RESUMO
Various semiconductor devices have been developed based on 2D heterojunction materials owing to their distinctive optoelectronic properties. However, to achieve efficient charge transfer at their interface remains a major challenge. Herein, an alloy heterojunction concept is proposed. The sulfur vacancies in ZnIn2S4 are filled with selenium atoms of PdSe2. This chemically bonded heterojunction can significantly enhance the separation of photocarriers, providing notable advantages in the field of photoelectric conversion. As a demonstration, a two-terminal photodetector based on the PdSe2/ZnIn2S4 heterojunction materials is fabricated. The photodetector exhibits stable operation in ambient conditions, showcasing superior performance in terms of large photocurrent, high responsivity (48.8 mA W-1) and detectivity (1.98 × 1011 Jones). To further validate the excellent optoelectronic performance of the heterojunction, a tri-terminal phototransistor is also fabricated. Benefiting from gate voltage modulation, the photocurrent is amplified to milliampere level, and the responsivity is increased to 229.14 mA W-1. These findings collectively demonstrate the significant potential of the chemically bonded PdSe2/ZnIn2S4 alloy heterojunction for future optoelectronic applications.
RESUMO
Numerous studies have indicated that N6-methyladenosine (m6A) and lncRNAs play pivotal roles in human cancer. However, the underlying functions and mechanisms of m6A-lncRNA in the physiological processes of breast cancer remain unclear. Here, we found that DSCAM-AS1 is an m6A-modified lncRNA that was overexpressed in breast cancer tissues and cells, indicating poor clinical prognosis. Gain/loss functional assays suggested that DSCAM-AS1 inhibited erastin-induced ferroptosis in breast cancer cells. Mechanistically, there were remarkable m6A modification sites on both the 3'-UTR of DSCAM-AS1 and the endogenous antioxidant factor SLC7A11. M6A methyltransferase methyltransferase-like 3 (METTL3) methylated both SLC7A11 and DSCAM-AS1. Moreover, DSCAM-AS1 recognized m6A sites on the SLC7A11 mRNA, thereby enhancing its stability. Taken together, these findings indicated a potential therapeutic strategy for breast cancer ferroptosis in an m6A-dependent manner.
Assuntos
Neoplasias da Mama , Ferroptose , Metiltransferases , RNA Longo não Codificante , Animais , Feminino , Humanos , Camundongos , Adenosina/análogos & derivados , Adenosina/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Progressão da Doença , Ferroptose/genética , Metiltransferases/metabolismo , Metiltransferases/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
Four yeast strains belonging to the basidiomycetous yeast genus Mrakia were isolated from diverse habitats in the Ny-Ålesund region (Svalbard, High Arctic): two from vascular plants, one from seawater and one from freshwater. Phylogenetic analysis, based on the ITS region and the D1/D2 domain of the 28S rRNA gene, identified these four strains as representing two novel species within the genus Mrakia. The names Mrakia polaris sp. nov. (MycoBank number: MB 852063) and Mrakia amundsenii sp. nov. (MycoBank number: MB 852064) are proposed. These two new species show distinct psychrophilic adaptations, as they exhibit optimal growth at temperatures between 10 and 15°C, while being unable to grow at 25°C. The holotype of M. polaris sp. nov. is CPCC 300345T, and the holotype of M. amundsenii sp. nov. is CPCC 300572T.
Assuntos
DNA Fúngico , Filogenia , Água do Mar , Análise de Sequência de DNA , Regiões Árticas , DNA Fúngico/genética , Água do Mar/microbiologia , Técnicas de Tipagem Micológica , Svalbard , RNA Ribossômico 28S/genética , Basidiomycota/genética , Basidiomycota/classificação , Basidiomycota/isolamento & purificação , Água Doce/microbiologia , Ecossistema , Temperatura Baixa , Saccharomycetales/classificação , Saccharomycetales/genética , Saccharomycetales/isolamento & purificaçãoRESUMO
A Gram-negative, ellipsoidal to short-rod-shaped, motile bacterium was isolated from Beijing's urban air. The isolate exhibited the closest kinship with Noviherbaspirillum aerium 122213-3T, exhibiting 98.4â% 16S rRNA gene sequence similarity. Phylogenetic analyses based on 16S rRNA gene sequences and genomes showed that it clustered closely with N. aerium 122213-3T, thus forming a distinct phylogenetic lineage within the genus Noviherbaspirillum. The average nucleotide identity and digital DNA-DNA hybridization values between strain I16B-00201T and N. aerium 122213-3T were 84.6 and 29.4â%, respectively. The respiratory ubiquinone was ubiquinone 8. The major fatty acids (>10â%) were summed feature 3 (C16:1ω6c/C16:1ω7c, 43.3â%), summed feature 8 (C18:1ω7c/C18:1ω6c, 15.9â%) and C12:0 (11.0â%). The polyamine profile showed putrescine as the predominant compound. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, unknown lipids and unknown phosphatidylaminolipids. The phenotypic, phylogenetic and chemotaxonomic results consistently supported that strain I16B-00201T represented a novel species of the genus Noviherbaspirillum, for which the name Noviherbaspirillum album sp. nov. is proposed, with I16B-00201T (=CPCC 100848T=KCTC 52095T) designated as the type strain. Its DNA G+C content is 59.4 mol%. Pan-genome analysis indicated that some Noviherbaspirillum species possess diverse nitrogen and aromatic compound metabolism pathways, suggesting their potential value in pollutant treatment.
Assuntos
Microbiologia do Ar , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Hibridização de Ácido Nucleico , Fosfolipídeos , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Ubiquinona , RNA Ribossômico 16S/genética , Pequim , DNA Bacteriano/genética , Ácidos Graxos/análise , Fosfolipídeos/análiseRESUMO
Lichens are dual organisms, with one major mycobiont and one major photobiont in each lichen symbiosis, which can survive extreme environmental conditions in the Arctic. However, the diversity and distribution of lichen photobionts in the Arctic remain poorly understood compared to their mycobiont partners. This study explored the diversity of lichen mycobionts and photobionts in 197 lichen samples collected from the Ny-Ålesund region (Svalbard, High Arctic). The nuclear ribosomal internal transcribed spacer (ITS) regions were sequenced and phylogenetic analyses were performed. The relationships between mycobionts and photobionts, as well as the association patterns, were also investigated. A total of 48 species of lichen mycobionts (16 families, nine orders) and 31 species/lineages of photobionts were identified. These 31 photobiont species belonged to one class (Trebouxiophyceae) and five genera, including 22 species of Trebouxia, five species of Asterochloris, two species of Chloroidium, one species of Symbiochloris, and one species of Coccomyxa. The results indicated that most analyzed lichen mycobionts could associate with multiple photobiont species, and the photobionts also exhibited a similar pattern. The results provided an important reference dataset for characterizing the diversity of lichen mycobionts and photobionts in the High Arctic region.
Assuntos
Líquens , Simbiose , Líquens/classificação , Líquens/microbiologia , Filogenia , Svalbard , Regiões Árticas , Biodiversidade , MicobiomaRESUMO
Research on the microbiome and resistome in polar environments, such as the Arctic, is crucial for understanding the emergence and spread of antibiotic resistance genes (ARGs) in the environment. In this study, soil and reindeer faeces samples collected from Ny-Ålesund (Svalbard, High Arctic) were examined to analyze the microbiome, ARGs, and biocide/metal resistance genes (BMRGs). The dominant phyla in both soil and faeces were Pseudomonadota, Actinomycetota, and Bacteroidota. A total of 2618 predicted Open Reading Frames (ORFs) containing antibiotic resistance genes (ARGs) were detected. These ARGs belong to 162 different genes across 17 antibiotic classes, with rifamycin and multidrug resistance genes being the most prevalent. We focused on investigating antibiotic resistance mechanisms in the Ny-Ålesund environment by analyzing the resistance genes and their biological pathways. Procrustes analysis demonstrated a significant correlation between bacterial communities and ARG/BMRG profiles in soil and faeces samples. Correlation analysis revealed that Pseudomonadota contributed most to multidrug and triclosan resistance, while Actinomycetota were predominant contributors to rifamycin and aminoglycoside resistance. The geochemical factors, SiO42- and NH4+, were found to significantly influence the microbial composition and ARG distribution in the soil samples. Analysis of ARGs, BMRGs, virulence factors (VFs), and pathogens identified potential health risks associated with certain bacteria, such as Cryobacterium and Pseudomonas, due to the presence of different genetic elements. This study provided valuable insights into the molecular mechanisms and geochemical factors contributing to antibiotic resistance and enhanced our understanding of the evolution of antibiotic resistance genes in the environment.
RESUMO
This study aimed to investigate the longitudinal association between theory of mind (ToM) and loneliness as well as the potential moderating effects of parenting style on this association. A total of 689 Chinese third-grade students (341 girls and 348 boys; Mage = 9.23 years, SD = 0.66) were recruited from eight primary schools and were followed from Grade 3 to Grade 5. These students reported their primary caregivers' parenting style in third grade and completed the same ToM task and loneliness questionnaire at each time point from Grade 3 to Grade 5. The study's results indicated a bidirectional relationship between ToM and loneliness, implying that children with less developed ToM abilities tend to feel lonelier and, conversely, that higher levels of loneliness are associated with lower ToM skills. Moreover, the study demonstrated that parenting style influenced the association between ToM and loneliness. Specifically, the impact of ToM at Grade 3 on reducing loneliness at Grade 4 was greater among children who experienced high levels of rejection from their caregivers compared with those with low levels of rejection. In addition, this study found that loneliness at Grade 3 had a greater influence on ToM at Grade 5 for children experiencing low levels of emotional warmth from their caregivers than for those who experienced high levels of emotional warmth. These findings highlight the significance of ToM as both a precursor and consequence of children's loneliness and emphasize the variation in these longitudinal relationships based on the parenting styles of primary caregivers.
Assuntos
Solidão , Teoria da Mente , Masculino , Criança , Feminino , Humanos , Solidão/psicologia , Estudantes , Poder Familiar/psicologia , Instituições AcadêmicasRESUMO
Three chromomycin derivatives, chromomycins A3 (1, CA3), A5 (2, CA5), and monodeacetylchromomycin A3 (3, MDA-CA3), were identified from the soil-derived Streptomyces sp. CGMCC 26516. A reinvestigation of the structure of CA5 is reported, of which the absolute configuration was unambiguously determined for the first time to be identical with that of CA3 based on nuclear magnetic resonance (NMR) data analysis as well as NMR and electronic circular dichroism calculations. Compounds 1-3 showed potent cytotoxicity against the non-small-cell lung cancer (NSCLC) cells (A549, H460, H157-c-FLIP, and H157-LacZ) and down-regulated the protein expression of c-FLIP in A549 cells. The IC50 values of chromomycins in H157-c-FLIP were higher than that in H157-LacZ. Furthermore, si-c-FLIP promoted anti-proliferation effect of chromomycins in NSCLC cells. In nude mice xenograft model, 1 and 2 both showed more potent inhibition on the growth of H157-lacZ xenografts than that of H157-c-FLIP xenografts. These results verify that c-FLIP mediates the anticancer effects of chromomycins in NSCLC.
RESUMO
Sulfur-driven autotrophic denitrification (S0dAD) was employed to remove residual nitrogen from the biological effluent of landfill leachate after partial nitrification and denitrification pretreatment. The performance of S0dAD were assessed with various NOx--N (NO2--N and NO3--N) loadings over a 185-day operational period. The results demonstrated that a notable NOx--N removal efficiency of 97.8 ± 2.0% was achieved under nitrogen removal rates of 0.12 ± 0.02 kg N/(m3· d), leading to total nitrogen concentrations of 8.6 ± 3.8 mg/L in the effluent. Batch experiments revealed competitive utilization of nitrogenous electron acceptors, with NO2--N demonstrating 2-4 times higher denitrification rates than NO3--N under coexistence conditions. Genus-level microbial community identified that Thiobacillus and Sulfurovum was highly enriched with as key denitrifying bacteria in the S0dAD system. These findings provide insights for advanced nitrogen removal coupling S0dAD with partial nitrification and denitrification process for landfill leachate treatment.
Assuntos
Desnitrificação , Nitrificação , Nitrogênio , Enxofre , Poluentes Químicos da Água , Nitrogênio/metabolismo , Enxofre/metabolismo , Poluentes Químicos da Água/metabolismo , Processos AutotróficosRESUMO
Mn2+ doped lead-free double perovskites are emerging afterglow materials that can avoid the usage of rare earth ions. However, the regulation of the afterglow time is still a challenge. In this work, the Mn doped Cs2Na0.2Ag0.8InCl6 crystals with afterglow emission at about 600â nm are synthesized by a solvothermal method. Then, the Mn2+ doped double perovskite crystals are crushed into different sizes. As the size decreases from 1.7 mm to 0.075 mm, the afterglow time decreases from 2070 s to 196 s. Steady-state photoluminescence (PL) spectra, time resolved PL, thermoluminescence (TL) reveal the afterglow time monotonously decreases due to the enhanced nonradiative surface trapping. The modulation on afterglow time will greatly promote their applications in various fields, such as bioimaging, sensing, encryption, and anti-counterfeiting. As a proof of concept, dynamic display of information is realized based on different afterglow times.
RESUMO
Background: Non-small cell lung cancer (NSCLC) is the most prevalent malignant tumor of the lung cancer, for which the molecular mechanisms remain unknown. In this study, we identified novel biomarkers associated with the pathogenesis of NSCLC aiming to provide new diagnostic and therapeutic approaches for NSCLC by bioinformatics analysis. Methods: From the Gene Expression Omnibus database, GSE118370 and GSE10072 microarray datasets were obtained. Identifying the differentially expressed genes (DEGs) between lung adenocarcinoma and normal samples was done. By using bioinformatics tools, a protein-protein interaction (PPI) network was constructed, modules were analyzed, and enrichment analyses were performed. The expression and prognostic values of 14 hub genes were validated by the GEPIA database, and the correlation between hub genes and survival in lung adenocarcinoma was assessed by UALCAN, cBioPortal, String and Cytoscape, and Timer tools. Results: We found three genes (PIK3R1, SPP1, and PECAM1) that have a clear correlation with OS in the lung adenocarcinoma patient. It has been found that lung adenocarcinoma exhibits high expression of SPP1 and that this has been associated with poor prognosis, while low expression of PECAM1 and PIK3R1 is associated with poor prognosis (P < 0.05). We also found that the expression of SPP1 was associated with miR-146a-5p, while the high expression of miR-146a-5p was related to good prognosis (P < 0.05). On the contrary, the lower miR-21-5p on upstream of PIK3R1 is associated with a higher surviving rate in cancer patients (P < 0.05). Finally, we found that the immune checkpoint genes CD274(PD-L1) and PDCD1LG2(PD-1) were also related to SPP1 in lung adenocarcinoma. Conclusions: The results indicated that SPP1 is a cancer promoter (oncogene), while PECAM1 and PIK3R1 are cancer suppressor genes. These genes take part in the regulation of biological activities in lung adenocarcinoma, which provides a basis for improving detection and immunotherapeutic targets for lung adenocarcinoma.
Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Perfilação da Expressão Gênica/métodos , Biomarcadores Tumorais/genética , Adenocarcinoma de Pulmão/genética , Prognóstico , Biologia Computacional/métodos , Regulação Neoplásica da Expressão GênicaRESUMO
Subplenones A-J (1-10), 10 new xanthone dimers, have been isolated and characterized from the endophytic fungus Subplenodomus sp. CPCC 401465, which resides within the Chinese medicinal plant Gentiana straminea. The isolation process was guided by antibacterial assays and molecular-networking-based analyses. The chemical structures of these compounds were elucidated through the interpretation of nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HRESIMS) data. Furthermore, the relative configuration of the compounds was determined using NMR and single-crystal X-ray diffraction analyses, and the absolute configuration was established using electronic circular dichroism calculations. All of the isolated compounds exhibited significant inhibitory activity against Gram-positive bacteria. Notably, compounds 1, 5, and 7 displayed remarkable inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 700698, with a minimum inhibitory concentration (MIC) of 0.25 µg/mL, and against vancomycin-resistant Enterococcus faecium (VRE) ATCC 700221, with MIC values ranging from 0.5 to 1.0 µg/mL.
Assuntos
Ascomicetos , Staphylococcus aureus Resistente à Meticilina , Plantas Medicinais , Xantonas , Antibacterianos/química , Testes de Sensibilidade Microbiana , Xantonas/farmacologia , Xantonas/química , Estrutura MolecularRESUMO
In the Arctic fjords, the marine mycobiome experiences significant changes under environmental conditions driven by climate change. However, research on the ecological roles and the adaptive mechanisms of marine mycobiome in the Arctic fjord remains insufficiently explored. The present study employed shotgun metagenomics to comprehensively characterize the mycobiome in 24 seawater samples from Kongsfjorden, a High Arctic fjord situated in Svalbard. It revealed the presence of a diverse mycobiome with eight phyla, 34 classes, 71 orders, 152 families, 214 genera, and 293 species. The taxonomic and functional composition of the mycobiome differed significantly among the three layers, i.e., upper layer (depth of 0 m), middle layer (depths of 30-100 m), and lower layer (depths of 150-200 m). Several taxonomic groups (e.g., phylum Ascomycota, class Eurotiomycetes, order Eurotiales, family Aspergillaceae, and genus Aspergillus) and KOs (e.g., K03236/EIF1A, K03306/TC.PIT, K08852/ERN1, and K03119/tauD) were significantly distinct among the three layers. Among the measured environmental parameters, depth, NO2-, and PO43- were identified as the key factors influencing the mycobiome composition. Conclusively, our findings revealed that the mycobiome was diverse in the Arctic seawater and significantly impacted by the variability of environmental conditions in the High Arctic fjord. These results will assist future studies in exploring the ecological and adaptive responses towards the changes within the Arctic ecosystems.
Assuntos
Micobioma , Humanos , Estuários , Ecossistema , Svalbard , Metagenômica , Água do Mar , Regiões ÁrticasRESUMO
Twenty-two metabolites were isolated from Penicillium sp. CPCC 401423 cultured on rice. The structures of all compounds were elucidated mainly by MS and NMR analysis as well as the necessary CD experimental evidence, of which penicillidione A (1), penicillidione B (2), (E)-4-[(4-acetoxy-3-methyl-2-butenyl)oxy]phenylacetic acid (3), (S)-2-hydroxy-2-{4-[(3-methyl-2-butenyl)oxy]phenyl} (4), (S)-4-(2,3-dihydroxy-3-methyl-butoxy)phenylacetic acid (5), (E)-4-[(3-carboxy-2-butenyl)oxy]benzoic acid (6), (Z)-4-[(4-hydroxy-3-methyl-2-butenyl)oxy]benzoic acid (7), open-cycled N-demethylmelearoride A (12), and penostatin M (16) were identified as new compounds. The cytotoxic activity against human pancreatic carcinoma cell line MIA PaCa-2a was detected. Among them, compounds 13-15 and 22 displayed significant cytotoxicity against MIA-PaCa-2 cells with IC50 values of 8.9, 36.5, 31.8, and 22.3 µM, respectively (positive control gemcitabine IC50 65.0 µM).
Assuntos
Antineoplásicos , Penicillium , Humanos , Penicillium/química , Antineoplásicos/química , Fenilacetatos , Linhagem Celular Tumoral , Ácido Benzoico , Estrutura MolecularRESUMO
BACKGROUND: Resistance to anti-tuberculosis (TB) drugs is a major issue in TB control, and demands the discovery of new drugs targeting the virulence factor ESX-1. METHODS: We first established a high-throughput screen (HTS) assay for the discovery of ESX-1 secretion inhibitors. The positive hits were then evaluated for the potency of diminishing the survival of virulent mycobacteria and reducing bacterial virulence. We further investigated the probability of inducing drug resistance and the underlying mechanism using mycobacterial protein fragment complementation. RESULTS: A robust HTS assay was developed to identify small molecules that inhibit ESX-1 secretion without impairing bacterial growth in vitro. A hit named IMB-BZ specifically inhibits the secretion of CFP-10 and reduces virulence in an ESX-1-dependent manner, therefore resulting in significant reduction in intracellular and in vivo survival of mycobacteria. Blocking the CFP-10-EccCb1 interaction directly or indirectly underlies the inhibitory effect of IMB-BZ on the secretion of CFP-10. Importantly, our finding shows that the ESX-1 inhibitors pose low risk of drug resistance development by mycobacteria in vitro as compared with traditional anti-TB drugs, and exhibit high potency against chronic mycobacterial infection. CONCLUSIONS: Targeting ESX-1 may lead to the development of novel therapeutics for tuberculosis. IMB-BZ holds the potential for future development into a new anti-TB drug.
Assuntos
Mycobacterium tuberculosis , Tuberculose , Sistemas de Secreção Tipo VII/metabolismo , Antituberculosos/farmacologia , Proteínas de Bactérias/metabolismo , Humanos , Tuberculose/tratamento farmacológico , VirulênciaRESUMO
A Gram-stain-negative, rod-shaped, microcystin-degrading bacterium, designated as CPCC 100929T, was isolated from a fresh water reservoir in Sichuan Province, PR China. This isolate grew well at 4-37 °C and pH 6.0-8.0, with optimal growth at 28-32 °C and pH 7.0, respectively. The major cellular fatty acids were C18:1 ω7c/C18:1 ω6c, C16:0, C18:1 ω7c 11-methyl and C19:0 cyclo ω8c. The predominant respiratory quinone was Q-10. Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine and phosphatidylcholine were detected in the polar lipids extraction. The 16S rRNA gene sequence of strain CPCC 100929T was closely related to those of members of the genus Shinella, with the highest similarity of 98.6â% to Shinella zoogloeoides DSM 287T and 97.4-98.4 % with other identified Shinella members. In the phylogenetic trees based on 16S rRNA gene sequences and the core-genes analysis, strain CPCC 100929T was included within the clade of the genus Shinella. The values of average nucleotide identity (81.4-86.7 %) and digital DNA-DNA hybridization (25.4-44.6â%) between strain CPCC 100929T and other Shinella species were all below the thresholds for bacterial species delineation, respectively. The genomic DNA G+C content of strain CPCC 100929T was 63.6 %. The genomic sequence analysis indicated that this species contained genes encoding peroxidase, bla carbapenemase and the key enzyme for microcystin bio degradation, as well as rich carbohydrate-active enzyme coding genes, which might endow the micro-organism with properties to adapt to diverse environments. Based on its phenotypic and genetic properties, we propose that strain CPCC 100929T (=T1A350T=KCTC 72957T) is the type strain of a novel species with the name Shinella lacus sp. nov.
Assuntos
Ácidos Graxos , Microcistinas , RNA Ribossômico 16S/genética , Filogenia , Composição de Bases , Microcistinas/genética , Ácidos Graxos/química , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Fosfolipídeos/química , Análise de Sequência de DNA , Ubiquinona/químicaRESUMO
BACKGROUND: Genomic analysis indicated that the genomes of ascomycetes might carry dozens of biosynthetic gene clusters (BGCs), yet many clusters have remained enigmatic. The ascomycete genus Epicoccum, belonging to the family Didymellaceae, is ubiquitous that colonizes different types of substrates and is associated with phyllosphere or decaying vegetation. Species of this genus are prolific producers of bioactive substances. The epicoccamides, as biosynthetically distinct mannosylated tetramate, were first isolated in 2003 from Epicoccum sp. In this study, using a combination of genome mining, chemical identification, genetic deletion, and bioinformatic analysis, we identified the required BGC epi responsible for epicoccamide A biosynthesis in Epicoccum sp. CPCC 400996. RESULTS: The unconventional biosynthetic gene cluster epi was obtained from an endophyte Epicoccum sp. CPCC 400996 through AntiSMASH-based genome mining. The cluster epi includes six putative open reading frames (epiA-epiF) altogether, in which the epiA encodes a tetramate-forming polyketide synthase and nonribosomal peptide synthetases (PKS-NRPS hybrid). Sequence alignments and bioinformatic analysis to other metabolic pathways of fungal tetramates, we proposed that the gene cluster epi could be involved in generating epicoccamides. Genetic knockout of epiA completely abolished the biosynthesis of epicoccamide A (1), thereby establishing the correlation between the BGC epi and biosynthesis of epicoccamide A. Bioinformatic adenylation domain signature analysis of EpiA and other fungal PKS-NRPSs (NRPs) indicated that the EpiA is L-alanine incorporating tetramates megasynthase. Furthermore, based on the molecular structures of epicoccamide A and deduced gene functions of the cluster epi, a hypothetic metabolic pathway for biosynthesizing compound 1 was proposed. The corresponding tetramates releasing during epicoccamide A biosynthesis was catalyzed through Dieckmann-type cyclization, in which the reductive (R) domain residing in terminal module of EpiA accomplished the conversion. These results unveiled the underlying mechanism of epicoccamides biosynthesis and these findings might provide opportunities for derivatization of epicoccamides or generation of new chemical entities. CONCLUSION: Genome mining and genetic inactivation experiments unveiled a previously uncharacterized PKS - NRPS hybrid-based BGC epi responsible for the generation of epicoccamide A (1) in endophyte Epicoccum sp. CPCC 400996. In addition, based on the gene cluster data, a hypothetical biosynthetic pathway of epicoccamide A was proposed.
Assuntos
Ascomicetos , Policetídeo Sintases , Policetídeo Sintases/genética , Monossacarídeos , Cetonas , Ascomicetos/genéticaRESUMO
Zelkovamycins F and G (1 and 2), two new natural cyclic octapeptides possessing the unprecedented nonproteinogenic amino acid residues l-α-methyl-threonine and l-α-methyl-allo-threonine, respectively, along with four new analogues, zelkovamycins H-K (3-6), were identified from the endophytic Kitasatospora sp. CPCC 204717. Their structures were elucidated by detailed analysis of NMR and HRESIMS/MS spectroscopic data. The configurations of amino acid residues were determined by Marfey's analysis combined with NMR calculations. Compounds 1, 2, and 4 showed potent antibacterial activity against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. The structure-activity relationship study revealed that the 2-methyl-3-oxobutyrine and sarcosine residues played important roles in their antibacterial activities. Zelkovamycin (7) and zelkovamycin E (8) exhibited significant antiviral activity against the hepatitis C virus.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Streptomycetaceae , Antibacterianos/química , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , TreoninaRESUMO
Chains of nickel nanoparticles coated with few nitrogen-doped graphitic carbon layers (Ni@NC) are synthesized by hydrogen-assisted pyrolysis of Ni-ZIF. Hydrogen and temperature can play key roles in the formation of oriented Ni@NC nanoparticle chains, and carbon shells can protect Ni nanoparticles from external oxidation and aggregations. Under the optimized potential (0.60 V vs. Ag/AgCl), the Ni@NC7H nanoparticle chains obtained at 700 °C under H2/Ar atmosphere (Ni@NC7H) demonstrate outstanding performances, such as high sensitivity of 1.44 mA mM-1 cm-2 (RSD = 1.0%), low detection limit of 0.34 µM (S/N = 3), broad linear range from 1 µM to 1.81 mM, and excellent application potential in artificial sweat and human serum. Therefore, the findings above indicate that this study will provide a general methodology for the synthesis of chains-like core-shell nanoparticle electrocatalysts for non-enzymatic glucose detection.
Assuntos
Grafite/química , Hidrogênio , Nanopartículas Metálicas/química , Estruturas Metalorgânicas/química , Níquel/química , Nitrogênio/química , Catálise , Eletroquímica , Glucose/química , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de TransmissãoRESUMO
Krüppel-like factor 2 (KLF2) is an atherosclerotic protective transcription factor that maintains endothelial cell homeostasis through its anti-inflammatory, anti-oxidant, and antithrombotic properties. The aim of this study was to discover KLF2 activators from microbial secondary metabolites and explore their potential molecular mechanisms. By using a high-throughput screening model based on a KLF2 promoter luciferase reporter assay, column chromatography, electrospray ionization mass spectrometry (ESI-MS), and nuclear magnetic resonance (NMR) spectra, trichostatin D (TSD) was isolated from the rice fermentation of Streptomyces sp. CPCC203909 and identified as a novel KLF2 activator. Real-time-quantitative polymerase chain reaction (RT-qPCR) results showed that TSD upregulated the mRNA level of KLF2 in endothelial cells. Functional assays showed that TSD attenuated monocyte adhesion to endothelial cells, decreased vascular cell adhesion protein 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) expression, and exhibited an anti-inflammatory effect in tumor necrosis factor alpha (TNFα)-induced endothelial cells. We further demonstrated through siRNA and western blot assays that the effects of TSD on monocyte adhesion and inflammation in endothelial cells were partly dependent on upregulating KLF2 expression and then inhibiting the NOD-like receptor protein 3 (NLRP3)/Caspase-1/interleukin-1beta (IL-1ß) signaling pathway. Furthermore, histone deacetylase (HDAC) overexpression and molecular docking analysis results showed that TSD upregulated KLF2 expression by inhibiting HDAC 4, 5, and 7 activities. Taken together, TSD was isolated from the fermentation of Streptomyces sp. CPCC203909 and first reported as a potential activator of KLF2 in this study. Furthermore, TSD upregulated KLF2 expression by inhibiting HDAC 4, 5, and 7 and attenuated endothelial inflammation via regulation of the KLF2/NLRP3/Caspase-1/IL-1ß signaling pathway.