A bacteriophage against Citrobacter braakii and its synergistic effect with antibiotics.

A bacteriophage BD49 specific for Citrobacter braakii was screened out and purified by double-layer plate method. It consists of a polyhedral head of 93.1 ± 1.2 nm long and 72.9 ± 4.2 nm wide, tail fibers, collar, sheath and baseplate. The bacteriophage was identified by morphology observed with transmission electron microscope (TEM), whole genome sequencing carried out by Illumina next generation sequencing (NGS) technique, and gene annotation based on Clusters of Orthologous Groups of proteins (COG) database. It was identified primarily as a member of Caudovirales by morphology and further determined as Caudovirales, Myoviridae, and Citrobacter bacteriophage by alignment of its whole genome sequence with the NCBI database and establishment of phylogenetic tree. The bacteriophage showed good environmental suitability with optimal multiplicity of infection (MOI) of 0.01, proliferation time of 80 min, optimum living temperature of 30-40 °C, and living pH of 5-10. In addition, it exhibited synergistic effect with ciprofloxacin against C. braakii in antibacterial tests.

Visible-Light-Promoted Radical Cascade Sulfone Alkylation/Cyclization of 2-Isocyanoaryl Thioethers Enabled by Electron Donor-Acceptor Complex Formation.

A photo-induced cascade sulfone alkylation/cyclization of 2-isocyanoaryl thioethers is explored. This visible-light-triggered reaction not only occurs under extremely mild reaction conditions but also does not require the presence of a photosensitizer. The photocatalytic process is triggered by the photochemical activity of in situ-generated electron donor-acceptor complexes, arising from the association of 2-isocyanoaryl thioethers and α-iodosulfones. The radical pathway was confirmed by UV-vis spectroscopy, radical trapping, Job's plot, and on/off irradiation experiments.

Cotransfer of resistance to cephalosporins, colistin, and fosfomycin mediated by an IncHI2/pSH16G4928-like plasmid in ESBL-producing monophasic Salmonella Typhimurium strains of pig origin.

AIMS: To assess the co-transmission risk of phenotypic and genetic resistance to cephalosporins, colistin, and fosfomycin in Salmonella strains collected along the whole pork production chain. METHODS AND RESULTS: From a total of 107 Salmonella isolates from samples collected in pig slaughterhouses and markets, 15 ESBL-producing Salmonella strains resistant to cefotaxime were identified by broth microdilution method and clavulanic acid inhibition test, including 14 monophasic Salmonella Typhimurium strains and one Salmonella Derby strain. Whole genome sequence analysis showed that nine monophasic S. Typhimurium strains coresistant to colistin and fosfomycin carried the resistance genes blaCTX-M-14, mcr-1, and fosA3. Conjugational transfer tests demonstrated that the phenotypic and genetic resistance to cephalosporins, colistin, and fosfomycin could cotransfer back and forth between Salmonella and Escherichia coli via an IncHI2/pSH16G4928-like plasmid. CONCLUSIONS: This study reports the cotransmission of phenotypic and genetic resistance to cephalosporins, colistin, and fosfomycin via an IncHI2/pSH16G4928-like plasmid in Salmonella strains of animal origin, giving an alarm for the prevention of the development and spread of bacterial multidrug resistance.

Enteropathogenic Escherichia coli is a predominant pathotype in healthy pigs in Hubei Province of China.

AIM: This study aims to investigate the prevalence of intestinal pathogenic Escherichia coli (InPEC) in healthy pig-related samples and evaluate the potential virulence of the InPEC strains. METHODS AND RESULTS: A multiplex PCR method was established to identify different pathotypes of InPEC. A total of 800 rectal swab samples and 296 pork samples were collected from pig farms and slaughterhouses in Hubei province, China. From these samples, a total of 21 InPEC strains were isolated, including 19 enteropathogenic E. coli (EPEC) and 2 shiga toxin-producing E. coli (STEC) strains. By whole-genome sequencing and in silico typing, it was shown that the sequence types and serotypes were diverse among the strains. Antimicrobial susceptibility assays showed that 90.48% of the strains were multi-drug resistant. The virulence of the strains was first evaluated using the Galleria mellonella larvae model, which showed that most of the strains possessed medium to high pathogenicity. A moderately virulent EPEC isolate was further selected to characterize its pathogenicity using a mouse model, which suggested that it could cause significant diarrhea. Bioluminescence imaging (BLI) was then used to investigate the colonization dynamics of this EPEC isolate, which showed that the EPEC strain could colonize the mouse cecum for up to 5 days.

Molecular Characteristics and Pathogenicity of Staphylococcus aureus Exotoxins.

Staphylococcus aureus stands as one of the most pervasive pathogens given its morbidity and mortality worldwide due to its roles as an infectious agent that causes a wide variety of diseases ranging from moderately severe skin infections to fatal pneumonia and sepsis. S. aureus produces a variety of exotoxins that serve as important virulence factors in S. aureus-related infectious diseases and food poisoning in both humans and animals. For example, staphylococcal enterotoxins (SEs) produced by S. aureus induce staphylococcal foodborne poisoning; toxic shock syndrome toxin-1 (TSST-1), as a typical superantigen, induces toxic shock syndrome; hemolysins induce cell damage in erythrocytes and leukocytes; and exfoliative toxin induces staphylococcal skin scalded syndrome. Recently, Panton-Valentine leucocidin, a cytotoxin produced by community-associated methicillin-resistant S. aureus (CA-MRSA), has been reported, and new types of SEs and staphylococcal enterotoxin-like toxins (SEls) were discovered and reported successively. This review addresses the progress of and novel insights into the molecular structure, biological activities, and pathogenicity of both the classic and the newly identified exotoxins produced by S. aureus.

Two-Dimensional Detergent Expansion Strategy for Membrane Protein Studies.

Detergents are the most frequently applied reagents in membrane protein (MP) studies. The limited diversity of one-head-one-tailed traditional detergents, however, is far from sufficient for structurally distinct MPs. Expansion of detergent repertoire has a continuous momentum. In line with the speculation that detergent pre-assembly exerts superiority, herein we report for the first time cross-conjugation of two series of monomeric detergents for constructing a two-dimensional library of dimeric detergents. Optimum detergents stood out with unique preferences in the systematic evaluation of individual MPs. Furthermore, unprecedented hybrid detergents 14M8G and 14M9G enabled high-quality EM study of transporter MsbA and NMR study of G protein-coupled receptor A2A AR, respectively. Given the abundance of cross-coupling chemistries, comprehensive diversity could be readily covered that would facilitate the finding of new detergents for the manipulation of thorny MPs and innovation of the functional and structural study in future.

Research Trends on Clinical Helicobacter pylori Eradication: A Bibliometric Analysis from 1983 to 2020.

BACKGROUND: Numerous studies related to Helicobacter pylori (H. pylori) eradication have been published since the discovery of H. pylori. This study aimed to use a quantitative method to assess the development of this field. MATERIALS AND METHODS: We performed a search of related articles from Web of Science published in 1983-2020 using a combination of the search terms "H. pylori" and "eradication". Eligible studies were included after a two-stage screening process, and the following data were extracted: title, author, institution, country, study type, sample size, eradication regimen, publication year, number of citations, journal, and H-index. RESULTS: A total of 1402 studies were finally identified. The results showed that the period from 1994-2003 was the most influential period in this field. Italy and the USA were dominant countries in this field, while China's publication number increased sharply in the last ten years. Baylor College of Medicine was the most influential institution. Alimentary Pharmacology Therapeutics was the most productive journal. The effects of H. pylori eradication on peptic ulcers and gastric cancer and H. pylori eradication therapy were the most cited topics in this field. After the publish of Maastricht/Florence Ⅳ guideline, the research of quadruple therapy was more than triple therapy. Bismuth-containing quadruple therapy became the most focused regimen after Maastricht/Florence Ⅴ guideline. CONCLUSIONS: In this study, we summarized the characteristics of the publications; identified the most influential countries, institutions, journals; identified the popular research topics and eradication regimen of clinical H. pylori eradication.

Effects of different amino acids and their configurations on methane yield and biotransformation of intermediate metabolites during anaerobic digestion.

Anaerobic digestion (AD) comprises a series of biochemical reactions, with methane as one of the target products. Amino acids (AAs) are important molecular and primary intermediate products when protein is the main component of organic waste/wastewater. The L (levorotatory, left-handed)-configuration is natural for AAs, while D (dextrorotatory, right-handed) -AAs also widely exist in the natural environment and can be generated by racemization. However, the effects and underlying mechanisms of natural AAs and their enantiomers on the methane yield and the underlying mechanisms remain unclear. In this study, the effects of certain widespread L-AAs and their enantiomers on two-stage AD and the mechanisms therein were investigated. The AAs enantiomers showed variable or even opposite effects on different processes. The methane yield from a model monosaccharide (glucose) decreased by 57% with D-leucine addition. The butyrate generation and the methane yield from propionate were sensitive to the AA configuration and were inhibited by D-leucine by 80% and 61.8%, respectively, with D-leucine addition, while the volatile fatty acids concentration was slightly increased with the addition of L-leucine. The related mechanisms were further investigated in terms of key enzymes and microbial communities. The addition of D-Leucine decreased acetic acid production from homoacetogens by 30.2% due to the inhibition of key enzymes involved in hydrogen generation and consumption. The transform of butyryl CoA to butyryl phosphate was the rate-limiting step, with the related enzyme (phosphotransbutylase) was inhibited by D-leucine. Furthermore, the bacteria related to butyric acid generation and organic matter degradation were inhibited by D-leucine, while the methanogenic archaea remained stable irrespective of leucine addition. The effect of D-AAs on microorganisms is related to the type of sludge. In this study, the methanogenetic seed sludge was granular and did not dissociate after treatment; however, the D-AAs could trigger biofilm disassembly and reduce the stability of the sludge floc. The study provides a novel method for regulating AD by adding specific AAs with L or D configuration.

Aqueous Phase Exfoliating Quasi-2D CsPbBr3 Nanosheets with Ultrahigh Intrinsic Water Stability.

All-inorganic cesium lead halide perovskite nanocrystals (NCs) have emerged as attractive optoelectronic materials due to the excellent optical and electronic properties. However, their environmental stability, especially in the presence of water, is still a significant challenge for their further commercialization. Here, ultrahigh intrinsically water-stable all-inorganic quasi-2D CsPbBr3 nanosheets (NSs) via aqueous phase exfoliation method are reported. Compared to conventional perovskite NCs, these unique quasi-2D CsPbBr3 nanosheets present an outstanding long-term water stability with 87% photoluminescence (PL) intensity remaining after 168 h under water conditions. Moreover, the photoluminescence quantum yields (PLQY) of quasi-2D CsPbBr3 NSs is up to 82.3%, and these quasi-2D CsPbBr3 NSs also present good photostability of keeping 85% PL intensity after 2 h under 365 nm UV light. Evidently, such quasi-2D perovskite NSs will open up a new way to investigate the intrinsic stability of all-inorganic perovskites and further promote the commercial development of perovskite-based optoelectronic and photovoltaic devices.

Determination of trace heavy metal elements in aqueous solution using surface-enhanced laser-induced breakdown spectroscopy.

Heavy metal pollution is one of the main problems in water pollution, which is harmful to humans. Surface-enhanced laser-induced breakdown spectroscopy (SENLIBS) has been applied to detect trace amounts of heavy metal elements in aqueous solution; however, it is still a big challenge to explore the relationship between the LIBS detection sensitivity and the substrate's physical properties. In this work, four typical substrates, zinc (Zn), magnesium alloy (Mg), nickel (Ni), and silicon (Si), were compared; and the mechanism of spectral enhancement by different substrates in SENLIBS was investigated. The results indicated that the limit of detection (LoD) of heavy metal elements on different substrates is positively proportional to the boiling of the substrate. That is mainly because a higher plasma excitation temperature and electron density are obtained, leading to more intense collision between particles. The signal enhancement is associated with the lower boiling point of the substrate (corresponding to a lower ablation threshold and higher ablation quantity from the substrate). As a result, the best LoD was 0.0011 mg/L for chromium (Cr) and 0.004 mg/L for lead (Pb) on an optimal Zn substrate, respectively. The LoDs were sufficiently low to meet the drinking water sanitation standard. These results showed that the detection sensitivity of heavy metal elements in aqueous solution can be improved by choosing a substrate with a lower boiling point in SENLIBS.

Accuracy improvement of quantitative analysis in spatially resolved fiber-optic laser-induced breakdown spectroscopy.

Fiber-optic laser-induced breakdown spectroscopy (FO-LIBS) has been employed in many applications because of the flexibility of optical fiber cable. However, the inhomogeneous elemental distribution of plasmas can cause a self-absorption effect and, hence, significantly hinder the determination of FO-LIBS. Here, to solve this flaw, we took iron (Fe), magnesium (Mg), and zinc (Zn) elements in aluminum alloy as examples to investigate the self-absorption reduction and accuracy improvement using spatially resolved FO-LIBS. Spatially resolved FO-LIBS means the spectra were collected at different positions along the direction parallel to the surface of the sample rather than at the center of the plasma. With this method, the self-absorption effect could be improved by selecting different acquisition positions along the X-axis. The root mean square error of cross-validations (RMSECV) for Fe, Mg, and Zn were reduced from 0.388, 0.348, and 0.097 wt. % to 0.172, 0.224, and 0.024 wt. %, respectively. Generally, spatial resolution is an effective method of self-absorption reduction and accuracy improvement in FO-LIBS.

Multielemental self-absorption reduction in laser-induced breakdown spectroscopy by using microwave-assisted excitation.

The self-absorption effect seriously affects the accuracy of determination in laser-induced breakdown spectroscopy (LIBS). In this work, we proposed to reduce multielemental self-absorption within a wide spectral range (200-900 nm) by using microwave-assisted excitation in LIBS (MAE-LIBS). Self-absorption reduction of sodium (Na), potassium (K), aluminum (Al), silicon (Si), and calcium (Ca) in potassium feldspar using MAE-LIBS was investigated. The mechanisms of self-absorption reduction in MAE-LIBS were also investigated. The results show that the serious self-absorption of spectral lines (Na and K) was reduced. The full widths at half maximum (FWHMs) of Na I 589.0 nm, Na I 589.6 nm, K I 766.5 nm, and K I 769.9 nm in potassium feldspar were reduced by 43%, 43%, 53%, and 47%, respectively. MAE-LIBS also has a little FWHM reduction for spectral lines with weak self-absorption. The results demonstrate that MAE-LIBS can simultaneously reduce multielemental self-absorption.

Determination of Carbon Content in Steels Using Laser-Induced Breakdown Spectroscopy Assisted with Laser-Induced Radical Fluorescence.

Carbon is a key element for steel properties but hard to be determined by laser-induced breakdown spectroscopy (LIBS). Utilizing the combination of carbon in analytes and nitrogen in ambient gas to generate carbon-nitrogen (CN) radicals, LIBS assisted with laser-induced radical fluorescence (LIBS-LIRF) was proposed to resonantly excite radicals instead of atoms in plasmas. The CN radicals in the B2Σ-A2Π band were stimulated by a 421.60 nm laser wavelength and emitted 388.34 nm fluorescence. The results show that the spectral intensity of the CN radicals was enhanced by 2 orders of magnitude using LIBS-LIRF. Then carbon content in steels was accurately and sensitively determined without spectral interference. The limits of detection (LoDs) were 0.039 and 0.013 wt % in air and nitrogen gas, respectively. The limits of quantification (LoQs) were 0.130 and 0.043 wt % in air and nitrogen gas, respectively. This work demonstrated the feasibility of LIBS to realize reliable carbon determination in steel industry.

On-stream analysis of iron ore slurry using laser-induced breakdown spectroscopy.

On-stream analysis of the element content in ore slurry has important significance in the control of the flotation process and full use of raw materials. Therefore, techniques that can monitor the chemistry in slurries online are required. Laser-induced breakdown spectroscopy (LIBS) is one of the potential approaches to online measurements due to its capability of in situ and real-time analysis. However, using LIBS for on-stream analysis of slurries is challenging due to the issues such as surface ripples, sample splashing, sedimentation, etc. To address these problems, we developed a slurry circulation system. The effects of slurry flow rate on LIBS spectra were investigated to achieve the optimal detecting surface for better repeatability of LIBS. The coefficient of determination R2 of the calibration curve for Fe element is 0.982, and the limit of detection of Fe element was estimated to be 0.075 wt. % under the optimized experimental parameters. The results show that this slurry circulation system is applicable to the on-stream slurry analysis.

Extraction of brain function pattern with visual-capture-task fMRI using dynamic time-window method in ADHD children.

Attention deficit/Hyperactivity disorder (ADHD) has a great impact on children's development. This paper uses a novel adaptive brain state extraction algorithm to construct a dynamic time-window brain network, which captures the brain function pattern characteristics of ADHD children with higher temporal resolution. The test data were acquired by functional magnetic resonance imaging (fMRI) obtained from 23 children with ADHD during the visual-capture-task [age: (8.27 ± 2.77)]. A spatial standard deviation method is used after the initial data processing, to extract the brain activity pattern state; An improved clustering algorithm is constructed to verify the changes made to the dynamic time-window brain network model. There can be seen clear differences between each state within 0.05 s after the test. The results show that our improved new framework can effectively obtain the characteristics of dynamic brain functional connection strength changes during the task. In addition, the new algorithm is able to capture the dynamic changes of the brain network, with an 80 % improvement compared to traditional methods for the average modularity value Q. This work demonstrates a novel approach to find out the pattern changes between dynamic brain function connections, which can be of great significance for the adjuvant treatment of children with ADHD.

Fractal Spiking Neural Network Scheme for EEG-Based Emotion Recognition.

Electroencephalogram (EEG)-based emotion recognition is of great significance for aiding in clinical diagnosis, treatment, nursing and rehabilitation. Current research on this issue mainly focuses on utilizing various network architectures with different types of neurons to exploit the temporal, spectral, or spatial information from EEG for classification. However, most studies fail to take full advantage of the useful Temporal-Spectral-Spatial (TSS) information of EEG signals. In this paper, we propose a novel and effective Fractal Spike Neural Network (Fractal-SNN) scheme, which can exploit the multi-scale TSS information from EEG, for emotion recognition. Our designed Fractal-SNN block in the proposed scheme approximately simulates the biological neural connection structures based on spiking neurons and a new fractal rule, allowing for the extraction of discriminative multi-scale TSS features from the signals. Our designed training technique, inverted drop-path, can enhance the generalization ability of the Fractal-SNN scheme. Sufficient experiments on four public benchmark databases, DREAMER, DEAP, SEED-IV and MPED, under the subject-dependent protocols demonstrate the superiority of the proposed scheme over the related advanced methods. In summary, the proposed scheme provides a promising solution for EEG-based emotion recognition.

Critical Involvement of the Thioredoxin Reductase Gene (trxB) in Salmonella Gallinarum-Induced Systemic Infection in Chickens.

Salmonella enterica serovar Gallinarum biovar Gallinarum (SG) causes fowl typhoid, a notifiable infectious disease in poultry. However, the pathogenic mechanism of SG-induced systemic infection in chickens remains unclear. Thioredoxin reductase (TrxB) is a redox protein crucial for regulating various enzyme activities in Salmonella serovar, but the role in SG-induced chicken systemic infection has yet to be determined. Here, we constructed a mutant SG strain lacking the trxB gene (trxB::Cm) and used chicken embryo inoculation and chicken oral infection to investigate the role of trxB gene in the pathogenicity of SG. Our results showed that trxB::Cm exhibited no apparent differences in colony morphology and growth conditions but exhibited reduced tolerance to H2O2 and increased resistance to bile acids. In the chicken embryo inoculation model, there was no significant difference in the pathogenicity of trxB::Cm and wild-type (WT) strains. In the chicken oral infection, the WT-infected group exhibited typical clinical symptoms of fowl typhoid, with complete mortality between days 6 and 9 post infection. In contrast, the trxB::Cm group showed a 100% survival rate, with no apparent clinical symptoms or pathological changes observed. The viable bacterial counts in the liver and spleen of the trxB::Cm-infected group were significantly reduced, accompanied by decreased expression of cytokines and chemokines (IL-1ß, IL-6, IL-12, CXCLi1, TNF-α, and IFN-γ), which were significantly lower than those in the WT group. These results show that the pathogenicity of the trxB-deficient strain was significantly attenuated, indicating that the trxB gene is a crucial virulence factor in SG-induced systemic infection in chickens, suggesting that trxB may become a potentially effective target for controlling and preventing SG infection in chickens.

Changes in Community Structure of Brain Dynamic Functional Connectivity States in Mild Cognitive Impairment.

Recent researches have noted many changes of short-term dynamic modalities in mild cognitive impairment (MCI) patients' brain functional networks. In this study, the dynamic functional brain networks of 82 MCI patients and 85 individuals in the normal control (NC) group were constructed using the sliding window method and Pearson correlation. The window size was determined using single-scale time-dependent (SSTD) method. Subsequently, k-means was applied to cluster all window samples, identifying three dynamic functional connectivity (DFC) states. Collective sparse symmetric non-negative matrix factorization (cssNMF) was then used to perform community detection on these states and quantify differences in brain regions. Finally, metrics such as within-community connectivity strength, community strength, and node diversity were calculated for further analysis. The results indicated high similarity between the two groups in state 2, with no significant differences in optimal community quantity and functional segregation (p < 0.05). However, for state 1 and state 3, the optimal community quantity was smaller in MCI patients compared to the NC group. In state 1, MCI patients had lower within-community connectivity strength and overall strength than the NC group, whereas state 3 showed results opposite to state 1. Brain regions with statistical difference included MFG.L, ORBinf.R, STG.R, IFGtriang.L, CUN.L, CUN.R, LING.R, SOG.L, and PCUN.R. This study on DFC states explores changes in the brain functional networks of patients with MCI from the perspective of alterations in the community structures of DFC states. The findings could provide new insights into the pathological changes in the brains of MCI patients.

Pharmacokinetics and tissue distribution of Yigong San in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM), Yigong San (YGS) is mainly used to treat dyspepsia caused by deficiency of spleen and stomach qi. Although the chemical composition and bioactivity of YGS has been well studied, the main in vivo compounds and their distribution in tissues still need to be made clearer. AIM OF THE STUDY: To elucidate the pharmacokinetic profiles and tissue distribution of eight main compounds of YGS in rats, and provide a reference for clinical application and new drug development. MATERIALS AND METHODS: UPLC-Q-Exactive-Orbitrap-MS was used to qualitatively characterize the parent compounds and their metabolites in the plasma of rats after oral administration of YGS. A sensitive, reliable, and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method using UPLC-AB Sciex QTRAP 5500 MS was established to quantitatively determine eight main compounds of YGS in rat plasma and tissues, including liquiritin, isoliquiritin, hesperidin, ginsenosides Rb1, Re and Rg1, atractylenolides I and II. RESULTS: The mean area under the concentration-time curve (AUC) values of ginsenoside Rb1, hesperidin, and liquiritin at low, medium, and high doses were greater than 150 ng h/mL. The elimination half-life (t1/2) values of ginsenoside Rb1, atractylenolides I and II (low and medium doses) were longer than 10 h. Peak time (Tmax) values of all compounds were shorter than 10 h. Except for atractylenolides, the maximum concentration (Cmax) values of the compounds were greater than 10 ng/mL. The eight compounds were detected in the heart, brain, liver, spleen and kidney at 0.25 h after oral administration. Liquiritin and isoliquiritin had higher exposure in the liver and heart. Hesperidin and ginsenosides Rb1, Re, and Rg1 are mainly distributed in the spleen and kidney. Atractylenolides I and II are mainly distributed in spleen, liver and kidney. CONCLUSIONS: All main compounds of YGS, i.e., liquiritin, isoliquiritin, hesperidin, ginsenosides Rb1, Re, and Rg1, and atractylenolides I and II are absorbed into plasma and widely distributed in various tissues. Among them, hesperidin, ginsenoside Rb1, and atractylenolide I are main in vivo compounds. They are mainly distributed in spleen, liver and kidney. The results of this study provide a basis for further in-depth development and application of YGS.