PubMed

J Fungi (Basel). 2023 Nov 17;9(11):1117. doi: 10.3390/jof9111117.ABSTRACTThe rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics. Hence, there is a need to search for new sources of antibiotics that either exhibit novel structures or express a new mechanism of action. The lichen Usnea, with its wide range of unique, biologically potent secondary metabolites, may solve this problem. In this study, Usnea species were collected in the Northern Philippines, identified through combined morphological and biochemical characterization, and tested for antimicrobial activities against the multidrug-resistant ESKAPE pathogens, i.e., Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae, two standard antibiotic-sensitive test bacteria, and a yeast. A total of 46 lichen specimens were collected and later identified as Usnea baileyi (10), U. diffracta (10), U. glabrata (12), U. longissima (4), and U. rubicunda (10). The results show that the crude extracts of the Usnea species exhibited promising in vitro inhibitory activities against standard antibiotic-sensitive (E. faecalis ATCC 29212) and multidrug-resistant (methicillin-resistant S. aureus and E. faecalis) Gram-positive bacteria. Additionally, lichen compounds of representative specimens per species were identified and profiled using thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). The detection of lichen acids (LA) via HPLC showed the presence of 24 peaks of lichen acids. TLC-bioautography identified the bioactive lichen acids as alectronic acid, connorstictic acid, consalazinic acid, diffractaic acid, echinocarpic acid, erythrin acid, galbinic acid, hypoconstictic acid, hyposalazinic acid, hypostictic acid, lobaric acid, menegazzaic acid, micareic acid, pannarin, salazinic acid, stictic acid, and usnic acid. Our study highlighted the wide spectrum of opportunities for using lichens for the discovery of potential antimicrobial agents.PMID:37998922 | DOI:10.3390/jof9111117

J Fungi (Basel). 2023 Nov 8;9(11):1090. doi: 10.3390/jof9111090.ABSTRACTAspergillus versicolor is ubiquitous in the environment and is particularly abundant in damp indoor spaces. Exposure to Aspergillus species, as well as other environmental fungi, has been linked to respiratory health outcomes, including asthma, allergy, and even local or disseminated infection. However, the pulmonary immunological mechanisms associated with repeated exposure to A. versicolor have remained relatively uncharacterized. Here, A. versicolor was cultured and desiccated on rice then placed in an acoustical generator system to achieve aerosolization. Mice were challenged with titrated doses of aerosolized conidia to examine deposition, lymphoproliferative properties, and immunotoxicological response to repeated inhalation exposures. The necessary dose to induce lymphoproliferation was identified, but not infection-like pathology. Further, it was determined that the dose was able to initiate localized immune responses. The data presented in this study demonstrate an optimized and reproducible method for delivering A. versicolor conidia to rodents via nose-only inhalation. Additionally, the feasibility of a long-term repeated exposure study was established. This experimental protocol can be used in future studies to investigate the physiological effects of repeated pulmonary exposure to fungal conidia utilizing a practical and relevant mode of delivery. In total, these data constitute an important foundation for subsequent research in the field.PMID:37998895 | DOI:10.3390/jof9111090

J Fungi (Basel). 2023 Oct 31;9(11):1064. doi: 10.3390/jof9111064.ABSTRACTIn the 1990s, a sampling network for the biomonitoring of forests using epiphytic lichen diversity was established in the eastern Iberian Peninsula. This area registered air pollution impacts by winds from the Andorra thermal power plant, as well as from photo-oxidants and nitrogen depositions from local and long-distance transport. In 1997, an assessment of the state of lichen communities was carried out by calculating the Index of Atmospheric Purity. In addition, visible symptoms of morphological injury were recorded in nine macrolichens pre-selected by the speed of symptom evolution and their wide distribution in the territory. The thermal power plant has been closed and inactive since 2020. During 2022, almost 25 years later, seven stations of this previously established biomonitoring were revaluated. To compare the results obtained in 1997 and 2022, the same methodology was used, and data from air quality stations were included. We tested if, by integrating innovative methodologies (NIRS) into biomonitoring tools, it is possible to render an integrated response. The results displayed a general decrease in biodiversity in several of the sampling plots and a generalised increase in damage symptoms in the target lichen species studied in 1997, which seem to be the consequence of a multifactorial response.PMID:37998870 | DOI:10.3390/jof9111064

J Fungi (Basel). 2023 Oct 30;9(11):1063. doi: 10.3390/jof9111063.ABSTRACTFlammulina velutipes is a renowned edible and medicinal fungus. Commercially cultivated F. velutipes occurs in two distinct phenotypes: white and yellow. However, the underlying mechanism contributing to the yellow phenotype and high nutritional value remain uncertain. We reconfirmed that the browning process in F. velutipes is attributable to melanin accumulation, although the initial yellow cap seemed unrelated to melanin. A transcriptomic and metabolomic joint analysis revealed that 477 chemical compounds categorized into 11 classes, among which 191 exhibited significantly different levels of accumulation between different phenotypes. Specifically, 12 compounds were unique to the yellow F. velutipes, including ferulic acid, and 3-Aminosalicylic acid. Free fatty acids and xanthine were identified as the primary compounds correlating with the yellow and oily cap. A total of 44,087 genes were identified, which were more homologous to Pleurotus ostreatus PC15. Structural genes such as PAL (phenylalanine ammonialyase), C4H (cinnamate 4-hydroxylase), C3H (Coumarin-3-hydroxylase), AoMT (caffeoyl coenzyme A-O-methyltransferase), and 4CL (4-coumarate: CoA ligase) were up-regulated, thereby activating the lignin biosynthesis and metabolism pathway. Additionally, FvbHLH1 can lead to the consumption of a huge amount of phenylalanine while generating flavonoids and organic acid compounds. Meanwhile, ferulic acid biosynthesis was activated. Therefore, this study clarifies the chemical and molecular bases for the yellow phenotype and nutritional value of F. velutipes.PMID:37998869 | DOI:10.3390/jof9111063

J Fungi (Basel). 2023 Oct 27;9(11):1057. doi: 10.3390/jof9111057.ABSTRACTRecent studies have found that many marine microbial polysaccharides exhibit distinct immune activity. However, there is a relative scarcity of research on the immunomodulatory activity of marine fungal exopolysaccharides. A novel water-soluble fungal exopolysaccharide ASP-1 was isolated from the fermentation broths of marine coral-associated fungus Aspergillus pseudoglaucus SCAU265, and purified by Diethylaminoethyl-Sepharose-52 (DEAE-52) Fast Flow and Sephadex G-75. Structural analysis revealed that ASP-1 had an average molecular weight of 36.07 kDa and was mainly composed of (1→4)-linked α-D-glucopyranosyl residues, along with highly branched heteropolysaccharide regions containing 1,4,6-glucopyranosyl, 1,3,4-glucopyranosyl, 1,4,6-galactopyranosyl, T(terminal)-glucopyranosyl, T-mannopyranosyl, and T-galactopyranosyl residues. ASP-1 demonstrated significant effects on the proliferation, nitric oxide levels, and the secretion of cytokines TNF-α and IL-6 in macrophage RAW264.7 cells. Metabolomic analysis provided insights into the potential mechanisms of the immune regulation of ASP-1, suggesting its involvement in regulating immune function by modulating amino acid anabolism, particularly arginine synthesis and metabolism. These findings provide fundamental scientific data for further research on its accurate molecular mechanism of immunomodulatory activity.PMID:37998863 | DOI:10.3390/jof9111057

Antibiotics (Basel). 2023 Nov 20;12(11):1643. doi: 10.3390/antibiotics12111643.ABSTRACTTerminalia petiolaris A. Cunn. Ex Benth. (genus: Terminalia, family: Combretaceae) is native to Australia. Terminalia spp. have traditionally been used to treat various ailments, including bacterial infections. Solvents of varying polarity were used to extract compounds from leaves of this species, and the extracts were tested against a panel of bacteria, including antibiotic-resistant strains. The methanolic and water extracts showed substantial inhibitory activity against several bacteria, including antibiotic-resistant strains in both disc diffusion and liquid dilution assays. Combining these extracts with selected conventional antibiotics enhanced the inhibition of bacterial growth for some combinations, while others showed no significant interaction. In total, two synergistic, twenty-five additive, twenty-three non-interactive and one antagonistic interaction were observed. The methanolic and ethyl acetate plant extracts were found to be non-toxic in Artemia franciscana nauplii toxicity assays. A liquid chromatography-mass spectrometry metabolomics analysis identified several flavonoid compounds, including miquelianin, trifolin and orientin, which might contribute to the observed activities. The potential modes of these active extracts are further discussed in this study.PMID:37998845 | DOI:10.3390/antibiotics12111643

Antibiotics (Basel). 2023 Nov 10;12(11):1615. doi: 10.3390/antibiotics12111615.ABSTRACTBiofilm formation and lipopolysaccharide (LPS) are implicated in the pathogenesis of gastrointestinal (GI) diseases caused by Gram-negative bacteria. Grape seeds, wine industry by-products, have antioxidant and antimicrobial activity. In the present study, the protective effect of procyanidin-rich grape seed extract (prGSE), from unfermented pomace of Vitis vinifera L. cv Bellone, on bacterial LPS-induced oxidative stress and epithelial barrier integrity damage has been studied in a model of Caco-2 cells. The prGSE was characterized at the molecular level using HPLC and NMR. The in vitro activity of prGSE against formation of biofilm of Salmonella enterica subsp. enterica serovar Typhimurium and Escherichia coli was investigated. In vivo, prGSE activity using infected Galleria mellonella larvae has been evaluated. The results show that the prGSE, if administered with LPS, can significantly reduce the LPS-induced permeability alteration. Moreover, the ability of the extract to prevent Reactive Oxygen Species (ROS) production induced by the LPS treatment of Caco-2 cells was demonstrated. prGSE inhibited the biofilm formation of E. coli and S. Typhimurium. In terms of in vivo activity, an increase in survival of infected G. mellonella larvae after treatment with prGSE was demonstrated. In conclusion, grape seed extracts could be used to reduce GI damage caused by bacterial endotoxin and biofilms of Gram-negative bacteria.PMID:37998817 | DOI:10.3390/antibiotics12111615

Curr Issues Mol Biol. 2023 Nov 13;45(11):9060-9075. doi: 10.3390/cimb45110568.ABSTRACTChaylte vine, the tender shoot of Sechium edule, is popular among vegetable consumers because of its high nutritional content, crisp texture, and unique flavor. Existing studies on the nutrient composition of chaylte vines are mostly simple chemical determinations, which have limited the breeding of specialized cultivars and the development of related industries. Using metabolomics combined with transcriptomics, this study analyzed the metabolic characteristics and related molecular mechanisms of two common varieties of chaylte vines: green-skinned (SG) and white-skinned (SW). Between the two varieties, a total of 277 differentially accumulated metabolites (DAMs) and 739 differentially expressed genes (DEGs) were identified. Furthermore, chemical assays demonstrated that the SW exhibited a higher total flavonoid content and antioxidant capacity. In conclusion, it was found that the SG samples exhibited a higher diversity of flavonoid subclasses compared to the SW samples, despite having a lower total flavonoid content. This inconsistent finding was likely due to the differential expression of the phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS) genes in the two varieties. These results laid the foundation for investigating the mechanisms involved in flavonoid regulation and the breeding of specialized S. edule cultivars for chaylte vine production.PMID:37998745 | DOI:10.3390/cimb45110568

Curr Issues Mol Biol. 2023 Nov 10;45(11):8989-9002. doi: 10.3390/cimb45110564.ABSTRACTThis study describes the cloning, expression and functional characterization of α-humulene synthase, responsible for the formation of the key aromatic compound α-humulene in agarwood originating from Aquilaria malaccensis. The partial sesquiterpene synthase gene from the transcriptome data of A. malaccensis was utilized for full-length gene isolation via a 3' RACE PCR. The complete gene, denoted as AmDG2, has an open reading frame (ORF) of 1671 bp and encodes for a polypeptide of 556 amino acids. In silico analysis of the protein highlighted several conserved motifs typically found in terpene synthases such as Asp-rich substrate binding (DDxxD), metal-binding residues (NSE/DTE), and cytoplasmic ER retention (RxR) motifs at their respective sites. The AmDG2 was successfully expressed in the E. coli:pET-28a(+) expression vector whereby an expected band of about 64 kDa in size was detected in the SDS-PAGE gel. In vitro enzyme assay using substrate farnesyl pyrophosphate (FPP) revealed that AmDG2 gave rise to two sesquiterpenes: α-humulene (major) and β-caryophyllene (minor), affirming its identity as α-humulene synthase. On the other hand, protein modeling performed using AlphaFold2 suggested that AmDG2 consists entirely of α-helices with short connecting loops and turns. Meanwhile, molecular docking via AutoDock Vina (Version 1.5.7) predicted that Asp307 and Asp311 act as catalytic residues in the α-humulene synthase. To our knowledge, this is the first comprehensive report on the cloning, expression and functional characterization of α-humulene synthase from agarwood originating from A. malaccensis species. These findings reveal a deeper understanding of the structure and functional properties of the α-humulene synthase and could be utilized for metabolic engineering work in the future.PMID:37998741 | DOI:10.3390/cimb45110564

Curr Issues Mol Biol. 2023 Nov 8;45(11):8894-8906. doi: 10.3390/cimb45110558.ABSTRACTPlant metabolomics is a rapidly advancing field of plant sciences and systems biology. It involves comprehensive analyses of small molecules (metabolites) in plant tissues and cells. These metabolites include a wide range of compounds, such as sugars, amino acids, organic acids, secondary metabolites (e.g., alkaloids and flavonoids), lipids, and more. Metabolomics allows an understanding of the functional roles of specific metabolites in plants' physiology, development, and responses to biotic and abiotic stresses. It can lead to the identification of metabolites linked with specific traits or functions. Plant metabolic networks and pathways can be better understood with the help of metabolomics. Researchers can determine how plants react to environmental cues or genetic modifications by examining how metabolite profiles change under various crop stages. Metabolomics plays a major role in crop improvement and biotechnology. Integrating metabolomics data with other omics data (genomics, transcriptomics, and proteomics) provides a more comprehensive perspective of plant biology. This systems biology approach enables researchers to understand the complex interactions within organisms.PMID:37998735 | DOI:10.3390/cimb45110558

Diagnostics (Basel). 2023 Nov 8;13(22):3401. doi: 10.3390/diagnostics13223401.ABSTRACTINTRODUCTION: Gastric cancer is the fourth most frequently diagnosed form of cancer and the third leading cause of cancer-related mortality worldwide. The aim of this review is to identify individual metabolic biomarkers and their association with accurate diagnostic values, which can predict gastric cancer metastasis.MATERIALS AND METHODS: After searching the keywords, 83 articles were found over a period of 13 years. One was eliminated because it was not written in English, and two were published outside the selected period. Seven scientific papers were qualified for this investigation after eliminating duplicates, non-related articles, systematic reviews, and restricted access studies.RESULTS: New metabolic biomarkers with predictive value for gastric cancer metastasis and for elucidating metabolic pathways of the metastatic process have been found. The pathogenic processes can be outlined as follows: pro-oxidant capacity, T-cell inactivation, cell cycle arrest, energy production and mitochondrial enzyme impairment, cell viability and pro-apoptotic effect, enhanced degradation of collagen extracellular matrix, migration, invasion, structural protein synthesis, and tumoral angiogenesis.CONCLUSION: Metabolic biomarkers have been recognized as independent risk factors in the molecular process of gastric cancer metastasis, with good diagnostic and prognostic value.PMID:37998537 | DOI:10.3390/diagnostics13223401

Biosensors (Basel). 2023 Nov 1;13(11):965. doi: 10.3390/bios13110965.ABSTRACTWe describe a competitive colorimetric assay that enables rapid and sensitive detection of galactose and reduced nicotinamide adenine dinucleotide (NADH) via colorimetric readouts and demonstrate its usefulness for monitoring NAD+-driven enzymatic reactions. We present a sensitive plasmonic sensing approach for assessing galactose concentration and the presence of NADH using galactose dehydrogenase-immobilized gold nanostars (AuNS-PVP-GalDH). The AuNS-PVP-GalDH assay remains turquoise blue in the absence of galactose and NADH; however, as galactose and NADH concentrations grow, the reaction well color changes to a characteristic red color in the presence of an alkaline environment and a metal ion catalyst (detection solution). As a result, when galactose is sensed in the presence of H2O2, the colored response of the AuNS-PVP-GalDH assay transforms from turquoise blue to light pink, and then to wine red in a concentration-dependent manner discernible to the human eye. This competitive AuNS-PVP-GalDH assay could be a viable analytical tool for rapid and convenient galactose quantification in resource-limited areas.PMID:37998140 | DOI:10.3390/bios13110965

Biology (Basel). 2023 Nov 16;12(11):1436. doi: 10.3390/biology12111436.ABSTRACTEwes undergo complex metabolic changes during pregnancy. Understanding the specific process of these changes is a necessary prerequisite in ewes for regulating and intervening in order to maintain pregnancies. However, there have been relatively few studies on the specific changes that occur in nutritional metabolism in pregnant ewes during early gestation, especially for some landrace ewes in highly cold areas. Therefore, this study aimed to (1) elucidate the changes in metabolites and microbial communities in pregnant ewes during early gestation using metabolomics and 16S ribosomal RNA gene (rDNA) amplicon sequencing approaches, and to (2) discover novel early pregnancy-induced biomarkers in the blood and faeces. Rams were placed together with ewes on D0 and removed on D45. During early gestation, blood and faecal samples were collected from ewes in a highly cold area for analysing the metabolites and microbial communities; these were retrospectively classified as the early gestation pregnant (EP) ewe group or the nonpregnant (NP) ewe group based on the lambing status recorded during the expected delivery period. The differences in the plasma biochemical parameters, plasma metabolites, and faecal microbial communities of pregnant and nonpregnant ewes were characterised. The GC, IL-6, O-acetyl-l-serine, L-glutamine, and 6-acetamido-2-oxohexanoic acid were screened out as potential biomarkers for evaluating the occurrence of early pregnancy. These novel early pregnancy-induced metabolites discovered in ewes might allow for the development of technologies to detect early pregnancies in sheep in highly cold areas.PMID:37998035 | DOI:10.3390/biology12111436

Biology (Basel). 2023 Oct 27;12(11):1378. doi: 10.3390/biology12111378.ABSTRACTWe investigated the effects of dietary delivered self-DNA in the model insect Drosophila melanogaster. Self-DNA administration resulted in low but significant lethality in Drosophila larvae and considerably extended the fly developmental time. This was characterized by the abnormal persistence of the larvae in the L2 and L3 stages, which largely accounted for the average 72 h delay observed in pupariation, as compared to controls. In addition, self-DNA exposure affected adult reproduction by markedly reducing both female fecundity and fertility, further demonstrating its impact on Drosophila developmental processes. The effects on the metabolites of D. melanogaster larvae after exposure to self-DNA were studied by NMR, LC-MS, and molecular networking. The results showed that self-DNA feeding reduces the amounts of all metabolites, particularly amino acids and N-acyl amino acids, which are known to act as lipid signal mediators. An increasing amount of phloroglucinol was found after self-DNA exposure and correlated to developmental delay and egg-laying suppression. Pidolate, a known intermediate in the γ-glutamyl cycle, also increased after exposure to self-DNA and correlated to the block of insect oogenesis.PMID:37997977 | DOI:10.3390/biology12111378

Mol Omics. 2023 Nov 24. doi: 10.1039/d3mo00163f. Online ahead of print.ABSTRACTType 1 diabetes (T1D) has been reported to cause systematic metabolic disorders, but metabolic changes in different intestinal segments of T1D remain unclear. In this study, we analyzed metabolic profiles in the jejunum, ileum, cecum and colon of streptozocin-induced T1D and age-matched control (CON) mice by an LC-MS-based metabolomics method. The results show that segment-specific metabolic disorders occurred in the gut of T1D mice. In the jejunum, we found that T1D mainly led to disordered amino acid metabolism and most amino acids were significantly lower relative to CON mice. Moreover, fatty acid metabolism was disrupted mainly in the ileum, cecum and colon of T1D mice, such as arachidonic acid, alpha-linolenic acid and linoleic acid metabolism. Thus, our study reveals spatial metabolic heterogeneity in the gut of T1D mice and provides a metabolic view on diabetes-associated intestinal diseases.PMID:37997452 | DOI:10.1039/d3mo00163f

Anal Chem. 2023 Nov 23. doi: 10.1021/acs.analchem.3c03595. Online ahead of print.ABSTRACTPhenotypic heterogeneity is commonly found among bacterial cells within microbial populations due to intrinsic factors as well as equipping the organisms to respond to external perturbations. The emergence of phenotypic heterogeneity in bacterial populations, particularly in the context of using these bacteria as microbial cell factories, is a major concern for industrial bioprocessing applications. This is due to the potential impact on overall productivity by allowing the growth of subpopulations consisting of inefficient producer cells. Monitoring the spread of phenotypes across bacterial cells within the same population at the single-cell level is key to the development of robust, high-yield bioprocesses. Here, we discuss the novel development of optical photothermal infrared (O-PTIR) spectroscopy to probe phenotypic heterogeneity within Bacillus strains by monitoring the production of the bioplastic poly-3-hydroxybutyrate (PHB) at the single-cell level. Measurements obtained on single-point and in imaging mode show significant variability in the PHB content within bacterial cells, ranging from whether or not a cell produces PHB to variations in the intragranular biochemistry of PHB within bacterial cells. Our results show the ability of O-PTIR spectroscopy to probe PHB production at the single-cell level in a rapid, label-free, and semiquantitative manner. These findings highlight the potential of O-PTIR spectroscopy in single-cell microbial metabolomics as a whole-organism fingerprinting tool that can be used to monitor the dynamic of bacterial populations as well as for understanding their mechanisms for dealing with environmental stress, which is crucial for metabolic engineering research.PMID:37997371 | DOI:10.1021/acs.analchem.3c03595

Expert Opin Drug Metab Toxicol. 2023 Nov 23. doi: 10.1080/17425255.2023.2288260. Online ahead of print.ABSTRACTINTRODUCTION: Idiosyncratic drug-induced liver injury (DILI) is a common cause of acute liver injury and can lead to death from acute liver failure or require liver transplantation. Although the total burden of liver injury is high, the frequency of DILI caused by specific agents is often low. As the liver injury is by per definition idiosyncratic, the prediction of which patients will develop liver injury from specific drugs is currently a very difficult challenge.AREAS COVERED: The current paper highlights the most important studies on prediction of DILI published in 2019-2023, including studies on genetic-, metabolomic- and demographic risk factors, concomitant medication and the role of comorbid liver diseases. Risk stratification using demographic-, metabolomic- and multigenetic risk factors is discussed.EXPERT OPINION: Great advances have been made in identifying genetic risk factors for DILI. Combining these risk factors with demographic information and other biomarkers into multigenetic risk models might become highly useful in risk stratifying patients exposed to DILI. However, more detailed mapping of genetic risk factors is needed. Results of these studies need to be validated in the selected ethnic groups before applicability and cost-effectiveness can be determined.PMID:37997265 | DOI:10.1080/17425255.2023.2288260

Genome Biol. 2023 Nov 23;24(1):265. doi: 10.1186/s13059-023-03107-4.ABSTRACTBACKGROUND: "Red tides" are harmful algal blooms caused by dinoflagellate microalgae that accumulate toxins lethal to other organisms, including humans via consumption of contaminated seafood. These algal blooms are driven by a combination of environmental factors including nutrient enrichment, particularly in warm waters, and are increasingly frequent. The molecular, regulatory, and evolutionary mechanisms that underlie the heat stress response in these harmful bloom-forming algal species remain little understood, due in part to the limited genomic resources from dinoflagellates, complicated by the large sizes of genomes, exhibiting features atypical of eukaryotes.RESULTS: We present the de novo assembled genome (~ 4.75 Gbp with 85,849 protein-coding genes), transcriptome, proteome, and metabolome from Prorocentrum cordatum, a globally abundant, bloom-forming dinoflagellate. Using axenic algal cultures, we study the molecular mechanisms that underpin the algal response to heat stress, which is relevant to current ocean warming trends. We present the first evidence of a complementary interplay between RNA editing and exon usage that regulates the expression and functional diversity of biomolecules, reflected by reduction in photosynthesis, central metabolism, and protein synthesis. These results reveal genomic signatures and post-transcriptional regulation for the first time in a pelagic dinoflagellate.CONCLUSIONS: Our multi-omics analyses uncover the molecular response to heat stress in an important bloom-forming algal species, which is driven by complex gene structures in a large, high-G+C genome, combined with multi-level transcriptional regulation. The dynamics and interplay of molecular regulatory mechanisms may explain in part how dinoflagellates diversified to become some of the most ecologically successful organisms on Earth.PMID:37996937 | DOI:10.1186/s13059-023-03107-4

World J Microbiol Biotechnol. 2023 Nov 24;40(1):21. doi: 10.1007/s11274-023-03816-9.ABSTRACTCr(VI) is a hazardous environmental pollutant that poses significant risks to ecosystems and human health. We successfully isolated a novel strain of Bacillus mobilis, strain CR3, from Cr(VI)-contaminated soil. Strain CR3 showed 86.70% removal capacity at 200 mg/L Cr(VI), and a good Cr(VI) removal capacity at different pH, temperature, coexisting ions, and electron donor conditions. Different concentrations of Cr(VI) affected the activity of CR3 cells and the removal rate of Cr(VI), and approximately 3.46% of total Cr was immobilized at the end of the reaction. The combination of SEM-EDS and TEM-EDS analysis showed that Cr accumulated both on the cell surface and inside the cells after treatment with Cr(VI). XPS analysis showed that both Cr(III) and Cr(VI) were present on the cell surface, and FTIR results indicated that the presence of Cr on the cell surface was mainly related to functional groups, such as O-H, phosphate, and -COOH. The removal of Cr(VI) was mainly achieved through bioreduction, which primarily occurred outside the cell. Metabolomics analysis revealed the upregulation of five metabolites, including phenol and L-carnosine, was closely associated with Cr(VI) reduction, heavy metal chelation, and detoxification mechanisms. In addition, numerous metabolites were linked to cellular homeostasis exhibited differential expression. Cr(VI) exerted inhibitory effects on the division rate and influenced critical pathways, including energy metabolism, nucleotide metabolism, and amino acid synthesis and catabolism. These findings reveal the molecular mechanism of Cr(VI) removal by strain CR3 and provide valuable insights to guide the remediation of Cr(VI)-contaminated sites.PMID:37996766 | DOI:10.1007/s11274-023-03816-9

Oncogene. 2023 Nov 23. doi: 10.1038/s41388-023-02884-3. Online ahead of print.ABSTRACTOvarian cancer has poor survival outcomes particularly for advanced stage, metastatic disease. Metastasis is promoted by interactions of stromal cells, such as cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME), with tumor cells. CAFs play a key role in tumor progression by remodeling the TME and extracellular matrix (ECM) to result in a more permissive environment for tumor progression. It has been shown that fibroblasts, in particular myofibroblasts, utilize metabolism to support ECM remodeling. However, the intricate mechanisms by which CAFs support collagen production and tumor progression are poorly understood. In this study, we show that the fibrillar collagen receptor, Discoidin Domain Receptor 2 (DDR2), promotes collagen production in human and mouse omental CAFs through arginase activity. CAFs with high DDR2 or arginase promote tumor colonization in the omentum. In addition, DDR2-depleted CAFs had decreased ornithine levels leading to decreased collagen production and polyamine levels compared to WT control CAFs. Tumor cell invasion was decreased in the presence CAF conditioned media (CM) depleted of DDR2 or arginase-1, and this invasion defect was rescued in the presence of CM from DDR2-depleted CAFs that constitutively overexpressed arginase-1. Similarly, the addition of exogenous polyamines to CM from DDR2-depleted CAFs led to increased tumor cell invasion. We detected SNAI1 protein at the promoter region of the arginase-1 gene, and DDR2-depleted CAFs had decreased levels of SNAI1 protein at the arginase-1 promoter region. Furthermore, high stromal arginase-1 expression correlated with poor survival in ovarian cancer patients. These findings highlight how DDR2 regulates collagen production by CAFs in the tumor microenvironment by controlling the transcription of arginase-1, and CAFs are a major source of arginase activity and L-arginine metabolites in ovarian cancer models.PMID:37996700 | DOI:10.1038/s41388-023-02884-3