan, India. Isolates were further screened based on their efficiency towards Zn tolerance and plant growth promoting activities. Four strains viz . ZTB15, ZTB24, ZTB28 and ZTB29 exhibited high degree of tolerance to Zn up to 62.5 mM. The Zn accumulation by these bacterial strains was also evidenced by AAS and SEM–EDS studies. Assessment of various plant growth promotion traits viz ., IAA, GA 3 , NH 3 , HCN, siderophores, ACC deaminase, phytase production and P, K, Si solubilization studies revealed that these ZTB strains may serve as an efficient plant growth promoter under in vitro conditions. Gluconic acid secreted by ZTB strains owing to mineral solubilization was therefore confirmed using high performance liquid chromatography. A pot experiment under Zn stress conditions was performed using maize ( Zea mays ) variety (FEM-2) as a test crop. Zn toxicity reduced various plant growth parameters; however, inoculation of ZTB strains alleviated the Zn toxicity and enhanced the plant growth parameters. The effects of Zn stress on antioxidant enzyme activities in maize under in vitro conditions were also investigated. An increase in superoxide dismutase, peroxidase, phenylalanine ammonia lyase, catalase and polyphenol oxidase activity was observed on inoculation of ZTB strains. Further, ZIP gene expression studies revealed high expression in the ZIP metal transporter genes which were declined in the ZTB treated maize plantlets. The findings from the present study revealed that ZTB could play an important role in bioremediation in Zn contaminated soils.

Worldwide, 40% population consumes wheat (Triticum aestivum L.) as a staple food that is low in zinc (Zn) content. Zn deficiency is a major micronutrient disorder in crop plants and humans worldwide, adversely impacting agricultural productivity, human health and socio-economic concern. Globally, the entire cycle of increasing the Zn concentration in wheat grains and its ultimate effect on grain yield, quality, human health & nutrition and socio-economic status of livelihood is less compared. So the present studies were planned to compare the worldwide studies for the alleviation of Zn malnutrition. Zn intake is affected by numerous factors from soil to crop, crop to food and food to humans. The post-harvest fortification, diversification in dietary habits, mineral supplementation and biofortification are various possible approaches to enhance the Zn concentration in food. The wheat grains Zn is influenced by the Zn application technique and time concerning crop developmental stages. The use of soil microorganisms mobilize unavailable Zn, and improve Zn assimilation, plant growth, yield and Zn content in wheat. Climate change can have an inverse impact on the efficiency of agronomic biofortification methods due to a reduction in grain-filling stages. Agronomic biofortification can improve Zn content, crop yield as well as quality and ultimately, have a positive impact on human nutrition, health and socioeconomic status of livelihood. Though bio-fortification research has progressed, some crucial areas are still needed to be addressed or improved to achieve the fundamental purpose of agronomic biofortification.

Seed priming is a state-of-the-art, low-cost, and environment-friendly strategy to improve seed germination, seed vigor, abiotic and biotic stress tolerance, and the yield of field and horticultural crops. Seed priming involves imbibing the seeds in a priming solution under a desired set of environmental conditions for a period followed by drying before the radicle protrusion. Several seed priming approaches including hydropriming, osmopriming, bio-priming, hormonal priming, nutrient priming, nanoparticle priming, and electropriming can be effectively employed under different environmental conditions to improve crop growth and stress resilience. Seed priming is known to trigger enzymatic, hormonal, physiological, transcriptomic, metabolomic, and proteomic regulations in seed embryos during seed germination and plant growth, which leads to faster and synchronized seed germination and higher abiotic and biotic stress tolerance in crop plants. Furthermore, seed priming can induce cross-tolerance between abiotic and biotic stressors and induce stress memory for higher resilience of the next generation to environmental stresses. The present review paper discusses the applications of seed priming in biotic and abiotic stress tolerance and the underlying abiotic and biotic stress tolerance physiological, biochemical, and molecular mechanisms of seed priming. Furthermore, we discuss the current challenges/bottlenecks in the widespread application of seed priming in crop production.

An ivory-coloured, motile, Gram-stain-negative bacterium, designated TW-1 T was isolated from oil-contaminated experimental soil in Kyonggi University. The phylogenetic analysis based on 16S rRNA gene sequence revealed, strain TW-1 T formed a lineage within the family Oxalobacteraceae and clustered as members of the genus Massilia . The closest members were M. pinisoli T33 T (98.8% sequence similarity), M. putida 6NM-7 T (98.6%), M. arvi THG-RS2O T (98.5%), M. phosphatilytica 12-OD1 T (98.3%) and M. niastensis 5516S-1 T (98.2%). The sole respiratory quinone is ubiquinone-8. The major cellular fatty acids are hexadeconic acid, cis -9, methylenehexadeconic acid, summed feature 3 and summed feature 8. The major polar lipids are phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. The DNA G + C content of the type strain is 66.3%. The average nucleotide identity (ANI) and in silico DNA–DNA hybridization (dDDH) relatedness values between strain TW-1 T and closest members were below the threshold value for species demarcation. The genome size is 7,051,197 bp along with 46 contigs and 5,977 protein-coding genes. The genome showed 5 putative biosynthetic gene clusters (BGCs) that are responsible for different secondary metabolites. Cluster 2 showed thiopeptide BGC with no known cluster blast, indicating TW-1 T might produce novel antimicrobial agent. The antimicrobial assessment also showed that strain TW-1 T possessed inhibitory activity against Gram-negative pathogens ( Escherichia coli and Pseudomonas aeruginosa ). This is the first report of the species in the genus Massilia which produces antimicrobial compounds. Based on the polyphasic study, strain TW-1 T represents novel species in the genus Massilia , for which the name Massilia antibiotica sp. nov. is proposed. The type strain is TW-1 T (= KACC 21627 T  = NBRC 114363 T ).

PurposeThis review of sediment source fingerprinting assesses the current state-of-the-art, remaining challenges and emerging themes. It combines inputs from international scientists either with track records in the approach or with expertise relevant to progressing the science.MethodsWeb of Science and Google Scholar were used to review published papers spanning the period 2013–2019, inclusive, to confirm publication trends in quantities of papers by study area country and the types of tracers used. The most recent (2018–2019, inclusive) papers were also benchmarked using a methodological decision-tree published in 2017.ScopeAreas requiring further research and international consensus on methodological detail are reviewed, and these comprise spatial variability in tracers and corresponding sampling implications for end-members, temporal variability in tracers and sampling implications for end-members and target sediment, tracer conservation and knowledge-based pre-selection, the physico-chemical basis for source discrimination and dissemination of fingerprinting results to stakeholders. Emerging themes are also discussed: novel tracers, concentration-dependence for biomarkers, combining sediment fingerprinting and age-dating, applications to sediment-bound pollutants, incorporation of supportive spatial information to augment discrimination and modelling, aeolian sediment source fingerprinting, integration with process-based models and development of open-access software tools for data processing.ConclusionsThe popularity of sediment source fingerprinting continues on an upward trend globally, but with this growth comes issues surrounding lack of standardisation and procedural diversity. Nonetheless, the last 2 years have also evidenced growing uptake of critical requirements for robust applications and this review is intended to signpost investigators, both old and new, towards these benchmarks and remaining research challenges for, and emerging options for different applications of, the fingerprinting approach.

Programmed cell death protein 1 (PD-1), expressed on tumor-infiltrating T cells, is a T cell exhaustion marker. The mechanisms underlying PD-1 upregulation in CD4 T cells remain unknown. Here we develop nutrient-deprived media and a conditional knockout female mouse model to study the mechanism underlying PD-1 upregulation. Reduced methionine increases PD-1 expression on CD4 T cells. The genetic ablation of SLC43A2 in cancer cells restores methionine metabolism in CD4 T cells, increasing the intracellular levels of S-adenosylmethionine and yielding H3K79me2. Reduced H3K79me2 due to methionine deprivation downregulates AMPK, upregulates PD-1 expression and impairs antitumor immunity in CD4 T cells. Methionine supplementation restores H3K79 methylation and AMPK expression, lowering PD-1 levels. AMPK-deficient CD4 T cells exhibit increased endoplasmic reticulum stress and Xbp1s transcript levels. Our results demonstrate that AMPK is a methionine-dependent regulator of the epigenetic control of PD-1 expression in CD4 T cells, a metabolic checkpoint for CD4 T cell exhaustion. The deprivation of amino acids in the tumor microenvironment affects T cell survival and activation. Here the authors show that reduced levels of methionine are associated with PD1 upregulation in CD4+ T cells and that methionine supplementation promotes CD4+ T cell dependent anti-tumor immune responses.

Background AMP-activated protein kinase (AMPK) is a metabolic sensor that maintains energy homeostasis. AMPK functions as a tumor suppressor in different cancers; however, its role in regulating antitumor immunity, particularly the function of regulatory T cells (Tregs), is poorly defined. Methods AMPKα1 fl/fl Foxp3 YFP-Cre , Foxp3 YFP-Cre , Rag1 −/− , and C57BL/6 J mice were used for our research. Flow cytometry and cell sorting, western blotting, immuno-precipitation, immuno-fluorescence, glycolysis assay, and qRT-PCR were used to investigate the role of AMPK in suppressing programmed cell death 1 (PD-1) expression and for mechanistic investigation. Results The deletion of the AMPKα1 subunit in Tregs accelerates tumor growth by increasing the expression of PD-1. Metabolically, loss of AMPK in Tregs promotes glycolysis and the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), a key enzyme of the mevalonate pathway. Mechanistically, AMPK activates the p38 mitogen-activated protein kinase (MAPK) that phosphorylates glycogen synthase kinase-3β (GSK-3β), inhibiting the expression of PD-1 in Tregs. Conclusion Our study identified an AMPK regulatory mechanism of PD-1 expression via the HMGCR/p38 MAPK/GSK3β signaling pathway. We propose that the AMPK activator can display synergic antitumor effect in murine tumor models, supporting their potential clinical use when combined with anti-PD-1 antibody, anti-CTLA-4 antibody, or a HMGCR inhibitor.

Widespread malnutrition of zinc (Zn), iodine (I), iron (Fe) and selenium (Se), known as hidden hunger, represents a predominant cause of several health complications in human populations where rice ( Oryza sativa L.) is the major staple food. Therefore, increasing concentrations of these micronutrients in rice grain represents a sustainable solution to hidden hunger. This study aimed at enhancing concentration of Zn, I, Fe and Se in rice grains by agronomic biofortification. We evaluated effects of foliar application of Zn, I, Fe and Se on grain yield and grain concentration of these micronutrients in rice grown at 21 field sites during 2015 to 2017 in Brazil, China, India, Pakistan and Thailand. Experimental treatments were: (i) local control (LC); (ii) foliar Zn; (iii) foliar I; and (iv) foliar micronutrient cocktail (i.e., Zn + I + Fe + Se). Foliar-applied Zn, I, Fe or Se did not affect rice grain yield. However, brown rice Zn increased with foliar Zn and micronutrient cocktail treatments at all except three field sites. On average, brown rice Zn increased from 21.4 mg kg–1 to 28.1 mg kg–1 with the application of Zn alone and to 26.8 mg kg–1 with the micronutrient cocktail solution. Brown rice I showed particular enhancements and increased from 11 μg kg–1 to 204 μg kg–1 with the application of I alone and to 181 μg kg–1 with the cocktail. Grain Se also responded very positively to foliar spray of micronutrients and increased from 95 to 380 μg kg–1. By contrast, grain Fe was increased by the same cocktail spray at only two sites. There was no relationship between soil extractable concentrations of these micronutrients with their grain concentrations. The results demonstrate that irrespective of the rice cultivars used and the diverse soil conditions existing in five major rice-producing countries, the foliar application of the micronutrient cocktail solution was highly effective in increasing grain Zn, I and Se. Adoption of this agronomic practice in the target countries would contribute significantly to the daily micronutrient intake and alleviation of micronutrient malnutrition in human populations.