Regulation Of Metabolites Research Articles

MYC2 Transcription Factors TwMYC2a and TwMYC2b Negatively Regulate Triptolide Biosynthesis in Tripterygium wilfordii Hairy Roots.

Triptolide, an important bioactive diterpenoid extracted from the plant Tripterygium wilfordii, exhibits many pharmacological activities. MYC2 transcription factor (TF) plays an important role in the regulation of various secondary metabolites in plants. However, whether MYC2 TF could regulate the biosynthesis of triptolide in T. wilfordii is still unknown. In this study, two homologous MYC2 TF genes, TwMYC2a and TwMYC2b, were isolated from T. wilfordii hairy roots and functionally characterized. The analyses of the phylogenetic tree and subcellular localization showed that they were grouped into the IIIe clade of the bHLH superfamily with other functional MYC2 proteins and localized in the nucleus. Furthermore, yeast one-hybrid and GUS transactivation assays suggested that TwMYC2a and TwMYC2b inhibited the promoter activity of the miltiradiene synthase genes, TwTPS27a and TwTPS27b, by binding to the E-box (CACATG) and T/G-box (CACGTT) motifs in their promoters. Transgenic results revealed that RNA interference of TwMYC2a/b significantly enhanced the triptolide accumulation in hairy roots and liquid medium by upregulating the expression of several key biosynthetic genes, including TwMS (TwTPS27a/b), TwCPS (TwTPS7/9), TwDXR, and TwHMGR1. In summary, our findings show that TwMYC2a and TwMYC2b act as two negative regulators of triptolide biosynthesis in T. wilfordii hairy roots and also provide new insights on metabolic engineering of triptolide in the future.

Gut Microbiota in Lupus: a Butterfly Effect?

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that typically displays chronic inflammatory tissue damage and miscellaneous circulatory autoantibodies, as well as distinctive type 1 interferon signatures. The etiology of SLE is unclear and currently is attributed to genetic predisposition and environmental triggers. Gut microbiota has recently been considered a critical environmental pathogenic factor in immune-related disorders, and studies are ongoing to uncover the key pathogens and the imputative mechanisms. Fundamental advancements on the role of the microbiota in SLE pathology have been achieved in recent years and are summarized in this review. Recent findings suggested that gut commensals could propagate autoimmunity via molecular mimicry in which ortholog-carrying microbes cross-activate autoreactive T/B cells and trigger the response against host autoantigens, or via bystander activation by stimulating antigen-presenting cells that present autoantigens and enhancing the expression of co-stimulatory molecules and cytokines, thus leading to the loss of self-tolerance and the production of autoantibodies. Additionally, the break of gut barrier and the translocation of gut commensals to inner organs can trigger immune dysregulation and inappropriate systemic inflammation. All these microbiota-mediated mechanisms could contribute to lupus immunopathogenesis and promote disease development in susceptible individuals. Evidence of the causative role of disturbed gut microbiome in SLE is still limited, and the related molecular mechanisms and pathways are largely elusive. However, the modification of gut microbiota, such as pathobiont vaccine, special diet, restricted consortium transplantation, as well as regulatory metabolites supplementation, might be promising strategies for lupus prophylaxis and treatment.

Plasma Membrane H+-ATPase SmPHA4 Negatively Regulates the Biosynthesis of Tanshinones in Salvia miltiorrhiza.

Salvia miltiorrhiza Bunge has been widely used in the treatment of cardiovascular and cerebrovascular diseases, due to the pharmacological action of its active components such as the tanshinones. Plasma membrane (PM) H+-ATPase plays key roles in numerous physiological processes in plants. However, little is known about the PM H+-ATPase gene family in S. miltiorrhiza (Sm). Here, nine PM H+-ATPase isoforms were identified and named SmPHA1–SmPHA9. Phylogenetic tree analysis showed that the genetic distance of SmPHAs was relatively far in the S. miltiorrhiza PM H+-ATPase family. Moreover, the transmembrane structures were rich in SmPHA protein. In addition, SmPHA4 was found to be highly expressed in roots and flowers. HPLC revealed that accumulation of dihydrotanshinone (DT), cryptotanshinone (CT), and tanshinone I (TI) was significantly reduced in the SmPHA4-OE lines but was increased in the SmPHA4-RNAi lines, ranging from 2.54 to 3.52, 3.77 to 6.33, and 0.35 to 0.74 mg/g, respectively, suggesting that SmPHA4 is a candidate regulator of tanshinone metabolites. Moreover, qRT-PCR confirmed that the expression of tanshinone biosynthetic-related key enzymes was also upregulated in the SmPHA4-RNAi lines. In summary, this study highlighted PM H+-ATPase function and provided new insights into regulatory candidate genes for modulating secondary metabolism biosynthesis in S. miltiorrhiza.

Pharmacological regulation of cytochrome P450 metabolites of arachidonic acid attenuates cardiac injury in diabetic rats

Diabetic cardiomyopathy (DCM) is a well-established complication of type 1 and type 2 diabetes associated with a high rate of morbidity and mortality. DCM is diagnosed at advanced and irreversible stages. Therefore, it is of utmost need to identify novel mechanistic pathways involved at early stages to prevent or reverse the development of DCM. In vivo experiments were performed on type 1 diabetic rats (T1DM). Functional and structural studies of the heart were executed and correlated with mechanistic assessments exploring the role of cytochromes P450 metabolites, the 20-hydroxyeicosatetraenoic acids (20-HETEs) and epoxyeicosatrienoic acids (EETs), and their crosstalk with other homeostatic signaling molecules. Our data displays that hyperglycemia results in CYP4A upregulation and CYP2C11 downregulation in the left ventricles (LV) of T1DM rats, paralleled by a differential alteration in their metabolites 20-HETEs (increased) and EETs (decreased). These changes are concomitant with reductions in cardiac outputs, LV hypertrophy, fibrosis, and increased activation of cardiac fetal and hypertrophic genes. Besides, pro-fibrotic cytokine TGF-ß overexpression and NADPH (Nox4) dependent-ROS overproduction are also correlated with the observed cardiac functional and structural modifications. Of interest, these observations are attenuated when T1DM rats are treated with 12-(3-adamantan-1-yl-ureido) dodecanoic acid (AUDA), which blocks EETs metabolism, or N-hydroxy-N'-(4-butyl-2-methylphenol)Formamidine (HET0016), which inhibits 20-HETEs formation. Taken together, our findings confer pioneering evidence about a potential interplay between CYP450-derived metabolites and Nox4/TGF-β axis leading to DCM. Pharmacologic interventions targeting the inhibition of 20-HETEs synthesis or the activation of EETs synthesis may offer novel therapeutic approaches to treat DCM.

Molecular Basis of the Distinct Metabolic Features in Shoot Tips and Roots of Tea Plants (Camellia sinensis): Characterization of MYB Regulator for Root Theanine Synthesis.

The physiological and metabolic differences between shoot tips and roots of tea plants are significant, and understanding them is required for improvement of tea quality and plant growth. A high-quality full-length transcriptome sequencing on tea plant roots and shoot tips by PacBio SMRT technology was done to gain a further understanding. Approximately 160699 and 166120 full-length transcripts were recovered in roots and shoots, respectively, including 31232 and 41068 novel isoforms and 16960 and 26029 alternative splicing (AS) isoforms. These supported 21699 full-length reads and 31232 and 41068 novel transcripts from root and shoot, respectively, including 1679 long noncoding RNAs (lncRNAs) and 2772 fusion transcripts, which significantly upgrade the Camellia sinensis genome annotation. The respective 6475 and 6981 transcripts in roots and shoots differ in 3'-untranslated regions. Meanwhile, extensive analyses of novel transcripts, ASs, and lncRNAs also revealed a large number of ASs and lincRNAs closely related to the regulation of characteristic secondary metabolites including catechins, theanine, and caffeine. Finally, a root-specific CsMYB6 was characterized to regulate theanine biosynthesis by genetic and molecular analyses. CsMYB6 directly bound to and activate the promoter of theanine synthetase gene (CsTSI). The study lays a foundation for the further investigation of metabolic genomics and regulation in tea plants.

Occurrence of carbamazepine, diclofenac, and their related metabolites and transformation products in a French aquatic environment and preliminary risk assessment

With questions emerging on the presence and risks associated with metabolites and transformation products (TPs) of organic contaminants in the aquatic environment, progress has been made in terms of monitoring and regulation of pesticide metabolites. However, less interest is shown for pharmaceutical residues, although their pseudo-persistence and adverse effects on non-target organisms are proven. This study provides original knowledge about the contamination of ten sites located along three French rivers (water, sediments, biofilms, clams) by pharmaceutical metabolites and TPs, as well as a preliminary environmental risk assessment. Studied compounds included carbamazepine with five metabolites and TPs, and diclofenac with three metabolites and TPs. Results show that metabolites and TPs are present in all studied compartments, with mean concentrations up to 0.52 µg L−1 in water, 229 ng g−1 in sediments, 2153 ng g−1 in biofilms, and 1149 ng g−1 in clams. QSAR estimations (OECD toolbox) were involved to predict the studied compounds ecotoxicities. QSAR models showed that diclofenac and its metabolites and TPs could be more toxic than carbamazepine and its metabolites and TPs to three aquatic species representing green algae, invertebrates, and fish. However, real ecotoxicological effects are still to be determined. The environmental risk assessment showed that hydroxydiclofenac, 2-[(2-chlorophenyl)-amino]-benzaldehyde and dibenzazepine could present a greater risk than other studied compounds for aquatic organisms. In addition, the risk associated with a mixture of diclofenac and its related metabolites and TPs has been found to be greater than that of the compounds considered individually.

The phytotoxin COR induces transcriptional reprogramming of photosynthetic, hormonal and defence networks in tomato.

Coronatine (COR) is a non-host specific phytotoxin secreted by Pseudomonas syringae pv. tomato that can induce leaf chlorosis and increase the virulence of pathogens during plant-pathogen interactions. Studies have shown that COR can regulate multiple physiological processes in plants, but its involvement in bacterial pathogenesis and plant growth regulation is not well understood. In this study, transcriptome sequencing was carried out on 4-week-old tomato leaves that were either mock-treated or treated with COR. Transcriptome sequencing led to the identification of 6144 differentially expressed genes (DEGs), of which 4361 genes were downregulated and 1783 genes were upregulated upon COR treatment. To obtain functional information on the DEGs, we annotated these genes using GO and KEGG databases. Functional classification analysis showed that the DEGs were primarily involved in photosynthesis, chlorophyll and carotenoid biosynthesis, jasmonic acid (JA) synthesis and phenylpropane metabolism. A total of 23 genes related to chlorophyll biosynthesis had significant changes, of which 22 genes were downregulated and one gene was upregulated, indicating that chlorophyll biosynthesis was inhibited upon COR treatment. A total of 17 photosystem I related genes and 22 photosystem II related genes involving 20 protein subunits were also downregulated. In the JA synthesis pathway, 25 genes were up regulated, and six genes were downregulated in COR treated samples. COR was also involved in the regulation of multiple secondary metabolites. The identified DEGs will help us better understand the virulence effects and physiological functions of COR and provide a theoretical basis for breeding resistance into economically important crops.

Liquid chromatography-mass spectrometry-based metabolomics study of the efficacy of Chinese medicine asthma-relieving decoction on respiratory syncytial virus infection

呼吸道合胞病毒(RSV)容易引发下呼吸道感染,尤其是小儿毛细支气管炎。中药定喘汤用于RSV感染的治疗在中国有着广泛的临床实践基础。由于中药体系的复杂性,其治疗机制和主要药效成分还不够明确。采用代谢组学方法分析中药药效,可以为传统中药治疗提供现代科学论证。该研究对大鼠各干预组分别采用中药定喘汤全方,宣、降、清分解剂以及利巴韦林灌胃治疗,正常组大鼠和RSV模型组大鼠均采用生理盐水灌胃。分别取大鼠在第0、3、7天的眼底血浆进行基于液相色谱-串联质谱法的非靶向代谢组学分析,以研究RSV感染引起的代谢组改变、定喘汤对RSV感染相关代谢物的调控及定喘汤的主要药效来源。对检测的代谢物离子进行多变量分析,建立主成分分析模型,结果显示在RSV感染及治疗进程中,中药定喘汤组与利巴韦林阳性对照组对RSV感染大鼠产生的总体代谢调控效果类似。在3种定喘汤分解剂中,组成成分为麻黄和白果的宣法分解剂对代谢组的调控作用与定喘汤更为接近,可能为定喘汤的主要药效来源。基于配对t检验发现大鼠在感染RSV后有83种代谢物发生了显著性改变,表明RSV感染可造成大鼠多条代谢通路紊乱。第3天时中药定喘汤对包括胆汁酸、氨基酸、有机酸、脂质等在内的代谢物有治疗效果。3种分解剂中,宣法分解剂对代谢物的调节作用与定喘汤类似,而降法分解剂和清法分解剂对大鼠因感染RSV引起的酰基肉碱的异常升高有明显下调作用。各组都有维持肠道菌群和免疫系统稳定的药效。该研究采用代谢组学方法评价定喘汤的药效,发现了定喘汤治疗后改变的代谢物的种类及变化规律,为定喘汤的治疗机理和活性成分的研究提供了理论支持。

Melatonin alters the secondary metabolite profile of grape berry skin by promoting VvMYB14-mediated ethylene biosynthesis

The interplay between melatonin and ethylene in the regulation of fruit metabolism and the underlying molecular mechanism of this interplay remain largely unclear. Here, widely targeted metabolomics analysis revealed a total of 464 metabolites present in berry skin. Among them, 27 significantly differentially accumulated metabolites (DAMs) were produced in response to melatonin treatment in the presence or absence of 1-MCP. Most of the DAMs were secondary metabolites, including flavonoids, phenolic acids, stilbenes, and flavonols. Additionally, the accumulation of 25 DAMs was regulated by melatonin via ethylene. RNA-seq analysis indicated that melatonin primarily regulated the pathways of plant hormone signal transduction and secondary metabolite biosynthesis via ethylene. Gene-metabolite association analysis showed that melatonin regulated the expression of the VvSTS1, VvF3H, VvLAR2, and VvDFR genes, suggesting that these genes may play key roles in regulating secondary metabolites in the skin; additionally, VvMYB14 and VvACS1 were suggested to be involved in the regulation of secondary metabolites. Further experiments revealed that melatonin induced the expression of VvMYB14 and that VvMYB14 increased ethylene production by transcriptionally activating VvACS1, thereby affecting the accumulation of secondary metabolites. Collectively, melatonin promotes ethylene biosynthesis and alters secondary metabolite accumulation through the regulation of VvACS1 by VvMYB14.

Itaconate confers tolerance to late NLRP3 inflammasome activation

SUMMARYItaconate is a unique regulatory metabolite that is induced upon Toll-like receptor (TLR) stimulation in myeloid cells. Here, we demonstrate major inflammatory tolerance and cell death phenotypes associated with itaconate production in activated macrophages. We show that endogenous itaconate is a key regulator of the signal 2 of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation after long lipopolysaccharide (LPS) priming, which establishes tolerance to late NLRP3 inflammasome activation. We show that itaconate acts synergistically with inducible nitric oxide synthase (iNOS) and that the ability of various TLR ligands to establish NLRP3 inflammasome tolerance depends on the pattern of co-expression of IRG1 and iNOS. Mechanistically, itaconate accumulation upon prolonged inflammatory stimulation prevents full caspase-1 activation and processing of gasdermin D, which we demonstrate to be post-translationally modified by endogenous itaconate. Altogether, our data demonstrate that metabolic rewiring in inflammatory macrophages establishes tolerance to NLRP3 inflammasome activation that, if uncontrolled, can result in pyroptotic cell death and tissue damage.

1-Methylnicotinamide is an immune regulatory metabolite in human ovarian cancer.

Immune regulatory metabolites are key features of the tumor microenvironment (TME), yet with a few exceptions, their identities remain largely unknown. Here, we profiled tumor and T cells from tumor and ascites of patients with high-grade serous carcinoma (HGSC) to uncover the metabolomes of these distinct TME compartments. Cells within the ascites and tumor had pervasive metabolite differences, with a notable enrichment in 1-methylnicotinamide (MNA) in T cells infiltrating the tumor compared with ascites. Despite the elevated levels of MNA in T cells, the expression of nicotinamide N-methyltransferase, the enzyme that catalyzes the transfer of a methyl group from S-adenosylmethionine to nicotinamide, was restricted to fibroblasts and tumor cells. Functionally, MNA induces T cells to secrete the tumor-promoting cytokine tumor necrosis factor alpha. Thus, TME-derived MNA contributes to the immune modulation of T cells and represents a potential immunotherapy target to treat human cancer.

Genome-Wide Characterization of Jasmonates Signaling Components Reveals the Essential Role of ZmCOI1a-ZmJAZ15 Action Module in Regulating Maize Immunity to Gibberella Stalk Rot.

Gibberella stalk rot (GSR) by Fusarium graminearum causes significant losses of maize production worldwide. Jasmonates (JAs) have been broadly known in regulating defense against pathogens through the homeostasis of active JAs and COI-JAZ-MYC function module. However, the functions of different molecular species of JAs and COI-JAZ-MYC module in maize interactions with Fusarium graminearum and regulation of diverse metabolites remain unknown. In this study, we found that exogenous application of MeJA strongly enhanced resistance to GSR. RNA-seq analysis showed that MeJA activated multiple genes in JA pathways, which prompted us to perform a genome-wide screening of key JA signaling components in maize. Yeast Two-Hybrid, Split-Luciferase, and Pull-down assays revealed that the JA functional and structural mimic coronatine (COR) functions as an essential ligand to trigger the interaction between ZmCOIa and ZmJAZ15. By deploying CRISPR-cas9 knockout and Mutator insertional mutants, we demonstrated that coi1a mutant is more resistant, whereas jaz15 mutant is more susceptible to GSR. Moreover, JA-deficient opr7-5opr8-2 mutant displayed enhanced resistance to GSR compared to wild type. Together, these results provide strong evidence that ZmJAZ15 plays a pivotal role, whereas ZmCOIa and endogenous JA itself might function as susceptibility factors, in maize immunity to GSR.

Dynamic control over feedback regulatory mechanisms improves NADPH flux and xylitol biosynthesis in engineered E. coli

We report improved NADPH flux and xylitol biosynthesis in engineered E. coli. Xylitol is produced from xylose via an NADPH dependent reductase. We utilize 2-stage dynamic metabolic control to compare two approaches to optimize xylitol biosynthesis, a stoichiometric approach, wherein competitive fluxes are decreased, and a regulatory approach wherein the levels of key regulatory metabolites are reduced. The stoichiometric and regulatory approaches lead to a 20-fold and 90-fold improvement in xylitol production, respectively. Strains with reduced levels of enoyl-ACP reductase and glucose-6-phosphate dehydrogenase, led to altered metabolite pools resulting in the activation of the membrane bound transhydrogenase and an NADPH generation pathway, consisting of pyruvate ferredoxin oxidoreductase coupled with NADPH dependent ferredoxin reductase, leading to increased NADPH fluxes, despite a reduction in NADPH pools. These strains produced titers of 200 g/L of xylitol from xylose at 86% of theoretical yield in instrumented bioreactors. We expect dynamic control over the regulation of the membrane bound transhydrogenase as well as NADPH production through pyruvate ferredoxin oxidoreductase to broadly enable improved NADPH dependent bioconversions or production via NADPH dependent metabolic pathways.

The versatile biochemistry of iron in macrophage effector functions.

Macrophages are mononuclear phagocytes with remarkable polarization ability that allow them to have tissue-specific functions during development, homeostasis, inflammatory and infectious disease. One particular trophic factor in the tissue environment is iron, which is intimately linked to macrophage effector functions. Macrophages have a well-described role in the control of systemic iron levels, but their activation state is also depending on iron-containing proteins/enzymes. Haemoproteins, dioxygenases and iron-sulphur (Fe-S) enzymes are iron-binding proteins that have bactericidal, metabolic and epigenetic-related functions, essential to shape the context-dependent macrophage polarization. In this review, I describe mainly pro-inflammatory macrophage polarization focussing on the role of iron biochemistry in selected haemoproteins and Fe-S enzymes. I show how iron, as part of haem or Fe-S clusters, participates in the cellular control of pro-inflammatory redox reactions in parallel with its role as enzymatic cofactor. I highlight a possible coordinated regulation of haemoproteins and Fe-S enzymes during classical macrophage activation. Finally, I describe tryptophan and α-ketoglutarate metabolism as two essential effector pathways in macrophages that use diverse iron biochemistry at different enzymatic steps. Through these pathways, I show how iron participates in the regulation of essential metabolites that shape macrophage function.

The vitamin E long-chain metabolite α-13′-COOH affects macrophage foam cell formation via modulation of the lipoprotein lipase system

The α-tocopherol-derived long-chain metabolite (α-LCM) α-13′-carboxychromanol (α-13′-COOH) is formed via enzymatic degradation of α-tocopherol (α-TOH) in the liver. In the last decade, α-13′-COOH has emerged as a new regulatory metabolite revealing more potent or even different effects compared with its vitamin precursor α-TOH. The detection of α-13′-COOH in human serum has further strengthened the concept of its physiological relevance as a potential regulatory molecule. Here, we present a new facet on the interaction of α-13′-COOH with macrophage foam cell formation. We found that α-13′-COOH (5 μM) increases angiopoietin-like 4 (ANGPTL4) mRNA expression in human THP-1 macrophages in a time- and dose-dependent manner, while α-TOH (100 μM) showed no effects. Interestingly, the mRNA level of lipoprotein lipase (LPL) was not influenced by α-13′-COOH, but α-TOH treatment led to a reduction of LPL mRNA expression. Both compounds also revealed different effects on protein level: while α-13′-COOH reduced the secreted amount of LPL protein via induction of ANGPTL4 cleavage, i.e. activation, the secreted amount of LPL in the α-TOH-treated samples was diminished due to the inhibition of mRNA expression. In line with this, both compounds reduced the catalytic activity of LPL. However, α-13′-COOH but not α-TOH attenuated VLDL-induced lipid accumulation by 35%. In conclusion, only α-13′-COOH revealed possible antiatherogenic effects due to the reduction of VLDL-induced foam cell formation in THP-1 macrophages. Our results provide further evidence for the role of α-13′-COOH as a functional metabolite of its vitamin E precursor.

Advances in fungal-assisted phytoremediation of heavy metals: A review

Trace metals such as manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) are essential for many biological processes in plant life cycles. However, in excess, they can be toxic and disrupt plant growth processes, which is economically undesirable for crop production. For this reason, processes such as homeostasis and transport control of these trace metals are of constant interest to scientists studying heavily contaminated habitats. Phytoremediation is a promising cleanup technology for soils polluted with heavy metals. However, this technique has some disadvantages, such as the slow growth rate of metal-accumulating plant species, low bioavailability of heavy metals, and long duration of remediation. Microbial-assisted phytoremediation is a promising strategy for hyperaccumulating, detoxifying, or remediating soil contaminants. Arbuscular mycorrhizal fungi (AMF) are found in association with almost all plants, contributing to their healthy performance and providing resistance against environmental stresses. They colonize plant roots and extend their hyphae to the rhizosphere region, assisting in mineral nutrient uptake and regulation of heavy metal acquisition. Endophytic fungi exist in every healthy plant tissue and provide enormous services to their host plants, including growth enhancement by nutrient acquisition, detoxification of heavy metals, secondary metabolite regulation, and enhancement of abiotic/biotic stress tolerance. The aim of the present work is to review the recent literature regarding the role of AMF and endophytic fungi in plant heavy metal tolerance in terms of its regulation in highly contaminated conditions.

Polysaccharides from fermented Momordica charantia L. with Lactobacillus plantarum NCU116 ameliorate metabolic disorders and gut microbiota change in obese rats.

Obesity is a chronic disease characterized by overweight resulting from fat accumulation, along with disturbance of metabolism and gut microbiota. Fermentation, as a green processing method, is beneficial for improving the nutrition capacity of food components. Polysaccharides are considered as one of the important components in food and are also potential supplements for anti-obesity treatment. This study aimed to investigate the anti-obesity effects of polysaccharides from fermented and non-fermented Momordica charantia L. with Lactobacillus plantarum NCU116 (FP and NFP) on obese rats by serum metabolomics and gut microbiota analysis. Metabolomics results revealed that abnormal lipid metabolism was formed due to obesity. The supplement of FP and NFP improved the glycerophospholipids, glycosphingolipids, and amino acid metabolism of the obese rats, which alleviated the hypercholesterolemia and overweight in rats. Furthermore, the disorder of gut microbiota was ameliorated by FP and NFP. FP promoted the growth of beneficial bacteria, such as phylum Firmicutes, Actinobacteria, and genera Anaerostipes, Coprococcus, Lactobacillus, and Bifidobacterium. FP also reduced several harmful bacteria belonging to the phylum Proteobacteria and genera Helicobacter. The positive correlation of the weight loss and lowering of serum lipids with the increased beneficial bacteria further elucidated that the anti-obesity effect of FP in obese rats is associated with the regulation of gut microbiota and serum metabolites. The results of this study could provide information for developing probiotic products in the future that may have beneficial effects on the prevention or treatment of obesity.

Macrophages: Restriction of TCA Cycle Intermediates

In hypoxic and excited tissues, oxygen (O2)- depen-gouge antimicrobial safeguards are disabled due to ashortage of O2. To acquire understanding into the mechanismsthat control bacterial disease under hypoxic condi-tions, we contaminated macrophages with the obligateintracellular pathogenCoxiella burnetii, the causativeagent of Q fever. Our investigations uncovered that hypoxia impededC. burnetiireplication in a hypoxia-inducible factor (HIF) 1asubordinate way. Mecha-nistically, under hypoxia, HIF1aimpaired the activityof STAT3, which thus diminished the intracellular levelof TCA cycle intermediates, including citrate, andimpededC. burnetiireplication in macrophages.However, bacterial reasonability was kept up, allowingthe tirelessness ofC. burnetii, which is a prerequisitefor the advancement of constant Q fever. This knowl-edge will open future examination roads on the way ogenesis of constant Q fever. Also, the regula-tion of TCA cycle metabolites by HIF1arepresentsa beforehand neglected component of host de-fense against intracellular microbes.

Ganoderma research activities and development in Namibia: A review

Medicinal mushrooms have provided a natural source of bioactive compounds since ancient times. Ganoderma is such a mushroom, which has worldwide recognition as a medicinally important mushroom. In this review, the authors provide a detailed summary of indigenous Ganoderma research in Namibia, looking at the ethnomycology, biological activity, physicochemical properties, food quality and safety, as well as cultivation of this mushroom. In this paper, all available records of Ganoderma research in Namibia were retrieved from the University of Namibia Institutional Repository with the keyword “Ganoderma”. Ten theses and four peer-reviewed articles with a total of 10 authors and 12 subjects, including ethnomedicinal plants, domestication, active compounds, medicinal and AIDS were reviewed. The main objective of this review is to guide researchers on the direction for future research and product development of Ganoderma in Namibia. The literature review highlights the potential to establish research and development activities of indigenous Namibian Ganoderma species. The study identifies an important knowledge gap on Ganoderma research, such as the complete morphological and molecular description of species, regulation and standardization of metabolites and characterization of novel compounds identified in indigenous Namibian Ganoderma. The domestication and cultivation of medicinal and edible mushrooms provide an excellent opportunity to contribute to the United Nations Sustainable Development Goals of promoting good health and well-being (SDG 3), nutrition (SDG 2: Zero Hunger), and income generation (SDG 1: no poverty).

Transition of aromatic volatile and transcriptome profiles during melon fruit ripening

Melon (Cucumis melo L.) is an important diploid crop with a wide variety of flavors due to its distinct aromatic volatile organic compounds (VOC). To understand the development of VOC profiles during fruit development, we performed metabolomic and transcriptomic analysis of two cantaloupe varieties over the course of fruit development. A total of 130 metabolites were detected in fruit samples, and 449014207 reads were mapped to the melon genome. A total of 4469 differentially expressed genes in fruits were identified and used to visualize the transition of VOC and transcriptomic profiles during the fruit development. A shift of VOC profiles in both varieties was observed from early-fruit profiles enriched in C5-C8 lipid-derived VOCs to late-fruit profiles abundant in C9 lipid-derived VOCs, apocarotenoids, and esters. The shift coincided with the expression of specific isoforms of lipid and carotenoid metabolizing enzymes as well as transcription factors involved in fruit ripening, metabolite regulation, and hormone signaling.