Search

Metagenomic next-generation sequencing (mNGS) is an effective method for detecting pathogenic pathogens of bloodstream infection (BSI). However, there is no consensus on whether the use of antibiotics affects the diagnostic performance of mNGS. We conducted a prospective clinical study aiming to evaluate the effect of antimicrobial treatment on mNGS. Blood samples were collected for mNGS testing within 24 h of culture-confirmed with BSI, with re-examination conducted every 2–3 days. A total of 38 patients with BSI were enrolled. The mNGS positive (mNGS-pos) rate declined sharply after the use of antibiotics, with only 17 (44.78%) patients remaining mNGS-pos while the rest were mNGS negative (mNGS-neg). The median duration of pathogen identification was significantly longer for mNGS compared to blood culture (BC) (4 days vs 1 days; P < 0.0001). A positivity duration of ≥ 3 days was an independent risk factor of septic shock (OR, 20.671; 95% CI, 1.958–218.190; P = 0.012). Patients with mNGS-pos and mNGS-neg differed by the median duration of fever (6 days vs 3 days; P = 0.038), rates of drug resistance (35.3% vs 4.8%; P = 0.017), rates of septic shock (47.1% vs 14.3%; P = 0.029), and 28-day mortality (29.4% vs 4.8%; P = 0.041). The antimicrobial treatment will greatly reduce the positive rate of mNGS. The duration of mNGS is significantly longer than that of BC. The prolonged duration of mNGS suggests an increased risk of septic shock and could be identified as a high-risk factor of adverse infection outcome, requiring more aggressive anti-infective treatment measures. [Display omitted] • Antibiotic use reduces the detection rate of mNGS for bloodstream infections. • mNGS is superior to blood culture in detecting pathogens after antibiotic treatment. • The duration of mNGS positivity is linked to septic shock and adverse infection outcomes. • Persistent mNGS positivity may indicate antimicrobial resistance and therapy failure. [ABSTRACT FROM AUTHOR]

[Display omitted] • {[Bi 6 O 3 (tza) 5 (NO 3) 2 (OH) 5 ]·H 2 O} n (Bi-MOF) can be synthesized gently and efficiently. • Bi-MOF has good thermal stability and mechanical insensitivity. • Copper-iron hetero-metallic compound (CuFe-MOF) has good mechanical insensitivity. • Bi-MOF and CuFe-MOF synergistically catalyze thermal decomposition of RDX and HMX. • Bi-MOF and CuFe-MOF synergistically enhance propellants' combustion performance. This study explores the potential of energetic metal–organic frameworks (E-MOFs) to enhance the combustion performance of solid propellants. A {[Bi 6 O 3 (tza) 5 (NO 3) 2 (OH) 5 ]·H 2 O} n (Bi-MOF) incorporating the energetic ligand tetrazole-1-acetic acid (Htza) was synthesized and evaluated for structural characteristics and properties. The catalytic thermal decomposition of cyclotrimethylene trinitramine (RDX) and cyclotetramethylene tetranitramine (HMX) by mixed systems was investigated. These systems consisted of Bi-MOF and copper-iron hetero-metallic compound ({[CuFe 3 O(tza) 6 (H 2 O) 3 ]·Cl·(NO 3) 2 ·4H 2 O} n , CuFe-MOF), previously reported by our group in different ratios. The effect of the mixed system with the highest synergy index on the combustion performance of composite modified double-base propellant (RDX-CMDB) and nitrate ester plasticized polyether propellant (HMX-NEPE) was investigated. The impact of varying carbon black (CB) contents on the catalytic performance of the mixed system was also examined. The results showed that Bi-MOF exhibits good thermal stability (T dec = 226.9 °C) and insensitivity (IS >40 J, FS >360 J). The mixed system, comprising Bi-MOF and CuFe-MOF in a 2:1 ratio (M 2), exhibited the highest synergistic indices (3.35 and 3.24) on thermal decomposition for RDX and HMX. RDX-CMDB and HMX-NEPE propellant formulations containing M 2 and a small amount of CB exhibited significant improvements in combustion performance. RDX-CMDB propellant exhibited up to an 80.6 % increase in burning rate and up to a 59.6 % reduction in pressure index. The pressure indices of NEPE without and with aluminum were reduced from 0.65 and 0.50 to 0.38 and 0.40, respectively (10–20 MPa, 1–20 MPa). These findings highlight the promise of the mixed system, formed by Bi-MOF and CuFe-MOF, as a potential combustion catalyst for RDX-CMDB and HMX-NEPE propellants. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the performance of QuantiFERON-TB Gold Plus (QFT-Plus) on Mycobacterium tuberculosis (MTB) infection test among registered village doctors from China.Methods: MTB infection of the registered village doctors in Zhongmu County were tested using QFT-Plus and two other interferon-gamma release assays (IGRAs) in parallel: QuantiFERON-TB Gold In-Tube (QFT) and T-SPOT.TB (T-SPOT). Retests were carried out for baseline positives at 3 and 6 months later, respectively.Results: A total of 616 village doctors were included in the baseline examination. The positivity of QFT, QFT-Plus and T-SPOT was 27.91% (168/602), 31.22% (187/599) and 27.70% (169/610), respectively. The concordance between QFT and QFT-Plus was 94.81% (Kappa coefficient: 0.87) and between T-SPOT and QFT-Plus was 88.93% (Kappa coefficient: 0.73). Reversions were frequently observed for all three assays. With respect to QFT-Plus, the quantitative results of reversions in the serial testing were mostly distributed in an "uncertain range" zone (0.2-0.7 IU/mL). Similar patterns of distribution were observed for QFT and T-SPOT as well.Conclusion: Village doctors should gain more attention as an at-risk group for TB infection control in rural China. Our results support, by means of serial testing, a good agreement between QFT-Plus and QFT in Chinese population. [ABSTRACT FROM AUTHOR]

Background: Frequent reversion has been commonly observed in serial QuantiFERON-TB Gold In-Tube (QFT) tests, which limited its accuracy in defining the status of Mycobacterium tuberculosis (MTB) infection. Serum cytokine profiles might provide additional information to clarify the infection status.Method: Based on a population-based cohort study aiming to track MTB infection acquisition and disease development, serum profiles of 12 cytokines were determined by bead-based multiplex assays in parallel with QFT and tuberculin skin tests (TST) to explore potential relation between serum cytokines and MTB infection status.Results: Totally, 309 subjects got QFT conversion in one year (2013-2014) and 46.92% (145/309) of them got reversion in 2015. The study subjects were classified into three groups according to their QFT and TST results in 2015 (QFT persistence positive, QFT-/TST + and QFT-/TST-). The serum levels of MCP-1 and IL-8 were significantly different among the three groups. Furthermore, level of IL-8 was dramatically lower in QFT-/TST- group as compared to the other two groups, and no significant difference was observed for QFT-/TST + group as comparing with persistent positive group.Conclusion: Our results suggested that the decreased serum level of IL-8 might be potential biomarker to identify QFT reversion caused by infection clearance. [ABSTRACT FROM AUTHOR]

To determine the agreement of Mycobacterium tuberculosis (MTB) antigen-based skin test (TBST) with interferon-gamma release assay (IGRA) in the elderly individuals aged ≥65 years beyond instruction for use in China. Based on the baseline survey of a randomized controlled trial with the objective of exploring suitable regimens for tuberculosis(TB) preventive treatment, MTB infection was tested using TBST and IGRA in parallel in rural residents aged 50–70 years using a cross-sectional study design. A total of 21 219 participants with both TBST and IGRA results were included in this analysis. The concordance between TBST and IGRA was 89.4% (95% CI, 89.0–89.8%) with a kappa coefficient of 0.61 (95% CI, 0.60–0.62). In those aged ≥65 years, the concordance was 86.5% (95% CI, 85.6–87.4%) with a kappa coefficient of 0.55 (95% CI, 0.52–0.58). 21.2% (35/165) of the participants with indeterminate IGRA results were TBST positive, and nine of them were aged ≥65 years. The consistent agreement between TBST and IGRA in individuals aged ≥65 years suggests that TBST has the potential to be used in the elderly with age beyond instruction for use in China. The respective diagnostic performance of each test will be analysed when the longitudinal data on incident TB is obtained in the future. [ABSTRACT FROM AUTHOR]

Bats are important mammal reservoirs of zoonotic pathogens. However, due to research limitations involving species, locations, pathogens, or sample types, the full diversity of viruses in bats remains to be discovered. We used next-generation sequencing technology to characterize the mammalian virome and analyze the phylogenetic evolution and diversity of mammalian viruses carried by bats from Haikou City and Tunchang County in Hainan Province, China. We collected 200 pharyngeal swab and anal swab samples from Rhinolophus affinis , combining them into nine pools based on the sample type and collection location. We subjected the samples to next-generation sequencing and conducted bioinformatics analysis. All samples were screened via specific PCR and phylogenetic analysis. The diverse viral reads, closely related to mammals, were assigned into 17 viral families. We discovered many novel bat viruses and identified some closely related to known human/animal pathogens. In the current study, 6 complete genomes and 2 partial genomic sequences of 6 viral families and 8 viral genera have been amplified, among which 5 strains are suggested to be new virus species. These included coronavirus, pestivirus, bastrovirus, bocavirus, papillomavirus, parvovirus, and paramyxovirus. The primary finding is that a SADS-related CoV and a HoBi-like pestivirus identified in R. affinis in Hainan Province could be pathogenic to livestock. This study expands our understanding of bats as a virus reservoir, providing a basis for further research on the transmission of viruses from bats to humans. [ABSTRACT FROM AUTHOR]

Highlights • Spi6 in host nonhematopoietic cells plays a dominant role in protecting against GVHD by a GzmB-independent mechanism. • Spi6 in host hematopoietic APCs surprisingly suppresses alloreactive T cell response. • Donor T cell–derived IFN-γ is important for inducing Spi6 expression and function in intestinal epithelial cells. Abstract Graft-versus-host disease (GVHD) is a serious complication after allogeneic hematopoietic cell transplantation (allo-HCT) that limits the therapeutic potential of this treatment. Host antigen-presenting cells (APCs) play a vital role in activating donor T cells that subsequently use granzyme B (GzmB) and other cytotoxic molecules to damage host normal tissues. Serine protease inhibitor 6 (Spi6), known as the sole endogenous inhibitor of GzmB, has been implicated in protecting T cells and APCs against GzmB-inflicted damage. In this study we used murine models to examine the previously unknown role of host-derived Spi6 in GVHD pathogenesis. Our results indicated that host Spi6 deficiency exacerbated GVHD as evidenced by significantly increased lethality and clinical and histopathologic scores. Using bone marrow chimera system, we found that Spi6 in nonhematopoietic tissue played a dominant role in protecting against GVHD and was significantly upregulated in intestinal epithelial cells after allo-HCT, whereas Spi6 in hematopoietic APCs surprisingly suppressed alloreactive T cell response. Interestingly, the protective effect of Spi6 and its expression in intestinal epithelial cells appeared to be independent of donor-derived GzmB. We used in silico modeling to explore potential targets of Spi6. Interaction tested in silico demonstrated that Spi6 could inhibit caspase-3 and caspase-8 with the same functional loop that inhibits GzmB but was not capable of forming stable interaction with caspase-1 or granzyme A. Using an in vitro co-culture system, we further identified that donor T cell–derived IFN-γ was important for inducing Spi6 expression in an intestinal epithelial cell line. Altogether, our data indicate that host Spi6 plays a novel, GzmB-independent role in regulating alloreactive T cell response and protecting intestinal epithelial cells. Therefore, enhancing host-derived Spi6 function has the potential to reduce GVHD. [ABSTRACT FROM AUTHOR]