SfREPAT38, a pathogen response gene (REPAT), is involved in immune response of Spodoptera frugiperda larvae through mediating Toll signalling pathway.

REPAT (response to pathogen) is an immune-associated gene family that plays important roles in insect immune response to pathogens. Although nine REPAT genes have been identified in Spodoptera frugiperda (Lepidoptera: Noctuidae) currently, their functions and mechanisms in the immune response to pathogens still remain unclear. Therefore, SfREPAT38, a pathogen response gene (REPAT) of S. frugiperda, was characterised and its function was analysed. The results showed that SfREPAT38 contains a signal peptide and a transcription activator MBF2 (multi-protein bridging factor 2) domain. Quantitative real-time polymerase chain reaction analysis showed that SfREPAT38 was highly expressed in the sixth-instar larvae (L6) and was the highest in expression in the midgut of L6. We found that the expression of SfREPAT38 could be activated by challenge with four microbial pathogens (Bacillus thuringiensis, Metarhizium anisopliae, Spodoptera exigua nuclearpolyhedrosis and Escherichia coli), except 12 h after E. coli infection. Furthermore, the SfREPAT38 expression levels significantly decreased at 24, 48 and 72 h after SfREPAT38 dsRNA injection or feeding. Feeding with SfREPAT38 dsRNA significantly decreased the weight gain of S. frugiperda, and continuous feeding led to the death of S. frugiperda larvae from the fourth day. Moreover, SfREPAT38 dsRNA injection resulted in a significant decrease of weight gain on the fifth day. Silencing SfREPAT38 gene down-regulated the expression levels of immune genes belonging to the Toll pathway, including SPZ, Myd88, DIF, Cactus, Pell and Toll18W. After treatment with SfREPAT38 dsRNA, S. frugiperda became extremely sensitive to the B. thuringiensis infection, and the survival rate dramatically increased, with 100% mortality by the eighth day. The weight of S. frugiperda larvae was also significantly lower than that of the control groups from the second day onwards. In addition, the genes involved in the Toll signalling pathway and a few antibacterial peptide related genes were down-regulated after treatment. These results showed that SfREPAT38 is involved in the immune response of S. frugiperda larvae through mediating Toll signalling pathway.

Integrated network analysis and experimental verification of the mechanisms employed by Compound Jixuecao Decoction to improve endoplasmic reticulum stress and apoptosis in chronic renal failure.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Jixuecao Decoction (CJD) is a traditional Chinese herbal medicine prescribed in China to treat chronic renal failure (CRF). Previous studies have shown that CJD affects cell apoptosis and proliferation. However, the mechanism of its renal protective action has not been characterized. AIM OF THE STUDY: To explore the mechanism(s) underlying the effect of CJD on endoplasmic reticulum stress (ERS) and apoptosis in the treatment of CRF using network pharmacology, molecular docking, molecular dynamics simulations, and in vivo studies. MATERIALS AND METHODS: The compounds comprising CJD were extracted from the Traditional Chinese Medicine Systems Pharmacology Database. A Swiss target prediction database and similarity integration approach were employed to identify potential targets of these components. The GeneCards and DisGeNET databases were used to identify targets associated with CRF, apoptosis, and ERS. The STRING database was employed to analyze the protein-protein interactions (PPIs) associated with drug-disease crossover. A chemical composition-shared target network was established, and critical pathways were identified through gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The Protein Data Bank database was used to search key proteins, while molecular docking and dynamics simulations were performed between the top four CJD active ingredients and proteins involved in apoptosis and ERS in CRF. Subsequent in vivo studies using a 5/6 nephrectomy rat model of CRF were performed to verify the findings. RESULTS: The 80 compounds identified in CJD yielded 875 target genes, of which 216 were potentially related to CRF. PPI network analysis revealed key targets via topology filtering. Enrichment analysis, molecular docking, and molecular dynamics simulation results suggested that CJD primarily targets mitofusin-2 (MFN2), B-cell lymphoma-2 (BCL2), BAX, protein kinase RNA-like ER kinase (PERK), and C/EBP homologous protein (CHOP) during CRF treatment. In vivo, CJD significantly increased the abundance of MFN2, BCL2, and significantly reduced the abundance of BAX, PERK, CHOP proteins in kidney tissues, indicating that CJD could improve apoptosis and ERS in CRF rats. CONCLUSIONS: This study provides evidence that CJD effectively delays CFR through modulation of the MFN2 and PERK-eIF2α-ATF4-CHOP signaling pathways.

GhMYC1374 regulates the cotton defense response to cotton aphids by mediating the production of flavonoids and free gossypol.

Myelocytomatosis (MYC) transcription factors (TFs) in plants are well-known regulators of plant defense against herbivores. However, the role and mechanism of MYC TFs in cotton (Gossypium hirsutum L.) defense against cotton aphids (Aphis gossypii Glover) remain still elusive. Herein, on the basis of aphid-induced cotton transcriptome analysis, GhMYC1374, a cotton MYC2-like TF that was highly induced by cotton aphid attack, has been identified that confers cotton aphid resistance in cotton. GhMYC1374 was an intranuclear transcription factor with three domains: bHLH-MYC_N, RBR and bHLH_AtAIB_like. GhMYC1374 was induced under cotton aphid feeding, exogenous methyl jasmonate (MeJA) and salicylic acid (SA) treatments. GhMYC1374 transient overexpression in cotton plants enhanced cotton aphid-resistance, while GhMYC1374 silence through VIGS (virus induced gene silencing) decreased cotton aphid-resistance. GhMYC1374 transient overexpression of in cotton plants activated the phenylpropane pathway and promoted the synthesis of flavonoids, and resistance to thus enhanced the cotton resistance against aphids. In contrast, GhMYC1374 silence inhibited the biosynthesis of flavonoids. In addition, GhMYC1374 also positively activated the expression of the biosynthetic genes of free gossypol, leading to the high content of free gossypol. Taken together, our results suggest that GhMYC1374 is involved in the cotton defense response against cotton aphids by regulating the biosynthesis of flavonoids and free gossypol.

GhMYB18 confers Aphis gossypii Glover resistance through regulating the synthesis of salicylic acid and flavonoids in cotton plants.

KEY MESSAGE: R2R3 MYB transcription factor GhMYB18 is involved in the defense response to cotton aphid by participating in the synthesis of salicylic acid and flavonoids. R2R3 MYB transcription factors (TFs) play crucial roles in plant growth and development as well as response to abiotic and biotic stresses. However, the mechanism of R2R3 MYB TFs in cotton response to aphid infestation remains largely unknown. Here, an R2R3 MYB transcription factor GhMYB18 was identified as a gene up-regulated from upland cotton (Gossypium hirsutum L.) under cotton aphid (Aphis gossypii Glover) infestation. GhMYB18, which has transcription activity, was localized mainly to nucleus and cell membranes. Transient overexpression of GhMYB18 in cotton activates salicylic acid (SA) and phenylpropane signaling pathways and promoted the synthesis of salicylic acid and flavonoids, which leads to enhancing the tolerance to cotton aphid feeding. In contrast, silencing of GhMYB18 increased the susceptibility of G. hirsutum to aphid. Additionally, GhMYB18 significantly promoted the activities of defense-related enzymes including catalase (CAT), peroxidase (POD), polyphenol oxidase (PPO) and phenylalanine ammonia-lyase (PAL). These results collectively suggest that GhMYB18 is involved in cotton defense response to cotton aphid attacks through regulating the synthesis of salicylic acid and flavonoids.

Complete Genome Sequence of Antibiotic-Producing Bacillus velezensis H208, Isolated from Ginger Rhizosphere in Laifeng County, China.

The genome of an antibiotic-producing bacterium, Bacillus velezensis H208, was sequenced. Strain H208 was isolated from ginger rhizosphere in Laifeng County, China. The genome consisted of 3,929,792 bp, with a GC content of 46.5%, and contained 3,773 protein-coding genes and 118 noncoding RNA genes.

A multilevel analysis of the impact of transitioning to grandparenthood on individuals' depression in England, Europe and China.

OBJECTIVES: The impact of grandparenting on depression is mediated by both macro- and micro-level factors, however, their combined examination between different country contexts is relatively rare. This study examined whether country level income and grandparents' gender influenced the relationship between the transition to grandparenthood and individuals' depression across England, Europe and China. METHODS: Multi-level linear regression analyses with restricted maximum likelihood estimation were performed covering 15 countries from the ELSA, the SHARE and the CHARLS 2010-15 in order to understand cross-country differences in this area. RESULTS: This study found significant cross-national variations in the effects of transitioning to grandparenthood on individuals' depression. Transitioning to grandparenthood reduced the depression score among both men and women in lower income countries, but increased it in higher income countries. Moreover, the gender gap in the effects of becoming a grandparent on one's depression was wider in lower income countries than higher income countries. CONCLUSIONS: Policymakers should pay attention to the support grandparents need, and systematically integrate childcare provided by grandparents into family policies. Policies supporting older people should take into account the way in which macro-level and micro-level factors combine to affect grandparents' well-being.

Metabolomics analysis of grains of wheat infected and noninfected with Tilletia controversa Kühn.

Dwarf bunt caused by the pathogen Tilletia controversa Kühn is one of the most serious quarantine diseases of winter wheat. Metabolomics studies provide detailed information about the biochemical changes at the cell and tissue levels of plants. In the present study, a liquid chromatography/mass spectrometry (LC/MS) metabolomics approach was used to investigate the changes in the grain metabolomics of infected and noninfected with T. controversa samples. PCA suggested that T. controversa-infected and noninfected samples were separated during the interaction. LC/MS analysis showed that 62 different metabolites were recorded in the grains, among which a total of 34 metabolites were upregulated and 28 metabolites were downregulated. Prostaglandins (PGs) and 9-hydroxyoctadecadienoic acids (9-HODEs) are fungal toxin-related substances, and their expression significantly increased in T. controversa-infected grains. Additionally, the concentrations of cucurbic acid and octadecatrienoic acid changed significantly after pathogen infection, which play a large role in plant defense. The eight different metabolic pathways activated during T. controversa and wheat plant interactions included phenylalanine metabolism, isoquinoline alkaloid biosynthesis, starch and sucrose metabolism, tyrosine metabolism, sphingolipid metabolism, arginine and proline metabolism, alanine, aspartate, and glutamate metabolism, and tryptophan metabolism. In conclusion, we found differences in the metabolic profiles of wheat grains after T. controversa infection. To our knowledge, this is the first study to evaluate the metabolites in wheat grains after T. controversa infection.

Identification of key miRNAs and their targets in peripheral blood mononuclear cells of IgA nephropathy using bioinformatics analysis.

BACKGROUND: Currently, renal biopsy is the gold standard for clinical diagnosis and evaluation the degrees of IgA nephropathy. However, renal biopsy is an invasive examination and not suitable for long-term follow-up IgA nephropathy. The activation of peripheral blood mononuclear cells (PBMCs) are related to IgA nephropathy, but the key molecular marker and target of PBMCs for evaluating the progression and prognosis of IgA nephropathy is still unclear. METHODS: We downloaded gene expression omnibus series 25590 (GSE25590) datasets, of which PBMCs from IgA nephrology (IgAN) and healthy patients, from the gene expression omnibus (GEO) database. Differentially expressed miRNAs (DEMs) between IgAN and healthy patients were identified. The Funrich software was used to predict the differentially expressed genes (DEGs). Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyzes of overlapping genes were analyzed at the function level on DAVID 6.8. We used search Tool for the retrieval of interacting genes (STRING) online database constructed the protein-protein interaction (PPI) network. Then we further analyzed the hub genes by Cytoscape software and the hub miRNA by TargetScan. RESULTS: We identified 418 DEMs from the GSE25590 datasets. The upstream transcription factors SP1 regulates most DEMs. According to the GO and KEGG results, the DEGs were enriched in the MAPK signaling pathway and small GTPase mediated signal transduction. SYN1, SYT4, RBFOX1, KCNC1, VAMP2, FBXO11, ASB9, SYT9, KLHL5, and KRAS were identified as hub genes. Hsa-miR-532-5p, hsa-miR-92a, hsa-miR-328, hsa-miR-137, hsa-miR-153, hsa-miR-9-5p, hsa-miR-140-5p, hsa-miR-217, hsa-miR-155, and hsa-miR-212 were predicted as hub miRNAs. CONCLUSIONS: The DEMs and DEGs re-analysis provided potential key genes and hub miRNA of PMBCs, which may help to monitor the happening and prognosis of IgAN.

Hesperetin alleviated glucocorticoid-induced inhibition of osteogenic differentiation of BMSCs through regulating the ERK signaling pathway.

The objective of this study is to investigate the protective role of hesperetin for the glucocorticoid-induced osteoporosis (GIOP) and related mechanisms. In this study, we investigated the protective effects of hesperetin on dexamethasone (DEX)-induced osteogenic inhibition in bone marrow mesenchymal stem cells (BMSCs). The mineralization, real-time quantitative polymerase chain reaction assays (RT-qPCR), immunofluorescence and western blot were used to assess the protective effects of hesperetin in DEX-treated BMSCs during osteogenic differentiation. Our results showed that hesperetin promoted alkaline phosphatase (ALP) activity and the mineralization in DEX-treated BMSCs during osteogenic differentiation. The expression of osteogenic mRNA and proteins further confirmed the protective effect of hesperetin in DEX-treated BMSCs. Furthermore, hesperetin activated ERK signal pathway in DEX-treated BMSCs. ERK inhibitor U0126 could abolish the protective effect of hesperein in DEX-treated BMSCs. In conclusion, our study demonstrated that hesperetin alleviated glucocorticoid-induced inhibition of osteogenic differentiation through ERK signal pathway in BMSCs. It may be a potential therapeutic agent for protecting against glucocorticoid-induced osteoporosis.

The effects of non-calcium-based phosphate binders versus calcium-based phosphate binders on cardiovascular calcification and bone remodeling among dialysis patients: a meta-analysis of randomized trials.

BACKGROUND: Vascular calcification significantly increases the rates of cardiovascular mortality in hemodialysis (HD) patients. Abnormalities in mineral metabolism may play a role in the pathogenesis of arterial calcification. Whether patients treated with non-calcium-based phosphate binders had reduced aortic vascular calcification compared to those treated with calcium-based phosphate binders is still unclear. METHODS: We searched multiple databases for studies published through August 2013 that evaluated the effects of non-calcium-based phosphate binders (NCBP) versus calcium-based phosphate binders (CBP) on cardiovascular calcification and bone remodeling among dialysis patients. We summarized test performance characteristics with the use of forest plots, fixed and random effects models, and Egger regression test. RESULTS: Eighteen eligible randomized controlled trials totaling 3676 patients were included. Meta-analysis results showed NCBP could significantly attenuate the progression of coronary artery calcification than CBP (WMD: -144.62, 95% CI: -285.62 to -3.63). The serum calcium levels significant lower in NCPB group than in CPB groups (WMD: -0.26, 95% CI: -0.37 to -0.14), but the serum iPTH levels were significantly higher in NCPB groups (WMD: 57.1, 95% CI: 13.42 to 100.78). The osteoid volume and osteoblast numbers were significant higher in NCPB group than in CPB group (WMD: 1.75, 95% CI: 0.78 to 2.73 for osteoid volume; WMD: 4.49, 95% CI: 1.83 to 7.15 for osteoblast numbers). The Egger regression test also showed no potential publication bias (p = 0.725). CONCLUSIONS: Based on available data, NCBPs have equally effective with CBPs for serum phosphate control. But there was significantly lower incidence of coronary artery calcification and a significant higher bone formatting rate in NCBP groups than in CBP groups. So we recommend NCBPs as phosphate binders for HD patients.