SARS-CoV-2 spike proteins (SP) can bind to the human angiotensin-converting enzyme 2 (ACE2) in human pulmonary alveolar epithelial cells (HPAEpiC) and trigger an inflammatory process. Angiotensin-(1-7) may have an anti-inflammatory effect through activation of Mas receptor. This study aims to investigate whether SARS-CoV-2 SP can induce inflammation through ACE2 in the alveolar epithelial cells which can be modulated through angiotensin-(1-7)/Mas receptor axis. HPAEpiC were treated with SARS-CoV-2 SP in the presence or absence of ACE2 antagonist-dalbavancin and Mas receptor agonist-angiotensin-(1-7). Proinflammatory cytokine production (IL-6 and IL-8) were measured at mRNA and protein levels. MAP kinase phosphorylation and transcription factor activation was determined by Western Blot. Mas receptor was blocked by either antagonist (A779) or knockdown (specific SiRNA). Experiments were replicated using A549 cells. SARS-CoV-2 SP (5 μg/mL) significantly induced MAP kinase (ERK1/2) phosphorylation, downstream transcription factor (activator protein-1, AP-1) activation and cytokine production (IL-6 and IL-8) at both mRNA and protein levels. Pretreatment with dalbavancin (10 μg/mL), or angiotensin-(1-7) (10 μM) significantly reduced ERK1/2 phosphorylation, AP-1 activation, and cytokine production. However, these angiotensin-(1-7)-related protective effects were significantly abolished by blocking Mas receptor with either antagonist (A799,10 μM) or SiRNA knockdown. SARS-CoV-2 SP can induce proinflammatory cytokine production, which can be inhibited by either ACE2 antagonist or Mas receptor agonist-angiotensin-(1-7). Angiotensin-(1-7)-related protective effect on cytokine reduction can be abolished by blocking Mas receptor. Our findings suggest that ACE2/angiotensin-(1-7)/Mas axis may serve as a therapeutic target to control inflammatory response triggered by SARS-CoV-2 SP.

Background/Objectives: Pseudomonas aeruginosa is a major cause of healthcare-associated infections, and the global rise of multidrug-resistant (MDR) strains has created an urgent need for alternative therapeutics. R- and F-type pyocins are phage tail-like bacteriocins that selectively kill P. aeruginosa by binding to lipopolysaccharide (LPS) receptors. We characterized O-serotype distribution and pyocin susceptibility among clinical isolates from central Taiwan to evaluate their therapeutic potential. Methods: A total of 109 ICU-derived P. aeruginosa isolates were analyzed. O-serotypes were determined by PCR, and pyocin gene carriage was confirmed by sequencing. Purified R1, R2, R5, F1, F2, F4, F7, and F12 pyocins were tested using spot assays. LPS profiles were examined by SDS-PAGE to explore structural correlates of resistance. Synergistic effects of combined R- and F-type pyocins were assessed in MDR isolates. Results: The most prevalent serotypes were O6 (23.9%), O2/O5/O16/O18/O20 (20.2%), O1 (16.5%), and O11/O17 (15.6%). Susceptibility was strongly serotype-dependent: O1 and O6 were highly sensitive to both pyocin types, whereas the O2/O5/O16/O18/O20 group showed marked resistance. SDS-PAGE demonstrated that resistant isolates possessed densely packed long-chain O-antigens, likely shielding LPS core receptors from pyocin binding. F-type pyocins exhibited bactericidal activity comparable to R-types, and R/F pyocin cocktails produced synergistic killing against MDR isolates. Conclusions: These findings provide an updated serotype profile of P. aeruginosa in Taiwan and highlight the importance of LPS structural variability in pyocin susceptibility. These results underscore the potential of pyocin-based cocktails as a promising precision-medicine strategy to inhibit the planktonic growth and biofilm formation of multidrug-resistant P. aeruginosa isolates.

Background: Idiopathic pulmonary fibrosis (IPF) carries a poor prognosis despite antifibrotic therapy. The Gender–Age–Physiology (GAP) index enables baseline risk assessment but does not capture longitudinal disease behavior. To determine whether combining baseline GAP score with early change in forced vital capacity (Δ1YFVC%) improves prediction of 2-year mortality in IPF. Methods: A prospective, multicenter observational cohort study conducted across three hospitals in Taiwan between 2018 and 2023. Patients with IPF receiving reimbursed antifibrotic therapy were enrolled. Individuals who died within six months, were lost to follow-up, or lacked one-year pulmonary function data were excluded. The primary outcome was 2-year mortality. Baseline GAP score and Δ1YFVC% were evaluated using a survival-tree model to determine prognostic cutoffs. Survival was analyzed using Kaplan–Meier curves and Cox proportional-hazards regression. Results: Among 156 patients included (median age 77 years; 76.3% male; median baseline FVC 73.5% predicted). 23 (14.7%) died within 2 years. The survival-tree model identified a key prognostic split by GAP ( 10.5 percentage points) was associated with increased mortality, even among patients with lower GAP scores (adjusted HR 3.30, p =0.010). Among patients with GAP ≥5, relatively stable lung function (Δ1YFVC% improved > 1.5 percentage points) was associated with lower mortality risk. Stratification based on GAP score and Δ1YFVC% significantly discriminated mortality risk groups (log-rank p <0.0001, concordance index 0.761) Conclusion: Integrating Δ1YFVC% with the GAP score provides a clinically applicable approach for risk stratification and may support the identification of high-risk patients during antifibrotic therapy.

Background: Acute exacerbations (AEs) drive disease progression and healthcare burden in chronic obstructive pulmonary disease (COPD). Although prior AE history is the strongest predictor of future events, it cannot guide risk assessment in AE-naïve patients, highlighting the need for new prediction tools. Method: In this retrospective multicentre cohort study, we enrolled training and validation cohorts from five hospitals. Baseline demographics, symptom scores, spirometry, blood eosinophils and comorbidities were extracted from electronic records. Multivariable logistic regression was used to identify predictors and convert into score-based models. Result: The training and validation cohorts included 310 and 86 AE-naïve patients with COPD, respectively. Independent predictors of 1-year AEs included coexisting asthma, modified Medical Research Council score ≥2, blood eosinophils ≥2%, per cent predicted forced expiratory volume in 1 s <50% and cardiovascular comorbidities (ie, heart failure and ischaemic cerebrovascular events). Three models were developed with areas under receiver operating characteristic curves of 0.727 to 0.750 and 0.717 to 0.728 in the training and validation cohorts, respectively. At the optimal cutoffs, the sensitivity ranged from 76.7% to 88.2% and specificity from 42.0% to 65.7%. Risk stratification separated patients into low-risk, intermediate-risk and high-risk groups in validation cohort, with increasing AE rates (0.10, 0.43 and 0.86 events/year, respectively; P for trend=0.0047). Conclusion: By incorporating baseline AE history, the externally validated, score-based prediction models provide a practical tool to estimate 1-year AE risk in patients with COPD.

Background: Disease stability (DS) has been proposed as a multidimensional measure of disease activity in chronic obstructive pulmonary disease, but its longitudinal behavior and the clinical relevance of early DS remain poorly characterized. Objectives: To characterize longitudinal DS and determine whether DS at 6 months is associated with DS at 12 months. Design: Retrospective multicenter cohort study conducted at four hospitals in Taiwan between January 2016 and December 2023. Methods: Patients with complete exacerbation records, spirometry data, and Chronic Airways Assessment Test (CAAT) data at baseline and at the 6- and 12-month assessments were included. DS was defined as the absence of moderate or severe exacerbations, <2-point worsening from baseline in CAAT score, and <100-mL decline in post-bronchodilator forced expiratory volume in one second. Multivariable logistic regression analyses were used to evaluate factors associated with DS and the association between 6- and 12-month DS. Results: Among 905 patients identified, 250 had complete longitudinal data and comprised the primary analytic cohort. DS was achieved by 114 patients (45.6%) at 6 months and 94 (37.6%) at 12 months. Among patients with and without 6-month DS, 68.4% and 11.8%, respectively, achieved 12-month DS. In the baseline multivariable model, prior moderate or severe exacerbations (adjusted odds ratio [aOR]: 0.25, 95% confidence interval [CI]: 0.12–0.53) and reliever use of ≥3 canisters/year (aOR: 0.50, 95% CI: 0.27–0.95) were associated with lower odds of 12-month DS. After additional adjustment for 6-month DS, achievement of 6-month DS was strongly associated with 12-month DS (aOR: 11.72, 95% CI: 5.67–24.22). This association remained consistent in the expanded ascertainable-outcome cohort (N = 544; aOR: 14.33, 95% CI: 7.30–28.14) and the multiple-imputation analysis of the full cohort (N = 905; aOR: 13.57, 95% CI: 8.39–21.93). Conclusion: Six-month DS was strongly associated with subsequent DS and may represent a clinically relevant intermediate milestone for characterizing disease trajectory and identifying patients who may benefit from closer monitoring and management reassessment.