NPJ Systems Biology and Applications最新文献_第2页

Multiscale Modeling of Embryonic Morphogenesis from Fertilization to Organogenesis. 从受精到器官发生的胚胎形态发生的多尺度建模。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-07-15 DOI: 10.1038/s41540-026-00788-y

Debanik Deb, Orishma Parida, Laasya Naduthota, Bandan Chakrabortty

引用次数: 0

Sleep restriction reprograms systemic immunity through NK and T cell crosstalk. 睡眠限制通过NK和T细胞串扰重编程系统免疫。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-07-14 DOI: 10.1038/s41540-026-00787-z

Zhengyang Qiu, Jichen Jin, Pengqi Zhang, Chen Li, Yongmei Xi

{"title":"Sleep restriction reprograms systemic immunity through NK and T cell crosstalk.","authors":"Zhengyang Qiu, Jichen Jin, Pengqi Zhang, Chen Li, Yongmei Xi","doi":"10.1038/s41540-026-00787-z","DOIUrl":"https://doi.org/10.1038/s41540-026-00787-z","url":null,"abstract":"Insufficient sleep is a recognized risk factor for inflammatory diseases, yet how sleep loss functionally perturbs immune regulation remains unclear. Here, we apply a multi-omics framework combining two-sample Mendelian randomization, sleep-restriction intervention microarray, and PBMC single-cell profiling to dissect immune consequences of sleep loss. Mendelian randomization associated genetically proxied sleeplessness/insomnia symptoms with alterations in 162 plasma proteins and increased risk across 94 clinical diagnosis traits. Gene expression microarray after sleep restriction confirmed immune activation and stress-response programs. Single-cell RNA sequencing revealed PBMC remodeling with increased NK/NKT cells and decreased γδ T cells and dendritic cells, alongside pro-inflammatory pathway activity. Ligand-receptor analysis identified altered intercellular communication patterns, characterized by increasing signals to NK cells and enhancing NK-T cell-associated interfaces. These findings nominate dysregulated NK cell-T cell crosstalk as a putative mechanism underlying sleep-related inflammation and provide prioritized targets for future validation.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448386","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}

引用次数: 0

The unreasonable likelihood of being: origin of life, terraforming, and AI. 不合理的存在可能性：生命的起源、地球化和人工智能。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-07-13 DOI: 10.1038/s41540-026-00785-1

Robert G Endres

引用次数: 0

Drug-tolerant persisters to TRAIL emerge from a dose-dependent surface in a cell-state continuum of sensitivity. 对TRAIL的耐药持久性在细胞状态敏感性连续体中从剂量依赖的表面出现。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-07-13 DOI: 10.1038/s41540-026-00782-4

Giada Fiandaca, Marielle Péré, Kelian Bonhomme, Madalena Chaves, Jérémie Roux

{"title":"Drug-tolerant persisters to TRAIL emerge from a dose-dependent surface in a cell-state continuum of sensitivity.","authors":"Giada Fiandaca, Marielle Péré, Kelian Bonhomme, Madalena Chaves, Jérémie Roux","doi":"10.1038/s41540-026-00782-4","DOIUrl":"https://doi.org/10.1038/s41540-026-00782-4","url":null,"abstract":"Clonal cancer cells show heterogeneous responses to cytotoxic drugs, raising the question of whether this variability reflects discrete phenotypes or a continuum of underlying cell states. We address this by quantifying single-cell caspase-8 activation dynamics after TRAIL treatment and developing an extended mechanistic model of the extrinsic apoptosis pathway that incorporates c-FLIP-mediated control of initiator caspase activation. Fitting this model to individual trajectories across multiple doses recovers cell-specific procaspase-8 and c-FLIP abundances, together with three kinetic parameters, and reproduces the full diversity of observed responses. Embedding these inferred parameters into a shared state space reveals that sensitive and tolerant outcomes do not correspond to discrete subpopulations. Instead, a single biochemical pathway generates a continuous distribution of cell states whose position at treatment determines fate. Linking each trajectory to its early activation rate identifies a dose-dependent hyperplane that partitions this landscape into apoptotic and tolerant regions. Increasing drug dose translates this decision surface predictably, altering the outcome only for cells positioned near the boundary. This geometric perspective explains fractional killing in clonal populations and shows how drug-tolerant persister cells can arise from reversible variation in cell state. It further suggests that shifting state-space distributions relative to the decision surface may offer new strategies to limit persistence.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437567","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}

引用次数: 0

Th2 bias and T-cell exhaustion characterize the immunopathology of non-tuberculous mycobacterial pulmonary disease. Th2偏倚和t细胞耗竭是非结核性分枝杆菌肺病的免疫病理特征。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-07-07 DOI: 10.1038/s41540-026-00784-2

Tingting Fang, Feifei Yuan, Yu Chen, Shuang Wan, Na Li, Yuyan Ma, Qingqing Wang, Wenting Jin, Qing Miao, Lijuan Hu, Jue Pan, Donghe Li, Bijie Hu

{"title":"Th2 bias and T-cell exhaustion characterize the immunopathology of non-tuberculous mycobacterial pulmonary disease.","authors":"Tingting Fang, Feifei Yuan, Yu Chen, Shuang Wan, Na Li, Yuyan Ma, Qingqing Wang, Wenting Jin, Qing Miao, Lijuan Hu, Jue Pan, Donghe Li, Bijie Hu","doi":"10.1038/s41540-026-00784-2","DOIUrl":"10.1038/s41540-026-00784-2","url":null,"abstract":"Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is an escalating global health concern with poorly defined immunological mechanisms, necessitating comprehensive profiling to guide therapeutic advances. We analyzed peripheral blood from 28 treatment-naïve NTM-PD patients (19 Mycobacterium avium complex, 9 Mycobacterium abscessus) and 27 matched controls using 42-marker mass cytometry (CyTOF) and Luminex multiplex assays. A random forest model identified predictive markers, while an in vitro murine macrophage model evaluated chemokine production. NTM-PD patients displayed significant immune shifts, including increased classical monocytes (CD14+ CD16-), reduced NKT-like cells (CD3+ CD56+), and elevated T-cell exhaustion markers (PD-1, TOX). This coincided with a Th1/Th2 balance shift characterized by heightened IL-13. Elevated IFN-γ-inducible chemokines CXCL9 and CXCL10 coexisted with this Th2-biased signature, indicating a complex, dysregulated inflammatory state. A model integrating immune-cell frequencies and cytokine profiles achieved robust diagnostic accuracy (AUC = 0.922) with prognostic potential. In vitro, NTM-infected macrophages produced substantial CXCL9 and CXCL10 levels relative to the LPS maximal activation benchmark, identifying them as a major cellular source. These findings propose an immunological framework wherein T-cell exhaustion and a Th2-biased microenvironment strongly correlate with NTM-PD pathogenesis. CXCL9, CXCL10, and IL-13 emerge as candidate therapeutic targets, while our predictive model offers a foundational approach for risk stratification.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405330","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}

引用次数: 0

Identification of phillyrin as a PPAR-γ ligand through network pharmacology and molecular modeling. 通过网络药理学和分子模型鉴定茶树苷为PPAR-γ配体。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-07-06 DOI: 10.1038/s41540-026-00780-6

Ling Huang, Zhizheng Fang, Rongchun Han, Xiaohui Tong

{"title":"Identification of phillyrin as a PPAR-γ ligand through network pharmacology and molecular modeling.","authors":"Ling Huang, Zhizheng Fang, Rongchun Han, Xiaohui Tong","doi":"10.1038/s41540-026-00780-6","DOIUrl":"https://doi.org/10.1038/s41540-026-00780-6","url":null,"abstract":"Insulin resistance is a core pathological hallmark of metabolic syndromes like type 2 diabetes mellitus. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a classical therapeutic target for improving insulin sensitivity, yet the clinical utility of its synthetic agonists faces diverse adverse reactions. We previously showed that phillyrin, an important component of Forsythia suspensa, could improve insulin resistance in obesity. However, its direct molecular targets remain not fully understood. Herein, we adopted a combined in silico and experimental approach to determine whether phillyrin could function as a ligand of PPAR-γ. We implemented a multi-scale strategy integrating network pharmacology, molecular modeling, with experimental verification. Network pharmacology analysis was employed to predict system-level targets and pathways associated with phillyrin. Subsequently, molecular docking and molecular dynamics simulations were conducted using computational chemistry methods to characterize the binding mode, dynamic stability, and binding free energy (MM-GBSA) of phillyrin within the PPAR-γ ligand-binding domain. Finally, key computational predictions were experimentally validated in insulin-resistant 3T3-L1 adipocytes and in a high-fat diet-induced murine model of insulin resistance.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397475","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}

引用次数: 0

Oncostatin M orchestrates collective epithelial migration via HIF1A activation. Oncostatin M通过HIF1A激活协调集体上皮迁移。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-07-06 DOI: 10.1038/s41540-026-00778-0

Ian C McLean, Sean M Gross, Tiera A Liby, Mark A Dane, Daniel S Derrick, Laura M Heiser

{"title":"Oncostatin M orchestrates collective epithelial migration via HIF1A activation.","authors":"Ian C McLean, Sean M Gross, Tiera A Liby, Mark A Dane, Daniel S Derrick, Laura M Heiser","doi":"10.1038/s41540-026-00778-0","DOIUrl":"10.1038/s41540-026-00778-0","url":null,"abstract":"Extracellular signals strongly influence cell behavior, yet the mechanisms by which specific ligands mediate changes in phenotype remain unclear. The cytokine Oncostatin M (OSM) regulates homeostasis, wound healing, inflammation, and cancer progression. We previously found that OSM induces collective cell migration (CCM), a process whereby cells move as cohesive units while retaining cell-cell contacts, in MCF10A mammary epithelial cells. Here, we investigated how OSM drives CCM by comparing its effects with those elicited by epidermal growth factor (EGF) and interferon gamma (IFNG), defining ligand-specific phenotypes and molecular networks. Integrative transcriptomic and proteomic analyses identified hypoxia-inducible factor-1 (HIF1A) and signal transducer and activator of transcription 3 (STAT3) as central regulators of OSM responses. Functional validation revealed that HIF1A drives transcriptional programs associated with hypoxia, metabolic reprogramming, and immune pathways. Complement signaling emerged as a downstream effector of HIF1A, and its inhibition disrupted OSM-induced clustering and CCM. These findings establish a mechanistic link between OSM signaling, HIF1A activation, and CCM, demonstrating how cytokine-driven transcriptional reprogramming coordinates epithelial cell migration. Analysis of public breast cancer data indicate that this pathway is active in human tumors and may contribute to tissue remodeling, repair, and metastasis.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397503","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}

引用次数: 0

Expanding the role of metabolism in whole plant models. 扩展代谢在整个植物模型中的作用。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-07-04 DOI: 10.1038/s41540-026-00773-5

Karuthedath Shaijal, Meera Joshi, Sanu Shameer

引用次数: 0

Modeling single nucleus microglia across species identifies immune pathways and therapeutic candidates in Alzheimer's disease. 跨物种单核小胶质细胞建模识别阿尔茨海默病的免疫途径和治疗候选。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-07-03 DOI: 10.1038/s41540-026-00775-3

Alexander Bergendorf, Jee Hyun Park, Brendan K Ball, Douglas K Brubaker

{"title":"Modeling single nucleus microglia across species identifies immune pathways and therapeutic candidates in Alzheimer's disease.","authors":"Alexander Bergendorf, Jee Hyun Park, Brendan K Ball, Douglas K Brubaker","doi":"10.1038/s41540-026-00775-3","DOIUrl":"10.1038/s41540-026-00775-3","url":null,"abstract":"Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss and behavioral changes. A pivotal influence on AD pathology is the dysregulation of microglia in the brain. Despite promising findings in mouse models, there are limitations to the translatable biological information across species due to differences in the physiology, timeline of disease, and human heterogeneity. To address these interspecies discrepancies, we developed a novel implementation of the Translatable Components Regression (TransComp-R) framework, which integrated microglial single-nucleus transcriptomic data to identify biological pathways in mice AD models predictive of human AD. We compared model variations with sparse and traditional principal component analysis (PCA), finding that standard PCA encoded more interpretable mouse PCs compared to sPCA despite limited differences in technical performance. Mouse PCs significantly differentiated human AD from control microglial cells in the BA41/42, BA6/8, hippocampus and entorhinal cortex brain regions. However, these PCs had limited separation of human AD from control microglia in the prefrontal cortex. Additionally, we identified gene signatures from FDA-approved drugs that correlated with significant mouse component loadings, including valproic-acid and calcifediol. This computational framework may support the discovery of cross-species disease similarities, including the identification of candidate pharmacological solutions that may translate across species.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382401","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}

引用次数: 0

Metabolic set theory: a generalized model of microbial interactions. 代谢集理论：微生物相互作用的广义模型。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-07-01 DOI: 10.1038/s41540-026-00774-4

Jyoti Jyoti, Hannah Zoller, Wolfgang Zu Castell, Marc-Thorsten Hütt

引用次数: 0