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Artemisia argyi (A. argyi) is a medicinal plant belonging to the Asteraceae family and Artemisia genus. Flavonoids abundant in A. argyi are associated with anti-inflammatory, anticancer, and antioxidative effects. Eupatilin and jaceosidin are representative polymethoxy flavonoids with medicinal properties significant enough to warrant the development of drugs using their components. However, the biosynthetic pathways and related genes of these compounds have not been fully explored in A. argyi. This study comprehensively analyzed the transcriptome data and flavonoids contents from four different tissues of A. argyi (young leaves, old leaves, trichomes collected from stems, and stems without trichomes) for the first time. We obtained 41,398 unigenes through the de-novo assembly of transcriptome data and mined promising candidate genes involved in the biosynthesis of eupatilin and jaceosidin using differentially expressed genes, hierarchical clustering, phylogenetic tree, and weighted gene co-expression analysis. Our analysis led to the identification of a total of 7,265 DEGs, among which 153 genes were annotated as flavonoid-related genes. In particular, we were able to identify eight putative flavone-6-hydroxylase (F6H) genes, which were responsible for providing a methyl group acceptor into flavone basic skeleton. Furthermore, five O-methyltransferases (OMTs) gene were identified, which were required for the site-specific O-methylation during the biosynthesis of eupatilin and jaceosidin. Although further validation would be necessary, our findings pave the way for the modification and mass-production of pharmacologically important polymethoxy flavonoids through genetic engineering and synthetic biological approaches.

The metabolome of strawberries at harvest determines their storage capacity. Therefore, dynamics of volatile production during storage of strawberry cultivated under diverse drainage ratios, T1 (12.0%), T2 (25.3%), T3 (36.4%), and T4 (56.5%), were evaluated. Among the various non-target VOCs analysis, there were some groups including aldehydes, esters, and furans occupied over 5% with exhibiting high coefficient of determination (R2) following the days after storage (DAS). Aldehydes content decreased over the storage period, while the esters (methyl butanoate, methyl hexanoate, ethyl hexanoate, and benzyl acetate) and furanones (furaneol and mesifuran) were increased as representing aroma compounds in strawberry ripening. Even on the same day, it was investigated that the release of VOCs linked to fruit decay was delayed in the groups (T1 and T2) that were given relatively little water compared to T3 and T4. The hexanal and ethyl hexanoate as an over-ripened signal showed a rapid increase from 4 DAS to 5 DAS in T3 and T4, respectively, while T1 and T2 showed significant increase from 5 DAS to 6 DAS. Relatively slower over-ripening tendency of T1 and T2 was supported by changes of firmness, total soluble solid content, anthocyanin content, and antioxidant activity during storage. T1 and T2 showed higher antioxidant activity at the harvest time and lower anthocyanin accumulation than T3 and T4. The present study elucidated that the preharvest drainage changes during cultivation was involved in fruit quality during strawberry storage. Besides, volatilomics analysis depicted that T2 as an optimal ratio, could delay the occurrence of stress and senescence, and guaranteed the strawberry yield. In conclusion, this study provided evidence that the practical application of drainage ratios could improve horticultural product quality even with low water use and VOCs might be considered an early indicator for strawberry fruit shelf-life.

Rapid industrialization and global warming have threatened the plants with multiple abiotic stresses, such as heavy metals and drought stress. For crop cultivation, the conventional approach of cleaning the soils by excavation is very costly and not feasible for large scale. Establishing toxin-free and drought-resistant crops is a major challenge in the environment under natural and anthropogenic pressure. In the past decades, copper contamination of agricultural land has become an emerging concern. For dry land reclamation, several new strategies, including bioremediation (phytoremediation and microbial remediation), have been used. Owing to the potential of Cu hyperaccumulators, the current project aims to enhance the drought tolerance and the phytoremediation potential of Solanum lycopersicum L. with the inoculation of copper and 12% polyethylene glycol (PEG)–induced drought stress–tolerant endophytic fungus Porostereum spadiceum AGH786 under the combined stress of copper heavy metal and PEG-induced drought stress. When S. lycopersicum L. was watered with individual stress of copper (Cu) concentration (400 ppm) in the form of copper sulfate (CuSO4.5H2O), 12% PEG–induced drought stress and the combined stress of both negatively affected the growth attributes, hormonal, metabolic, and antioxidant potential, compared with control. However, the multistress-resistant AGH786 endophytic fungus ameliorated the multistress tolerance response in S. lycopersicum L. by positively affecting the growth attributes, hormonal, metabolic, and antioxidant potential, and by restricting the root-to-shoot translocation of Cu and inducing its sequestration in the root tissues of affected plants. AGH786-associated plants exhibited a reduction in the severity of copper (Cu) and drought stress, with higher levels of SlCOPT (Cu transporters) and SlMT (metallothionine) gene expressions in root and shoot tissues, indicating that AGH786 contributed to resistance to copper metal toxicity and drought stress in the host S. lycopersicum L.

Studies on glutamine (Gln) metabolism have illuminated the vital role of Gln in cellular functions and its potential as a biomarker for disease detection. Despite the increasing interest in Gln metabolism, in-depth evaluations are challenging owing to limitations of conventional Gln-measuring methods. Thus, we developed a ligand-induced dimerization-based sensor for Gln, termed Q-SHINE, by splitting a glutamine binding protein into two separate domains. Q-SHINE enables highly accurate and convenient measurement of Gln concentration in bio-fluid samples, and the detection range is optimal for physiological Gln levels. Genetically encoded Q-SHINE sensors could also visualize intracellular Gln levels and quantify cytoplasmic and mitochondrial Gln change in living cells, which enabled detection of various cell responses to extracellular Gln supplement.

Rapid industrialization and global warming have threatened the plants with multiple abiotic stresses, such as heavy metals and drought stress. For crop cultivation, the conventional approach of cleaning the soils by excavation is very costly and not feasible for large scale. Establishing toxin-free and drought-resistant crops is a major challenge in the environment under natural and anthropogenic pressure. In the past decades, copper contamination of agricultural land has become an emerging concern. For dry land reclamation, several new strategies, including bioremediation (phytoremediation and microbial remediation), have been used. Owing to the potential of Cu hyperaccumulators, the current project aims to enhance the drought tolerance and the phytoremediation potential of

Traveling wave solutions of reaction-diffusion equations are well-studied for Lipschitz continuous monostable and bistable reaction functions. These special solutions play a key role in mathematical biology and in particular in the study of ecological invasions. However, if there are more than two stable steady states, the invasion phenomenon may become more intricate and involve intermediate steps, which leads one to consider not a single but a collection of traveling waves with ordered speeds. In this paper we show that, if the reaction function is discontinuous at the stable steady states, then such a collection of traveling waves exists and even provides a special solution which we call a terrace solution. More precisely, we will address both the existence and uniqueness of the terrace solution.

Barley is a major cereal crop with a wide ecological range, and its lignocellulosic residues have the potential to be used as a feedstock for various purposes, including biofuel production. Lignocellulosic biomass is an abundant renewable source of carbon energy. However, its heterogeneous properties and intrinsic recalcitrance caused by cell wall lignification have lowered the biorefinery efficiency. The reduced lignin content and/or altered lignin structure have been desirable traits for lignocellulosic feedstock. We report the reduction of lignin content in barley by CRISPR/Cas9‐mediated mutagenesis of caffeic acid O‐methyltransferase 1 (HvCOMT1), the lignin biosynthetic gene responsible for lignin syringyl unit formation. The transgene‐free, homozygous HvCOMT1 mutant was generated and analyzed for its cell wall composition, saccharification efficiency, and bioethanol production performance. The mutant had 14% lower total lignin content and 34% higher fermentable glucose recovery rate, compared to the wild‐type (WT). The bioethanol concentration and yield from the hydrolysates of the mutant biomass were 14.3 g/L and 0.46 g/g total sugar, respectively. This result was 34% and 12% higher than those obtained from WT (10.7 g/L and 0.41 g/g total sugar). Under controlled environmental conditions, the overall growth performance of the HvCOMT1 mutant was similar to WT, with no distinct morphological variations between them. The HvCOMT1 mutant barley could offer improved quality lignocellulosic feedstock for efficient lignocellulosic biofuel production.

Korean ginseng is a source of functional foods and medicines; however, its productivity is hindered by abiotic stress factors, such as light. This study investigated the impacts of darkness and different light wavelengths on the metabolomics and anti-cancer activity of ginseng extracts. Hydroponically-grown Korean ginseng was shifted to a light-emitting diodes (LEDs) chamber for blue-LED and darkness treatments, while white fluorescent (FL) light treatment was the control. MCF-7 breast cancer and lipopolysaccharide (LPS)-induced BV-2 microglial cells were used to determine chemo-preventive and neuroprotective potential. Overall, 53 significant primary metabolites were detected in the treated samples. The levels of ginsenosides Rb1, Rb2, Rc, Rd, and Re, as well as organic and amino acids, were significantly higher in the dark treatment, followed by blue-LED treatment and the FL control. The dark-treated ginseng extract significantly induced apoptotic signaling in MCF-7 cells and dose-dependently inhibited the NF-κB and MAP kinase pathways in LPS-induced BV-2 cells. Short-term dark treatment increased the content of Rd, Rc, Rb1, Rb2, and Re ginsenosides in ginseng extracts, which promoted apoptosis of MCF-7 cells and inhibition of the MAP kinase pathway in BV-2 microglial cells. These results indicate that the dark treatment might be effective in improving the pharmacological potential of ginseng.

The development and promotion of biofortified foods plants are a sustainable strategy for supplying essential micronutrients for human health and nutrition. We set out to identify quantitative trait loci (QTL) associated with carotenoid content in cowpea sprouts. The contents of carotenoids, including lutein, zeaxanthin, and β-carotene in sprouts of 125 accessions were quantified via high-performance liquid chromatography. Significant variation existed in the profiles of the different carotenoids. Lutein was the most abundant (58 ± 12.8 mg/100 g), followed by zeaxanthin (14.7 ± 3.1 mg/100 g) and β-carotene (13.2 ± 2.9 mg/100 g). A strong positive correlation was observed among the carotenoid compounds (

Gray mold disease is one of the most frequently occurring diseases in strawberries. Given that it spreads rapidly, rapid countermeasures are necessary through the development of early diagnosis technology. In this study, hyperspectral images of strawberry leaves that were inoculated with gray mold fungus to cause disease were taken; these images were classified into healthy and infected areas as seen by the naked eye. The areas where the infection spread after time elapsed were classified as the asymptomatic class. Square regions of interest (ROIs) with a dimensionality of 16 × 16 × 150 were acquired as training data, including infected, asymptomatic, and healthy areas. Then, 2D and 3D data were used in the development of a convolutional neural network (CNN) classification model. An effective wavelength analysis was performed before the development of the CNN model. Further, the classification model that was developed with 2D training data showed a classification accuracy of 0.74, while the model that used 3D data acquired an accuracy of 0.84; this indicated that the 3D data produced slightly better performance. When performing classification between healthy and asymptomatic areas for developing early diagnosis technology, the two CNN models showed a classification accuracy of 0.73 with regards to the asymptomatic ones. To increase accuracy in classifying asymptomatic areas, a model was developed by smoothing the spectrum data and expanding the first and second derivatives; the results showed that it was possible to increase the asymptomatic classification accuracy to 0.77 and reduce the misclassification of asymptomatic areas as healthy areas. Based on these results, it is concluded that the proposed 3D CNN classification model can be used as an early diagnosis sensor of gray mold diseases since it produces immediate on-site analysis results of hyperspectral images of leaves.

The presence of nutritional and health-benefiting compounds has increased awareness of orphan leafy vegetables such as Cleome gynandra (CG), whose phytochemicals vary among accessions and organs during growth. This study investigated the polyphenol accumulation and antioxidant activities (AOA) of eight CG accessions from the vegetative stage to the seed set stage. Plants were separated into leaves and stem (LS), flowers, and silique organs, and extracts were analyzed for total phenolic content (TPC), total flavonoid content (TFC), rutin and astragalin content, and AOA using 2,2-diphenyl-1-picrylhydrazyl-hydrate (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS). There were significant interaction effects of growth stages and accessions that contributed to changes in compounds content and AOA. TPC accumulated in plant generative parts, whereas flavonoids accumulated in young plant organs. HPLC profiling revealed that rutin was the most abundant compound in all organs, with flowers having the highest levels, while astragalin was only found in flowers. Silique extracts, particularly accession KF-14, recorded the highest TPC, which corresponded to the strongest radical scavenging activity in ABTS and DPPH assays and a strong linear correlation. The germplasm contained accessions with significantly different and varying levels of bioactive compounds and AOA. These findings potentiate the exploitation of CG organs such as siliques for AOA, flowers for rutin and astragalin, and young shoots for flavonoids. Moreover, the significant accumulation of the compounds in particular accessions of the germplasms suggest that such superior accessions may be useful candidates in genetic breeding programs to improve CG vegetable.

The presence of nutritional and health-benefiting compounds has increased awareness of orphan leafy vegetables such as Cleome gynandra (CG), whose phytochemicals vary among accessions and organs during growth. This study investigated the polyphenol accumulation and antioxidant activities (AOA) of eight CG accessions from the vegetative stage to the seed set stage. Plants were separated into leaves and stem (LS), flowers, and silique organs, and extracts were analyzed for total phenolic content (TPC), total flavonoid content (TFC), rutin and astragalin content, and AOA using 2,2-diphenyl-1-picrylhydrazyl-hydrate (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS). There were significant interaction effects of growth stages and accessions that contributed to changes in compounds content and AOA. TPC accumulated in plant generative parts, whereas flavonoids accumulated in young plant organs. HPLC profiling revealed that rutin was the most abundant compound in all organs, with flowers having the highest levels, while astragalin was only found in flowers. Silique extracts, particularly accession KF-14, recorded the highest TPC, which corresponded to the strongest radical scavenging activity in ABTS and DPPH assays and a strong linear correlation. The germplasm contained accessions with significantly different and varying levels of bioactive compounds and AOA. These findings potentiate the exploitation of CG organs such as siliques for AOA, flowers for rutin and astragalin, and young shoots for flavonoids. Moreover, the significant accumulation of the compounds in particular accessions of the germplasms suggest that such superior accessions may be useful candidates in genetic breeding programs to improve CG vegetable.

Auxin is the reciprocal signaling molecule, which interferes with other phyto-hormonal and physiological processes during plant–microbes interaction. In this regard, Bipolaris spp., a growth-promoting endophytic fungus was used to inoculate pre-stressed Zea mays seedlings with yucasin (IAA inhibitor). The IAA-deficient host was heavily colonized by the endophyte that subsequently promoted the host growth and elevated the IAA levels with a peak value at 72 h. However, the seedling growth was inhibited later (i.e., at 120 h) due to the high levels of IAA that interfered with the activity of phytoalexins and brassinosteroids. Such interference also modulated the endophytic fungus from symbiotic to biotrophic pathogen that left the host plants defenseless.

Leaf angle and grain size are important agronomic traits affecting rice productivity directly and/or indirectly through modulating crop architecture. OsBC1, as a typical bHLH transcription factor, is one of the components comprising a complex formed with LO9-177 and OsBUL1 contributing to modulation of rice leaf inclination and grain size. In the current study, two homologues of OsBC1, OsBCL1 and OsBCL2 were functionally characterized by expressing them under the control of OsBUL1 promoter, which is preferentially expressed in the lamina joint and the spikelet of rice. Increased leaf angle and grain length with elongated cells in the lamina joint and the grain hull were observed in transgenic rice containing much greater gibberellin A3&nbsp, (GA3) levels than WT, demonstrating that both OsBCL1 and OsBCL2 are positive regulators of cell elongation at least partially through increased GA biosynthesis. Moreover, the cell elongation was likely due to cell expansion rather than cell division based on the related gene expression and, the cell elongation-promoting activities of OsBCL1 and OsBCL2 were functional in a dicot species, Arabidopsis.

Cowpea [Vigna unguiculata (L.) Walp] is a globally important food security crop. However, it is susceptible to pest and disease; hence, constant breeding efforts based on its diversity are required for its improvement. The present study aims to investigate the genetic diversity, population structure, and linkage disequilibrium (LD) among 274 cowpea accessions from different origins. A total of 3,127 single nucleotide polymorphism (SNP) markers generated using diversity array technology (DArT) was used. Population structure, neighbor‐joining clustering, and principal component analyses indicated three subpopulations within the germplasm. Results of STRUCTURE analysis and discriminant analysis of principal components (DAPC) were complementary in assessing the structuration of the diversity among the germplasm, with the grouping of the accessions improved in DAPC. Genetic distances of 0.005–0.44 were observed among accessions. Accessions from western and central Africa, eastern and central Africa, and Asia were predominant and distributed across all subpopulations. The subpopulations had fixation indexes of 0.48–0.56. Analysis of molecular variance revealed that within subpopulation variation accounted for 81% of observed genetic variation in the germplasm. The subpopulations mainly consisted of inbred lines (inbreeding coefficient = 1) with common alleles, although they were from different geographical regions. This reflects considerable seed movement and germplasm exchange between regions. The LD was characterized by low decay for great physical distances between markers. The LD decay distance varied among chromosomes with the average distance of 80–100 kb across the genome. Thus, crop improvement is possible, and the LD will facilitate genome‐wide association studies on quality attributes and critical agronomic traits in cowpea.

Leaf angle and grain size are important agronomic traits affecting rice productivity directly and/or indirectly through modulating crop architecture. OsBC1, as a typical bHLH transcription factor, is one of the components comprising a complex formed with LO9-177 and OsBUL1 contributing to modulation of rice leaf inclination and grain size. In the current study, two homologues of OsBC1, OsBCL1 and OsBCL2 were functionally characterized by expressing them under the control of OsBUL1 promoter, which is preferentially expressed in the lamina joint and the spikelet of rice. Increased leaf angle and grain length with elongated cells in the lamina joint and the grain hull were observed in transgenic rice containing much greater gibberellin A3 (GA3) levels than WT, demonstrating that both OsBCL1 and OsBCL2 are positive regulators of cell elongation at least partially through increased GA biosynthesis. Moreover, the cell elongation was likely due to cell expansion rather than cell division based on the related gene expression and, the cell elongation-promoting activities of OsBCL1 and OsBCL2 were functional in a dicot species, Arabidopsis.

Background: Ginseng (Panax ginseng Meyer) is an essential source of pharmaceuticals and functional foods. Ginseng productivity has been compromised by high light (HL) stress, which is one of the major abiotic stresses during the ginseng cultivation period. The genetic improvement for HL tolerance in ginseng could be facilitated by analyzing its genetic and molecular characteristics associated with HL stress. Methods: Genome-wide analysis of gene expression was performed under HL and recovery conditions in 1-year-old Korean ginseng (P. ginseng cv. Chunpoong) using the Illumina HiSeq platform. After de novo assembly of transcripts, we performed expression profiling and identified differentially expressed genes (DEGs). Furthermore, putative functions of identified DEGs were explored using Gene Ontology terms and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis. Results: A total of 438 highly expressed DEGs in response to HL stress were identified and selected from 29,184 representative transcripts. Among the DEGs, 326 and 114 transcripts were upregulated and downregulated, respectively. Based on the functional analysis, most upregulated and a significant number of downregulated transcripts were related to stress responses and cellular metabolic processes, respectively. Conclusion: Transcriptome profiling could be a strategy to comprehensively elucidate the genetic and molecular mechanisms of HL tolerance and susceptibility. This study would provide a foundation for developing breeding and metabolic engineering strategies to improve the environmental stress tolerance of ginseng. Keywords: High light stress, Panax ginseng, Photoinhibition, Photoprotection, Transcriptome analysis

The effect of salt treatment on Brassica carinata (BC) microgreens grown under different light wavelengths on glucosinolates (GLs) and phenolic compounds were evaluated. Quantifiable GLs were identified using ultra-high performance-quadrupole time of flight mass spectrometry. Extracts’ ability to activate antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)) was evaluated on human colorectal carcinoma cells (HCT116). Furthermore, BC compounds’ ability to activate expression of nuclear transcription factor-erythroid 2 related factor (Nrf2) and heme-oxygenase-1 (HO-1) proteins was examined using specific antibodies on HCT116 cells. Sinigrin (SIN) was the abundant GLs of the six compounds identified and its content together with total aliphatic GLs increased in saline conditions. Fluorescent (FL) and blue plus red (B1R1) lights were identified as stable cultivation conditions for microgreens, promoting biomass and glucobrassicin contents, whereas other identified individual and total indole GLs behaved differently in saline and non-saline environments. Blue light-emitting diodes and FL light in saline treatments mostly enhanced SIN, phenolics and antioxidant activities. The increased SOD and CAT activities render the BC microgreens suitable for lowering oxidative stress. Additionally, activation of Nrf2, and HO-1 protein expression by the GLs rich extracts, demonstrate their potential to treat and prevent oxidative stress and inflammatory disorders. Therefore, effective salt treatments and light exposure to BC microgreens present an opportunity for targeted regulation of growth and accumulation of bioactive metabolites.

Ganoderma lucidum extract is a potent traditional remedy for curing various ailments. Drying is the most important postharvest step during the processing of Ganoderma lucidum. The drying process mainly involves heat (36 h at 60 °C) and freeze-drying (36 h at −80 °C). We investigated the effects of different postharvest drying protocols on the metabolites profiling of Ganoderma lucidum using GC-MS, followed by an investigation of the anti-neuroinflammatory potential in LPS-treated BV2 microglial cells. A total of 109 primary metabolites were detected from heat and freeze-dried samples. Primary metabolite profiling showed higher levels of amino acids (17.4%) and monosaccharides (8.8%) in the heat-dried extracts, whereas high levels of organic acids (64.1%) were present in the freeze-dried samples. The enzymatic activity, such as ATP-citrate synthase, pyruvate kinase, glyceraldehyde-3-phosphatase dehydrogenase, glutamine synthase, fructose-bisphosphate aldolase, and D-3-phosphoglycerate dehydrogenase, related to the reverse tricarboxylic acid cycle were significantly high in the heat-dried samples. We also observed a decreased phosphorylation level of the MAP kinase (Erk1/2, p38, and JNK) and NF-κB subunit p65 in the heat-dried samples of the BV2 microglia cells. The current study suggests that heat drying improves the production of ganoderic acids by the upregulation of TCA-related pathways, which, in turn, gives a significant reduction in the inflammatory response of LPS-induced BV2 cells. This may be attributed to the inhibition of NF-κB and MAP kinase signaling pathways in cells treated with heat-dried extracts.

Plants are susceptible to various environmental constrains, including heat stress due to their sessile nature. Endophytic fungi can be used as a novel technique to protect crop plants against the injurious effects of thermal stress. Endophytic fungi were isolated from Adiantum capillus-veneris L. and tested against heat stress in Glycine max L. and Helianthus annuus L. The results exhibited increased levels of the plant’s chlorophyll, height and biomass in Aspergillus foetidus (AdR-13) inoculated host crop species. Conversely, a significant decrease in lipid peroxidation and reactive oxygen species (ROS) production was noted in A. foetidus-associated host crop species. Likewise, the amounts of ROS-degrading antioxidants (glutathione reductase (GR), peroxidase (POD), ascorbic acid oxidase (AAO), superoxide dismutase (SOD), catalase (CAT)) as well as phenolics were increased, while the amounts of proline and abscisic acid (ABA) were decreased in fungal-associated test crops. Total lipids, proteins and sugars were noted to be high in A. foetidus-associated test crops. From the results, we concluded that A. foetidus have a role in heat stress mitigation that might help to sustain the production of important crops in the future.

Heavy metal contamination due to anthropogenic activities is a great threat to modern humanity. A novel and natural technique of bioremediation using microbes for detoxification of heavy metals while improving plants’ growth is the call of the day. In this study, exposing soybean plants to different concentrations (i.e., 10 and 50 ppm) of chromium and arsenic showed a severe reduction in agronomic attributes, higher reactive oxygen species production, and disruption in the antioxidant system. Contrarily, rhizobacterial isolate C18 inoculation not only rescued host growth, but also improved the production of nonenzymatic antioxidants (i.e., flavonoids, phenolic, and proline contents) and enzymatic antioxidants i.e., catalases, ascorbic acid oxidase, peroxidase activity, and 1,1-diphenyl-2-picrylhydrazyl, lower reactive oxygen species accumulation in leaves. Thereby, lowering secondary oxidative stress and subsequent damage. The strain was identified using 16 S rDNA sequencing and was identified as Pseudocitrobacter anthropi. Additionally, the strain can endure metals up to 1200 ppm and efficient in detoxifying the effect of chromium and arsenic by regulating phytohormones (IAA 59.02 µg/mL and GA 101.88 nM/mL) and solubilizing inorganic phosphates, making them excellent phytostimulant, biofertilizers, and heavy metal bio-remediating agent.

Frankincense tree (Boswellia sacra Fluek) has been poorly known on how it responds to tapping and wound-recovery process at molecular levels. Here, we used RNA-sequencing analysis to profile transcriptome of B. sacra after 30 min, 3 h and 6 h of post-tapping. Results showed 5525 differentially expressed genes (DEGs) that were related to terpenoid biosynthesis, phytohormonal regulation, cellular transport, and cell-wall synthesis. Plant-growth-regulators were applied exogenously which showed regulation of endogenous jasmonates and resulted in rapid recovery of cell-wall integrity by significantly up-regulated gene expression of terpenoid biosynthesis (germacrene-D synthase, B-amyrin synthase, and squalene epioxidase-1) and cell-wall synthesis (xyloglucan endotransglucosylase, cellulose synthase-A, and cell-wall hydrolase) compared to control. These findings suggest that tapping immediately activated several cell-developmental and regeneration processes, alongwith defense-induced terpenoid metabolism, to improve the healing process in epidermis. Exogenous growth regulators, especially jasmonic acid, can drastically help tree recovery from tissue degeneration and might help in tree conservation purposes.

CD4+ T cells are crucial for the pathogenesis of rheumatoid arthritis (RA). Here, we evaluated gene expression in CD4+ T cells in early RA, and main purpose of present study was to seek the changes in CD4+ T-cell-related cytokines according to RA progression.Early RA was defined as methotrexate (MTX)-naïve patients. Established RA was defined as patients with more than 6 months of DMARDs. Patients with osteoarthritis were evaluated as controls. Microarray analysis was used to identify overexpressed genes in CD4+ T cells, and RT-qPCR was used to validate. Plasma cytokine were measured in patients with early and established RA, and correlations with disease activity were assessed in patients with early RA, whereas clinical prognosis was assessed in established patients with RA.Thirty-four genes showed overexpression in CD4+ T cells from patients with early RA compared with OA controls. Nineteen were related to interferon (IFN)-γ, and eight were related to interleukin (IL)-17A. Plasma levels of IL-17A, IL-6, IL-12, and TNF-α correlated with IFN-γ, and correlation coefficient was highest between DAS28-ESR and plasma IFN-γ levels in patients with early RA (Rho=0.553, p=0.0025). In established RA with low disease activity, drug reduction group showed lower plasma IFN-γ and IL-17A than drug maintenance/relapse group (13.61±5.75 vs. 29.89±18.72, p0.001; and 10.91±3.92 vs. 21.04±12.81 pg/mL, p0.001, respectively).The IFN-γ and IL-17 gene signature in CD4+ T cells was significantly increased in early RA. Patients with established RA with low levels of IFN-γ and IL-17A could be eligible for dose reduction.

Background: Genetic diversity in a germplasm is crucial for continuous improvement of crop varieties. A panel of 274 cowpea (Vigna unguiculata L.) accessions of unknown genetic diversity was assembled from diverse sources. This study used 3127 SNP markers, generated with the diversity array technology (DArT), to assess genetic diversity, population structure and linkage disequilibrium (LD) in the assembled germplasm.Results: The structure analysis inferred three subpopulations within the germplasm, which was confirmed by Neighbour-Joining (NJ) clustering and principal component analysis (PCA). Low genetic distances (0.005 to 0.44) were observed between accessions. Accessions from Africa; West and Central Africa (113 accessions), East and Central Africa (93 accessions), and Asia (53 accessions) were predominant in the germplasm; and distributed across all subpopulations. High fixation indexes (0.48 ≤ FST≤0.56) were obtained for the inferred subpopulations. AMOVA revealed a very large contribution (99%) of within subpopulations variation to the observed genetic variation in the germplasm. However, the expected heterozygosity (He) was higher than the observed heterozygosity (Ho), indicating high proportion of inbred lines in the germplasm. Linkage Disequilibrium (LD) was observed in the germplasm, particularly on chromosome 6, which showed a low decay along the physical genetic distance between markers in the genome.Conclusions: Significant genetic structuration exists in the assembled cowpea germplasm which shows there is a potential for improvement of the crop. The subgroups consisted mainly of inbred lines which, although from different geographical regions shared alleles in common reflecting high movement of seeds and exchange of germplasm between regions. The presence of linkage disequilibrium in the germplasm paves a way for prospective whole genome-wide association studies in cowpea for quality attributes and important agronomic traits.

Background: CD4+ T cells are crucial for the pathogenesis of rheumatoid arthritis (RA). The roles of gene overexpression in CD4+ T cells and the predictive roles of Th1- and Th17-related cytokines have not been clearly defined in patients with RA. Here, we investigated gene expression levels in CD4+ T cells in methotrexate (MTX)-naïve early RA (eRA) and evaluated changes in CD4+ T-cell-related cytokines during eRA. Methods: Patients with anti-citrullinated protein antibody (ACPA)-positive MTX-naïve eRA were recruited. Patients with osteoarthritis were evaluated as controls. Microarray analysis was used to identify overexpressed genes in CD4+ T cells, and reverse transcription quantitative polymerase chain reaction was used to validate the identified genes. Plasma cytokine levels were measured, and correlations with disease activity were assessed.Results: Thirty-four genes showed overexpression in CD4+ T cells from patients with ACPA-positive MTX-naïve eRA compared with controls. Nineteen were related to interferon (IFN)-γ, and nine were related to interleukin (IL)-17A; five were related to both IFN-γ and IL-17A. Plasma levels of five cytokines were elevated in the ACPA-positive MTX-naïve eRA group compared with those in the control group, and C-X-C motif chemokine ligand 10 was significantly elevated in the ACPA-positive MTX-naïve eRA group compared with that in the established active RA and OA groups. In established RA with low disease activity, the drug-free remission group/drug reduction group showed significantly lower IFN-γ and IL-17A levels than the drug maintenance group and relapse after drug reduction group. Conclusion: Our T2 research of IFN-γ emphasized that, not only the Th17 immune response, but the Th1 immune response is also very important for the RA pathogenesis. Concurrent increase in IFN-γ and IL-17 were observed in active stage of ACPA-positive MTX-naïve eRA, and the plasma levels of them could be useful for new clinical biomarkers before and/or after treatment of RA.

Hydroponic plant culturing requires the concentration of nutrients in the supplied solution to be maintained at a constant level. For example, phosphate ion concentration directly affects crop growth, which necessitates the development of convenient and rapid techniques for on-site phosphate quantitation. Herein, we developed a new low-cost colorimetric method of quick on-site phosphate quantitation based on a modification of the conventional molybdenum colorimetric method. Specifically, the nutrient solution treated with ascorbic acid and molybdate was analyzed by colorimetric method after 10 min incubation, and a phosphate quantitation protocol was proposed. To verify this protocol, 50 nutrient solution samples with concentrations of 0–200 ppm were used to develop a model and perform a validation experiment, and the PLSR (Partial Least Squares Regression) and PCR (Principal Component Regression) models were developed and validated using a crossvalidation method and sample transmission spectra. The PLSR model, employing smoothing preprocessing at a 5 nm wavelength spacing, exhibited the best prediction performance and showed an error of ~10% within the measurement range during verification. In addition, an artificial neural network-based model achieved R2=0.93 for the training set and R2=0.86 for the validation set. Finally, we developed convenient-to-use software for phosphate ion quantitation by the presented method and performed a demonstration test.

Rootstock variety influences leaf metabolic profiles in a grafted citrus tree, but influence also depends on the scion. Proper selection of rootstocks in tree fruit crops such as citrus is important for successful production. Despite a large number of commercially available rootstocks, studies have mostly been limited to basic horticultural observations. We used untargeted gas chromatography-time of flight-mass spectrometry (GC-TOF MS) based metabolomics to understand the biochemical influence of rootstock on 2-year-old field-grown ‘Cara Cara’ navel orange (Citrus sinensis L. Osbeck) and ‘Hirado Buntan’ pummelo (C. grandis L. Osbeck) trees grown on four rootstock cultivars with different genetic background. Five hundred unique metabolites were quantified in all trees, of which 147 were chemically identified. In navel orange trees, 48 root metabolites differed significantly in concentrations among rootstocks, compared with 29 metabolites in pummelo trees. In navel orange trees, raffinose, conduritol beta-epoxide, allantoic acid, myo-inositol, gamma-tocopherol, and beta gentiobiose were among the compounds that contributed most to this variation. In pummelo trees, hexitol, allantoic acid, glucoheptulose, tryptophan, gamma-tocopherol, glycerol-3-galactoside, and raffinose were among the most discriminating metabolites, but only allantoic acid passed significance criteria. Rootstock was also found to influence the quantities of 226 metabolites in leaves of the navel orange scion. Conduritol-beta-epoxide and myo-inositol were among the metabolites most influenced by rootstock. In contrast, the influence of rootstock on the pummelo scion was less prominent, with only six metabolites displaying significant differences. Our findings demonstrate that rootstock variety can influence the metabolic profile of the leaves in a grafted tree, but that the extent of the effect is also influenced by the scion. The majority of root metabolites that discriminated most between rootstocks did not display the same rootstock-specific discrimination in the leaves, suggesting tissue specificity or limited movement across the graft union.

The effect of salt treatment on Brassica carinata (BC) microgreens grown under different light wavelengths on glucosinolates (GLs) and phenolic compounds were evaluated. Quantifiable GLs were identified using ultra-high performance-quadrupole time of flight mass spectrometry. Extracts’ ability to activate antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)) was evaluated on human colorectal carcinoma cells (HCT116). Furthermore, BC compounds’ ability to activate expression of nuclear transcription factor-erythroid 2 related factor (Nrf2) and heme-oxygenase-1 (HO-1) proteins was examined using specific antibodies on HCT116 cells. Sinigrin (SIN) was the abundant GLs of the six compounds identified and its content together with total aliphatic GLs increased in saline conditions. Fluorescent (FL) and blue plus red (B1R1) lights were identified as stable cultivation conditions for microgreens, promoting biomass and glucobrassicin contents, whereas other identified individual and total indole GLs behaved differently in saline and non-saline environments. Blue light-emitting diodes and FL light in saline treatments mostly enhanced SIN, phenolics and antioxidant activities. The increased SOD and CAT activities render the BC microgreens suitable for lowering oxidative stress. Additionally, activation of Nrf2, and HO-1 protein expression by the GLs rich extracts, demonstrate their potential to treat and prevent oxidative stress and inflammatory disorders. Therefore, effective salt treatments and light exposure to BC microgreens present an opportunity for targeted regulation of growth and accumulation of bioactive metabolites.

Ganoderma lucidum extract is a potent traditional remedy for curing various ailments. Drying is the most important postharvest step during the processing of Ganoderma lucidum. The drying process mainly involves heat (36 h at 60 °C) and freeze-drying (36 h at −80 °C). We investigated the effects of different postharvest drying protocols on the metabolites profiling of Ganoderma lucidum using GC-MS, followed by an investigation of the anti-neuroinflammatory potential in LPS-treated BV2 microglial cells. A total of 109 primary metabolites were detected from heat and freeze-dried samples. Primary metabolite profiling showed higher levels of amino acids (17.4%) and monosaccharides (8.8%) in the heat-dried extracts, whereas high levels of organic acids (64.1%) were present in the freeze-dried samples. The enzymatic activity, such as ATP-citrate synthase, pyruvate kinase, glyceraldehyde-3-phosphatase dehydrogenase, glutamine synthase, fructose-bisphosphate aldolase, and D-3-phosphoglycerate dehydrogenase, related to the reverse tricarboxylic acid cycle were significantly high in the heat-dried samples. We also observed a decreased phosphorylation level of the MAP kinase (Erk1/2, p38, and JNK) and NF-κB subunit p65 in the heat-dried samples of the BV2 microglia cells. The current study suggests that heat drying improves the production of ganoderic acids by the upregulation of TCA-related pathways, which, in turn, gives a significant reduction in the inflammatory response of LPS-induced BV2 cells. This may be attributed to the inhibition of NF-κB and MAP kinase signaling pathways in cells treated with heat-dried extracts.

This study was aimed at investigating the therapeutic effects of BITRAP, a bispecific fusion protein targeting TNF-α and IL-21, on the development of autoimmune arthritis in humans and mice. To verify the effects of BITRAP in human, peripheral blood mononuclear cells were cultured with BITRAP under IL-17-producing T (Th17) cell-polarizing conditions or osteoclast differentiation conditions. BITRAP treatment inhibited the production of IL-17 and vascular endothelial growth factor but increased the production of IL-10 in CD4+ T cells, as well as directly suppressed osteoclastogenesis. Collagen-induced arthritis (CIA) and IL-1R antagonist (IL-1Ra) knockout mice were treated with BITRAP. Following injection in CIA mice, BITRAP rapidly migrated into the inflamed joints and remained there for 72 hours. Application of BITRAP attenuated the severity of autoimmune arthritis in CIA and IL-1Ra knockout mice by reducing the numbers of inflammatory cytokine-expressing cells and Th17 cells and antibody secretion. Finally, BITRAP suppressed STAT3 phosphorylation, as well as production of IL-17 and TNF-α, in murine splenic CD4+ T cells. These findings suggest that BITRAP, a bispecific fusion protein targeting TNF-α and IL-21, may be an effective treatment to overcome the limitations of anti-TNF therapy for patients with rheumatoid arthritis.

The dried Ganoderma lucidum (GL) has been widely used for its pharmacological properties and bioactive ganoderic acids (GAs). Herein, extraction procedures combining ultra-sonication and heating were optimized using response surface methodology based on four variables (antioxidant activity, anti-diabetic activity, total GAs content, and total polysaccharide content) and principal component analysis. The extraction of freeze-dried GL at temperatures between 64.2 and 70 °C for 1.2 h maximized the antioxidant activity and GA content, whereas the polysaccharide content and anti-diabetic activity were maximized by extraction between 66.8 and 70 °C for more than 2.8 h. Heat-dried GL extracted at 50 °C for 3 h provided the greatest anti-inflammatory activity against HaCaT cells by suppressing the response to inflammation related cytokines at mRNA levels. These results suggest that extraction conditions might be a limiting factor for target-oriented investigations, and optimized extraction methods may improve the potential effect and quality of harvested GL products.

A revertible discrete velocity kinetic model is introduced when the environment is spatially heterogeneous. It is proved that the parabolic scale singular limit of the model exists and satisfies a new heterogeneous diffusion equation that depends on the diffusivity and the turning frequency together. An energy functional is introduced which takes into account spatial heterogeneity in the velocity field. The monotonicity of the energy functional is the key to obtain uniform estimates needed for the weak convergence proof. The Div-Curl lemma completes the strong convergence proof.

IL-12p40 homodimer, a natural antagonist of IL-12 and IL-23, performs an important role in the expression of proinflammatory cytokines that is essential for Th1 and Th17 immune responses. Here, we reveal the therapeutic and immunosuppressive effect of the IL-12p40 subunit ((p40)2-Fc) in an experimental autoimmune arthritis model. We hypothesized that (p40)2-Fc may reduce the inflammatory response and the activation of T cells. In this study, we intraperitoneally injected (p40)2-Fc into collagen induced arthritis (CIA) mice to identify whether (p40)2-Fc attenuates CIA severity. (p40)2-Fc reduced the development of CIA, joint inflammation and cartilage destruction. (p40)2-Fc also significantly decreased the concentration of serum immunoglobulin as well as the number of T cells and C II specific T cells. In addition, osteoclastogenesis in (p40)2-Fc treated mice was down-regulated compared to the mice treated with (p40)2-Fc control. We observed that (p40)2-Fc treatment alleviates arthritis in mice with CIA, reducing inflammation and osteoclast differentiation. These findings suggest that (p40)2-Fc can be a potential therapeutic approach for autoimmune arthritis.

Pulmonary thromboembolism (PTE) is rarely reported in Behçet's disease (BD) due to its distinctive thrombus-forming mechanism. In BD, the inflammation on vessel walls causes venous thrombosis. The thrombi are considered to be tethered to the inflamed walls making embolization less frequent. Thus, immunosuppressive agents are the mainstay of treatment. However, the necessity of anticoagulation therapy is controversial because of its uncertain efficacy of resolving thrombi and the possibility of fatal side effects of hemorrhage. A 25-year-old man with recurrent oral aphthae visited with abrupt onset of dyspnea and chest pain. Based on history, imaging studies and laboratory results, he was diagnosed with BD with vascular involvement and antiphospholipid syndrome (APS), causing PTE from deep vein thrombosis. The co-existing APS may have further promoted the thrombosis, shifting his blood profile toward the hypercoagulable state. Immunosuppressive therapy with glucocorticoid and azathioprine, and concomitant anticoagulation with warfarin were achieved successfully without any fatal complications. When atypical features of vascular involvement in BD develop, other coexisting diseases should be considered to design an optimal therapeutic plan.

Ginseng is a perennial herb used as valuable traditional medicine for more than three thousand years. Ginsenosides are the major group of pharmacologically active components of ginseng, and they are effective against various diseases. Present study was designed to investigate the impact of foliar silicon sprays on growth characteristics, physiological traits, and pharmaceutical quality of 6-year-old ginseng plants. Three different concentrations i.e. 50 mg/L, 100 mg/L, and 200 mg/L of Si was used as foliar treatment. Compared to control, stem hardness was enhanced up to 54% in 100 mg/L treatment followed by 38% in 50 mg/L and 36% in 200 mg/L. SEM analysis showed that the density of epidermal cells was 21-25% higher in Si-treated plants than that in the control plants. Cuticle thickness was found higher in Si treated plants as compared to control. Overall a total of 25%, 38%, and 54% of cuticle thickness and 43%, 49%, and 63% ginseng roots production was observed in plants treated with Si treatment of 50 mg/L, 100 mg/L, and 200 mg/L, respectively. Results suggest that out of three different concentrations of Si treatments, 200 mg/L found to be most effective in overall higher Si content in leaves with thick cuticle and higher root production, 100 mg/L treatment showed high photosynthesis rate followed by stomatal conductance, chlorophyll content and stem hardness. 50 mg/L was found to be least effective. Out of 12 ginsenosides analyzed in 6-year-old ginseng roots, the most common were AP, Rg1, Rb1, and Re. The content of ginsenosides per gram of ginseng roots did not show any significant differences among treatments, but overall, ginsenosides contents were higher in Si-treated plants because of increased root growth triggered by increased Si level. Our study show that the application of aerial sprays with elevated Si levels increases the growth, promotes the physiological and morphological traits and increases the yield of 6-year-old ginseng plants. In addition, this study implied the importance of Si for commercial production of high-quality ginseng roots.

Glucosinolates (GSs) are common anionic plant secondary metabolites in the order Brassicales. Together with glucosinolate hydrolysis products (GSHPs), they have recently gained much attention due to their biological activities and mechanisms of action. We review herein the health benefits of GSs/GSHPs, approaches to improve the plant contents, their bioavailability and bioactivity. In this review, only literature published between 2010 and March 2020 was retrieved from various scientific databases. Findings indicate that these compounds (natural, pure, synthetic, and derivatives) play an important role in human/animal health (disease therapy and prevention), plant health (defense chemicals, biofumigants/biocides), and food industries (preservatives). Overall, much interest is focused on in vitro studies as anti-cancer and antimicrobial agents. GS/GSHP levels improvement in plants utilizes mostly biotic/abiotic stresses and short periods of phytohormone application. Their availability and bioactivity are directly proportional to their contents at the source, which is affected by methods of food preparation, processing, and extraction. This review concludes that, to a greater extent, there is a need to explore and improve GS-rich sources, which should be emphasized to obtain natural bioactive compounds/active ingredients that can be included among synthetic and commercial products for use in maintaining and promoting health. Furthermore, the development of advanced research on compounds pharmacokinetics, their molecular mode of action, genetics based on biosynthesis, their uses in promoting the health of living organisms is highlighted.

Rheumatology was first recognized as a distinct clinical specialty in Korea just 35 years ago. Young professors who were trained in rheumatology in the USA and afterwards returned to Korea contributed substantially to advances in rheumatology clinical practice, educational programmes and research activities. They also established the Korean Rheumatism Association, later renamed the Korean College of Rheumatology. These young rheumatologists had a major role not only in raising the level of clinical and scientific activities, but also in promoting academic exchanges around the Asia-Pacific region, the USA and Europe. Subsequently, Korea's rapid economic growth and high education level enabled rheumatology to advance rapidly. Today, continued efforts are required to raise the standard of clinical and basic research, to optimize clinical practice with regard to new biologic agents, to exploit personalized and targeted therapies for the rheumatic diseases, and to meet the medical demands of Korea's ageing society.

Objectives Pulmonary arterial hypertension (PAH) is a major cause of mortality in connective tissue disease (CTD). The survival rates and mortality-predictive factors of a nationwide registry of Korean patients with CTD-PH measured by echocardiography were determined. Methods Patients with CTD-PH were enrolled between April 2008 and December 2012. Hemodynamic parameters and clinical data (WHO-functional class [FC], organ involvement, laboratory tests and treatment agents) were recorded. Survival rates were calculated by using the Kaplan–Meier method. Mortality-associated factors were examined by Cox proportional hazards regression analysis. Results In total, 174 incident PH cases (61 with systemic lupus erythematosus, 50 with systemic sclerosis, 10 with mixed CTD, 22 with rheumatoid arthritis (RA) and 31 with other CTDs) were diagnosed by Doppler echocardiography. Of these, 25 (14%) died during the 3.8 ± 2.7 year follow-up period after PH diagnosis. The 1- and 3-year survival rates were 90.7% and 87.3%, respectively. Compared to the other CTD-PHs, RA-PH had the lowest survival rates (56% 3 year survival; P = 0.022). Multiple regression analysis revealed that low diffusion capacity of carbon monoxide (DLCO), pleural effusion and diabetes mellitus were poor prognostic factors (P = 0.008, 0.04 and 0.009, respectively). Anti-UI-RNP (ribonucleoprotein) antibody positivity was protective (P = 0.022). In patients with WHO-FC III/IV, patients who received vasodilators had lower mortality than those who did not (P = 0.038). Conclusions In Korean patients with CTD-PH, the 3-year survival rate was 87%. Low diffusion capacity of carbon monoxide (DLCO), pleural effusion and diabetes mellitus were independent poor prognostic factors. Anti-UI-RNP antibody was protective. Prompt PAH-specific vasodilator therapy may improve the survival of patients with severe CTD-PH.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that is characterized by the generation of immune responses to various nuclear components. Impaired clearance of apoptotic cells and loss of tolerance to self-antigens are involved both in the initiation and in the propagation of the disease. Dendritic cells (DCs) are key factors in the balance between autoimmunity and tolerance and play a role linking innate and adaptive immunity. DCs, particularly plasmacytoid DCs (pDCs), are the main source of type I interferon (IFN) cytokines, which contribute to the immunopathogenesis of SLE. There is accumulating evidence that pDCs and type I IFN cytokines take the leading part in the development of SLE. In this review, we discuss recent data regarding the role of pDCs and type I IFN cytokines in the pathogenesis of SLE and the potential for employing therapies targeting against aberrant regulation of the pDC-type I IFN axis for treating SLE.

Transcriptional analysis that uncovers fruit ripening-related gene regulatory networks is increasingly important to maximize quality and minimize losses of economically important fruits such as plums. RNA sequencing (RNA-Seq) and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) are important tools to perform high-throughput transcriptomics. The success of transcriptomics depends on the high-quality transcripts from polyphenolic- and polysaccharide-enriched plum fruits, whereas reliability of quantification data relies on accurate normalization using suitable reference gene(s). We optimized a procedure for high-quality RNA isolation from vegetative and reproductive tissues of climacteric and non-climacteric plum cultivars and conducted high-throughput transcriptomics. We identified 20 candidate reference genes from significantly non-differentially expressed transcripts of RNA-Seq data and verified their expression stability using qRT-PCR on a total of 141 plum samples which included flesh, peel, and leaf tissues of several cultivars collected from three locations over a 3-year period. Stability analyses of threshold cycle (C T) values using BestKeeper, delta (Δ) CT, NormFinder, geNorm, and RefFinder software revealed S AND protein-related trafficking protein (MON), elongation factor 1 alpha (EF1α), and initiation factor 5A (IF5A) as the best reference genes for precise transcript normalization across different tissue samples. We monitored spatiotemporal expression patterns of differentially expressed transcripts during the developmental process after accurate normalization of qRT-PCR data using combination of two best reference genes. This study also offers a guideline to select best reference genes for future gene expression studies in other plum cultivars.

Aim The aim of this study was to investigate the incidence of tuberculosis (TB) following anti-tumor necrosis factor (TNF) therapy in an intermediate TB burden area and to compare the risk between drugs and diseases. Methods The data were obtained from a nationwide database maintained by the Health Insurance Review and Assessment Service. The study population comprised of patients who were prescribed with TNF inhibitors from 2005 to 2009. TB cases were selected based on prescription of anti-TB medications. Results Of 8421 patients in the study population, 1729 patients with latent TB prophylaxis were identified and 102 patients developed TB. The incidence of TB was 1017 per 100 000 person-years. When divided into four groups according to the main diagnosis and using an ankylosing spondylitis group as a reference, the incidence of TB was highest in patients with inflammatory bowel disease (IBD) (incidence rate ratio [IRR] 5.97, 95% confidence interval [CI] 3.34–10.66), followed by patients with rheumatoid arthritis (IRR 1.02, 95% CI 0.57–1.83) and those with psoriatic arthritis (IRR 1.00, 95% CI 0.14–7.30). Comparison between drugs showed a significantly lower incidence of TB in patients treated with etanercept (reference), highest incidence in those treated with infliximab (IRR 6.8, 95% CI 3.74–12.37) and an intermediate incidence in patients treated with adalimumab (IRR 3.45, 95% CI 1.82–6.55). Conclusions The difference in TB risk between TNF inhibitors was similar with countries of low TB burden. This study suggests that particular attention is required for patients treated with TNF monoclonal antibodies.

Ethnomedicinal knowledge of plant-derived bioactives could help us in discovering new therapeutic compounds of great potential. Certainly, dandelion has been used in traditional ethno-medicinal systems (i.e., Chinese, Arabian, Indian, and Native American) to treat different types of cancer. Though, dandelion is highly vigorous, but the potential mode of action is still unclear. In the current study, the antiproliferative activity of methanolic extracts of dandelion root (MEDr) on cell viability of HepG2, MCF7, HCT116, and normal Hs27 was investigated. It was observed that MEDr (500 μg/mL) drastically decreased the growth of HepG2 cell line, while the effect on MCF7 and HCT116 cell lines was less pronounced and no effect has been observed in Hs27 cell lines. The MEDr also enhanced the phosphorylation level of AMPK of HepG2 cells, which considered crucial in cancer treatment and other metabolic diseases. The AMPK activation by MEDr noticed in the current study has never been reported previously. The results regarding the number of apoptotic cells (HepG2 cells) were in line with the cell viability test. The current observations clearly demonstrated the potency of MEDr against liver cancer with validation that dandelion could control AMPK and thus cancer in the treated cell lines.

Dysfunction of T helper 17 (Th17) cells leads to chronic inflammatory disorders. Signal transducer and activator of transcription 3 (STAT3) orchestrates the expression of proinflammatory cytokines and pathogenic cell differentiation from interleukin (IL)-17-producing Th17 cells. However, the pathways mediated by STAT3 signaling are not fully understood. Here, we observed that Fos-related antigen 1 (FRA1) and JUNB are directly involved in STAT3 binding to sites in the promoters of Fosl1 and Junb. Promoter binding increased expression of IL-17 and the development of Th17 cells. Overexpression of Fra1 and Junb in mice resulted in susceptibility to collagen-induced arthritis and an increase in Th17 cell numbers and inflammatory cytokine production. In patients with rheumatoid arthritis, FRA1 and JUNB were colocalized with STAT3 in the inflamed synovium. These observations suggest that FRA1 and JUNB are associated closely with STAT3 activation, and that this activation leads to Th17 cell differentiation in autoimmune diseases and inflammation.

In the pursuit of sustainable agriculture through environment and human health friendly practices, we evaluated the potential of a novel gibberellins (GAs) producing basidiomycetous endophytic fungus Porostereum spadiceum AGH786, for alleviating salt stress and promoting health benefits of soybean. Soybean seedlings exposed to different levels of NaCl stress (70 and 140 mM) under greenhouse conditions, were inoculated with the AGH786 strain. Levels of phytohormones including GAs, JA and ABA, and isoflavones were compared in control and the inoculated seedlings to understand the mechanism through which the stress is alleviated. Gibberellins producing endophytic fungi have been vital for promoting plant growth under normal and stress conditions. We report P. spadiceum AGH786 as the ever first GAs producing basidiomycetous fungus capable of producing six types of GAs. In comparison to the so for most efficient GAs producing Gibberella fujikuroi, AGH786 produced significantly higher amount of the bioactive GA3. Salt-stressed phenotype of soybean seedlings was characterized by low content of GAs and high amount of ABA and JA with reduced shoot length, biomass, leaf area, chlorophyll contents, and rate of photosynthesis. Mitigation of salt stress by AGH786 was always accompanied by high GAs, and low ABA and JA, suggesting that this endophytic fungus reduces the effect of salinity by modulating endogenous phytohormones of the seedlings. Additionally, this strain also enhanced the endogenous level of two isoflavones including daidzen and genistein in soybean seedlings under normal as well as salt stress conditions as compared to their respective controls. P. spadiceum AGH786 boosted the NaCl stress tolerance and growth in soybean, by modulating seedlings endogenous phytohormones and isoflavones suggesting a valuable contribution of this potent fungal biofertilizer in sustainable agriculture in salt affected soils.

In the pursuit of sustainable agriculture through environment and human health friendly practices, we evaluated the potential of a novel gibberellins (GAs) producing basidiomycetous endophytic fungus Porostereum spadiceum AGH786, for alleviating salt stress and promoting health benefits of soybean. Soybean seedlings exposed to different levels of NaCl stress (70 and 140 mM) under greenhouse conditions, were inoculated with the AGH786 strain. Levels of phytohormones including GAs, JA and ABA, and isoflavones were compared in control and the inoculated seedlings to understand the mechanism through which the stress is alleviated. Gibberellins producing endophytic fungi have been vital for promoting plant growth under normal and stress conditions. We report P. spadiceum AGH786 as the ever first GAs producing basidiomycetous fungus capable of producing six types of GAs. In comparison to the so for most efficient GAs producing Gibberella fujikuroi, AGH786 produced significantly higher amount of the bioactive GA3. Salt-stressed phenotype of soybean seedlings was characterized by low content of GAs and high amount of ABA and JA with reduced shoot length, biomass, leaf area, chlorophyll contents, and rate of photosynthesis. Mitigation of salt stress by AGH786 was always accompanied by high GAs, and low ABA and JA, suggesting that this endophytic fungus reduces the effect of salinity by modulating endogenous phytohormones of the seedlings. Additionally, this strain also enhanced the endogenous level of two isoflavones including daidzen and genistein in soybean seedlings under normal as well as salt stress conditions as compared to their respective controls. P. spadiceum AGH786 boosted the NaCl stress tolerance and growth in soybean, by modulating seedlings endogenous phytohormones and isoflavones suggesting a valuable contribution of this potent fungal biofertilizer in sustainable agriculture in salt affected soils.

Objective.To investigate the expression of fractalkine and identify the clinical effects of fractalkine and its receptor (CX3CR1) in patients with primary Sjögren syndrome (pSS).Methods.Serum fractalkine levels were determined by ELISA. Immunohistochemical staining was done to compare the expression of fractalkine and CX3CR1 between salivary glands (SG) of patients with SS and controls. The cells to be merged with fractalkine were evaluated by confocal microscopy. Type of CX3CR1-expressing cells among infiltrating lymphocytes in SG was analyzed by confocal microscopy. Further, associations among fractalkine, proinflammatory cytokines, and clinical profiles were investigated.Results.Serum fractalkine levels in patients with pSS were higher than those in the control group (p = 0.026). SG expression of fractalkine and its receptor was upregulated in patients with pSS compared to that in the controls by immunohistochemistry. Higher histological grade was associated with more fractalkine-positive cells per total epithelial cells. Epithelial cells were the main fractalkine-expressing cell type in the SG. Serum fractalkine levels were significantly correlated with proinflammatory cytokines levels (interleukin 17: r = 0.685, p = 0.029; tumor necrosis factor-α: r = 0.444, p = 0.003), antinuclear antibody (r = 0.349, p = 0.022), and immunoglobulin G levels (r = 0.325, p = 0.044). Serum fractalkine levels in patients with extraglandular manifestations of pSS were significantly higher than in those without extraglandular manifestations (p = 0.026).Conclusion.Fractalkine and CX3CR1 may play a role in the pathogenesis of pSS, including extraglandular manifestations.