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Antimicrobial resistance has become one of the major threats to human health. Therefore, there is a strong need for novel antimicrobials with new mechanisms of action. The kingdom of fungi is an excellent source of antimicrobials for this purpose because it encompasses countless fungal species that harbor unusual metabolic pathways. Previously, we have established a library of secondary metabolites from 10,207 strains of fungi. Here, we screened for antimicrobial activity of the library against seven pathogenic bacterial strains and investigated the identity of the active compounds using ethyl acetate extraction, activity-directed purification using HPLC fractionation and chemical analyses. We initially found 280 antimicrobial strains and subsequently identified 17 structurally distinct compounds from 26 strains upon further analysis. All but one of these compounds, berkchaetoazaphilone B (BAB), were known to have antimicrobial activity. Here, we studied the antimicrobial properties of BAB, and found that BAB affected energy metabolism in both prokaryotic and eukaryotic cells. We conclude that fungi are a rich source of chemically diverse secondary metabolites with antimicrobial activity.

In order to improve the reliability and safety of power supply and reduce the failure rate of switchgear, this paper designs a novel high-voltage switchgear which is reliable and safe. A simulation model for electric field and temperature field simulation is established to check the insulation and temperature rise performance of the new designing switchgear. The electric field simulation results show that the place where there has connection or corner has strong chance to occur partial discharge. The heat field results reveal that even in the condition of passing through current with long operation time, the maximum temperature rise of the switchgear is 55.9 K and 48.7 K respectively, which is lower than the standard design requirement 70 K. Some measures can be taken to improve the insulation and temperature rise performance of the new switchgear, such as polishing the connection or using stainless steel at the top of the switchgear.

The change in the optical fiber state and the status of transmission line often leads to the change of strain in its composite optical fiber. This paper attempts to use a commercial BOTDR (Brillouin optical time-domain reflectometry) to monitor the strain of optical fiber composited in transmission line. The Brillouin spectra of typical optical fiber used in the transmission line are measured by a commercial BOTDR at room temperature, the spectra are fitted and the key parameters are calculated, and then the strain along whole optical fiber is obtained by demodulation. The results show that BOTDR can effectively monitor the optical fiber strain, and the mean standard deviation of strain measured for multiple measurements under the same condition is only about 8 με, which can stastify the requirements of practical cases. The work of this paper lays a foundation for the strain measurement of transmission line.

Due to imperfect manufacturing technology, design defects and environmental impact, the failure rate of 10 kV switchgear is very high. For this reason, based on taken present situation of traditional switchgear and the current technical requirements for switchgear into account, a new reliable and safe modular high voltage switchgear design method is presented in this paper, which can reduce the failure rate of switchgear and improve the reliability of power supply. The electric field and temperature rise simulation model are established to check the reasonability and validity. By using the finite element software, the simulation results show that the design in this paper has a maximum temperature rise of 55 K for the main cabinet and a maximum temperature rise of 45 K for the deputy cabinet, which is far below the international standard of 70 K. The areas where the partial discharge is likely to occur within the switchgear are places such as the connection between bus-bar and cabinet, bus-bar joint and bus-bar corner. In order to avoid potential dangers, the discharge point must be located in time to prevent insulation fault of electrical equipment of the high voltage switchgear. The simulation results demonstrate that the design method in this paper greatly improve the reliability of switchgear and meets the demands of power system.

The thermophilic fungus Oidiodendron flavum is a saprobe that is commonly isolated from soil. Here, we identified a Gram-positive bacteria-selective antimicrobial secondary metabolite from this fungal species, harzianic acid (HA). Using Bacillus subtilis strain 168 combined with several assays, we found that HA targeted the cell membrane, though only at high concentrations. To further study the antimicrobial activity of HA, we isolated an HA-resistant strain, Bacillus subtilis strain M9015, and discovered that the mutant has more translucent colonies, has cross resistance to rifampin, and harbors five mutations in the coding region of four distinct genes. Further analysis of these genes indicated that the mutation in atpE might be responsible for the translucency of the colony, and mutation in yusO for resistance to both HA and rifampin. We conclude that HA is a multi-target antimicrobial agent against Gram-positive bacteria.

Antimicrobial resistance is a major threat to human health. Basic knowledge of antimicrobial mechanism of action (MoA) is imperative for patient care and for identification of novel antimicrobials. However, the process of antimicrobial MoA identification is relatively laborious. Here, we developed a simple, quantitative time-lapse fluorescence imaging method, Dynamic Bacterial Morphology Imaging (DBMI), to facilitate this process. It uses a membrane dye and a nucleoid dye to track the morphological changes of single Bacillus subtilis cells in response to antimicrobials for up to 60 min. DBMI of bacterial cells facilitated assignment of the MoAs of 14 distinct, known antimicrobial compounds to the five main classes. Using this method, we found that the poorly studied antimicrobial, harzianic acid, a secondary metabolite that we purified from the fungal culture of Oidiodendron flavum, targets the cell envelope. We conclude that DBMI is a simple method, which facilitates rapid classification of the MoA of antimicrobials in functionally distinct classes.

Very large overcurrent and overvoltage will occur when the disconnectors switching the main device to backup device for live maintenance, which will threaten the reliability of the switchgear. Therefore, a research about the reliability of switchgear under the switching condition is carried out. Based on the analysis of the transient switching process, the overcurrent and overvoltage are obtained. Then, a 3D FEM model to study the insulating properties and temperature rise characteristics of the switchgear are set up respectively, and the electric field and temperature rise are calculated. The results show that: 1) 17.3kV overvoltage and 1.42kA overcurrent are generated during the switching process;2) The maximum field strength and temperature rise can reach 3.65 kV / cm and 65K respectively, which still meet the requirement of switchgear design standard.

Cell envelope proteinases (CEPs) play essential roles in lactic acid bacteria growth in milk and health-promoting properties of fermented dairy products. The genome of Lactobacillus rhamnosus CGMCC11055 possesses two putative CEP genes prtP and prtR2, and the PrtP displays the distinctive domain organization from PrtR2 reported. The PrtP was purified and biochemically characterized. The results showed that the optimal activity occurred at 44 °C, pH 6.5. p-Amidinophenylmethylsulfonyl fluoride obviously inhibited enzymatic activity, suggesting PrtP was a member of serine proteinases. Under the optimal conditions, β-casein was a favorite substrate over αS1- and κ-casein, and 35 oligopeptides were identified in the β-casein hydrolysate, including the phosphoserine peptide and bioactive isoleucine-proline-proline. By analysis of the amino acid sequences of those oligopeptides, proline was the preferred residue at the breakdown site. Therefore, we speculated that PrtP was a new type of CEPs from Lb. rhamnosus.

The twin-arginine translocation (Tat) system, which is used for folded protein secretion, is rare in lactic acid bacteria (LAB). Previously, a Tat system composed of TatAS and TatCS subunits (the subscript S denotes a Streptococcus thermophilus origin) was identified in S. thermophilus CGMCC 7.179. In the present study, the tatAS and tatCS genes were cloned and functionally analyzed in Escherichia coli DE3 tat-deficient mutants. The E. coli tatABCDE-deficient mutant complemented with tatCSAS exhibited shortened cellular chains, but its ability to grow in the presence of sodium dodecyl sulfate (SDS) was not restored, suggesting that the S. thermophilus Tat system could partially replace that of E. coli. Surprisingly, the E. coli tatABE-deficient mutant complemented with tatAS and the E. coli tatC-deficient mutant complemented with tatCS displayed relatively normal cellular morphology and enhanced tolerance to SDS. These results suggest that TatAS and TatCS could serve as active protein translocases in E. coli DE3 tat-deficient mutants. Moreover, TatAS acted as a bifunctional subunit to fulfill the roles of both TatA and TatB of E. coli DE3. Thus, this minimal Tat system would be a promising candidate to translocate recombinant proteins in LAB.

Phage endolysins have received increased attention in recent times as potential antibacterial agents and the biopreservatives in food production processes. Staphylococcus aureus is one of the most common pathogens in bacterial food poisoning outbreaks. In this study, the endolysin Lysdb, one of the two-component cell lysis cassette of Lactobacillus delbrueckii phage phiLdb, was shown to possess a muramidase domain and catalytic sites with homology to Chalaropsis-type lysozymes. Peptidoglycan hydrolytic bond specificity determination revealed that Lysdb was able to cleave the 6-O-acetylated peptidoglycans present in the cell walls of S. aureus. Turbidity reduction assays demonstrated that Lysdb could effectively lyse the S. aureus live cells under acidic and mesothermal conditions. To further evaluate the ability of Lysdb as a potential antibacterial agent against S. aureus in cheese manufacture, Lactobacillus casei BL23 was engineered to constitutively deliver active Lysdb to challenge S. aureus in lab-scale cheese making from raw milk. Compared with the raw milk, the viable counts of S. aureus were reduced by 10(5)-fold in the cheese inoculated with the engineered L. casei strain during the fermentation process, and the pathogenic bacterial numbers remained at a low level (10(4) CFU/g) after 6 weeks of ripening at 10 °C. Taken together, all results indicated that the Lysdb has the function as an effective tool for combating S. aureus during cheese manufacture from raw milk.

This paper presents the methane detection at low concentration based on 2f harmonic signal to achieve highly sensitive monitoring. Since methane is the characteristic gas in power transformer oil once a thermal fault at low temperature (

The major obstacle to the use of neuropeptides in the pharmacotherapy of brain diseases is their delivery to the CNS. This report presents a novel method for the in vitro molecular packaging of peptides that allows their delivery across the blood-brain barrier (BBB) following systemic administration. The molecular packaging is intended both to disguise the peptide nature of the molecule, thus protecting it from a plethora of vascular and BBB peptidases, and to "lock in" the peptide precursor. The delivered peptide-precursor complex is designed to undergo sequential metabolism, resulting in the release of the active peptide. The proposed method for the CNS delivery of neuroactive peptides results in the brain delivery of the intact peptide sequence, and the delivered peptides exhibit appropriate pharmacological activity. This method may be applicable to delivery of a variety of peptides to the CNS and hence opens the possibility of peptide therapy for CNS diseases that are particularly common in the elderly.

Gln-Leu-Pro-Gly, a progenitor sequence for the thyrotropin-releasing hormone (TRH) analogue [Leu(2)]TRH (pGlu-Leu-Pro-NH(2)), was covalently and bioreversibly modified on its N- and C-termini (by a 1,4-dihydrotrigonellyl and a cholesteryl group, respectively) to create lipoidal brain-targeting systems for the TRH analogue. The mechanism of targeting and the recovery of the parent peptide at the target site involve several enzymatic steps, including the oxidation of the 1,4-dihydropyridine moiety. Due to the lipid insolublity of the peptide pyridinium conjugate obtained after this reaction, one of the rudimentary steps of brain targeting (i.e., trapping in the central nervous system) can be accomplished. Our design also included spacer amino acid(s) inserted between the N-terminal residue of the progenitor sequence and the dihydrotrigonellyl group to facilitate the posttargeting removal of the attached modification. The release of the TRH analogue in the brain is orchestrated by a sequential metabolism utilizing esterase/lipase, peptidyl glycine alpha-amidating monooxygenase (PAM), peptidase cleavage, and glutaminyl cyclase. In addition to in vitro experiments to prove the designed mechanism of action, the efficacy of brain targeting for [Leu(2)]TRH administered in the form of chemical-targeting systems containing the embedded progenitor sequence was monitored by the antagonistic effect of the peptide on the barbiturate-induced anesthesia (measure of the activational effect on cholinergic neurons) in mice, and considerable improvement was achieved over the efficacy of the parent peptide upon using this paradigm.