scholarly journals Inhibition Molecular Mechanism of the Novel Fungicidal N-(naphthalen-1-yl) phenazine-1-carboxamide against Rhizoctonia solani

Agronomy ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2532
Author(s):  
Ya Zhang ◽  
Chong Wang ◽  
Shuangqing Liu ◽  
Xiaolan Liao

To explore the molecular mechanism through which the novel fungicide N-(naphthalen-1-yl) phenazine-1-carboxamide (NNPCN) inhibits Rhizoctonia solani, we clarified the target and mode of action, explored lead compounds, and developed novel fungicides. Methods: Growth observation, scanning electron microscopy, transmission electron microscopy, transcriptome sequencing technology, quantitative real-time PCR (qRT-PCR), physiological and biochemical determination, and reverse molecular docking technology were used to study the effects of this compound on the microscopic morphology of R. solani. The differentially expressed genes (DEGs), functions, and metabolic pathways were analyzed. The genes displaying significant differences were randomly selected for qRT-PCR verification and confirmed by physiological and biochemical determination to construct their binding mode with key targets. The results showed that the mycelium treated with NNPCN produced a red secretion and exhibited progressive creeping growth. Under a scanning electron microscope, hyphal swelling, uneven thickness, fractures, deformities, and hyphal surface warts increased. Under a transmission electron microscope, the cell wall was separated, the subcellular organelles were disintegrated, and the septum disappeared. Furthermore, there were 6838 DEGs under NNPCN treatment, including 291 significant DEGs, of which 143 were upregulated and 148 downregulated. Ten DEGs were randomly selected for qRT-PCR verification, and the gene expression trend was consistent with the transcriptome sequencing results. Gene Ontology enrichment analysis showed that the DEGs were significantly enriched in cell wall glucan decomposition and metabolism, cell membrane synthesis, metabolism, composition, organic hydroxyl compounds, oxidoreductase activity, and transition metal ion binding. Metabolic pathway enrichment analysis showed that there were 16 significant metabolic pathways, such as steroid biosynthesis and ABC transporters. Further study found that genes, such as the glycosyl hydrolase family 10 domain-containing protein, which is related to glucan catabolic process function as tied to the cell wall, were downregulated. Lipid oxidation, modification, and other genes related to the cell membrane were also downregulated. Secondly, genes related to lipid modification, lipid metabolism processes, integral components of the membrane, and other ABC transporters were downregulated. Fatty-acid oxidation and carbohydrate metabolic processes, which are related to antioxidant and metabolic functions, displayed significant differences in their target genes. Nitrite reductase [NADH] activity and mitochondrial organization gene expression were downregulated. These results revealed that target genes may involved in the cell wall, cell membrane, antioxidant and metabolism, nitrogen metabolism, and mitochondria. The results of the physiological and biochemical tests showed that NNPCN decreased the β-1,3-glucanase, malondialdehyde, and ATPase activities and nucleic acid leakage but increased the activity of nitrate reductase. The results of the reverse molecular docking showed that NNPCN could freely bind to target proteins such as β-1,3-glucanase, ABC transporter, and NADPH nitrate reductase, whereby NNPCN could bind to glucanase via van der Waals and electrostatic forces and to ABC transporter and NADPH nitrate reductase via hydrogen bonding. Conclusion: The mechanism via which NNPCN inhibits R. solani may be related to the cell wall structure, cell membrane damage, antioxidant activity, and metabolism.

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhaoyi Lu ◽  
Kai Su ◽  
Xiaomin Wang ◽  
Mingjie Zhang ◽  
Shiyin Ma ◽  
...  

Introduction: tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs, are divided into two categories: tRNA-related fragments (tRFs) and tRNA halves (tiRNAs). Abnormal expression of tsRNAs has been found in diverse cancers, which indicates that further understanding of the function of tsRNAs will help identify new biomarkers and potential therapeutic targets. Until now, the underlying roles of tsRNAs in primary nasopharyngeal carcinoma (NPC) are still unknown.Methods: tRF and tiRNA sequencing was performed on four pairs of NPC tissues and healthy controls. Thirty pairs of NPC samples were used for quantitative real-time polymerase chain reaction (qRT-PCR) verification, and the ROC analysis was used to evaluate the diagnostic efficiency initially. Target prediction and bioinformatics analysis of validated tRFs and tiRNAs were conducted to explore the mechanisms of tsRNAs in NPC’s pathogenesis.Results: A total of 158 differentially expressed tRFs and tiRNAs were identified, of which 88 are upregulated and 70 are downregulated in NPC. Three validated tRFs in the results of qRT-PCR were consistent with the sequencing data: two upregulations (tRF-1:28-Val-CAC-2 and tRF-1:24-Ser-CGA-1-M3) and one downregulation (tRF-55:76-Arg-ACG-1-M2). The GO and KEGG pathway enrichment analysis showed that the potential target genes of validated tRFs are widely enriched in cancer pathways. The related modules may play an essential role in the pathogenesis of NPC.Conclusions: The tsRNAs may become a novel class of biological diagnostic indicators and possible targets for NPC.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rebeca Escutia-Gutiérrez ◽  
J. Samael Rodríguez-Sanabria ◽  
C. Alejandra Monraz-Méndez ◽  
Jesús García-Bañuelos ◽  
Arturo Santos-García ◽  
...  

AbstractmiRNAs are involved in the development of metabolic associated fatty liver disease (MAFLD) and nonalcoholic steatohepatitis (NASH). We aimed to evaluate modifications by prolonged-release pirfenidone (PR-PFD) on key hepatic miRNAs expression in a MAFLD/NASH model. First, male C57BL/6J mice were randomly assigned into groups and fed with conventional diet (CVD) or high fat and carbohydrate diet (HFD) for 16 weeks. At the end of the eighth week, HFD mice were divided in two and only one half was treated with 300 mg/kg/day of PR-PFD mixed with food. Hepatic expression of miRNAs and target genes that participate in inflammation and lipid metabolism was determined by qRT-PCR and transcriptome by microarrays. Increased hepatic expression of miR-21a-5p, miR-34a-5p, miR-122-5p and miR-103-3p in MAFLD/NASH animals was reduced with PR-PFD. Transcriptome analysis showed that 52 genes involved in lipid and collagen biosynthesis and inflammatory response were downregulated in PR-PFD group. The expression of Il1b, Tnfa, Il6, Tgfb1, Col1a1, and Srebf1 were decreased in PR-PFD treated animals. MAFLD/NASH animals compared to CVD group showed modifications in gene metabolic pathways implicated in lipid metabolic process, inflammatory response and insulin resistance; PR-PFD reversed these modifications.


2021 ◽  
Author(s):  
Limei Pan ◽  
Lingyun Wan ◽  
Lisha Song ◽  
Lili He ◽  
Ni Jiang ◽  
...  

Abstract Background Loranthus (Taxillus chinensis) is an important medicinal and parasitic plant that attacks other plants for living. To reveal the mechanisms of haustorium development, we employed an iTRAQ proteomics-based approach to identify differentially abundant proteins (DAPs) of fresh seeds (CK), baby (FB), and adult haustoria (FD). Results A total of 563 and 785 DAPs were successfully quantified in the early/later developmental stage, respectively. Pathway enrichment analysis indicated that the DAPs mainly associated with metabolic pathways, ribosome, phenylpropanoid biosynthesis and photosynthesis. In the meantime, DAPs associated with phytohormone signaling pathway changed markedly. Furthermore, we evaluated the contents change of phytohormone during the haustoria development. These results indicated that phytohormone is very important for haustorium development. qRT-PCR validation showed that the mRNA expression levels were consistent with the protein variation, suggesting that our result were reliable. Conclusions To the best of our knowledge, this is the first haustoria proteomes of loranthus, and our findings will improve our understanding of the molecular mechanism of haustoria development.


2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Jiaming Yao ◽  
Junbin Yan ◽  
Jinting Wu ◽  
Jianshun Yu ◽  
Beihui He ◽  
...  

Background. San-Huang-Chai-Zhu formula (SHCZF) has been used to improve cholestasis for many years. This study aims to predict the possible gene targets of SHCZF in treating acute intrahepatic cholestasis (AIC) in rats. Materials and Methods. Eighteen SD rats were randomly assigned to the normal group, ANIT group, and ANIT + SHCZF group. Alpha-naphthylisothiocyanate (ANIT) was used to induce AIC. Serum biochemical indexes were detected in each group. After treatment, the livers were collected and used to extract RNA. The library was constructed by TruSeq RNA, sequenced by Illumina, and analyzed by various bioinformatics methods. qRT-PCR was used to verify the target genes related to the efficacy of SHCZF. Results. Serum ALT, AST, ALP, and TBIL were significantly higher in the ANIT group than in the normal group. Serum ALT and AST levels in the ANIT + SHCZF group were substantially lower than those in the ANIT group. A total of 354 intersected genes were screened by expression level correlation and PCA analysis, GO and KEGG pathway enrichment analysis, and WGCNA and STEM analysis. Then, 4 overlapping genes were found by pathway/BP/gene network construction. SHCZF reversed the downregulation of expression of CYP4A1 and HACL1 and the upregulation of expression of DBI and F11R induced by ANIT. In addition, the qRT-PCR result showed that mRNA expression of CYP4A1, HACL1, and F11R genes in the liver was consistent with the prediction result of bioinformatics analysis. Conclusion. CYP4A1, HACL1, and F11R are genes related to the occurrence of ANIT-induced AIC in rats and may be considered as targets of SHCZF for the treatment of AIC.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7882 ◽  
Author(s):  
Chao Wei ◽  
Jian-Jun Gao

Aim The study aims to identify differentially expressed microRNAs (DEMs) in gastric cancer (GC) and explore the expression, prognosis and downstream regulation role of miR-383-5p in GC. Methods The GC miRNA-Seq and clinical information were downloaded from Firebrowse which stores integrated data sourced from The Cancer Genome Atlas database. The DEMs were identified with limma package in R software at the cut-off criteria of P < 0.05 and |log2 fold change| > 1.0 (|log2FC| > 1.0). The expression of miR-383-5p in GC cell lines and 54 paired GC tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The overall survival curve of miR-383-5p and the association between its expression and clinicopathological features were explored. Wound healing and cell counting kit-8 assays were performed to investigate the capacity of miR-383-5p in cell proliferation and migration. The downstream target genes were predicted by bioinformatics tools (miRDB, TargetScan and starBase). The consensus target genes were selected for gene functional enrichment analysis by FunRich v3.0 software. The luciferase reporter assay was performed to verify the potential targeting sites of miR-383-5p on lactate dehydrogenase A (LDHA). Results A total of 21 down-regulated miRNAs (including miR-383-5p) and 202 up-regulated miRNAs were identified by analyzing GC miRNA-Seq data. Survival analysis found that patients with low miR-383-5p expression had a shorter survival time (median survival time 21.1 months) than those with high expression (46.9 months). The results of qRT-PCR indicated that miR-383-5p was downregulated in GC cell lines and tissues, which was consistent with miRNA-Seq data. The expression of miR-383-5p was significantly associated with tumor size and differentiation grade. Besides, overexpression of miR-383-5p suppressed GC cells proliferation and migration. A total of 49 common target genes of miR-383-5p were obtained by bioinformatics tools and gene functional enrichment analysis showed that these predicted genes participated in PI3K, mTOR, c-MYC, TGF-beta receptor, VEGF/VEGFR and E-cadherin signaling pathways. The data showed that expression of miR-383-5p was negatively correlated with target LDHA (r = −0.203). Luciferase reporter assay suggested that LDHA was a target of miR-383-5p. Conclusion The present study concluded that miR-383-5p was downregulated and may act as a tumor suppressor in GC. Furthermore, its target genes were involved in important signaling pathways. It could be a prognostic biomarker and play a vital role in exploring the molecular mechanism of GC.


2010 ◽  
Vol 60 (3) ◽  
pp. 537-541 ◽  
Author(s):  
K. Martin ◽  
J. Schäfer ◽  
P. Kämpfer

A Gram-positive, yellow-pigmented, branched-hyphae-forming micro-organism, strain 09-Be-007T, was isolated from the wall of an indoor environment. Based on 16S rRNA gene sequence similarity studies, strain 09-Be-007T belonged to the genus Promicromonospora. The novel isolate showed sequence similarities of 98.8 % to Promicromonospora aerolata V54AT, 98.9 % to Promicromonospora vindobonensis V45T, 98.1 % to Promicromonospora sukumoe DSM 44121T, 98.2 % to Promicromonospora kroppenstedtii RS16T, 96.7 % to Promicromonospora flava CC 0387T and 97.8 % to Promicromonospora citrea DSM 43110T, the type strain of the type species of this genus. Cell wall sugars of strain 09-Be-007T were galactose, rhamnose and glucose. The diagnostic diamino acid of the cell-wall peptidoglycan was lysine. The major menaquinones detected were MK-9(H4) and MK-9(H6). Major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol. Major fatty acids were iso-C15 : 0 and anteiso-C15 : 0; moderate amounts of anteiso-C17 : 0, iso-C16 : 0 and iso-C15 : 1 were also found. All these data supported the affiliation of strain 09-Be-007T to the genus Promicromonospora. DNA–DNA hybridization values and physiological and biochemical data enabled strain 09-Be-007T to be differentiated genotypically and phenotypically from the six recognized species of the genus Promicromonospora. For these reasons, strain 09-Be-007T represents a novel species, for which the name Promicromonospora umidemergens sp. nov. is proposed, with 09-Be-007T (=DSM 22081T=CCM 7634T) as the type strain.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11698
Author(s):  
Qingqing Wang ◽  
Xiaoyan Yu ◽  
Ningning Yang ◽  
Lu Xu ◽  
Yunfeng Zhou

Background Growing evidence has suggested that enhancer RNAs (eRNAs), a set of long non-coding RNAs (lncRNAs) that were derived from active enhancer regions, play critical roles in regulating gene expression in human cancers. Nevertheless potential functions of eRNAs in esophageal cancer ESCA have not yet been expounded. Here, this study aimed to explore key prognostic eRNAs in ESCA. Methods LncRNAs that were transcribed from active enhancer regions were analyzed utilizing the PreSTIGE algorithm, followed by prediction of their target genes. Based on the ESCA RNA-seq data from the TANRIC database, overall survival (OS)-related eRNAs were determined. The correlation between AC007255.1 expression and various clinical traits of ESCA was calculated. Functional enrichment analysis was presented based on its co-expressed genes. Based on the TIMER database, we analyzed correlations between AC007255.1 expression and immune infiltration levels. qRT-PCR was utilized to validate the expression of AC007255.1 and PRR15 in ESCA and normal tissues. Results Totally, 2,695 lncRNAs were transcribed from active enhancer regions. Among them, 33 were significantly related to OS. AC007255.1 was a key eRNA. PRR15 was a target gene of AC007255.1 (correlation coefficient r = 0.936). Patients with high AC007255.1 expression indicated poor OS time. There were significant correlations between AC007255.1 expression and clinical characteristics like pathological TNM, grade and stage. AC007255.1 was closely related to tight junction and neutrophil activation involved in immune response. Moreover, AC007255.1 expression was related to the infiltration levels of B cell, dendritic cell and neutrophil. qRT-PCR results confirmed that AC007255.1 and PRR15 were both up-regulated in ESCA tissues, and there was a positive correlation between the two. Conclusion Our findings identified a novel immune-related eRNA AC007255.1 in ESCA, which could be a promising prognostic factor for ESCA.


1997 ◽  
Vol 161 ◽  
pp. 491-504 ◽  
Author(s):  
Frances Westall

AbstractThe oldest cell-like structures on Earth are preserved in silicified lagoonal, shallow sea or hydrothermal sediments, such as some Archean formations in Western Australia and South Africa. Previous studies concentrated on the search for organic fossils in Archean rocks. Observations of silicified bacteria (as silica minerals) are scarce for both the Precambrian and the Phanerozoic, but reports of mineral bacteria finds, in general, are increasing. The problems associated with the identification of authentic fossil bacteria and, if possible, closer identification of bacteria type can, in part, be overcome by experimental fossilisation studies. These have shown that not all bacteria fossilise in the same way and, indeed, some seem to be very resistent to fossilisation. This paper deals with a transmission electron microscope investigation of the silicification of four species of bacteria commonly found in the environment. The Gram positiveBacillus laterosporusand its spore produced a robust, durable crust upon silicification, whereas the Gram negativePseudomonas fluorescens, Ps. vesicularis, andPs. acidovoranspresented delicately preserved walls. The greater amount of peptidoglycan, containing abundant metal cation binding sites, in the cell wall of the Gram positive bacterium, probably accounts for the difference in the mode of fossilisation. The Gram positive bacteria are, therefore, probably most likely to be preserved in the terrestrial and extraterrestrial rock record.


2021 ◽  
Vol 15 (8) ◽  
pp. 927-936 ◽  
Author(s):  
Yan Peng ◽  
Yuewu Liu ◽  
Xinbo Chen

Background: Drought is one of the most damaging and widespread abiotic stresses that can severely limit the rice production. MicroRNAs (miRNAs) act as a promising tool for improving the drought tolerance of rice and have become a hot spot in recent years. Objective: In order to further extend the understanding of miRNAs, the functions of miRNAs in rice under drought stress are analyzed by bioinformatics. Method: In this study, we integrated miRNAs and genes transcriptome data of rice under the drought stress. Some bioinformatics methods were used to reveal the functions of miRNAs in rice under drought stress. These methods included target genes identification, differentially expressed miRNAs screening, enrichment analysis of DEGs, network constructions for miRNA-target and target-target proteins interaction. Results: (1) A total of 229 miRNAs with differential expression in rice under the drought stress, corresponding to 73 rice miRNAs families, were identified. (2) 1035 differentially expressed genes (DEGs) were identified, which included 357 up-regulated genes, 542 down-regulated genes and 136 up/down-regulated genes. (3) The network of regulatory relationships between 73 rice miRNAs families and 1035 DEGs was constructed. (4) 25 UP_KEYWORDS terms of DEGs, 125 GO terms and 7 pathways were obtained. (5) The protein-protein interaction network of 1035 DEGs was constructed. Conclusion: (1) MiRNA-regulated targets in rice might mainly involve in a series of basic biological processes and pathways under drought conditions. (2) MiRNAs in rice might play critical roles in Lignin degradation and ABA biosynthesis. (3) MiRNAs in rice might play an important role in drought signal perceiving and transduction.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jing Mao ◽  
Tianmei Li ◽  
Di Fan ◽  
Hongli Zhou ◽  
Jianguo Feng ◽  
...  

Abstract Background Recent studies have shown that circular RNA (circRNA) is rich in microRNA (miRNA) binding sites. We have previously demonstrated that the antidepressant effect of ketamine is related to the abnormal expression of various miRNAs in the brain. This study determined the expression profile of circRNAs in the hippocampus of rats treated with ketamine. Methods The aberrantly expressed circRNAs in rat hippocampus after ketamine injection were analyzed by microarray chip, and we further validated these circRNAs by quantitative reverse-transcription PCR (qRT-PCR). The target genes of the different circRNAs were predicted using bioinformatic analyses, and the functions and signal pathways of these target genes were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Results Microarray analysis showed that five circRNAs were aberrantly expressed in rat hippocampus after ketamine injection (fold change > 2.0, p < 0.05). The results from the qRT-PCR showed that one of the circRNAs was significantly increased (rno_circRNA_014900; fold change = 2.37; p = 0.03), while one was significantly reduced (rno_circRNA_005442; fold change = 0.37; p = 0.01). We discovered a significant enrichment in several GO terms and pathways associated with depression. Conclusion Our findings showed the abnormal expression of ketamine-induced hippocampal circRNAs in rats.


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