Clinical characteristics of respiratory tract infection caused by Klebsiella pneumoniae in immunocompromised patients: a retrospective cohort study

PurposeWith advancements in medical technology and the growth of an aging society, the number of immunocompromised patients has increased progressively. Klebsiella pneumoniae (K. pneumoniae) is one of the most common opportunistic pathogens, causing a severe disease burden. We aimed to further clarify the differences in respiratory tract K. pneumoniae infections between immunocompromised and immunocompetent populations.MethodsWe retrospectively compared cases of respiratory tract K. pneumoniae infection in immunocompromised and immunocompetent patients admitted to Ruijin Hospital in Shanghai between January 2019 and August 2020 to clarify the differences between the two groups.ResultsWe enrolled 400 immunocompromised patients and 386 immunocompetent patients. Compared to the immunocompetent group, immunocompromised patients were more likely to develop bacteremia and shock and to require mechanical ventilation support during hospitalization. Immunocompromised patients also had a greater probability of polymicrobial infection and a higher rate of antibacterial resistance to carbapenem, which resulted in a higher intensive care unit admission rate, 30-day case fatality rate (CFR), and 6-month CFR. Multivariate analysis indicated that immunocompromised patients with respiratory diseases (odds ratio [OR], 2.189; 95% confidence interval [CI], 1.103-4.344; P = 0.025) and cardiovascular diseases (OR, 2.008; 95% CI, 1.055-3.822; P = 0.034), using mechanical ventilation (OR, 3.982; 95% CI, 2.053-7.722; P = 0.000), or infected with multidrug-resistant K. pneumoniae (OR, 3.870; 95%, 1.577-9.498; P = 0.003) were more likely to have a higher 30-day CFR.ConclusionThe disease burden of K. pneumoniae infection in immunocompromised patients is high. Immunocompromised patients who presented with respiratory diseases and cardiovascular diseases, used mechanical ventilation, or were infected with multidrug-resistant K. pneumoniae experienced a higher 30-day mortality rate

Dephosphorylated Polymerase I and Transcript Release Factor Prevents Allergic Asthma Exacerbations by Limiting IL-33 Release

BackgroundAsthma is a chronic inflammatory disease characterized by airway inflammation and airway hyperresponsiveness (AHR). IL-33 is considered as one of the most critical molecules in asthma pathogenesis. IL-33 is stored in nucleus and passively released during necrosis. But little is known about whether living cells can release IL-33 and how this process is regulated.ObjectiveWe sought to investigate the role of polymerase I and transcript release factor (PTRF) in IL-33 release and asthma pathogenesis.MethodsOvalbumin (OVA)-induced asthma model in PTRF+/− mice were employed to dissect the role of PTRF in vivo. Then, further in vitro experiments were carried out to unwind the potential mechanism involved.ResultsIn OVA asthma model with challenge phase, PTRF+/− mice showed a greater airway hyper-reaction, with an intense airway inflammation and more eosinophils in bronchoalveolar lavage fluid (BALF). Consistently, more acute type 2 immune response in lung and a higher IL-33 level in BALF were found in PTRF+/− mice. In OVA asthma model without challenge phase, airway inflammation and local type 2 immune responses were comparable between control mice and PTRF+/− mice. Knockdown of PTRF in 16HBE led to a significantly increased level of IL-33 in cell culture supernatants in response to LPS or HDM. Immunoprecipitation assay clarified Y158 as the major phosphorylation site of PTRF, which was also critical for the interaction of IL-33 and PTRF. Overexpression of dephosphorylated mutant Y158F of PTRF sequestered IL-33 in nucleus together with PTRF and limited IL-33 extracellular secretion.ConclusionPartial loss of PTRF led to a greater AHR and potent type 2 immune responses during challenge phase of asthma model, without influencing the sensitization phase. PTRF phosphorylation status determined subcellular location of PTRF and, therefore, regulated IL-33 release

Intratracheal administration of adipose derived mesenchymal stem cells alleviates chronic asthma in a mouse model

Abstract Background Adipose-derived mesenchymal stem cell (ASCs) exerts immunomodulatory roles in asthma. However, the underlying mechanism remains unclear. The present study aimed to explore the effects and mechanisms of ASCs on chronic asthma using an ovalbumin (OVA)-sensitized asthmatic mouse model. Methods Murine ASCs (mASCs) were isolated from male Balb/c mice and identified by the expression of surface markers using flow cytometry. The OVA-sensitized asthmatic mouse model was established and then animals were treated with the mASCs through intratracheal delivery. The therapy effects were assessed by measuring airway responsiveness, performing immuohistochemical analysis, and examining bronchoalveolar lavage fluid (BALF). Additionally, the expression of inflammatory cytokines and lgE was detected by CHIP and ELISA, respectively. The mRNA levels of serum indices were detected using qRT-PCR. Results The mASCs grew by adherence with fibroblast-like morphology, and showed the positive expression of CD90, CD44, and CD29 as well as the negative expression of CD45 and CD34, indicating that the mASCs were successfully isolated. Administering mASCs to asthmatic model animals through intratracheal delivery reduced airway responsiveness, the number of lymphocytes (P < 0.01) and the expression of lgE (P < 0.01), IL-1β (P < 0.05), IL-4 (P < 0.001), and IL-17F (P < 0.001), as well as increased the serum levels of IL-10 and Foxp3, and the percentage of CD4 + CD25 + Foxp3+ Tregs in the spleen, and reduced the expression of IL-17 (P < 0.05) and RORγ. Conclusions Intratracheal administration of mASCs alleviated airway inflammation, improved airway remodeling, and relieved airway hyperresponsiveness in an OVA-sensitized asthma model, which might be associated with the restoration of Th1/Th2 cell balance by mASCs

Transcriptomic Analysis of Seasonal Gene Expression and Regulation during Xylem Development in “Shanxin” Hybrid Poplar (Populus davidiana × Populus bolleana)

Xylem development is a key process for wood formation in woody plants. To study the molecular regulatory mechanisms related to xylem development in hybrid poplar P. davidiana × P. bolleana, transcriptome analyses were conducted on developing xylem at six different growth stages within a single growing season. Xylem development and differentially expressed genes in the six time points were selected for a regulatory analysis. Xylem development was observed in stem sections at different growth stages, which showed that xylem development extended from the middle of April to early August and included cell expansion and secondary cell wall biosynthesis. An RNA-seq analysis of six samples with three replicates was performed. After transcriptome assembly and annotation, the differentially expressed genes (DEGs) were identified, and a Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and expression analysis of the DEGs were performed on each sample. On average, we obtained &gt;20 million clean reads per sample, which were assembled into 84,733 nonredundant transcripts, of which there were 17,603 unigenes with lengths &gt;1 kb. There were 14,890 genes that were differentially expressed among the six stages. The upregulated DEGs were enriched in GO terms related to cell wall biosynthesis between S1 vs. S2 or S3 vs. S4 and, in GO terms, related to phytohormones in the S1 vs. S2 or S4 vs. S5 comparisons. The downregulated DEGs were enriched in GO terms related to cell wall biosynthesis between S4 vs. S5 or S5 vs. S6 and, in GO terms, related to hormones between S1 vs. S2 or S2 vs. S3. The KEGG pathways in the DEGs related to “phenylpropanoid biosynthesis”, “plant hormone signal transduction” and “starch and sucrose metabolism” were significantly enriched among the different stages. The DEGs related to cell expansion, polysaccharide metabolism and synthesis, lignin synthesis, transcription factors and hormones were identified. The identification of genes involved in the regulation of xylem development will increase our understanding of the molecular regulation of wood formation in trees and, also, offers potential targets for genetic manipulation to improve the properties of wood

The Imbalance of FOXP3/GATA3 in Regulatory T Cells from the Peripheral Blood of Asthmatic Patients

Background. Treg cells play an important role in the pathogenic progress of asthma. Objective. To address the alterations of Treg cells in asthma. Methods. Proliferation-and function-associated markers of Treg cells along with the percentage of Treg cells producing some cytokine from asthmatics and healthy subjects were analyzed by flow cytometry. Besides, the expressions of USP21 and PIM2 in Treg cells were measured by cell immunochemistry after Treg cells were sorted. Results. Treg cells from asthmatic patients showed lower proliferation activity and were more likely to be apoptotic. These cells expressed lower levels of GITR, CTLA-4, Nrp-1, and IL-10 compared to those from the healthy control. Th2-like Treg cells increased in asthmatic patients, while the percentage of IFN-r+ Treg cells was similar between two groups. Moreover, the percentage of IL-4+ Treg cells is related to the asthma control. Treg cells from asthmatic patients expressed more FOXP3 as well as GATA3; the expression level of GATA3 negatively correlated with FEV1%pred. Increased expressions of USP21 and PIM2 in Treg cells from asthmatic patients were found. Conclusion. Treg cells decreased in asthmatic patients, with an impaired immunosupression function and a Th2-like phenotype, which may be due to overexpression of GATA3 and FOXP3, regulated by USP21 and PIM2, respectively

Research progresses of fibers in asphalt and cement materials: A review

Asphalt mixtures and cement concrete are an important material in the construction of roads, highways and buildings, and there has been a lot of research about the improvement of their performance. Among them, fibers are commonly used in the construction industry because of their superior properties as reinforcing materials that can provide a proper interfacial action between the fibers and the substrate. This review classifies fibers into natural fibers, inorganic fibers and polymer fibers according to their sources and properties. It summarizes and compares the characteristics, modification methods, usage requirements and research status of each type of fiber in asphalt and cement construction materials, and analyzes the problems and challenges faced by fibers in their applications. The evaluation results show that various types of fibers can enhance the fracture resistance, tensile strength and rutting resistance of asphalt to a certain extent, improve the high temperature performance and viscoelasticity of asphalt, and have a certain effect on the fatigue resistance and road water resistance of asphalt mixes. The fibers also provide better tensile, compressive and abrasion resistance to cement concrete and improve the brittleness and crack resistance of ordinary cement. Besides, for some defects of various types of fibers in construction materials, such as biodegradability, dispersibility and surface inertness of fibers, the targeted modification of fibers is introduced based on physical and chemical modification methods to improve the performance impact of modified fibers in various conditions of application

Fungal and bacterial microbiome dysbiosis and imbalance of trans-kingdom network in asthma

Abstract Background Fungal and bacterial microbiota play an important role in development of asthma. We aim to characterize airway microbiome (mycobiome, bacteriome) and functional genes in asthmatics and controls. Methods Sputum microbiome of controls, untreated asthma patients and inhaled corticosteroid (ICS) receiving patients was detected using high throughput sequencing. Metagenomic sequencing was used to examine the functional genes of microbiome. Results 1. Mycobiome: α diversity was lower in untreated asthma group than that in controls. Mycobiome compositions differed among the three groups. Compared with controls, untreated asthma group has higher abundance of Wallemia, Mortierella and Fusarium. Compared with untreated asthma patients, ICS receiving patients has higher abundance of Fusarium and Mortierella, lower frequency of Wallemia, Alternaria and Aspergillus. 2. Bacteriome: α diversity was lower in untreated asthma group than that in controls. There are some overlaps of bacteriome compositions between controls and untreated asthma patients which were distinct from ICS receiving patients. Untreated asthma group has higher Streptococcus than controls. 3. Potential fungal and bacterial biomarkers of asthma: Trametes, Aspergillus, Streptococcus, Gemella, Neisseria, etc. 4. Correlation network: There are dense and homogenous correlations in controls but a dramatically unbalanced network in untreated asthma and ICS receiving patients, which suggested the existence of disease-specific inter-kingdom and intra-kingdom alterations. 5. Metagenomic analysis: functional pathways were associated with the status of asthma, microbiome and functional genes showed different correlations in different environment. Conclusion We showed mycobiome and bacteriome dysbiosis in asthma featured by alterations in biodiversity, community composition, inter-kingdom and intra-kingdom network. We also observed several functional genes associated with asthma

Twelve-Wavelength-Switchable Thulium-Doped Fiber Laser With a Multimode Fiber Bragg Grating

In this article, a precisely controlled, switchable thulium-doped fiber laser (TDFL) with high optical signal-to-noise ratio (OSNR) is proposed and demonstrated. A home-made multimode fiber Bragg grating (MMFBG) with multireflection peaks was used as an optical filter to select the desired lasing channel. Using a manually controlled fusion splicer, the axial misalignment was applied between the single mode fiber and the MMFBG to switch the output wavelength. In the experiment, the number of switchable lasing lines was up to 12, and the fluctuation of the center wavelength and output power was less than 0.03 nm and 0.67 dB, respectively. A maximum slope efficiency of 1.3&#x0025; was obtained when the axial misalignment was 0 &#x03BC;m, and the OSNR was higher than 65 dB. In addition, the proposed fiber laser was used as an optical fiber laser sensor to quantify the strain applied on the MMFBG, and a sensitivity of 1.16 pm&#x002F;&#x03BC;&#x03F5; was obtained