Integrative biology : quantitative biosciences from nano to macro最新文献

{"title":"Predicting gut metabolites from gut microbiome and their interpretability analysis of IBD prediction based on LIME.","authors":"Jing Liu, Kun Li, Yu Zhang, Kai Huang, Xiao Guan","doi":"10.1093/intbio/zyaf023","DOIUrl":"10.1093/intbio/zyaf023","url":null,"abstract":"<p><p>The pathophysiology of inflammatory bowel disease (IBD) is influenced by the gut microbiome and gut metabolite, but understanding how IBD is affected remains challenging. It is crucial to understand which features affect IBD in order to effectively diagnose the disease. Traditional technology for measuring metabolite features is time-consuming and costly. The abundance of metabolite features in IBD patients is altered depending to changes in the abundance of gut microbiome. LSTM-VAE is proposed to predict gut metabolite features using gut microbiome of IBD patients. The pathogenesis of IBD is investigated by LSTM-VAE without gut metabolite data. In order to explore IBD is affected by the features, GBDT-LR is used to predict IBD disease using the gut microbiome and the generated gut metabolites. GBDT-LR achieved high-precision prediction, with an accuracy of 0.97 at the genus level and 0.95 at the species level. It is noteworthy that LIME is used to explain the prediction process of GBDT-LR, solving the prediction of the 'black box model'. The cost of measuring intestinal metabolites were reduced in this study and the researches were assisted in the diagnosis and drug research of IBD diseases. Insight Box Dysbiosis of the gut microbiota and the resulting abnormal metabolites were influenced in the IBD, promoting inflammatory responses and damaging intestinal barrier function. LSTM-VAE was proposed to predict changes in gut metabolite features in IBD patients without the need for direct measurement of costly and time-consuming metabolite data. Furthermore, high-precision prediction of IBD based on gut microbiome data was demonstrated and metabolite features were generated in the GBDT-LR, achieving accuracy rates of 0.97 at the genus level and 0.95 at the species level. Additionally, the LIME is employed to interpret the \"black box\" prediction process of GBDT-LR. The cost of measuring gut metabolites was reduced, but also strong support for the diagnosis and drug development of IBD was provided.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"18 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147648671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delineating the interactions among mutual miRNAs and target genes associated with Parkinson's disease, endoplasmic reticulum stress and autophagy pathways: a computational analysis.","authors":"Lakshmi Sankaranarayanan, Jagan Muniyandi, Yerragudi Saicharan Reddy, Sachin Kalyani, Sudha Rani Sadras","doi":"10.1093/intbio/zyag005","DOIUrl":"10.1093/intbio/zyag005","url":null,"abstract":"<p><p>MicroRNAs have been implicated in the pathophysiology of several diseases including Parkinson's disease (PD). Endoplasmic reticulum (ER) stress mediated unfolded protein response (UPR) pathway and autophagy play a vital role in preventing the accumulation of α-synuclein, which is one among the major causes of PD. This study presents data on the interactions among miRNAs and genes involved in PD, ER stress and autophagy pathways analysed using computational tools. When the interactions among selected 89 miRNAs and 44 genes were visualised using Cytoscape, three miRNAs- hsa-miR-34a-5p, hsa-miR-9-5p and hsa-miR-214-3p were selected as hub-miRNAs based on their degree of interaction. Further, functional annotation and functional interaction analyses were carried out for the target genes of these hub-miRNAs. Based on ontology and enrichment analyses data, the targets of miR-34a-5p and miR-9-5p such as BCL2, BECN1, ATG5, HMGB1, and ATG7 were observed to be involved in apoptosis and autophagy. Further, the functional interactions of ATG5-BECN1 and BECN1-HMGB1 emphasised their integrative roles in autophagy. On the other hand, the targets of miR-214-3b such as XBP1, ATF4, BCL2L11, and BAX were found to be associated with ER stress and apoptosis. Also, functional interactions observed between XBP1-ATF4, ATF4-BCL2L11, and BCL2L11-BAX highlighted their integrative roles in neuronal apoptosis and ER stress pathways. Overall findings indicated that dysfunctions of these miRNAs might contribute to neuronal apoptosis through their regulatory roles in autophagy and ER stress pathways.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"18 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147319295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bivalency of natalizumab promotes inhibition of dynamic VLA-4 adhesion beyond affinity gain.","authors":"Marie-Pierre Valignat, Martine Biarnes-Pelicot, Dominique Touchard, Audrey Rico-Lamy, Patrick Chames, Olivier Theodoly, Philippe Robert","doi":"10.1093/intbio/zyag015","DOIUrl":"https://doi.org/10.1093/intbio/zyag015","url":null,"abstract":"<p><p>Natalizumab, a monoclonal IgG4 antibody used in the treatment of multiple sclerosis (MS), inhibits α4β1 (very late antigen-4, VLA-4)-binding to vascular cell adhesion molecule-1 (VCAM-1), thereby reducing leukocyte recruitment to inflamed tissues. The intricate mechanisms underlying these effects remain unclear, particularly concerning the heavy-chain shuffling of IgG4. We conducted an in vitro study to quantify the impact of bivalent IgG and monovalent Fab forms of natalizumab on the capture and migration of human primary memory T lymphocytes under shear stress, using VCAM-1 and CXCL12-coated surfaces. IgG natalizumab at concentrations near its cell surface EC50 (half-maximal effective concentration) showed significant of capture and resistance of adherent cells to shear stress, whereas significantly higher doses of Fab natalizumab, up to 100-fold greater than its cell surface EC50, were needed to achieve similar effects. These findings highlight that receptor occupancy alone may not adequately predict the functional outcomes of inhibitor antibodies. For optimal therapeutic effect, inhibition of cell-surface adhesion may require specific kinetic and geometric binding properties of antibodies. Insight Box This study shows how natalizumab functionally inhibits α4β1 (very late antigen-4, VLA-4)-mediated T-cell adhesion by integrating quantitative affinity measurements with dynamic assays performed under shear stress. We show that the antibody's bivalency provides a major functional advantage, enabling strong inhibition of cell capture and adhesion at concentrations near its EC50 (half-maximal effective concentration), whereas monovalent Fab fragments require 10- to 100-fold higher doses. These findings offer biological insight into why receptor occupancy alone cannot predict adhesion inhibition. By combining cell-based affinity quantification with real-time adhesion and migration assays, our work reveals how kinetic and geometric properties of antibody-integrin interactions shape immune cell dynamics, informing the rational design of next-generation integrin-targeting therapeutics.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"18 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148650413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptation to solvent environment in toll-like receptor 5: kernel-based evolutionary analysis of membrane-bound and soluble forms in Epinephelus coioides.","authors":"Alper Karagöl, Taner Karagöl","doi":"10.1093/intbio/zyag011","DOIUrl":"10.1093/intbio/zyag011","url":null,"abstract":"<p><p>Toll-like receptor 5 (TLR5) is a conserved member of the innate immune system and known for its ability to detect bacterial flagellin. Interestingly, the orange-spotted grouper (Epinephelus coioides), possess both membrane-bound (mTLR5) and soluble (sTLR5) forms of TLR5, which is not observed in mammals. We analyzed sequence characteristics, amino acid composition, and physicochemical properties of both proteins to understand the basis for their differing solubility and polarity. Superposition of Alphafold3 predicted structures quantified the structural similarities with a RMSD value of 1.361 Å. Contrary to the conserved tertiary structures, our results reveal distinct amino acid preferences between sTLR5 and mTLR5. Asymmetric evolutionary dynamics and kernel causality were thereby investigated using generalized correlation coefficients. The dependence analysis revealed that TLR5 evolution shows multidirectional dynamics between soluble and membrane-bound forms, as 2 amino acids (M and V) shift membrane-to-solvent, 2 shift solvent-to-membrane (H and Y). The T < =>V and D > K substitutions required two base changes and therefore introduced a mutational bias. Regression analysis of the homologous sequences indicated T < =>V changes may have supported by alanine intermediates. These findings provide insights into the functional diversification of TLR5 and broader implications on the diversification of immune system proteins. Insight Box This study investigates the evolutionary patterns towards adapting a solvent environment in TLR5 by comparing the membrane-bound (mTLR5) and soluble (sTLR5) forms from the Epinephelus coioides. Contrary to the conserved tertiary structures, our results reveal distinct amino acid preferences between sTLR5 and mTLR5. We show that adaptation is bidirectional and strategically localized, preserving ligand recognition while enabling immune modulation in extracellular space. Understanding these adaptations offer new perspectives on immune responses, particularly in conditions involving dysregulated TLR5 signalling, such as chronic inflammation and autoimmune diseases.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"18 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148152753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trim45 promotes the occurrence and development of cervical cancer by inhibiting the cGAS/STING signaling pathway.","authors":"Huhu Zhang, Xi Chen, Banghui Wang, Lingxi Li, Xiaolei Dong, Yiming Zhang, Bing Li","doi":"10.1093/intbio/zyag009","DOIUrl":"10.1093/intbio/zyag009","url":null,"abstract":"<p><p>Cervical cancer is a gynecological malignancy closely associated with high-risk human papillomavirus infection. Trim45, a member of the E3 ubiquitin ligase family, is highly expressed in cervical cancer tissues; however, its specific mechanistic contribution to disease progression remains incompletely understood. By integrating single-cell sequencing, functional assays, and molecular profiling, we found that single-cell sequencing and IHC analyses revealed high Trim45 expression in cervical cancer tissues from patients with HPV-18 infection. Furthermore, we uncovered a novel mechanism by which Trim45 promotes cervical cancer progression: Trim45 suppresses the cGAS/STING signaling pathway activity by mediating ANXA2, which subsequently upregulates the expression of the key glycolytic enzymes HK2 and ENO2, enhances the aerobic glycolysis capacity of tumor cells, and ultimately promotes cervical cancer proliferation and metastasis. Collectively, these findings elucidate the molecular mechanism by which Trim45 drives the malignant progression of cervical cancer through the \"ANXA2-cGAS/STING-glycolysis\" axis. Statement of Integration, Innovation and Insight This study integrates single-cell sequencing and functional assays to reveal that Trim45, highly expressed in HPV-18 positive cervical cancer, suppresses the cGAS/STING innate immune signaling pathway by mediating ANXA2. This suppression subsequently upregulates the key glycolytic enzymes HK2 and ENO2, thereby enhancing aerobic glycolysis in tumor cells, and promotes proliferation and metastasis. These findings uncover a novel Trim45-ANXA2-cGAS/STING-glycolysis axis, offering potential therapeutic co-targets.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"18 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148020457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential therapeutic targets for obstructive sleep Apnea were identified through network pharmacology, WGCNA, machine learning, immune infiltration analysis, and ceRNA network.","authors":"Fengwei Xie, Dikun Zhu, Zhitong Yang, Jie Sun, Tao Huang, Qian Xian, Dingyu Guo, Yuyin Lin, Lingyue Song, Ming Zhong, Yiming Liu, Tianhuang Yuan, Lingpin Pang, Xishi Sun","doi":"10.1093/intbio/zyag013","DOIUrl":"https://doi.org/10.1093/intbio/zyag013","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Our study aims to explore the early genomic diagnostic markers of OSA and the corresponding drug prediction targets using network pharmacology analysis, and to elucidate the etiology and pathogenesis of OSA from the genetic level.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We selected OSA-related gene datasets (GSE135917 and GSE38792) from the Gene Expression Omnibus (GEO). Principal component analysis (PCA) was performed to remove outlier samples, and batch correction was applied to the two datasets. The raw expression matrix was log2-transformed, and samples were divided into normal and OSA groups. Differentially expressed genes (DEGs) were identified, and WGCNA analysis was performed on these DEGs to identify mitochondria-associated hub genes, followed by functional enrichment analysis, PPI network construction, core lncRNA-related ceRNA network construction. We then screened core genes with a high risk of OSA. Based on the core genes, we established an easy-to-use nomogram and verified its accuracy in identifying OSA patients then performed a differential expression analysis of the core genes, GSEA and GSVA analyses, and immune infiltration analysis. Finally, we constructed the disease prediction model and predicted the drug targets, thereby obtain a genomic prediction model for OSA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;After PCA and batch correction, an expression matrix comprising 13 normal samples and 19 OSA patient samples was finally included. We identified 1500 differentially expressed genes (DEGs) through differential expression analysis, then screened 61 hub genes by WGCNA analysis, and established an OSA-associated ceRNA network containing 75 predictive miRNAs, 129 lncRNAs and 5 mRNAs. Six robust key genes were identified through PPI network construction: TUFM, CYCS, UQCRC1, COX4I1, TIMM50, and NDUFV1. Finally, after LASSO regression and nomogram validation, a predictive model containing 2 core genes (UQCRC1 and COX4I1) was obtained, and its area under the ROC curve (AUC) was 0.919. Drug target prediction of the core genes showed that 1-Methyl-4-phenyl-2,3-dihydropyridinium CTD 00002003, Cube root extract CTD 00006707, Disodium selenite CTD 00007229, and mitotane CTD 00006344 had good effects.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Our current findings provide a rationale for identifying therapeutic targets in the diagnosis and treatment of OSA. In addition, these findings have the potential to facilitate the translation of our study to clinical applications in the future. Insight Box Different from other single-gene predictors of OSA, network pharmacological analysis identified differential genes and explored biomolecular markers of OSA from multi-gene and multi-target perspectives through enrichment analysis, construction of ceRNA gene network, and correlation analysis and explore early genomic diagnostic indicators of OSA and corresponding drug prediction targets using network pharmacological analysis and to elucidate ","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"18 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148650398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MARCH1 attenuates lung adenocarcinoma by blocking macrophage M2 polarization and cisplatin resistance through reducing SLC25A17 stability.","authors":"Huifeng Wang, Yanyan Sun, Rui Zi, Tingting Shi, Hui Dong","doi":"10.1093/intbio/zyag004","DOIUrl":"10.1093/intbio/zyag004","url":null,"abstract":"<p><p>Cisplatin (DDP) resistance constitutes a major obstacle associated with poor prognosis in patients with lung adenocarcinoma (LUAD). Membrane-associated RING-CH finger protein 1 (MARCH1) contributed to shaping an inflamed tumor microenvironment, which is linked to chemotherapy resistance in LUAD patients. However, its role and underlying mechanisms in DDP-resistant LUAD patients remains to be elucidated. Herein, we observed that MARCH1 was downregulated in DDP-resistant lung cancer tissues, and low MARCH1 expression was correlated with poor prognosis of LUAD patients. MARCH1 overexpression enhanced DDP sensitivity, suppressed proliferation and invasion, and promoted apoptosis in DDP/A549 cells. Co-culture experiments revealed that MARCH1 overexpression suppressed the polarization of tumor-associated macrophages toward the M2 phenotype, as validated by ELISA, flow cytometry, Western blotting, and immunofluorescence staining. MARCH1 contributed to shape the tumor immune microenvironment, affecting immunostimulators, MHC molecules, chemokines, and receptors. Moreover, co-immunoprecipitation and ubiquitination experiments confirmed that MARCH1 facilitated the ubiquitination and degradation of solute carrier family 25 member 17 (SLC25A17). Rescue experiments demonstrated that overexpression of SLC25A17 attenuated the enhancement of DDP sensitivity evoked by MARCH1 reintroduction through promoting M2 macrophage polarization. Additionally, the tumor-suppressive effect of MARCH1 in LUAD was confirmed in vivo. In conclusion, our findings indicated that MARCH1 suppressed lung cancer progression by blocking macrophage M2 polarization and DDP resistance through ubiquitinating SLC25A17, thus providing a new mechanism for cisplatin resistance in LUAD.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"18 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147319292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered lymphatic stroma model applications in central nervous system leukemia.","authors":"Jennifer H Hammel, Hailey E Murphy, Khadijat O Oyediran, Peter M Gordon, L Monet Roberts","doi":"10.1093/intbio/zyag012","DOIUrl":"10.1093/intbio/zyag012","url":null,"abstract":"<p><p>Central nervous system (CNS) involvement frequently occurs in acute lymphoblastic leukemia (ALL), but many questions remain about how leukemia cells access, persist in, and exploit the CNS. The CNS is protected by the meninges, which are fluid-filled membranes that surround the brain. Within the meninges, meningeal lymphatic vessels, located within the dura mater, drain cerebrospinal fluid to the deep cervical lymph nodes for immunosurveillance, providing a potential pathway for leukemia cells to enter or exit the CNS. Here, we utilized tissue engineered models of the meningeal lymphatics and lymph node stroma to probe how leukemia cells interact with these key microenvironments. We first demonstrated that standard-of-care chemotherapeutics can perturb the meningeal lymphatics, particularly lymphatic endothelial cells. Next, we showed that soluble factors from the meningeal lymphatics conferred a modest upward trend in leukemia cell growth, while soluble factors from the lymph node model under flow significantly promoted leukemia cell migration. Finally, we showed that leukemia cells migrate through the lymph node model under both static and flow conditions. Overall, we have demonstrated the feasibility of using engineered lymphatic models to study leukemia cell behavior in the CNS with the goal of expanding the available experimental platforms for understanding CNS metastasis and relapse. Insight Box Leukemia commonly infiltrates the central nervous system (CNS), requiring intensive CNS-directed therapies that are often ineffective and cause both acute and long-term toxicities, especially in pediatric patients. The meningeal lymphatics and the deep cervical lymph nodes constitute a pivotal axis in CNS immunity, facilitating drainage of fluid and waste, and enabling peripheral immune surveillance in response to CNS-derived signals. Here, we employ in vitro models of the meningeal lymphatics and lymph node stroma to examine their crosstalk in influencing leukemia cell growth and migration. These engineered platforms serve as valuable tools for uncovering mechanistic insights into the meningeal-lymph node axis in the context of CNS-leukemia relapse.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"18 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148230506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune, metabolic, and steroidogenesis-associated profiles of miR-940, miR-375, and miR-326 in adrenocortical carcinoma.","authors":"Javad Omidi","doi":"10.1093/intbio/zyag016","DOIUrl":"https://doi.org/10.1093/intbio/zyag016","url":null,"abstract":"<p><p>Adrenocortical carcinoma (ACC) has remained a highly aggressive endocrine malignancy characterized by extensive molecular heterogeneity and limited therapeutic options. In the present study, the regulatory significance of hsa-miR-940, hsa-miR-375, and hsa-miR-326, previously identified as central hubs within an ACC competing endogenous RNA (ceRNA) network, was comprehensively characterized through integrative transcriptomic, prognostic, and pathway-level analyses using TCGA-ACC tumor samples. Network topology analysis, target prediction, survival modeling, pathway enrichment, protein-protein interaction analysis, therapeutic-response evaluation, and pan-cancer expression characterization were subsequently performed to investigate the biological relevance of these central miRNAs. Distinct network-topology differences were identified between tumor and normal ceRNA networks, with hsa-miR-940 demonstrating increased tumor-associated regulatory centrality, whereas hsa-miR-326 exhibited comparatively higher centrality within normal adrenal networks. Survival analyses further demonstrated that elevated expression of the combined three-miRNA signature was associated with significantly reduced overall survival in patients with ACC (HR = 3.52, p = 1.36E-03). Functional enrichment analyses revealed extensive associations with complement activation, steroidogenic regulation, mitochondrial bioenergetics, extracellular matrix remodeling, immune-associated signaling, lipid metabolism, and apoptosis-related pathways. Protein-protein interaction analysis additionally identified highly interconnected immune- and metabolism-associated hub genes, including CCL2, C3, SERPING1, PPARGC1A, and CFH, within the hsa-miR-940 regulatory network. Cross-cancer analyses further demonstrated substantial context-dependent expression heterogeneity across tumor types. The integrative findings presented in this study support the biological plausibility that hsa-miR-940, hsa-miR-375, and hsa-miR-326 may participate in coordinated regulatory programs associated with ACC progression and endocrine tumor adaptation. Insight box This study explores how three small regulatory molecules, known as microRNAs (miR-940, miR-375, and miR-326), may influence the development and progression of adrenocortical carcinoma (ACC), a rare and aggressive adrenal cancer. By analyzing large-scale gene expression data from tumor and normal adrenal tissues, important differences were identified in immune-related, metabolic, and hormone-associated biological processes linked to these microRNAs. The findings suggest that these molecules may contribute to how ACC tumors grow, adapt, and interact with their surrounding environment. This work demonstrates how integrative computational and biological analyses can help uncover potential biomarkers and future therapeutic targets in rare cancers such as ACC.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"18 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148650350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of decidual natural killer cells cell heterogeneity and dynamic evolution in recurrent miscarriage based on single cell RNA-seq analysis.","authors":"Binbin Fu, Huijing Wang","doi":"10.1093/intbio/zyag021","DOIUrl":"https://doi.org/10.1093/intbio/zyag021","url":null,"abstract":"<p><strong>Purpose: </strong>This study used scRNA-seq to explore the underlying mechanisms of decidual natural killer cells affecting recurrent miscarriage (RM).</p><p><strong>Methods: </strong>We obtained the GSE214607 scRNA-seq dataset from Gene Expression Omnibus (GEO) database, containing data from 5 normal and 3 RM pregnancy samples. The 'Seurat' and 'Harmony' R package was used for the scRNA-seq analysis. Differentially expressed genes among cell subpopulations were identified using FindAllMarkers function, and the 'Monocle2' package was employed to construct pseudo-time trajectories. Finally, the 'CellChat' package was used to analyze ligand-receptor interactions between cells.</p><p><strong>Results: </strong>Our analysis revealed altered immune cell composition in RM, with reduced decidual NK (dNK), decidual stromal, and epithelial glandular cells but increased Mono/Macro proportions. Two dNK subclusters were identified: PAEP-high (linked to growth factor signaling) and LGALS1-high (involved in glycolysis and platelet function). Despite similar subcluster frequencies, RM samples showed elevated interferon response genes (e.g. IFITM1, ISG15) and diminished migration/activation signals. Pseudo-time analysis highlighted progressive gene expression changes during RM. CellChat revealed reduced Vascular Endothelial Growth Factor (VEGF) signaling, indicating impaired angiogenesis, and enhanced TNF, MHC-II, and FAS/FASL interactions, suggesting increased inflammation and trophoblast apoptosis. These findings implicate dNK dysfunction in RM and suggest potential therapeutic targets.</p><p><strong>Conclusions: </strong>Our findings demonstrate dNK cell dysfunction in RM, marked by heightened interferon signaling and aberrant crosstalk with trophoblasts. Integrative analysis of public transcriptomic data suggests that dNK cell-directed interventions represent a putative therapeutic avenue for RM. Insight RM linked to decidual immune imbalance with reduced dNK and increased monocytes/macrophages. Two dNK subclusters (PAEP-high, LGALS1-high) with specific gene expression pattern in RM. RM shows impaired angiogenesis, inflammation, and trophoblast apoptosis in dNK cell-mediated signaling pathways. Dysfunctional dNK cells drive RM, revealing potential therapeutic targets for treatment.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"18 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}