Neutrophil extracellular traps (NETs) are intricate fibrous structures released by neutrophils in response to specific stimuli. These structures are composed of depolymerized chromatin adorned with histones, granule proteins, and cytosolic proteins. NETs are formed via two distinct pathways known as suicidal NETosis, which involves NADPH oxidase (NOX), and vital NETosis, which is independent of NOX. Certain proteins found within NETs exhibit strong cytotoxic effects against both pathogens and nearby host cells. While NETs play a defensive role against pathogens, they can also contribute to tissue damage and worsen inflammation. Despite extensive research on the pathophysiological role of NETs, less attention has been paid to their components, which form a unique structure containing various proteins that have significant implications in a wide range of diseases. This review aims to elucidate the components of NETs and provide an overview of their impact on host defense against invasive pathogens, autoimmune diseases, and cancer.

Presepsin Predicts Severity and Secondary Bacterial Infection in COVID-19 by Bioinformatics Analysis: Introduction. Novel coronavirus pneumonia (COVID-19) is an acute respiratory disease caused by the novel coronavirus SARS-CoV-2. Severe and critical illness, especially secondary bacterial infection (SBI) cases, accounts for the vast majority of COVID-19-related deaths. However, the relevant biological indicators of COVID-19 and SBI are still unclear, which significantly limits the timely diagnosis and treatment. Methods. The differentially expressed genes (DEGs) between severe COVID-19 patients with SBI and without SBI were screened through the analysis of GSE168017 and GSE168018 datasets. By performing Gene Ontology (GO) enrichment analysis for significant DEGs, significant biological processes, cellular components, and molecular functions were selected. To understand the high-level functions and utilities of the biological system, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed. By analyzing protein-protein interaction (PPI) and key subnetworks, the core DEGs were found. Results. 85 DEGs were upregulated, and 436 DEGs were downregulated. The CD14 expression was significantly increased in the SBI group of severe COVID-19 patients ( ). The area under the curve (AUC) of CD14 in the SBI group in severe COVID-19 patients was 0.9429. The presepsin expression was significantly higher in moderate to severe COVID-19 patients ( ). Presepsin has a diagnostic value for moderate to severe COVID-19 with the AUC of 0.9732. The presepsin expression of COVID-19 patients in the nonsurvivors was significantly higher than that in the survivors ( ). Conclusion. Presepsin predicts severity and SBI in COVID-19 and may be associated with prognosis in COVID-19.

The lung microbiome has emerged as a pivotal area of research in human health. Despite the increasing number of publications, there is a lack of research that comprehensively and objectively presents the current status of lung microbiome-related studies. Thus, this study aims to address this gap by examining over two decades of publications through bibliometric analysis. The original bibliographic data of this study were obtained from the Web of Science Core Collection, focusing on publications from 2003 to 2023. The analysis included the data extraction and examination of authors, affiliations, countries, institutions, abstracts, keywords, references, publication dates, journals, citations, H-indexes, and journal impact factors. A total of 845 publications were identified, showing an increasing trend in both publications and citations over the years, particularly in the last decade. The analysis highlighted the most productive authors, institutions, and countries/regions, and identified potential partners for interested researchers. Co-citation analysis revealed that lung microbiome- and infectious/pulmonary disease-related studies are at the forefront of the field. The hotspots and frontiers of the lung microbiome field have progressed from basic composition to exploring specific mechanisms and the clinical value of diseases. In conclusion, this study provides a comprehensive overview of the current research status and trends in the field of the lung microbiome over the past two decades and highlights the areas that need more attention and research efforts. It offers valuable insights for researchers and institutions and identifies key hotspots and frontiers, which can serve as references for related researchers and future research.

Corticosteroid therapy is currently recommended by clinical guidelines for severe patients with HIV-associated Pneumocystis jirovecii pneumonia (PJP). Howe

Background: Klebsiella pneumoniae (KP) infection is a growing global threat because of increasing antimicrobial resistance and high mortality. We systematically estimated mortality at different endpoints and synthesized adjusted factors associated with death to inform risk assessment and management. Methods: We searched PubMed, Web of Science, Embase, and the Cochrane Library for studies published from January 1991 to June 2025 (CRD42023456620). Prespecified meta-analyses included predictors reported by ≥ 3 studies, with ≥ 1 reporting a significant adjusted association. Adjusted odds ratios (ORs) and hazard ratios (HRs) were synthesized separately. Fixed- or random effects models were selected according to heterogeneity. Subgroup analyses examined study-level characteristics. Results: We included 121 studies involving 21,660 patients (6235 deaths; 28.8%, 95% CI 28.2–29.4). Pooled mortality was 21.7% (95% CI 16.4–27.5) at 14/15 days, 33.3% (95% CI 29.9–36.8) at 28/30 days, 34.6% (95% CI 24.1–45.8) at 90 days, and 29.3% (95% CI 23.0–36.0) in hospital. Among studies published after 2020, 28/30-day mortality was 35.1% (95% CI 30.4–40.0), without significant differences by publication period. Separate OR and HR analyses consistently identified carbapenem-resistant KP (CRKP), greater comorbidity and disease severity, malignancy, sepsis/septic shock, and inappropriate empirical therapy as adverse prognostic factors of 28/30-day mortality, whereas appropriate targeted and combination therapies were associated with lower mortality. Risk of bias and publication period partly explained heterogeneity in selected OR estimates. Conclusions: Mortality from KP infection remained substantial across 14/15-, 28/30-, and 90-day follow-up, with 28/30-day mortality exceeding 35% among studies published after 2020, although differences between publication periods were not statistically significant. Effect-measure-specific analyses identified antimicrobial resistance, comorbidity, disease severity, and treatment appropriateness as clinically relevant prognostic factors, which may inform individualized management. Systematic review registration: PROSPERO CRD42023456620

Gram-negative bacteria pose a significant threat to global health due to their high prevalence, multidrug resistance, and association with various infections. Zinc, an essential trace element, plays a dual role in host–microbe interactions, being crucial for both host immune function and bacterial metabolism. Maintaining optimal zinc homeostasis is essential for effective host defense and microbial survival. We comprehensively examine the multifaceted roles of zinc in host–microbe interactions, particularly focusing on its implications for the pathogenicity of Gram-negative bacteria and host immunity. As part of nutritional immunity, hosts have evolved zinc-mediated antimicrobial strategies that manipulate metal availability at the host–pathogen interface, including zinc limitation that restricts bacterial access to this essential nutrient and zinc intoxication that exposes invading bacteria to cytotoxic zinc concentrations. In Gram-negative bacteria, zinc homeostasis, maintained through zinc transporters and efflux systems, critically governs bacterial virulence, biofilm formation, and survival under host-imposed nutritional immunity. By integrating current advances, this review highlights zinc homeostasis as a central determinant of host–pathogen interactions and a promising target for combating multidrug-resistant Gram-negative infections. Understanding these complex zinc-mediated mechanisms provides new perspectives for developing metal-targeted therapeutic strategies.