The aging of mesenchymal stromal cells (MSCs) is characterized by impaired osteogenic differentiation and enhanced adipogenic differentiation. Studies have identified stanniocalcin‑1 (STC1) as a core component of the senescence‑associated secretory phenotype and a regulator of osteoblast maturation; however, its role in MSC biology remains poorly understood. In the present study, bone marrow‑derived MSCs were used and in vitro functional assays together with molecular and omics‑based analyses were performed to investigate the role of STC1. It was observed that STC1 expression was upregulated in aged MSCs and during both osteogenic and adipogenic differentiation. Small interfering RNA‑mediated depletion of STC1 reduced cellular senescence and notably impaired osteogenic differentiation, whereas adipogenic and chondrogenic differentiation were not significantly affected. RNA sequencing revealed that STC1 knockdown led to the downregulation of osteogenesis‑related genes and the concomitant upregulation of inflammatory factors. Genes associated with closing differentially accessible regions (DARs) were enriched in osteogenic pathways, whereas those associated with opening DARs were predominantly involved in inflammatory responses. Mechanistically, STC1 knockdown led to the activation of NF‑κB signaling. Pharmacological inhibition assays using NF‑κB inhibitors were performed to validate pathway involvement. Pharmacological inhibition of NF‑κB signaling significantly mitigated the impairment in osteogenic differentiation and attenuated the inflammatory response induced by STC1 depletion. Collectively, these findings suggest that STC1 is involved in the regulation of osteogenic differentiation and inflammatory signaling through the modulation of NF‑κB activity in MSCs. Furthermore, targeting STC1 while inhibiting NF‑κB signaling may represent a promising therapeutic strategy for alleviating MSC dysfunction and age‑related bone loss.

Background Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by high mortality with no specific treatments. Fibroblast growth factor 10 (FGF10) is recognized for its tissue repair and anti-inflammatory roles in injured lungs; however, its clinical relevance and mechanistic role in ARDS remain unclear.Methods Serum FGF10 levels were measured in patients with ARDS and analyzed for associations with clinical outcomes. An LPS-induced mouse model of acute lung injury (ALI) was used to evaluate the effects of FGF10 treatment in vivo. Single-cell RNA sequencing of lineage-traced alveolar epithelial cells (AECs) was performed to identify transcriptional changes following FGF10 administration. In vitro co-culture systems involving macrophages or neutrophils with AECs were established to investigate immune cell-specific mechanisms.Results We found that serum FGF10 levels were significantly reduced in ARDS patients, and this reduction correlated with poor prognosis. Moreover, FGF10 treatment alleviated lung inflammation by decreasing inflammatory cell infiltration and pro-inflammatory cytokine release in mice. Leveraging single-cell RNA sequencing of lineage tracing alveolar epithelial cells (AECs), we identified that the mRNA expression of Ripk1, Casp8, and Casp3 were decreased after FGF10 treatment. In in vitro co-culture experiments, we noticed that FGF10 did not inhibit macrophage pyroptosis. Instead, FGF10 effectively blocked the downstream RIPK1/caspase-8/caspase-3/gasdermin E (GSDME) signaling pathway in AECs. Additionally, FGF10 suppressed AMP-activated protein kinase (AMPK) activation by modulating ATP production, thereby preventing RIPK1 cleavage.Conclusion FGF10 alleviates acute lung injury by inhibiting AMPK-RIPK1/caspase-8/caspase-3/GSDME-mediated pyroptosis in AECs primed by distinct immune cell populations, supporting its potential as a therapeutic strategy for ARDS.Key points Our study reveals a marked decrease of serum FGF10 levels in ARDS patients, correlating with P/F ratio, hospitalisation days and mortality rates. We clarify how FGF10 prevents AECs' pyroptosis triggered by different immune cell infiltrations in different ways. FGF10 restored ATP levels to attenuate RIPK1 phosphorylation via AMPK to disrupt pyroptosis in the AECs.

Aim: Mesenchymal stem cells (MSCs) have shown therapeutic potential in acute lung injury (ALI); however, the key functional components and their roles in regulating pulmonary vascular endothelial permeability remain unclear. This study aimed to identify functional proteins within MSC-derived exosomes (MSC-Exo) and elucidate their roles in regulating pulmonary vascular endothelial permeability to enhance MSC-Exo-based therapy. Methods: Proteomic analysis identified neuropilin-1 (NRP1) as a candidate functional protein in MSC-Exo. Functional assays, including annexin V flow cytometry for apoptosis, colony formation assays for proliferation, and Transwell migration and wound healing assays, were performed to assess these processes in injured pulmonary microvascular endothelial cells (PMVECs). Immunofluorescence and Western blotting were used to evaluate NRP1 localization, p130Cas phosphorylation and matrix metalloproteinases 1 (MMP1)/9 expression. In ALI rat models, histopathology, Evans blue extravasation, and immunohistochemistry were used to assess lung injury and vascular permeability. Results: NRP1-enriched MSC-Exo reduced apoptosis, enhanced colony formation, and promoted migration in PMVECs. Mechanistically, NRP1 modulated the Bcl-2/Bax ratio, inhibited caspase 3/9 activation, and promoted p130Cas phosphorylation with increased MMP1/9 expression. NRP1 also colocalized with PDGFR-α, suggesting a potential role in PDGF-BB signaling. In vivo, NRP1-overexpressing exosome showed superior efficacy in reducing pulmonary edema, vascular leakage, and restoring tight junction proteins, whereas NRP1 depletion impaired these effects. Conclusion: NRP1 in MSC-Exo enhances endothelial repair by promoting proliferation and migration while inhibiting apoptosis. In vivo, NRP1-enriched MSC-Exo improve vascular barrier function and attenuate lung injury, supporting their therapeutic potential in ALI.

Dental tissues development involves two distinct cell lineages: mesenchymal cells (derived from the cranial neural crest) and epithelial cells (derived from oral ectoderm and pharyngeal epithelium). Emerging evidence highlights the remarkable functional heterogeneity of cranial neural crest-derived dental mesenchymal stem cells (DMSCs), exhibiting pluripotency, self-renewal, and differentiation capacities. This heterogeneity enables a single DMSC population to generate specialized subpopulations with unique roles in teeth and periodontal tissues formation. Significant progress has been made in characterizing six major types of DMSCs and two populations of closely related cells: Tooth germ progenitor cells (TGPCs) and dental follicle stem cells (DFSCs), critical during early morphogenesis; Stem cells from human exfoliated deciduous teeth (SHEDs) and apical papilla stem cells (SCAPs), pivotal for root development; Dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), gingival mesenchymal stem cells (GMSCs) and alveolar bone mesenchymal stem cells (ABMSCs), essential for maintaining and regenerating mature dental tissues. A key breakthrough has unveiled the development and hierarchy of DMSCs by applying new techniques like single-cell RNA sequencing (scRNA-seq). To integrate insights into the development of teeth and periodontal tissues, this review synthesizes current knowledge on both developmental heterogeneity and subpopulation heterogeneity within DMSCs and related cells. These insights not only advance fundamental understanding of the developmental mechanisms of teeth and periodontal tissues, but also establish a promising framework for achieving more efficient tissue regeneration and repair engineering.

ABSTRACT Background Pyroptosis is a recently identified form of programmed cell death that plays an important role in cancer initiation and progression. However, the function of pyroptosis in lung adenocarcinoma (LUAD) remains unclear. The study integrated proteomic and single‐cell RNA sequence (scRNA‐seq) data to investigate the potential role of pyroptosis‐related proteins (PRPs) in the tumor microenvironment (TME) and their associations with tumor immunity, prognosis, and therapeutic response. Methods A comprehensive proteomic analysis was conducted on 103 lung adenocarcinoma patients. We integrated scRNA‐seq data with bioinformatics analyses to evaluate prognostic and immunological characteristics. Unsupervised clustering based on the PRP expression identified three subtypes. We then used gene set enrichment analysis (GSEA) to assess biological functions. We applied TME and CIBERSORT algorithms to analyze immune cell infiltration. Next, we performed functional enrichment, immune infiltration, and cell–cell communication analyses using scRNA‐seq data grouped according to the proteomic subtypes. We constructed a PRP‐related prognostic signature using least absolute shrinkage and selection operator (LASSO)‐Cox regression analysis. Finally, we validated the expression and functional significance of selected proteins by immunohistochemistry, Western blotting, quantitative PCR, and in vitro loss‐of‐function assays. Results We identified multiple PRPs that correlated with clinicopathologic characteristics, patient prognosis, and immune infiltration patterns in the TME. We further identified three distinct molecular subtypes, including lipid metabolism, signaling transduction, and immune activation. Among these subtypes, the lipid metabolism subtype showed the best prognosis. ScRNA‐seq analysis further supported the immune characteristics of three subtypes and revealed distinct cellular interaction networks and ligand‐receptor pairs. We also established and validated a PRP‐related prognostic score that effectively predicted overall survival in patients with LUAD. In addition, the PRP score was significantly associated with tumor immune status and sensitivity to chemotherapeutic agents. Conclusion Our integrated analysis of proteomic and scRNA‐seq data demonstrated that PRPs are closely associated with the tumor‐immune‐stromal microenvironment, clinicopathological features, and prognosis in LUAD. These findings improve our understanding of the biological roles of PRPs in LUAD and may provide new strategies for prognostic evaluation and immunotherapy development.

The lungs interface directly with the external environment, exposing them to airborne pathogens like endotoxins. We investigated whether the vagus nerve, which innervates the lungs-detects such pathogens. Using transcriptomics, tissue clearance imaging, electrophysiology, and cell-specific knockout models, we discovered that vagal sensory endings synapse with pulmonary neuroendocrine cells (PNECs). These nerve endings detect bacterial endotoxins primarily through the pain receptor TRPA1, not via Toll-like receptor 4 (TLR4). This detection triggers electrical excitation in vagal neurons and upregulates neuropeptide (e.g., αCGRP) production in the nodose ganglia. Released αCGRP then acts back on PNECs, stimulating their neuropeptide synthesis and proliferation. This creates a feed-forward loop that amplifies endotoxin-induced lung inflammation. Our findings reveal a critical neural circuit between the nodose ganglion and PNECs that regulates pulmonary inflammatory responses.

IntroductionChronic pain is a major global health problem that significantly affects quality of life and increases the risk of cardiovascular diseases.MethodsUsing the Global Burden of Disease (GBD) 2021 data, this study analyzed temporal trends in chronic pain across 204 countries and territories from 1990 to 2021. We further examined the influence of the Socio-demographic Index (SDI), explored age- and sex-specific patterns, and projected the future burden of chronic pain through 2032. Cardiovascular diseases data were also analyzed for correlations with chronic pain.ResultsResults showed a significant positive association between SDI and age-standardized prevalence rate (ASPR), with higher burdens in more developed regions, especially for cancer- and arthritis-related pain. Apart from headaches, most types of chronic pain—including low back pain, neck pain, osteoarthritis-related pain, and rheumatoid arthritis-related pain—were more prevalent in older adults. Females were generally more affected by musculoskeletal and arthritis-related pain, while males showed higher rates of gout- and pancreatitis-related pain. Projections suggest that the prevalence of rheumatoid arthritis and other musculoskeletal pain will continue to rise, whereas gout-, back-, neck-, and pancreatitis-related pain are expected to decline. Notably, chronic pain showed significant positive correlations with several cardiovascular diseases, including ischemic heart disease and stroke.DiscussionThe global burden of chronic pain remains substantial and unevenly distributed by sex, age, and SDI level. The observed association between chronic pain and cardiovascular diseases highlights the need for integrated management strategies targeting both conditions.

Sporadic epidemics of coxsackievirus A4 (CVA4) have been reported worldwide. However, the lack of the whole genome sequence has restricted the study of the gene characterization and evolution of CVA4. In this study, four whole genome sequences and 17 VP1 sequences of CVA4 identified from Linyi, northern China, in summer 2024 were used for genetic characterization and phylogenetic analysis. Four genotypes (A, B, C, and D) and five subgenotypes (C1-C5) were identified based on VP1 sequences. The Linyi CVA4 strains belong to subgenotype C2, which has also been the main prevalent subgenotype in China in recent years. The Linyi CVA4 strains exhibited high homology with the CVA4 prototype strain in the P1 region while exhibited higher homology with some non-CVA4 EV-A strains identified in China, including five CVA2 strains, three CVA5 strains, three CVA6 strains, one CVA8 strain, one CVA12 strain, and one CVA14 strain in the P2 and P3 regions. Recombination analysis of the whole genome sequences of the Linyi CV4 strains revealed that two Linyi CVA4 strains might be recombinants of one Shanghai CVA4 strain (KJ541163) and one Jiangsu CVA2 strain (OL519580). One Linyi CVA4 strain might be a recombinant of one Shandong CVA2 strain (MK967660) and one Shanghai CVA4 strain (KJ541163).

BACKGROUND:Lineage tracing is an emerging technology with the outstanding advantage of labeling stem cells and their descendants with temporal and spatial specificity in vivo. We aimed to systematically review the research advances of distal lung epithelial progenitors via lineage tracing strategies. RESULTS:The distal lung, including bronchioles and alveoli, carries the respiratory function and is the central region involved in acute respiratory distress syndrome and other diseases. Many endogenous epithelial stem cell/progenitor lineages such as Club cells, alveolar type II cells, bronchioalveolar stem cells, and basal-like progenitors that contribute to distal lung regeneration have been identified and are engaged in repairing lung injury for various reasons. Advances in lineage tracing technology have provided tremendous support in characterizing progenitor lineages, identifying new progenitor cell lineages, and discovering regulators of their behaviors. CONCLUSIONS:The important role of distal lung epithelial progenitors and lineage tracing methods has been highlighted in recent years. Relevant studies provide a perspective for further deepening lineage tracing in lung progenitor research and laying the groundwork for endogenous stem cell therapies in the future.

The lungs are organs exposed to the external environment, and the air we inhale contains various pathogens, such as endotoxins. The vagus nerve, which innervates the lungs, may play a role in detecting pathogens that invade the lungs. Through transcriptome analysis, tissue clearance imaging, electrical excitability recording, and gene- and cell-specific knockout experiments, we found that vagus nerve endings innervate pulmonary neuroendocrine cells (PNECs). These nerve endings sense bacterial endotoxins via pain receptors (TRPA1) rather than toll-like receptors (TLR4), eliciting electrical excitation and enhancing the production of neuropeptides (αCGRP) in the nodose ganglia. In turn, αCGRP released by sensory neurons from the nodose ganglia promotes both neuropeptide production and the proliferation of PNECs, thereby amplifying endotoxin-induced lung inflammatory responses. This reveals that the neural circuits between the nodose ganglion and PNECs play a critical role in regulating lung inflammatory responses. ### Competing Interest Statement The authors have declared no competing interest.

Acute respiratory distress syndrome (ARDS) is a severe clinical condition characterized by widespread inflammation and fluid accumulation in the lungs. Endothelial cell (EC) metabolic changes in acute lung injury (ALI) and their relationship to injury remain unclear. Transcriptomic and lipidomic analyses revealed downregulation of PUFA synthesis pathways, particularly omega-3 PUFAs, in pulmonary ECs during LPS-induced ALI. Activation of the PUFA metabolic pathway, through FADS1/2 overexpression or omega-3 fatty acid supplementation, protected ECs from ferroptosis and restored barrier function. In vivo, pulmonary EC-specific overexpression of FADS1/2 contributed to the alleviation of ALI. Overexpression of whole lung FADS1/2, combined with alpha-linolenic acid (ALA) supplementation, also significantly mitigated ALI. PARK7 is identified as an endogenous regulator of FADS1/2, acting through the BMP-BMPR-SMAD1/5/9 signaling. Driven by histone H3K14 lactylation, which is also promoted by the downregulation of FADS1/2, PARK7 upregulation restored FADS1/2 expression and counteracted ferroptosis, thereby forming a protective feedback loop. This study elucidates a novel regulatory axis involving the two major metabolic changes-downregulation of PUFA synthesis and upregulation of histone lactylation-in ALI pathogenesis, which are interconnected through the PARK7-BMP signaling pathway. Targeting this axis offers potential therapeutic strategies for mitigating endothelial dysfunction and ferroptosis in ARDS/ALI.

IntroductionCodon usage bias (CUB) can influence host-microbe interactions and stress adaptation. In this study, we aimed to investigate how codon usage bias (CUB) similarity between Arabidopsis thaliana and Bacillus amyloliquefaciens influences their interaction and contributes to the adaptation of A. thaliana to high calcium stress.MethodsThe CUB indices of both species were computed, and genes with high correlations were identified. The transcriptome sequencing data of gene expression in A. thaliana cultured under normal and high calcium conditions, with and without B. amyloliquefaciens treatment was used to analyze the expression of A. thaliana genes with CUB similar to that of B. amyloliquefaciens in relation with the adaptation of A. thaliana to high calcium stress and the interaction between both organisms.ResultsWe identified 19210 A. thaliana genes with CUB similar to B. amyloliquefaciens and 95 B. amyloliquefaciens-responsive and calcium-responsive genes in A. thaliana, which were involved in transport, carbohydrate metabolism, and response to chemical, and cellular homeostasis. Differential expression analysis showed a total of 733 A. thaliana genes with CUB similar to B. amyloliquefaciens to be dysregulated, among which 47 changed when A. thaliana was cultivated in the presence of the B. amyloliquefaciens LZ04 strain, 643 under high calcium condition and 43 with calcium treatment and the presence of the B. amyloliquefaciens LZO4 strain. The gene ontology (GO) biological processes termed among others of response to endogenous stimulus, response to oxygen containing compound, response to organic substance, response to abiotic and biotic stimuli, response to stress, and response to light stimulus, regulation of hormone levels, response to nutrient levels, post-embryonic plant morphogenesis, metabolic process, cell growth.DiscussionThese findings highlight the importance of CUB in the interaction between A. thaliana and B. amyloliquefaciens as well as in the adaptation of A. thaliana to high calcium stress. They also show the underlying regulatory role of B. amyloliquefaciens, which could help develop new tactics for improving A. thaliana growth and yield in karst regions. A more elaborate analysis of the value of CUB in the interaction of these two organisms could assist in engineering host- sensitive micro-organism strains and enhance the microbial-based approaches for the improvement of A. thaliana growth and yield in such areas and for managing abiotic stress in crops.

The mechanisms of endothelial cell injury in acute lung injury (ALI) remain unclear, and effective interventional strategies targeting endothelial cells are limited. Sodium 4-phenylbutyrate (Na-PBA), a histone deacetylase inhibitor, can potentially reduce oxidative damage. Its effects on pyroptosis and its relationship with PARK7, a redox-regulating protein, remain unclear. Using a lipopolysaccharide (LPS)-induced ALI mouse model, we evaluated Na-PBA's effects on lung tissue damage, inflammatory markers, and endothelial pyroptosis. In vitro, human umbilical vein endothelial cells (HUVECs) were treated with LPS, Nigericin, and Na-PBA to assess pyroptosis and oxidative stress responses. RNA sequencing, immunoblotting, gene knockdown, and overexpression were utilized to explore molecular mechanisms. Na-PBA pretreatment alleviated lung injury, reduced pulmonary edema, and lowered inflammatory cytokines in LPS-ALI mice. It significantly decreased oxidative stress and pyroptosis of endothelial cells via the cytochrome c (Cyt c)-caspase9-caspase3-GSDME pathway in vivo and in vitro. Na-PBA pretreatment increased PARK7 expression in HUVECs. Na-PBA depended on PARK7 to protect against HUVEC injury and GSDME-mediated pyroptosis in vitro and relied on PARK7 expression in endothelial cells to mitigate ALI in vivo. Na-PBA upregulated PARK7 through HDAC inhibition, which could be amplified through a positive feedback loop involving NRF2. Finally, upregulation of PARK7 may alleviate downstream caspase activation and pyroptosis by stabilizing mitochondria and inhibiting Cyt c leakage from mitochondria. In conclusion, Na-PBA alleviates ALI by modulating oxidative stress and pyroptosis through the PARK7-dependent Cyt c-caspase9-caspase3-GSDME pathway. This study's results provide a novel therapeutic approach for mitigating endothelial cell injury in lung diseases.

Vagus nerve regulates viral infection and inflammation via the alpha 7 nicotinic acetylcholine receptor (α7 nAChR); however, the role of α7 nAChR in ZIKA virus (ZIKV) infection, which can cause severe neurological diseases such as microcephaly and Guillain-Barré syndrome, remains unknown. Here, we first examined the role of α7 nAChR in ZIKV infection in vitro. A broad effect of α7 nAChR activation was identified in limiting ZIKV infection in multiple cell lines. Combined with transcriptomics analysis, we further demonstrated that α7 nAChR activation promoted autophagy and ferroptosis pathways to limit cellular ZIKV viral loads. Additionally, activation of α7 nAChR prevented ZIKV-induced p62 nucleus accumulation, which mediated an enhanced autophagy pathway. By regulating proteasome complex and an E3 ligase NEDD4, activation of α7 nAChR resulted in increased amount of cellular p62, which further enhanced ferroptosis pathway to reduce ZIKV infection. Moreover, utilizing in vivo neonatal mouse models, we showed that α7 nAChR is essential in controlling the disease severity of ZIKV infection. Taken together, our findings identify an α7 nAChR-mediated effect that critically contributes to limiting ZIKV infection, and α7 nAChR activation offers a novel strategy for combating ZIKV infection and its complications.

Reducing inflammatory damage and improving alveolar epithelium regeneration are two key approaches to promoting lung repair in acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Stimulation of cholinergic α7 nicotinic acetylcholine receptor (α7nAChR, coded by Chrna7) signaling could dampen lung inflammatory injury. However, whether activation of α7nAChR in alveolar type II (AT2) cells promotes alveolar epithelial injury repair and underlying mechanisms is elusive. Here, we found that α7nAChR was expressed on AT2 cells and was upregulated in response to LPS-induced ALI. Meanwhile, deletion of Chrna7 in AT2 cells impeded lung repair process and worsened lung inflammation in ALI. Using in vivo AT2 lineage-labeled mice and ex vivo AT2 cell-derived alveolar organoids, we demonstrated that activation of α7nAChR expressed on AT2 cells improved alveolar regeneration by promoting AT2 cells to proliferate and subsequently differentiate toward alveolar type I cells. Then, we screened out the WNT7B signaling pathway by the RNA-Seq analysis of in vivo AT2 lineage-labeled cells and further confirmed its indispensability for α7nAChR activation-mediated alveolar epithelial proliferation and differentiation. Thus, we have identified a potentially unrecognized pathway in which cholinergic α7nAChR signaling determines alveolar regeneration and repair, which might provide us a novel therapeutic target for combating ALI.

In mammals, early organogenesis begins soon after gastrulation, accompanied by specification of various type of progenitor/precusor cells. In order to reveal dynamic chromatin landscape of precursor cells and decipher the underlying molecular mechanism driving early mouse organogenesis, we performed single-cell ATAC-seq of E8.5-E10.5 mouse embryos. We profiled a total of 101,599 single cells and identified 41 specific cell types at these stages. Besides, by performing integrated analysis of scATAC-seq and public scRNA-seq data, we identified the critical cis-regulatory elements and key transcription factors which drving development of spinal cord and somitogenesis. Furthermore, we intersected accessible peaks with human diseases/traits-related loci and found potential clinical associated single nucleotide variants (SNPs). Overall, our work provides a fundamental source for understanding cell fate determination and revealing the underlying mechanism during postimplantation embryonic development, and expand our knowledge of pathology for human developmental malformations.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is characterized by diffuse alveolar injury primarily caused by an excessive inflammatory response. Regrettably, the lack of effective pharmacotherapy currently available contributes to the high mortality rate in patients with this condition. Xuebijing (XBJ), a traditional Chinese medicine recognized for its potent anti-inflammatory properties, exhibits promise as a potential therapeutic agent for ALI/ARDS. This study aimed to explore the preventive effects of XBJ on ALI and its underlying mechanism. To this end, we established an LPS-induced ALI model and treated ALI mice with XBJ. Our results demonstrated that pre-treatment with XBJ significantly alleviated lung inflammation and increased the survival rate of ALI mice by 37.5%. Moreover, XBJ substantially suppressed the production of TNF-α, IL-6, and IL-1β in the lung tissue. Subsequently, we performed a network pharmacology analysis and identified identified 109 potential target genes of XBJ that were mainly involved in multiple signaling pathways related to programmed cell death and anti-inflammatory responses. Furthermore, we found that XBJ exerted its inhibitory effect on gasdermin-E-mediated pyroptosis of lung cells by suppressing TNF-α production. Therefore, this study not only establishes the preventive efficacy of XBJ in ALI but also reveals its role in protecting alveolar epithelial cells against gasdermin-E-mediated pyroptosis by reducing TNF-α release.