Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease associated with a substantially increased risk of lung cancer. Yet IPF is still primarily conceptualized and communicated as a disease of progressive fibrosis. This creates an important diagnostic challenge: worsening cough, breathlessness, fatigue, functional decline, or weight loss may be attributed to progression of fibrosis even when malignancy is also a possibility. In the absence of standardized cancer surveillance guidelines for IPF, ensuring that patients understand their elevated cancer risk becomes particularly important. We argue that cancer-risk education can serve an important epistemic function. Drawing on the concept of hermeneutical injustice, we suggest that patients taught to understand their symptoms primarily through the framework of progressive fibrosis may lack an important interpretive resource for recognizing changes in their illness experience. Cancer-risk education should therefore be incorporated into initial and follow-up counseling for patients with IPF. The goal is not to make patients responsible for diagnosing cancer or to generate anxiety around every new symptom. Rather, education can close an interpretive gap, helping patients recognize that fibrosis and malignancy are not mutually exclusive explanations for clinical change and allowing them to participate as knowledgeable interpreters of their illness.

Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic and fatal interstitial lung disease. The etiology of IPF remains to be fully elucidated and its prognosis remains poor with a short survival period. Solute carrier family 7 member 5 (SLC7A5) is an amino acid transporter that is responsible for the transportation of large neutral amino acids. The expression of SLC7A5 was found to be significantly upregulated in patients with IPF, as well as in the lung tissues of mice with bleomycin (BLM)‑induced pulmonary fibrosis and in human lung fibroblasts induced by transforming growth factor‑β1 (TGF‑β1). Both SLC7A5 knockdown and the use of the selective SLC7A5 inhibitor JPH203 affected the function of TGF‑β1‑induced myofibroblasts by inhibiting the PI3K/AKT/mTOR pathway. In vivo, JPH203 improved BLM‑induced pulmonary fibrosis in mice by inhibiting the activation of the PI3K/AKT/mTOR signaling pathway. Therefore, SLC7A5 may represent a new therapeutic target for IPF. Future research should focus on therapeutic strategies regulating this target for translation into potential effective treatments for IPF in clinical practice.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic interstitial pneumonia of unknown etiology, in which macrophages serve as central orchestrators of the pathological microenvironment. During IPF progression, the alveolar macrophage pool undergoes a critical compositional shift: tissue-resident alveolar macrophages (TR-AMs) are progressively depleted and replaced by monocyte-derived alveolar macrophages (Mo-AMs) harboring a distinct pro-fibrotic transcriptional and metabolic identity. These populations differ fundamentally in their baseline metabolic programs, and both undergo further reprogramming within the fibrotic niche that sustains myofibroblast activation and extracellular matrix (ECM) deposition. This review systematically examines how metabolic reprogramming across three principal axes (glucose metabolism, lipid metabolism, and amino acid metabolism) drives pro-fibrotic macrophage polarization in IPF. Within each axis, alterations in metabolic flux and intermediate accumulation converge to reinforce the pro-fibrotic phenotype, promote fibroblast activation, and perpetuate ECM deposition. Importantly, these metabolic alterations differ between TR-AM and Mo-AM subpopulations in ways that reflect their distinct ontogenetic origins and predispose Mo-AMs to preferential pro-fibrotic polarization within the fibrotic microenvironment. Building on this mechanistic framework, we systematically categorize pharmacological modulators targeting these metabolic checkpoints and evaluate the integration of advanced drug delivery systems for precision intervention within the alveolar macrophage niche. This review ultimately proposes a therapeutic strategy that co-targets macrophage ontogenetic origin, polarization state, and metabolic reprogramming as an interconnected axis, offering new perspectives for re-educating macrophages to attenuate fibrotic progression in IPF.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disease with an extremely poor prognosis, and the rate of disease progression varies significantly among patients. Therefore, accurate prognostic assessment is crucial for clinical management. Traditional pulmonary function parameters, such as the absolute value of forced vital capacity (FVC) and the rate of decline in FVC as a percentage of predicted value (FVC%), serve as important bases for predicting disease progression and mortality. In recent years, prognostic prediction models have evolved from single indicators to composite scoring systems that integrate physiological, imaging, clinical manifestations, and even biomarkers. Furthermore, emerging indicators such as quantitative assessment of fibrosis extent on high-resolution computed tomography (HRCT), serum biomarkers, and artificial intelligence-based radiomics analysis provide powerful tools for earlier and more accurate identification of patients at risk of rapid disease progression. However, how to effectively incorporate these emerging indicators into clinical practice and clinical trials remains a current challenge. Future research should focus on validating and optimizing multi-omics prediction models, exploring their application value in individualized risk stratification and guiding treatment decisions for patients, with the ultimate goal of improving the long-term prognosis of IPF patients.

"High-demand sectors" are characterized by substantial physical, psychological, and emotional demands, alongside persistent recruitment and retention challenges. Despite growing interest in shaping healthy organizations, research has largely focused on workplace- or individual-level determinants. The aim of this study was to deepen the understanding of organizational-level health-promoting factors by exploring experienced managers' perspectives and visions regarding the promotion of a healthy work environment in high-demand sectors.

The mechanisms underlying the progression of pulmonary fibrosis in idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases remain unclear. Increased extracellular matrix stiffness is a hallmark of fibrotic lung diseases. Monocyte-derived macrophages can promote fibrosis progression. However, there is limited understanding of how the mechanical properties of the fibrotic microenvironment influence macrophage phenotypes. Profibrotic macrophages are apoptosis-resistant, and this phenotype is modulated by enhanced mitochondrial bioenergetics. The objective of the study was to determine how lung tissue stiffness impacts macrophage phenotypes and fibrotic progression. We demonstrate that mechanoactivated macrophages exhibit apoptosis-resistance, increased expression of the antiapoptotic protein Bcl-xL and increased mitochondrial oxidative phosphorylation. Critically, the metabolic reprogramming observed in mechanoactivated macrophages is dependent on increased glutaminolysis. Inhibition of glutaminolysis attenuated apoptosis resistance in mechanoactivated macrophages. Moreover, inhibition of Bcl-xL in vivo protected mice against experimental pulmonary fibrosis. Lastly, mechanoactivated primary IPF macrophages produce more profibrotic cytokines and promote extracellular matrix production in precision-cut lung slices. We describe a mechanism for acquired macrophage apoptosis resistance dependent on metabolic reprogramming regulated by extracellular matrix stiffness. Our results identify mechanoactivated apoptosis-resistant macrophages as pro-fibrotic mediators, suggesting a novel therapeutic target in IPF and related fibrotic disorders.

Pulmonary lymphatic vessels are essential for interstitial fluid balance and macromolecular clearance, yet the endothelial mechanisms regulating lymphatic vessel function during chronic fibroproliferative lung injury remain undefined. Here, we demonstrate that the lineage-defining transcription factor ERG in lymphatic endothelial cells (LECs) governs junctional plasticity and fluid drainage in pulmonary fibrosis. In human idiopathic pulmonary fibrosis (IPF) lungs, lymphatic ERG expression is markedly downregulated. Lineage-specific inducible deletion of Erg in murine LECs (Erg-CKO) unexpectedly conferred robust protection against bleomycin-induced pulmonary fibrosis, significantly dampening acute inflammation, reducing edema, and preserving pulmonary compliance. Mechanistically, loss of ERG enhanced lymphatic drainage capacity in vivo. Transcriptomic profiling of isolated LECs revealed that ERG deficiency activates actomyosin contractile pathways and selectively upregulates Endothelin Receptor Type B ( Ednrb ), driving junctional remodeling from continuous zippers into discontinuous button-like configurations that facilitate interstitial fluid entry. Pharmacological blockade of EDNRB with BQ-788 abolished junctional reorganization, eliminated the enhanced lymphatic drainage, and completely reversed the anti-fibrotic protection in Erg-CKO mice. Together, our findings identify an endothelial ERG-EDNRB regulatory axis that controls lymphatic junctional architecture and demonstrate that promoting lymphatic clearance via endothelial junctional remodeling represents a viable therapeutic strategy for fibrotic vascular remodeling.

Severe respiratory viral disease varies widely among individuals and often reflects immunopathology rather than inadequate pathogen control, suggesting that previous immune history can prime the lungs towards disease tolerance. Here we show that nerve- and airway-associated macrophages (NAMs), a subset of interstitial macrophages, expand ephemerally after type 2 inflammation induced by Nippostrongylus brasiliensis. We therefore hypothesized that NAMs acquire epigenetically imprinted trained immunity and tested this using a heterologous challenge model in which mice that were previously infected with N. brasiliensis were challenged 4-6 weeks later with lethal H1N1 influenza. All of the N. brasiliensis-conditioned mice survived, whereas all of the unconditioned controls succumbed by days 5-6. Protection occurred without reduced viral burden or enhanced T cell responses, instead tracking with reduced immunopathology, amplified type 2 cues, increased efferocytosis and accelerated tissue repair. Using NAM-DTR mice, we show that conditioned NAMs are necessary and sufficient for protection: depletion or replacement with unconditioned NAMs abrogated survival, whereas adoptive transfer of conditioned NAMs conferred tolerance without enhancing viral clearance. Genomic analyses implicated an IL-4-STAT6-PPARγ and ARG1 chromatin program that imprints a pro-resolving and reparative NAM state driving tissue repair, type 2 immunity and efferocytosis during lethal respiratory viral infections. Finally, meta-analysis of human lung single-cell atlases from cohorts of healthy individuals and individuals with IPF and COPD revealed context-dependent NAM-like repair programs. These findings establish local trained immunity in lung-resident macrophages as a mechanism of disease tolerance and a therapeutic entry point for severe inflammatory respiratory infections.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease closely associated with aging, yet the contribution of cellular senescence to fibrotic remodeling and its therapeutic implications remain incompletely understood. Syringin, a phenylpropanoid glycoside derived from Acanthopanax senticosus, has been reported to possess anti-inflammatory and antioxidant activities, but its role in IPF has not been elucidated. In this study, bulk lung transcriptomic data from the GTEx project and nine IPF cohorts were integrated with IPF scRNA-seq data to characterize senescence-associated fibrotic programs. A systems-level compound prioritization strategy incorporating reversed gene expression scoring, network proximity analysis, drug-likeness and toxicity evaluation was applied to identify candidate molecules. The results revealed a pronounced aging-associated transcriptomic profile in IPF lungs, with strong concordance between age-related and IPF-related gene programs. Single-cell analyses further identified senescent fibroblast populations as key cellular hubs characterized by elevated expression of SASP factors. Syringin was subsequently validated in TGFβ1-stimulated fibroblasts, and a murine model of bleomycin-induced pulmonary fibrosis. Syringin consistently attenuated fibroblast activation, cellular senescence markers, and pulmonary fibrosis in vivo and in vitro. Mechanistically, syringin markedly reversed the activation of replication stress-associated signaling pathways. Molecular docking and CETSA suggested a potential interaction between syringin and CHK1. Furthermore, CHK1 knockdown partially abrogated the regulatory effects of syringin on the ATR/CHK1-p53 signaling cascade, supporting CHK1 as a functional mediator of syringin activity. Collectively, these findings identify syringin as a natural small molecule with anti-senescent and anti-fibrotic properties, and may represent a potential therapeutic strategy for IPF.

Atmospheric mercury (Hg) can undergo long-range transport before depositing into ecosystems, where it may be methylated and bioaccumulated in food webs, creating ecological and health concerns. High-resolution, process-based Hg source-receptor analyses are computationally intensive, limiting systematic evaluation of region-sector emission-control scenarios. To address this, atmospheric Hg response models (RMs) using a ResNetCNN-LSTM architecture trained on emissions, meteorological fields, and Community Multiscale Air Quality (CMAQ)-simulated speciated Hg concentrations and depositions. Coupling the RMs with iterative proportional fitting establishes an RM-IPF framework for efficient multi-region, multi-sector source contribution analysis. Out-of-sample tests showed that the RMs reproduced CMAQ-simulated, rather than directly observed, speciated Hg concentrations and depositions, with mean Pearson correlation coefficients exceeding 0.93 across all targets. Sensitivity analyses yielded response patterns consistent with key CMAQ processes, including dry deposition of gaseous elemental Hg, wet scavenging of reactive Hg, and chemical transformations among Hg species. By integrating RM-derived regional constraints with CMAQ-simulated sectoral constraints, RM-IPF closely reproduced CMAQ brute-force source contribution estimates while avoiding exhaustive zero-out simulations. In Guangdong, China, RM-IPF identified cement production in northern Guangdong and waste incineration in the Pearl River Delta as the largest contributors to anthropogenic Hg concentration (22.96%) and deposition (24.36%), respectively. Distinct dominant contributors highlight that emission control priorities depend on management objectives. This framework enables rapid scenario assessment and source-receptor analysis, supporting targeted Hg emission controls under the Minamata Convention on Mercury.