Xudong Tang

Phosphorene nanoribbon as a promising candidate for thermoelectric applications

In this work, the electronic properties of phosphorene nanoribbons with different width and edge configurations are studied by using density functional theory. It is found that the armchair phosphorene nanoribbons are semiconducting while the zigzag nanoribbons are metallic. The band gaps of armchair nanoribbons decrease monotonically with increasing ribbon width. By passivating the edge phosphorus atoms with hydrogen, the zigzag series also become semiconducting, while the armchair series exhibit a larger band gap than their pristine counterpart. The electronic transport properties of these phosphorene nanoribbons are then investigated using Boltzmann theory and relaxation time approximation. We find that all the semiconducting nanoribbons exhibit very large values of Seebeck coefficient and can be further enhanced by hydrogen passivation at the edge. Taking pristine armchair nanoribbons and hydrogen-passivated zigzag naoribbons with width N = 7, 8, 9 as examples, we calculate the lattice thermal conductivity with the help of phonon Boltzmann transport equation and evaluate the width-dependent thermoelectric performance. Due to significantly enhanced Seebeck coefficient and decreased thermal conductivity, we find that at least one type of phosphorene nanoribbons can be optimized to exhibit very high figure of merit (ZT values) at room temperature, which suggests their appealing thermoelectric applications.

The synergy of honokiol and fluconazole against clinical isolates of azole-resistant Candida albicans

Aims:  To evaluate the interaction of fluconazole (FLC) and honokiol (HNK) in vitro and vivo against azole‐resistant (azole‐R) clinical isolates of Candida albicans.

Transcriptional and Functional Analysis of the Effects of Magnolol: Inhibition of Autolysis and Biofilms in Staphylococcus aureus

Background The targeting of Staphylococcus aureus biofilm structures are now gaining interest as an alternative strategy for developing new types of antimicrobial agents. Magnolol (MOL) shows inhibitory activity against S. aureus biofilms and Triton X-100-induced autolysis in vitro, although there are no data regarding the molecular mechanisms of MOL action in bacteria. Methodology/Principal Findings The molecular basis of the markedly reduced autolytic phenotype and biofilm inhibition triggered by MOL were explored using transcriptomic analysis, and the transcription of important genes were verified by real-time RT-PCR. The inhibition of autolysis by MOL was evaluated using quantitative bacteriolytic assays and zymographic analysis, and antibiofilm activity assays and confocal laser scanning microscopy were used to elucidate the inhibition of biofilm formation caused by MOL in 20 clinical isolates or standard strains. The reduction in cidA, atl, sle1, and lytN transcript levels following MOL treatment was consistent with the induced expression of their autolytic repressors lrgA, lrgB, arlR, and sarA. MOL generally inhibited or reversed the expression of most of the genes involved in biofilm production. The growth of S. aureus strain ATCC 25923 in the presence of MOL dose-dependently led to decreases in Triton X-100-induced autolysis, extracellular murein hydrolase activity, and the amount of extracellular DNA (eDNA). MOL may impede biofilm formation by reducing the expression of cidA, a murein hydrolase regulator, to inhibit autolysis and eDNA release, or MOL may directly repress biofilm formation. Conclusions/Significance MOL shows in vitro antimicrobial activity against clinical and standard S. aureus strains grown in planktonic and biofilm cultures, suggesting that the structure of MOL may potentially be used as a basis for the development of drugs targeting biofilms.

Transcriptional and functional analysis shows sodium houttuyfonate-mediated inhibition of autolysis in Staphylococcus aureus.

Sodium houttuyfonate (SH), an addition compound of sodium bisulfite and houttuynin,showed in vitro antibacterial activity against 21 Staphylococcus aureus (S. aureus) strains grown in planktonic cultures. Microarray results showed decreased levels of autolysin atl, sle1, cidA and lytN transcripts in the SH-treated strain as compared to the control strain, consistent with the induction of the autolytic repressors lrgAB and sarA and with the downregulation of the positive regulators agrA and RNAIII. Triton X-100-induced autolysis was significantly decreased by SH in S. aureus ATCC 25923, and quantitative bacteriolytic assays and zymographic analysis demonstrated SH-mediated reduction of extracellular murein hydrolase activity in these cells. Anti-biofilm assay showed that SH is poorly active against S. aureus grown in biofilm cultures, whereas SH diminished the amounts of extracellular DNA (eDNA) of S. aureus in a dose-dependent manner, which suggested that SH may impede biofilm formation by reducing the expression of cidA to inhibit autolysis and eDNA release in the early phase. Some of the microarray results were confirmed by real-time RT-PCR.

Allicin-induced global gene expression profile of Saccharomyces cerevisiae

To understand the response mechanisms of fungus cells upon exposure to the natural fungicide allicin, we performed commercial oligonucleotide microarrays to determine the overall transcriptional response of allicin-treated Saccharomyces cerevisiae strain L1190. Compared with the transcriptional profiles of untreated cultures, 147 genes were significantly upregulated, and 145 genes were significantly downregulated in the allicin-treated cells. We interpreted the microarray data with the hierarchical clustering tool, T-profiler. Major transcriptional responses were induced by allicin and included the following: first, Rpn4p-mediated responses involved in proteasome gene expression; second, the Rsc1p-mediated response involved in iron ion transporter activity; third, the Gcn4p-mediated response, also known as general amino acid control; finally, the Yap1p-, Msn2/4p-, Crz1p-, and Cin5p-mediated multiple stress response. Interestingly, allicin treatment, similar to mycotoxin patulin and artificial fungicide thiuram treatment, was found to induce genes involved in sulfur amino acid metabolism and the defense system for oxidative stress, especially DNA repair, which suggests a potential mutagenicity for allicin. Quantitative real-time reverse transcription-polymerase chain reaction was performed for selected genes to verify the microarray results. To our knowledge, this is the first report of the global transcriptional profiling of allicin-treated S. cerevisiae by microarray.

Fosfomycin enhances phagocyte-mediated killing of Staphylococcus aureus by extracellular traps and reactive oxygen species

The successful treatment of bacterial infections is the achievement of a synergy between the host’s immune defences and antibiotics. Here, we examined whether fosfomycin (FOM) could improve the bactericidal effect of phagocytes, and investigated the potential mechanisms. FOM enhanced the phagocytosis and extra- or intracellular killing of S. aureus by phagocytes. And FOM enhanced the extracellular killing of S. aureus in macrophage (MФ) and in neutrophils mediated by extracellular traps (ETs). ET production was related to NADPH oxidase-dependent reactive oxygen species (ROS). Additionally, FOM increased the intracellular killing of S. aureus in phagocytes, which was mediated by ROS through the oxidative burst process. Our results also showed that FOM alone induced S. aureus producing hydroxyl radicals in order to kill the bacterial cells in vitro. In a mouse peritonitis model, FOM treatment increased the bactericidal extra- and intracellular activity in vivo, and FOM strengthened ROS and ET production from peritoneal lavage fluid ex vivo. An IVIS imaging system assay further verified the observed in vivo bactericidal effect of the FOM treatment. This work may provide a deeper understanding of the role of the host’s immune defences and antibiotic interactions in microbial infections.

Genome-wide transcription analyses in Mycobacterium tuberculosis treated with lupulone

Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, still causes higher mortality than any other bacterial pathogen until now. With the emergence and spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR-TB) strains, it becomes more important to search for alternative targets to develop new antimycobacterial drugs. Lupulone is a compound extracted from Hops (Hurnulus lupulus), which exhibits a good antimicrobial activity against M. tuberculosis with minimal inhibitory concentration (MIC) value of 10 μg/mL, but the response mechanisms of lupulone against M. tuberculosis are still poorly understood. In this study, we used a commercial oligonucleotide microarray to determine the overall transcriptional response of M. tuberculosis H37Rv triggered by exposure to MIC of lupulone. A total of 540 genes were found to be differentially regulated by lupulone. Of these, 254 genes were upregulated, and 286 genes were downregulated. A number of important genes were significantly regulated which are involved in various pathways, such as surface-exposed lipids, cytochrome P450 enzymes, PE/PPE multigene families, ABC transporters, and protein synthesis. Real-time quantitative RT-PCR was performed for choosed genes to verified the microarray results. To our knowledge, this genome-wide transcriptomics approach has produced the first insights into the response of M. tuberculosis to a lupulone challenge.

Aflatoxin B1 Induces Reactive Oxygen Species-Mediated Autophagy and Extracellular Trap Formation in Macrophages

Aflatoxins are a group of highly toxic mycotoxins with high carcinogenicity that are commonly found in foods. Aflatoxin B1 (AFB1) is the most toxic member of the aflatoxin family. A recent study reported that AFB1 can induce autophagy, but whether AFB1 can induce extracellular traps (ETs) and the relationships among innate immune responses, reactive oxygen species (ROS), and autophagy and the ETs induced by AFB1 remain unknown. Here, we demonstrated that AFB1 induced a complete autophagic process in macrophages (MΦ) (THP-1 cells and RAW264.7 cells). In addition, AFB1 induced the generation of MΦ ETs (METs) in a dose-dependent manner. In particular, the formation of METs significantly reduced the AFB1 content. Further analysis using specific inhibitors showed that the inhibition of either autophagy or ROS prevented MET formation caused by AFB1, indicating that autophagy and ROS were required for AFB1-induced MET formation. The inhibition of ROS prevented autophagy, indicating that ROS generation occurred upstream of AFB1-induced autophagy. Taken together, these data suggest that AFB1 induces ROS-mediated autophagy and ETs formation and an M1 phenotype in MΦ.

Phenotype and expression profile analysis of Staphylococcus aureus biofilms and planktonic cells in response to licochalcone A

Staphylococcus aureus is one of the most important pathogens in humans and animals. The formation of biofilm by S. aureus is considered an important mechanism of antimicrobial resistance. Therefore, finding effective drugs against the biofilm produced by S. aureus has been a high priority. Licochalcone A (LAA), a natural plant product, was reported to have antibacterial activities and showed good activity against all 21 tested strains of S. aureus biofilm and planktonic cells. To detect the possible molecular mechanism of LAA against S. aureus biofilm or planktonic cells, Affymetrix GeneChips were used to determine the global comparative transcription of S. aureus biofilm and planktonic cells triggered by treatment with sub-bactericidal and sub-inhibitory concentrations of LAA, respectively. LAA significantly altered (greater than a 2- or less than −2-fold change) the expression of 693 genes in planktonic cells and 817 genes in biofilm. The levels of genes encoding autolysis-associated proteins, cell wall proteins, pathogenic factors, protein synthesis genes, and enzymes involved in capsule synthesis were significantly altered in LAA-treated S. aureus. Furthermore, some differences observed in the microarray analysis were verified by real-time RT–PCR. To our knowledge, this is the first observation of phenotype and expression profiles of S. aureus biofilm and planktonic cells in response to LAA treatment.

Genome-wide expression profiling of the response to linezolid in Mycobacterium tuberculosis.

Tuberculosis (TB) is still one of the most common causes of death in the world. The emergence of multidrug-resistant and extensively drug-resistant (XDR-TB) Mycobacterium tuberculosis (M. tuberculosis) strains has increased the importance of searching for alternative targets to develop new antimycobacterial drugs. Linezolid, the first of oxazolidinones, is active in vitro against M. tuberculosis, but the response mechanisms of M. tuberculosis to linezolid are still poorly understood. To reveal the possible mechanism of action of linezolid against M. tuberculosis, commercial oligonucleotide microarrays were used to analyze the genome-wide transcriptional changes triggered by treatment with subinhibitory concentrations of linezolid. Quantitative real-time RT-PCR was performed for selected genes to verify the microarray results. A total of 729 genes were found to be differentially regulated by linezolid. Among these, 318 genes were upregulated, and 411 genes were downregulated. A number of important genes were significantly regulated that are involved in various pathways, such as protein synthesis, sulfite metabolism, and genes involved in the cell envelope and virulence. This genome-wide transcriptomics approach produced the first insights into the response of M. tuberculosis to a linezolid challenge.