Precision miRNA profiling: Electrochemiluminescence powered by CRISPR-Cas13a and hybridization chain reaction.

The article details a groundbreaking platform for detecting microRNAs (miRNAs), crucial biomolecules involved in gene regulation and linked to various diseases. This innovative platform combines the CRISPR-Cas13a system's precise ability to specifically target and cleave RNA molecules with the amplification capabilities of the hybridization chain reaction (HCR). HCR aids in signal enhancement by creating branched DNA structures. Additionally, the platform employs electrochemiluminescence (ECL) for detection, noted for its high sensitivity and low background noise, making it particularly effective. A key application of this technology is in the detection of miR-17, a biomarker associated with multiple cancer types. It exhibits remarkable detection capabilities, characterized by low detection limits (14.38 aM) and high specificity. Furthermore, the platform's ability to distinguish between similar miRNA sequences and accurately quantify miR-17 in cell lysates underscores its significant potential in clinical and biomedical fields. This combination of precise targeting, signal amplification, and sensitive detection positions the platform as a powerful tool for miRNA analysis in medical diagnostics and research.

Chromosome-level genome assembly of Hippophae tibetana provides insights into high-altitude adaptation and flavonoid biosynthesis.

BACKGROUND: As an endemic shrub of the Qinghai-Tibetan Plateau (QTP), the distribution of Hippophae tibetana Schlecht. ranges between 2800 and 5200 m above sea level. As the most basal branch of the Hippophae genus, H. tibetana has an extensive evolutionary history. The H. tibetana is a valuable tree for studying the ecological evolution of species under extreme conditions. RESULTS: Here, we generated a high-quality chromosome-level genome of H. tibetana. The total size of the assembly genome is 917 Mb. The phylogenomic analysis of 1064 single-copy genes showed a divergence between 3.4 and 12.8 Mya for H. tibetana. Multiple gene families associated with DNA repair and disease resistance were significantly expanded in H. tibetana. We also identified many genes related to DNA repair with signs of positive selection. These results showed expansion and positive selection likely play important roles in H. tibetana's adaptation to comprehensive extreme environments in the QTP. A comprehensive genomic and transcriptomic analysis identified 49 genes involved in the flavonoid biosynthesis pathway in H. tibetana. We generated transgenic sea buckthorn hairy root producing high levels of flavonoid. CONCLUSIONS: Taken together, this H. tibetana high-quality genome provides insights into the plant adaptation mechanisms of plant under extreme environments and lay foundation for the functional genomic research and molecular breeding of H. tibetana.

Electrochemical biosensing for E.coli detection based on triple helix DNA inhibition of CRISPR/Cas12a cleavage activity.

BACKGROUND: Escherichia coli (E.coli) is both a commensal and a foodborne pathogenic bacterium in the human gastrointestinal tract, posing significant potential risks to human health and food safety. However, one of the major challenges in E.coli detection lies in the preparation and storage of antibodies. In traditional detection methods, antibodies are indispensable, but their instability often leads to experimental complexity and increased false positives. This underscores the need for new technologies and novel sensors. Therefore, the development of a simple and sensitive method for analyzing E.coli would make significant contributions to human health and food safety. RESULTS: We constructed an electrochemical biosensor based on triple-helical DNA and entropy-driven amplification reaction (EDC) to inhibit the cleavage activity of Cas12a, enabling high-specificity detection of E.coli. Replacing antibodies with nucleic acid aptamers (Apt) as recognition elements, we utilized the triple-helical DNA generated by the binding of DNA2 and DNA5/DNA6 double-helical DNA through the entropy-driven amplification reaction to inhibit the collateral cleavage activity of clustered regularly interspaced short palindromic repeats gene editing system (CRISPR) and its associated proteins (Cas). By converting E.coli into electrical signals and recording signal changes in the form of square wave voltammetry (SWV), rapid detection of E.coli was achieved. Optimization of experimental conditions and data detection under the optimal conditions provided high sensitivity, low detection limits, and high specificity. SIGNIFICANCE: With a minimal detection limit of 5.02 CFU/mL and a linear range of 1 × 102 - 1 × 107 CFU/mL, the suggested approach was successfully verified to analyze E.coli at various concentrations. Additionally, after examining E.coli samples from pure water and pure milk, the recoveries ranged between 95.76 and 101.20%, demonstrating the method's applicability. Additionally, it provides a feasible research direction for the detection of pathogenic bacteria causing other diseases using the CRISPR/Cas gene editing system.

Pan-cancer analysis of the oncogenic role of the core osteosarcoma gene VCAN in human tumors.

OBJECTIVE: Versican (VCAN), a member of the multifunctional glycoprotein family, is involved in various aspects of cancer progression. However, the role of VCAN in diverse cancers remains poorly defined. This research aimed to investigate the correlation between VCAN expression and the oncogenic role, as well as visualize its prognostic landscape in pan-cancer. METHODS: Raw data in regard to VCAN expression in cancer patients were acquired from GEO GeneChip public database in NCBI. Besides, we selected microarray data GSE16088 for analysis. We retrieved the genes associated with osteosarcoma (OS) from the OMIM database and identified their intersection with the core module. VCAN was suggested to be a potential marker gene for OS. Subsequently, we conducted Gene Set Enrichment Analysis (GSEA) to explore gene functional enrichment. Moreover, we performed pan-cancer analysis on VCAN to gain a comprehensive understanding of its implications across various cancer types. RESULTS: The VCAN expression in the tumor tissue was higher than that in normal tissue. Elevated expression of VCAN was associated with high the tumor stage and poor long-term survival. There was a significant positive correlation between VCAN and cancer fibroblasts in all pan cancers. Moreover, FBN1 was the intersection gene of VCAN-related genes and linker genes. ANTXR1, COL5A2, CSGALNACT2, and SPARC were the target genes of VCAN genes. GSEA analysis showed that VCAN was mainly enriched in the extracellular matrix (ECM) signaling pathway. CONCLUSION: VCAN can be used as a marker molecule for the early diagnosis of OS and holds significance as a molecule in cases of OS with distant metastasis. The ECM signaling pathway may be a core pathway in OS development and distant metastasis. These findings shed new light on therapeutics of cancers.

Inverting the DNA tetrahedron: A novel strategy for sensitive and stable detection of aging-related enzyme MMP2.

In the current study, a novel electrochemiluminescence biosensor based on the entropy-driven DNA tetrahedron for the detection of matrix metalloproteinase 2 (MMP2), an enzyme that regulates extracellular matrix remodeling and affects aging was reported. The biosensor utilizes an inverted DNA tetrahedron structure, which exposes three vertices to the solution, as molecular recognition units for capturing specific biomolecules. The biosensor also employs a ratiometric method and an entropy-driven reaction, which enhance the response rate and sensitivity of the detection. The biosensor can detect MMP2 with a detection limit of 55.2 fM, which is lower than that of conventional sensors. The biosensor also exhibits excellent stability and reproducibility, and can accurately measure MMP2 levels in complex samples, such as human serum. The paper demonstrates the feasibility and effectiveness of using the "inverted" DNA tetrahedron structure and the entropy-driven process to construct interfacial biosensors. The paper also discusses the potential applications of the biosensor in clinical diagnosis and anti-aging research, where MMP2 plays a crucial role in tissue damage and repair. The paper provides a valuable contribution to the field of biosensor development, and opens up new possibilities for using DNA nanotechnology for sensitive and reliable detection of various biomolecules.

Novel citrinin derivatives from fungus Penicillium sp. TW131-64 and their antimicrobial activities.

Six new citrinin derivatives (1, 2, 4, 10, 11, and 16), along with fourteen known analogues, were acquired from Penicillium sp. TW131-64, a marine-derived fungus strain. The chemical structures of new compounds were identified through adopting various spectroscopic methods in combination with X-ray diffraction technology and comparison of the experimental electronic circular dichroism (ECD) with calculated ones. Among them, compounds 1-4 were nitrogen-containing citrinin derivatives existing in enantiomers which were resolved by chiral chromatography. A putative biosynthetic pathway for compounds 1-4 was proposed. Additionally, the antimicrobial activities of these compounds were detected by the broth microdilution assays. Citrinin derivatives 1, 2, 4 and their corresponding enantiomers (1a, 2a, 4a, 1b, 2b, and 4b) exhibited potent antimicrobial activities towards Helicobacter pylori standard strains and multidrug-resistant strains (MIC values ranging from 0.25 to 8 µg/mL), which were comparable or even better than metronidazole. Moreover, compounds 1a and 1b also showed remarkable broad antimicrobial effects towards Staphylococcus aureus, Enterococcus faecalis, methicillin-resistant Staphylococcus aureus (MRSA), Bacillus subtilis, vancomycin-resistant Enterococcus faecium (VRE), and Candida albicans. In summary, our studies demonstrated that citrinin enantiomers 1a-4a and 1b-4b, especially 1a and 1b, can be lead compounds in the research and development (R & D) of novel antimicrobial drugs. KEY POINTS: • 3 novel nitrogen-containing citrinin derivatives (1, 2, 4) were isolated. • citrinin derivatives 1-4 in enantiomers were resolved by chiral chromatography. • citrinin derivatives 1a and 1b showed broad and significant antimicrobial effects.

Molecular Networking-Guided Isolation of Cyclopentapeptides from the Hydrothermal Vent Sediment Derived Fungus Aspergillus pseudoviridinutans TW58-5 and Their Anti-inflammatory Effects.

Repetitive isolation of known compounds remains a major challenge in natural-product-based drug discovery. LC-MS/MS-based molecular networking has become a highly efficient strategy for the discovery of new natural products from complex mixtures. Herein, we report a molecular networking-guided isolation procedure, which resulted in the discovery of seven new cyclopentapeptides, namely, pseudoviridinutans A-F (1-7), from the marine-derived fungus Aspergillus pseudoviridinutans TW58-5. Compounds 1-7 feature a rare amino acid moiety, O,ß-dimethyltyrosine, observed for the first time from a marine-derived fungus. The planar structures of 1-7 were elucidated by detailed analyses of IR, UV, HR ESI-Q-TOF MS, and 1D and 2D NMR spectroscopic data. Meanwhile, their absolute configurations were determined through a combination of Marfey's method and X-ray diffraction. Subsequent bioassay revealed the anti-inflammation potential of 1-7, especially 6, which inhibited the production of nitric oxide (NO), a vital inflammatory mediator, in LPS-induced murine macrophage RAW264.7 cells by regulating the expression level of NLRP3 and iNOS.

Histone H3K9 acetylation modulates gene expression of key enzymes in the flavonoid and abscisic acid pathways and enhances drought resistance of sea buckthorn.

The effect of histone H3K9 acetylation modification on gene expression and drought resistance in drought-resistant tree species is not clear. Using the chromatin immunoprecipitation (ChIP) method, this study obtained nine H3K9 acetylated protein-interacting DNAs from sea buckthorn seedlings, and the ChIP sequencing result predicted about 56,591, 2217 and 5119 enriched region peaks in the control, drought and rehydration comparative groups, respectively. Gene functional analysis of differential peaks from three comparison groups revealed that 105 pathways were involved in the drought resistance process, and 474 genes were enriched in the plant hormone signaling transduction pathways. Combined ChIP-seq and transcriptome analysis revealed that six genes related to abscisic acid synthesis and signaling pathways, 17 genes involved in flavonoid biosynthesis, and 15 genes involved in carotenoid biosynthesis were positively regulated by H3K9 acetylation modification under drought stress. Under drought stress conditions, the content of abscisic acid and the expression of related genes were significantly up-regulated, while the content of flavonoids and the expression of key enzymes involved in their synthesis were largely down-regulated. Meanwhile, after exposure to histone deacetylase inhibitors (trichostatin A), the change of abscisic acid and flavonoids content and their related gene expression were slowed down under drought stress. This study will provide an important theoretical basis for understanding the regulatory mechanisms of histone acetylation modifications in sea buckthorn drought resistance.

Entropy-driven assisted T7 RNA polymerase amplification-activated CRISPR/Cas13a activity for SARS-CoV-2 detection in human pharyngeal swabs and environment by an electrochemiluminescence biosensor.

In this study, we introduce an electrochemiluminescence (ECL) sensing platform based on the "Entropy-driven triggered T7 amplification-CRISPR/Cas13a system" (EDT-Cas). This platform combines a programmable entropy-driven cycling strategy, T7 RNA polymerase, and the CRISPR/Cas13a system to amplify the determination of the SARS-CoV-2 RdRp gene. The Ti3C2Tx-compliant ECL signaling molecule offers unique benefits when used with the ECL sensing platform to increase the assay sensitivity and the electrode surface modifiability. To obtain the T7 promoter, the SARS-CoV-2 RdRp gene may first initiate an entropy-driven cyclic amplification response. Then, after recognizing the T7 promoter sequence on the newly created dsDNA, T7 RNA polymerase starts transcription, resulting in the production of many single-stranded RNAs (ssRNAs), which in turn trigger the action of CRISPR/Cas13a. Finally, Cas13a/crRNA identifies the transcribed ssRNA. When it cleaves the ssRNA, many DNA reporter probes carrying -U-U- are cleaved on the electrode surface, increasing the ECL signal and allowing for the rapid and highly sensitive detection of SARS-CoV-2. With a detection limit of 7.39 aM, our method enables us to locate the SARS-CoV-2 RdRp gene in clinical samples. The detection method also demonstrates excellent repeatability and stability. The SARS-CoV-2 RdRp gene was discovered using the "Entropy-driven triggered T7 amplification-CRISPR/Cas13a system" (EDT-Cas). The developed ECL test had excellent recoveries in pharyngeal swabs and environmental samples. It is anticipated to offer an early clinical diagnosis of SARS-CoV-2 and further control the spread of the pandemic.

DNAzyme-driven bipedal DNA walker for label-free and signal-on electrochemical detection of amyloid-ß oligomer.

As a common technique for detecting AßO, the enzyme-linked immunosorbent assay (ELISA) method is time-consuming, high in cost, and poor in stability. Therefore, it is necessary to develop a highly sensitive, method-simple and low-cost method for the selective detection of AßO. Here, we created a novel signal-on and label-free electrochemical aptamer sensor for the detection of AßO based on a DNAzyme-driven DNA bipedal walking strategy. Compared with common DNA walkers, bipedal DNA walkers exhibit larger walking areas and faster walking kinetics, and provide higher amplification efficiency. The DNAwalker is powered by an Mg2+-dependent DNAzyme, and the binding-induced DNAwalker continuously clamps the MB, unlocking several active G-quadruplex-forming sequences. These G-quadruplexes can be further combined by hemin to generate a G-quadruplex/heme complex, resulting in an amperometric signal, resulting in a broad proportional band from 0.1 pM to 1 nM and an excellent detection range of 46 fM. A bipedal DNA walker aptamer sensor can detect human serum AßO with remarkable specificity, high reproducibility and practical application value.

Cytotoxic shornephines and asterresins from the hydrothermal vent associated fungus Aspergillus terreus CXX-158-20.

A previously unreported alkaloid, bearing an undescribed 5/7/8 tricyclic heterocyclic skeleton, shornephine D, an undescribed diketomorpholine (DKM) shornephine B, two undescribed diketomorpholine derivatives shornephine C and seco-shornephine B methyl ester, an undescribed indole-isoquinoline alkaloid asterresin C, three undescribed indole alkaloids asterresins A-B and D, together with five known compounds, were isolated from the culture of hydrothermal vent associated fungus Aspergillus terreus CXX-158-20. Their structures were unambiguously determined by nuclear magnetic resonance (NMR), mass spectrometry, Mosher's method, 13C NMR calculation in combination with DP4+, and ECD calculations. Shornephine D and asterresin C represent two undescribed heterocyclic skeletons. Asterresin D and giluterrin exhibited cytotoxicity activities with IC50 values of 3.96 µM and 7.97 µM against A549 cell line. Asterresin D exhibited cytotoxicity activities with IC50 values of 12.36 µM and 12.48 µM against Namalwa and U266 cell lines. Asterresin A and giluterrin exhibited synergistic effect with adriamycin against MCF-7 cell line.

Citrinin Monomer, Trimer, and Tetracyclic Alkaloid Derivatives from the Hydrothermal Vent-Associated Fungus Penicillium citrinum TW132-59.

Five new unusual citrinin-derived alkaloids with a tetracyclic core, citrinidines A-E (1-5), two new amide alkaloids, methyl (2S,8E)-1'-(2-methyl-3-oxodec-8-enamido) butanoate (6) and (2S,8E)-2-methyl-3-oxodec-8-enamide (7), a new unusual citrinin trimer, tricitrinol C (8), a new citrinin acetal-ketal derivative, citrininol (9), together with four known citrinin monomers (10-13), and three known citrinin dimers (14-16), were isolated from the fermentation of hydrothermal vent-associated fungus Penicillium citrinum TW132-59. Their structures were unambiguously determined by nuclear magnetic resonance (NMR), mass spectrometry, Mosher's method, 13C NMR calculation in combination with DP4+, and ECD calculations. A plausible biosynthetic pathway of all new compounds (1-9) was proposed. Citrinin trimer (8) exhibited potent cytotoxicity activity with an IC50 value of 1.34 ± 0.11 µM, and compounds 1 and 15 showed moderate cytotoxicity with IC50 values of 17.50 ± 1.43 and 9.45 ± 0.55 µM, respectively, against A549 cell line.

Exploring gabosine and chlorogentisyl alcohol derivatives from a marine-derived fungus as EcGUS inhibitors with informatic assisted approaches.

ß-Glucuronidase catalyzes the cleavage of glucuronosyl-O-bonds, whose inhibitors reduce the level of toxic substances present in the intestine caused by anti-cancer and anti-inflammatory therapies. Herein, we presented a new tool, Bioactive Fractions Filtering Platform (BFFP), which is able to reliably discern active candidate node from crude extracts. The source code for the BFFP is available on GitHub (https://github.com/BioGavin/msbff). With the assistant of BFFP, 25 gabosine and chlorogentisyl alcohol derivatives including 19 new compounds were isolated from a marine-derived fungus Epicoccum sp. GST-5. Compounds 7, 9-15 possessed an unusual hybrid skeleton of gabosine and chlorogentisyl alcohol units. Compounds 9-12, 16 and 17 possessed a novel three-membered spiral ring skeleton with one/two gabosine and one/two chlorogentisyl alcohol units. Compound 25 represented new gabosine-derived skeleton possessing an unusual 6/6/6/5/6 condensed ring system. All isolates were evaluated for in vitro E. coli ß-glucuronidase (EcGUS) inhibitory activity. 14 Compounds demonstrated superior inhibitory activity (IC50 = 0.24-4.61 µM) to that of standard d-saccharic acid 1,4-lactone (DSL, IC50 = 56.74 ± 4.01 µM). Compounds with chlorogentisyl alcohol moiety, such as 17 (IC50 = 0.24 ± 0.02 µM) and 1 (IC50 = 0.74 ± 0.03 µM), exhibited the most potent inhibitory activity. Furthermore, literature based QSAR profiling by applying PCA and OPLS analysis was carried out to analyze the features of compounds against EcGUS, revealing that the introduction of substituents able to form polar interactions with binding sites of receptor would lead to more active structures.

Apelin Alleviates Meniscus Endothelial Cell Apoptosis in Osteoarthritis.

Osteoarthritis (OA) is a degenerative disease characterized by articular cartilage and/or chondrocyte destruction, and although it has long been considered as a primary disease, the importance of meniscus endothelial cell modulation in the subchondral microenvironment has recently drawn attention. Previous studies have shown that apelin could potentially inhibit cellular apoptosis; however, it remains unclear whether apelin could play a protective role in protecting the endothelium in the OA meniscus. In this study, with the advantages of single-cell RNA sequencing (scRNA-seq) data, in combination with flow cytometry, we identified two endothelial subclusters in the meniscus, featured by high expression of Homeobox A13 (HOXA13) and Ras Protein-Specific Guanine Nucleotide Releasing Factor 2 (RASGRF2), respectively. Compared with control patients, both subclusters decreased in absolute cell numbers and exhibited downregulated APJ endogenous ligand (APLN, coding for apelin) and upregulated apelin receptor (APLNR, coding apelin receptor). Furthermore, we confirmed that in OA, decreased endothelial cell numbers, including both subclusters, were related to intrinsic apoptosis factors: one more relevant to caspase 3 (CASP3) and the other to BH3-Interacting Domain Death agonist (BID). In vitro culturing of meniscal endothelial cells purified from patients proved that apelin could significantly inhibit apoptosis by downregulating these two factors in endothelial cell subclusters, suggesting that apelin could potentially serve as a therapeutic target for patients with OA.

Two New Prenylated Glycine Derivatives from the Marine-Derived Fungus Fusarium sp. TW56-10.

Two new prenylated glycine derivatives N-({4-[(3-methylbut-2-en-1-yl)oxy]phenyl}acetyl)glycine (1) and methyl N-({4-[(3-methylbut-2-en-1-yl)oxy]phenyl}acetyl)glycinate (2), along with nine known compounds (3-11) were purified from the marine-derived fungus Fusarium sp. TW56-10. Their chemical structures were determined by spectroscopic evidence, including extensive nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) data, infrared radiation (IR) and Ultraviolet spectra (UV). Compound 4 (8-O-methylfusarubin) exhibited cytotoxic activity with IC50 value of 11.45 µM for A549 cells.

New diketopiperazine alkaloid and polyketides from marine-derived fungus Penicillium sp. TW58-16 with antibacterial activity against Helicobacter pylori.

Marine-derived fungi can usually produce structurally novel and biologically potent metabolites. In this study, a new diketopiperazine alkaloid (1) and two new polyketides (10 and 11), along with 8 known diketopiperazine alkaloids (2-9) were isolated from marine-derived fungus Penicillium sp. TW58-16. Their structures were fully elucidated by analyzing UV, IR, HR-ESI-MS, 1D, and 2D NMR spectroscopic data. The absolute configurations of the new compounds 1, 10 and 11 were ascertained by X-ray diffraction (Cu Kα radiation) and comparing their CD data with those reported. In addition, the antibacterial activities of these compounds against Helicobacter pylori in vitro were assessed. Results showed that compounds 3, 6, 8 and 9 displayed moderate antibacterial activity against standard strains and drug-resistant clinical isolates of H. pylori in vitro. This result demonstrates that diketopiperazine alkaloids could be lead compounds to be explored for the treatment of H. pylori infection.

Long non-coding RNA TUG1 promotes the osteogenic differentiation of bone marrow mesenchymal stem cells by regulating the AMPK/mTOR/autophagy pathway.

Promoting the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts is an effective strategy against osteoporosis. Long non-coding RNAs are closely implicated in BMSC osteogenic differentiation. The present study explored the expression pattern and biological role of taurine upregulated gene 1 (TUG1) in osteogenic differentiation. The expressions of TUG1 and osteogenic markers following the osteogenic induction of BMSCs were detected. The functional relevance of TUG1 was evaluated by performing gain- and loss-of-function tests. Inhibitors of AMP-activated protein kinase (AMPK) autophagy were applied to ascertain the effects of TUG1 on the osteogenic differentiation of BMSCs. TUG1 expression increased during the osteogenic differentiation of BMSCs. The overexpression of TUG1 was promoted, whereas the knockdown of TUG1 was suppressed, by BMSC osteogenic differentiation. Mechanically, TUG1 promoted the osteogenesis of BMSCs via the AMPK-mammalian target of rapamycin (mTOR)-autophagy signaling pathway. Blocking AMPK and autophagy could abrogate the osteogenic role of TUG1 in BMSCs. These results demonstrated that TUG1 promoted the osteogenic differentiation of BMSCs by regulating the AMPK/mTOR/autophagy axis, suggesting that targeting TUG1 may be a potential therapy for osteoporosis.

Bioinformatics Analysis of ZBTB16 as a Prognostic Marker for Ewing's Sarcoma.

OBJECTIVE: The purpose of this study is to identify novel biomarkers for the prognosis of Ewing's sarcoma based on bioinformatics analysis. METHODS: The GSE63157 and GSE17679 datasets contain patient and healthy control microarray data that were downloaded from the Gene Expression Omnibus (GEO) database and analyzed through R language software to obtain differentially expressed genes (DEGs). Firstly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment, protein-protein interaction (PPI) networks, and Cytoscape Molecular Complex Detection (MCODE) plug-in were then used to compute the highest scores of the module. After survival analysis, the hub genes were lastly obtained from the two module genes. RESULTS: A total of 1181 DEGs were identified from the two GSEs. Through MCODE and survival analysis, we obtain 53 DEGs from the module and 29 overall survival- (OS-) related genes. ZBTB16 was the only downregulated gene after Venn diagrams. Survival analysis indicates that there was a significant correlation between the high expression of ZBTB16 and the OS of Ewing's sarcoma (ES), and the low expression group had an unfavorable OS when compared to the high expression group. CONCLUSIONS: High expression of ZBTB16 may serve as a predictor biomarker of poor prognosis in ES patients.

Comparative Metabolomics Reveals Fungal Conversion of Co-Existing Bacterial Metabolites within a Synthetic Aspergillus-Streptomyces Community.

In nature, secondary metabolites have been proven to be the essential communication media between co-occurring microorganisms and to influence their relationship with each other. In this study, we conducted a metabolomics survey of the secondary metabolites of an artificial co-culture related to a hydrothermal vent fungal-bacterial community comprising Aspergillus sclerotiorum and Streptomyces and their reciprocal relationship. The fungal strain was found to increase the secretion of notoamides and the compound cyclo(Pro-Trp) produced by the actinomycetes strain was discovered to be the responsible molecule. This led to the hypothesis that the fungi transformed cyclo(Pro-Trp) synthesized by the actinomycetes as the biosynthetic precursors of notoamides in the chemical communication. Further analysis showed Streptomyces sp. WU20 was efficient in transforming amino acids into cyclo(Pro-Trp) and adding tryptophan as well as proline into the chemical communication enhanced the induction of the notoamide accumulation. Thus, we propose that the microbial transformation during the synthetic metabolically-mediated chemical communication might be a promising means of speeding up the discovery of novel bioactive molecules. The objective of this research was to clarify the mechanism of microbial transformation for the chemical communication. Besides, this research also highlights the utility of mass spectrometry-based metabolomics as an effective tool in the direct biochemical analysis of community metabolites.