Alpha-linolenic Acid Metabolism Research Articles

Mechanisms of cordycepin in the treatment of pulmonary arterial hypertension in rats based on metabonomics and transcriptomics

Pulmonary arterial hypertension (PAH) is a fatal disease featured by high morbidity and mortality. Although Cordycepin is known for its anti-inflammatory, antioxidant and immune-enhancing effects, its role in PAH treatment and the underlying mechanisms remain unclear. The therapeutic effects of Cordycepin on rats with PAH were investigated using a monocrotaline (MCT)-induced rat model. The metabolic effects of Cordycepin were assessed based on the plasma metabolome. The potential mechanisms of Cordycepin in PAH treatment were investigated through transcriptome sequencing and validated in pulmonary artery smooth muscle cells (PASMC). Evaluations included hematoxylin and eosin staining for pulmonary vascular remodeling, CCK-8 assay, EDU, and TUNEL kits for cell viability, proliferation, and apoptosis, respectively, and western blot for protein expression. Cordycepin significantly reduced right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) in PAH rats, and mitigated pulmonary vascular remodeling. Plasma metabolomics showed that Cordycepin could reverse the metabolic disorders in the lungs of MCT-induced PAH rats, particularly impacting linoleic acid and alpha-linolenic acid metabolism pathways. Transcriptomics revealed that the P53 pathway might be the primary pathway involved, and western blot results showed that Cordycepin significantly increased P53 and P21 protein levels in lung tissues. Integrated analysis of transcriptomics and metabolomics suggested that these pathways were mainly enriched in linoleic acid metabolism and alpha-linolenic acid metabolism pathway. In vitro experiments demonstrated that Cordycepin significantly inhibited the PDGFBB (PD)-induced abnormal proliferation and migration of PASMC and promoted PD-induced apoptosis. Meanwhile, Cordycepin enhanced the expression levels of P53 and P21 proteins in PD-insulted PASMC. However, inhibitors of P53 and P21 eliminated these effects of Cordycepin. Cordycepin may activate the P53–P21 pathway to inhibit abnormal proliferation and migration of PASMC and promote apoptosis, offering a potential approach for PAH treatment.

Gestational Long Term High-Altitude Hypoxia and Metabolomic Reprogramming in Uterine Arteries of Adult Sheep

Long term hypoxic stress during pregnancy causes a reduction in uterine blood flow, compromising oxygen and nutrient delivery to the fetus. There are multiple epigenetic factors involved in the structural and functional impairments that underlie the impairments in uterine arterial function. Evidence indicates that oxidative stress plays an important role to the decrements in blood flow following high altitude pregnancy. The purpose of the current study was to test the hypothesis that changes in oxylipin and endocannabinoid signaling are important to the increases in oxidative stress along with changes in glucose and fat metabolism. To further understand the mechanisms associated with disruption of uterine artery blood flow due to high altitude pregnancy, we examined a high altitude pregnant sheep model. Pregnant and non-pregnant sheep were housed either at low (700m) or high altitude (3801 meters) for 110+ days of pregnancy. Uterine arteries were excised from pregnant and non-pregnant sheep and targeted as well as untargeted metabolomic analyses were performed to test the hypothesis that hypoxia increases oxidative stress and reduces oxidative metabolism. Enrichment analysis of the metabolites show that hypoxia impacted several key biochemical pathways. At high altitude there were decreases in Alpha Linolenic Acid and Linoleic Acid Metabolism along with reductions in Pyruvate Metabolism and antioxidants. Further to this, there was an increase in the metabolism of Arachidonic Acid, Glycerolipids, and Methionine, which are linked to inflammation, cell signaling, and cell growth. Fully understanding how increased oxidative stress and inflammatory pathways along with decreased antioxidant capacity and changes in cellular metabolism is tied to malformations in uterine arterial structure and function following high altitude gestation is an active area of investigation. This work was supported by the National Institutes of Health Grants NIH R01HL155295, R01HL149608, R03HD098477, P01HD083132, and U24DK097154. Additional support was provided by the Loma Linda University School of Medicine and West Coast Metabolomics Center. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Crosstalk between endothelial cells and dermal papilla entails hair regeneration and angiogenesis during aging

IntroductionTissues maintain their function through interaction with microenvironment. During aging, both hair follicles and blood vessels (BV) in skin undergo degenerative changes. However, it is elusive whether the changes are due to intrinsic aging changes in hair follicles or blood vessels respectively, or their interactions. ObjectiveTo explore how hair follicles and blood vessels interact to regulate angiogenesis and hair regeneration during aging. MethodsSingle-cell RNA-sequencing (scRNA-seq) analyses were used to identify the declined ability of dermal papilla (DP) and endothelial cells (ECs) during aging. CellChat and CellCall were performed to investigate interaction between DP and ECs. Single-cell metabolism (scMetabolism) analysis and iPATH were applied to analyze downstream metabolites in DP and ECs. Hair-plucking model and mouse cell organoid model were used for functional studies. ResultsDuring aging, distance and interaction between DP and ECs are decreased. DP interacts with ECs, with decreased EDN1-EDNRA signaling from ECs to DP and CTF1-IL6ST signaling from DP to ECs during aging. ECs-secreted EDN1 binds to DP-expressed EDNRA which enhances Taurine (TA) metabolism to promote hair regeneration. DP-emitted CTF1 binds to ECs-expressed IL6ST which activates alpha-linolenic acid (ALA) metabolism to promote angiogenesis. Activated EDN1-EDNRA-TA signaling promotes hair regeneration in aged mouse skin and in organoid cultures, and increased CTF1-IL6ST-ALA signaling also promotes angiogenesis in aged mouse skin and organoid cultures. ConclusionsOur finding reveals reciprocal interactions between ECs and DP. ECs releases EDN1 sensed by DP to activate TA metabolism which induces hair regeneration, while DP emits CTF1 signal received by ECs to enhance ALA metabolism which promotes angiogenesis. Our study provides new insights into mutualistic cellular crosstalk between hair follicles and blood vessels, and identifies novel signaling contributing to the interactions of hair follicles and blood vessels in normal and aged skin.

Transcriptome differential expression analysis of defoliation of two different lemon varieties.

'Allen Eureka' is a bud variety of Eureka lemon with excellent fruiting traits. However, it suffers from severe winter defoliation that leads to a large loss of organic nutrients and seriously affects the tree's growth and development as well as the yield of the following year, and the mechanism of its response to defoliation is still unclear. In order to investigate the molecular regulatory mechanisms of different leaf abscission periods in lemon, two lemon cultivars ('Allen Eureka' and 'Yunning No. 1') with different defoliation traits were used as materials. The petiole abscission zone (AZ) was collected at three different defoliation stages, namely, the pre-defoliation stage (CQ), the mid-defoliation stage (CZ), and the post-defoliation stage (CH). Transcriptome sequencing was performed to analyze the gene expression differences between these two cultivars. A total of 898, 4,856, and 3,126 differentially expressed genes (DEGs) were obtained in CQ, CZ, and CH, respectively, and the number of DEGs in CZ was the largest. GO analysis revealed that the DEGs between the two cultivars were mainly enriched in processes related to oxidoreductase, hydrolase, DNA binding transcription factor, and transcription regulator activity in the defoliation stages. KEGG analysis showed that the DEGs were concentrated in CZ and involved plant hormone signal transduction, phenylpropanoid biosynthesis, glutathione metabolism, and alpha-linolenic acid metabolism. The expression trends of some DEGs suggested their roles in regulating defoliation in lemon. Eight gene families were obtained by combining DEG clustering analysis and weighted gene co-expression network analysis (WGCNA), including β-glucosidase, AUX/IAA, SAUR, GH3, POD, and WRKY, suggesting that these genes may be involved in the regulation of lemon leaf abscission. The above conclusions enrich the research related to lemon leaf abscission and provide reliable data for the screening of lemon defoliation candidate genes and analysis of defoliation pathways.

Excessive level of dietary insect protein negatively changed growth metabolomic and transcriptomic profiles of largemouth bass (Micropterus salmoides)

Hermetia illucens (HI) meal is a promising substitute for fish meal (FM) in the feeds of farmed fish. However, the impacts of dietary HI meal on largemouth bass (LMB) remain unknown. In this study, we formulated three isonitrogenous and isolipid diets with 0% (HI0, control), 20% (HI20) and 40% (HI40) of FM substituted by HI meal. A total of 270 juvenile largemouth bass with an initial body weight of 10.02 ± 0.03 g were used (30 fish per tank). After an 80-day feeding trial, the fish fed with the HI40 diet demonstrated decreased growth performance and protein efficiency ratio (PER), and increased liver oxidative indices and lipid accumulation compared to the control (P < 0.05). Transcriptomic analysis revealed the effects of high dietary HI meal on liver gene expression. Consistent with the reduced growth and disturbed liver oxidative status, the upregulated genes were enriched in the biological processes associated with protein catabolism and endoplasmic reticulum (ER) stress; while the downregulated genes were enriched in cellular proliferation, growth, metabolism, immunity and maintenance of tissue homeostasis. Differential metabolites in the liver samples were also identified by untargeted metabolomic assay. The results of joint transcriptomic–metabolomic analyses revealed that the pathways such as one carbon pool by folate, propanoate metabolism and alpha-linolenic acid metabolism were disturbed by high dietary HI meal. In summary, our data revealed the candidate genes, metabolites and biological pathways that account for the adverse effects of high HI meal diet on the growth and health of LMB.

Fine Mapping of qAL5.2 Controlling Anther Length in Oryza sativa.

Anther length is the critical floral trait determining hybrid rice seed production and is controlled by many quantitative trait loci (QTL). However, the cloning of genes specifically controlling anther size has yet to be reported. Here, we report the fine mapping of qAL5.2 for anther size using backcross inbred lines (BILs) in the genetic background of Oryza sativa indica Huazhan (HZ). Gene chip analysis on the BC4F2 and BC5F1 population identified effective loci on Chr1, Chr5, and Chr8 and two genomic regions on Chr5, named qAL5.1 and qAL5.2. qAL5.2 was identified in both populations with LOD values of 17.54 and 10.19, which explained 35.73% and 25.1% of the phenotypic variances, respectively. Ultimately qAL5.2 was localized to a 73 kb region between HK139 and HK140 on chromosome 5. And we constructed two near-isogenic lines (NILs) for RNA-seq analysis, named NIL-qAL5.2HZ and NIL-qAL5.2KLY, respectively. The result of the GO enrichment analysis revealed that differential genes were significantly enriched in the carbohydrate metabolic process, extracellular region, and nucleic acid binding transcription, and KEGG enrichment analysis revealed that alpha-linolenic acid metabolism was significantly enriched. Meanwhile, candidate genes of qAL5.2 were analyzed in RNA-seq, and it was found that ORF8 is differentially expressed between NIL-qAL5.2HZ and NIL-qAL5.2KLY. The fine mapping of qAL5.2 conferring anther length will promote the breed improvement of the restorer line and understanding of the mechanisms driving crop mating patterns.

Identification of differentially expressed genes and metabolism signaling pathway in the spleen of broilers supplemented with probiotic Bacillus spp.

Probiotics are essential in the body’s nutrients, improving the ratio of meat to meat, immune response, and preventing diseases. In this study, RNA-sequencing (RNA-seq) was used to identify the differentially expressed genes (DEGs), enriched related pathways, and Gene Ontology (GO) terms among blank negative control (NC), supplemented with Bacillus spp. (BS) and commercial probiotic (PC) groups after a 42-day fed supplementation. The results showed that 2005, 1356, and 2189 DEGs were significantly altered in BS vs. NC, PC vs NC, and BS vs PC groups, respectively. On the other hand, 9 DEGs were further validated by qRT-PCR, indicating that the qRT-PCR and RNA-Seq results were more consistent. Therefore, the GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of DEGs showed that the DEGs were mainly enriched to metabolism signalling pathways (alpha-linolenic acid metabolism, linoleic acid metabolism, tryptophan metabolism, tyrosine metabolism, ether lipid metabolism, and metabolic pathway, etc) and immune response pathways (cytokine-cytokine receptor interaction, MAPK signalling pathway, and intestinal immune network for IgA production, neuroactive ligand-receptor interaction etc). These results will provide a better understanding of the role of probiotics in chicken development and provide basic information on the genetic development of chickens.

Toxicity and transcriptome sequencing analyses of Acipenser schrenckii under titanium dioxide nanoparticles stress

Increasing utilization of titanium dioxide nanoparticles (TiO2-NPs), with a wide range of applications, has resulted in the increased release of the material into the environment. In this study, we combined Illumina short-line RNA sequencing (RNA-Seq) and PacBio Iso-sequencing methods to obtain the transcriptome of Acipenser schrenckii livers treated with 5.27 (TH), 0.527 (TM), and 0.0527 mg/L (TL) TiO2-NPs for 14 days to elucidate the mechanisms underlying the effects of TiO2-NPs on sturgeons. In total, 39.67G subread bases and 31092 de-redundant transcripts (8929 unigenes) were obtained from A. schrenckii livers, with a mean length of 2289 bp. Moreover, 293 differentially expressed genes (DEGs) related to TiO2-NP stress were identified using DESeq; 175, 174, and 62 DEGs were identified in the TH vs. TC, TM vs. TC, and TL vs. TC groups. The Kyoto Encyclopedia of Genes and Genomes pathways of DEGs related to immunity (neuroactive ligand-receptor interaction, rheumatoid arthritis, NF-kappa B signaling pathway, and graft-versus-host disease) were significantly altered by TiO2-NP exposure, and the expression of interleukin-8, a possible biomarker for environmental pollution, was significantly upregulated. The pathways of alpha-linolenic acid metabolism, glycerolipid metabolism, and arachidonic acid metabolism associated with the defense against oxidative stress were also influenced by TiO2-NP exposure. The activity of carboxyl ester lipase involved in glycerolipid metabolism was rapidly downregulated in the TH and TM groups which may play a major role in glycerolipid metabolism regulation. The expression patterns of eight selected genes were generally consistent with the quantitative real-time PCR analysis results.

Exploring the mechanism of Huanglian ointment in alleviating wound healing after anal fistula surgery through metabolomics and proteomics

Anal fistula is a common anal and intestinal disease. The wound of anal fistula surgery is open and polluting, which is the most difficult to heal among all surgical incisions. To investigate the mechanism of Huanglian ointment (HLO) on wound healing after anal fistula incision. The S. aureus infected wound in SD rats were used to imitate poor healing wound after anal fistula surgery. SD rats with wound sites (n = 24) were randomly divided into four groups (Control group, Model group, Potassium permanganate (PP) treatment group, and HLO treatment group). The wound healing rate was evaluated, HE staining was used to evaluate the pathological changes of each group, ELISA was used to detect the secretion of inflammatory factors in each group, and the mechanism was explored through metabolomics and proteomics in plasma rat. Compared to other groups, the rate of wound healing in the HLO group was higher on days 7 and 14. Histological analysis showed that collagen and fibroblast in HLO rats were significantly increased, inflammatory cells were reduced, and vascular endothelial permeability was increased. ELISA results showed that the secretion of inflammatory factors in HLO rats was significantly lower. Significant proteins and metabolites were identified in the wound tissues of the infected rats and HLO-treated rats, which were mainly attributed to Cdc42, Ctnnb1, Actr2, Actr3, Arpc1b, Itgam, Itgb2, Cttn, Linoleic acid metabolism, d-Glutamine and d-glutamate metabolism, Phenylalanine, tyrosine and tryptophan biosynthesis, Phenylalanine metabolism, alpha-Linolenic acid metabolism, and Ascorbate and aldarate metabolism. In conclusion, this study showed that HLO can promote S. aureus infected wound healing, and the data provide a theoretical basis for the treatment of wounds after anal fistula surgery with HLO.

Transcriptome analysis reveals the mechanism of NaHCO3 promoting tobacco leaf maturation.

NaHCO3 accelerates the aging of tobacco leaves; however, the underlying molecular mechanisms have not been elucidated. This study aimed to explore the mechanism of NaHCO3 in the promotion of tobacco leaf maturation using transcriptome analysis. Leaves on plants or detached leaves of the tobacco variety, Honghua Dajinyuan, were sprayed with or without 1% NaHCO3. The leaf yellowing was observed, the pigment content and enzyme activities were determined and RNA sequencing (RNA-seq) was performed. Spraying NaHCO3 onto detached leaves was found to promote leaf yellowing. Pigment content, catalase activity, and superoxide dismutase activity significantly decreased, whereas peroxidase activity and malondialdehyde content significantly increased. RNA-seq demonstrated that spraying with NaHCO3 upregulated genes associated with cysteine and methionine metabolism; alpha-linolenic acid metabolism; and phenylalanine, tyrosine, and tryptophan biosynthesis and downregulated genes related to photosynthesis and carotenoid biosynthesis. Genes correlated with autophagy-other, valine, leucine, and isoleucine degradation, and the MAPK signaling pathway were upregulated while those correlated with DNA replication, phenylalanine, and tyrosine and tryptophan biosynthesis were downregulated in detached leaves sprayed with NaHCO3 compared with the plant leaves sprayed with NaHCO3. Overall, this study is the first to elucidate the molecular and metabolic mechanisms of NaHCO3 in the promotion of tobacco leaf maturation.

Poria cocos polysaccharides alleviate cyclophosphamide-induced immunosuppression effects in silkworm and their metabolic profiling analysis

The present study investigated the immune regulatory mechanisms of Poria cocos polysaccharides (PS) in a cyclophosphamide (CTX)-induced immunosuppression silkworm model. We found that PS increased the superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities, as well as reactive oxygen species (ROS) levels in the fat body or haemocytes of CTX-treated silkworms. PS also strongly stimulated the immunity of silkworms by increasing haemocyte counts and PO activity and upregulating the mRNA expression of immune-related genes. We further investigated the metabolic profile of the fat body after PS treatment using liquid chromatography–massspectrometry/mass spectrometry (LC–MS/MS) and identified 236 differentially expressed metabolites. Among them, nine metabolites related to amino acid metabolism were present at high levels in the PS-treated group, whereas the contents of metabolites involved in sphingolipid metabolism and alpha-linolenic acid metabolism were significantly decreased after PS treatment. The amino acid metabolism pathways and lipid metabolism pathways were found to be significantly altered in the PS-treated group, which indicates that PS may regulate the immune system of silkworms by reprogramming lipid and amino acid metabolism. This study provides new insight into the immune regulatory effect of PS in animals.

Metabolome Revealed the Potential Mechanism of Fusarium Wilt Resistance in Bitter Gourd (Momordica charantia) Based on Liquid Chromatography with Mass Spectrometry.

Fusarium wilt fungus infection of bitter gourd, a major melon vegetable crop, results in massive yield reduction. Through extensive testing, some Fusarium wilt-resistant bitter melon varieties have been produced, but the molecular mechanism of their resistance to the fungus remains unknown. Importantly, after bitter melon plants are infected with Fusarium oxysporum f. sp. momordicae (FOM), apart from altering their gene expression levels, numerous metabolites are produced because of the interaction with the fungus. In the current study, an untargeted metabolomics analysis was performed to investigate the metabolic difference between resistant and susceptible bitter gourd varieties at various timepoints postinoculation with FOM based on liquid chromatography with mass spectrometry. A total of 1,595 positive ion mode and 922 negative ion mode metabolites were identified. Between the resistant and susceptible bitter gourd varieties, 213 unique differentially abundant metabolites (DAMs) were identified, and they were mainly enriched in the alpha-linolenic acid metabolism pathway. By comparing the postinoculation with preinoculation timepoints in the resistant and susceptible bitter gourd varieties, 93 and 159 DAMs were identified, respectively. These DAMs were mainly related to beta-alanine metabolism, among others. Multiple metabolites in the biosynthesis of the phenylpropanoid pathway showed greater variability in the susceptible than the resistant varieties, which may be related to senescence and mortality in the susceptible variety. These results provide new insights into the understanding of metabolite changes after FOM infection and a theoretical foundation for the elucidation of the bitter gourd disease resistance mechanism.

A Phytophthora infestans RXLR effector PiAVR3b suppresses plant immunity by perturbing jasmonic acid biosynthesis

P. infestans, the causative agent of the most destructive potato disease, significantly diminishes crop yields. The pathogen's RXLR effector, PiAVR3b, dampens pattern-triggered immunity (PTI) and mitigates cell necrosis caused by other effectors, thus playing a pivotal role in P. infestans infection. The mechanism by which PiAVR3b undermines plant defenses, however, has remained obscure. Our research establishes that PiAVR3b's transient expression promotes P. infestans colonization in Nicotiana benthamiana and that PiAVR3b-transgenic potato lines show reduced PTI to flg22 and heightened susceptibility to P. infestans. Transcriptomic analysis indicate that PiAVR3b expression downregulates genes associated with phenylpropanoid, monoterpenoid biosynthesis, and phenylalanine, alpha-linolenic acid metabolism, leading to a substantial reduction in jasmonic acid (JA) synthesis. Moreover, application of methyl jasmonate (MeJA) on both wild-type and transgenic lines bolsters resistance to P. infestans and activates JA signaling pathways. Our findings reveal that PiAVR3b is a virulence factor that compromises JA-mediated defense, thus facilitating P. infestans invasion.

Assessment of progression of pulmonary fibrosis based on metabonomics and analysis of intestinal microbiota

The main purpose of this study was to explore the changes of biomarkers in different developmental stages of bleomycin-induced pulmonary fibrosis (PF) in rats via comprehensive pathophysiology, UPLC-QTOF/MS metabonomic technology, and 16S rRNA gene sequencing of intestinal microbiota. The rats were randomly divided into normal control and 1-, 2- and 4-week model group. The rat model of PF was established by one-time intratracheal instillation of bleomycin. The levels of inflammatory and fibrosis-related factors such as hydroxyproline (HYP), type III procollagen (COL-III), type IV collagen (COL-IV), hyaluronidase (HA), laminin (LN), interleukin (IL)-1β, IL-6, malondialdehyde (MDA) increased and superoxide dismutase (SOD) decreased as the PF cycle progressed. In the 1-, 2- and 4-week model group, 2, 19 and 18 potential metabolic biomarkers and 3, 16 and 12 potential microbial biomarkers were detected, respectively, which were significantly correlated. Glycerophospholipid metabolism pathway was observed to be an important pathway affecting PF at 1, 2 and 4 weeks; arginine and proline metabolism pathways significantly affected PF at 2 weeks. Linoleic acid metabolism pathway exhibited clear metabolic abnormalities at 2 and 4 weeks of PF, and alpha-linolenic acid metabolism pathway significantly affected PF at 4 weeks.

Enhancement effects and mechanisms of iron filings on the performance of anaerobic co-digestion of hulless barley straw and pig manure

In order to study the enhancing effects and mechanisms of iron filings in anaerobic co-digestion (co-AD), we investigated the effects of different concentrations of iron filings (0 g L−1, 6 g L −1, 10 g L −1, 14 g L −1, 18 g L −1) on the co-AD of hulless barley straw and pig manure, based on medium-temperature batch anaerobic digestion. The results revealed that the addition of iron filings improved the methane production performance of co-AD, and that cumulative methane production was the highest (375.26 mL g−1 VS) when the addition concentration was 14 g L −1, which was 21.33 % higher than that of the treatment group without added iron filings. The addition of an appropriate amount iron filings can also provide certain economic benefits. The addition of iron filings increased the relative abundances of bacterial groups such as Fermentimonas, Proteiniphilum, Syner-01, Ercella, Thermovirga, unclassified Synergistaceae and unclassified Anaerolineaceae as well as acetate trophic methanogens such as Methanothrix and Methanosarcina, but it did not promote the growth of hydrogenotrophic methanogens. The addition of iron filings increased the electron transport system (ETS) activity of the co-AD and enhanced the enrichment of microorganisms involved in direct interspecies electron transfer (DIET), such as Methanothrix, Methanosarcina and unclassified Anaerolineaceae. This may represent one of the key reasons behind the observed increase in methane production. A metabolomic analysis found that the presence of 47 metabolites may have been related to the addition of iron filings, suggesting that their addition significantly affected the related metabolic pathways of the co-AD. The differential metabolites were mainly enriched in metabolic pathways such as ATP-binding cassette (ABC) transport, purine metabolism, linoleic acid metabolism, and alpha-linolenic acid metabolism.

The causal relationship between serum metabolites and the risk of psoriasis: a Mendelian randomization and meta-analysis study.

To explore the influence of serum metabolites on the risk of psoriasis. In the initial stage, we applied Mendelian randomization to evaluate the association between 1,400 serum metabolites and the risk of psoriasis. Causal effects were primarily assessed through the Inverse-Variance Weighted method and Wald Ratio's odds ratios, and 95% confidence intervals. False Discovery Rate was used for multiple comparison corrections. Sensitivity analyses were conducted using Cochran's Q Test, MR-PRESSO. MR-Steiger Test was employed to check for reverse causality. In the validation stage, we sought other sources of psoriasis GWAS data to verify the initial results and used meta-analysis to combine the effect sizes to obtain robust causal relationships. In addition, we also conducted metabolic pathway enrichment analysis on known metabolites that have a causal relationship with the risk of psoriasis in both stages. In the initial stage, we identified 112 metabolites causally associated with psoriasis, including 32 metabolite ratios and 80 metabolites (69 known and 11 unknown). In the validation stage, 24 metabolites (16 known, 1 unknown, and 7 metabolite ratios) were confirmed to have a causal relationship with psoriasis onset. Meta-analysis results showed that the overall effect of combined metabolites was consistent with the main analysis in direction and robust in the causal relationship with psoriasis onset. Of the 16 known metabolites, most were attributed to lipid metabolism, with 5 as risk factors and 8 as protective factors for psoriasis. Peptidic metabolite Gamma-glutamylvaline levels had a negative causal relationship with psoriasis, while exogenous metabolite Catechol sulfate levels and amino acid 3-methylglutaconate levels had a positive causal relationship with the disease onset. The metabolites associated with psoriasis risk in the two stages are mainly enriched in the following metabolic pathways: Glutathione metabolism, Alpha Linolenic Acid and Linoleic Acid Metabolism, Biosynthesis of unsaturated fatty acids, Arachidonic acid metabolism, Glycerophospholipid metabolism. Circulating metabolites may have a potential causal relationship with psoriasis risk, and targeting specific metabolites may benefit psoriasis diagnosis, disease assessment, and treatment.

Evaluation of aphid resistance on different rose cultivars and transcriptome analysis in response to aphid infestation

BackgroundThe rose is one of the most important ornamental flowers in the world for its aesthetic beauty but can be attacked by many pests such as aphids. Aphid infestation causes tremendous damage on plant tissues leading to harmed petals and leaves. Rose cultivars express different levels of resistance to aphid infestation yet the information remains unclear. Not only that, studies about the transcriptional analysis on defending mechanisms against aphids in rose are limited so far.ResultsIn this study, the aphid resistance of 20 rose cultivars was evaluated, and they could be sorted into six levels based on the number ratio of aphids. And then, a transcriptome analysis was conducted after aphid infestation in one high resistance (R, Harmonie) and one highly susceptibility (S, Carefree Wonder) rose cultivar. In open environment the majority of rose cultivars had the highest aphid number at May 6th or May 15th in 2020 and the resistance to infestation could be classified into six levels. Differential expression analysis revealed that there were 1,626 upregulated and 767 downregulated genes in the R cultivar and 481 upregulated and 63 downregulated genes in the S cultivar after aphid infestation. Pathway enrichment analysis of the differentially expressed genes revealed that upregulated genes in R and S cultivars were both enriched in defense response, biosynthesis of secondary metabolites (phenylpropanoid, alkaloid, and flavonoid), carbohydrate metabolism (galactose, starch, and sucrose metabolism) and lipid processing (alpha-linolenic acid and linolenic acid metabolism) pathways. In the jasmonic acid metabolic pathway, linoleate 13S-lipoxygenase was specifically upregulated in the R cultivar, while genes encoding other crucial enzymes, allene oxide synthase, allene oxide cyclase, and 12-oxophytodienoate reductase were upregulated in both cultivars. Transcription factor analysis and transcription factor binding search showed that WRKY transcription factors play a pivotal role during aphid infestation in the R cultivar.ConclusionsOur study indicated the potential roles of jasmonic acid metabolism and WRKY transcription factors during aphid resistance in rose, providing clues for future research.

Key role of hormone signal transduction and lipid metabolism in the development of Nitraria sibirica leaves: An integrated metabolomic and transcriptomic analysis

Plant growth is a complex process controlled by a variety of genetic and environmental variables. Nitraria sibirica Pall. is a multi-purpose euhalophyte with economic and medicinal value. However, the molecular mechanisms underlying the changes at different growth stages in N. sibirica remain unreported. In this study, the morphology and physiological characteristics of N. sibirica were compared at the vegetative, full flowering, and fruiting stages. Metabolomics and transcriptomics were used to describe metabolite accumulation and transcriptome expression at different stages, and the relationship between gene expression patterns and metabolite accumulation was studied based on a joint analysis of the two approaches. The results indicated significant variations in the morphological and physiological characteristics of N. sibirica at different growth stages (P < 0.05). Transcriptome and metabolome samples corresponding to the three stages were clearly distinguished, and the metabolite and gene module showed high consistency. The amount of DEMs and DEGs decreased as leaf growth progressed. Differentially expressed genes (DEGs) predominantly belonged to the MYB transcription family, whereas differentially expressed metabolites (DEMs) were dominated by lipids and lipid-like molecules. DEGs were mainly enriched in plant hormone signal transduction, cutin, suberine, and wax biosynthesis pathways, whereas DEMs were mainly enriched in linoleic acid, alpha-linolenic acid metabolism, and phenylpropane biosynthesis pathways. Combined transcriptomic and metabolomic analyses revealed that plant hormone signal transduction, linoleic acid, alpha-linolenic acid, cutin, suberine, and wax biosynthesis were the most significant key pathways for the co-enrichment of DEMs and DEGs. Pearson correlation analysis showed that physiological traits were strongly correlated with DEGs, whereas morphological traits were strongly correlated with DEMs. Moreover, a strong correlation was also observed between DEMs and DEGs. In conclusion, this research provides insights into the metabolic and transcriptional regulatory networks involved in plant development.

Dietary Serine Supplementation Improves Growth Performance, Intramuscular Fat Content, and Composition of Gut Microbes and Metabolites in Growing–Finishing Pigs

Serine is widely involved in antioxidant synthesis, immune response, and fat metabolism. However, it remains unclear whether dietary serine supplementation affects fat deposition in the skeletal muscles of pigs. Thus, we explored the effects of dietary serine supplementation on growth performance, meat quality, and composition of gut microbes and their metabolites in growing–finishing pigs. Forty-eight boars weighing approximately 20 kg were fed either a basal diet or a basal diet supplemented with 0.15% serine. The results showed that dietary serine increased the daily weight gain of pigs and improved serum antioxidant capacity as indicated by the decreased malondialdehyde content and increased glutathione and superoxide dismutase content. Pigs supplemented with serine had better meat quality, as shown by the lower drip loss and higher IMF content. Furthermore, dietary serine increased the relative abundance of Streptococcus and Lactobacillus and decreased the relative abundance of Clostridium_sensu_stricto_1 and Terrisporobacter. Differential microbial metabolites were mostly enriched in metabolic pathways related to lipid synthesis, such as alpha-linolenic acid metabolism and steroid hormone biosynthesis. Correlation analysis showed that the altered metabolites were closely related to the intestinal microbiota. In conclusion, our results suggested that serine serves as a potential additive for improving IMF content in growing–finishing pigs.

Mechanism of Peppermint Extract-Induced Delay of 'Packham's Triumph' Pear (Pyrus communis L.) Postharvest Ripening.

Postharvest ripening is correlated to the quality and shelf life of European pear fruit. In this study, the effects of peppermint extract on fruit phenotype, related physiological activities, and aroma components during postharvest ripening of the European pear variety 'Packham's Triumph' were examined. Fruit treated with 2.0 g L-1 peppermint extract for 12 h showed delayed softening by 4 d compared with that of the untreated control group. The peak values of ethylene and respiratory rate in fruit were reduced to a certain extent after peppermint extract treatment; however, the peppermint extract did not delay the occurrence of the respiratory climacteric peak. Peppermint extract treatment also did not significantly increase the content of the characteristic peppermint aroma in pear fruit. Further, widely targeted metabolome analysis revealed 298 significantly different metabolites, with flavonoids (40%) and lipid compounds (15%) accounting for the highest proportion on the first day after treatment. The Kyoto Encyclopedia of Genes and Genomes pathway result showed significant enrichment in the metabolic pathways of biosynthesis of flavonoid, isoflavonoid, flavone and flavonol, linoleic acid, and alpha-linolenic acid metabolism following peppermint extract treatment. The combined analysis of transcriptome and metabolome data showed significant enrichment in linoleic acid metabolism and alpha-linolenic acid metabolism on the first, third, and fifth days after peppermint extract treatment. This study indicates that peppermint extract mainly affects the pear fruit softening process in the early stage after treatment.