Clinical Characteristics and Outcomes of the Phenotypes of COPD-Bronchiectasis Association.

INTRODUCTION: Although COPD may frequently co-exist with bronchiectasis [COPD-bronchiectasis associated (CBA)], little is known regarding the clinical heterogeneity. We aimed to identify the phenotypes and compare the clinical characteristics and prognosis of CBA. METHODS: We conducted a retrospective cohort study involving 2928 bronchiectasis patients, 5158 COPD patients, and 1219 patients with CBA hospitalized between July 2017 and December 2020. We phenotyped CBA with a two-step clustering approach and validated in an independent retrospective cohort with decision-tree algorithms. RESULTS: Compared with patients with COPD or bronchiectasis alone, patients with CBA had significantly longer disease duration, greater lung function impairment, and increased use of intravenous antibiotics during hospitalization. We identified five clusters of CBA. Cluster 1 (N=120, CBA-MS) had predominantly moderate-severe bronchiectasis, Cluster 2 (N=108, CBA-FH) was characterized by frequent hospitalization within the previous year, Cluster 3 (N=163, CBA-BI) had bacterial infection, Cluster 4 (N=143, CBA-NB) had infrequent hospitalization but no bacterial infection, and Cluster 5 (N=113, CBA-NHB) had no hospitalization or bacterial infection in the past year. The decision-tree model predicted the cluster assignment in the validation cohort with 91.8% accuracy. CBA-MS, CBA-BI, and CBA-FH exhibited higher risks of hospital re-admission and intensive care unit admission compared with CBA-NHB during follow-up (all P<0.05). Of the five clusters, CBA-FH conferred the worst clinical prognosis. CONCLUSION: Bronchiectasis severity, recent hospitalizations and sputum culture findings are three defining variables accounting for most heterogeneity of CBA, the characterization of which will help refine personalized clinical management.

Advances in pharmacotherapy for bronchiectasis in adults.

INTRODUCTION: Bronchiectasis has become a growing concern of chronic airway disease because of the enormous socioeconomic burden. Four cardinal interdependent components - impaired airway defense, recurrent airway infections, inflammatory response, and airway damage, in conjunction with the underlying etiology, have collectively played a role in modulating the vicious vortex of the pathogenesis and progression of bronchiectasis. Current pharmacotherapy aims to target at these aspects to break the vicious vortex. AREAS COVERED: The authors retrieve and review, in MEDLINE, Web of Science and ClinicalTrials.gov registry, the studies about pharmacotherapy for bronchiectasis from these aspects: antibiotics, mucoactive medications, bronchodilators, anti-inflammatory drug, and etiological treatment. EXPERT OPINION: Future drug development and clinical trials of bronchiectasis need to pay more attention to the different phenotypes or endotypes of bronchiectasis. There is a need for the development of novel inhaled antibiotics that could reduce bacterial loads, improve quality-of-life, and decrease exacerbation risks. More efforts are needed to explore the next-generation neutrophil-targeted therapeutic drugs that are expected to ameliorate respiratory symptom burden, reduce exacerbation risks, and hinder airway destruction in bronchiectasis.

Anti-Interferon-γ Autoantibodies Impair T-Lymphocyte Responses in Patients with Talaromyces marneffei Infections.

Background: Although anti-IFN-γ autoantibodies predispose patients to Talaromyces marneffei infection, whether this is mediated by T cell attenuation remains elusive. Methods: Total peripheral blood mononuclear cells (PBMCs) from healthy donors or patients with T. marneffei infection were stimulated with M158-66, and immunodominant influenza H1N1 peptide, or heat-inactivated T. marneffei in the presence of serum from anti-IFN-γ autoantibody-positive patients or healthy controls. The percentages of IFN-γ+TNF+CD8+ T cells and IFN-γ+CD4+ T cells were determined by flow cytometry and cytokines released in the supernatant were detected by Cytometric Bead Array. Furthermore, PBMCs from patients with T. marneffei infection and healthy individuals were stimulated with IFN-γ and anti-CD3/CD28 beads, and the levels of STAT1 and STAT3 phosphorylation were detected by Western blot. Results: The M1-reactive CD8+ T cells that expressed IFN-γ+ TNF-α+ of healthy controls were clearly reduced in serum with high-titer anti-IFN-γ autoantibodies. In addition, the CD4+ T cell response, designated by the expression of IFN-γ, against T. marneffei in PBMCs of patients were significantly decreased when cultured in high-titer anti-IFN-γ autoantibody serum culture, compared to the healthy compartments. Moreover, the release of the cytokines IFN-γ, TNF-α and IL-2 was significantly decreased, while IL-10 was significantly increased. There was no significant difference in the phosphorylation levels of STAT1 and STAT3 protein between patients and healthy controls after IFN-γ or anti-CD3/CD28 beads stimulation. Conclusion: Anti-IFN-γ autoantibodies presence in the serum inhibited CD4+ Th1 and CD8+ T cell immune responses. There was no congenital dysfunction of STAT1 and STAT3 in anti-IFN-γ autoantibody-positive patients with T. marneffei infection. These results suggest that the production of anti-IFN-γ autoAbs impair T-lymphocyte responses.

[Effects of biochar combined with nitrification/urease inhibitors on soil active nitrogen emissions from subtropical paddy soils]. / ç”Ÿç‰©ç‚­é æ–½ç¡åŒ–/è„²é ¶æŠ‘åˆ¶å‰‚å¯¹äºšçƒ­å¸¦æ°´ç¨»åœŸæ´»æ€§æ°®æ°”ä½“æŽ’æ”¾çš„å½±å“.

We examined the effects of biochar and urease inhibitors/nitrification inhibitors on nitrification process, ammonia and N2O emission in subtropical soil, and determined the best combination of biochar with nitrification and urease inhibitors. This work could provide a theoretical basis for the mitigation of the negative environmental risk caused by reactive nitrogen gas in the application of nitrogen fertilizer. A indoor aerobic culture test was conducted with seven treatments [urea+biochar (NB), urea+nitrification inhibitor (N+NI), urea+urease inhibitor (N+UI), urea+nitrification inhibitor+urease inhibitor (N+NIUI), urea+nitrification inhibitor+biochar (NB+NI), urea+urease inhibitor+biochar (NB+UI), urea+nitrification inhibitor+urease inhibitor+biochar (NB+NIUI)] and urea (N) as the control. The dynamics of soil inorganic nitrogen content, N2O emission and the volatility of ammonia volatilization were observed under combined application of biochar with urease inhibitor (NBPT)/nitrification inhibitor (DMPP). The results showed that:1)Compared to the control (5.11 mg N·kg-1·d-1) during the incubation period, NB treatment significantly increased therate constant of nitrification by 33.9%, and N+NI treatment significantly reduced the nitrification rate constant by 22.9%. NB treatment significantly increased the abundance of ammonia oxidizing bacteria (AOB) by 56.0%. 2) Compared with N treatment, N+NI and NB+NI treatments signi-ficantly enhanced the cumulative emission of NH3 by 49%. The N+UI treatment reduced the cumulative loss of NH3. The inhibition effect of NB+UI treatment was more significant. 3) The emission rate of N2O was highest in the first 10 days after fertilization. The N2O emission under NB treatment was the earliest, and that of N treatment was the highest (5.87 µg·kg-1·h-1). The combined application of DMPP and NBPT performed the best in reducing soil N2O emission. We estimated global warming potential (GWP) of the direct N2O and indirect N2O (NH3) emissions. Compared with N treatments, N+NI and NB+NI treatments increased the GWP by 34.8% and 40.9%, respectively. While the NB and NB+UI treatments significantly reduced the GWP by 45.9% and 60.5%, the combination of biochar and urease inhibitor had the best effect on reduction of GWP of soil active nitrogen emissions.

Exhaled Volatile Organic Compounds for Identifying Patients With Chronic Pulmonary Aspergillosis.

Background: Diagnosing chronic pulmonary aspergillosis is a major challenge in clinical practice. The development and validation of a novel, sensitive and specific assay for diagnosing chronic pulmonary aspergillosis is urgently needed. Methods: From April 2018 to June 2019, 53 patients with chronic pulmonary aspergillosis (CPA), 32 patients with community-acquired pneumonia (CAP) and 48 healthy controls were recruited from the First Affiliated Hospital of Guangzhou Medical University. Clinical characteristics and samples were collected at enrollment. All exhaled breath samples were analyzed offline using thermal desorption single-photon ionization time-of-flight mass spectrometry; to analyze the metabolic pathways of the characteristic volatile organic compounds, serum samples were subjected to ultrahigh-performance liquid chromatography. Results: We identified characteristic volatile organic compounds in patients with chronic pulmonary aspergillosis, which mainly consisted of phenol, neopentyl alcohol, toluene, limonene and ethylbenzene. These compounds were assessed using a logistic regression model. The sensitivity and specificity were 95.8 and 96.9% for discriminating patients in the CPA group from those in the CAP group and 95.8 and 97.9% for discriminating patients in the CPA group from healthy controls, respectively. The concentration of limonene (m/z 136) correlated significantly positively with anti-Aspergillus fumigatus IgG antibody titers (r = 0.420, P < 0.01). After antifungal treatment, serum IgG and the concentration of limonene (m/z 136) decreased in the subgroup of patients with chronic pulmonary aspergillosis. Conclusions: We identified VOCs that can be used as biomarkers for differential diagnosis and therapeutic response prediction in patients with chronic pulmonary aspergillosis.

Serum Sphingolipids Aiding the Diagnosis of Adult HIV-Negative Patients with Talaromyces marneffei Infection.

Increasing attention has been directed to Talaromyces marneffei (T. marneffei) infection in HIV-negative patients due to its high mortality rate. However, nonspecific symptoms and biological characteristics similar to those of other common pathogenic fungi complicate the rapid and accurate diagnosis of T. marneffei infection. Sphingolipids (SPLs) are bioactive lipids involved in the regulation of various physiological and pathological processes and have been identified as serum biomarkers for several diseases. This study employed a sphingolipidomic approach established in our previous work to explore the use of serum SPLs in the diagnosis of HIV-negative patients with T. marneffei infection. Additional clinical cohorts of patients infected with other microorganisms were also recruited. We found that sphinganine (Sa) (d16:0) exhibited obvious depletion after infection; moreover, its level in patients with T. marneffei infection was significantly lower than that in patients infected with other microorganisms. Therefore, Sa (d16:0) was considered a specific diagnostic biomarker for T. marneffei infection, and 302.71 nM was selected as the optimal cutoff value with a diagnostic sensitivity of 87.5% and specificity of 100%. These results suggested that determination of serum Sa (d16:0) levels can be used as a new alternative tool for the rapid diagnosis of T. marneffei infection in HIV-negative patients.

Clinical findings of Talaromyces marneffei infection among patients with anti-interferon-γ immunodeficiency: a prospective cohort study.

BACKGROUND: Talaromyces marneffei (T. marneffei) infection has been associated with adult-onset immunodeficiency due to anti-IFN-γ autoantibodies. We aimed to investigate the clinical features of non-HIV-infected patients with T. marneffei infection in southern China. METHODS: Between January 2018 and September 2020, we enrolled patients with T. marneffei infection who were HIV-negative (group TM, n = 42), including anti-IFN-γ autoantibody-positive (group TMP, n = 22) and anti-IFN-γ autoantibody-negative (group TMN, n = 20) patients and healthy controls (group HC, n = 40). Anti-IFN-γ autoantibodies were detected by ELISA. Clinical characteristics and clinical laboratory parameters were recorded. RESULTS: Compared with anti-IFN-γ autoantibody-negative patients with T. marneffei infection, anti-IFN-γ autoantibody-positive patients did not have underlying respiratory disease; more frequently exhibited dissemination of systemic infections with severe pleural effusion; had higher WBC counts, C-reactive protein levels, erythrocyte sedimentation rates, and neutrophil and CD8+ T cell counts; had lower hemoglobin levels; and were more likely to have other intracellular pathogen infections. Most of these patients had poor outcomes despite standardized antimicrobial therapy. CONCLUSION: T. marneffei-infected patients with higher anti-IFN-γ autoantibody titers have more severe disease and complex clinical conditions.

[Effects of phosphorus fertilizer application methods and types on the yield and phosphorus uptake of winter wheat.] / ç£·è‚¥æ–½ç”¨æ–¹å¼åŠç±»åž‹å¯¹å†¬å°éº¦äº§é‡å’Œç£·ç´ å¸æ”¶çš„å½±å“.

A field micro-plot experiment was conducted to determine the effect of different placement methods and types of phosphorus (P) fertilizer on winter wheat growth and phosphorus uptake. P fertilizer types included monocalcium phosphate (MCP) and diammonium phosphate (DAP). P fertilizer application methods included: 1) surface broadcasting (S); 2) banding 5 cm below seeds (B0); 3) banding 5 cm below and 3 cm away from seeds (B3); 4) banding 5 cm below and 10 cm away from seeds (B10); 5) mixing with the 20% of the top soil below seeds (M). The result showed that B0 had the best effect on increasing yield, reached 7.63 t·hm-2 in MCP-B0 and 7.99 t·hm-2 in DAP-B0, which increased 10.3% and 10.7%, respectively compared with surface broadcasting. B10 had the lowest grain yield (6.60-6.77 t·hm-2). The total P uptake by wheat in B0 and M was at a relatively high level (34.42-35.60 kg·hm-2), B10 performed worst at all growth stages of wheat, while P uptake of DAP-B10 was 11.9% higher than MCP-B10. These results indicated that concentrating P fertilizer in a short distance near the seeds was an optimized application method for winter wheat in this region, and DAP performed better than MCP on P uptake and utilization of wheat under far banding.

Enhanced fluorescence detection using liquid-liquid extraction in a microfluidic droplet system.

Reducing the fluorescence background in microfluidic assays is important in obtaining accurate outcomes and enhancing the quality of detections. This study demonstrates an integrated process including cell labelling, fluorescence background reduction, and biomolecule detection using liquid-liquid extraction in a microfluidic droplet system. The cellular lipids in Chlorella vulgaris and NIH/3T3 cells were labelled with a hydrophobic dye, Nile red, to investigate the performance of the proposed method. The fluorescence background of the lipid detection can be reduced by 85% and the removal efficiency increased with the volume of continuous phase surrounding a droplet. The removal rate of the fluorescence background increased as the surface area to volume ratio of a droplet increased. Before Nile red was removed from the droplet, the signal to noise ratio was as low as 1.30 and it was difficult to distinguish cells from the background. Removing Nile red increased the signal to noise ratio to 22 and 34 for Chlorella vulgaris and NIH/3T3, respectively, and these were 17 fold and 10 fold of the values before extraction. The proposed method successfully demonstrates the enhancement of fluorescence detection of cellular lipids and has great potential in improving other fluorescence-based detections in microfluidic systems.