ABSTRACT
Fruit ripening is accompanied by dramatic changes in color, texture, and flavor and is regulated by transcription factors (TFs) and epigenetic factors. However, the detailed regulatory mechanism remains unclear. Gene expression patterns suggest that PpNAC1 (NAM/ATAF1/2/CUC) TF plays a major role in peach (Prunus persica) fruit ripening. DNA affinity purification (DAP)-seq combined with transactivation tests demonstrated that PpNAC1 can directly activate the expression of multiple ripening-related genes, including ACC synthase1 (PpACS1) and ACC oxidase1 (PpACO1) involved in ethylene biosynthesis, pectinesterase1 (PpPME1), pectate lyase1 (PpPL1), and polygalacturonase1 (PpPG1) related to cell wall modification, and lipase1 (PpLIP1), fatty acid desaturase (PpFAD3-1), and alcohol acyltransferase1 (PpAAT1) involved in volatiles synthesis. Overexpression of PpNAC1 in the tomato (Solanum lycopersicum) nor (nonripening) mutant restored fruit ripening, and its transient overexpression in peach fruit induced target gene expression, supporting a positive role of PpNAC1 in fruit ripening. The enhanced transcript levels of PpNAC1 and its target genes were associated with decreases in their promoter mCG methylation during ripening. Declining DNA methylation was negatively associated with increased transcripts of DNA demethylase1 (PpDML1), whose promoter is recognized and activated by PpNAC1. We propose that decreased methylation of the promoter region of PpNAC1 leads to a subsequent decrease in DNA methylation levels and enhanced transcription of ripening-related genes. These results indicate that positive feedback between PpNAC1 and PpDML1 plays an important role in directly regulating expression of multiple genes required for peach ripening and quality formation.
Subject(s)
Prunus persica , Prunus persica/genetics , Prunus persica/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Fruit/genetics , Fruit/metabolism , DNA Methylation/genetics , Gene Expression Regulation, Plant , DNA/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Ethylenes/metabolismABSTRACT
Benzaldehyde (BAld) is one of the most widely distributed volatiles that contributes to flavor and defense in plants. Plants regulate BAld levels through various pathways, including biosynthesis from trans-cinnamic acid (free BAld), release from hydrolysis of glycoside precursors (BAld-H) via multiple enzymatic action steps, and conversion into downstream chemicals. Here, we show that BAld-H content in peach (Prunus persica) fruit is up to 100-fold higher than that of free BAld. By integrating transcriptome, metabolomic and biochemical approaches, we identified glycoside hydrolase PpGH28BG1 as being involved in the production of BAld-H through the hydrolysis of glycoside precursors. Overexpressing and silencing of PpGH28BG1 significantly altered BAld-H content in peach fruit. Transgenic tomatoes heterologously expressing PpGH28BG1 exhibited a decrease in BAld-H content and an increase in SA accumulation, while maintaining fruit weight, pigmentation, and ethylene production. These transgenic tomato fruits displayed enhanced immunity against Botrytis cinerea compared to wild type (WT). Induced expression of PpGH28BG1 and increased SA content were also observed in peach fruit when exposed to Monilinia fructicola infection. Additionally, elevated expression of PpGH28BG1 promoted fruit softening in transgenic tomatoes, resulting in a significantly increased emission of BAld compared to WT. Most untrained taste panelists preferred the transgenic tomatoes over WT fruit. Our study suggests that it is feasible to enhance aroma and immunity in fruit through metabolic engineering of PpGH28BG1 without causing visible changes in the fruit ripening process.
ABSTRACT
The human malaria parasite Plasmodium falciparum (P.â falciparum) continues to pose a significant public health challenge, leading to millions of fatalities globally. Halofuginone (HF) has shown a significant anti-P.â falciparum effect, suggesting its potential as a therapeutic agent for malaria treatment. In this study, we synthesized a photoaffinity labeling probe of HF to identify its direct target in P.â falciparum. Our results reveal that ubiquitin carboxyl-terminal hydrolase 3 (PfUCHL3) acts as a crucial target protein of HF, which modulates parasite growth in the intraerythrocytic cycle. In particular, we discovered that HF potentially forms hydrogen bonds with the Leu10, Glu11, and Arg217 sites of PfUCHL3, thereby inducing an allosteric effect by promoting the embedding of the helix 6' region on the protein surface. Furthermore, HF disrupts the expression of multiple functional proteins mediated by PfUCHL3, specifically those that play crucial roles in amino acid biosynthesis and metabolism in P.â falciparum. Taken together, this study highlights PfUCHL3 as a previously undisclosed druggable target of HF, which contributes to the development of novel anti-malarial agents in the future.
ABSTRACT
Terpenes are volatile compounds responsible for aroma and the postharvest quality of commercially important xiangfei (Torreya grandis) nuts, and there is interest in understanding the regulation of their biosynthesis. Here, a transcriptomics analysis of xiangfei nuts after harvest identified 156 genes associated with the terpenoid metabolic pathway. A geranyl diphosphate (GPP) synthase (TgGPPS) involved in production of the monoterpene precursor GPP was targeted for functional characterization, and its transcript levels positively correlated with terpene levels. Furthermore, transient overexpression of TgGPPS in tobacco (Nicotiana tabacum) leaves or tomato (Solanum lycopersicum) fruit led to monoterpene accumulation. Analysis of differentially expressed transcription factors identified one basic helix-loop-helix protein (TgbHLH95) and one basic leucine zipper protein (TgbZIP44) as potential TgGPPS regulators. TgbHLH95 showed significant transactivation of the TgGPPS promoter, and its transient overexpression in tobacco leaves led to monoterpene accumulation, whereas TgbZIP44 directly bound to an ACGT-containing element in the TgGPPS promoter, as determined by yeast 1-hybrid test and electrophoretic mobility shift assay. Bimolecular fluorescence complementation, firefly luciferase complementation imaging, co-immunoprecipitation, and GST pull-down assays confirmed a direct protein-protein interaction between TgbHLH95 and TgbZIP44 in vivo and in vitro, and in combination these proteins induced the TgGPPS promoter up to 4.7-fold in transactivation assays. These results indicate that a TgbHLH95/TgbZIP44 complex activates the TgGPPS promoter and upregulates terpene biosynthesis in xiangfei nuts after harvest, thereby contributing to its aroma.
Subject(s)
Taxaceae , Transcription Factors , Transcription Factors/genetics , Transcription Factors/metabolism , Nuts/metabolism , Terpenes/metabolism , Monoterpenes/metabolism , Taxaceae/metabolism , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolismABSTRACT
OBJECTIVE: This study aimed to investigate the efficacy of rTMS in the treatment of poststroke epilepsy and the effect of rTMS on patients' cognitive function and depressive status. METHODS: One hundred and twenty-one poststroke epilepsy patients with mild cognitive impairment and depressive status admitted to the Department of Neurology of the Second People's Hospital of Nanning from January 1, 2017, to April 31, 2023, were selected and divided into the rTMS treatment group (treated group) and the control group. MMSE scores and HAMD scores were recorded before and after treatment. The frequency of EEG spiky waves recorded before and after treatment within 24 h and the frequency of any clinical seizure form (the number of clinical seizures within 1 month after treatment) and changes in observed indices before and after treatment were calculated. The differences between the data of the two groups were analyzed, to further assess the efficacy of rTMS in the treatment of poststroke epilepsy and the rTMS' effects on cognition and depression. RESULTS: Compared with drug treatment alone, rTMS significantly decreased clinical seizures and epileptiform discharges after stroke, especially in patients with lesions in the frontal, temporal, and parietal lobes. Compared with drug treatment alone, rTMS treatment can effectively reduce cognitive impairment and mood disorders, such as depression, especially for patients with lesions in the frontal and temporal lobes. The results of this experiment suggest that rTMS treatment does not increase adverse effects. CONCLUSION: rTMS reduces clinical seizures while improving cognitive impairment and depression in patients with epilepsy. Therefore, we suggest that low-frequency rTMS can be used as an adjunctive treatment for patients with epilepsy and provide some ideas and references for the treatment of epilepsy with cognitive impairment and depression.
Subject(s)
Epilepsy , Humans , Treatment Outcome , Epilepsy/therapy , Epilepsy/etiology , Seizures/etiology , Transcranial Magnetic Stimulation/methods , CognitionABSTRACT
PURPOSE: To systematically review the prevalence of motoric cognitive risk syndrome (MCR) among community-dwelling older adults and provide evidence-based support for policymakers planning health and social care policies. METHOD: Web of Science, PubMed, and Cochrane Library databases were searched for cross-sectional, prospective cohort, or population-based longitudinal studies of community-dwelling older adults aged ≥60 years with MCR from inception of the database through December 18, 2021. RESULTS: Seventeen studies were included. Pooled prevalence of MCR was found to be 10% (95% confidence interval [8%, 12%], I2 = 98.4%). Results of a subgroup analysis revealed a combined prevalence of MCR of 8.2% in males and 9.2% in females. Pooled prevalence of MCR was 9.7% in Asia and 10.2% in other regions. CONCLUSION: Prevalence of MCR in community-dwelling older adults is high. Our research may improve the epidemiological understanding of MCR, draw attention to older adults with MCR, and thus promote research of MCR and the formulation of relevant public health policies. With early identification and intervention of MCR, cognitive function can be improved, and the onset of dementia can be delayed or prevented. [Journal of Gerontological Nursing, 50(4), 16-24.].
Subject(s)
Independent Living , Humans , Aged , Prevalence , Male , Female , Aged, 80 and over , Cognitive Dysfunction/epidemiology , Middle Aged , Risk Factors , SyndromeABSTRACT
We report a case of Babesia microti infection in an immunocompetent child <5 years of age that caused fever and severe intravascular hemolysis. Physicians in China should be aware of babesiosis, especially in the differential diagnosis of immune hemolytic anemia with negative results for antiglobulin tests.
Subject(s)
Babesia microti , Babesiosis , Humans , Child , Hemolysis , Babesiosis/diagnosis , China , FeverABSTRACT
BACKGROUND: The evolutionarily conserved Polycomb Repressive Complex 2 (PRC2) plays a vital role in epigenetic gene repression by depositing tri-methylation on lysine residue K27 of histone H3 (H3K27me3) at the target loci, thus participating in diverse biological processes. However, few reports about PRC2 are available in plant species with large and complicated genomes, like cotton. RESULTS: Here, we performed a genome-wide identification and comprehensive analysis of cotton PRC2 core components, especially in upland cotton (Gossypium hirsutum). Firstly, a total of 8 and 16 PRC2 core components were identified in diploid and tetraploid cotton species, respectively. These components were classified into four groups, E(z), Su(z)12, ESC and p55, and the members in the same group displayed good collinearity, similar gene structure and domain organization. Next, we cloned G. hirsutum PRC2 (GhPRC2) core components, and found that most of GhPRC2 proteins were localized in the nucleus, and interacted with each other to form multi-subunit complexes. Moreover, we analyzed the expression profile of GhPRC2 genes. The transcriptome data and quantitative real-time PCR (qRT-PCR) assays indicated that GhPRC2 genes were ubiquitously but differentially expressed in various tissues, with high expression levels in reproductive organs like petals, stamens and pistils. And the expressions of several GhPRC2 genes, especially E(z) group genes, were responsive to various abiotic and biotic stresses, including drought, salinity, extreme temperature, and Verticillium dahliae (Vd) infection. CONCLUSION: We identified PRC2 core components in upland cotton, and systematically investigated their classifications, phylogenetic and synteny relationships, gene structures, domain organizations, subcellular localizations, protein interactions, tissue-specific and stresses-responsive expression patterns. Our results will provide insights into the evolution and composition of cotton PRC2, and lay the foundation for further investigation of their biological functions and regulatory mechanisms.
Subject(s)
Cell Nucleus , Gossypium , Gossypium/genetics , Phylogeny , Diploidy , DroughtsABSTRACT
Artemisinin is an endoperoxide bond-containing sesquiterpene lactone showing potent antimalarial effect as well as antitumor and antivirus activities. Inspired by this unique pharmacorphore, researchers around the world developed numerous Artemisinin derivatives. Among these derivatives, the C-10 carba analogues of artemisinin are frequently reported. However, the stereochemistry of C-10 carba analogues of artemisinin is overlooked and the corresponding mixture of stereoisomers are used. Herein, we reported for the first time stereochemistry and antimalarial activity of C-10 carba analogues of artemisinin. We employed two approaches to obtain the pure isomer of C-10 carba analogues and presented an interesting observation about their antimalarial activities. The minor isomer with large-sized substitute and S configuration at C-10 position had much lower antimalarial effect than the major isomer with R configuration. The study will shed light on the development of effective antimalarial drugs based on ART.
Subject(s)
Antimalarials , Artemisinins , Antimalarials/pharmacology , Artemisinins/pharmacology , StereoisomerismABSTRACT
Due to poor management and the lack of environmental awareness, lots of masks (an emerging form of plastic pollution) are discarded into the environment during the COVID-19, thereby jeopardizing the health of humans and the environment. Our study introduces a novel perspective by examining the impact of physical damage on the microbial composition of masks in the water environment. We focus on the variations in biofilm formation on each layer of both damaged and undamaged masks, which allows us to understand more about the biofilm on each layer and the significant changes that occur when masks are physically damaged. Research has shown that the community structure of microorganisms on discarded masks can be altered in just ten days, showing an evolution from undifferentiated pioneer colonizing species ("non-picky") to adaptive dominant species ("picky"). Especially, considering that discarded masks were inevitably damaged, we found that the biomass on the damaged samples is 1.62-2.38 times higher than that of the undamaged samples, respectively. Moreover, the microbial community structure on it was also significantly different. Genes involved in biogeochemical cycles of nutrients are more enriched in damaged masks. When damaged, the colonization process and community structure in the middle layer significantly differ from those in the inner and outer layers and even enrich more pathogenic bacteria. Based on the above, it is evident that the environmental risk of masks cannot be assessed as a whole, and the middle layer carries a higher risk.
ABSTRACT
During embryo implantation, apoptosis is inevitable. These apoptotic cells (ACs) are removed by efferocytosis, in which macrophages are filled with a metabolite load nearly equal to the phagocyte itself. A timely question pertains to the relationship between efferocytosis-related metabolism and the immune behavior of decidual macrophages (dMΦs) and its effect on pregnancy outcome. Here, we report positive feedback of IL-33/ST2-AXL-efferocytosis leading to pregnancy failure through metabolic reprogramming of dMΦs. We compared the serum levels of IL-33 and sST2, along with IL-33 and ST2, efferocytosis and metabolism of dMΦs, from patients with normal pregnancies and unexplained recurrent pregnancy loss (RPL). We revealed disruption of the IL-33/ST2 axis, increased apoptotic cells and elevated efferocytosis of dMΦs from patients with RPL. The dMΦs that engulfed many apoptotic cells secreted more sST2 and less TGF-ß, which polarized dMΦs toward the M1 phenotype. Moreover, the elevated sST2 biased the efferocytosis-related metabolism of RPL dMΦs toward oxidative phosphorylation and exacerbated the disruption of the IL-33/ST2 signaling pathway. Metabolic disorders also lead to dysfunction of efferocytosis, resulting in more uncleared apoptotic cells and secondary necrosis. We also screened the efferocytotic molecule AXL regulated by IL-33/ST2. This positive feedback axis of IL-33/ST2-AXL-efferocytosis led to pregnancy failure. IL-33 knockout mice demonstrated poor pregnancy outcomes, and exogenous supplementation with mouse IL-33 reduced the embryo losses. These findings highlight a new etiological mechanism whereby dMΦs leverage immunometabolism for homeostasis of the microenvironment at the maternal-fetal interface.
Subject(s)
Apoptosis , Interleukin-1 Receptor-Like 1 Protein/metabolism , Interleukin-33/metabolism , Proto-Oncogene Proteins/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Abortion, Spontaneous/immunology , Abortion, Spontaneous/pathology , Animals , Decidua/cytology , Female , Humans , Interleukin-1 Receptor-Like 1 Protein/blood , Interleukin-1 Receptor-Like 1 Protein/genetics , Interleukin-33/blood , Interleukin-33/deficiency , Interleukin-33/genetics , Macrophages/cytology , Macrophages/metabolism , Membrane Potential, Mitochondrial/drug effects , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitochondria/metabolism , Oligomycins/pharmacology , Oxidative Phosphorylation , Pregnancy , Protein Kinase Inhibitors/pharmacology , Signal Transduction/drug effects , Axl Receptor Tyrosine KinaseABSTRACT
Flavor-associated volatile chemicals make major contributions to consumers' perception of fruits. Although great progress has been made in establishing the metabolic pathways associated with volatile synthesis, much less is known about the regulation of those pathways. Knowledge of how those pathways are regulated would greatly facilitate efforts to improve flavor. Volatile esters are major contributors to fruity flavor notes in many species, providing a good model to investigate the regulation of volatile synthesis pathways. Here we initiated a study of peach (Prunus persica L. Batsch) fruits, and identified that the alcohol acyltransferase PpAAT1 contributes to ester formation. We next identified the transcription factor (TF) PpNAC1 as an activator of PpAAT1 expression and ester production. These conclusions were based on in vivo and in vitro experiments and validated by correlation in a panel of 30 different peach cultivars. Based on homology between PpNAC1 and the tomato (Solanum lycopersicum) TF NONRIPENING (NOR), we identified a parallel regulatory pathway in tomato. Overexpression of PpNAC1 enhances ripening in a nor mutant and restores synthesis of volatile esters in tomato fruits. Furthermore, in the NOR-deficient mutant tomatoes generated by CRISPR/Cas9, lower transcript levels of SlAAT1 were detected. The apple (Malus domestica) homolog MdNAC5 also stimulates MdAAT1 expression via binding to this gene's promoter. In addition to transcriptional control, epigenetic analysis showed that increased expression of NACs and AATs is associated with removal of the repressive mark H3K27me3 during fruit ripening. Our results support a conserved molecular mechanism in which NAC TFs activate ripening-related AAT expression, which in turn catalyzes volatile ester formation in multiple fruit species.
Subject(s)
Epigenesis, Genetic , Esters/metabolism , Food Quality , Fruit/metabolism , Gene Expression Regulation, Plant , Malus/metabolism , Prunus persica/metabolism , Solanum lycopersicum/metabolism , Transcription Factors/metabolism , Volatile Organic Compounds/metabolism , Transcription Factors/physiologyABSTRACT
Quantum key distribution (QKD) and quantum key agreement (QKA) are two main branches of key establishment in quantum cryptography. However, the research of QKA falls far behind that of QKD, especially in practicability. The main reason is that QKA needs to resist not only the outside eavesdropping but also the participant cheating. Resisting dishonest participant is more difficult than resisting outside eavesdropping, especially when the apparatuses are imperfect. Actually, existing QKA protocols cannot tolerate the channel loss and have to rely on stable quantum storage. To solve this problem, we give a new quantum multi-party key agreement protocol based on the error-correcting code. Our protocol is loss tolerant, and the participants can measure the received qubits immediately in one of two conjugate bases, without storage, so our protocol can eliminate the requirement of quantum storage. Besides, our protocol is more fair because it can partially discriminate dishonest participants' cheating from outside eavesdropping (previously, these two attacks are generally checked simultaneously via decoy states but cannot be discriminated), as a result, dishonest participants generally will not cheat at the cost of losing good reputation.
ABSTRACT
Calmodulin-binding transcription activator (CAMTA) is a transcription factor family containing calmodulin (CaM) binding sites and is involved in plant development. Although CAMTAs in Arabidopsis have been extensively investigated, the functions of CAMTAs remain largely unclear in peaches. In this study, we identified five peach CAMTAs which contained conserved CG-1 box, ANK repeats, CaM binding domain (CaMBD) and IQ motifs. Overexpression in tobacco showed that PpCAMTA1/2/3 were located in the nucleus, while PpCAMTA4 and PpCAMTA5 were located in the plasma membrane. Increased expression levels were observed for PpCAMTA1 and PpCAMTA3 during peach fruit ripening. Expression of PpCAMTA1 was induced by cold treatment and was inhibited by ultraviolet B irradiation (UV-B). Driven by AtCAMTA3 promoter, PpCAMTA1/2/3 were overexpressed in Arabidopsis mutant. Here, we characterized peach PpCAMTA1, representing an ortholog of AtCAMTA3. PpCAMTA1 expression in Arabidopsis complements the developmental deficiencies of the camta2,3 mutant, and restored the plant size to the wild type level. Moreover, overexpressing PpCAMTA1 in camta2,3 mutant inhibited salicylic acid (SA) biosynthesis and expression of SA-related genes, resulting in a susceptibility phenotype to Pst DC3000. Taken together, our results provide new insights for CAMTAs in peach fruit and indicate that PpCAMTA1 is associated with response to stresses during development.
Subject(s)
Arabidopsis , Prunus persica , Arabidopsis/metabolism , Calmodulin/metabolism , Ectopic Gene Expression , Fruit/genetics , Fruit/metabolism , Gene Expression Regulation, Plant , Plant Development , Plant Proteins/genetics , Plant Proteins/metabolism , Prunus persica/genetics , Prunus persica/metabolism , Salicylic Acid/metabolism , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
Linalool is one of the common flavour-related volatiles across the plant kingdom and plays an essential role in determining consumer liking of plant foods. Although great process has been made in identifying terpene synthase (TPS) genes associated with linalool synthesis, much less is known about regulation of this pathway. We initiated study by identifying PpTPS3 encoding protein catalysing enantiomer (S)-(+)-linalool synthesis, which is a major linalool component (Ë70%) observed in ripe peach fruit. Overexpression of PpTPS3 led to linalool accumulation, while virus-induced gene silencing of PpTPS3 led to a 66.5% reduction in linalool content in peach fruit. We next identified transcription factor (TF) PpbHLH1 directly binds to E-box (CACATG) in the PpTPS3 promoter and activates its expression based on yeast one-hybrid assay and EMSA analysis. Significantly positive correlation was also observed between PpbHLH1 expression and linalool production across peach cultivars. Peach fruit accumulated more linalool after overexpressing PpbHLH1 in peach fruit and reduced approximately 54.4% linalool production after silencing this TF. DNA methylation analysis showed increased PpTPS3 expression was associated with decreased 5 mC level in its promoter during peach fruit ripening, but no reverse pattern was observed for PpbHLH1. Arabidopsis and tomato fruits transgenic for peach PpbHLH1 synthesize and accumulate higher levels of linalool compared with wild-type controls. Taken together, these results would greatly facilitate efforts to enhance linalool production and thus improve flavour of fruits.
Subject(s)
Prunus persica , Acyclic Monoterpenes , DNA Methylation , Fruit/genetics , Fruit/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Prunus persica/geneticsABSTRACT
Cotton Verticillium wilt caused by Verticillium dahliae (V. dahliae) is one of the most destructive fungal diseases and is difficult to control. However, resistant germplasm resources are scarce in cotton. Many studies have shown that host-induced gene silencing (HIGS) is a practical and effective technology in crop disease prevention by silencing virulence genes of pathogens. Acetolactate synthase (ALS) contains a catalytic subunit ILV2 and a regulatory subunit ILV6, which catalyzes the first common step reaction in branched-chain amino acid (BCAA) biosynthesis. We identified two acetolactate synthases, VdILV2 and VdILV6, which are homologs of ILV2 and ILV6, respectively, in Magnaporthe oryzae. To characterize the function of VdILV2 and VdILV6 in V. dahliae, we suppressed their expression in the strong pathogenic isolate Vd991 by using HIGS technology. VdILV2- or VdILV6-silenced V. dahliae had a dramatic reduction in pathogenicity. The results indicated that VdILV2 and VdILV6 are involved in the pathogenicity of V. dahliae. HIGS of VdILV2 or VdILV6 provides a novel fungicide target and an effective control to resist Verticillium wilt caused by V. dahliae.
Subject(s)
Acetolactate Synthase/genetics , Gossypium/microbiology , Plant Diseases/microbiology , Verticillium/enzymology , Verticillium/genetics , Disease Resistance , Gene Expression Regulation, Fungal , Gene Silencing , Gossypium/physiology , Host-Pathogen Interactions , Verticillium/physiologyABSTRACT
Nitrate esters have been used in clinical practice for more than one century for the treatment of angina. Their clinical effectiveness is due to vasodilator activity in arteries through a method of delivering nitric oxide or a nitric oxide-like compound. Recently, an increasing numbers of functions of this molecule in biology and pathophysiology have been discovered. Macrophage polarization shift in epicardial adipose tissue (EAT) has been demonstrated to be correlated with the severity of coronary artery disease (CAD). In this study, we aimed to investigate whether nitrate esters could improve coronary atherosclerosis through inhibition of macrophage polarization shift in EAT. A case-control study enrolled 48 subjects in 2 groups: CAD patients with or without nitrate esters treatment. Infiltration of M1/M2 macrophages and the expressions of pro-inflammatory and anti-inflammatory cytokines in EAT and subcutaneous white adipose tissue were investigated by immunohistochemical stain among subjects undergoing coronary artery bypass graft surgery. The expression levels of metabolic genes were investigated by real-time reverse transcription-polymerase chain reaction (RT-PCR). We found that nitrate ester treatment significantly inhibited NF-кB activity and decreased macrophage infiltration and M1/M2 macrophage ratio in EAT in patients with CAD. The expressions of pro-inflammatory cytokines were significantly decreased, along with significantly elevated expressions of anti-inflammatory cytokines in CAD patients with nitrate ester treatment, corresponding EAT dysfunction was ameliorated and the severity of patients with CAD (Gensini score) was significantly decreased. The protective effects on macrophage polarization and EAT function through NF-кB activity inhibition suggested a potential mechanism of nitrate esters in alleviating the severity of CAD.
Subject(s)
Adipose Tissue, White/drug effects , Anti-Inflammatory Agents/therapeutic use , Coronary Artery Disease/drug therapy , Esters/therapeutic use , Macrophages/drug effects , NF-kappa B/metabolism , Nitrates/therapeutic use , Pericardium/drug effects , Adipose Tissue, White/metabolism , Adipose Tissue, White/pathology , Aged , Case-Control Studies , Coronary Artery Disease/metabolism , Coronary Artery Disease/pathology , Cytokines/metabolism , Female , Humans , Inflammation Mediators/metabolism , Macrophages/metabolism , Macrophages/pathology , Male , Middle Aged , Pericardium/metabolism , Pericardium/pathology , Severity of Illness Index , Signal TransductionABSTRACT
Verticillium dahliae (V. dahliae) infects roots and colonizes the vascular vessels of host plants, significantly reducing the economic yield of cotton and other crops. In this study, the protein VdTHI20, which is involved in the thiamine biosynthesis pathway, was characterized by knocking out the corresponding VdTHI20 gene in V. dahliae via Agrobacterium tumefaciens-mediated transformation (ATMT). The deletion of VdTHI20 resulted in several phenotypic defects in vegetative growth and conidiation and in impaired virulence in tobacco seedlings. We show that VdTHI20 increases the tolerance of V. dahliae to UV damage. The impaired vegetative growth of ΔVdTHI20 mutant strains was restored by complementation with a functional copy of the VdTHI20 gene or by supplementation with additional thiamine. Furthermore, the root infection and colonization of the ΔVdTHI20 mutant strains were suppressed, as indicated by green fluorescent protein (GFP)-labelling under microscope observation. When the RNAi constructs of VdTHI20 were used to transform Nicotiana benthamiana, the transgenic lines expressing dsVdTHI20 showed elevated resistance to V. dahliae. Together, these results suggest that VdTHI20 plays a significant role in the pathogenicity of V. dahliae. In addition, the pathogenesis-related gene VdTHI20 exhibits potential for controlling V. dahliae in important crops.
Subject(s)
Biosynthetic Pathways , DNA Repair , Fungal Proteins/metabolism , Pyrimidines/biosynthesis , Verticillium/metabolism , Verticillium/pathogenicity , Biosynthetic Pathways/drug effects , Biosynthetic Pathways/genetics , DNA Repair/drug effects , Fluorescence , Fungal Proteins/genetics , Gene Deletion , Gene Expression Regulation, Fungal/drug effects , Gene Expression Regulation, Fungal/radiation effects , Genetic Complementation Test , Green Fluorescent Proteins/metabolism , Mutation/genetics , Mycelium/drug effects , Mycelium/growth & development , Mycelium/metabolism , Plant Roots/drug effects , Plant Roots/microbiology , Plants, Genetically Modified , Thiamine/pharmacology , Nicotiana/microbiology , Ultraviolet Rays , Verticillium/drug effects , Verticillium/growth & development , Virulence/drug effects , Virulence/genetics , Virulence/radiation effectsABSTRACT
Endometriosis (EMS) is a chronic inflammatory disease characterized by the presence of extrauterine endometrial tissues. It has been previously reported that the refluxed blood containing viable endometrial tissues and the defective elimination of peritoneal macrophages in the pelvic cavity may involve in EMS pathogenesis. However, the mechanism by which macrophages exhibit attenuated phagocytic capability in EMS remains undetermined. Herein, we found that heme, the byproduct of lysed erythrocytes, accumulated abnormally in the peritoneal fluid (PF) of patients with EMS (14.22 µmol/L, 95% confidence interval (CI): 12.54-16.71), compared with the EMS-free group (9.517 µmol/L, 95% CI: 8.891-10.1053). This abnormal accumulation was not associated with the color of PF, phase of the menstrual cycle or severity of the disease. The reduced phagocytic ability of peritoneal macrophages (pMφs) was observed in the EMS group. Consistently, a high-concentration (30 µmol/L) heme treatment impaired EMS-pMφs phagocytosis more than a low-concentration (10 µmol/L) heme treatment. A similar phenomenon was observed in the EMS-free control pMφs (Ctrl-pMφs) and the CD14+ peripheral monocytes (CD14+ Mos). These results indicated that a high heme concentration exhibits a negative effect on macrophage phagocytosis, which supplements the mechanism of impaired scavenger function of pMφs in EMS.
Subject(s)
Ascitic Fluid/chemistry , Endometriosis/metabolism , Heme/analysis , Macrophages/metabolism , Peritoneal Diseases/metabolism , Phagocytosis/physiology , Adult , Endometriosis/pathology , Female , Humans , Macrophages/pathology , Middle Aged , Young AdultABSTRACT
Sugarcane yellow leaf virus (SCYLV), the causal agent of yellow leaf, is widespread in Florida. Two field trials were set up, one on organic soil and one on mineral soil, to investigate the rate and timing of sugarcane infection by SCYLV under field conditions and the effect of the virus on yield. Each trial consisted of plots planted with healthy or SCYLV-infected seed cane of two commercial cultivars. Virus prevalence varied from 83 to 100% in plots planted with infected seed cane regardless of cultivar, location, and crop season. On organic soil, plants of virus-free plots became progressively infected in plant cane and first ratoon crops. On mineral soil, healthy sugarcane became initially infected in the first ratoon crop. After three crop seasons, the highest SCYLV prevalence rates were 33 and 7% on organic and mineral soils, respectively. No significant negative effect of SCYLV on yield was found in plant cane crop regardless of cultivar and soil type. However, yield reductions in ratoon crops varied from nonsignificant to 27% depending on cultivar and soil type. Low virus prevalence observed after three crop seasons suggested that planting virus-free seed cane should limit the impact of SCYLV on sugarcane production in Florida.