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Objectives We sought to analyze the antimicrobial resistance trends of Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) isolated from patients.Methods Twelve commonly used antibiotics from E. coli and K. pneumoniae isolated every year from 2016 to 2021 were analyzed to identify trends in antimicrobial resistance over time using univariate tests of trend and multivariate regression models to account for the effects of patient demographics.Results The numbers of E. coli and K. pneumoniae strains increased, while the rates of E. coli and K. pneumoniae remained stable. The number and rate of extended-spectrum beta-lactamase (ESBL)-producing E. coli and K. pneumoniae increased. Statistically significant increases in the proportions of E. coli and ESBL-producing E. coli isolates resistant to meropenem, cefepime, cefoperazone-sulbactam, piperacillin-tazobactam, cotrimoxazole, amikacin, ciprofloxacin, and fosfomycin were observed, and increases in the non-ESBL-producing E. coli resistance rates to cefepime, ceftazidime, and piperacillin-tazobactam were observed. Similarly, the proportions of K. pneumoniae and ESBL-producing K. pneumoniae resistant to imipenem, meropenem, cefoxitin, cefepime, ceftazidime, cefoperazone-sulbactam, piperacillin-tazobactam, ciprofloxacin, and fosfomycin increased during the study, while the non-ESBL-producing K. pneumoniae resistance rates to cefazolin and fosfomycin increased.Conclusions Increases in ESBL-producing E. coli and K. pneumoniae resistance to multiple classes of antimicrobials and the marked increase in carbapenem-resistant K. pneumoniae were the most remarkable changes observed from 2016 to 2021. This paper provides important information for governments and clinicians to track antimicrobial resistance and will provide insights into antimicrobial strategies.

Structure-controlled synthesis of Pd nanocrystals has received much attention recently due to their remarkable catalytic performance. To get deep insight into the mechanism of kinetically controlled overgrowth and the relationship between structure and electrocatalytic performance, palladium concave nanocubes (PdCNs) with high-index facets were synthesized through a facile none-seeded routine induced by hexadecylpyridinium bromide (CTAB). The structural changes of PdCNs along with the concentration of CTAB, reaction time and temperature were investigated by transmission electron microscopy and X-ray diffraction. It was indicated that Pd nanocubes first grew into larger size with numerous interstices inside the PdCNs, and then the inner interstices were filled along with oxidative etching on the surface. The electrocatalytic activities of PdCNs with different structures were evaluated toward the electro-oxidation of methanol. The result showed that the electrocatalytic activity weakened with the decrease in interstices, which demonstrated that interstices played a more crucial role than the concave structures.

Palladium nanoparticles with a uniform shape and specific surface structure have gained tremendous attention owing to their fascinating catalytic performance. Herein, Pd porous nanocubes (PdPNs) were successfully synthesized through a facile one-pot non-seeded routine using 1-hexadecyl-3-methyl imidazolium bromide (HMIB) as the capping agent. The as-prepared PdPNs had a cubic shape and highly porous feature with an average size of 45.4 nm. The morphology evolution along with time was investigated by transmission electron microscopy and a possible formation mechanism of PdPNs was proposed. The effects of the concentration of HMIB and temperature on the structure and electrocatalytic activity were also investigated. The PdPNs showed superior catalytic activity (jf = 13.11 mA cm−2) in methanol electro-oxidation in an alkaline medium to solid Pd nanocubes (jf = 7.25 mA cm−2) and a commercial Pd/C catalyst (jf = 0.11 mA cm−2). Meanwhile, PdPNs exhibited excellent stability, which was inferred from the current density remaining at 86.3% of the initial value after 1500 cycles.

Our previous proteomic analysis showed that small RNA SprC (one of the small pathogenicity island RNAs) ofGene expression profiles were obtained fromA total of 2497 transcripts were identified, of which 60 transcripts expressions inThis study offered valuable and reliable information about the regulatory roles of SprC in

Mixed grains are often encountered in heavy forgings. Taking 316LN austenitic stainless steel as an investigated material, two kinds of grain structures were tested for observation of microscopic deformation heterogeneity: uniform fine grains and mixed structures with millimeter-grade coarse grains (MCGs). Tensile tests, optical microscope (OM) observations, EBSD tests as well as crystal plasticity (CP) simulations were performed. Results showed that obvious slip bands were observed in the MCGs. During the deformation, the MCGs exhibited single slip bands if they were with soft orientation, and cross slip bands if they were with hard orientation. The fine grains were seen easily rotated in the deformation, forming distinguished bumpy grain boundaries, while the MCGs displayed smooth and collapsed grain morphology. The interior MCGs undertook severer deformation than the fine grains, which showed the strain partitioning ability of MCGs was limited. This deformation behavior is possible to lead the crack initiation in the interface among MCGs and surrounding fine grains.

Graphical abstract, Highlights • Pd/rGO catalysts were synthesized by a one-pot sonochemical method. • A unique coral-like porous structure of 2D Pd nanosheets was formed assisted by CTAB under ultrasonification. • A high ultrasonic power promotes the formation of porous structure. • A possible formation process of 2D nanosheets was proposed. • Pd/rGO shows favorable ORR activity and stability., Two dimensional (2D) Pd nanosheets supported on reduced graphene oxide (Pd/rGO) were prepared through a sonochemical routine induced by cetyltrimethylammonium bromide (CTAB). Coral-like porous Pd nanosheets (Pd/rGO-u) were obtained under the sonication condition (25 kHz, 600 W, ultrasonic transducer), while square Pd nanosheets (Pd/rGO-c) were produced via traditional chemical reduction. The size of Pd nanosheets of Pd/rGO-u and Pd/rGO-c are 69.7 nm and 59.7 nm, and the thickness are 4.6 nm and 4.4 nm, respectively. The carrier GO was proved to be partially reduced to rGO with good electrical conductivity and oxygen-containing groups facilitated a good dispersion of Pd nanosheets. The interaction between GO and CTAB made the alkyl chain assembles to a 2D lamella micelles which limit the growth of Pd atoms resulting in the formation of 2D nanosheets. A high ultrasonic power promotes the reduction and the formation of porous structure. Additionally, Pd/rGO-u exhibited a favorable electrocatalytic performance toward oxygen reduction reaction (ORR) in alkaline condition, which provided a potential synthetic strategy assisted by sonication for high-performance 2D materials.

Objective Goal of this work is to assess the feasibility to perform COVID-19 RNA tests within hospitals and communities experiencing SARS-CoV-2 virus outbreaks, to ultimately provide recommendations for hospitals with so-called fever clinics. In China, these specialised clinics within a hospital, specifically receive outpatients who have fever symptoms.Methods A team with expertise in the Exposure Analysis of Critical Control Points (EACCP) framework first identified potential infection routes during the testing for SARS-CoV-2, then constructed and tested flow diagrams, which were confirmed under actual conditions, demonstrating the feasibility to be carried out in hospitals with fever clinics. The team determined critical control points to mitigate the exposure risks at each control point.Findings The sampling and inactivation steps of clinical samples in fever clinics appeared to be associated with particularly high risk levels of exposure to SARS-CoV-2. Moderate levels of exposure were associated with storage and transportation of samples for inactivation; Low risk levels were associated with the transportation, storage and detection steps after inactivation.Conclusion To minimise risks of infection for personnel, optimised processes to carry out SARS-CoV-2 RNA tests in hospitals with fever clinics in China are proposed. The high risk of SARS-CoV-2 exposure during procedures preceding testing are the sampling and biological inactivation, which can be reduced by using full personal protective equipment and the use of BSL2 facilities in fever clinics or mobile BSL2 platforms. The implementation of the Exposure Analysis of Critical Control Points framework could facilitate rapid responses to outbreaks of emerging infectious diseases.

Background The data on the prevalence of resistance to mupirocin (MUP), fusidic acid (FA) and retapamulin (RET) in methicillin-resistant Staphylococcus aureus (MRSA) from China are still limited. This study aimed to examine these three antibiotics resistance in 1206 MRSA clinical isolates from Eastern China. Phenotypic MUP, FA and RET resistance was determined by minimum inhibitory concentrations (MICs), and genotypic by PCR and DNA sequencing of the mupA/B, fusB-D, cfr, vgaA/Av/ALC/B/C/E, lsaA-C/E and salA and mutations in ileS, fusA/E, rplC, and 23S RNA V domain. The genetic characteristics of resistance isolates were conducted by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Results Overall MRSA MUP, FA and RET resistance was low (5.1, 1.0 and 0.3%, respectively). MupA was the mechanism of high-level MUP resistance. All low-level MUP resistance isolates possessed an equivocal mutation N213D in IleS; of these, 2 reported an additional V588F mutation with an impact on the Rossman fold. FusA mutations, such as L461K, H457Q, H457Y and V90I were the primary FA mechanisms among high-level resistance isolates, most of which also contained fusC; however, all low-level resistance strains carried fusB. Except lsaE gene detected in one isolate, no other resistance mechanisms tested were found among RET-resistant isolates. Additionally, sixteen PFGE types (A-P) were observed, among which type B was the most common (49/76, 64.5%), followed by types E and G (4/76, 5.3% each) and types C and M (3/76, 3.9% each). All resistant strains were divided into 15 ST types by MLST. ST764 (24/76, 31.6%), ST630 (11/76, 14.5%), ST239 (9/76, 11.8%) and ST5 (7/76, 9.2%) were the major types. PFGE type B isolates with the aforementioned STs were mainly found in mupirocin resistant isolates. Conclusions MUP, FA and RET exhibited highly activity against the MRSA isolates. Acquired genes and chromosome-borne genes mutations were responsible for MUP and FA resistance; however, the mechanism for some RET-resistant isolates remains to be further elucidated. Also, the surveillance to MUP in MRSA should be strengthened to prevent elevated resistance due to the expansion of clones.

BACKGROUND: It has been reported that infectious agents contribute to the atherosclerotic process. However, it is unclear whether Staphylococcus aureus superantigen (SAg) toxic shock syndrome toxin-1 (TSST-1) has an effect on atherosclerosis progression. The present study was designed to investigate the pathogenic role of TSST-1 exposure in the atherosclerotic process in rabbits. METHODS: New Zealand White rabbits were exposed to TSST-1 through Alzet miniosmotic pumps with a constant pumping rate. Aortic atherosclerosis was evaluated by histological and morphometric methods. Using a biochemical analyzer/enzyme-linked immunosorbent assay/immunostaining, we further analyzed various atherosclerosis-related factors. RESULTS: The gross atherosclerotic lesion area in the aortic arch increased by 15.3% in high-fat-diet rabbits exposed to TSST-1 compared to that in the control group. In the atherosclerotic lesions, TSST-1 exposure increased the content of smooth muscle cells. Moreover, TSST-1 treatment up-regulated serum tumor necrosis factor alpha (TNF-α) level, but did not affect serum lipids (except for triglycerides) and endotoxin in the rabbits. CONCLUSIONS: Our data validated that chronic stimulation with TSST-1 facilitates the progression of atherosclerosis in rabbits independently of endotoxins, indicating that S. aureus and its SAgs may be targets to prevent and treat atherosclerosis.

Network trace signature matching is one reliable approach to detect active Remote Control Trojan, (RAT). Compared to statistical-based detection of malicious network traces in the face of known RATs, the signature-based method can achieve more stable performance and thus more reliability. However, with the development of encrypted technologies and disguise tricks, current methods suffer inaccurate signature descriptions and inflexible matching mechanisms. In this paper, we propose to tackle above problems by presenting MBTree, an approach to detect encryption RATs Command and Control (C&C) communication based on host-level network trace behavior. MBTree first models the RAT network behaviors as the malicious set by automatically building the multiple level tree, MLTree from distinctive network traces of each sample. Then, MBTree employs a detection algorithm to detect malicious network traces that are similar to any MLTrees in the malicious set. To illustrate the effectiveness of our proposed method, we adopt theoretical analysis of MBTree from the probability perspective. In addition, we have implemented MBTree to evaluate it on five datasets which are reorganized in a sophisticated manner for comprehensive assessment. The experimental results demonstrate the accurate and robust of MBTree, especially in the face of new emerging benign applications., Accepted in IEEE Transactions on Information Forensics and Security (TIFS)

The appearance and growth of social networking brings an exponential growth of information. One of the main solutions proposed for this information overload problem are recommender systems, which provide personalized results. Most existing social recommendation approaches consider relation information to improve recommendation performance in the static context. However, relations are likely to evolve over time in the dynamic network. Therefore, temporal information is an essential ingredient to making social recommendation. In this paper, we propose a novel social recommendation model based on evolving relation network, named SoERec. The learned evolving relation network is a heterogeneous information network, where the strength of relation between users is a sum of the influence of all historical events. We incorporate temporally evolving relations into the recommendation algorithm. We empirically evaluate the proposed method on two widely-used datasets. Experimental results show that the proposed model outperforms the state-of-the-art social recommendation methods.

We have entered the post-antibiotic era. Phage therapy has recently been given renewed attention because bacteriophages are easily available and can kill bacteria. Many reports have demonstrated successful phage treatment of bacterial infection, whereas some studies have shown that phage therapy is not as effective as expected. In general, establishment of a standard operating procedure will ensure the success of phage therapy. In this paper, the whole operating procedure for phage therapy in clinical practice is explored and analyzed to comprehensively understand the success of using phage for the treatment of bacterial infectious disease in the future. The procedure includes the following: enrollment of patients for phage therapy; establishment of phage libraries; pathogenic bacterial isolation and identification; screening for effective phages against pathogenic bacteria; phage formulation preparation; phage preparation administration strategy and route; monitoring the efficacy of phage therapy; and detection of the emergence of phage-resistant strains. Finally, we outline the whole standard operating procedure for phage therapy in clinical practice. It is believed that phage therapy will be used successfully, especially in personalized medicine for the treatment of bacterial infectious diseases. Hopefully, this procedure will provide support for the entry of phage therapy into the clinic as soon as possible.

Mention as a key feature on social networks can break through the effect of structural trapping and expand the visibility of a message. Although existing works usually use rank learning as implementation strategy before performing mention recommendation, these approaches may interfere with the influening factor exploration and cause some biases. In this paper, we propose a novel Context-aware Mention recommendation model based on Probabilistic Matrix Factorization (CMPMF). This model considers four important mention contextual factors including topic relevance, mention affinity, user profile similarity and message semantic similarity to measure the relevance score from users and messages dimensions. We fuse these mention contextual factors in latent spaces into the framework of probabilistic matrix factorization to improve the performance of mention recommendation. Through evaluation on a real-world dataset from Weibo, the empirically study demonstrates the effectiveness of discovered mention contextual factors. We also observe that topic relevance and mention affinity play a much significant role in the mention recommendation task. The results demonstrate our proposed method outperforms the state-of-the-art algorithms.

Staphylococcus aureus is the main pathogen that causes skin and skin structure infections and is able to survive and persist in keratinocytes of the epidermis. Since the evolution of multidrug-resistant bacteria, the use of phages and their lysins has presented a promising alternative approach to treatment. In this study, a cell wall hydrolase (also called lysin) derived from Staphylococcus phage JD007 (JDlys) was identified. JDlys showed strong lytic activity against methicillin-resistant Staphylococcus aureus (MRSA) strains from different sources and of different multilocus sequence typing (MLST) types. Furthermore, a fusion protein consisting of a cell-penetrating peptide derived from the trans -activating transcription (Tat) factor fused to JDlys (CPP Tat -JDlys) was used to kill MRSA bacteria causing intracellular infections. CPP Tat -JDlys, in which the fusion of CPP Tat to JDlys had almost no effect on the bacteriolytic activity of JDlys, was able to effectively eliminate intracellular MRSA bacteria and alleviate the inflammatory response and cell damage caused by MRSA. Specifically, CPP Tat -JDlys was able to combat MRSA-induced murine skin infections and, consequently, expedite the healing of cutaneous abscesses. These data suggest that the novel antimicrobial CPP-JDlys may be a worthwhile candidate as a treatment for skin and skin structure infections caused by MRSA. IMPORTANCE S. aureus is the main cause of skin and skin structure infections due to its ability to invade and survive in the epithelial barrier. Due to the overuse of antibiotics in humans and animals, S. aureus has shown a high capacity for acquiring and accumulating mechanisms of resistance to antibiotics. Moreover, most antibiotics are usually limited in their ability to overcome the intracellular persistence of bacteria causing skin and skin structure infections. So, it is critical to seek a novel antimicrobial agent to eradicate intracellular S. aureus . In this study, a cell-penetrating peptide fused to lysin (CPP-JDlys) was engineered. Our results show that CPP-JDlys can enter keratinocytes and effectively eliminate intracellular MRSA. Meanwhile, experiments with mice revealed that CPP-JDlys efficiently inhibits the proliferation of MRSA in murine skin and thus shortens the course of wound healing. Our results indicate that the CPP-fused lysin has potential for use for the treatment of skin infections caused by MRSA.

Mast cells and basophils are effector cells in the pathophysiology of allergic diseases. Targeted elimination of these cells may be a promising strategy for the treatment of allergic disorders. Our present study aims at targeted delivery of anti-FceRIα Fab-conjugated celastrol-loaded micelles toward FceRIα receptors expressed on mast cells and basophils to have enhanced anti-allergic effect. To achieve this aim, we prepared celastrol-loaded (PEO-block-PPO-block-PEO, Pluronic) polymeric nanomicelles using thin-film hydration method. The anti-FceRIα Fab Fragment was then conjugated to carboxyl groups on drug-loaded micelles via EDC amidation reaction. The anti-FceRIα Fab-conjugated celastrol-loaded micelles revealed uniform particle size (93.43 ± 12.93 nm) with high loading percentage (21.2 ± 1.5% w/w). The image of micelles showed oval and rod like. The anti-FceRIα Fab-conjugated micelles demonstrated enhanced cellular uptake and cytotoxity toward target KU812 cells than non-conjugated micelles in vitro. Furthermore, diffusion of the drug into the cells allowed an efficient induction of cell apoptosis. In mouse model of allergic asthma, treatment with anti-FceRIα Fab-conjugated micelles increased lung accumulation of micelles, and significantly reduced OVA-sIgE, histamine and Th2 cytokines (IL-4, IL-5, TNF-α) levels, eosinophils infiltration and mucus production. In addition, in mouse model of passive cutaneous anaphylaxis, anti-FceRIα Fab-conjugated celastrol-loaded micelles treatment significantly decreased extravasated evan's in the ear. These results indicate that anti-FceRIα Fab-conjugated celastrol-loaded micelles can target and selectively kill mast cells and basophils which express FceRIα, and may be efficient reagents for the treatment of allergic disorders and mast cell related diseases.

The objective of the study was to analyze the treatment outcomes for staghorn stones in patients with solitary kidney using either the single-tract or the multi-tract minimally invasive percutaneous nephrolithotomy (MPCNL). We retrospectively reviewed 105 patients who underwent MPCNL for staghorn calculi in solitary kidney from 2012 to 2014. The patients who underwent the single-tract approach (71 patients) were assigned to Group 1. The 34 patients who underwent the multi-tract approach (34 patients) were assigned to Group 2. We recorded and compared the patient's demographics, intraoperative parameters, and post-operative outcomes. We also analyzed any complications as a result of the particular procedure, as well as any resulting stone-free rates (SFRs). The mean number of access tracts was 2.38 ± 0.70 (range 2-4) for Group 2. The mean operative time was longer for Group 2, p = 0.01. The initial SFR was 52.1% for Group 1 and 47.1% for Group 2 after the one-session procedure, p = 0.63.The final SFR improved to 83.1 and 79.4% for both groups following auxiliary treatment, p = 0.65. The mean hemoglobin drop was higher in Group 2 as compared to Group 1, p < 0.01. There was no significant difference in the change of mean serum creatinine in either group. There were fewer overall complications in Group 1 than in Group 2 (23.9 vs. 44.1%). Almost half of the patients who underwent multi-tract MPCNL required an additional procedure to achieve satisfactory stone clearance. The results showed that single-tract MPCNL might be a better treatment option for staghorn stones in a solitary kidney with the same therapeutic outcome, but with less complications.

Aim: To explore the complete gene networks regulated by small RNA SprC and its targets in Staphylococcus aureus. Materials & methods: The isobaric tags for relative and absolute quantitation and bioinformatic methods were utilized to identify and analyze the target proteins affected by SprC in S. aureus N315. Results: Proteomic analysis showed that the expression of 44 proteins was modulated by SprC. Further, bioinformatic analysis displayed that these affected proteins mainly associated with metabolic and cellular process, biological regulation and catalytic activity. Conclusion: Our data provide a rich resource of SprC targets in S. aureus, although the mechanism of regulation by SprC is yet to be elucidated.

Objectives To investigate the prevalence and associated factors of kidney stones among adults in China. Subjects and methods A nationwide cross-sectional survey was conducted among persons aged 18 and older across China from May 2013 to July 2014. Participants underwent urinary tract ultrasonographic examinations, questionnaires, and provided blood and urine samples to analyze. Kidney stones were defined as particles in size of 4 mm or greater. Prevalence was defined as the proportion of participants with kidney stone and binary logistic regression was used to estimate the associated factors. Results A total of 12570 individuals (45.2% men) with an average age of 48.8±15.3 (18-96) years were selected and invited to participate in the study. And 9310 (40.7% men) individuals completed the investigation, with a response rate of 74.1%. The prevalence of kidney stones was 6.4% (95% confidence interval (CI):5.9, 6.9), and the age- and sex-adjusted prevalence was 5.8% (95% CI: 5.3, 6.3; 6.5% in men and 5.1% in women). Binary logistic regression analysis showed that male, rural residents, age, family history of urinary stones, concurrent with diabetes mellitus and hyperuricemia, increased consumption of meat, and excessive sweating were all statistical significantly associated with increased risk of kidney stones. By contrast, consumed more tea, legume, and fermented vinegar were statistical significantly associated with decreased risk of kidney stones formation Conclusion Kidney stones are common disease among Chinese adults and about one in seventeen adults are affected currently. Some Chinese dietary habits may lower risk of kidney stones formation. This article is protected by copyright. All rights reserved.

Staphylococcus phages of the Myoviridae family have a wide host range and potential applications in phage therapy. In this report, safety assessments of these phages were conducted based on their complete genome sequences. The complete genomes of Staphylococcus phages of the Myoviridae family were analyzed, and the Open Reading Frame (ORFs) were compared with a pool of virulence and antibiotic resistance genes using the BLAST algorithm. In addition, the lifestyle of the phages (virulent or temperate) was also confirmed using PHACTS. The results showed that all phages were lytic and did not contain resistance or virulence genes based on bioinformatic analyses, excluding the possibility that they could be vectors for the dissemination of these undesirable genes. These findings suggest that the phages are safe at the genome level. The SceD-like transglycosylase, which is a biomarker for vancomycin-intermediate strains, was widely distributed in the phage genomes. Approximately 70% of the ORFs encoded in the phage genomes have unknown functions; therefore, their roles in the antibiotic resistance and virulence of Staphylococcus aureus are still unknown and require consideration before use in phage therapy.

The ultrafine Pd nanoparticles (PdNPs) supported on N-doped partially reduced graphene oxide (Pd/PNGO) were in-situ synthesized by nitrogen glow discharge plasma using a one-step method without any protective agents and chemical reducing agents. The N-doping and reduction of graphene oxide occurred simultaneously as the reduction of Pd2+. The as-prepared Pd/PNGO was characterized by XRD, TEM, FT-IR, Raman spectra and XPS analysis. The particle size of PdNPs distributes in the range of 1.03–3.46 nm with average size of 2.51 nm. The ultrafine PdNPs are highly dispersed on PNGO with less agglomeration due to the in-situ reduction. The interaction between PdNPs and N/O functional groups on N-doped partially reduced graphene oxide (PNGO) plays a crucial role on particle size and dispersion. The catalyst performed excellent catalytic property for reduction of 4-nitrophenol (4-NP) at room temperature. The turnover frequency (TOF) is 366.9 h−1, which is 35 times than that of commercial Pd/C catalyst.

The virulence-attenuated Leptospira interrogans serovar Lai strain IPAV was derived by prolonged laboratory passage from a highly virulent ancestral strain isolated in China. We studied the genetic variations of IPAV that render it avirulent via comparative analysis against the pathogenic L. interrogans serovar Lai strain 56601. The complete genome sequence of the IPAV strain was determined and used to compare with, and then rectify and reannotate the genome sequence of strain 56601. Aside from their highly similar genomic structure and gene order, a total of 33 insertions, 53 deletions and 301 single-nucleotide variations (SNVs) were detected throughout the genome of IPAV directly affecting 101 genes, either in their 5′ upstream region or within their coding region. Among them, the majority of the 44 functional genes are involved in signal transduction, stress response, transmembrane transport and nitrogen metabolism. Comparative proteomic analysis based on quantitative liquid chromatography (LC)-MS/MS data revealed that among 1 627 selected pairs of orthologs, 174 genes in the IPAV strain were upregulated, with enrichment mainly in classes of energy production and lipid metabolism. In contrast, 228 genes in strain 56601 were upregulated, with the majority enriched in the categories of protein translation and DNA replication/repair. The combination of genomic and proteomic approaches illustrated that altered expression or mutations in critical genes, such as those encoding a Ser/Thr kinase, carbon-starvation protein CstA, glutamine synthetase, GTP-binding protein BipA, ribonucleotide-diphosphate reductase and phosphate transporter, and alterations in the translational profile of lipoproteins or outer membrane proteins are likely to account for the virulence attenuation in strain IPAV.

Sputum is the most common sample collected from patients suffering from lower respiratory tract infections and it is crucial for the bacterial identification of these infections. In this study, we enrolled 101 sputum samples from 101 patients with lower respiratory tract infections. Initially, pyrosequencing of the 16S rDNA V3 hypervariable regions of the bacteria contained in the sputum was utilized as a culture-independent approach for microbiota analysis. For comparison, clinical laboratory tests using a culture-dependent automated bacterial identification system for the same cohort of sputum samples were also done. By pyrosequencing, >70,000 DNA fragments were found and classified into 129 bacterial genera after being analyzed by the Ribosomal Database Project (RDP) process. Most sequences belonged to several predominant genera, such as Streptococcus and Staphylococcus, indicating that these genera play an important role in lower respiratory tract infections. In addition, some sequences belonging to potential causative agents, such as Mycoplasma, Haemophilus, and Moraxella, were also found, but these sequences were not found by clinical laboratory tests. For the nine genera detected by both methods, the methods’ sensitivities were compared and the results showed that pyrosequencing was more sensitive, except for Klebsiella and Mycobacterium. Significantly, this method revealed much more complicated bacterial communities and it showed a promising ability for the detection of bacteria.

Mast cells and basophils are effector cells in the pathophysiology of allergic diseases. Targeted elimination of these cells may be a promising strategy for the treatment of allergic disorders. Our present study aims at targeted delivery of anti-FcεRIα Fab-conjugated celastrol-loaded micelles toward FcεRIα receptors expressed on mast cells and basophils to have enhanced anti-allergic effect. To achieve this aim, we prepared celastrol-loaded (PEO-block-PPO-block-PEO, Pluronic) polymeric nanomicelles using thin-film hydration method. The anti-FcεRIα Fab Fragment was then conjugated to carboxyl groups on drug-loaded micelles via EDC amidation reaction. The anti-FcεRIα Fab-conjugated celastrol-loaded micelles revealed uniform particle size (93.43 ± 12.93 nm) with high loading percentage (21.2 ± 1.5% w/w). The image of micelles showed oval and rod like. The anti-FcεRIα Fab-conjugated micelles demonstrated enhanced cellular uptake and cytotoxity toward target KU812 cells than non-conjugated micelles in vitro. Furthermore, diffusion of the drug into the cells allowed an efficient induction of cell apoptosis. In mouse model of allergic asthma, treatment with anti-FcεRIα Fab-conjugated micelles increased lung accumulation of micelles, and significantly reduced OVA-sIgE, histamine and Th2 cytokines (IL-4, IL-5, TNF-α) levels, eosinophils infiltration and mucus production. In addition, in mouse model of passive cutaneous anaphylaxis, anti-FcεRIα Fab-conjugated celastrol-loaded micelles treatment significantly decreased extravasated evan's in the ear. These results indicate that anti-FcεRIα Fab-conjugated celastrol-loaded micelles can target and selectively kill mast cells and basophils which express FcεRIα, and may be efficient reagents for the treatment of allergic disorders and mast cell related diseases.

Palladium nanocrystals with a variety of shapes have received particular interest in recent years due to their unique properties in catalysis. Herein, Pd concave nanocubes with high-index facets (Pd-CNs) was synthesized by a simple water-based route without seeds using L-ascorbic acid (AA) as the reduction agent in the presence of CTAB. X-ray diffraction and transmission electron microscopy were employed to demonstrate the formation of concave structures with high-index facets of the Pd-CNs with an average size of 17.5 nm. The as-prepared Pd-CNs presented significantly higher catalytic activity than commercial Pd/C (an average particle size of 4.7 nm) in the electro-oxidation of methanol, but exhibited weaker property in Suzuki coupling reaction, which provided an evidence for the effect of shape and size on different reactions.

Pulmonary tuberculosis (TB) has gained attention in recent decades because of its rising incidence trend; simultaneously, increasing numbers of studies have identified the relationship between microbiota and chronic infectious diseases. In our work, we enrolled 32 patients with primary TB characterised by unilateral TB lesion formation diagnosed by chest radiographic exam. Bronchoalveolar lavage fluid was taken from both lungs. Twenty-four healthy people were chosen as controls. Pyrosequencing was performed on the V3 hypervariable region of 16S rDNA in all bacterial samples and used as a culture-independent method to describe the phylogenetic composition of the microbiota. Through pyrosequencing, 271,764 amplicons were detected in samples and analysed using tools in the Ribosomal Database Project (RDP) and bioinformatics. These analyses revealed significant differences in the microbiota in the lower respiratory tract (LRT) of TB patients compared with healthy controls; in contrast, the microbiota of intra/extra-TB lesions were similar. These results showed that the dominant bacterial genus in the LRT of TB patients was Cupriavidus and not Streptococcus, which resulted in a significant change in the microbiota in TB patients. The abundance of Mycobacteria and Porphyromonas significantly increased inside TB lesions when compared with non-lesion-containing contralateral lungs. From these data, it can be concluded that Cupriavidus plays an important role in TB’s secondary infection and that in addition to Mycobacteria, Porphyromonas may also be a co-factor in lesion formation. The mechanisms underlying this connection warrant further research.

Pathogenic Leptospira spp. causes leptospirosis in China and throughout the world. Here, we have sequenced two L . interrogans moderately virulent vaccine strains JDL03 (serovar Canicola) and JDL10 (serovar Hebdomadis) used in China. We selected a subproteomic approach to identify surface-exposed proteins including OMPs and extracellular proteins of these two strains plus a highly virulent vaccine strain 56601 (serovar Lai). Comparative surface-exposed proteome among the three strains indicated 81 cores, 61 dispensable and 122 unique surface-exposed proteins. Finally, the 10 highly conserved surface-exposed or subsurface proteins included two known cross-reactive antigens (LipL32 and LA_3469) and another two novel antigens (LA_0136 and LA_0505) displaying conserved immunoreactivity among 15 Chinese epidemic serovars. Furthermore, many potential virulence factors were detected in these identified surface-exposed proteins, such as Loa22, LipL32, LenC, LenF and OmpL37. Interestingly, LipL45, ClpA and ClpB, exhibiting obvious amino acid mutations among str .56601, str .JDL03 and JDL10, might contribute to virulence differences observed among these strains. Additionally, specific surface-exposed proteins in virulent str .56601 were considered to be key virulence determinants, such as Zn-dependent protease, cholesterol oxidase precursor, and so on. In all, we had relatively complete surface-exposed subproteomes of L . interrogans , which will enhance our understanding of leptospiral pathogenesis and key virulence determinants. Biological significance The present work demonstrates the use of genomic sequencing and subproteomic studies for the identification of potential vaccine and diagnostic antigen candidates against leptospirosis. The data show the conserved surface-exposed proteins to be novel potentially vaccine/diagnostic candidates. Furthermore, the data also show that LipL45, ClpA, ClpB and a lipoprotein from these three strains plus another highly virulent strain Fiocruz L1-130 contain specific amino acid mutations in strains JDL03 and JDL10. The surface-exposed subproteome of pathogenic L . interrogans could provide valuable information to gain a more complete understanding of leptospiral pathogenesis and virulence determinants.