Regulation Of Metabolites Research Articles

Transcriptome and metabolome revealed the effects of hypoxic environment on ovarian development of Tibetan sheep

Many studies on the adaptability of Tibetan sheep to hypoxia have been reported, but little attention has been paid to the reproduction of Tibetan sheep living at an altitude of more than 4000 m. In this study, the ovaries of Alpine Merino sheep (AM) living in middle-high altitude areas (2500 m) and the ovaries of Gangba Tibetan sheep (GB) and Huoba Tibetan sheep (HB) living in ultra-high altitude areas (4400 m or more) were collected. Through morphological, transcriptomics and metabolomics, the effects of ultra-high altitude areas on Tibetan sheep ovarian development and the molecular mechanism of sheep's adaptability to ultra-high altitude environment were explored. The results showed that the number of granulosa cells in AM was significantly higher than that in GB and HB. The transcriptome revealed several genes related to follicular development, such as DAPL1, IGFBP1, C5, GPR12, STRA6, BMPER, etc., which were mainly enriched in related pathways such as cell growth and development. Through metabolomics analysis, it was found that the differential metabolites between the three groups of sheep were mainly lipids and lipid-like small molecules, such as Glycerol 3-Phosphate, PC (16: 0 / 18: 3 (9Z, 12Z, 15Z)), mainly enriched in lipid metabolism and other related pathways. The results of combined analysis showed that Tryptophan metabolism and Steroid hormone biosynthesis may have a significant effect on Tibetan sheep follicular development. Some genes (including HSD17B7, CYP11A1, CYP19, HSD3B1, CYP17, etc.) and some metabolites (including Cortisone, 2-Methoxyestrone, etc.) are enriched in these pathways, regulating ovarian and follicular development by affecting estrogen, progesterone, etc.. The results further revealed the molecular mechanism of Tibetan sheep to adapt to the ultra-high altitude environment and maintain normal ovarian and follicular development through the regulation of genes and metabolites.

Genome-wide identification and expression analysis of the WRKY gene family reveal essential roles in abiotic stress responses and polysaccharides and flavonoids biosynthesis in Platostoma palustre (Blume) A. J. Paton

BackgroundPlatostoma palustre (Blume) A. J. Paton is an economic crop with medicinal and edible properties. WRKY transcription factors are widely involved in the growth and development, response to adversity stress, and hormone transduction of plants. The identification of the WRKY gene family has been completed in many plants, however, it has not yet been identified and analyzed at the genome-wide level in P. palustre.ResultsIn this study, we identified 133 PpWRKY gene family members (PpWRKYs) at the whole genome level of P. palustre, which were unevenly distributed on 15 chromosomes. Based on their protein structure and phylogenetic characteristics, the 133 PpWRKYs were divided into 3 subgroups. Segmental duplication events might play a crucial role in the expansion of the PpWRKY gene family. Through the transcriptome expression data analysis, the expression profiles of PpWRKY genes under Cd, red light, salt, and drought stresses were analyzed in this study, suggesting that WRKY transcription factors may play a crucial role in responding to different abiotic stresses in P. palustre. Notably, PpWRKY92 exhibited simultaneous responses to Cd, light intensity, salt, and drought stresses. Additionally, PpWRKY21, 75, 90, 52, 124, 39, 115, 122, 20, and 76 demonstrated a strong correlation with both monosaccharides and flavonoids. Taken together, PpWRKY20, 39, 75, 76, 90, 92, 115, 122, and 124 were found to be associated with the abiotic stress response and polysaccharides and flavonoids biosynthesis in P. palustre, except the low-expressed PpWRKY21 and 52.ConclusionThe present study laid the foundation for the abiotic stress response and metabolite regulation of this gene family in P. palustre.

Metabolic alterations of endothelial cells under transient and persistent hypoxia: study using a 3D microvessels-on-chip model

ABSTRACT Numerous signaling pathways are activated during hypoxia to facilitate angiogenesis, promoting interactions among endothelial cells and initiating downstream signaling cascades. Although the pivotal role of the nitric oxide (NO) response pathway is well-established, the involvement of arginine-specific metabolism and bioactive lipid mechanisms in 3D flow-activated in vitro models remains less understood. In this study, we explored the levels of arginine-specific metabolites and bioactive lipids in human coronary artery endothelial cells (HCAECs) under both transient and persistent hypoxia. We compared targeted metabolite levels between a 2D static culture model and a 3D microvessels-on-chip model. Notably, we observed robust regulation of NO metabolites in both transient and persistent hypoxic conditions. In the 2D model under transient hypoxia, metabolic readouts of bioactive lipids revealed increased oxidative stress markers, a phenomenon not observed in the 3D microvessels. Furthermore, we made a novel discovery that the responses of bioactive lipids were regulated by hypoxia inducible factor-1α (HIF-1α) in the 2D cell culture model and partially by HIF-1α and flow-induced shear stress in the 3D microvessels. Immunostaining confirmed the HIF-1α-induced regulation under both hypoxic conditions. Real-time oxygen measurements in the 3D microvessels using an oxygen probe validated that oxygen levels were maintained in the 3D model. Overall, our findings underscore the critical regulatory roles of HIF-1α and shear stress in NO metabolites and bioactive lipids in both 2D and 3D cell culture models.

The ABC transporter SmABCG1 mediates tanshinones export from the peridermic cells of Salvia miltiorrhiza root.

Plants have mechanisms to transport secondary metabolites from where they are biosynthesized to the sites where they function, or to sites such as the vacuole for detoxification. However, current research has mainly focused on metabolite biosynthesis and regulation, and little is known about their transport. Tanshinone, a class diterpenoid with medicinal properties, is biosynthesized in the periderm of Salvia miltiorrhiza roots. Here, we discovered that tanshinone can be transported out of peridermal cells and secreted into the soil environment and that the ABC transporter SmABCG1 is involved in the efflux of tanshinone ⅡA and tanshinone Ⅰ. The SmABCG1 gene is adjacent to the diterpene biosynthesis gene cluster in the S. miltiorrhiza genome. The temporal-spatial expression pattern of SmABCG1 is consistent with tanshinone accumulation profiles. SmABCG1 is located on the plasma membrane and preferentially accumulates in the peridermal cells of S. miltiorrhiza roots. Heterologous expression in Xenopus laevis oocytes demonstrated that SmABCG1 can export tanshinone ⅡA and tanshinone Ⅰ. CRISPR/Cas9-mediated mutagenesis of SmABCG1 in S. miltiorrhiza hairy roots resulted in a significant decrease in tanshinone contents in both hairy roots and the culture medium, whereas overexpression of this gene resulted in increased tanshinone contents. CYP76AH3 transcript levels increased in hairy roots overexpressing SmABCG1 and decreased in knockout lines, suggesting that SmABCG1 may affect the expression of CYP76AH3, indirectly regulating tanshinone biosynthesis. Finally, tanshinone ⅡA showed cytotoxicity to Arabidopsis roots. These findings offer new perspectives on plant diterpenoid transport and provide a new genetic tool for metabolic engineering and synthetic biology research.

Copper inactivates DcsB by oxidizing the metal ligand Cys86 to sulfinic acid.

Nω-hydroxy-l-arginine amidinohydrolase (EC:3.5.3.25), an enzyme in the d-cycloserine (d-CS) biosynthetic pathway of Streptomyces lavendulae, catalyzes the hydrolysis of an arginase inhibitor, Nω-hydroxy-l-arginine, to produce l-ornithine and hydroxyurea, despite being homologous to arginase. Like arginase, the enzyme (DcsB) possesses two manganese ions (MnA and MnB) essential for the enzymatic reaction at the bottom of the cavity formed within the molecule. However, one of the MnA ligands in DcsB is Cys86, whereas the corresponding residues in arginase are histidine. In this study, we determined the crystal structure of Mn-free DcsB to elucidate the installation mechanism of the manganese ions. The flipping of the His111 residue after the formation of the coordination bond to the second manganese ion may facilitate the installation of MnB and the closing of the cavity entrance to retain MnA and MnB at the active site. Copper ions, which are known to be a positive regulator of many secondary metabolites in Streptomyces species, were found to irreversibly inactivate the catalytic activity of DcsB. Mass spectrometric and crystallographic analyses of the Cu(II)-treated DcsB indicated that Cys86 is oxidized to sulfinic acid. The d-CS biosynthesis in the producing microorganism may be negatively regulated by the concentration of intracellular copper ions, which mediates the oxidative stress.

Metabolic Reprogramming of Fibroblastic Reticular Cells in Immunity and Tolerance

ABSTRACTFibroblastic reticular cells (FRCs) are pivotal stromal components that maintain the structure of secondary lymphoid tissues and modulate the immune responses within the lymphoid microenvironment. In response to specific immune or inflammatory stimuli, such as infection or autoimmune triggers, FRCs undergo significant metabolic reprogramming. This process, originally characterized in cancer research, involves the regulation of key metabolic enzymes, pathways, and metabolites, resulting in functional transformations of these cells. Specifically, viruses stimulate FRCs to enhance the tricarboxylic acid cycle, while rheumatoid arthritis and sepsis prompt FRCs to increase oxidative phosphorylation. These changes enable FRCs to adapt their functions, such as proliferation or cytokine secretion, thereby effectively regulating the immune microenvironment to meet the dynamic needs of the immune system. This review provides a comprehensive update on the metabolic reprogramming of FRCs, highlighting how these changes support immune tolerance and response under varied physiological conditions.

Macrophytes mitigate Microcystis aeruginosa-induced fish appetite suppression via intestinal metabolite regulation

Cyanobacterial blooms and aquatic macrophytes can affect the health, physiology, and behavior of freshwater fish. Changes in food intake can be a key indicator of stress in teleost fish, while changes in metabolite abundance in the gut can indicate a shift in metabolic priorities, including response to environmental stressors. Here, we exposed stone moroko (Pseudorasbora parva) to the cyanobacterium Microcystis aeruginosa and/or the macrophyte Ottelia acuminata and analyzed changes in fish health, appetite regulation, and intestinal metabolome after 96-h exposures. We found that O. acuminata treatment didn’t change the tested indicators, while exposure to M. aeruginosa increased concentrations of appetite-inhibiting factors, such as CART and GLP-1, and decreased concentrations of stimulatory factors like orexin. Exploration of the metabolome following exposure revealed that the appetite-inhibiting influence of M. aeruginosa was positively correlated with key metabolites of lipid, amino acid, and cholesterol metabolism, especially those associated with bile acid synthesis and secretion. Further, the presence of O. acuminata decreased the adverse effects of M. aeruginosa among neuro-endocrine regulatory factors, which could be explained by altered regulation of intestinal amino acid metabolites. The deeper mechanism by which O. acuminata moderates the harmful effects of M. aeruginosa remains to be identified.

Integrative Transcriptomic and Metabolomic Analysis Reveals Quinoa Leaf Response Mechanisms to Different Phosphorus Concentrations During Filling Stage

Quinoa is an annual self-pollinating plant rich in polyphenols, flavonoids, saponins, and amino acids; its protein balance closely aligns with the ideal recommendation set by the Food and Agriculture Organization. Therefore, quinoa is considered the most suitable “all-nutrient food”. Phosphorus fertilization plays an important role in restricting the growth and development of quinoa; however, the effects of phosphorus fertilizer on quinoa growth remain unclear. Therefore, we conducted metabolome and transcriptome analyses on quinoa leaves during the filling stage, subjecting plants to different doses of phosphorus fertilizer. Overall, phosphorus treatment exerted a significant impact on the phenotypic characteristics of quinoa. Specifically, through a combined analysis of ultra-performance liquid chromatography–tandem mass spectrometry and transcriptome analysis, we identified the alteration and regulation of specific metabolites and genes within flavonoid biosynthesis pathways; this comprehensive evaluation helped elucidate the response mechanism of quinoa leaves during the grouting stage under various phosphorus conditions. Ultimately, the results of this study provide a reference for the selection of quinoa cultivars that exhibit tolerance to low- or high-phosphorus stress; additionally, we offer a theoretical basis for the rational application of phosphorus fertilizer and the enhancement of phosphorus utilization efficiency.

Integrative Proteome and Metabolomics Analyses of Cryptococcus neoformans Responses to Melanin Substrates Niger seed and L-DOPA.

Melanin, as a pivotal antioxidant pigment, plays a critical role in the pathogenicity of Cryptococcus neoformans. However, the underlying signaling pathways responsible for melanin biosynthesis in C. neoformans are not yet fully elucidated. In this study, proteome and metabolomics analyses were conducted to investigate the response of C. neoformans to melanin substrate Niger seed or L-DOPA. The proteome analysis identified significant differential expression of proteins in cells treated with Niger seed compared to L-DOPA, with distinct functional enrichment patterns observed. Subcellular localization analysis showed unique protein distribution in cells treated with each substrate. Metabolomics analysis revealed distinct metabolic profiles in response to Niger seed or L-DOPA, with notable differences in metabolite regulation between the two treatments. KEGG classification highlighted specific metabolic pathways affected by each substrate. Overall, this study provides valuable insights into the complex regulatory mechanisms underlying C. neoformans response to melanin substrates.

Bacterial Secondary Metabolites Embedded in Producer Cell Membranes and Antibiotics Targeting Their Biosynthesis.

The bacterial cell membrane primarily houses lipids, carbohydrates, and proteins forming a barrier and interface that maintains cellular integrity, supports homeostasis, and senses environmental changes. Compared to lipid components and excreted secondary metabolites, compounds embedded in the producer cell membrane are often overlooked due to their low abundance and niche-specific functions. The accumulation of findings has led to an increased appreciation of their crucial roles in bacterial cell biochemistry, physiology, and ecology, as well as their impact on mutualistic and pathogenic bacteria-eukaryote interactions. This review highlights the structures, biosynthesis, regulation, and ecological functions of membrane-embedded secondary metabolites. It also discusses antibiotics that target their biosynthetic pathways, aiming to inspire the development of antibiotics specific to pathogenic bacteria without harming human cells.

Genome-wide investigation of MYB gene family in Areca catechu and potential roles of AcTDF in transgenic Arabidopsis.

MYB protein, a crucial transcription factor, holds crucial importance in plant growth, development, stress responses, and secondary metabolite regulation. While MYB proteins have been extensively studied, research on MYBs within the palm family, particularly in Areca catechu, remains limited. This study identified 259 MYB genes in Areca catechu, including 105 1R-MYBs, 150 R2R3-MYBs, 3 3R-MYBs, and 1 4R-MYBs. Physicochemical properties, collinearity, and gene structure of these genes were analyzed. The AcMYB is distributed across 16 chromosomes of A.catechu and has 119 and 195 homologs in Arabidopsis and rice, respectively. Cis-acting elements in the promoter region suggest roles in plant hormones, growth, development, and stress. R2R3-MYB genes were divided into eight groups based on tissue expression profiles. The flowering-related gene AcTDF is highly expressed in male flowers. Overexpression of AcTDF in Arabidopsis promotes early flowering, upregulates AtSOC1 and AtFUL, and enhances tolerance to drought and salt stress. These results provide valuable insights for the identification and analysis of the MYB gene family in Areca catechu and offer a basis for the subsequent verification of its related functions and the role and significance of its role in the evolution of palms.

Effects of nanoplastics on the growth, transcription, and metabolism of rice (Oryza sativa L.) and synergistic effects in the presence of iron plaque and humic acid

Nanoplastics (NPs) can adversely affect living organisms. However, the uptake of NPs by plants and the physiological and molecular mechanisms underlying NP-mediated plant growth remain unclear, particularly in the presence of iron minerals and humic acid (HA). In this study, we investigated NP accumulation in rice (Oryza sativa L.) and the physiological effects of exposure to polystyrene NPs (0, 20, and 100 mg L−1) in the presence of iron plaque (IP) and HA. NPs were absorbed on the root surface and entered cells, and confocal laser scanning microscopy confirmed NP uptake by the roots. NP treatments decreased root superoxide dismutase (SOD) activity (28.9–44.0%) and protein contents (31.2–38.6%). IP and HA (5 and 20 mg L−1) decreased the root protein content (20.44–58.3% and 44.2–45.2%, respectively) and increased the root lignin content (22.3–27.5% and 19.2–29.6%, respectively) under NP stress. IP inhibited the NP-induced decreasing trend of SOD activity (19.2–29.5%), while HA promoted this trend (48.7–50.3%). Transcriptomic and metabolomic analysis (Control, 100NPs, and IP-100NPs-20HA) showed that NPs inhibited arginine biosynthesis, and alanine, aspartate, and glutamate metabolism and activated phenylpropanoid biosynthesis related to lignin. The coexistence of IP and HA had positive effects on the amino acid metabolism and phenylpropanoid biosynthesis induced by NPs. Regulation of genes and metabolites involved in nitrogen metabolism and secondary metabolism significantly altered the levels of protein and lignin in rice roots. These findings provide a scientific basis for understanding the environmental risk of NPs under real environmental conditions.

A polysaccharide from edible red seaweed Bangia fusco-purpurea prevents obesity in high-fat diet-induced C57BL/6 mice

The study aimed to investigate the impacts of a polysaccharide (BFP) from Bangia fusco-purpurea on high-fat diet (HFD)-induced obesity in C57BL/6 mice, as well as its underlying mechanisms. Our results showed that orally administrated BFP was more effective than inulin (INU) in reducing body weight and fat accumulation in obese mice, indicating its anti-obesity effect. BFP effectively improved the compositions and metabolites of intestinal microbiota in obese mice, leading to enhanced energy metabolism and lipid metabolism, thus contributing to its anti-obesity effect. Notably, the better anti-obesity effect of BFP compared to INU were attributed to their varying degrees of modulation of specific intestinal microbial taxa, such as Clostridium and Aerococcus, as well as the regulation of differential metabolites (including biotin, piperine, G6P, etc.) also varies. Also, both in vitro (3T3-L1 preadipocytes) and in vivo (HFD-induced obese mice) models confirmed that BFP achieved anti-obesity effect attributed to enhance energy metabolism, promote lipolysis, increase fatty acid oxidation, and inhibit adipogenesis via activating the AMP-activated protein kinase and Acetyl-CoA carboxylase signaling pathways and suppressing the peroxisome proliferator-activated receptor γ expression. Our findings suggest that BFP has the potential to be used as prebiotics, dietary agents, and nutritional supplements against obesity.

Metabolomic biomarkers in amniotic fluid for early diagnosis of preterm birth and fetal growth restriction.

Preterm birth, affecting about 10% of pregnancies, significantly contributes to perinatal morbidity and mortality. Recent research indicates that metabolomics could enhance pregnancy outcomes and reduce costs by identifying biomarkers related to common pregnancy complications. Our team focused on analyzing amniotic fluid collected during the second trimester to identify potential biomarkers for preterm birth using 1H-NMR metabolomic analysis. We compared amniotic fluid samples from women who delivered prematurely with those who delivered at term. Multivariate principal component analysis revealed dimethylglycine, glucose, myo-inositol, and succinic acid as potential biomarkers for preterm birth prognosis and early diagnosis. Further analysis demonstrated distinct regulation patterns of these metabolites in relation to fetal growth centiles. For instance, dimethylglycine and glucose were upregulated in fetuses above the 20th centile, while citrate and succinate were upregulated in those below it. With Area Under the Curve (AUROC) values over 0.75 and p-values less than 0.05, these metabolites show promise as reliable biomarkers for predicting fetal growth restriction. This approach could significantly impact maternal-fetal medicine by facilitating early diagnosis and personalized interventions. Future research should focus on validating these findings in larger populations and exploring the underlying mechanisms of metabolite regulation.

Integrated serum pharmacochemistry, 16S rDNA sequencing, and metabolomics to reveal the material basis and mechanism of Shouhui Tongbian capsule against diphenoxylate-induced slow transit constipation in rats

BackgroundSlow transit constipation (STC) is highly prevalent and has rising incidence. Shouhui Tongbian capsule (SHTB) is a traditional Chinese Medicine formula with extensive and highly efficacious usage in STC treatment, however, its mechanism of action, especially the regulation of microbiome and lipid metabolites, remains unclear.MethodsAfter quality control of SHTB using LC‒MS to obtain its material basis, we tried to elucidate the cohesive modulatory network of SHTB against STC using hyphenated methods from microbiomics, lipidomics, mass spectrometry imaging (MSI) and molecular methods.ResultsSHTB could repair intestinal barrier damage, reduce systemic inflammation and increase intestinal motility in a diphenoxylate-induced STC rat model. Based on 16S rDNA sequencing results, SHTB rehabilitated the abnormal changes in Alloprevotella, Coprococcus, Marvinbryantia, etc., which were associated with STC symptoms. Meanwhile, microbial functional prediction showed that lipid metabolism was improved with SHTB administration. The differential lipids, including fatty acids, lysophosphatidylcholine, phosphatidylcholine, sphingomyelin triglyceride and ceramide, that are closely related to STC disease and SHTB efficacy. Furthermore, SHTB significantly reversed the abnormal expression of these key target enzymes in colon samples, including CTP-phosphocholine cytidylyltransferase, CTP-phosphoethanolamine cytidylyltransferase, phosphatidic acid phosphatase, acid sphingomyelinase etc.ConclusionsCombined analysis demonstrated that SHTB reducing lipid accumulation and recovery of intestinal microbial homeostasis was the critical mechanism by which SHTB treats STC.

Exploring the leaf regeneration cycles response of Zostera japonica to ocean acidification

Ocean acidification is one of the major global environmental problems facing humankind today, and it has far-reaching impacts on marine organisms and the entire marine ecosystem. Zostera japonica, an important supporting species of intertidal seagrass beds, exhibits high photosynthetic productivity and plays an important role in the carbon cycle of nearshore waters. However, little is known about the characteristics, processes, and mechanisms of its response to ocean acidification. In this study, we conducted a 120-day acidification experiment in Z. japonica; here, plants underwent four leaf regeneration cycles to reveal the response mechanism of Z. japonica to ocean acidification (OA). We found that acidification significantly affected the seedling stage of Z. japonica, impacting leaf regeneration cycles by altering physiological and molecular responses. In one leaf regeneration cycle, the short-term exposure to CO2 affected the seagrass parameters, such as the regulation of inorganic carbon uptake modes and the regulation of photosynthesis between the dark and light reactions, with the potential to affect the carbon sinks of the marine organisms. The long-term effects on the regulation of antioxidant enzymes and antioxidant metabolites, caused an improvement in the marine life adaptation to OA. In a comparison of the different leaf regeneration cycles, the response pattern of Z. japonica showed an offset of the acidification during the short cycles and an adaption to the acidification during the long cycles. This study revealed the response mechanism of Z. japonica to OA at different time scales and could provide a theoretical basis for accurately assessing the impact of OA on seagrass and the entire seagrass bed ecosystem.

CRISPR/Cas9 mediated CHS2 mutation provides a new insight into resveratrol biosynthesis by causing a metabolic pathway shift from flavonoids to stilbenoids in Vitis davidii cells

Abstract Resveratrol is an important phytoalexin that adapts to and responds to stressful conditions, plays various roles in health and medical therapies. However, it is only found in a limited number of plant species in low concentrations, which hinders its development and utilization. Chalcone synthase (CHS) and stilbene synthase (STS) catalyze the same substrates to produce flavonoids and resveratrol, respectively. However, it remains unclear how CHS and STS compete in metabolite synthesis. In this study, two CHS2 mutant cell lines (MT1 and MT2) were generated using CRISPR/Cas9 genome editing. These CHS2 mutant cell lines exhibited abundant mutations in CHS2, leading to the premature termination of protein translation and subsequent CHS2 knockout. Amplicon sequencing confirmed comprehensive CHS2 knockout in MT1, whereas the wild-type sequence remained predominant in the MT2 cell line. Transcriptome and RT-qPCR results showed a significant downregulation of genes involved in flavonoid biosynthesis, including CHS2, CHS3, F3H, F3’H, DFR, FLS, LDOX, among others, resulting in decreased flavonoid accumulation, such as anthocyanins, proanthocyanidins, quercetin, and kaempferol. Conversely, STS genes involved in stilbenoid biosynthesis were upregulated competing with the flavonoid pathway. Consequently, there was a marked increase in stilbenoids, including resveratrol, piceatannol, piceid and pterostilbene, with a 4.1-fold increase in resveratrol and a 5.3-fold increase in piceid (a derivative of resveratrol) observed in CHS2 mutant cell lines. This research demonstrates that CHS2 mutation induces a shift from flavonoid biosynthesis towards stilbenoid biosynthesis, offering new insights into metabolite biosynthesis and regulation, as well as an alternative solution for natural resveratrol production, and a novel breeding approach for eliminating non-target agronomic traits using CRISPR-Cas9.

Untargeted Metabolite Profiling of Wild and In Vitro Propagated Sabah Jewel Orchid Macodes limii J.J. Wood & A.L. Lamb.

Macodes limii J.J. Wood & A.L. Lamb is a terrestrial jewel orchid native to Sabah, recognised for its sparkling golden-yellow venations, uniformly distributed on its leaves. Despite its high ornamental value, the exploration of the plant's medicinal potential remains ambiguous. The current study was conducted to gain a fundamental understanding of the metabolite composition and regulation in M. limii plants from two different growing environments: wild and in vitro cultivation, as well as to analyse their phytochemical contents and antioxidant activity. The metabolite profiling of the M . limii plant extracts through gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis has tentatively identified compounds from various classes including sugars, carbohydrates, sugar alcohols, amino acids, organic acids, phenolic derivatives and lipid and lipid-like compounds. Subsequently, the multivariate statistical analysis confirmed the existence of significant metabolite variations across distinct growth environments. Notably, the leaf extract derived from wild-grown plants displayed the highest levels of total phenolic and flavonoid content, contributing significantly to its higher antioxidant activity as measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The discovery has offered a fundamental understanding of the metabolites in M. limii jewel orchids, indicating that in vitro regenerated plants may represent a viable alternative for further investigating their therapeutic potential, thus helping to alleviate the impact on wild populations.

CNDP2: An Enzyme Linking Metabolism and Cardiovascular Diseases?

The heart requires a substantial amount of energy to function, utilising various substrates including lipids, glucose and lactate as energy sources. In times of increased stress, lactate becomes the primary energy source of the heart, but persistently elevated lactate levels are linked to poor patient outcomes and increased mortality. Recently, carnosine dipeptidase II (CNDP2) was discovered to catalyse the formation of Lac-Phe, an exercise-induced metabolite derived from lactate, which has been shown to suppress appetite in mice and reduce adipose tissue in humans. This review discusses CNDP2, including its role in lactate clearance, carnosine hydrolysis, oxidative stress regulation, and involvement in metabolite regulation. The association between CNDP2 and cardiometabolic and renal diseases is also explored, and knowledge gaps are highlighted. CNDP2 appears to be a complex participant in human physiological processes and disease, necessitating additional research to unveil its functions and potential therapeutic applications.

Functional Verification of Transcription Factor comp54181_c0 in Monascus purpureus.

Monacolin K is a valuable secondary metabolite produced after a period of fermentation by Monascus purpureus; however, our current understanding of the regulatory mechanisms of its synthesis remains incomplete. This study conducted functional analysis on the key transcription factor, comp54181_c0, that is involved in the synthesis of monacolin K in Monascus. Mutant strains with either knockout or overexpression of comp54181_c0 were constructed using CRISPR/Cas9. A comparison between the knockout and overexpression strains revealed changes in fungal morphology and growth, with a significant increase in the production of Monascus pigments and monacolin K when comp54181_c0 was absent. Real-time fluorescence quantitative PCR analysis revealed that comp54181_c0 significantly influenced the transcription of key genes related to monacolin K biosynthesis in Monascus. In conclusion, our study elucidates the crucial role of comp54181_c0 in Monascus, enriches our understanding of fungal secondary metabolite development and regulation, and provides a foundation for the development and regulation of Monascus and monacolin K production.