Guo F, Yang Z, She J
… +4 more, Fang C, Hu Y, Huang H, Gao L
Cell Prolif
· 2026 May · PMID 41146589
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Sleep deprivation (SD) is a common issue among pregnant women. Maternal SD led to adverse effects on offspring health such as cognitive impairment through dysregulated metabolic pathways. However, it remains unknown whet...Sleep deprivation (SD) is a common issue among pregnant women. Maternal SD led to adverse effects on offspring health such as cognitive impairment through dysregulated metabolic pathways. However, it remains unknown whether maternal SD increases the offspring's susceptibility to nonalcoholic steatohepatitis (NASH) development. Here, we induced maternal SD during pregnancy and observed that maternal SD during pregnancy promoted the development of diet-induced NASH in offspring of both sexes in adulthood, with exacerbation of liver weight gain, hepatic steatosis, fibrosis, and hepatic dysfunction. The primary hepatocytes isolated from SD offspring were also more susceptible to palmitate acid-induced lipotoxic injury. Mechanistically, the detrimental effects of maternal SD were associated with augmented activation of inflammatory and apoptosis pathways in offspring liver tissues, which were attributed to upregulation of the transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). The melatonin signalling is reported to be pivotally affected by sleep disturbance both at the circulation and the placenta, and our further analysis revealed that melatonin supplementation during maternal SD normalised NR4A3 expression in offspring liver and alleviated the increased steatohepatitis susceptibility in offspring. Taken together, these results suggest that maternal SD during pregnancy predisposes offspring to NASH development in adulthood via an NR4A3-dependent mechanism, and maternal melatonin supplementation may hold promise for improving liver health in the offspring.
Srivastava PP, Bhasin S, Sharma P
… +7 more, Desai OM, Yadav K, Ayushma, Chakraborty R, Parvez S, Ramachandran R, Minocha S
Cell Prolif
· 2026 May · PMID 41108067
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Regeneration of the central nervous system (CNS) is a complex and tightly regulated process, yet the precise molecular players and transcriptional regulators involved remain incompletely understood. Here, we identify Hos...Regeneration of the central nervous system (CNS) is a complex and tightly regulated process, yet the precise molecular players and transcriptional regulators involved remain incompletely understood. Here, we identify Host Cell Factor-1 (Hcfc1), a transcriptional co-regulator, and O-GlcNAc transferase (Ogt), which cleaves and O-GlcNAcylates HCF-1, as crucial regulators of zebrafish brain and retinal regeneration. We uncover their interplay with the Hippo/Yap signalling pathway, a well-known regulator of tissue growth and repair. Knockdown of hcfc1a/b or Ogt activity inhibition disrupts regeneration and reduces Yap levels, while Yap inhibition alone also impairs regeneration. Strikingly, overexpression of constitutively active Yap5SA rescues proliferation defects caused by Hcfc1 depletion and Ogt inhibition in retinal regeneration. Further, yap1 knockdown reduces hcfc1a/b levels, suggesting potential feedback regulation. These findings reveal a previously unrecognised regulatory axis involving Hcfc1, Ogt, and the Hippo/Yap pathway, which governs CNS regeneration. Targeting this pathway could offer a strategy for enhancing CNS regeneration.
Liu Q, Zheng H, Liu J
… +3 more, Gao M, Lin F, Liao L
Cell Prolif
· 2026 Feb · PMID 41090983
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Pulmonary vascular endothelial cells (VECs) are essential for the normal function of the lung, through maintaining vascular barrier integrity, regulating blood flow, and participating in inflammatory responses to safegua...Pulmonary vascular endothelial cells (VECs) are essential for the normal function of the lung, through maintaining vascular barrier integrity, regulating blood flow, and participating in inflammatory responses to safeguard oxygen exchange and physiological homeostasis. The occurrence and development of various pulmonary diseases all take the injury of pulmonary VECs as an important pathological hub, which directly affects the therapeutic effect and prognosis recovery of patients. The injury mechanisms of pulmonary VECs present multi-dimensional network characteristics, involving inflammation and oxidative stress, genetic factors, cellular senescence, metabolic abnormalities, and immune dysregulation. Due to the unique physiological structure of the lungs, traditional drugs often encounter significant challenges in clinical application such as insufficient targeting, low bioavailability, and systemic side effects. In order to overcome the existing treatment bottlenecks, it is crucial to implement an in-depth analysis of the molecular mechanism of pulmonary VECs injury. This review systematically explores the mechanisms of pulmonary VECs injury, evaluates novel therapeutic strategies targeting pulmonary VECs' dysfunction, and discusses the challenges and future prospects of clinical translation. The goal is to shift pulmonary diseases treatment from symptom management to precise molecular intervention.
Zou Y, Zhang J, Mao W
… +5 more, Jiang S, Xu C, Meng J, Dong H, Mou Y
Cell Prolif
· 2026 May · PMID 41077631
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Open skin wounds caused by burns, trauma, or underlying diseases impose substantial clinical challenges and significantly compromise patients' quality of life due to their complex management and high risk of scarring. In...Open skin wounds caused by burns, trauma, or underlying diseases impose substantial clinical challenges and significantly compromise patients' quality of life due to their complex management and high risk of scarring. In this study, we explore the therapeutic potential of apoptotic vesicles derived from interleukin-10-treated fibroblasts (IL10_ApoEVs) in promoting cutaneous wound healing and mitigating fibrotic scar formation. Our results demonstrate that IL10_ApoEVs enhance mitochondrial function and oxidative phosphorylation (OXPHOS), while concurrently suppressing glycolytic activity in fibroblasts. Importantly, IL10_ApoEVs markedly inhibit the Hedgehog signalling pathway, a key driver of fibrogenesis in various tissues, as evidenced by the downregulation of Shh and Gli1 expression. This modulation leads to attenuated aberrant extracellular matrix (ECM) deposition and promotes a favourable shift in collagen composition. This is characterized by increased type III collagen and reduced type I collagen, which is indicative of more elastic and functionally integrated tissue remodelling. These findings suggest that IL10_ApoEVs contribute to a regenerative microenvironment that supports scarless or minimally fibrotic healing. Collectively, our work highlights the promising application of IL10_ApoEVs in regenerative medicine and provides mechanistic insights into their dual role in metabolic reprogramming and antifibrotic signalling modulation during tissue repair.
Luo L, Huang F, Fang G
… +6 more, Sun Y, Deng L, Liao Y, Chen X, Chen Z, Lin X
Cell Prolif
· 2026 Feb · PMID 41077623
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Luteolin alleviates DSS-induced ulcerative colitis in mice by targeting the NLRP3 inflammasome, as it shows no effect in NLRP3 mice. It inhibits NLRP3 activation and IL-1β secretion in macrophages by reducing ROS, mtROS...Luteolin alleviates DSS-induced ulcerative colitis in mice by targeting the NLRP3 inflammasome, as it shows no effect in NLRP3 mice. It inhibits NLRP3 activation and IL-1β secretion in macrophages by reducing ROS, mtROS and calcium levels via AMPK binding and signalling. Metabolomic changes suggest lipid metabolism involvement. Luteolin represents a promising NLRP3-targeted therapeutic candidate for UC.
Chen Q, Lv J, Xie X
… +3 more, Zhu H, Xiao Z, Peng Y
Cell Prolif
· 2026 Apr · PMID 41017384
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Advancements in the generation of human pluripotent stem cell-derived natural killer (PSC-NK) cells have attracted considerable attention within the biomedical research community, offering a promising off-the-shelf techn...Advancements in the generation of human pluripotent stem cell-derived natural killer (PSC-NK) cells have attracted considerable attention within the biomedical research community, offering a promising off-the-shelf technique for universal immune therapy. However, this technique is associated with certain ethical, safety, and regulatory challenges, including ensuring genomic stability, preventing contamination and adhering to rigorous ethical standards for cell sourcing and obtaining informed consent. Addressing these challenges would require robust quality control, transparent data-sharing practices, and cross-border collaboration to ensure alignment with ethical and scientific standards. Future development must therefore focus on patient safety, data privacy and equitable access within a comprehensive ethical framework. These measures are crucial for maintaining public trust in and enabling the responsible clinical integration of PSC-NK therapies, thereby supporting their advancement while maintaining a balance between innovation and societal and ethical considerations.
Hao X, Shi H, Wu D
… +10 more, Liang R, Zhao T, Sun W, Wang Y, Yu X, Luo X, Yan Y, Lu J, Wang H, Wang J
Cell Prolif
· 2026 Apr · PMID 40984022
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The normal growth and development of skeletal muscle are crucial for the proper function of organisms. During myoblast development, cell death is a fundamental physiological process, and skeletal muscle damage involves v...The normal growth and development of skeletal muscle are crucial for the proper function of organisms. During myoblast development, cell death is a fundamental physiological process, and skeletal muscle damage involves various types of cell death, including ferroptosis. However, ferroptosis-related biomarkers in skeletal muscle damage remain unclear. This study aimed to investigate the mechanisms by which lipocalin-2 (LCN2), a key protein of iron metabolism, regulates skeletal muscle regeneration post damage by mediating ferroptosis. When the gastrocnemius muscle (GAS) of mice is acutely injured, LCN2 is significantly upregulated early in the injury. In vitro, LCN2 participates in the inhibition of proliferation and differentiation of C2C12 cells via erastin-induced ferroptosis. Transcriptomic analysis after the overexpression of LCN2 revealed that the one with the most significant difference among all of the differentially expressed genes (DEGs) was aconitate decarboxylase 1 (Acod1). The inhibition of myogenic factors' expression by LCN2 was associated with the activation of the ferroptosis signalling pathway, partly attributed to the mitochondrial dysfunction. The ACOD1 inhibitor attenuated mitochondria-associated ferroptosis induced by LCN2 and alleviated the inhibitory effect of LCN2 on cell viability. These findings highlight the therapeutic potential of targeting the LCN2-ACOD1 signalling to promote myogenesis, providing promising strategies for facilitating the regeneration of skeletal muscle after injury and the treatment of muscle-related diseases.
Xie CC, Wang T, Liu XR
… +8 more, Wang Y, Dang Q, Ding T, Xu JQ, Yu XJ, Lin H, Xu XW, Qin Y
Cell Prolif
· 2026 Feb · PMID 40969122
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The malignant transformation of cancer cells is underpinned by the dysregulation of essential cellular processes, including genome stability maintenance, DNA repair, transcriptional control and signal transduction. These...The malignant transformation of cancer cells is underpinned by the dysregulation of essential cellular processes, including genome stability maintenance, DNA repair, transcriptional control and signal transduction. These processes are not randomly distributed but are spatiotemporally coordinated through dynamic molecular assemblies. Recent advances have highlighted the pivotal role of biomolecular condensates, membraneless compartments formed via liquid-liquid phase separation (LLPS), in compartmentalising and regulating these key functions. LLPS enables the concentration and organisation of proteins and nucleic acids, creating distinct biochemical environments that facilitate cellular decision-making. Importantly, aberrant phase separation has been increasingly implicated in the acquisition of cancer hallmarks, such as sustained proliferative signalling, resistance to cell death and immune evasion. In this review, we summarise the physicochemical principles of LLPS, examine its emerging roles in oncogenic transformation and discuss the therapeutic potential of targeting phase separation in cancer. Our findings highlight LLPS as a novel and versatile regulatory layer in tumour biology and an emerging frontier in precision oncology.
Li Y, Li T, Jin F
… +10 more, Liu S, Xu D, Wei Z, Gao X, Cai W, Mao N, Yang F, Zhang H, Shi Y, Xu H
Cell Prolif
· 2025 Dec · PMID 40967637
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Targeting macrophage SCTR mitigates integrated profibrotic, inflammatory, ER stress, and senescent pathways, preserving lung function and revealing a novel therapeutic strategy for silicosis.Targeting macrophage SCTR mitigates integrated profibrotic, inflammatory, ER stress, and senescent pathways, preserving lung function and revealing a novel therapeutic strategy for silicosis.
Zhu L, Xu K, Ding Y
… +9 more, Liu K, Liu J, Hou Z, Niu R, Yang N, Qin H, Hu B, Zhang Y, Li W
Cell Prolif
· 2026 May · PMID 40958204
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Adeno-associated virus (AAV) has emerged as the predominant viral vector in clinical gene therapy. However, its widespread application confronts critical challenges, including pre-existing neutralising antibodies in 40%-...Adeno-associated virus (AAV) has emerged as the predominant viral vector in clinical gene therapy. However, its widespread application confronts critical challenges, including pre-existing neutralising antibodies in 40%-80% of the population, species-dependent therapeutic discrepancies, and suboptimal tropism specificity. While current AAV capsid modification strategies (e.g., directed evolution and rational design) have advanced the field, their implementation has been hampered by incomplete mechanistic understanding and persistent translational roadblocks, necessitating the need for the discovery of novel AAV capsids. In this study, we systematically captured 1925 natural AAV variants from non-human primate (NHP) tissues by integrating multiple Polymerase Chain Reaction (PCR) primers and deep long-read sequencing technology, significantly expanding the natural capsid library by more than 20-fold and identifying 1274 representative AAV11 family variants. Based on the co-evolution analysis of these natural AAV11 variants, we designed the engineered variant AAV11.P5V6, which showed significantly enhanced transduction efficiency in human and NHP primary hepatocytes in vitro and achieved efficient targeting in a mouse central nervous system model. In addition, AAV11 and its variants maintain a strong antibody escape ability in human serum and immune animal models, exhibiting unique serological characteristics with almost no cross-neutralisation reaction with AAV8 and AAV9, confirming its low serum prevalence and immune evasion advantages. This study established a systematic framework of 'natural discovery-evolutionary analysis-functional optimization', providing a new paradigm for the development of next-generation AAV vectors with clinical-grade tissue specificity, low immunogenicity, and cross-species compatibility.
Zhao X, Qiu Y, Chen J
… +6 more, Wang D, Wang Z, Ma S, Liu Y, Liu G, Bi Z
Cell Prolif
· 2026 Feb · PMID 40947310
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Breast cancer remains the most prevalent malignancy among women, and radiotherapy plays a pivotal role in reducing local recurrence and improving prognosis. However, the emergence of radioresistance in a subset of patien...Breast cancer remains the most prevalent malignancy among women, and radiotherapy plays a pivotal role in reducing local recurrence and improving prognosis. However, the emergence of radioresistance in a subset of patients significantly compromises treatment efficacy, underscoring the need for a deeper understanding of the underlying molecular mechanisms. In recent years, non-coding RNAs (ncRNAs) have emerged as key regulators of gene expression and have garnered increasing attention for their roles in mediating radioresistance in breast cancer. This review systematically summarises the major molecular mechanisms by which ncRNAs contribute to breast cancer radioresistance, including cell cycle regulation, DNA damage repair, programmed cell death (e.g., apoptosis, autophagy and ferroptosis), oxidative stress response, tumour microenvironment remodelling and maintenance of cancer stem cell properties. On the translational front, RNA-based therapeutic approaches-including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), miRNA mimics and CRISPR/Cas9-offer promising avenues for radiosensitisation, yet face substantial clinical hurdles. These include immune activation, poor delivery specificity, intracellular trafficking barriers and limited stability. Advances in chemical modifications and nanoparticle-based delivery systems-such as redox-responsive nanocarriers-have shown potential in enhancing the efficacy and safety of ncRNA-targeted therapies. Despite encouraging progress, clinical translation remains constrained by a lack of methodological standardisation, insufficient high-quality clinical data, limited biomarker reliability, suboptimal target selection and unresolved safety concerns. Future efforts should prioritise optimisation of delivery platforms, validation of multi-ncRNA biomarker panels in large, multicentre cohorts and integration of multi-omics data to reconstruct comprehensive regulatory networks, ultimately accelerating the clinical deployment of ncRNA-based radiosensitisation strategies.
Zhang H, Zhang L, Feng Z
… +4 more, Li X, Qiu Z, Wang X, Qian L
Cell Prolif
· 2026 Apr · PMID 40930719
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The mature mammalian heart has limited ability for self-repair and regeneration. Here, we establish phosphoglycerate dehydrogenase (PHGDH) as a crucial key for cardiomyocyte proliferation, with diminishing expression dur...The mature mammalian heart has limited ability for self-repair and regeneration. Here, we establish phosphoglycerate dehydrogenase (PHGDH) as a crucial key for cardiomyocyte proliferation, with diminishing expression during postnatal cardiac development. PHGDH overexpression promoted myocardial regeneration and cardiac function in apical resection-operated mice, whereas inhibition by NCT-503 inhibited these processes. In vitro, PHGDH stimulated the proliferation of cardiomyocytes (CMs), while NCT-503 abolished its effect. Mechanistically, PHGDH activated the cell cycle and TGF-β/Smad signalling. Moreover, PHGDH significantly enhances cardiac repair and stimulates cardiomyocyte proliferation in adult mice following myocardial infarction. Our study demonstrates that upregulating PHGDH promotes CM proliferation and myocardial regeneration, offering a promising therapeutic target for myocardial repair.
Ou L, Qiao S, Liao Z
… +13 more, Tan X, Huang H, Zhou Z, Luo R, Zeng W, Yang Y, Zhang Z, Chen J, Wang S, Jiang Y, Hao J, Shen Y, Shao L
Cell Prolif
· 2026 Apr · PMID 40908637
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Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe complication in patients undergoing long-term bisphosphonate therapy, while our knowledge on the pathogenesis of BRONJ is far from sufficient. Gamma del...Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe complication in patients undergoing long-term bisphosphonate therapy, while our knowledge on the pathogenesis of BRONJ is far from sufficient. Gamma delta (γδ) T cells predominantly distribute in mucosal tissues and play an important role in both immune modulation and bone metabolism; however, the mechanism of γδ T cells in the pathogenesis of BRONJ has not been elucidated. Here, we induced BRONJ-like lesions in wild-type (WT) and T-cell receptor delta-deficient (TCRδ) mice via intraperitoneal zoledronate injection. Our findings revealed that γδ T cells infiltrating BRONJ lesions suppressed osteoblast differentiation, whereas γδ T cell depletion in TCRδ mice restored osteogenic function and significantly reduced BRONJ lesion incidence. Mechanistically, we identified matrix metalloproteinase 3 (MMP3) secreted by activated γδ T cells as a critical enzyme cleaving membrane-bound Sema4D (mSema4D) into soluble Sema4D (sSema4D). This cleavage product bound to Plexin-B1/2 receptors on osteoblasts, activating the mTOR signalling pathway to inhibit osteogenic differentiation (ALP/Runx2 downregulation). To promote the repair of BRONJ lesions, we engineered a dual-functional composite hydrogel (Gel-BG@ab) combining PLGA-PEG-PLGA with mesoporous bioactive glass (BG) and anti-Sema4D antibodies. This composite hydrogel achieved sustained antibody release, effectively neutralising sSema4D, restoring osteoblast activity and reducing the formation of BRONJ-like lesions in vivo. This study provides evidence of MMP3-Sema4D-Plexin-B1/2/mTOR crosstalk in BRONJ and introduces a targeted biomaterial strategy to disrupt pathogenic feedback loops. The Gel-BG@ab is the integration of immunomodulation and regenerative medicine, providing both theoretical and technical insights for the immune-material combination therapy of BRONJ.
Wu Y, Zhang J, Zhu W
… +10 more, Zhu X, Liu Y, Wang X, Zhao T, Zhang C, Zhang Z, Shi W, Shi R, Zhou Z, Xu S
Cell Prolif
· 2025 Dec · PMID 40903212
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ARPC1B cancer stem cells (CSCs) in pancreatic cancer are identified as a subpopulation resistant to gemcitabine. In our study, drug repositioning, molecular docking, and surface plasmon resonance (SPR) technique jointly...ARPC1B cancer stem cells (CSCs) in pancreatic cancer are identified as a subpopulation resistant to gemcitabine. In our study, drug repositioning, molecular docking, and surface plasmon resonance (SPR) technique jointly revealed that CK-636 can directly target ARPC1B protein with high affinity. In vitro cytotoxicity, ex vivo organoid cultures, in vivo xenograft and orthotopic gemcitabine-resistant pancreatic cancer model demonstrated that combination therapy of gemcitabine plus CK-636 showed a superior anti-tumor effect compared with gemcitabine monotherapy. Our study demonstrated that CK-636 can act as a rational adjuvant to overcome gemcitabine resistance in pancreatic cancer therapy.
Cell Prolif
· 2026 Apr · PMID 40873114
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Progressive non-alcoholic fatty liver disease (NAFLD) may culminate in severe complications, including fibrosis, cirrhosis and hepatocellular carcinoma, yet therapeutic breakthroughs remain elusive, necessitating novel p...Progressive non-alcoholic fatty liver disease (NAFLD) may culminate in severe complications, including fibrosis, cirrhosis and hepatocellular carcinoma, yet therapeutic breakthroughs remain elusive, necessitating novel pharmacological strategies. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist clinically approved for type 2 diabetes and obesity management, has demonstrated pleiotropic effects in preclinical NAFLD models. In this study, we investigated semaglutide's therapeutic efficacy and mechanisms in a human liver organoids (hLOs) model of NAFLD. Utilising microengineered array chips, human induced pluripotent stem cells (hiPSCs) were differentiated into hLOs with functional hepatic properties. NAFLD pathology was induced via free fatty acid (FFA) exposure, recapitulating disease hallmarks such as steatosis, inflammatory cytokine elevation and fibrogenic activation. Semaglutide treatment at 50 nM significantly attenuated lipid deposition caused by FFAs and reduced triglyceride levels by 8-fold and cholesterol levels by 1.8-fold. It also inhibited the expression of pro-inflammatory markers (IL-6, IL-8, TNF-α) by about 1.5-2 fold and increased the level of lipolytic genes by about 45%. These findings elucidate the therapeutic potential of semaglutide in attenuating key NAFLD-associated pathologies and establish a robust in vitro platform for preclinical drug evaluation. The study provides critical insights into targeted NAFLD interventions and supports the translation of GLP-1-based therapies into clinical practice, addressing an unmet need in hepatology.
Li Y, Yan Z, Dai Y
… +6 more, Cai H, Chen Y, Chen Y, Jin R, Sun W, Wang H
Cell Prolif
· 2026 May · PMID 40862609
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Macrophages and bone marrow mesenchymal stem cells (BMSCs) share a close relationship within the osteoimmune microenvironment. During mechanically induced bone formation, macrophages respond to stimuli and regulate this...Macrophages and bone marrow mesenchymal stem cells (BMSCs) share a close relationship within the osteoimmune microenvironment. During mechanically induced bone formation, macrophages respond to stimuli and regulate this microenvironment, influencing BMSCs' proliferation and differentiation. However, the underlying mechanisms remain incompletely understood. In our study, we employed a cellular tension system and found that mechanical tension altered mitochondrial dynamics in macrophages, leading to increased mitochondrial fission. Using a macrophage-BMSC direct co-culture system, we demonstrated that macrophages transferred mitochondria to BMSCs, a process enhanced by tension. This enhancement was associated with Drp1-mediated mitochondrial fission, as Drp1 knockdown in macrophages abolished the effect. Additionally, using in vitro co-culture and in vivo tibial injection models, we found that mitochondria-rich extracellular vesicles (Mito-EVs) secreted by mechanically stretched macrophages promoted BMSCs' osteogenesis and enhanced bone formation via the CD200 receptor (CD200R)-CD200 interaction. Our findings reveal a pivotal role for mitochondrial transfer in promoting osteogenesis during mechanotransduction, highlighting a novel mechanism of intercellular communication in bone biology.
Jiang Y, Shen Y, Zhang Q
… +9 more, Liu Z, Liu Y, Peng J, Yang X, Gao F, Ou XH, Sun QY, Zhang Q, Wang G
Cell Prolif
· 2026 Mar · PMID 40855999
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H1N1, a globally pervasive subtype of influenza A virus (IAV), poses an ongoing threat to human health and occasionally leads to multi-organ dysfunction in severe cases. Evidence confirms that the H1N1 virus is enabled t...H1N1, a globally pervasive subtype of influenza A virus (IAV), poses an ongoing threat to human health and occasionally leads to multi-organ dysfunction in severe cases. Evidence confirms that the H1N1 virus is enabled to penetrate the placental barrier; however, the underlying mechanisms by which maternal infection contributes to detrimental fetal outcomes remain elusive. In this study, a systematic literature review and meta-analysis demonstrated a strong association between maternal H1N1 infection during pregnancy and adverse fetal outcomes. Using a chicken embryo model, we found that the H1N1 virus specifically targets the developing liver and lung tissues, activates immune and stromal cells, and induces localised inflammatory responses, thereby triggering excessive oxidative stress. The resulting imbalance in oxidative stress disrupts antioxidant defence systems and promotes ferroptosis in parenchymal cells. Persistent ferroptosis subsequently initiates tissue repair processes, activates fibroblasts, and leads to aberrant extracellular matrix deposition, ultimately contributing to early fibrosis in the liver and lung tissues. Collectively, this study elucidates the molecular mechanisms by which H1N1 selectively infects fetal liver and lung, inducing ferroptosis-mediated parenchymal cell death and tissue fibrosis, thereby impairing fetal development. These findings provide novel theoretical insights for the clinical management and prevention of H1N1-associated maternal-fetal infections and adverse pregnancy outcomes.