Metabolites from the Induced Expression of Cryptic Single Operons Found in the Genome of Burkholderia pseudomallei

Bacterial genome sequencing projects routinely uncover gene clusters that are predicted to encode the biosynthesis of uncharacterized small molecules. A subset of these cryptic genetic elements appears as individual operons. Here we investigate potential single-operon biosynthetic systems found in the genome of the pathogenic bacterium Burkholderia pseudomallei. Placing these operons under the control of an inducible promoter led to the production of seven new metabolites. Among the molecules we identified are inhibitors of type-4 phosphodiesterases, suggesting that previously cryptic biosynthetic operons may encode metabolites that could contribute to microbial virulence by disrupting host signaling pathways

Metabolites from the Induced Expression of Cryptic Single Operons Found in the Genome of Burkholderia pseudomallei

Bacterial genome sequencing projects routinely uncover gene clusters that are predicted to encode the biosynthesis of uncharacterized small molecules. A subset of these cryptic genetic elements appears as individual operons. Here we investigate potential single-operon biosynthetic systems found in the genome of the pathogenic bacterium Burkholderia pseudomallei. Placing these operons under the control of an inducible promoter led to the production of seven new metabolites. Among the molecules we identified are inhibitors of type-4 phosphodiesterases, suggesting that previously cryptic biosynthetic operons may encode metabolites that could contribute to microbial virulence by disrupting host signaling pathways

Two-Dimensional Tetragonal TiC Monolayer Sheet and Nanoribbons

We report a two-dimensional tetragonal Titanium Carbide (TiC) monolayer sheet with distinguished structure and properties based on comprehensive first-principles calculations. The TiC sheet exhibits a novel zigzag-shaped buckling structure with all atoms being quasiplanar tetracoordinate, as favored by strong in-plane C2p–Ti3d bonding and synergetic out-of-plane electronic delocalization. This unique structure endows the sheet with high kinetic stability and anisotropic mechanical properties. Moreover, the TiC sheet displays orientation-dependent electronic properties derived from its special rectangular symmetry, with indirect band gap of ∼0.2 eV and substantial ferromagnetism along its edges, thus promising for wide applications in nanoelectronics

Metabolites from the Induced Expression of Cryptic Single Operons Found in the Genome of Burkholderia pseudomallei

Bacterial genome sequencing projects routinely uncover gene clusters that are predicted to encode the biosynthesis of uncharacterized small molecules. A subset of these cryptic genetic elements appears as individual operons. Here we investigate potential single-operon biosynthetic systems found in the genome of the pathogenic bacterium Burkholderia pseudomallei. Placing these operons under the control of an inducible promoter led to the production of seven new metabolites. Among the molecules we identified are inhibitors of type-4 phosphodiesterases, suggesting that previously cryptic biosynthetic operons may encode metabolites that could contribute to microbial virulence by disrupting host signaling pathways

DataSheet2_Single-cell transcriptome analysis reveals the clinical implications of myeloid-derived suppressor cells in head and neck squamous cell carcinoma.docx

Head and neck squamous cell carcinoma (HNSC) is the most common malignant tumor that arises in the epithelium of the head and neck regions. Myeloid-derived suppressor cells (MDSCs) are one of the tumor-infiltrating immune cell populations, which play a powerful role in inhibiting anti-tumor immune response. Herein, we employed a single-cell RNA sequencing (scRNA-seq) dataset to dissect the heterogeneity of myeloid cells. We found that SPP1+ tumor-associated macrophages (TAMs) and MDSCs were the most abundant myeloid cells in the microenvironment. By cell cluster deconvolution from bulk RNA-seq datasets of larger patient groups, we observed that highly-infiltrated MDSC was a poor prognostic marker for patients’ overall survival (OS) probabilities. To better apply the MDSC OS prediction values, we identified a set of six MDSC-related genes (ALDOA, CD52, FTH1, RTN4, SLC2A3, and TNFAIP6) as the prognostic signature. In both training and test cohorts, MDSC-related prognostic signature showed a promising value for predicting patients’ prognosis outcomes. Further parsing the ligand-receptor pairs of intercellular communications by CellChat, we found that MDSCs could frequently interact with cytotoxic CD8+ T cells, SPP1+ TAMs, and endothelial cells. These interactions likely contributed to the establishment of an immunosuppressive microenvironment and the promotion of tumor angiogenesis. Our findings suggest that targeting MDSCs may serve as an alternative and promising target for the immunotherapy of HNSC.</p

Table_1_Causal association of gut microbiota on spondyloarthritis and its subtypes: a Mendelian randomization analysis.xlsx

BackgroundDespite establishing an association between gut microbiota and spondyloarthritis (SpA) subtypes, the causal relationship between them remains unclear.MethodsGut microbiota data were obtained from the MiBioGen collaboration, and SpA genome-wide association study (GWAS) summary data were obtained from the FinnGen collaboration. We conducted a two-sample Mendelian randomization (MR) analysis using the inverse-variance-weighted method supplemented with four additional MR methods (MR-Egger, weighted median, simple mode, and weighted mode). Pleiotropy and heterogeneity were also assessed. Reverse MR analysis was used to detect reverse causal relationships.ResultsWe identified 23 causal links between specific gut microbiota taxa and SpA levels. Of these, 22 displayed nominal causal associations, and only one demonstrated a robust causal connection. Actinobacteria id.419 increased the risk of ankylosing spondylitis (AS) (odds ratio (OR) = 1.86 (95% confidence interval (CI): 1.29–2.69); p = 8.63E−04). The family Rikenellaceae id.967 was associated with a reduced risk of both AS (OR = 0.66 (95% CI: 0.47–0.93); p = 1.81E−02) and psoriatic arthritis (OR = 0.70 (95% CI: 0.50–0.97); p = 3.00E−02). Bacillales id.1674 increased the risk of AS (OR = 1.23 (95% CI: 1.00–1.51); p = 4.94E−02) and decreased the risk of enteropathic arthritis (OR = 0.56 (95% CI: 0.35–0.88); p = 1.14E−02). Directional pleiotropy, or heterogeneity, was not observed. No reverse causal associations were observed between the diseases and the gut microbiota.ConclusionOur MR analysis suggested a genetic-level causal relationship between specific gut microbiota and SpA, providing insights into the underlying mechanisms behind SpA development mediated by gut microbiota.</p

Table_2_Causal association of gut microbiota on spondyloarthritis and its subtypes: a Mendelian randomization analysis.xlsx

BackgroundDespite establishing an association between gut microbiota and spondyloarthritis (SpA) subtypes, the causal relationship between them remains unclear.MethodsGut microbiota data were obtained from the MiBioGen collaboration, and SpA genome-wide association study (GWAS) summary data were obtained from the FinnGen collaboration. We conducted a two-sample Mendelian randomization (MR) analysis using the inverse-variance-weighted method supplemented with four additional MR methods (MR-Egger, weighted median, simple mode, and weighted mode). Pleiotropy and heterogeneity were also assessed. Reverse MR analysis was used to detect reverse causal relationships.ResultsWe identified 23 causal links between specific gut microbiota taxa and SpA levels. Of these, 22 displayed nominal causal associations, and only one demonstrated a robust causal connection. Actinobacteria id.419 increased the risk of ankylosing spondylitis (AS) (odds ratio (OR) = 1.86 (95% confidence interval (CI): 1.29–2.69); p = 8.63E−04). The family Rikenellaceae id.967 was associated with a reduced risk of both AS (OR = 0.66 (95% CI: 0.47–0.93); p = 1.81E−02) and psoriatic arthritis (OR = 0.70 (95% CI: 0.50–0.97); p = 3.00E−02). Bacillales id.1674 increased the risk of AS (OR = 1.23 (95% CI: 1.00–1.51); p = 4.94E−02) and decreased the risk of enteropathic arthritis (OR = 0.56 (95% CI: 0.35–0.88); p = 1.14E−02). Directional pleiotropy, or heterogeneity, was not observed. No reverse causal associations were observed between the diseases and the gut microbiota.ConclusionOur MR analysis suggested a genetic-level causal relationship between specific gut microbiota and SpA, providing insights into the underlying mechanisms behind SpA development mediated by gut microbiota.</p

Metabolites from the Induced Expression of Cryptic Single Operons Found in the Genome of Burkholderia pseudomallei

Bacterial genome sequencing projects routinely uncover gene clusters that are predicted to encode the biosynthesis of uncharacterized small molecules. A subset of these cryptic genetic elements appears as individual operons. Here we investigate potential single-operon biosynthetic systems found in the genome of the pathogenic bacterium Burkholderia pseudomallei. Placing these operons under the control of an inducible promoter led to the production of seven new metabolites. Among the molecules we identified are inhibitors of type-4 phosphodiesterases, suggesting that previously cryptic biosynthetic operons may encode metabolites that could contribute to microbial virulence by disrupting host signaling pathways

Physical Limit of Nonlinear Brownian Oscillators in Quantum Trap

Quantum trap, a quantum and thermal fluctuations-induced nonmonotonous potential, offers a chance to build up microscopic mechanical systems completely dominated by fluctuations. Here, we explore the physical limit of the effective damping ratio of the nonlinear Brownian oscillator in a quantum trap, set by the finite separation for avoiding molecular-scale effects on the trap potential and the surface confinement effect-induced diverging damping and random forces. The quasiharmonic approximations and Langevin dynamics simulations show that the lowest effective damping ratios of the suspended Au plate and Au sphere upon a Teflon coating of 10 nm can be ∼210 and ∼145, respectively, at room temperature. Perforation is proposed as an effective route to reduce the damping ratio (down to 6.4) by attenuating the surface confinement effect. An unexpected result due to the temperature dependences of dielectric function and viscosity of ethanol is a further reduced damping ratio at 400 K (1.3). The nonlinear Brownian oscillator in the quantum trap shows promise of probing near-boundary hydrodynamics at nanoscale