Anna Jaeschke, Matt S Hepburn, Alireza Mowla, Brendan F Kennedy, Chii J Chan
{"title":"Three-dimensional quantitative micro-elastography reveals alterations in spatial elasticity patterns in murine ovaries during ageing.","authors":"Anna Jaeschke, Matt S Hepburn, Alireza Mowla, Brendan F Kennedy, Chii J Chan","doi":"10.1038/s42003-025-08835-w","DOIUrl":"10.1038/s42003-025-08835-w","url":null,"abstract":"<p><p>Fibrosis and tissue stiffening are hallmarks of ovarian ageing, linked to a decrease in fertility. However, the lack of three-dimensional (3D) characterization of ovary elasticity limits our understanding of localized elasticity patterns and their connection to tissue composition. Here, we developed an integrated approach to link ovarian elasticity, volume, and cell-matrix composition using quantitative micro-elastography (QME), a label-free, non-invasive method to study 3D microscale elasticity in conjunction with immunofluorescence microscopy. QME reveals distinct spatial elasticity patterns in ovarian compartments, namely follicles and corpora lutea (CLs), and local elasticity alterations in different age cohorts. CL elasticity significantly increases, and follicle elasticity changes minimally with age. CLs show size-dependent elasticity changes, while follicles exhibit distinct spatial variations in elasticity correlated with the emergence of theca cell layers during follicle development. These findings have the potential to guide novel diagnostics and therapeutic targets to improve women's reproductive health and longevity.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1409"},"PeriodicalIF":5.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211909","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}
Tom Boerstler, Daniil Kachkin, Elizaveta Gerasimova, Naime Zagha, Federica Furlanetto, Negar Nayebzade, Luke Zappia, Michelle Boisvert, Michaela Farrell, Sonja Ploetz, Iryna Prots, Martin Regensburger, Claudia Günther, Juergen Winkler, Pooja Gupta, Fabian Theis, Marisa Karow, Sven Falk, Beate Winner, Florian Krach
{"title":"Deciphering brain organoid heterogeneity by identifying key quality determinants.","authors":"Tom Boerstler, Daniil Kachkin, Elizaveta Gerasimova, Naime Zagha, Federica Furlanetto, Negar Nayebzade, Luke Zappia, Michelle Boisvert, Michaela Farrell, Sonja Ploetz, Iryna Prots, Martin Regensburger, Claudia Günther, Juergen Winkler, Pooja Gupta, Fabian Theis, Marisa Karow, Sven Falk, Beate Winner, Florian Krach","doi":"10.1038/s42003-025-08855-6","DOIUrl":"10.1038/s42003-025-08855-6","url":null,"abstract":"<p><p>Brain organoids derived from human pluripotent stem cells (hPSCs) hold immense potential for modeling neurodevelopmental processes and disorders. However, their experimental variability and undefined organoid selection criteria for analysis hinder reproducibility. As part of the Bavarian ForInter consortium, we generated 72 brain organoids from distinct hPSC lines. We conducted a comprehensive analysis of their morphological and cellular characteristics at an early stage of their development. In our assessment, the Feret diameter emerged as a reliable, single parameter that characterizes brain organoid quality. Transcriptomic analysis of our organoid identified the abundance of unintended mesodermal differentiation as a major confounder of unguided brain organoid differentiation, correlating with Feret diameter. High-quality organoids consistently displayed a lower presence of mesenchymal cells. These findings provide a framework for enhancing brain organoid standardization and reproducibility, underscoring the need for morphological quality controls and considering the influence of mesenchymal cells on organoid-based modeling.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1412"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205968","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}
Narjes Ansari, Chengwen Liu, Florent Hédin, Jérôme Hénin, Jay W Ponder, Pengyu Ren, Jean-Philip Piquemal, Louis Lagardère, Krystel El Hage
{"title":"Targeting RNA with small molecules using state-of-the-art methods provides highly predictive affinities of riboswitch inhibitors.","authors":"Narjes Ansari, Chengwen Liu, Florent Hédin, Jérôme Hénin, Jay W Ponder, Pengyu Ren, Jean-Philip Piquemal, Louis Lagardère, Krystel El Hage","doi":"10.1038/s42003-025-08809-y","DOIUrl":"10.1038/s42003-025-08809-y","url":null,"abstract":"<p><p>Targeting RNA with small molecules represents a promising yet relatively unexplored avenue for the design of new drugs. Nevertheless, challenges arise from the lack of computational models and techniques able to accurately model RNA systems, and predict their binding affinities to small molecules. Here, we tackle these difficulties by developing a tailored state-of-the-art approach for absolute binding free energy calculations of RNA-binding small molecules. For this, we combine the advanced AMOEBA polarizable force field to the newly developed lambda-Adaptive Biasing Force scheme associated to refined restraints allowing for efficient sampling. To capture the free energy barrier associated to challenging RNA conformational changes, we combine machine learning-based collective variables with enhanced sampling simulations. Applying this computational protocol to a complex Riboswitch-like RNA target demonstrates quantitative predictions. These results pave the way for the routine application of free energy simulations in RNA-targeted drug discovery, thus providing a significant reduction in their failure rate.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1405"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205921","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}
Marco Chittò, David Tutschner, Ulrich Dobrindt, Anzhela Galstyan, Michael Berger
{"title":"Photosensitizer-specific bacterial stress responses in Escherichia coli reveal distinct targets in photoinduced inactivation.","authors":"Marco Chittò, David Tutschner, Ulrich Dobrindt, Anzhela Galstyan, Michael Berger","doi":"10.1038/s42003-025-08881-4","DOIUrl":"10.1038/s42003-025-08881-4","url":null,"abstract":"<p><p>The ongoing antibiotic crisis calls for alternative antimicrobial strategies. Antimicrobial photodynamic therapy (aPDT) offers a sustainable option, employing a light-activated photosensitizer (PS) to generate cytotoxic reactive oxygen species (ROS). The non-selective nature of these ROS helps minimize the risk of resistance development. Despite the development of numerous PSs, limited data on their exact mechanisms and bacterial targets still hinders broader clinical use. The focus of this study is to address this gap by capturing pathway-specific responses to sub-lethal photodynamic stress using a panel of transcriptional biosensors in E. coli K-12 strain MG1655. Our results indicate that methylene blue (MB) primarily causes oxidative stress in the cytosol while silicon phthalocyanine derivative (SiPc) induces envelope stress at physiological conditions. By monitoring well-characterized stress response pathways, our method offers a valuable tool for elucidating the physiological effects of aPDT and guiding more detailed mechanistic or transcriptomic studies.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1413"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205929","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}
{"title":"Intermittent fasting attenuates glial hyperactivation and photoreceptor degeneration in a NaIO<sub>3</sub>-induced mouse model of age-related macular degeneration.","authors":"Jingzhen Li, Beibei Wang, Pinjie Liu, Xuecheng Qiu, Qiyun Bian, Congxin Shen, Yanyan Li, Mengwen Shao, Meng Li","doi":"10.1038/s42003-025-08815-0","DOIUrl":"10.1038/s42003-025-08815-0","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss, with limited treatments available. Recent studies suggest intermittent fasting (IF) may offer neuroprotective benefits for aging and age-related disorders, but its efficacy in AMD has not yet been established. Here, using a sodium iodate (NaIO<sub>3</sub>)-induced AMD model in male mice, we find that pretreatment with an IF diet regimen mitigates NaIO<sub>3</sub>-induced cellular damage and loss of both retinal pigment epithelium (RPE) and photoreceptors. Visual function tests indicate that IF preserves vision in NaIO<sub>3</sub>-treated mice. Transcriptome analyses show IF counteracts NaIO<sub>3</sub>-induced transcriptional dysregulation, affecting genes related to reactive oxygen species (ROS), inflammation, and photoreceptor structure. Further experimental results confirm that IF effectively reduces ROS levels and inhibits the activation of microglia and Muller cells in the retina. Collectively, these findings indicate that IF reduces ROS production and inflammation in NaIO<sub>3</sub>-induced retinal damage, providing a potential therapeutic strategy for oxidative stress-induced retinal degenerative diseases, including AMD.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1408"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205973","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}
Karlo Komorowski, Jakob Reichmann, Lika Drakhlis, Robert Zweigerdt, Tim Salditt
{"title":"3D histology of human heart-forming organoids by X-ray phase-contrast tomography.","authors":"Karlo Komorowski, Jakob Reichmann, Lika Drakhlis, Robert Zweigerdt, Tim Salditt","doi":"10.1038/s42003-025-08876-1","DOIUrl":"10.1038/s42003-025-08876-1","url":null,"abstract":"<p><p>Three-dimensional (3D) imaging is crucial for elucidating the complex structure of organoid models which involve complex spatial cellular and tissue organization in 3D. While a variety of volume imaging methods, including novel light microscopy tools, are now well established to probe the cellular complexity of organoids in 3D, the gold standard for obtaining a precise morphological picture is histology, a traditionally 2D imaging technique that relies on slicing the specimen and therefore has severe limitations in scalability and volumetric imaging. X-ray phase-contrast tomography (XPCT) has emerged as an imaging modality capable of extending conventional histology into the third dimension. While it has been applied to various types of animal and human tissues, its applicability to organoid systems, however, is yet in its infancy. Here, we use XPCT for 3D histology of unstained and formalin-fixed paraffin-embedded human heart-forming organoids (HFOs) at multiple scales and with isotropic resolution. Derived from human pluripotent stem cells, HFOs are a complex and highly structured in vitro model of early heart, foregut and vasculature development, resembling the early human heart-forming region. Using highly coherent synchrotron radiation, we show that HFOs and their different tissue elements can be visualized in their full three-dimensionality and at subcellular scale.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1411"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206001","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}
Ziyuan Wang, Mei-Juan Tu, Ziyang Liu, Katherine K Wang, Yinshan Fang, Ning Hao, Hao Helen Zhang, Jianwen Que, Xiaoxiao Sun, Ai-Ming Yu, Hongxu Ding
{"title":"A reference-guided iterative approach to polish the nanopore sequencing basecalling for therapeutic RNA quality control.","authors":"Ziyuan Wang, Mei-Juan Tu, Ziyang Liu, Katherine K Wang, Yinshan Fang, Ning Hao, Hao Helen Zhang, Jianwen Que, Xiaoxiao Sun, Ai-Ming Yu, Hongxu Ding","doi":"10.1038/s42003-025-08811-4","DOIUrl":"10.1038/s42003-025-08811-4","url":null,"abstract":"<p><p>Nucleotide modifications deviate nanopore sequencing readouts, therefore generating artifacts during the basecalling of sequence backbones. Here, we present a reference-guided, iterative approach to polish modification-disturbed basecalling results. We show that such an approach is uniquely suitable for training biomolecule-specific high-accuracy basecallers, by improving the basecalling of both artificially-synthesized and real-world molecules. With demonstrated efficacy and reliability, we exploit the approach to precisely basecall therapeutic RNAs consisting of artificial or natural modifications. We first analyzed vaccine mRNAs, which are artificially modified to promote stability and reduce immunogenicity. Specifically, we quantified the sequence purity and integrity, the two most important quality metrics to be controlled during mRNA vaccine production. We also analyzed BioRNAs, which are human tRNA-based carriers for therapeutic RNA interference (RNAi) agents. Specifically, we examined modification hotspots, which are naturally incorporated in vivo during BioRNA production and essential for therapeutic efficacy. Our analysis expands the scope of therapeutic RNA quality control, from the conventional sequence-level to the current modification status-level.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1406"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205952","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}
Jing Liu, Danni Chen, Tao Xia, Shengzi Zeng, Gui Xue, Xiaoqing Hu
{"title":"Slow-wave sleep and REM sleep differentially contribute to memory representational transformation.","authors":"Jing Liu, Danni Chen, Tao Xia, Shengzi Zeng, Gui Xue, Xiaoqing Hu","doi":"10.1038/s42003-025-08812-3","DOIUrl":"10.1038/s42003-025-08812-3","url":null,"abstract":"<p><p>Sleep consolidates memories. Yet how sleep preserves precise memories while transforming them into abstract and categorical knowledge remains unclear. Using electroencephalography and representational similarity analysis, we examined memory representational transformation across overnight sleep. We focused on item-level representations, which reflect specific details of individual memories, and category-level representations, which capture shared conceptual features across items from the same category. Our results showed that after sleep, item-level representations were reduced, while category-level representations were preserved. Notably, a higher ratio of rapid eye movement (REM) to slow-wave sleep (SWS) predicted greater item-level reduction and category-level enhancement. Additionally, theta (4-7 Hz) and beta (15-25 Hz) power during REM sleep were positively associated with these memory representational transformations, whereas slow oscillation-related (1-1.25 Hz) power during SWS showed the opposite pattern. Our findings suggest the differential roles of SWS and REM in balancing memory preservation and transformation.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1407"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206014","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}
Kai Doberstein, Johannes Panther, Eric Hahnen, Lisa Richters, Philip C Schouten, Philipp Harter, Florian Heitz, Stefan Kommoss, Sebastian Berlit, Benjamin Tuschy, Marc Sütterlin, Frederik Marmé
{"title":"Long non-coding RNAs as a biomarker for homologous recombination deficiency and parp inhibitor sensitivity in high-grade serous ovarian cancers.","authors":"Kai Doberstein, Johannes Panther, Eric Hahnen, Lisa Richters, Philip C Schouten, Philipp Harter, Florian Heitz, Stefan Kommoss, Sebastian Berlit, Benjamin Tuschy, Marc Sütterlin, Frederik Marmé","doi":"10.1038/s42003-025-08836-9","DOIUrl":"10.1038/s42003-025-08836-9","url":null,"abstract":"<p><p>Homologous recombination deficiency (HRD) and sensitivity to PARP inhibitors are key determinants of therapeutic response in high-grade serous ovarian cancer (HGSC), yet predictive biomarkers beyond BRCA1/2 mutations or genomic HRD scores remain inadequate. Here, we investigate the potential of long non-coding RNAs (lncRNAs) as predictive markers of HRD and PARP inhibitor response. We identify a panel of lncRNAs that stratifies HGSC tumors by HRD status and drug sensitivity. Among these, ENSG00000272172.1 is significantly upregulated in HRD-positive tumors and is detectable in both formalin-fixed tissue and plasma, supporting its use as a minimally invasive biomarker. Functional analyses reveal that this lncRNA contributes to genome stability by modulating replication dynamics. These findings highlight a previously unrecognized role for lncRNAs in the HRD phenotype and suggest translational potential for ENSG00000272172.1 in guiding clinical decision-making.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1410"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205963","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}
{"title":"PaRPI predicts RNA-Protein interactions from cross-protocol and cross-batch RNA-binding protein datasets.","authors":"Liangchen Peng, Lijun Quan, Lingkun Meng, Zhihong Zhang, Shengju Zhang, Zhijun Zhang, Yi Zhang, Qiufeng Chen, Bei Zhang, Lexin Cao, Tingfang Wu, Qiang Lyu","doi":"10.1038/s42003-025-08807-0","DOIUrl":"10.1038/s42003-025-08807-0","url":null,"abstract":"<p><p>RNA-binding proteins (RBPs) play a pivotal role in the regulation of gene expression, with their interactions with RNA reflecting the biological functions and regulatory mechanisms. However, current computational methods are typically tailored to specific RBPs and depend on specific protocols and batches of biological experiments. To overcome these challenges, we propose a method called PaRPI, which aims to predict RNA-protein binding sites in a bidirectional RBP-RNA selection manner. PaRPI groups all RBP datasets based on cell lines, integrating experimental data from different protocols and batches, thereby enabling the development of a unified computational model that effectively captures both shared and distinct interaction patterns among different proteins. Our results demonstrate that PaRPI achieves exceptional performance in accurately identifying binding sites, surpassing state-of-the-art models on 261 RBP datasets from eCLIP and CLIP-seq experiments. Furthermore, PaRPI stands out for its robust generalization capabilities, uniquely able to predict interactions with previously unseen RNA and protein receptors. We also investigate the impact of disease-associated variants on RBP binding and evaluate PaRPI's components and semantic embeddings, demonstrating its capability to dissect complex interaction networks. PaRPI enables large-scale exploration of RNA-protein interactions, facilitating future studies on gene regulation and disease mechanisms.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1396"},"PeriodicalIF":5.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12485180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198615","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}