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Staphylococcus aureus is a notorious pathogen responsible for various severe diseases. Due to the emergence of drug-resistant strains, the prevention and treatment of S. aureus infections have become increasingly challenging. Vancomycin is considered to be one of the last-resort drugs for treating most methicillin-resistant S. aureus (MRSA), so it is of great significance to further reveal the mechanism of vancomycin resistance. VraFG is one of the few important ABC (ATP-binding cassette) transporters in S. aureus that can form TCS (two-component systems)/ABC transporter modules. ABC transporters can couple the energy released from ATP hydrolysis to translocate solutes across the cell membrane. In this study, we obtained a strain with decreased vancomycin susceptibility after serial passaging and selection. Subsequently, whole-genome sequencing was performed on this laboratory-derived strain MWA2 and a novel single point mutation was discovered in vraF gene, leading to decreased sensitivity to vancomycin and daptomycin. Furthermore, the mutation reduces autolysis of S. aureus and downregulates the expression of lytM, isaA, and atlA. Additionally, we observed that the mutant has a less net negative surface charge than wild-type strain. We also noted an increase in the expression of the dlt operon and mprF gene, which are associated with cell surface charge and serve to hinder the binding of cationic peptides by promoting electrostatic repulsion. Moreover, this mutation has been shown to enhance hemolytic activity, expand subcutaneous abscesses, reflecting an increased virulence. This study confirms the impact of a point mutation of VraF on S. aureus antibiotic resistance and virulence, contributing to a broader understanding of ABC transporter function and providing new targets for treating S. aureus infections.

Purpose – To cope with the severe situation of the global climate, China proposed the “30 60” dual-carbon strategic goal. Based on this background, the purpose of this paper is to investigate scientifically and reasonably the interprovincial pattern of China’s power carbon emission intensity and further explore the causes of differences on this basis. Design/methodology/approach – Considering the principle of “shared but differentiated responsibilities,” this study measures the carbon emissions within the power industry from 1997 to 2019 scientifically, via the panel data of 30 provinces in China. The power carbon emission intensity is chosen as the indicator. Using the Dagum Gini coefficient to explore regional differences and their causes. Findings – The results of this paper show that, first, China’s carbon emission intensity from the power industry overall is significantly different. From the perspective of geospatial distribution, the three regions have unbalanced characteristics. Second, according to the decomposition results of the Gini coefficient, the overall difference in power carbon emission intensity is generally expanding. The geospatial and economic development levels are examined separately. The gaps between the eastern and economically developed regions are the smallest, and the regional differences are the source of the overall disparity. Research limitations/implications – Further exploring the causes of differences on this basis is crucial for relevant departments to formulate differentiated energy conservation and emission reduction policies. This study provides direction for analyzing the green and low carbon development of China’s power industry. Practical implications – As an economic indicator of green and low-carbon development, CO2 intensity of power industry can directly reflect the dependence of economic growth on the high emission of electricity and energy. and further exploring the causes of differences on this basis is crucial for relevant departments to formulate differentiated energy conservation and emission reduction policies. Social implications – For a long time, with the rapid economic development, resulting in the unresolved contradiction between low energy efficiency and high carbon emissions. To this end, scientifically and reasonably investigating the interprovincial pattern of China’s power carbon emission intensity, and further exploring the causes of differences on this basis, is crucial for relevant departments to formulate differentiated energy conservation and emission reduction policies. Originality/value – Third, considering the influence of spatial factors on the convergence of power carbon emission intensity, a variety of different spatial weight matrices are selected. Based on the β-convergence theory from both absolute and conditional perspectives, we dig deeper into the spatial convergence of electricity carbon emission intensity across the country and the three regions.

Abstract Treatment of Staphylococcus aureus infections is a constant challenge due to emerging resistance to vancomycin, a last-resort drug. S-nitrosylation, the covalent attachment of a nitric oxide (NO) group to a cysteine thiol, mediates redox-based signaling for eukaryotic cellular functions. However, its role in bacteria is largely unknown. Here, proteomic analysis revealed that S-nitrosylation is a prominent growth feature of vancomycin-intermediate S. aureus. Deletion of NO synthase (NOS) or removal of S-nitrosylation from the redox-sensitive regulator MgrA or WalR resulted in thinner cell walls and increased vancomycin susceptibility, which was due to attenuated promoter binding and released repression of genes involved in cell wall metabolism. These genes failed to respond to H2O2-induced oxidation, suggesting distinct transcriptional responses to alternative modifications of the cysteine residue. Furthermore, treatment with a NOS inhibitor significantly decreased vancomycin resistance in S. aureus. This study reveals that transcriptional regulation via S-nitrosylation underlies a mechanism for NO-mediated bacterial antibiotic resistance.

ABSTRACT Acinetobacter baumannii is of growing concern for global health owing to its ability to evade the immune system and develop resistance to antibiotics. We analyzed A. baumannii using the National Center for Biotechnology Information (https://www.ncbi.nlm.nih.gov/pathogens) database and observed that the ST369 strain isolated in China constituted over 50% of the globally prevalent ST369 clones. This finding highlights the significant impact of ST369 on public health in China. In this study, we examined eight strains of multidrug-resistant A. baumannii ST369 isolated from a provincial hospital in China. We conducted whole-genome sequencing, comparative genomic analysis, and phenotypic experiments, and used the Galleria mellonella infection model to achieve a comprehensive understanding of the organism. In our study, we identified two mutations, G540A and G667D, on the wzc gene of A. baumannii ST369 that can potentially affect bacterial virulence and viscosity. We also verified the impact of these mutations on virulence and resistance. In addition, we examined two proteins, AB46_0125 and AB152_03903, which may play a role in virulence. These findings establish a foundation for future studies on clinical ST369 isolates harboring such mutations. IMPORTANCE Acinetobacter baumannii is a major health threat due to its antibiotic resistance and ability to cause nosocomial infections. Epidemiological studies indicated that the majority of globally prevalent ST369 clones originated from China, indicating a significant impact on public health in the country. In this study, we conducted whole-genome sequencing, comparative genomics, and Galleria mellonella infection model on eight A. baumannii ST369 isolates collected from a provincial hospital in China to comprehensively understand the organism. We identified two mutations (G540A and G667D) on the wzc gene that can affect bacterial virulence and viscosity. We confirmed their impact on resistance and virulence. We also investigated the potential involvement of AB46_0125 and AB152_03903 proteins in virulence. This finding provides a theoretical reference for further research on A. baumannii ST369 clinical isolates with similar mutations.

Klebsiella pneumoniae is an opportunistic pathogen that mainly causes nosocomial infections and hospital-associated pneumonia in elderly and immunocompromised people. However, multidrug-resistant hypervirulent K. pneumoniae (MDR-hvKp) has emerged recently as a serious threat to global health that can infect both immunocompromised and healthy individuals. It is scientifically established that plasmid-mediated regulator of mucoid phenotype genes (rmpA and rmpA2) and other virulence factors (aerobactin and salmochelin) are mainly responsible for this phenotype. In this study, we collected 23 MDR-hvKp isolates and performed molecular typing, whole genome sequencing, comparative genomic analysis, and phenotypic experiments, including the Galleria mellonella infection model, to reveal its genetic and phenotypic features. Meanwhile, we discovered two MDR-hvKp isolates (22122315 and 22091569) that showed a wide range of hypervirulence and hypermucoviscosity without rmpA and rmpA2 and any virulence factors. In phenotypic experiments, isolate 22122315 showed the highest hypervirulence (infection model) with significant mucoviscosity, and conversely, isolate 22091569 exhibited the highest mucoviscosity (string test) with higher virulence compared to control. These two isolates carried carbapenemase (blaKPC − 2), β-lactamase (blaOXA − 1, blaTEM − 1B), extended-spectrum β-lactamase (ESBL) genes (blaCTX − M − 15, blaSHV − 106), outer membrane protein-coding genes (ompA), fimbriae encoding genes (ecpABCDER), and enterobactin coding genes (entAB, fepC). In addition, single nucleotide polymorphism analysis indicated that both isolates, 22122315 and 22091569, were found to have novel mutations in loci FEBNDAKP_03184 (c. 2084A > C, p. Asn695Thr), and EOFMAFIB_02276 (c. 1930C > A, p. Pro644Thr), respectively. Finally, NCBI blast analysis suggested these mutations are located in the wzc of the capsule polysaccharide (cps) region and are responsible for putative tyrosine kinase. This study would be a strong reference for enhancing the current understanding of identifying the MDR-hvKp isolates that lacked both mucoid regulators and virulence factors.

The financial technology (FinTech) has promoted the wide application of FinTech with the help of artificial intelligence, blockchain, cloud computing, data science and other new technologies. Trust evaluation has become a forward-looking issue for the rapid development of FinTech. The existing trust evaluation methods of FinTech do not consider the impact of the timeliness, reliability and non-invasive factors of trust on trust evaluation, which results in low accuracy of trust evaluation and incapability of effectively identifying malicious behaviors of users. Firstly, this paper introduces the blockchain technology to construct a four-layer architecture structure and multiple trust evaluation indicators based on blockchain service data. Secondly, the paper proposes a blockchain based FinTech trust evaluation mechanism (BFTEM), which utilizes blockchain to record relevant data and multiple trust parameters during the transmission process of each block, and verify the trust degree issued by the trust holder through the comprehensive trust value of the user. Finally, the block generation time, throughput, delayed response time and comprehensive trust value are experimentally studied through simulation experiments. Simulation experiments show that BFTEM mechanism can better improve the security and reliability of FinTech data, and has advantages in improving the accuracy of trust evaluation and expanding potential applications.

Abstract Background: It is well known that carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a more problematic public health issue due to its widespread spread worldwide. In China, ST11-type CRKP is the most prevalent CRKP, but ST15-type CRKP, a recently prevalent high-risk clone, has emerged widely throughout China, posing a serious public health risk. Therefore, we conducted an epidemiological of an outbreak of ST15 CRKP of producing CTX-M-15, KPC-2 and SHV-106 in a tertiary hospital in Anhui, China, to Understanding the potential risks of the current STT15 CRKP outbreak. Results: From July 2021 to December 2021, 13 ST15 CRKP isolates were identified by collecting non-repeated clinical multidrug-resistant isolates, with all capsular typing of serotype KL19. All ST15 CRKP isolates were resistant to cephalosporins, carbapenems and quinolones, but were sensitive to amikacin, tigecycline and polymyxin B. In addition, isolates carried bla SHV−106 (100%), bla KPC−2 (69%), bla CTX−M−15 (69%), bla TEM−1B (69%), bla OXA−1 (62%) and bla LAP−2 (8%), as well as iron chelators (iutA, ybt, fyuA, ent, fepA, irp1, irp2, 100%) were detected. In phenotyping experiments, all ST15 CRKP exhibited lower growth rates than NTUH-K2044, and all ST15 CRKP did not exhibit mucoviscositty characteristics. However, in the Galleria mellonella infection model, isolates 21081212, 21081241 and 21091216 were more lethal than the hypervirulent isolates NTUH-K2044. Sequencing results showed that the genetic environment surrounding the genes bla SHV−106, bla KPC−2, bla CTX−M−15, bla OXA−1 and bla TEM−1B were all identical in the ST15 CRKP isolates. Phylogenetic analysis showed that 13 ST15 CRKP isolates were divided into three subgroups, and when placed in global analysis, 10 of them were highly homologous to isolates from Jiangsu, two were highly homologous to isolates from Zhejiang, and one was homologous to an isolate from an unlabelled region. Conclusion: Our research shows that ST15 CRKP, which carries multiple β-lactamases genes and siderophores-encoding genes, may be evolving to hypervirulence and may have spread widely in localised areas. Therefore, environmental surveillance and clinical infection control in hospitals should be strengthened to prevent further spread of ST15 CRKP.

Abstract Background Gastric microbial dysbiosis were reported to be associated with gastric cancer (GC). This study aimed to explore the variation, diversity, and composition patterns of gastric bacteria in stages of gastric carcinogenesis based on the published datasets. Methods We conducted a gastric microbial analysis using 10 public datasets based on 16S rRNA sequencing, including 1270 gastric biopsies of 109 health control, 183 superficial gastritis (SG), 135 atrophic gastritis (AG), 124 intestinal metaplasia (IM), 94 intraepithelial neoplasia (IN), 344 GC, and 281 adjacent normal tissues. And QIIME2-pipeline, DESeq2, NetMoss2, vegan, igraph, and RandomForest were used for the data processing and analysis. Results We identified three gastric microbial communities among all the gastric tissues. The first community (designate as GT-H) was featured by the high abundance of Helicobacter. The other two microbial communities, namely GT-F, and GT-P, were featured by the enrichment of phylum Firmicutes and Proteobacteria, respectively. The distribution of GC-associated bacteria, such as Fusobacterium, Peptostreptococcus, Streptococcus, and Veillonella were enriched in tumor tissues, and mainly distributed in GT-F type microbial communities. Compared with SG, AG, and IM, the bacterial diversity in GC was significantly reduced. And the strength of microbial interaction networks was initially increased in IM but gradually decreased from IN to GC. In addition, Randomforest models constructed in in GT-H and GT-F microbial communities showed excellent performance in distinguishing GC from SG and precancerous stages, with varied donated bacteria. Conclusions This study identified three types of gastric microbiome with different patterns of composition which helps to clarify the potential key bacteria in the development of gastric carcinogenesis.

ABSTRACT Staphylococcus aureus is a pathogenic bacterium with a widespread distribution that can cause diverse severe diseases. The membrane-bound nitrate reductase NarGHJI serves respiratory function. However, little is known about its contribution to virulence. In this study, we demonstrated that narGHJI disruption results in the downregulation of virulence genes (e.g., RNAIII, agrBDCA, hla, psmα, and psmβ) and reduces the hemolytic activity of the methicillin-resistant S. aureus (MRSA) strain USA300 LAC. Moreover, we provided evidence that NarGHJI participates in regulating host inflammatory response. A mouse model of subcutaneous abscess and Galleria mellonella survival assay demonstrated that the ΔnarG mutant was significantly less virulent than the wild type. Interestingly, NarGHJI contributes to virulence in an agr-dependent manner, and the role of NarGHJI differs between different S. aureus strains. Our study highlights the novel role of NarGHJI in regulating virulence, thereby providing a new theoretical reference for the prevention and control of S. aureus infection. IMPORTANCE Staphylococcus aureus is a notorious pathogen that poses a great threat to human health. The emergence of drug-resistant strains has significantly increased the difficulty of preventing and treating S. aureus infection and enhanced the pathogenic ability of the bacterium. This indicates the importance of identifying novel pathogenic factors and revealing the regulatory mechanisms through which they regulate virulence. The nitrate reductase NarGHJI is mainly involved in bacterial respiration and denitrification, which can enhance bacterial survival. We demonstrated that narGHJI disruption results in the downregulation of the agr system and agr-dependent virulence genes, suggesting that NarGHJI participates in the regulation of S. aureus virulence in an agr-dependent manner. Moreover, the regulatory approach is strain specific. This study provides a new theoretical reference for the prevention and control of S. aureus infection and reveals new targets for the development of therapeutic drugs.

Abstract Background Mobile colistin resistance like gene (mcr-like gene) is a new type of polymyxin resistance gene that can be horizontally transferred in the Enterobacteriaceae. This has brought great challenges to the treatment of multidrug-resistant Escherichia coli and K. pneumoniae. Results K. pneumoniae 16BU137 and E. coli 17MR471 were isolated from the bus and subway handrails in Guangzhou, China. K. pneumoniae 19PDR22 and KP20191015 were isolated from patients with urinary tract infection and severe pneumonia in Anhui, China. Sequence analysis indicated that the mcr-1.1 gene was present on the chromosome of E. coli 17MR471, and the gene was in the gene cassette containing pap2 and two copies of ISApl1.The mcr-1.1 was found in the putative IncX4 type plasmid p16BU137_mcr-1.1 of K. pneumoniae 16BU137, but ISApl1 was not found in its flanking sequence. Mcr-8 variants were found in the putative IncFIB/ IncFII plasmid pKP20191015_mcr-8 of K. pneumoniae KP20191015 and flanked by ISEcl1 and ISKpn26. Conclusion This study provides timely information on Enterobacteriaceae bacteria carrying mcr-like genes, and provides a reference for studying the spread of mcr-1 in China and globally.

New technologies such as Internet, cloud computing, artificial intelligence (AI) and blockchain have greatly promoted the innovation of financial industry structure and paradigm, improved the efficiency of financial services and brought the spillover of the financial technology (FinTech) risk. The existing financial regulation methods cannot meet the needs of the development of FinTech, therefore, there is an urgent need to improve the trust mechanism. Blockchain can effectively solve the problems of security and trust in FinTech. This paper will explore the expression method of trust index in blockchain, and build based on blockchain a multi-dimensional trust index system and evaluation mechanism (MDTEM) for FinTech. Firstly, a four-level blockchain structure has been built, including cloud level blockchain, Internet level blockchain, contract level blockchain and application level blockchain in the FinTech ecological environment to ensure the security, reliability and trustworthiness of financial services. Secondly, according to the trust structure of blockchain on FinTech payment behavior, the index system and evaluation mechanism of direct trust, indirect trust, recommendation trust and feedback trust of FinTech based on blockchain are designed. Finally, the trust simulation experiment of FinTech mechanism is carried out from three aspects: data sending, data transmission, data reception and delivery success rate. Simulation results show that the proposed MDTEM trust mechanism can better improve the safe and reliable application of FinTech trust mechanism.

Klebsiella pneumoniae has become a primary threat to global health because of its virulence and resistance. In 2015, China reported multidrug-resistant (MDR) and hypervirulent K. pneumoniae (hvKp) isolates. The emergence of MDR-hvKp poses a significant threat to public health. We collected 76 MDR K. pneumoniae isolates from the same hospital, of which there were a total of six MDR-hvKp isolates. We performed multilocus sequence typing (MLST) and capsular typing, whole genome sequencing, comparative genome analysis, and phylogenetic analysis as well as phenotypic experiments, including growth curves, mucoviscosity assay, Galleria mellonella infection model, human whole blood survival, and human neutrophil bactericidal assay to further characterize the samples. We identified six large plasmids carrying extended spectrum β-lactamase (ESBL) genes or carbapenemase genes (blaCTX–M–65, blaKPC–2, blaSHV–12, blaSHV–158), 9 plasmids containing other drug resistance genes, and 7 hypervirulence plasmids carrying rmpA and rmpA2 in ST11 MDR-hvKp isolates. Some of these plasmids were identical, whereas others differed only by insertion elements. In addition, we identified a plasmid, p21080534_1, that carries hypervirulence genes (iucABCD, iutA, rmpA2), a carbapenemase gene (blaKPC–2), and an ESBL gene (blaSHV–12), as well as MDR-hvKp 21072329, which did not carry rmpA or rmpA2, but exhibited hypervirulence and hypermucoviscosity. ST11 MDR-hvKp derived from hypervirulence and multidrug resistance plasmids not only causes significant treatment difficulties, but also represents an unprecedented challenge to public health. Therefore, urgent measures are needed to limit further spread.

It is known that the extradosed cable-stayed bridge, a hybrid bridge, possesses the virtues of both classic cable-stayed bridges and girder bridges in mechanical behaviors. In this paper, the sensitivity of seismic fragility demand parameters (SFDP) of a high-speed railway extradosed cable-stayed bridge is studied systematically along with the consideration of structural parameter uncertainty. Based on the probability distribution and correlation of random parameters, the Latin hypercube sampling method is adopted herein. The dynamic 3D finite element model of the employed bridge is established by using powerful and attractive OpenSEES nonlinear software. A nonlinear incremental dynamic analysis is performed to consider the randomness of structural parameters using sampling analysis. Some important conclusions are drawn indicating that the structural design parameter uncertainty predominantly has influence on the SFDP for fragility analysis of bridge structures. The design parameters of extradosed cable-stayed bridges are categorized and identified as primary, secondary and insensitive parameters. The high sensitivity parameters of extradosed cable-stayed bridges for fragility analysis include friction coefficient of bearing, concrete bulk density, damping ratio, peak compressive strength of confined concrete, component size and peak strain of confined concrete. Additionally, the strength and strain of unconfined concrete cannot be ignored. Furthermore, the uncertainty of structural design parameters fails to be responsible for the cable force responses due to larger girder stiffness. The structural design parameter uncertainty has a significant influence on the responses of extradosed cable-stayed bridges for seismic fragility analysis.

The construction industry lacks a comprehensive and overall scheme for the use and management of building information modeling (BIM) in the whole building life cycle, especially the use of BIM technology for asset management and facility management. However, there is little understanding and implementation of enterprise BIM. BIM influences and changes the new project management mode of the whole life cycle of construction projects from design to construction. The safety, audit, responsibility and value of BIM are the forward-looking problems in current BIM, but it is difficult to realize the whole process value management based on the contribution of all parties, it is not conducive to the popularization and application of BIM. From the perspective of new technology and the whole life cycle, this paper analyzes the development and promotion of Blockchain technology to construction projects, and puts forward the fusion point of BIM and Blockchain technology: multi-user, multi-stage, multi-target data fusion and traceability mechanism; It is a consensus process model of multi-party collaboration, interest balance, non-destructive transmission of building information, responsibility traceability and customer satisfaction. It realizes the supporting framework and implementation ideas of BIM and Blockchain technology in construction projects from the aspects of design technology, construction management, material scheduling and whole life cycle construction. This paper will provide some new ideas for the whole life cycle collaborative management of digital construction.

ABSTRACTStaphylococcus aureus is a major human pathogen that causes a great diversity of community- and hospital-acquired infections. Rsp, a member of AraC/XylS family of transcriptional regulators (AFTRs), has been reported to play an important role in the regulation of virulence determinants in S. aureus via an agr-dependent pathway. Here we demonstrated that Rsp could bind to the rsp promoter to positively regulate its own expression. We then constructed an isogenic rsp deletion strain and compared the haemolysis in the wild-type and rsp mutant strains. Our results indicated that the rsp mutant strain displayed decreased haemolytic activity, which was correlated with a dramatic decrease in the expression of hla and psm. Furthermore, we analysed the regulatory effects of Rsp in the agr mutant strain and found that they are agr-independent. Electrophoretic mobility shift assay indicated that Rsp can directly bind to the promoter regions of hla and psm. The mouse model of subcutaneous abscess showed that the rsp mutant strain displayed a significant defect in virulence compared to the wild-type strain. These findings reveal that Rsp positively regulates the virulence of S. aureus by promoting the expression of hla and psm through direct binding to their promoter regions.

Opportunistic network takes advantage of the contact opportunities introduced by node movement for data transmission. Data is usually piggybacked during the movement of the carrier, which guarantees its independence, however, the system performance is impaired. Inspired from the motion nature of nodes, this paper proposes an adaptive motion based opportunistic routing protocol to address the problem. It develops a data forwarding priority model from the perspective of data communication and determines data transmission rules in combination with node activity range partition scheme. A differential replica transfer strategy is thus proposed to achieve a tradeoff between transmission efficiency and system overhead. A free motion degree model is constructed based on which a utility function is deduced to choose appropriate nodes for data relaying. The simulation results show that the proposed algorithm achieves higher packet delivery ratio and less transmission latency while satisfying application requirements and restraining network overhead.

The mobile ad hoc network (MANET) is a kind of dynamic, easy to construct and universal network, which has been widely concerned by a large number of researchers. Graph theory provides an effective theoretical tool for MANETs modeling and analysis. Clustering is one of the most effective methods to measure network performance with different attributes. This paper gives the basic concept of graph kernel and discusses the principle of optimizing graph kernel and multi-graph kernel. In this paper, we propose a Graph Kernel based Clustering Algorithm in MANETs (GKCA). The GKCA algorithm gives the basic concept of graph kernel, discusses the principle of optimizing graph kernel and multi-graph kernel, and proposes the basic principle based on $d$ -hop graph kernel. GKCA algorithm uses shortest path (SP) to connect different cluster head nodes for packet transmission. The performance of GKCA algorithm, such as the control packets ratio, packets loss ratio, and average end-to-end delay are experimentally evaluated using network simulation (NS2) software. Experimental analysis shows that the proposed approach is efficient, and its performance advantage in dynamic mobile networks is promising.

BackgroundGastric microbiota may be involved in gastric cancer. The relationship between gastrointestinal microbes and the risk of gastric cancer is unclear. This study aimed to explore the gastric and intestinal bacteria associated with gastritis and gastric precancerous lesions. We conducted a case-control study by performing 16S rRNA gene analysis of gastric biopsies, juices, and stool samples from 148 cases with gastritis or gastric precancerous lesions from Anhui and neighboring provinces, China. And we validated our findings in public datasets.ResultsAnalysis of microbial sequences revealed decreased bacterial alpha diversity in gastric bacteria during the progression of gastritis. Helicobacter pylori was the main contributor to the decreased microbial composition and diversity in the gastric mucosa and had little influence on the microbiota of gastric juice and feces. The gastric mucosal genera Gemella, Veillonella, Streptococcus, Actinobacillus, and Hemophilus had the higher degree of centrality across the progression of gastric precancerous lesions. And Acinetobacter may contribute to the occurrence of intraepithelial neoplasia. In addition, the microbial model of H. pylori-positive gastric biopsies and feces showed value in the prediction of gastric precancerous lesions.ConclusionsThis study identified associations between gastric precancerous lesions and gastric microbiota, as well as the changes in intestinal microbiota, and explored their values in the prediction of gastric precancerous lesions.

The community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causes severe pandemics primarily consisting of skin and soft tissue infections. However, the underlying pathomechanisms of the bacterium are yet to fully understood. The present study identifies LcpB protein, which belongs to the LytR-A-Psr (LCP) family, is crucial for cell wall synthesis and virulence in S. aureus. The findings revealed that LcpB is a pyrophosphatase responsible for wall teichoic acid synthesis. The results also showed that LcpB regulates enzyme activity through specific key arginine sites in its LCP domain. Furthermore, knockout of lcpB in the CA-MRSA isolate ST59 resulted in enhanced hemolytic activity, enlarged of abscesses, and increased leukocyte infiltration. Meanwhile, we also found that LcpB regulates virulence in agr-independent manner and the key sites for pyrophosphatase of LcpB play critical roles in regulating the virulence. In addition, the results showed that the role of LcpB was different between methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA). This study therefore highlights the dual role of LcpB in cell wall synthesis and regulation of virulence. These insights on the underlying molecular mechanisms can thus guide the development of novel anti-infective strategies.

Recently network function virtualization has been proposed to execute virtual network functions (VNF) on software middle-boxes hosted on commodity servers (substrate nodes). Normally, a request needs to invoke several VNFs in a particular order. As we know, activating and running a substrate node comes at a certain energy cost, and deploying a service chain requires several open substrate nodes which lead to high energy consumption. Furthermore, the deployment of service chains also needs to consume bandwidth resource on a substrate network. After embedment of some service chains, the substrate network may consist of many links with fragmented remaining resources that are too little to be utilized by any other requests. The nodes resources than cannot be fully utilized and are expended quickly, which causes low resources utilization. Since the resources of the physical network are limited, due to their faster consumption, the acceptance ratio remains very low. In this paper, we aim to investigate the problem of high energy consumption, low resources utilization and low acceptance ratio in embedment concurrently. To tackle this problem, we consider deploying service chains on splitted paths to utilize the fragmented resources and minimize the number of open nodes to save the energy consumption. To minimize the number of open nodes, we first formulate the embedment of a service chain as a mixed integer linear program with binary constraints on nodes and continuous constraints on flows. For the purpose of supporting an operation of max-cut that support splitted paths, we consider constructing a network flow model by setting the cost weight based on the state of the nodes. Then, we devise service chains constrained Min-Cost Flow (SC-MCF) Algorithm to find an optimal splitted path with minimal cost weight. Finally, we conduct extensive experiments based on two real topologies EasyNet and GrNet. The experiments show that our proposed SC-MCF Algorithm decreases the number of open nodes and increases the acceptance ratio while saving the resources in the long run.

With the treatment failure by vancomycin and poor clinical outcomes, the emergence and spread of vancomycin intermediate-resistant Staphylococcus aureus (VISA) has raised more concerns in recent years. While most VISA strains are isolated from methicillin-resistant S. aureus (MRSA), the mechanism underlying the generation of VISA from methicillin-susceptible S. aureus (MSSA) is still largely unknown. Here, we identified a total of 10 mutations in 9 genes through comparative genome analysis from laboratory-derived VISA strain. We verified the role of a novel mutation of WalK (I237T) and our results further indicated that the introduction of WalK (I237T) by allelic replacement can confer vancomycin resistance in MSSA with common VISA characteristics, including thickened cell walls, reduced autolysis, and attenuated virulence. Consistent with these phenotypes, real-time quantitative reverse transcription-PCR revealed the altered expression of several genes associated with cell wall metabolism and virulence control. In addition, electrophoretic mobility shift assay indicated that WalR can directly bind to the promoter regions of oatA, sle1, and mgt, fluorescence-based promoter activity and β-galactosidase assays revealed WalK (I237T) can alter promoter activities of oatA, mgt, and sle1, thus regulating genes expression. These findings broaden our understanding of the regulatory network by WalKR system and decipher the molecular mechanisms of developmental VISA resistance in MSSA with point mutations.

Staphylococcus aureus is a gram-positive pathogenic bacterium and is capable of secreting numerous toxins interfering directly with the host to cause acute infections. Rbf, a transcriptional regulator of AraC/XylS family, has been reported to promote biofilm formation in polysaccharide intercellular adhesion (PIA) mediated manner to cause chronic infections. In this study, we revealed the new virulence-mediated role of Rbf that can negatively regulate the hemolytic activity. Furthermore, Rbf can specifically bind to the hla and psmα promoters to repress their expression, resulting in significantly decreased production of phenol-soluble modulins α (PSMα) and alpha-toxin. Accordingly, the rbf mutant strain exhibited the increased pathogenicity compared to the wild-type (WT) strain in a mouse subcutaneous abscess model, representing a type of acute infection by S. aureus. Collectively, our results provide a novel insight into the virulence regulation and acute infections mediated by Rbf in S. aureus.

A plethora of toxin-antitoxin systems exist in bacteria and has multilateral roles in bacterial pathogenesis and virulence. Toxin-antitoxin systems have been involved in persister cell formation in Escherichia coli and Mycobacterium but have not been reported to be associated with Staphylococcus aureus persistence. Persistence is the ability of bacterial cells to tolerate unfavorable conditions and multiple stresses. There are less known and more unknown factors that either alleviate or aggravate bacterial persistence phenomenon. For the first time, we reported a new chromosomally encoded tripartite toxin-antitoxin system and its role in S. aureus persister cell formation. The toxin gene is bacteriostatic in action and counterbalanced by antitoxin RNA that could basepair with the toxin mRNA and formed a duplex. The transcriptional regulator positively regulates the toxin expression under certain stress conditions. The toxin ectopic induction increased S. aureus susceptibility to norfloxacin, ciprofloxacin, and ofloxacin. Whole-genome RNA sequencing revealed that MDR efflux pump norA is significantly down-regulated by toxin ectopic induction. The deletion of norA from S. aureus genome reduced resistance toward ciprofloxacin, norfloxacin, and ofloxacin, as well as resulted in a decrease in minimal inhibitory concentration while complementation of norA successfully restored the phenotypes. The persistence assay of the norA mutant revealed that deletion of norA increased persister cell survival in S. aureus. Altogether, we have provided insight into the first tripartite type-I TA system and revealed the role of MDR NorA in the persister cell formation of S. aureus.

Solar-driven electrochromic smart windows with energy-storage ability are promising for energy-saving buildings. In this work, a flexible photoelectrochromic device (PECD) was designed for this purpose. The PECD is composed of two flexible transparent conductive layers, a photocatalytic layer, an electrochromic material layer, and a transparent electrolyte layer. The photocatalytic layer is a dye-sensitized TiO2 thick film and the electrochromic layer is a WO3 thin film, which also possesses a supercapacitive property. Under illumination, dye-sensitized TiO2 thick film realizes photo-drive electrochromism that the WO3 changes from colorless to blue with large optical modulation. Meanwhile, the PECD has an electrochemical supercapacitance showing an energy storage property of 21 mF·cm−2 (114.9 F·g−1 vs the mass of WO3), stable mechanical performance and long cycle performance. The PECD can effectively adjust the transmittance of visible and near-infrared light without any external power supply, realizing zero energy consumption, and can convert solar energy into electrical energy for storage.

ABSTRACT CRISPR-Cas (clustered regularly interspaced short palindromic repeat [CRISPR]-CRISPR-associated protein [Cas]) systems can provide protection against invading genetic elements by using CRISPR RNAs (crRNAs) as a guide to locate and degrade the target DNA. CRISPR-Cas systems have been classified into two classes and five types according to the content of cas genes. Previous studies have indicated that CRISPR-Cas systems can avoid viral infection and block plasmid transfer. Here we show that chromosomal targeting by the Staphylococcus aureus type III-A CRISPR-Cas system can drive large-scale genome deletion and alteration within integrated staphylococcal cassette chromosome mec (SCCmec). The targeting activity of the CRISPR-Cas system is associated with the complementarity between crRNAs and protospacers, and 10- to 13-nucleotide truncations of spacers partially block CRISPR attack and more than 13-nucleotide truncation can fully abolish targeting, suggesting that a minimal length is required to license cleavage. Avoiding base pairings in the upstream region of protospacers is also necessary for CRISPR targeting. Successive trinucleotide complementarity between the 5′ tag of crRNAs and protospacers can disrupt targeting. Our findings reveal that type III-A CRISPR-Cas systems can modulate bacterial genome stability and may serve as a high-efficiency tool for deleting resistance or virulence genes in bacteria. IMPORTANCE Staphylococcus aureus is a pathogen that can cause a wide range of infections in humans. Studies have suggested that CRISPR-Cas systems can drive the loss of integrated mobile genetic elements (MGEs) by chromosomal targeting. Here we demonstrate that CRISPR-mediated cleavage contributes to the partial deletion of integrated SCCmec in methicillin-resistant S. aureus (MRSA), which provides a strategy for the treatment of MRSA infections. The spacer within artificial CRISPR arrays should contain more than 25 nucleotides for immunity, and consecutive trinucleotide pairings between a selected target and the 5′ tag of crRNA can block targeting. These findings add to our understanding of the molecular mechanisms of the type III-A CRISPR-Cas system and provide a novel strategy for the exploitation of engineered CRISPR immunity against integrated MGEs in bacteria for clinical and industrial applications.

The trust mechanism and trust model of mobile banking is especially urgent because of its high cognitive risk and poor experience. This article studies several key factors that affect the trust mechanism of mobile banking, such as structure assurance, ubiquity, information quality, initial trust, perceived ease of use and experience. The results show that structure assurance is a most important factor influencing trust tendencies, and ubiquity, information quality, perceived satisfaction and perceived ease of use are some other key factors that affect initial trust and experience. The initial trust directly affects the users' sense of experience of mobile banking and decides the tendency of trust, which affects the actual use. Therefore, the mobile phone banks need to pay more attention to the initial sense of trust and experience to promote user acceptance and trust mobile banking services.

Staphylococcus aureus is a nosocomial pathogen that can cause chronic to persistent infections. Among different mediators of pathogenesis, toxin-antitoxin (TA) systems are emerging as the most prominent. These systems are frequently studied in Escherichia coli and Mycobacterial species but rarely explored in S. aureus. In the present study, we thoroughly analyzed the S. aureus genome and screened all possible TA systems using the Rasta bacteria and toxin-antitoxin database. We further searched E. coli and Mycobacterial TA homologs and selected 67 TA loci as putative TA systems in S. aureus. The host inhibition of growth (HigBA) TA family was predominantly detected in S. aureus. In addition, we detected seven pathogenicity islands in the S. aureus genome that are enriched with virulence genes and contain 26 out of 67 TA systems. We ectopically expressed multiple TA genes in E. coli and S. aureus that exhibited bacteriostatic and bactericidal effects on cell growth. The type I Fst toxin created holes in the cell wall while the TxpA toxin reduced cell size and induced cell wall septation. Besides, we identified a new TA system whose antitoxin functions as a transcriptional autoregulator while the toxin functions as an inhibitor of autoregulation. Altogether, this study provides a plethora of new as well as previously known TA systems that will revitalize the research on S. aureus TA systems.

In this paper, we study the bandwidth reservation issue in wireless ad hoc networks with directional antennas. Providing Quality of Service (QoS) support in the wireless ad hoc networks is one of the topics that have received a lot of attention in recent years. QoS provisioning is needed to support multimedia and real-time application in wireless networks. In the Time Division Multiple Accesses (TDMA) frame, the bandwidth is measured by the number of the data time slots. Control slots in the traditional TDMA frame can be used for transmission of the control packets, rather than the transmission of the data packets. We focus on the problem of how to make full use of slots to transmit data packets and do not affect control packets transmission. The purpose is to improve the time slot utilization rate. Based on our proposed modified TDMA frame, a novel time slot reservation algorithm is presented to achieve maximal available path bandwidth. Directional antennas allow transmission energy to be concentrated on a narrow range along a particular direction, which can significantly increase the data rate. The performance of our scheme is analyzed and implemented. Simulation results show that the proposed scheme performs better.

The prophage is one of the most important components of variable regions in bacterial genomes. Some prophages carry additional genes that may enhance the toxicity and survival ability of their host bacteria. This phenomenon is predominant in Staphylococcus aureus, a very common human pathogen. Bioinformatics analysis of several staphylococcal prophages revealed a highly conserved 40-bp untranslated region upstream of the int gene. A small transcript encoding phage integrase was identified to be initiated from the region, demonstrating that the untranslated region contained a promoter for int. No typical recognition sequence for either sigma(A) or sigma(B) was identified in the 40-bp region. Experiments both in vitro and in vivo demonstrated that sigma(H) recognized the promoter and directed transcription. Genetic deletion of sigH altered the int expression, and subsequently, the excision proportion of prophage DNAs. Phage assays further showed that sigH affected the ability of spontaneous lysis and lysogenization in S. aureus, suggesting that sigH plays a role in stabilizing the lysogenic state. These findings revealed a novel mechanism of prophage integration specifically regulated by a host-source alternative sigma factor. This mechanism suggests a co-evolution strategy of staphylococcal prophages and their host bacteria.

Klebsiella pneumoniae is an opportunistic pathogen that mainly causes nosocomial infections and hospital-associated pneumonia in elderly and immunocompromised people. However, multidrug-resistant hypervirulent K. pneumoniae (MDR-hvKp) has emerged recently as a serious threat to global health that can infect both immunocompromised and healthy individuals. It is scientifically established that plasmid-mediated regulator of mucoid phenotype genes (rmpA and rmpA2) and other virulence factors (aerobactin and salmochelin) are mainly responsible for this phenotype. In this study, we collected 23 MDR-hvKp isolates and performed molecular typing, whole genome sequencing, comparative genomic analysis, and phenotypic experiments, including the Galleria mellonella infection model, to reveal its genetic and phenotypic features. Meanwhile, we discovered two MDR-hvKp isolates (22122315 and 22091569) that showed a wide range of hypervirulence and hypermucoviscosity without rmpA and rmpA2 and any virulence factors. In phenotypic experiments, isolate 22122315 showed the highest hypervirulence (infection model) with significant mucoviscosity, and conversely, isolate 22091569 exhibited the highest mucoviscosity (string test) with higher virulence compared to control. These two isolates carried carbapenemase (blaKPC − 2), β-lactamase (blaOXA − 1, blaTEM − 1B), extended-spectrum β-lactamase (ESBL) genes (blaCTX − M − 15, blaSHV − 106), outer membrane protein-coding genes (ompA), fimbriae encoding genes (ecpABCDER), and enterobactin coding genes (entAB, fepC). In addition, single nucleotide polymorphism analysis indicated that both isolates, 22122315 and 22091569, were found to have novel mutations in loci FEBNDAKP_03184 (c. 2084A > C, p. Asn695Thr), and EOFMAFIB_02276 (c. 1930C > A, p. Pro644Thr), respectively. Finally, NCBI blast analysis suggested these mutations are located in the wzc of the capsule polysaccharide (cps) region and are responsible for putative tyrosine kinase. This study would be a strong reference for enhancing the current understanding of identifying the MDR-hvKp isolates that lacked both mucoid regulators and virulence factors. [ABSTRACT FROM AUTHOR]