Physical activity (PA) and structured exercise are established cornerstones of cystic fibrosis (CF) management. While CFTR modulators have transformed treatment, the psychological factors affecting sustained PA adherence, particularly motivational regulation and PA enjoyment, require further investigation. This study aimed to determine whether percent predicted forced expiratory volume in one second (ppFEV₁) is independently associated with autonomous motivation and PA enjoyment in adults with CF, after adjusting for CFTR modulator therapy status and sex.

A cross-sectional study was conducted at a specialised CF centre (N = 200). Participants completed validated questionnaires assessing motivational regulation (Behavioural Regulation Questionnaire-2, BREQ-2) and PA enjoyment (Physical Activity Enjoyment Scale, PACES). Clinical data, including the ppFEV₁, were obtained from medical records. Multivariate general linear models (GLM), partial correlations, and hierarchical regression analyses were utilised.

Cross-sectional analyses showed that ppFEV₁ was independently associated with intrinsic motivation (β = .233, p < .001), the relative autonomy index (RAI) (β = .203, p = .004) and the PACES total score (β = .201, p = .004). After CFTR modulator therapy status and sex were accounted for, the additional variance explained by the ppFEV₁ was statistically significant but modest (ΔR² = .054, .041, and .040, respectively). Neither the CFTR modulator therapy status nor sex was significantly associated with the assessed motivational or enjoyment outcomes.

Although ppFEV₁ showed small, independent associations with autonomous motivational regulation and PA enjoyment in adults with CF, lung function should not be used as a proxy for motivational support needs. To provide person-centred, SDT-informed support that encourages sustained participation in PA, the motivational regulation and enjoyment of PA should be assessed directly in adults with CF.

Acute lung injury (ALI) involves alveolar-capillary barrier disruption, inflammatory amplification, oxidative stress, and loss of alveolar architecture. This study developed pH-responsive chitosan-coated spanlastic nanovesicles as a pharmaceutical platform for lung-targeted delivery of Brilliant Blue G (BBG), a P2X7 receptor antagonist. BBG-loaded spanlastics were prepared by thin-film hydration and optimized using a 2³ factorial design assessing the effects of Span 60:BBG ratio, Span 60:edge activator ratio, and edge activator type on vesicle size, zeta potential, and entrapment efficiency. The optimized formulation was coated with chitosan to achieve surface cationization, enhance colloidal stability, support mucoadhesive interaction with lung tissue, and provide pH-responsive release. BBG-Ch-SPNs exhibited nanoscale size, positive zeta potential, high entrapment efficiency, acceptable hemocompatibility, and sustained drug release, with greater BBG liberation under acidic conditions relevant to inflamed lung microenvironments. Release kinetic analysis supported diffusion-controlled release with pH-dependent polymer relaxation, while stability testing confirmed preservation of vesicle size, surface charge, and drug entrapment over three months. In vivo, BBG-Ch-SPNs improved pulmonary retention and lung exposure compared with free BBG and uncoated spanlastics, demonstrating enhanced lung-targeting efficiency. Therapeutically, BBG-Ch-SPNs reduced BALF protein leakage, LDH activity, NOx levels, and leukocyte influx while preserving alveolar architecture and limiting septal thickening, edema, and inflammatory infiltration. These effects were accompanied by restored antioxidant defenses and suppression of P2X7R/NF-κB/NLRP3 inflammasome signaling. Overall, chitosan-coated spanlastics improved BBG formulation performance, pH-responsive delivery, pulmonary biodistribution, and therapeutic efficacy, supporting their potential as a targeted nanotherapeutic system for ALI.

Nanomedicine has progressed far beyond its early role as an experimental drug-carrier toolbox and today stands as a clinically validated enabling technology. Liposomal formulations and albumin-bound nanoparticles have transformed cancer therapy, while lipid nanoparticle (LNP) platforms accelerated the rapid development and global deployment of SARS-CoV-2 mRNA vaccines-demonstrating how nanoscale engineering can reshape therapeutic response, manufacturing speed, and public health impact. With these successes as foundation, the field is rapidly expanding into more sophisticated delivery systems including cell-hitchhiking nanoparticles, biomimetic multivalent vaccines, implantable immunotherapy depots, high-loading polymeric micelles, organ-targeted gene and RNA carriers, and bio-hybrid extracellular vesicle and mitochondrial therapies. These platforms aim not only to transport drugs, but to modulate immunity, direct regeneration, and enable precision intervention at the cellular and molecular scale. This perspective summarizes the current landscape of biomedical nanotechnologies and outlines how their continued evolution positions nanomedicine as an enabling science driving the next generation of therapeutics.

Despite widespread vaccination, Bordetella pertussis (Bp) cases are resurging globally. Although CD4+ T cells are known to be essential for sustained protection, the antigens they recognize are not fully characterized, hindering vaccine refinement. Using immunopeptidomics, bioinformatics, and functional T cell assays, we identified high-affinity epitopes from reference and clinical Bp strains presented on MHC-II I-Ab. A subset of these epitopes stimulated systemic and mucosal CD4+ T cells of mice immunized with heat-killed Bp, and peripheral blood T cells from humans vaccinated with the whole-cell pertussis vaccine. Mice immunized with a subunit vaccine comprising two recombinant proteins identified in our screen were subsequently challenged with Bp. Bacterial burden was nearly eliminated from the lower respiratory tract and significantly reduced in the upper respiratory tract. Th1/Th17-polarized CD4+ tissue-resident memory T cells (Trms) were induced in nasal and pulmonary tissues. Depleting memory CD4+ T cells before challenge abolished protection, confirming that antigen-specific CD4+ T cells are critical for clearing Bp from the respiratory tract. Our integrated antigen identification and T cell assay approach revealed previously untested Bp antigens that elicit protective CD4+ T cell-mediated immunity, suggesting that incorporating them into new vaccines may help curb the resurgence of pertussis.

Hemoptysis is a common and challenging clinical emergency, frequently secondary to high-prevalence diseases in China-such as pulmonary tuberculosis, bronchiectasis, lung cancer, and pulmonary mycosis-as well as respiratory interventional procedures. Patients with life-threatening massive hemoptysis can succumb to asphyxia or hemorrhagic shock within minutes. Currently, clinical practices in hemoptysis management across China exhibit significant disparities among different regions and hospital tiers, characterized by an overall deficit in rescue capabilities and high rates of mortality and disability. The establishment of hemoptysis centers, drawing on the experience of chest pain centers and stroke centers, has become imperative. Several hospitals across various provinces and municipalities in China have already established Hemoptysis Centers, yielding favorable clinical outcomes, and an increasing number of hospitals nationwide are actively advancing the development of these centers. To ensure the standardized and orderly establishment of these centers, the Chinese Thoracic Society, the Chinese Antituberculosis Association, the Interventional Pulmonology Group of the Chinese Association of Chest Physicians, and the Hemoptysis Expert Committee of the Haemorrhage Professional Committee of the Chinese Research Hospital Association convened national experts in related fields to formulate these Expert Recommendations on the standardized established of hemoptysis centers. As the first consensus of their kind both domestically and internationally, these recommendations aim to standardize the establishment of Hemoptysis Centers, promote the development of a nationwide Hemoptysis Center network, improve the success rate of hemoptysis treatment, and reduce the mortality and disability rates of affected patients.

SARS-CoV-2 continues to evolve. The subvariant BA.3.2 (Cicada), a derivative of the Omicron BA.3 subtype first detected in late 2024, harbors multiple spike protein mutations, ORF7 and ORF8 deletions, and has recently evolved sublineages (BA.3.2.1 and BA.3.2.2), rendering it a critical target for epidemiological surveillance. The BA.3.2.2 sublineage, represented by RE.2.2, shows a marked upward trend in late 2025. Using surface plasmon resonance, we found that RE.2.2's spike (S) protein receptor-binding domain (RBD) exhibits relatively high affinity for human receptor angiotensin-converting enzyme 2, with structural analysis identifying the R493Q reverse mutation as the key determinant. Pseudovirus infection and antibody neutralization assays demonstrated that RE.2.2 exhibited a distinct neutralization profile compared to contemporaneous dominant subvariants. Notably, several antibodies that previously lacked neutralizing activity (e.g., S2K146 and L4.65) to other subvariants regained neutralizing potency against RE.2.2, which was associated with key mutations including G446D. Profiling of RE.2.2 RBD binding to ACE2 orthologs across species showed no significant difference in species tropism from the representative Omicron BA.1. Importantly, RE.2.2 exhibits the newly emerged N-linked glycosylation at spike protein N529 (absent in all other subvariants), a modification potentially associated with immune evasion or spike protein conformational dynamics. In addition, we corroborated the "O-follow-N" glycosylation observation as previously reported, where O-linked glycans preferentially localize near N-glycosylation sites, implying coordinated glycan organization as an extra layer of spike regulation. These findings illuminate the evolutionary characteristics, functional changes, and the constrained virus immune escape of BA.3.2.2 (RE.2.2), providing critical insights into antibody development and variant surveillance.

Chronic obstructive pulmonary disease (COPD) is a disease characterized by airflow obstruction. Peroxiredoxin 6 (PRDX6) is vital in antioxidant defense and phospholipid metabolism, and linked to disease occurrence and progression. Ubiquitin-specific protease 19 (USP19), a deubiquitinating enzyme involved in protein stability regulation, has been implicated in inflammatory diseases and cellular stress responses, yet its role in COPD remains largely unknown. The objective of this study is to investigate the impact and the underlying mechanism of PRDX6 on cigarette smoke extract (CSE)-induced cell injury and ferroptosis, with a focus on the regulatory roles of USP19 and histone deacetylase 6 (HDAC6).

The expression levels of the genes were detected by reverse transcription-quantitative polymerase chain reaction (qRT-PCR) and western blot. The Cell counting kit-8 (CCK-8) was utilized to assess cell viability. Cell apoptosis was detected by flow cytometry. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected using the enzyme-linked immunosorbent assay (ELISA). The iron ion (Fe2+), reactive oxygen species (ROS), and glutathione (GSH) kits were used to evaluate the ferroptosis index. The Biological General Repository for Interaction Datasets (BioGRID), Hitpredict database, and Ubibrowser database were used to predict protein interactions. Protein modifications and protein-protein interactions were verified using co-immunoprecipitation (CoIP). The treatment with cycloheximide (CHX) was used to verify protein stability. The rat COPD model was used for in vivo validation. Hematoxylin-eosin (HE), Masson's trichrome (Masson) and Periodic Acid-Schiff (PAS) staining were utilized for the assessment of lung injury. Immunohistochemistry (IHC) analysis was conducted to assess the levels of PRDX6 present in rat lung tissue.

In CSE-induced 16HBE cells, upregulating PRDX6 expression mitigated the decline in cellular viability, prevented apoptosis, suppressed inflammatory reactions, and halted ferroptosis. HDAC6 facilitated CSE-induced cellular damage and ferroptosis by mediating the deacetylation modification of PRDX6. USP19 enhanced the stability of HDAC6 by deubiquitination, thereby exacerbating CSE-induced cellular damage and ferroptosis. The elevated levels of PRDX6 mitigated cellular damage and ferroptosis in the rat COPD models.

USP19 modulates PRDX6 expression by deubiquitinating HDAC6, thereby promoting CSE-induced cellular damage and ferroptosis. This deepens our understanding on COPD pathogenic mechanism and may offer a new perspective for COPD treatment.

The COVID-19 pandemic led to economic and policy changes that increased Medicaid enrollment and reduced disenrollment. Tracking the impact of these changes on the composition of enrollees is crucial for resource allocation and program evaluation. However, Medicaid data currently lack the necessary demographic, social, and economic information about enrollees.

Enhance Medicaid enrollment data by linking it with nationally representative survey data to compare the composition of enrollees across various social determinants of health characteristics before and after the COVID-19 pandemic.

We utilize individual-level Medicaid enrollment records (TAF, 2018-2021) before and during the pandemic, linked to restricted American Community Survey (ACS, 2021) microdata.

Almost 95% of enrollees in our analytic sample received an anonymous identifier (Protected Identification Key), and nearly 1% were found in ACS data. By comparing Medicaid enrollees in different enrollment cohorts, we find that the pandemic caused significant compositional changes, particularly among the newly enrolled. Our findings indicate that those experiencing a major health or economic shock, either directly or through a family member, relied on Medicaid, likely as a temporary source of health insurance during the pandemic.

Linking individual-level records between Medicaid and ACS data effectively addresses a crucial gap in current data capacity. The integrated data can be utilized, repurposed, and expanded by incorporating additional survey and administrative records to enhance the utility of Medicaid data for future research.

Mineralocorticoid receptor antagonists (MRAs) reduce mortality in heart failure, yet whether eplerenone and spironolactone differ in effectiveness remains uncertain owing to the absence of head-to-head trials.

To compare all-cause mortality, heart failure hospitalization, major adverse cardiovascular events (MACE), and chronic kidney disease (CKD) progression between new users of eplerenone and spironolactone with heart failure.

Retrospective, new-user cohort study using the TriNetX Global Collaborative Network (171 healthcare organizations). Adults with heart failure receiving a first MRA prescription were matched 1 : 1 by propensity score. Prespecified subgroup analyses were performed in heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF).

After matching (38 952 pairs), all standardized mean differences (SMDs) were below 0.10 except serum potassium (SMD 0.18). At 36 months, eplerenone was associated with lower all-cause mortality [11.75 vs. 14.58%; hazard ratio 0.795, 95% confidence interval (CI) 0.765-0.827; P < 0.0001], heart failure hospitalization (hazard ratio 0.917, 95% CI 0.902-0.932), MACE (hazard ratio 0.900, 95% CI 0.886-0.915), and CKD progression (hazard ratio 0.803, 95% CI 0.745-0.867; all P < 0.0001). In HFrEF, eplerenone was associated with significantly lower rates across all outcomes. In HFpEF, mortality did not differ significantly (hazard ratio 0.946, 95% CI 0.876-1.021; P = 0.162), and spironolactone was associated with lower MACE (hazard ratio 1.135, 95% CI 1.087-1.184) and heart failure hospitalization (hazard ratio 1.144, 95% CI 1.108-1.181; both P < 0.0001).

In this large propensity score-matched cohort, eplerenone was associated with lower mortality, MACE, and CKD progression than spironolactone overall and in HFrEF. In HFpEF, spironolactone was favoured for MACE and heart failure hospitalization, with no significant difference in mortality. These hypothesis-generating findings support prospective head-to-head trials.

Fragmented QRS (fQRS) is an electrocardiographic marker of myocardial injury associated with adverse outcomes in acute coronary syndromes. This study aimed to examine its prognostic value within the acute coronary occlusion myocardial infarction (ACOMI) classification framework.

We retrospectively analyzed 996 patients with Type 1a or Type 1b ACOMI-compatible ECGs. The primary endpoint was all-cause mortality. A prespecified multivariable Cox regression model with 10 covariates was used. Model discrimination was assessed using the area under the ROC curve (AUC).

fQRS was present in 237 patients (23.7%). During a median follow-up of 618 days (IQR: 398-725 days), 127 deaths occurred (12.6%). Kaplan-Meier analysis showed significantly lower survival in fQRS-positive patients (79.3% vs. 89.7%; P < 0.001). On multivariable Cox regression, fQRS was an independent predictor of mortality [hazard ratio (HR): 1.702; 95% confidence interval (CI) 1.050-2.760; P = 0.032], alongside the GRACE risk score (HR: 1.021; P < 0.001) and left ventricular ejection fraction (HR: 0.955; P < 0.001). fQRS improved model discrimination (AUC: 0.784-0.800; ΔAUC = +0.016). In the Type 1a subgroup, a signal toward increased fQRS-associated mortality was observed (HR: 1.662; P = 0.056), though this did not reach statistical significance. The fQRS × ECG type interaction was nonsignificant (P-interaction = 0.733); subgroup findings should be regarded as hypothesis-generating.

fQRS on admission ECG is independently associated with all-cause mortality in ACOMI patients and may serve as a simple adjunctive marker for risk stratification, though prospective validation is needed.