Communications Biology最新文献_第9页

scMalignantFinder distinguishes malignant cells in single-cell and spatial transcriptomics by leveraging cancer signatures. scMalignantFinder通过利用肿瘤特征来区分单细胞和空间转录组学中的恶性细胞。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-27 DOI: 10.1038/s42003-025-07942-y

Qiaoni Yu, Yuan-Yuan Li, Yunqin Chen

{"title":"scMalignantFinder distinguishes malignant cells in single-cell and spatial transcriptomics by leveraging cancer signatures.","authors":"Qiaoni Yu, Yuan-Yuan Li, Yunqin Chen","doi":"10.1038/s42003-025-07942-y","DOIUrl":"10.1038/s42003-025-07942-y","url":null,"abstract":"Single-cell RNA sequencing (scRNA-seq) is a powerful tool for characterizing tumor heterogeneity, yet accurately identifying malignant cells remains challenging. Here, we propose scMalignantFinder, a machine learning tool specifically designed to distinguish malignant cells from their normal counterparts using a data- and knowledge-driven strategy. To develop the tool, multiple cancer datasets were collected, and the initially annotated malignant cells were calibrated using nine carefully curated pan-cancer gene signatures, resulting in over 400,000 single-cell transcriptomes for training. The union of differentially expressed genes across datasets was taken as the features for model construction to comprehensively capture tumor transcriptional diversity. scMalignantFinder outperformed existing automated methods across two gold-standard and eleven patient-derived scRNA-seq datasets. The capability to predict malignancy probability empowers scMalignantFinder to capture dynamic characteristics during tumor progression. Furthermore, scMalignantFinder holds the potential to annotate malignant regions in tumor spatial transcriptomics. Overall, we provide an efficient tool for detecting heterogeneous malignant cell populations.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"504"},"PeriodicalIF":5.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Muscone-specific olfactory protein MjavOBP3 identified as the putative scent-marking pheromone in the Sunda pangolin (Manis javanica). 在巽他穿山甲（Manis javanica）中鉴定出的麝香特异性嗅觉蛋白MjavOBP3是推测的气味标记信息素。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-26 DOI: 10.1038/s42003-025-07925-z

Zhongbo Yu, Tao Meng, Tengcheng Que, Luyao Yu, Yichen Zhou, Meihong He, Haijing Wang, Yingjiao Li, Liling Liu, Wenjian Liu, Yinliang Wang, Bingzhong Ren

{"title":"Muscone-specific olfactory protein MjavOBP3 identified as the putative scent-marking pheromone in the Sunda pangolin (Manis javanica).","authors":"Zhongbo Yu, Tao Meng, Tengcheng Que, Luyao Yu, Yichen Zhou, Meihong He, Haijing Wang, Yingjiao Li, Liling Liu, Wenjian Liu, Yinliang Wang, Bingzhong Ren","doi":"10.1038/s42003-025-07925-z","DOIUrl":"10.1038/s42003-025-07925-z","url":null,"abstract":"Pangolins are mammals of important conservation interest, as only eight extant species remain globally and all are considered to be at risk of extinction. The Sunda pangolin (Manis javanica) is a burrowing and nocturnal animal with poor vision, thus intraspecies communication such as mating, warning, and scent-marking relies on olfaction. The specific pheromone involved in intraspecies communication in pangolins remains unknown. In this study, all odorant-binding proteins in Sunda pangolins are functionally expressed and screened against a panel of 32 volatiles that derived from the pangolin urine, feces, and anal gland secretions. Using reverse chemical ecology, we reveal that M. javanica odorant-binding protein 3 (MjavOBP3) possesses the highest binding affinity to muscone. We also apply a behavior-tracking assay to show that muscone is more attractive to male individuals than to females, suggesting that muscone is a scent-marking pheromone in the Sunda pangolin. Further, our molecular modeling shows that Tyr117 contributes the most to muscone binding, which is further validated by site-directed mutagenesis. These findings identify the scent-marking mechanism in pangolins, highlighting the potential of muscone to support monitoring and conservation of this endangered animal.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"498"},"PeriodicalIF":5.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

m⁶A modification regulates cell proliferation via reprogramming the balance between glycolysis and pentose phosphate pathway. m6A修饰通过重编程糖酵解和戊糖磷酸途径之间的平衡来调节细胞增殖。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-26 DOI: 10.1038/s42003-025-07937-9

Jian-Fei Xi, Biao-Di Liu, Guo-Run Tang, Ze-Hui Ren, Hong-Xuan Chen, Ye-Lin Lan, Feng Yin, Zigang Li, Wei-Sheng Cheng, Jinkai Wang, Lili Chen, Shao-Chun Yuan, Zhang Zhang, Guan-Zheng Luo

{"title":"m6A modification regulates cell proliferation via reprogramming the balance between glycolysis and pentose phosphate pathway.","authors":"Jian-Fei Xi, Biao-Di Liu, Guo-Run Tang, Ze-Hui Ren, Hong-Xuan Chen, Ye-Lin Lan, Feng Yin, Zigang Li, Wei-Sheng Cheng, Jinkai Wang, Lili Chen, Shao-Chun Yuan, Zhang Zhang, Guan-Zheng Luo","doi":"10.1038/s42003-025-07937-9","DOIUrl":"10.1038/s42003-025-07937-9","url":null,"abstract":"N6-methyladenosine (m6A) stands as the predominant modification in eukaryotic mRNA and is involved in various biological functions. Aberrant m6A has been implicated in abnormal cellular phenotypes, including defects in stem cell differentiation and tumorigenesis. However, the precise effects of m6A on cell proliferation and the underlining mechanism of metabolic gene regulation remain incompletely understood. Here, we established a cellular environment with low-m6A levels and observed a severe impairment of cell proliferation. Mechanistic studies revealed that the depletion of m6A on TIGAR mRNA led to increased expression, subsequently inhibiting glycolysis while promoting the pentose phosphate pathway (PPP). A genome-wide CRISPR-Cas9 screen identified numerous genes involved in cell proliferation that are sensitive to m6A modification, with G6PD emerging as a key regulator. Integration of gene expression and survival data from cancer patients suggested that patients with elevated G6PD expression may exhibit enhanced responsiveness to tumor growth inhibition through m6A suppression. Our findings elucidate the critical role of m6A in cell proliferation, highlighting the therapeutic potential of targeting m6A-mediated metabolic pathways in cancer.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"496"},"PeriodicalIF":5.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

The lifelong nonlinear development of spatial variability of brain signals. 脑信号空间变异性的终身非线性发展。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-26 DOI: 10.1038/s42003-025-07939-7

Chengxiao Yang, Gen Li, Xiujuan Jing, Yifeng Wang, Jin H Yan, Georg Northoff

{"title":"The lifelong nonlinear development of spatial variability of brain signals.","authors":"Chengxiao Yang, Gen Li, Xiujuan Jing, Yifeng Wang, Jin H Yan, Georg Northoff","doi":"10.1038/s42003-025-07939-7","DOIUrl":"10.1038/s42003-025-07939-7","url":null,"abstract":"The physiological information carried by brain signals is distinguished by their mean and variability. Research has indicated that both the variability of local signals and the spatial mean of the whole-brain signal (known as the global signal, GS) are sensitive to brain development. This raises the question of whether the spatial variability of the whole-brain signal, referred to as global variability (GV), could potentially serve as a more specific marker of brain development. We first established the reliability of GV and its topography (GVtopo) using data from the Human Connectome Project (HCP). Then, we examined the age-related patterns of GV and GVtopo in the Nathan Kline Institute Rockland Sample (NKI-RS; N = 968, ages ranging from 6 to 85 years) and validated these findings in an independent dataset from Southwest University (SALD; N = 492, ages ranging from 19 to 80 years). Our results demonstrated the robustness of GV and GVtopo, with intra-class correlation coefficients surpassing 0.61. Both GV and GVtopo exhibited distinct non-linear developmental trajectories, differring from those of GS and its topography. Furthermore, GV demonstrated substantial age-predictive capability, underscoring its potential as a valuable marker of brain development and its significance for future age-related research.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"500"},"PeriodicalIF":5.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Microtubules as a versatile reference standard for expansion microscopy. 微管作为扩展显微镜的通用参考标准。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-26 DOI: 10.1038/s42003-025-07967-3

Rajdeep Chowdhury, Tiago Mimoso, Abed Alrahman Chouaib, Nikolaos Mougios, Donatus Krah, Felipe Opazo, Sarah Köster, Silvio O Rizzoli, Ali H Shaib

{"title":"Microtubules as a versatile reference standard for expansion microscopy.","authors":"Rajdeep Chowdhury, Tiago Mimoso, Abed Alrahman Chouaib, Nikolaos Mougios, Donatus Krah, Felipe Opazo, Sarah Köster, Silvio O Rizzoli, Ali H Shaib","doi":"10.1038/s42003-025-07967-3","DOIUrl":"10.1038/s42003-025-07967-3","url":null,"abstract":"Expansion microscopy (ExM) is continually improving, and new ExM variants need to be validated on well-defined biological structures. There is no consensus on validation structures for ExM, especially as nuclear pore complexes or DNA nanorulers are not popular for ExM studies. Here we propose that microtubules should be used for ExM validation. The diameter of microtubules immunostained using primary and secondary antibodies is sufficiently large for the validation of techniques with resolutions better than 50 nm. For techniques with higher precision (up to ~10 nm), microtubules can be assembled and imaged in vitro, using a protocol that we introduce here. Alternatively, a cellular extraction procedure can be employed, followed by labeling the peptide chains of the tubulin molecules with NHS-ester fluorophores. Finally, for nanometer-scale techniques, single tubulin molecules can be analyzed. We conclude that microtubules are valuable structures for the validation of ExM and related technologies.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"499"},"PeriodicalIF":5.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Multimodal SARS-CoV-2 interactome sketches the virus-host spatial organization. 多模态SARS-CoV-2相互作用组描绘了病毒-宿主的空间组织。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-26 DOI: 10.1038/s42003-025-07933-z

Guillaume Dugied, Estelle Mn Laurent, Mikaël Attia, Jean-Pascal Gimeno, Kamel Bachiri, Payman Samavarchi-Tehrani, Flora Donati, Yannis Rahou, Sandie Munier, Faustine Amara, Mélanie Dos Santos, Nicolas Soler, Stevenn Volant, Natalia Pietrosemoli, Anne-Claude Gingras, Georgios A Pavlopoulos, Sylvie van der Werf, Pascal Falter-Braun, Patrick Aloy, Yves Jacob, Anastassia Komarova, Yorgos Sofianatos, Etienne Coyaud, Caroline Demeret

{"title":"Multimodal SARS-CoV-2 interactome sketches the virus-host spatial organization.","authors":"Guillaume Dugied, Estelle Mn Laurent, Mikaël Attia, Jean-Pascal Gimeno, Kamel Bachiri, Payman Samavarchi-Tehrani, Flora Donati, Yannis Rahou, Sandie Munier, Faustine Amara, Mélanie Dos Santos, Nicolas Soler, Stevenn Volant, Natalia Pietrosemoli, Anne-Claude Gingras, Georgios A Pavlopoulos, Sylvie van der Werf, Pascal Falter-Braun, Patrick Aloy, Yves Jacob, Anastassia Komarova, Yorgos Sofianatos, Etienne Coyaud, Caroline Demeret","doi":"10.1038/s42003-025-07933-z","DOIUrl":"10.1038/s42003-025-07933-z","url":null,"abstract":"An accurate spatial representation of protein-protein interaction networks is needed to achieve a realistic and biologically relevant representation of interactomes. Here, we leveraged the spatial information included in Proximity-Dependent Biotin Identification (BioID) interactomes of SARS-CoV-2 proteins to calculate weighted distances and model the organization of the SARS-CoV-2-human interactome in three dimensions (3D) within a cell-like volume. Cell regions with viral occupancy were highlighted, along with the coordination of viral proteins exploiting the cellular machinery. Profiling physical intra-virus and virus-host contacts enabled us to demonstrate both the accuracy and the predictive value of our 3D map for direct interactions, meaning that proteins in closer proximity tend to interact physically. Several functionally important virus-host complexes were detected, and robust structural models were obtained, opening the way to structure-directed drug discovery screens. This PPI discovery pipeline approach brings us closer to a realistic spatial representation of interactomes, which, when applied to viruses or other pathogens, can provide significant information for infection. Thus, it represents a promising tool for coping with emerging infectious diseases.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"501"},"PeriodicalIF":5.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

The metabolic significance of peripheral tissue clocks. 外周组织时钟的代谢意义。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-26 DOI: 10.1038/s42003-025-07932-0

A Louise Hunter, David A Bechtold

引用次数: 0

Single-nucleus multiomic analysis of Beckwith-Wiedemann syndrome liver reveals PPARA signaling enrichment and metabolic dysfunction. Beckwith-Wiedemann综合征肝脏单核多组学分析揭示PPARA信号富集和代谢功能障碍。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-26 DOI: 10.1038/s42003-025-07961-9

Snehal Nirgude, Elisia D Tichy, Zhengfeng Liu, Sanam L Kavari, Rose D Pradieu, Mariah Byrne, Feikun Yang, Luis Gil-de-Gómez, Brandon Mamou, Kathrin M Bernt, Wenli Yang, Suzanne MacFarland, Michael Xie, Jennifer M Kalish

{"title":"Single-nucleus multiomic analysis of Beckwith-Wiedemann syndrome liver reveals PPARA signaling enrichment and metabolic dysfunction.","authors":"Snehal Nirgude, Elisia D Tichy, Zhengfeng Liu, Sanam L Kavari, Rose D Pradieu, Mariah Byrne, Feikun Yang, Luis Gil-de-Gómez, Brandon Mamou, Kathrin M Bernt, Wenli Yang, Suzanne MacFarland, Michael Xie, Jennifer M Kalish","doi":"10.1038/s42003-025-07961-9","DOIUrl":"10.1038/s42003-025-07961-9","url":null,"abstract":"Beckwith-Wiedemann Syndrome (BWS) is an epigenetic overgrowth syndrome caused by methylation changes in the human 11p15 chromosomal locus. Patients with BWS may exhibit hepatomegaly, as well as an increased risk of hepatoblastoma. To understand the impact of these 11p15 changes in the liver, we performed a multiomic study [single nucleus RNA-sequencing (snRNA-seq) + single nucleus assay for transposable-accessible chromatin-sequencing (snATAC-seq)] of both BWS-liver and nonBWS-liver tumor-adjacent tissue. Our approach uncovers hepatocyte-specific enrichment of processes related to peroxisome proliferator-activated receptor alpha (PPARA). To confirm our findings, we differentiated a BWS induced pluripotent stem cell model into hepatocytes. Our data demonstrate the dysregulation of lipid metabolism in BWS-liver, which coincides with observed upregulation of PPARA during hepatocyte differentiation. BWS hepatocytes also exhibit decreased neutral lipids and increased fatty acid β-oxidation. We also observe increased reactive oxygen species byproducts in BWS hepatocytes, coinciding with increased oxidative DNA damage. This study proposes a putative mechanism for overgrowth and cancer predisposition in BWS liver due to perturbed metabolism.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"495"},"PeriodicalIF":5.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

A combined mathematical and experimental approach reveals the drivers of time-of-day drug sensitivity in human cells. 数学和实验相结合的方法揭示了人类细胞中药物敏感性的驱动因素。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-25 DOI: 10.1038/s42003-025-07931-1

Nica Gutu, Hitoshi Ishikuma, Carolin Ector, Ulrich Keilholz, Hanspeter Herzel, Adrián E Granada

{"title":"A combined mathematical and experimental approach reveals the drivers of time-of-day drug sensitivity in human cells.","authors":"Nica Gutu, Hitoshi Ishikuma, Carolin Ector, Ulrich Keilholz, Hanspeter Herzel, Adrián E Granada","doi":"10.1038/s42003-025-07931-1","DOIUrl":"10.1038/s42003-025-07931-1","url":null,"abstract":"The circadian clock plays a pivotal role in regulating various aspects of cancer, influencing tumor growth and treatment responses. There are significant changes in drug efficacy and adverse effects when drugs are administered at different times of the day, underscoring the importance of considering the time of day in treatments. Despite these well-established findings, chronotherapy approaches in drug treatment have yet to fully integrate into clinical practice, largely due to the stringent clinical requirements for proving efficacy and safety, alongside the need for deeper mechanistic insights. In this study, we employ a combined mathematical and experimental approach to systematically investigate the factors influencing time-of-day drug sensitivity in human cells. Here we show how circadian and drug properties independently shape time-of-day profiles, providing valuable insights into the temporal dynamics of treatment responses. Understanding how drug efficacy fluctuates throughout the day holds immense potential for the development of personalized treatment strategies aligned with an individual's internal biological clock, revolutionizing cancer treatment by maximizing therapeutic benefits. Moreover, our framework offers a promising avenue for refining future drug screening efforts, paving the way for more effective and targeted therapies across diverse tissue types.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"491"},"PeriodicalIF":5.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Longitudinal excitation-inhibition balance altered by sex and APOE-ε4. 纵向兴奋抑制平衡受性别和APOE-ε4的影响。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-03-25 DOI: 10.1038/s42003-025-07876-5

Andrew P Burns, Igor Fortel, Liang Zhan, Orly Lazarov, R Scott Mackin, Alexander P Demos, Barbara Bendlin, Alex Leow

{"title":"Longitudinal excitation-inhibition balance altered by sex and APOE-ε4.","authors":"Andrew P Burns, Igor Fortel, Liang Zhan, Orly Lazarov, R Scott Mackin, Alexander P Demos, Barbara Bendlin, Alex Leow","doi":"10.1038/s42003-025-07876-5","DOIUrl":"10.1038/s42003-025-07876-5","url":null,"abstract":"Neuronal hyperexcitation affects memory and neural processing across the Alzheimer's disease (AD) cognitive continuum. Levetiracetam, an antiepileptic, shows promise in improving cognitive impairment by restoring the neural excitation/inhibition balance in AD patients. We previously identified a hyper-excitable phenotype in cognitively unimpaired female APOE-ε4 carriers relative to male counterparts cross-sectionally. This sex difference lacks longitudinal validation; however, clarifying the vulnerability of female ε4-carriers could better inform antiepileptic treatment efficacy. Here, we investigated this sex-by-ε4 interaction using a longitudinal design. We used resting-state fMRI and diffusion tensor imaging collected longitudinally from 106 participants who were cognitively unimpaired for at least one scan event but may have been assessed to have clinical dementia ratings corresponding to early mild cognitive impairment over time. By including scan events where participants transitioned to mild cognitive impairment, we modeled the trajectory of the whole-brain excitation-inhibition ratio throughout the preclinical cognitively healthy continuum and extended to early impairment. A linear mixed model revealed a significant three-way interaction among sex, ε4-status, and time, with female ε4-carriers showing a significant hyper-excitable trajectory. These findings suggest a possible pathway for preventative therapy targeting preclinical hyperexcitation in female ε4-carriers.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"488"},"PeriodicalIF":5.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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