The FASEB Journal最新文献

{"title":"Correction to \"The Excelsatoxin A-Receptor TMEM233 Modulates Nav1.8\".","authors":"","doi":"10.1096/fj.202601596","DOIUrl":"10.1096/fj.202601596","url":null,"abstract":"","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"40 8","pages":"e71776"},"PeriodicalIF":4.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: Molecular Profiling Unveils Pyroptosis Markers in Preterm Birth.","authors":"","doi":"10.1096/fsb2.71816","DOIUrl":"10.1096/fsb2.71816","url":null,"abstract":"<p><strong>Retraction: </strong>X. Li, Z. Huang, J. Bai, A. Che, J. Zhou, and H. Yang, \"Molecular Profiling Unveils Pyroptosis Markers in Preterm Birth,\" The FASEB Journal 38, no. 24 (2024): e70112, https://doi.org/10.1096/fj.202302716RR. The above article, published online on 14 December 2024 in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the journal Editor-in-Chief, Loren E. Wold; the Federation of American Societies for Experimental Biology (FASEB); and Wiley Periodicals LLC. Following publication, the authors requested that the article be retracted because of an error in the funding information. Upon further investigation consistent with a retraction request, the publisher also discovered that Figure 4B was duplicated from an earlier article by different authors (da Silva Nunes Barreto et al. 2022: https://doi.org/10.3390/bioengineering10010016). Due to the unauthorized reuse of the image, the editor has lost confidence in the data reported, and the article must therefore be retracted. The authors did not respond to the notice of retraction.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"40 8","pages":"e71816"},"PeriodicalIF":4.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147724580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Omics and Machine Learning-Uncovered FLT1-Mediated Epithelial-Endothelial Crosstalk in Cellular Senescence Driving Clear Cell Renal Cell Carcinoma Malignancy.","authors":"Mouyuan Sun, Huchao Mao, Yaxian Luo, Mei Yang, Zhixu He, Shuangyang Li, Zhichao Liu, Lianjie Peng, Quanjie Zhang, Jingyu Zhang, Yan Zhang","doi":"10.1096/fj.202503291RR","DOIUrl":"10.1096/fj.202503291RR","url":null,"abstract":"<p><p>Clear cell renal cell carcinoma (ccRCC) is distinguished by the absence of definitive diagnostic markers and efficacious treatment modalities, factors that collectively contribute to its unfavorable clinical prognosis. The targeting of senescent cells has recently emerged as a promising therapeutic strategy. Nevertheless, the precise role of cellular senescence in the pathophysiology of ccRCC has yet to be comprehensively elucidated. This study sought to investigate the role of cellular senescence levels in ccRCC through comprehensive transcriptomic, proteomic, spatial transcriptomic, and single-cell analyses. The study determined that elevated levels of cellular senescence contribute to a suppressed immune microenvironment, thereby exacerbating the prognosis for ccRCC patients. We utilized an extensive array of machine learning algorithms, in conjunction with multi-omics technologies, validated through immunofluorescence, RT-qPCR, and additional techniques, to collectively identify FLT1 as a pivotal single gene driving ccRCC progression. Our work reveals a FLT1-centered network of related factors, where FLT1 acts as the core single gene, closely associated with key factors VEGFA and AKT1. This network mediates crosstalk between endothelial and epithelial cells: endothelial cells expressing FLT1 alone, AKT1 alone, or co-expressing FLT1/AKT1 exhibited enhanced malignancy; among epithelial cells, proximal tubular epithelial cells with high VEGFA expression (a factor closely related to FLT1) represented the most aggressive subtype and acted as \"pioneer cells\" driving tumor progression. This FLT1-centric mechanism is evolutionarily conserved, as validated in mouse single-cell datasets. Clinically, ccRCC patients with low expression of the FLT1-centered network (particularly low FLT1) showed better responses to immunotherapy. For patients with high FLT1 expression, a combination therapy targeting this network-screened via molecular docking and dynamics simulations-may improve prognosis. This includes FLT1 inhibitors (Sorafenib, Regorafenib, Lenvatinib), supplemented by AKT1 inhibitors (Capivasertib) and VEGFA inhibitors (Bevacizumab) to suppress FLT1-associated malignant cell populations.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"40 8","pages":"e71784"},"PeriodicalIF":4.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13091186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147724610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate Immunity and Microbial Recognition in Reproduction: From Barrier Defense to Maternal-Fetal Tolerance.","authors":"Xianlin Rao, Li Zou, Yao Yao, Changling Liu","doi":"10.1096/fj.202601196R","DOIUrl":"10.1096/fj.202601196R","url":null,"abstract":"<p><p>Reproduction requires the innate immune system to perform two opposing tasks simultaneously: prevent microbial invasion while preserving tolerance to sperm, the semi-allogeneic embryo, and the developing fetus. This review proposes a unified barrier defense-tolerance framework to explain how reproductive success depends on the coordinated integration of epithelial and mucus barriers, antimicrobial peptides, complement, tissue-resident innate immune cells, pattern-recognition receptor signaling, microbial ecology, and endocrine-metabolic regulation across the female and male reproductive tracts and the maternal-fetal interface. We summarize how Toll-like receptors, NOD-like receptors, RIG-I-like receptors, and cGAS-STING pathways shape early reproductive events, including gamete quality control, sperm transit, implantation, placentation, and antiviral defense, and how tightly constrained physiological inflammation supports tissue remodeling, whereas excessive or unresolved activation contributes to infertility, recurrent pregnancy loss, preeclampsia, fetal growth restriction, and preterm birth. We further examine microbiota-host interactions in reproduction, emphasizing that evidence is strongest for cervicovaginal communities, while endometrial, placental, and male genital microbiota findings require more cautious interpretation because of low-biomass sampling, contamination risk, and limited reproducibility. Beyond local microbial niches, gut-derived metabolites emerge as important regulators of immune tone and barrier function in reproductive tissues. We also discuss downstream effector mechanisms, including inflammasomes, regulated cell death, extracellular vesicles, and soluble innate mediators, and evaluate their translational relevance for biomarker development and targeted intervention. Overall, reproductive disorders are best viewed as systems-level outcomes of disturbed interactions among host barriers, innate sensing thresholds, microbial signals, and metabolic context, providing a conceptual basis for future multi-omics and mechanism-driven reproductive immunology.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"40 8","pages":"e71799"},"PeriodicalIF":4.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13075463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147678506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal Low-Fat and High-Fat Diet Decreases Survival and Alters Cytokine Signaling in Neonatal Mice With Staphylococcus epidermidis Sepsis.","authors":"Lauren Bodilly, Sarah Weiner, Kara Misel-Wuchter, Jennifer Bermick","doi":"10.1096/fj.202502656RR","DOIUrl":"10.1096/fj.202502656RR","url":null,"abstract":"<p><p>Maternal malnutrition increases susceptibility to sepsis and mortality in neonates. The reason for this increased susceptibility remains unknown. We aimed to evaluate bacterial burden and serum cytokine levels in septic neonatal mice born to dams fed diets with different dietary fat content. 6-week-old C57BL/6 dams were placed on a low-fat (LFD) (10% kcal from fat), control (CD) (18% kcal from fat), or high-fat (HFD) (60% kcal from fat) diet for 3 weeks before breeding. Sepsis was induced in P4-P6 offspring via intraperitoneal Staphylococcus epidermidis injection. Mice were monitored for survival. At 12 h after sepsis, serum and peritoneal wash fluid were collected for bacterial count and serum cytokine levels. In the absence of infection, P4-P6 offspring had untargeted serum metabolomics performed. Septic offspring of dams fed LFD and HFD had significantly higher mortality than offspring of dams fed CD. There was no difference in serum or peritoneal wash bacterial loads. Maternal diet and S. epidermidis sepsis caused changes in basal serum cytokine levels, with HFD causing decreased cytokine elevation during sepsis. Maternal LFD and HFD altered similar metabolomic pathways in offspring. Maternal LFD and HFD decrease survival during neonatal sepsis and alter serum cytokines and the metabolome, supporting a role for maternal nutrition in neonatal immune function and infection susceptibility.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"40 8","pages":"e71794"},"PeriodicalIF":4.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147678629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of STARD7 Impairs Mitochondrial Phospholipid Homeostasis and Contributes to Mitochondrial Myopathy.","authors":"Yasuhiro Horibata, Tomoki Sato, Masahide Ohyama, Sae Yuyama, Masahiko Itoh, Shinji Miura, Akimitsu Konishi, Hiroyuki Sugimoto","doi":"10.1096/fj.202504528R","DOIUrl":"10.1096/fj.202504528R","url":null,"abstract":"<p><p>Mitochondria are composed of phospholipid bilayers rich in phosphatidylcholine (PC). StAR-related lipid transfer domain-containing protein 7 (STARD7) functions as a lipid transfer protein that plays a crucial role in maintaining mitochondrial PC homeostasis. In this study, we investigated the physiological role of STARD7 in skeletal muscle using muscle-specific knockout (mKO) mice. STARD7 expression was markedly higher in the soleus, a mitochondria-dense slow-twitch muscle, compared with fast-twitch fibers. Although muscle fibers from mKO mice exhibited no apparent structural abnormalities, their endurance exercise capacity was markedly reduced. RNA-seq analysis revealed suppressed expression of fast-twitch-related genes accompanied by a reduction in fast-twitch fibers. At the mitochondrial level, respiratory chain complexes remained intact, but oxygen consumption was consistently decreased. Targeted lipidomic analysis showed decreased levels of PC, cardiolipin (CL), and coenzyme Q in mKO mitochondria, particularly in the soleus. Conversely, expression of CL biosynthetic enzymes was unchanged, and an in vitro binding assay indicated that STARD7 preferentially transfers linoleic acid-containing PC required for CL remodeling. Furthermore, electron microscopy revealed disorganized cristae structures, whereas 4-HNE-modified proteins, mtDNA content, and OPA1 processing remained unaffected. Together, these findings demonstrate that STARD7 plays an essential role in maintaining mitochondrial integrity and function in skeletal muscle, and its loss likely contributes to the pathogenesis of mitochondrial myopathy.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"40 8","pages":"e71777"},"PeriodicalIF":4.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147700364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"G2E3 Suppresses the Tumor-Killing Function of CD8⁺ T Cells in Hepatocellular Carcinoma by Boosting CLCN2 Ubiquitination.","authors":"Fan Zhou, Ting Chen, Xingguo Tan, Jun Yu, Mengzhi Xiao, Jun Guo","doi":"10.1096/fj.202503004RR","DOIUrl":"10.1096/fj.202503004RR","url":null,"abstract":"<p><p>In the pathogenesis of hepatocellular carcinoma (HCC), impaired CD8⁺ T cell function is a critical factor in immune evasion. Although CLCN2 has been implicated in immunomodulation, its role in regulating CD8⁺ T cell-mediated antitumor immunity in HCC remains unclear. The expression of G2E3 in HCC was analyzed using the TCGA database, qPCR, and western blot. The UbiBrowser database was employed to predict CLCN2 as a downstream substrate of G2E3. Protein interactions were validated via Co-IP and in vivo ubiquitination assays. IFN-γ, TNF-α, and Granzyme B levels were measured using ELISA kits, while CD44 and CD134 levels in CD8⁺ T cells were examined via flow cytometry. The cytotoxic activity of CD8⁺ T cells against HCC cells was evaluated using an LDH assay. An allograft mouse tumor model was utilized to determine whether the G2E3-CLCN2 axis drove HCC progression by suppressing T cell immunity. We herein discovered that G2E3 was highly expressed in HCC and positively linked with poor prognosis. Mechanistically, G2E3 functioned as an E3 ubiquitin ligase, mediating the ubiquitination and subsequent degradation of CLCN2. Rescue experiments revealed that CLCN2 enhanced the antitumor activity of CD8⁺ T cells, whereas G2E3 overexpression attenuated this effect. Furthermore, in an allograft mouse tumor model, activation of the G2E3-CLCN2 axis reduced CD8⁺ T cell infiltration and activity in tumors, thereby driving tumor growth. This investigation elucidates the molecular mechanism by which HCC suppresses CD8⁺ T cell function to facilitate immune escape, suggesting that targeting the G2E3-CLCN2 axis may represent a potential therapeutic strategy to enhance antitumor immunity.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"40 8","pages":"e71719"},"PeriodicalIF":4.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147724584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"HMGB1-Induced Aberrant Autophagy Contributes to Insulin Resistance in Granulosa Cells in PCOS\".","authors":"","doi":"10.1096/fj.202601691","DOIUrl":"10.1096/fj.202601691","url":null,"abstract":"","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"40 8","pages":"e71800"},"PeriodicalIF":4.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147678484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Validation of DLD as a Cuproptosis-Associated Biomarker in Preeclampsia.","authors":"Shuisen Zheng, Xiaoling Chen, Wanrou Tang, Danlin Yang, Qing Han","doi":"10.1096/fj.202504941R","DOIUrl":"10.1096/fj.202504941R","url":null,"abstract":"<p><p>Preeclampsia (PE), characterized by new-onset hypertension and proteinuria after 20 weeks of gestation, presents substantial risks to both mother and fetus. Cuproptosis represents a newly identified form of regulated cell death; its potential association with PE pathogenesis remains unclear. We retrieved the GSE60438 dataset from the GEO database and identified 557 differentially expressed genes (DEGs) associated with PE. Weighted gene co-expression network analysis (WGCNA) was performed, and by intersecting the DEGs with WGCNA module genes, we obtained 198 candidate PE-related genes. KEGG and GO enrichment analyses revealed their potential biological functions, with significant enrichment in lipoic acid metabolism, the tricarboxylic acid (TCA) cycle, and components of the mitochondrial matrix. By further intersecting the DEGs, WGCNA module genes, and cuproptosis-related genes, we identified DLD as the hub cuproptosis-related gene in PE. GSEA further revealed its involvement in key metabolic pathways. The expression of DLD in PE and normal placental tissues was detected by qRT-PCR and immunohistochemical staining. Loss or gain-of-function tests were performed to assess the effects of DLD on the proliferation, migration, and invasion of HTR-8/SVneo cells. Concurrently, pyruvate and citrate levels were quantified with commercial kits, and intracellular ultrastructure was examined by transmission electron microscopy. Herein, we detected increased DLD in the PE placental tissues. In vitro studies showed that knockdown of DLD promoted trophoblast proliferation, migration, and invasion; conversely, overexpression of DLD showed the opposite effect. Concurrently, DLD overexpression induced metabolic dysregulation in tricarboxylic acid (TCA) cycle intermediates as well as distinct mitochondrial ultrastructural alterations. Our study demonstrated that DLD, a cuproptosis-related gene, is significantly upregulated in PE and functionally impairs trophoblast activity, suggesting its pathogenic role may be mediated through cuproptosis.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"40 8","pages":"e71787"},"PeriodicalIF":4.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13089668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147718815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Potential Novel Molecular Interaction in Bronchiolitis Obliterans Syndrome in Lung Transplantation Patients: The Role of SERPINA3 and Osteoprotegerin.","authors":"Yanzhe Liu, Eline A van der Ploeg, Theo Borghuis, R Ian Menz, Wim Timens, Judith M Vonk, Barbro N Melgert, C Tji Gan, Janette K Burgess","doi":"10.1096/fj.202503694R","DOIUrl":"10.1096/fj.202503694R","url":null,"abstract":"<p><p>Chronic lung allograft dysfunction significantly limits survival after lung transplantation. The obstructive phenotype bronchiolitis obliterans syndrome (BOS) is characterized by the abnormal activation of airways epithelium, fibrotic changes with excessive extracellular matrix deposition, and airway obliteration. Mast cells, through mediators such as tryptase and chymase, play a role in lung fibrosis. The proteins osteoprotegerin (OPG) and SERPIN family member A 3 (SERPINA3) have been associated with lung fibrosis progression. Tryptase-mast cells can produce OPG, while chymase interacts with SERPINA3. This study aimed to investigate if and how SERPINA3, OPG, and tryptase/chymase-positive mast cells are related to fibrotic airway obliteration and potentially show an association with BOS severity. Serum SERPINA3 levels in BOS and non-BOS were examined using ELISA. In BOS lung tissue, non-cartilaginous airways were classified into normal, partially obstructed, and completely obstructed airways. Immunohistochemistry detected SERPINA3, OPG, chymase, and tryptase. Colocalization of and interactions between SERPINA3, OPG, and tryptase were assessed by immunofluorescence, proximity ligation assay, and AlphaFold modeling. SERPINA3 serum levels in BOS patients were higher compared to non-BOS patients. A low percentage of SERPINA3 and OPG was detected in partially and completely obstructed airways. Cells positive for OPG and SERPINA3 colocalized with tryptase-mast cells in airways. OPG colocalized with SERPINA3, and they positively correlated in partially obstructed airways. In completely obstructed airways, OPG, SERPINA3, and tryptase all positively correlated with each other. These findings suggest mast cells express SERPINA3 and OPG, and these proteins potentially form a complex in lung tissue, possibly contributing to airway remodeling in BOS.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"40 8","pages":"e71748"},"PeriodicalIF":4.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13094457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147724467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}