Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Knockout of amino acid transporter gene OsLHT1 accelerates leaf senescence and enhances resistance to rice blast fungus

Mon, 03/04/2023 - 12:00
J Exp Bot. 2023 Apr 3:erad125. doi: 10.1093/jxb/erad125. Online ahead of print.ABSTRACTPlant amino acid transporters (AATs) regulate not only long-distance transport and reallocation of nitrogen (N) from source to sink organs, but also amount of amino acids in leaves hijacked by invaded pathogens. However, the function of AATs in plant defense responses to pathogen infection remains unknown. In this study, we found that rice amino acid transporter gene OsLHT1 was expressed in leaves and up-regulated by maturing, N starvation and inoculation of blast fungus Magnaporthe oryzae. Knockout of OsLHT1 resulted in development stage- and N supply-dependent premature senescence of leaves at vegetative growth stage. In comparison to wild type, Oslht1 mutant lines showed sustained rusty red spots on fully mature leaf blades irrespective of N supply levels. Notably, no relationship between the severity of leaf rusty red spots and concentration of total N or amino acids was found in Oslht1 mutants at different developmental stages. Disruption of OsLHT1 altered transport and metabolism of amino acids and biosynthesis of flavones and flavonoids, enhanced expression of jasmonic acid- and salicylic acid-related defense genes and production of jasmonic acid and salicylic acid, accumulation of reactive oxygen species. OsLHT1 inactivation dramatically prevented the leaf invasion of M. oryzae, the hemi-biotrophic ascomycete fungus. Overall, these results establish a module connecting the activity of amino acid transporter with leaf metabolism and defense to rice blast fungus.PMID:37010326 | DOI:10.1093/jxb/erad125

Multi-copper oxidases SKU5 and SKS1 coordinate cell wall formation using apoplastic redox-based reactions in roots

Mon, 03/04/2023 - 12:00
Plant Physiol. 2023 Apr 3:kiad207. doi: 10.1093/plphys/kiad207. Online ahead of print.ABSTRACTThe primary cell wall is a fundamental plant constituent that is flexible but sufficiently rigid to support the plant cell shape. Although many studies have demonstrated that reactive oxygen species (ROS) serve as important signaling messengers to modify the cell wall structure and affect cellular growth, the regulatory mechanism underlying the spatial-temporal regulation of ROS activity for cell wall maintenance remains largely unclear. Here, we demonstrate a role of the Arabidopsis (Arabidopsis thaliana) multi-copper oxidase-like protein skewed 5 (SKU5) and its homolog SKU5-similar 1 (SKS1) in root cell wall formation through modulating ROS homeostasis. Loss of SKU5 and SKS1 function resulted in aberrant division planes, protruding cell walls, ectopic deposition of iron, and NADPH oxidase-dependent ROS overproduction in the root epidermis-cortex and cortex-endodermis junctions. A decrease of ROS level or inhibition of NADPH oxidase activity rescued the cell wall defects of sku5 sks1 double mutants. SKU5 and SKS1 proteins were activated by iron treatment, and iron over-accumulated in the walls between root epidermis and cortex cell layers of sku5 sks1. The glycosylphosphatidylinositol-anchored motif was crucial for membrane association and functionality of SKU5 and SKS1. Overall, our results identified SKU5 and SKS1 as regulators of ROS at the cell surface for regulation of cell wall structure and root cell growth.PMID:37010107 | DOI:10.1093/plphys/kiad207

Cancer-associated fibroblast-secreted glucosamine alters the androgen biosynthesis program in prostate cancer via HSD3B1 upregulation

Mon, 03/04/2023 - 12:00
J Clin Invest. 2023 Apr 3;133(7):e161913. doi: 10.1172/JCI161913.ABSTRACTAfter androgen deprivation, prostate cancer frequently becomes castration resistant (CRPC), with intratumoral androgen production from extragonadal precursors that activate the androgen receptor pathway. 3β-Hydroxysteroid dehydrogenase-1 (3βHSD1) is the rate-limiting enzyme for extragonadal androgen synthesis, which together lead to CRPC. Here, we show that cancer-associated fibroblasts (CAFs) increased epithelial 3βHSD1 expression, induced androgen synthesis, activated the androgen receptor, and induced CRPC. Unbiased metabolomics revealed that CAF-secreted glucosamine specifically induced 3βHSD1. CAFs induced higher GlcNAcylation in cancer cells and elevated expression of the transcription factor Elk1, which induced higher 3βHSD1 expression and activity. Elk1 genetic ablation in cancer epithelial cells suppressed CAF-induced androgen biosynthesis in vivo. In patient samples, multiplex fluorescent imaging showed that tumor cells expressed more 3βHSD1 and Elk1 in CAF-enriched areas compared with CAF-deficient areas. Our findings suggest that CAF-secreted glucosamine increases GlcNAcylation in prostate cancer cells, promoting Elk1-induced HSD3B1 transcription, which upregulates de novo intratumoral androgen synthesis to overcome castration.PMID:37009898 | DOI:10.1172/JCI161913

Identification of serum exosomal metabolomic and proteomic profiles for remote ischemic preconditioning

Mon, 03/04/2023 - 12:00
J Transl Med. 2023 Apr 3;21(1):241. doi: 10.1186/s12967-023-04070-1.ABSTRACTBACKGROUND: Remote ischemic preconditioning (RIPC) refers to a brief episode of exposure to potential adverse stimulation and prevents injury during subsequent exposure. RIPC has been shown to increase tolerance to ischemic injury and improve cerebral perfusion status. Exosomes have a variety of activities, such as remodeling the extracellular matrix and transmitting signals to other cells. This study aimed to investigate the potential molecular mechanism of RIPC-mediated neuroprotection.METHODS: Sixty adult male military personnel participants were divided into the control group (n = 30) and the RIPC group (n = 30). We analyzed the differential metabolites and proteins in the serum exosomes of RIPC participants and control subjects.RESULTS: Eighty-seven differentially expressed serum exosomal metabolites were found between the RIPC and control groups, which were enriched in pathways related to tyrosine metabolism, sphingolipid metabolism, serotonergic synapses, and multiple neurodegeneration diseases. In addition, there were 75 differentially expressed exosomal proteins between RIPC participants and controls, which involved the regulation of insulin-like growth factor (IGF) transport, neutrophil degranulation, vesicle-mediated transport, etc. Furthermore, we found differentially expressed theobromine, cyclo gly-pro, hemopexin (HPX), and apolipoprotein A1 (ApoA1), which are associated with neuroprotective benefits in ischemia/reperfusion injury. In addition, five potential metabolite biomarkers, including ethyl salicylate, ethionamide, piperic acid, 2, 6-di-tert-butyl-4-hydroxymethylphenol and zerumbone, that separated RIPC from control individuals were identified.CONCLUSION: Our data suggest that serum exosomal metabolites are promising biomarkers for RIPC, and our results provide a rich dataset and framework for future analyses of cerebral ischemia‒reperfusion injury under ischemia/reperfusion conditions.PMID:37009888 | DOI:10.1186/s12967-023-04070-1

Multi-omics for biomarker approaches in the diagnostic evaluation and management of abdominal pain and irritable bowel syndrome: what lies ahead

Mon, 03/04/2023 - 12:00
Gut Microbes. 2023 Jan-Dec;15(1):2195792. doi: 10.1080/19490976.2023.2195792.ABSTRACTReliable biomarkers for common disorders of gut-brain interaction characterized by abdominal pain, including irritable bowel syndrome (IBS), are critically needed to enhance care and develop individualized therapies. The dynamic and heterogeneous nature of the pathophysiological mechanisms that underlie visceral hypersensitivity have challenged successful biomarker development. Consequently, effective therapies for pain in IBS are lacking. However, recent advances in modern omics technologies offer new opportunities to acquire deep biological insights into mechanisms of pain and nociception. Newer methods for large-scale data integration of complementary omics approaches have further expanded our ability to build a holistic understanding of complex biological networks and their co-contributions to abdominal pain. Here, we review the mechanisms of visceral hypersensitivity, focusing on IBS. We discuss candidate biomarkers for pain in IBS identified through single omics studies and summarize emerging multi-omics approaches for developing novel biomarkers that may transform clinical care for patients with IBS and abdominal pain.PMID:37009874 | DOI:10.1080/19490976.2023.2195792

Altered acylcarnitine metabolism and inflexible mitochondrial fuel utilization characterize the loss of neonatal myocardial regeneration capacity

Mon, 03/04/2023 - 12:00
Exp Mol Med. 2023 Apr 3. doi: 10.1038/s12276-023-00967-5. Online ahead of print.ABSTRACTMyocardial regeneration capacity declines during the first week after birth, and this decline is linked to adaptation to oxidative metabolism. Utilizing this regenerative window, we characterized the metabolic changes in myocardial injury in 1-day-old regeneration-competent and 7-day-old regeneration-compromised mice. The mice were either sham-operated or received left anterior descending coronary artery ligation to induce myocardial infarction (MI) and acute ischemic heart failure. Myocardial samples were collected 21 days after operations for metabolomic, transcriptomic and proteomic analyses. Phenotypic characterizations were carried out using echocardiography, histology and mitochondrial structural and functional assessments. In both groups, MI induced an early decline in cardiac function that persisted in the regeneration-compromised mice over time. By integrating the findings from metabolomic, transcriptomic and proteomic examinations, we linked regeneration failure to the accumulation of long-chain acylcarnitines and insufficient metabolic capacity for fatty acid beta-oxidation. Decreased expression of the redox-sensitive mitochondrial Slc25a20 carnitine-acylcarnitine translocase together with a decreased reduced:oxidized glutathione ratio in the myocardium in the regeneration-compromised mice pointed to a defect in the redox-sensitive acylcarnitine transport to the mitochondrial matrix. Rather than a forced shift from the preferred adult myocardial oxidative fuel source, our results suggest the facilitation of mitochondrial fatty acid transport and improvement of the beta-oxidation pathway as a means to overcome the metabolic barrier for repair and regeneration in adult mammals after MI and heart failure.PMID:37009793 | DOI:10.1038/s12276-023-00967-5

Phenylalanine metabolism and tetrahydrobiopterin bio-availability in COVID-19 and HIV

Mon, 03/04/2023 - 12:00
Heliyon. 2023 Apr;9(4):e15010. doi: 10.1016/j.heliyon.2023.e15010. Epub 2023 Mar 28.ABSTRACTVarious metabolomics studies have reported increased phenylalanine serum concentrations in SARS-CoV-2 positive cases and have correlated increased phenylalanine with COVID-19 severity. In this study, we report similar results based upon metabolomics analysis of serum collected from a South African cohort of adults with confirmed COVID-19. The novelty of this study is the inclusion of HIV positive cases in the African context. We found that pre-existing HIV co-infection exacerbates the disruption of phenylalanine metabolism in COVID-19. What is lacking in literature is biological context and deeper understanding of perturbed phenylalanine metabolism in COVID-19. We delve deep into the metabolism of phenylalanine in COVID-19 and posit new insights for COVID-19 cases co-infected with HIV; namely, HIV-COVID-19 co-infected individuals do not have sufficient bioavailability of tetrahydrobiopterin (BH4). Hence, we identify BH4 as a potential supplement to alleviate/lessen COVID-19 symptoms.PMID:37009248 | PMC:PMC10043972 | DOI:10.1016/j.heliyon.2023.e15010

Integrative multi-omics approaches to explore immune cell functions: Challenges and opportunities

Mon, 03/04/2023 - 12:00
iScience. 2023 Mar 9;26(4):106359. doi: 10.1016/j.isci.2023.106359. eCollection 2023 Apr 21.ABSTRACTAs modern biological sciences evolve from investigation of individual molecules and pathways to growing emphasis on global and systems-based processes, increasing efforts have focused on combining the study of genomics with that of the other omics technologies, including epigenomics, transcriptomics, quantitative proteomics, global analyses of post-translational modifications (PTMs) and metabolomics, to characterize specific biological or pathological processes. In addition, emerging genome-wide functional screening technologies further help researchers identify key regulators of immune functions. Derived from these multi-omics technologies, single cell sequencing analysis on multiple layers offers an overview of intra-tissue or intra-organ immune cell heterogeneity. In this review, we summarize advances in multi-omics tools to explore immune cell functions and applications of these multi-omics approaches in the analysis of clinical immune disorders, aiming to provide an outlook on the potential opportunities and challenges that these technologies pose in future investigation in the field of immunology.PMID:37009227 | PMC:PMC10060681 | DOI:10.1016/j.isci.2023.106359

Integrated Analysis of Tracheobronchial Fluid from Before and After Cardiopulmonary Bypass Reveals Activation of the Integrated Stress Response and Altered Pulmonary Microvascular Permeability

Mon, 03/04/2023 - 12:00
Yale J Biol Med. 2023 Mar 31;96(1):23-42. doi: 10.59249/KFYZ8002. eCollection 2023 Mar.ABSTRACTObjective: We aim to comprehensively describe the transcriptional activity and signaling of pulmonary parenchymal and immune cells before and after cardiopulmonary bypass (CPB) by using a multi-omic approach coupled with functional cellular assays. We hypothesize that key signaling pathways from specific cells within the lung alter pulmonary endothelial cell function resulting in worsening or improving disease. Methods: We collected serial tracheobronchial lavage samples from intubated patients less than 2-years-old undergoing surgery with CPB. Samples were immediately processed for single cell RNA sequencing (10x Genomics). Cell clustering, cell-type annotation, and visualization were performed, and differentially expressed genes (DEG) between serial samples were identified. Metabolomic and proteomic analyses were performed on the supernatant using mass spectrometry and a multiplex assay (SomaScan) respectively. Functional assays were done using electric cell-substrate impedance sensing to measure resistance across human pulmonary microvascular endothelial cells (HPMECs). Results: Analysis of eight patients showed a heterogeneous mixture of pulmonary parenchymal and immune cells. Cell clustering demonstrated time-dependent changes in the transcriptomic signature indicating altered cellular phenotypes after CPB. DEG analysis was represented by genes involved in host defense, innate immunity, and the mitochondrial respiratory transport chain. Ingenuity pathway analysis showed upregulation of the integrated stress response across all cell types after CPB. Metabolomic analysis demonstrated upregulation of ascorbate and aldarate metabolism. Unbiased proteomic analysis revealed upregulation of proteins involved in cytokine and chemokine pathways. Post-CPB patient supernatant improved HMPEC barrier function, suggesting a protective cellular response to CPB. Conclusion: Children who undergo CPB for cardiac surgery have distinct cell populations, transcriptional activity, and metabolism that change over time. The response to ischemia-reperfusion injury in the lower airway of children appears to be protective, with the need to identify potential targets through future investigations.PMID:37009190 | PMC:PMC10052603 | DOI:10.59249/KFYZ8002

Dietary ribose supplementation improves flesh quality through purine metabolism in gibel carp (<em>Carassius auratus gibelio</em>)

Mon, 03/04/2023 - 12:00
Anim Nutr. 2022 Dec 31;13:50-63. doi: 10.1016/j.aninu.2022.12.006. eCollection 2023 Jun.ABSTRACTSince the aquaculture industry is currently observing a deterioration in the flesh quality of farmed fish, the use of nutrients as additives to improve the flesh quality of farmed fish species is a viable strategy. The aim of this study was to investigate the effect of dietary D-ribose (RI) on the nutritional value, texture and flavour of gibel carp (Carassius auratus gibelio). Four diets were formulated containing exogenous RI at 4 gradient levels: 0 (Control), 0.15% (0.15RI), 0.30% (0.30RI) and 0.45% (0.45RI). A total of 240 fish (150 ± 0.31 g) were randomly distributed into 12 fibreglass tanks (150 L per tank). Triplicate tanks were randomly assigned to each diet. The feeding trial was carried out in an indoor recirculating aquaculture system for 60 d. After the feeding trial, the muscle and liver of gibel carp were analysed. The results showed that RI supplementation did not result in any negative impact on the growth performance and 0.30RI supplementation significantly increased the whole-body protein content compared to the control group. The contents of collagen and glycogen in muscle were enhanced by RI supplementation. The alterations in the flesh indicated that RI supplementation improved the texture of the flesh in terms of its water-holding capacity and hardness, therefore improving the taste. Dietary RI facilitated the deposition of amino acids and fatty acids in the muscle that contributed to the meaty taste and nutritional value. Furthermore, a combination of metabolomics and expression of key genes in liver and muscle revealed that 0.30RI activated the purine metabolism pathways by supplementing the substrate for nucleotide synthesis and thereby promoting the deposition of flavour substance in flesh. This study offers a new approach for providing healthy, nutritious and flavourful aquatic products.PMID:37009072 | PMC:PMC10064418 | DOI:10.1016/j.aninu.2022.12.006

Relationships between sensory properties and metabolomic profiles of different apple cultivars

Mon, 03/04/2023 - 12:00
Food Chem X. 2023 Mar 14;18:100641. doi: 10.1016/j.fochx.2023.100641. eCollection 2023 Jun 30.ABSTRACTFlavor is a critical factor in apple quality. To better understand apple flavor, this study aimed to identify the relationships between sensory attributes and the chemical composition (volatiles and non-volatiles) of apples using a combined metabolomic and sensory evaluation. Sensory results showed the positive (apple, fruity, pineapple, sweetness, sourness) and negative (cucumber) flavor attributes of apples. A metabolomic analysis with statistical correlations revealed significant metabolites related to the flavor attributes of apples. Volatile esters (e.g., hexyl acetate and 2-methylbutyl acetate for apple and fruity notes) and non-volatile sugars and acids (total sugars, tartaric acid, and malic acid for balanced sweet and tart flavors) were associated with the apple flavor preferred by consumers. Some aldehydes and alcohols (e.g., (E)-2-nonenal) contributed to a negative hedonic perception (cucumber). The collected information demonstrated the roles of key chemical compounds in apple flavor quality, and may be applicable to quality control.PMID:37008726 | PMC:PMC10053392 | DOI:10.1016/j.fochx.2023.100641

Metabolic effects of diclofenac on the aquatic food chain - <sup>1</sup> H-NMR study of water flea-zebrafish system

Mon, 03/04/2023 - 12:00
Toxicol Res. 2023 Feb 14;39(2):307-315. doi: 10.1007/s43188-022-00167-9. eCollection 2023 Apr.ABSTRACTIn the environment, aquatic organisms are not only directly exposed to pollutants, but the effects can be exacerbated along the food chain. In this study, we investigated the effect of the food (water flea) on the secondary consumer (zebrafish) with the exposure diclofenac (DCF) Both organisms were exposed to an environmentally relevant concentrations (15 µg/L) of diclofenac for five days, and zebrafish were fed exposed and non-exposed water fleas, respectively. Metabolites of the water fleas were directly analyzed using HRMAS NMR, and for zebrafish, polar metabolite were extracted and analyzed using liquid NMR. Metabolic profiling was performed and statistically significant metabolites which affected by DCF exposure were identified. There were more than 20 metabolites with variable importance (VIP) score greater than 1.0 in comparisons in fish groups, and identified metabolites differed depending on the effect of exposure and the effect of food. Specifically, exposure to DCF significantly increased alanine and decreased NAD + in zebrafish, which means energy demand was increased. Additionally, the effects of exposed food decreased in guanosine, a neuroprotective metabolite, which explained that the neurometabolic pathway was perturbated by the feeding of exposed food. Our results which short-term exposed primary consumers to pollutants indirectly affected the metabolism of secondary consumers suggest that the long-term exposure further study remains to be investigated.PMID:37008688 | PMC:PMC10050267 | DOI:10.1007/s43188-022-00167-9

Different changes of bacterial diversity and soil metabolites in tea plants-legume intercropping systems

Mon, 03/04/2023 - 12:00
Front Plant Sci. 2023 Mar 16;14:1110623. doi: 10.3389/fpls.2023.1110623. eCollection 2023.ABSTRACTAs an essential agroforestry, intercropping legumes can improve the physical, chemical, and biological fertility of the soil in tea plantations. However, the effects of intercropping different legume species on soil properties, bacterial communities, and metabolites remain elusive. In this study, the 0-20 cm and 20-40 cm soils of three planting patterns (T1: tea plants/mung bean intercropping, T2: tea plants/adzuki bean intercropping, T3: tea plants/mung bean and adzuki bean intercropping) were sampled to explore the diversity of the bacterial community and soil metabolites. The findings showed that, as compared to monocropping, intercropping systems had greater concentrations of organic matter (OM) and dissolved organic carbon (DOC). Notably, pH values were significantly lower, and soil nutrients increased in intercropping systems compared with monoculture in 20-40 cm soils, especially in T3. In addition, intercropping resulted in an increased relative abundance of Proteobacteria but a decreased relative abundance of Actinobacteria. 4-methyl-Tetradecane, acetamide, and diethyl carbamic acid were key metabolites mediating the root-microbe interactions, especially in tea plants/adzuki intercropping and tea plants/mung bean, adzuki bean mixed intercropping soils. Co-occurrence network analysis showed that arabinofuranose, abundant in tea plants and adzuki bean intercropping soils, showed the most remarkable correlation with the soil bacterial taxa. Our findings demonstrate that intercropping with adzuki beans is better at enhancing the diversity of soil bacteria and soil metabolites and is more weed-suppressing than other tea plants/legume intercropping systems.PMID:37008505 | PMC:PMC10060988 | DOI:10.3389/fpls.2023.1110623

Recent insights into metabolic and signalling events of directional root growth regulation and its implications for sustainable crop production systems

Mon, 03/04/2023 - 12:00
Front Plant Sci. 2023 Mar 16;14:1154088. doi: 10.3389/fpls.2023.1154088. eCollection 2023.ABSTRACTRoots are sensors evolved to simultaneously respond to manifold signals, which allow the plant to survive. Root growth responses, including the modulation of directional root growth, were shown to be differently regulated when the root is exposed to a combination of exogenous stimuli compared to an individual stress trigger. Several studies pointed especially to the impact of the negative phototropic response of roots, which interferes with the adaptation of directional root growth upon additional gravitropic, halotropic or mechanical triggers. This review will provide a general overview of known cellular, molecular and signalling mechanisms involved in directional root growth regulation upon exogenous stimuli. Furthermore, we summarise recent experimental approaches to dissect which root growth responses are regulated upon which individual trigger. Finally, we provide a general overview of how to implement the knowledge gained to improve plant breeding.PMID:37008498 | PMC:PMC10060999 | DOI:10.3389/fpls.2023.1154088

Integrated transcriptome, metabolome and phytohormone analysis reveals developmental differences between the first and secondary flowering in <em>Castanea mollissima</em>

Mon, 03/04/2023 - 12:00
Front Plant Sci. 2023 Mar 16;14:1145418. doi: 10.3389/fpls.2023.1145418. eCollection 2023.ABSTRACTINTRODUCTION: Chestnut (Castanea mollissima BL.) is an important woody grain, and its flower formation has a significant impact on fruit yield and quality. Some chestnut species in northern China re-flower in the late summer. On the one hand, the second flowering consumes a lot of nutrients in the tree, weakening the tree and thus affecting flowering in the following year. On the other hand, the number of female flowers on a single bearing branch during the second flowering is significantly higher than that of the first flowering, which can bear fruit in bunches. Therefore, these can be used to study the sex differentiation of chestnut.METHODS: In this study, the transcriptomes, metabolomes, and phytohormones of male and female chestnut flowers were determined during spring and late summer. We aimed to understand the developmental differences between the first and secondary flowering stages in chestnuts. We analysed the reasons why the number of female flowers is higher in the secondary flowering than in the first flowering and found ways to increase the number of female flowers or decrease the number of male flowers in chestnuts.RESULTS: Transcriptome analysis of male and female flowers in different developmental seasons revealed that EREBP-like mainly affected the development of secondary female flowers and HSP20 mainly affected the development of secondary male flowers. KEGG enrichment analysis showed that 147 common differentially-regulated genes were mainly enriched from circadian rhythm-plant, carotenoid biosynthesis, phenylpropanoid biosynthesis, and plant hormone signal transduction pathways. Metabolome analysis showed that the main differentially accumulated metabolites in female flowers were flavonoids and phenolic acids, whereas the main differentially accumulated metabolites in male flowers were lipids, flavonoids, and phenolic acids. These genes and their metabolites are positively correlated with secondary flower formation. Phytohormone analysis showed that abscisic and salicylic acids were negatively correlated with secondary flower formation. MYB305, a candidate gene for sex differentiation in chestnuts, promoted the synthesis of flavonoid substances and thus increased the number of female flowers.DISCUSSION: We constructed a regulatory network for secondary flower development in chestnuts, which provides a theoretical basis for the reproductive development mechanism of chestnuts. This study has important practical implications for improving chestnut yield and quality.PMID:37008486 | PMC:PMC10060901 | DOI:10.3389/fpls.2023.1145418

Integrated transcriptome and metabonomic analysis of key metabolic pathways in response to cadmium stress in novel buckwheat and cultivated species

Mon, 03/04/2023 - 12:00
Front Plant Sci. 2023 Mar 17;14:1142814. doi: 10.3389/fpls.2023.1142814. eCollection 2023.ABSTRACTINTRODUCTION: Buckwheat (Fagopyrum tataricum), an important food crop, also has medicinal uses. It is widely planted in Southwest China, overlapping with planting areas remarkably polluted by cadmium (Cd). Therefore, it is of great significance to study the response mechanism of buckwheat under Cd stress and further develop varieties with excellent Cd tolerance.METHODS: In this study, two critical periods of Cd stress treatment (days 7 and 14 after Cd treatment) of cultivated buckwheat (Pinku-1, named K33) and perennial species (F. tatari-cymosum Q.F. Chen) (duoku, named DK19) were analyzed using transcriptome and metabolomics.RESULTS: The results showed that Cd stress led to changes in reactive oxygen species (ROS) and the chlorophyll system. Moreover, Cd-response genes related to stress response, amino acid metabolism, and ROS scavenging were enriched or activated in DK19. Transcriptome and metabolomic analyses highlighted the important role of galactose, lipid (glycerophosphatide metabolism and glycerophosphatide metabolism), and glutathione metabolism in response to Cd stress in buckwheat, which are significantly enriched at the gene and metabolic levels in DK19.DISCUSSION: The results of the present study provide valuable information for a better understanding of the molecular mechanisms underlying Cd tolerance in buckwheat and useful clues for the genetic improvement of drought tolerance in buckwheat.PMID:37008482 | PMC:PMC10064074 | DOI:10.3389/fpls.2023.1142814

Drought stress in 'Shine Muscat' grapevine: Consequences and a novel mitigation strategy-5-aminolevulinic acid

Mon, 03/04/2023 - 12:00
Front Plant Sci. 2023 Mar 15;14:1129114. doi: 10.3389/fpls.2023.1129114. eCollection 2023.ABSTRACTDrought is a common and serious abiotic stress in viticulture, and it is urgent to select effective measures to alleviate it. The new plant growth regulator 5-aminolevulinic acid (ALA) has been utilized to alleviate abiotic stresses in agriculture in recent years, which provided a novel idea to mitigate drought stress in viticulture. The leaves of 'Shine Muscat' grapevine (Vitis vinifera L.) seedlings were treated with drought (Dro), drought plus 5-aminolevulinic acid (ALA, 50 mg/L) (Dro_ALA) and normal watering (Control) to clarify the regulatory network used by ALA to alleviate drought stress in grapevine. Physiological indicators showed that ALA could effectively reduce the accumulation of malondialdehyde (MDA) and increase the activities of peroxidase (POD) and superoxide dismutase (SOD) in grapevine leaves under drought stress. At the end of treatment (day 16), the MDA content in Dro_ALA was reduced by 27.63% compared with that in Dro, while the activities of POD and SOD reached 2.97- and 5.09-fold of those in Dro, respectively. Furthermore, ALA reduces abscisic acid by upregulating CYP707A1, thus, relieving the closure of stomata under drought. The chlorophyll metabolic pathway and photosynthetic system are the major pathways affected by ALA to alleviate drought. Changes in the genes of chlorophyll synthesis, including CHLH, CHLD, POR, and DVR; genes related to degradation, such as CLH, SGR, PPH and PAO; the RCA gene that is related to Rubisco; and the genes AGT1 and GDCSP related to photorespiration form the basis of these pathways. In addition, the antioxidant system and osmotic regulation play important roles that enable ALA to maintain cell homeostasis under drought. The reduction of glutathione, ascorbic acid and betaine after the application of ALA confirmed the alleviation of drought. In summary, this study revealed the mechanism of effects of drought stress on grapevine, and the alleviating effect of ALA, which provides a new concept to alleviate drought stress in grapevine and other plants.PMID:37008472 | PMC:PMC10061586 | DOI:10.3389/fpls.2023.1129114

Comparative analyses of functional traits based on metabolome and economic traits variation of <em>Bletilla striata</em>: Contribution of intercropping

Mon, 03/04/2023 - 12:00
Front Plant Sci. 2023 Mar 17;14:1147076. doi: 10.3389/fpls.2023.1147076. eCollection 2023.ABSTRACTThe intercropping practice has been regarded as a practical land-use selection to improve the management benefits of Bletilla striata plantations. The reports about the variety of economic and functional traits of Bletilla pseudobulb under intercropping systems were limited. The present study investigated the variation of economic and functional traits of Bletilla pseudobulb under different intercropping systems (the deep-rooted intercropping system: B. striata - Cyclocarya paliurus, CB; and the shallow-rooted intercropping system: B. striata - Phyllostachys edulis, PB). The functional traits were analyzed through non-targeted metabolomics based on GC-MS. The results indicated that the PB intercropping system significantly decreased the yield of Bletilla pseudobulb while significantly increasing the total phenol and flavonoids compared with the control (CK). However, there were no significant differences in all economic traits between CB and CK. The functional traits among CB, PB, and CK were separated and exhibited significant differences. Under different intercropping systems, B. striata may adopt different functional strategies in response to interspecific competition. The functional node metabolites (D-galactose, cellobiose, raffinose, D-fructose, maltose, and D-ribose) were up-regulated in CB, while the functional node metabolites (L-valine, L-leucine, L-isoleucine, methionine, L-lysine, serine, D-glucose, cellobiose, trehalose, maltose, D-ribose, palatinose, raffinose, xylobiose, L-rhamnose, melezitose, and maltotriose) were up-regulated in PB. The correlation between economic and functional traits depends on the degree of environmental stress. Artificial neural network models (ANNs) accurately predicted the variation in economic traits via the combination of functional node metabolites in PB. The correlation analysis of environmental factors indicated that Ns (including TN, NH4 +-, and NO3 --), SRI (solar radiation intensity), and SOC were the main factors that affected the economic traits (yield, total phenol, and total flavonoids). TN, SRI, and SOC were the main factors affecting the functional traits of the Bletilla pseudobulb. These findings strengthen our understanding of the variation of economic and functional traits of Bletilla pseudobulb under intercropping and clarify the main limiting environmental factors under B. striata intercropping systems.PMID:37008465 | PMC:PMC10064063 | DOI:10.3389/fpls.2023.1147076

Correlation analysis between jejunum metabolites and immune function in Saba and Landrace piglets

Mon, 03/04/2023 - 12:00
Front Vet Sci. 2023 Mar 16;10:1069809. doi: 10.3389/fvets.2023.1069809. eCollection 2023.ABSTRACTThe immune function of the intestinal mucosa plays a crucial role in the intestinal health of hosts. As signaling molecules and precursors of metabolic reactions, intestinal chyme metabolites are instrumental in maintaining host immune homeostasis. Saba (SB) pigs, a unique local pig species in central Yunnan Province, China. However, research on jejunal metabolites in this species is limited. Here, we used immunohistochemistry and untargeted metabolomics by liquid chromatography mass spectrometry (LC-MS/MS) to study differences in jejunal immunophenotypes and metabolites between six Landrace (LA) and six SB piglets (35 days old). The results showed that the levels of the anti-inflammatory factor interleukin 10 (IL-10) were markedly higher in SB piglets than in LA piglets (P < 0.01), while the levels of the proinflammatory factors IL-6, IL-1β, and Toll-like receptor 2 (TLR-2) were markedly lower (P < 0.01). Furthermore, the levels of mucin 2 (MUC2) and zona occludens (ZO-1), which are related to mucosal barrier function, were significantly higher in SB piglets than in LA piglets (P < 0.01), as were villus height, villus height/crypt depth ratio, and goblet cell number (P < 0.05). Differences in jejunal chyme metabolic patterns were observed between the two piglets. In the negative ion mode, cholic acid metabolites ranked in the top 20 and represented 25% of the total. Taurodeoxycholic acid (TDCA) content was significantly higher in SB piglets than in LA piglets (P < 0.01). TDCA positively correlated with ZO-1, villus height, villus height/crypt depth ratio, and goblet cell number. These results suggest that SB pigs have a strong jejunal immune function and that TDCA was positively regulates jejunal immunity and mucosal barrier function. Our findings provide a reference for understanding intestinal immune function in different pig breeds and for the discovery of potential biomarkers to help solve health issues related to pig production.PMID:37008364 | PMC:PMC10060822 | DOI:10.3389/fvets.2023.1069809

Integrated Multi-Omics Techniques and Network Pharmacology Analysis to Explore the Material Basis and Mechanism of Simiao Pill in the Treatment of Rheumatoid Arthritis

Mon, 03/04/2023 - 12:00
ACS Omega. 2023 Mar 20;8(12):11138-11150. doi: 10.1021/acsomega.2c07959. eCollection 2023 Mar 28.ABSTRACTThe Simiao pill (SMP) is a classic prescription that has shown anti-inflammatory, analgesic, and immunomodulatory effects and is clinically used to treat inflammatory diseases, such as rheumatoid arthritis (RA) and gouty arthritis, for which the effects and mechanism of action remain largely unknown. In this study, serum samples from RA rats were analyzed using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry based metabolomics technology and liquid chromatography with tandem mass spectrometry proteomics technology together with network pharmacology to explore the pharmacodynamic substances of SMP. To further verify the above results, we constructed a fibroblast-like synoviocyte (FLS) cell model and administered phellodendrine for the test. All these clues suggested that SMP can significantly reduce the level of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in complete Freund's adjuvant rat serum and improve the degree of foot swelling; combined with metabolomics, proteomics, and network pharmacological technology, it is determined that SMP plays a therapeutic role through the inflammatory pathway, and phellodendrine is found to be one of the pharmacodynamic substances. By constructing an FLS model, it is further determined that phellodendrine could effectively inhibit the activity of synovial cells and reduce the expression level of inflammatory factors by downregulating the expression level of related proteins in the TLR4-MyD88-IRAK4-MAPK signal pathway to alleviate joint inflammation and cartilage injury. Overall, these findings suggested that phellodendrine is an effective component of SMP in the treatment of RA.PMID:37008152 | PMC:PMC10061593 | DOI:10.1021/acsomega.2c07959

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