Biology Direct最新文献

{"title":"Synthetic horizontal gene transfer for ecosystem restoration.","authors":"Victor Maull, Guim Aguadé-Gorgorió, Victor de Lorenzo, Ricard Solé","doi":"10.1186/s13062-026-00919-9","DOIUrl":"10.1186/s13062-026-00919-9","url":null,"abstract":"<p><p>Restoring endangered ecosystems has become a pressing issue as the effects of global warming continue to harm existing communities. During the last decade, several studies have suggested the use of synthetic biology as a tool to protect these biodiverse communities by increasing their functionality. A critical example concerns soil microbiome communities in drylands, where increasing water retention by some of the constituent species could effectively protect the ecosystem from abrupt degradation. However, how to effectively deploy a functional synthetic construct that can scale its impact to the community level remains an open question. Recent experimental research has designed recombinant gene plasmids with the capacity to horizontally transfer across soil microbial communities. Here, we explore the impacts of synthetic horizontal gene transfer in models of ecological consortia. We define a consumer-resource model in which species can share an engineered plasmid that reduces resource loss, effectively coupling multispecies dynamics and gene spreading. By doing so, we identify a wide range of parameters and the optimal gene transfer conditions for which the intervention promotes biodiversity and biomass gains, while regulating gene propagation and the spread of engineered organisms. Our work provides a first step toward understanding the mechanisms and opportunities of engineered plasmid transfer in multispecies ecological communities.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"21 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179577","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":"STING‑regulated Ca²⁺-TGF‑β axis drives airway remodeling and lung function decline in asthma: a multi‑omics mechanistic study.","authors":"Zhiqin Zhu, Qingao Xiao, Runjin Cai, Enyu Qi, Xiaoxiao Gong, Jiale Tang, Xiaozhao Li, Juntao Feng","doi":"10.1186/s13062-026-00940-y","DOIUrl":"https://doi.org/10.1186/s13062-026-00940-y","url":null,"abstract":"<p><strong>Background: </strong>The progressive lung function decline in severe asthma is poorly explained by traditional inflammation‑centered paradigms. Calcium (Ca²⁺) dysregulation and transforming growth factor‑β (TGF‑β) signaling have been implicated, but the molecular link between them and their upstream regulators remain elusive.</p><p><strong>Methods: </strong>We integrated clinical CT imaging, proteomics (6 asthma vs. 6 healthy controls), public transcriptomic data (GSE63142, GSE68479), single‑cell RNA‑sequencing (GSE193816, GSE185048), and functional studies in STING knockout mice and airway epithelial cells. GO and KEGG enrichment, LASSO regression, Spearman correlation, immunohistochemistry, immunofluorescence, co‑immunoprecipitation, western blot, mitochondrial function assays (MitoSOX/JC‑1), Fura‑2 calcium imaging, RNA‑seq and ELISA were used to systematically evaluate the role of the STING‑PPM1F‑Ca²⁺‑TGF‑β axis in asthma airway remodeling.</p><p><strong>Results: </strong>Using logistic regression, we found that disease severity, age, pulmonary function parameters and eosinophil count independently predicted the presence of tracheal cartilage calcification, with the model achieving excellent discrimination (AUC > 0.92). Proteomics identified PPM1F, CAMK2G, MICU2 and CIB1 as key calcium‑metabolism proteins co‑enriched in calcium signaling and TGF‑β pathways; PPM1F expression strongly correlated with reduced FEV₁% (r = - 0.94, p = 0.005) and recurrent exacerbation risk (p < 0.01). Functionally, OVA induced time‑dependent mitochondrial ROS elevation and membrane potential dissipation, triggered cytosolic mtDNA release, and activated STING downstream p‑TBK1 signaling. STING activation directly mobilized intracellular Ca²⁺ via both store release and extracellular influx, as demonstrated by Fura‑2 imaging. STING knockout or silencing abolished OVA‑induced PPM1F upregulation and TGF‑β/Smad activation, and attenuated airway pathology. Co‑immunoprecipitation confirmed direct PPM1F‑TGF‑β physical interaction. Single‑cell transcriptomics revealed SFTPC⁺ epithelial cell expansion and high NKX2‑1/FOXA2 activity; multiplex immunofluorescence further identified SCGB1A1⁺SFTPC⁺ double‑positive cells in asthmatic airways, suggesting a potential phenotypic transition of club cells toward an AT2-like state.</p><p><strong>Conclusions: </strong>The STING‑regulated Ca²⁺-TGF‑β axis, activated by mitochondrial stress‑induced mtDNA release, is associated with airway remodeling and lung function decline in asthma. PPM1F is a potential biomarker for asthma severity and recurrent exacerbations; targeting STING or PPM1F may offer new therapeutic strategies for severe asthma.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"21 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13479581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788160","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":"Expression and mechanistic roles of long non-coding RNAs in diabetic cataract: a systematic review and meta-analysis.","authors":"Kai-Yang Chen, Hoi-Chun Chan, Chi-Ming Chan","doi":"10.1186/s13062-026-00888-z","DOIUrl":"10.1186/s13062-026-00888-z","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetic cataract (DC) is a lens-opacity complication of diabetes driven by hyperglycemia-related oxidative, apoptotic, metabolic, and epithelial-mesenchymal transition (EMT) pathways. This review evaluated the expression and mechanistic roles of long non-coding RNAs (lncRNAs) and lncRNA-related epitranscriptomic regulators in DC.</p><p><strong>Methods: </strong>PubMed, Embase, Cochrane Library, Scopus, Web of Science, and Google Scholar were searched to 1 June 2026 without language restriction. Ex vivo, in vitro, transcriptomic, epitranscriptomic, and mechanistic studies were included. Two reviewers screened records, extracted data, and assessed bias using the JBI checklist. Random-effects meta-analysis pooled Fisher-z-transformed correlations; bias and certainty were assessed using funnel plot, exploratory Egger's test, and GRADE-adapted criteria.</p><p><strong>Results: </strong>Thirteen studies were included. Eight expression datasets showed a significant association between DC and lncRNA or lncRNA-linked epitranscriptomic dysregulation (pooled r = 0.445, 95% CI 0.338-0.541; p = 0.001), with low heterogeneity (I² = 1.2%; Q = 7.088; df = 7; p = 0.42; τ² = 0.00037; τ = 0.019; prediction interval 0.308-0.563). LINC01508, MAFA-AS1, MIAT, GAS5, XIST, MALAT1, KCNQ1OT1, and METTL16 were upregulated, whereas NEAT1 was downregulated. MALAT1, GAS5, XIST, PVT1, KCNQ1OT1, FOXD3-AS1, NEAT1, RMRP, METTL3, METTL16, FTO, METTL14, WTAP, ALKBH5, and YTHDF-family regulators converged on ceRNA signaling, apoptosis, oxidative stress, EMT, proliferation, mitochondrial dysfunction, ICAM-1 stabilization, and m⁶A-linked DKK1/Wnt/β-catenin regulation. Leave-one-out estimates ranged from r = 0.422 to 0.502; year-based meta-regression did not materially change the result.</p><p><strong>Conclusion: </strong>DC is associated with coordinated lncRNA and epitranscriptomic dysregulation across oxidative, apoptotic, EMT, mitochondrial, proliferative, and m⁶A-regulated pathways.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"21 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720517","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":"Effects of homozygous PARK7 gene mutations L166P and M26I on BNIP3/BNIP3L interactions and ER-mitochondria proximity.","authors":"Jiannan Wu, Kuiqi Jin, Mengmeng Shen, Xiaoyi Lai, Jingjing Guo, Tingting Wang, Zhenzhen Tian, Junqiang Yan","doi":"10.1186/s13062-026-00928-8","DOIUrl":"10.1186/s13062-026-00928-8","url":null,"abstract":"<p><p>Mutations in PARK7, which encodes DJ-1, cause autosomal recessive early-onset Parkinson's disease. DJ-1 contributes to mitochondrial homeostasis and ER-mitochondria communication, but how the pathogenic L166P and M26I variants affect BNIP3/BNIP3L-associated phenotypes remains incompletely understood. Here, we examined DJ-1 variant-dependent changes in BNIP3/BNIP3L interactions, mitochondrial morphology, ER-mitochondria proximity-associated readouts, and global intracellular Ca²⁺ responses in PC-12 and SH-SY5Y cell models. AlphaFold3-based interface prediction, co-immunoprecipitation, and GST pull-down assays supported interactions involving DJ-1, BNIP3, and BNIP3L, including binding to selected BNIP3- and BNIP3L-derived peptide regions. DJ-1 WT and M26I showed detectable binding to BNIP3-derived regions, whereas the unstable L166P variant showed reduced BNIP3 binding even after partial restoration of L166P abundance with MG132. Reciprocal co-immunoprecipitation and knockdown experiments further supported an association between BNIP3 and BNIP3L in these cells. In L166P expressing cells with GRP75 knockdown, BNIP3 depletion increased the ER-mitochondria distance and reduced the length of the ER-mitochondria proximity region. Colocalization analyses showed DJ-1 variant-dependent changes in proximity-associated imaging readouts, while immunoblotting identified reduced VDAC1 and MFN1 levels after BNIP3 depletion in mutant expressing cells. BNIP3 depletion reduced the relative 2-APB evoked Fluo-4 response in WT, L166P and M26I expressing cells by 40.7%, 76.7%, and 42.5%, respectively. Overall, these findings may reflect altered DJ-1/BNIP3/BNIP3L interaction profiles and BNIP3 sensitive changes in ER-mitochondria proximity associated and global intracellular Ca²⁺ readouts, particularly in L166P-expressing cells, although direct validation is still required.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"21 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928671","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":"Enhanced neuroprotection effects of transcranial direct current stimulation combined with 6-Gingerol in copper-overloaded traumatic brain injury via mGluR1.","authors":"Bo Zhang, Jiawei Zhou, Fengkai Liu, Dayong Cui, Xinyu Liu, Dan Wang","doi":"10.1186/s13062-026-00886-1","DOIUrl":"https://doi.org/10.1186/s13062-026-00886-1","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the neuroprotective effects and underlying mechanisms of transcranial direct current stimulation (tDCS) combined with 6-Gingerol (6G) in a rat model of traumatic brain injury (TBI) complicated by copper overload, with particular emphasis on microglial polarization and mGluR1 signaling.</p><p><strong>Methods: </strong>A controlled cortical impact (CCI) was used to establish TBI in rats, followed by induction of copper overload via oral administration of copper sulfate. Animals were randomly assigned to sham, TBI, copper-overloaded TBI, and copper-overloaded TBI treated with 6G, tDCS, or their combination, with or without the mGluR1 inhibitor LY367385. Neurological function and cognition were evaluated using the modified neurological severity score (mNSS) and Morris water maze. Brain copper content, oxidative stress markers, and neuronal apoptosis were assessed by biochemical assays, Western blotting, and TUNEL staining. Microglial polarization was examined by immunofluorescence and qRT-PCR, and the involvement of mGluR1 signaling was verified pharmacologically.</p><p><strong>Results: </strong>Combined tDCS and 6G treatment significantly improved neurological function and spatial learning compared with monotherapy or untreated copper-overloaded TBI. This combination reduced cerebral copper accumulation, attenuated oxidative stress, and decreased neuronal apoptosis. Furthermore, it promoted microglial polarization toward the anti-inflammatory M2 phenotype while suppressing M1-associated inflammatory markers. Inhibition of mGluR1 partially abolished these neuroprotective effects, indicating a critical role of mGluR1 signaling.</p><p><strong>Conclusion: </strong>tDCS combined with 6G provides enhanced neuroprotection in copper-overloaded TBI by regulating copper homeostasis, suppressing oxidative stress, promoting microglial M2 polarization, and engaging mGluR1-dependent signaling pathways. These findings suggest a promising combinational therapeutic strategy for TBI complicated by metal dysregulation.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"21 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166682","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":"Polydatin mitigates cigarette smoke-induced pulmonary apoptosis by regulating Bim via FoxO3 post-translational modifications and modulating the gut microenvironment.","authors":"Longfei Lv, Tianyu Lu, Rui Wang, Xiang Li, Youbin Cui, Li Ren, Jie Zhang","doi":"10.1186/s13062-026-00924-y","DOIUrl":"https://doi.org/10.1186/s13062-026-00924-y","url":null,"abstract":"<p><strong>Background: </strong>Cigarette smoke-mediated chronic pulmonary damage constitutes a critical predisposing factor for chronic obstructive pulmonary disease and lung cancer pathogenesis. Polydatin, a naturally occurring stilbenoid characterized by its potent anti-inflammatory and antioxidant properties, has yet to be fully elucidated regarding its protective role and the underlying molecular mechanisms in CSE-induced pulmonary injury.</p><p><strong>Methods: </strong>Cigarette smoke extract (CSE)-induced lung injury murine models and MLE12 cells were treated with polydatin or other conditions. The investigation encompassed both intravital and extracorporeal modalities. Evaluations included pulmonary index, histopathology, oxidative stress markers, transcriptomic sequencing, protein expression (AKT/FoxO3/Bim), apoptosis (TUNEL), intestinal metabolomics, 16S rRNA microbiota profiling, and immunohistochemical staining of colon tissue.</p><p><strong>Results: </strong>The administration of polydatin dose-dependently in vivo alleviated CSE-induced systemic impairments including weight loss, pulmonary edema, and oxidative stress concurrently demonstrating high biocompatibility and low systemic toxicity. Furthermore, it modulates the intestinal microecology by depleting g__Pantoea and g__Enterococcus abundance, concurrently restoring mucosal barrier integrity via the enhancement of ZO-1 and Occludin levels. Mechanistic analysis demonstrated that polydatin directly interacts with AKT1 at the Thr308 residue, thereby reversing the CSE-induced attenuation of AKT1 and FoxO3 (Ser253) phosphorylation. This restoration facilitates the nuclear-to-cytoplasmic translocation of FoxO3 and subsequent downregulation of the pro-apoptotic protein Bim. This regulatory cascade effectively curtails apoptosis and DNA fragmentation, with a concomitant decrease in Bax and Cleaved-Caspase 3 expression.</p><p><strong>Conclusions: </strong>In conclusion, polydatin exerts suitable protective effects against CSE-induced pulmonary injury by attenuating apoptosis through the AKT-FoxO3-Bim signaling cascade and simultaneously orchestrating the gut microenvironment. These findings highlight the potential of polydatin as a promising natural therapeutic agent for lung disorders.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"21 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104167","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":"SLC25A12 mitigates mitochondrial dysfunction in myoblast senescence, and alleviates cuproptosis-related changes under copper stress.","authors":"Shengwei Wang, Weigen Wu, Hua Yin, Qiushuo Chen, Ling Zhang, Wen He","doi":"10.1186/s13062-026-00918-w","DOIUrl":"https://doi.org/10.1186/s13062-026-00918-w","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenia is an age-related muscle wasting condition that currently lacks specific diagnostic biomarkers and effective treatments. This study aimed to identify mitochondria-related biomarkers for sarcopenia via integrated multi-omics.</p><p><strong>Methods: </strong>Human transcriptomic datasets and machine learning algorithms were integrated to screen core mitochondria-related biomarkers for sarcopenia. In vivo validation was performed utilizing 24-month-old naturally aging mice exhibiting sarcopenia features. In vitro, SLC25A12 was either overexpressed or silenced in C2C12 myoblasts subjected to D-galactose-induced senescence or copper stress. Pathophysiological changes and molecular mechanisms were subsequently evaluated via immunofluorescence, mitochondrial functional assays, and Western blotting. Additionally, single-cell RNA sequencing combined with a Geneformer model was employed in MuSCs for in silico perturbation analysis.</p><p><strong>Results: </strong>Transcriptomic and machine learning analyses identified SLC25A12 as a core mitochondria-related gene, exhibiting consistent downregulation in both human sarcopenia cohorts and 24-month-old aging mice. In vitro, SLC25A12 overexpression in C2C12 myoblasts significantly ameliorated senescence induced by D-galactose and preserved mitochondrial function, highlighted by increased EdU incorporation and restored membrane potential. Furthermore, under copper stress, elevated SLC25A12 levels effectively alleviated cuproptosis-related alterations, including restricting mitochondrial copper overload, suppressing DLAT oligomerization, and partially restoring impaired EdU incorporation. Conversely, SLC25A12 knockdown consistently aggravated these phenotypes in both models. Notably, in silico Geneformer-based perturbation of SLC25A12 in MuSCs predicted its regulatory roles in cellular senescence, mitochondrial function, and copper homeostasis. In vitro experiments further demonstrated that SLC25A12 overexpression partially restored suppressed PI3K/AKT signaling under senescent stress conditions.</p><p><strong>Conclusion: </strong>SLC25A12 expression ameliorates myoblast senescence and mitochondrial dysfunction, while also attenuating cuproptosis-related changes under copper stress. SLC25A12 knockdown exacerbates these phenotypes. Taken together, SLC25A12 represents a potential regulator and therapeutic target for skeletal muscle aging.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"21 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13483632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788181","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":"SF1 regulates the transcription of FDX1 to promote cuproptosis in pediatric sepsis-related acute lung injury by interacting with cJUN.","authors":"Yanrong Wang, Junhua Sun, Lifen Zhang, Shenghu Zhou, Fang Zhao","doi":"10.1186/s13062-026-00915-z","DOIUrl":"10.1186/s13062-026-00915-z","url":null,"abstract":"<p><strong>Background: </strong>Pediatric sepsis, a major cause of acute lung injury (ALI), involves a dysregulated host response. Cuproptosis is a novel copper-dependent cell death process regulated by Ferredoxin 1 (FDX1). However, its role in pediatric sepsis-associated ALI is unknown. This study investigated the upstream regulation mechanism of FDX1, and its role in pediatric sepsis-related ALI.</p><p><strong>Methods: </strong>Peripheral blood mononuclear cells (PBMCs) were collected from septic children and healthy controls. All enrolled pediatric subjects were divided into three groups: healthy control group (N = 40), sepsis without ALI group (N = 30), and sepsis with ALI group (N = 30). The clinical significance of FDX1, steroidogenic factor 1 (SF1), and Jun proto-oncogene (cJUN) was assessed by qRT-PCR. A septic ALI cell model was established using LPS-treated BEAS-2B cells. Functional assays (CCK-8, TUNEL, ELISA) assessed viability, apoptosis, and inflammation. An in vivo cecal ligation and puncture (CLP) model was employed to confirm the role of FDX1. Molecular mechanisms (transcriptional regulation, protein interaction) were examined via ChIP, dual-luciferase, and Co-IP.</p><p><strong>Results: </strong>FDX1, SF1, and cJUN levels were significantly elevated in pediatric sepsis patients, especially in those complicated with ALI, and the three genes were positively correlated with each other. In vitro, LPS induced BEAS-2B cell injury, inflammation, and cuproptosis. FDX1 overexpression exacerbated these effects, while its knockdown exerted protective effects. Mechanistically, SF1 directly bound to the FDX1 promoter to activate its transcription. SF1 physically interacted with cJUN, and they synergistically enhanced FDX1 transcription. Knockdown of cJUN abolished SF1-mediated FDX1 upregulation and its pro-cuproptotic effects. In vivo experiments demonstrated that FDX1 knockdown attenuated CLP-induced lung injury, inflammation, and cuproptosis.</p><p><strong>Conclusions: </strong>SF1, cJUN, and FDX1 may be closely involved in pediatric sepsis-related ALI. The physical interaction between SF1 and cJUN potentially modulates FDX1 transcription, which may contribute to cuproptosis and pediatric sepsis-related ALI progression.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"21 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149011851","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":"Multiomics, multi-species profiling, and animal validation identify mitoxyperilysis as a conserved therapeutic target in metabolic dysfunction-associated steatohepatitis.","authors":"Hanjie Liu, Cong Qi, Ruixia Lu, Chuan An, Yangzhiyuan Wang, Shumiao Li, Rui Zhu, Xingzhong Feng, Huijuan Gao","doi":"10.1186/s13062-026-00902-4","DOIUrl":"https://doi.org/10.1186/s13062-026-00902-4","url":null,"abstract":"<p><strong>Background & aims: </strong>Metabolic dysfunction-associated steatohepatitis (MASH) is driven by complex intercellular communication and regulated cell death pathways. Mitoxyperilysis, a recently characterized form of regulated lytic cell death, remains poorly defined in MASH. Here, we integrated multiomics, cross-species transcriptomics, machine learning, and in vivo models to dissect mitoxyperilysis activation and its therapeutic relevance in MASH.</p><p><strong>Methods: </strong>Single‑cell and spatial transcriptomic datasets from mouse and human MASH livers were analyzed. Cell-cell communication was inferred using CellChat, and metabolite‑mediated cell-cell communication (mCCC) was assessed with MEBOCOST. Mitoxyperilysis activity was scored via AUCell and AddModuleScore. Eleven machine learning classifiers identified transcriptomic signatures distinguishing MASH from controls, and key regulators were subjected to in silico knockout (scTenifoldKnk). A choline‑deficient, L‑amino acid‑defined high‑fat diet (CDAHFD) mouse model was used for in vivo validation.</p><p><strong>Results: </strong>Single‑cell profiling revealed that mitoxyperilysis activity was highly enriched in myeloid cells, particularly monocyte‑derived macrophages (Mo‑Macrophages) and neutrophils, and was strongly induced by high‑fat high‑sucrose diet. CellChat and mCCC analyses demonstrated that Mo‑Macrophages served as central hubs of rewired inflammatory and metabolic crosstalk in MASH. Spatial transcriptomics confirmed the expansion of pro‑inflammatory hepatocyte subsets and conserved upregulation of mitoxyperilysis components (e.g. BAX, TLR4, NINJ1) in both mouse and human MASH. Cross‑species profiling across mouse, rat, hamster, non‑human primate, and human datasets demonstrated evolutionarily conserved activation of the entire mitoxyperilysis pathway. Machine learning identified Bax as the sole overlapping driver gene linking diet‑induced transcriptomic signatures to mitoxyperilysis. In silico Bax ablation perturbed lipid metabolism and immune pathways. In CDAHFD-induced MASH mice with typical pathological phenotypes, core mitoxyperilysis genes were transcriptionally upregulated, and Bax/Bid/Bak1 upregulation was validated at the protein level. While RhoA mRNA increased, total RhoA protein remained stable, with its ubiquitination elevated and activity suppressed.</p><p><strong>Conclusions: </strong>Mitoxyperilysis is an evolutionarily conserved, myeloid‑enriched pathway activated in MASH. Bax acts as a critical regulatory node, while RhoA is modulated via ubiquitination and functional suppression. Targeting this axis may provide a novel therapeutic strategy for MASH.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"21 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149236898","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":"ZRANB1-mediated EZH2 stabilization drives S100B/S100A4 transcriptional activation and corneal neovascularization in alkali burns.","authors":"Fangyuan Liu, Ying Xiao, Yeping Huang, Yang Liu, Zhiyou Peng, Yulin Wang","doi":"10.1186/s13062-026-00892-3","DOIUrl":"10.1186/s13062-026-00892-3","url":null,"abstract":"<p><p>Alkali burn is one of the main causes of corneal injury. Corneal neovascularization caused by alkali burns aggravates corneal damage, resulting in aberrant vascular proliferation and consequent visual impairment. The present study investigated the role of enhancer of zeste homolog 2 (EZH2) in alkali burn‑induced corneal neovascularization. Through integrated bioinformatics and experimental approaches, we identified S100B, S100A4 and PI3K/AKT pathway activation as key drivers of alkali-induced corneal injury. In corneal alkali burn mice, knockdown of S100B or S100A4 attenuated corneal neovascularization and suppressed PI3K/AKT/FoxO3a pathway. EZH2 was upregulated in alkali-burn models and transcriptionally activated S100B and S100A4 via direct promoter binding. The deubiquitinase ZRANB1 was identified to stabilize EZH2 protein through deubiquitination, thereby amplifying its transcriptional activity. In alkali-injured human corneal epithelial cells, EZH2 overexpression enhanced cell viability, angiogenic capacity, migration and invasion ability, which was reversed by S100B or S100A4 knockdown. In vivo, EZH2 overexpression exacerbated PI3K/AKT/FoxO3a pathway activation and corneal neovascularization via regulating S100B or S100A4. Collectively, this study demonstrated that ZRANB1-mediated stabilization of EZH2 drove pathological corneal angiogenesis in corneal alkali burns by activating S100B/S100A4-PI3K/AKT/FoxO3a axis. These findings provided novel therapeutic targets for corneal alkali burns.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"21 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223218","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}