Communications Biology最新文献_第7页

Cortical connectivity, local dynamics and stability correlates of global conscious states. 皮质连通性，局部动态和整体意识状态的稳定性相关。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-30 DOI: 10.1038/s42003-025-08782-6

Yun Zhao, Naotsugu Tsuchiya, Mario Boley, Vidushani Dhanawansa, Yueyang Liu, Philippa J Karoly, Andria Pelentritou, William Woods, David Liley, Levin Kuhlmann

{"title":"Cortical connectivity, local dynamics and stability correlates of global conscious states.","authors":"Yun Zhao, Naotsugu Tsuchiya, Mario Boley, Vidushani Dhanawansa, Yueyang Liu, Philippa J Karoly, Andria Pelentritou, William Woods, David Liley, Levin Kuhlmann","doi":"10.1038/s42003-025-08782-6","DOIUrl":"10.1038/s42003-025-08782-6","url":null,"abstract":"Waking levels of human consciousness are known to be supported by the integrity of complex structures and processes in the brain, yet how they are exactly regulated by neurobiological mechanisms remains uncertain. Here a space-time-resolved inference-based framework is applied to estimate the neurophysiological variables of a whole-cortex model and analyze the neural mechanism correlates of global consciousness by way of a correlation analysis between behavioural and neural variable time-series. Using magnetoencephalography (MEG) data from 15 participants under Xenon-induced anesthesia, interconnected neural mass models (NMMs) were developed and time-evolving regional neurophysiological variables and inter-regional connectivity strengths were inferred from the data. Analyses revealed significant correlations between consciousness levels and inter-regional connectivity, particularly in posterior parietal, occipital, and prefrontal regions. Moreover, results support a parietal, rather than frontal, network backbone to facilitate global consciousness. Regional-level analyses further identified correlates of consciousness within the posterior parietal and occipital regions. Lastly, reductions in consciousness were linked to stabilized cortical dynamics, reflected by changes in the eigenmodes of the system. This framework provides a novel, inference-based approach to investigating consciousness, offering a time-resolved perspective on neural mechanism correlates during altered states.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1391"},"PeriodicalIF":5.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12485199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198575","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

CCAAT/enhancer binding protein beta (C/EBPβ) regulates the formation of the ovarian reserve. CCAAT/增强子结合蛋白β (C/EBPβ)调节卵巢储备的形成。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-30 DOI: 10.1038/s42003-025-08798-y

Xiaoyuan Zhang, Yue Zeng, Zhanzhong Qiao, Kexin Qin, Pei Li, Jiamao Yan, Teng Zhang, Yang Zhou, Junjie Wang, Wei Shen

{"title":"CCAAT/enhancer binding protein beta (C/EBPβ) regulates the formation of the ovarian reserve.","authors":"Xiaoyuan Zhang, Yue Zeng, Zhanzhong Qiao, Kexin Qin, Pei Li, Jiamao Yan, Teng Zhang, Yang Zhou, Junjie Wang, Wei Shen","doi":"10.1038/s42003-025-08798-y","DOIUrl":"10.1038/s42003-025-08798-y","url":null,"abstract":"The primordial follicle (PF) pool (also known as ovarian reserve) is the only source of functional eggs during the reproductive lifespan, which formed at embryonic stage in most female mammals and is no longer renewed. CCAAT/enhancer binding protein beta (C/EBPβ) is a transcription factor (TF) and widely expressed in adult ovarian granulosa cells, but its role in the early ovarian development remains unclear. Here, we showed that C/EBPβ was enhanced during PF formation process in mice, and underwent nuclear translocation in germ cells along with the PF assembly (PFA) process. Importantly, the in vitro knockdown of C/EBPβ could inhibit the related proteins expression, resulting in the obstruction of PF formation. Mechanistically, the chromatin accessibility analysis revealed that C/EBPβ binds to the promoter region of the histone acetylase encoding gene Ep300 to promotes its expression, and enhance neurotrophic tyrosine receptor kinase (NTRK) signaling (required for PF formation) by maintaining chromatin accessibility of Furin promoter region. Interestingly, our results verified that the nuclear translocation of C/EBPβ is regulated by its phosphorylation level, and Lamin B1 acts as a \"gatekeeper\" molecule for the process. In summary, this report suggests that C/EBPβ is a key regulator for the establishment of ovarian reserve in mice.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1394"},"PeriodicalIF":5.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198493","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

Dynamic developmental signatures of facial expression processing differ by emotion. 面部表情加工的动态发展特征因情绪而异。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-30 DOI: 10.1038/s42003-025-08808-z

Hua Bai, Jake J Son, Nathan M Petro, Danielle L Rice, Grace C Ende, Ryan J Glesinger, Hannah J Okelberry, Jason A John, Anna T Coutant, Erica L Steiner, Vince D Calhoun, Yu-Ping Wang, Julia M Stephen, Brittany K Taylor, Giorgia Picci, Tony W Wilson

{"title":"Dynamic developmental signatures of facial expression processing differ by emotion.","authors":"Hua Bai, Jake J Son, Nathan M Petro, Danielle L Rice, Grace C Ende, Ryan J Glesinger, Hannah J Okelberry, Jason A John, Anna T Coutant, Erica L Steiner, Vince D Calhoun, Yu-Ping Wang, Julia M Stephen, Brittany K Taylor, Giorgia Picci, Tony W Wilson","doi":"10.1038/s42003-025-08808-z","DOIUrl":"10.1038/s42003-025-08808-z","url":null,"abstract":"Facial expressions are critical social cues for deciphering others' emotional states and intentions. While the neural architecture supporting emotional face processing is well established, few studies have examined the developmental trajectory of the underlying oscillatory dynamics. Using magnetoencephalography in a large typically-developing sample (6-17 years-old), we quantified neural oscillations during gender judgments of angry, happy, and neutral faces. Alpha/beta responses to neutral faces increased with age in the posterior superior temporal cortices and decreased in the prefrontal cortex, indicating a shift toward posterior processing. Gamma oscillations increased with age for angry and neutral faces in the temporoparietal junction and fusiform, suggesting enhanced specialization for processing threatening and ambiguous stimuli. Happy faces elicited age-related gamma decreases in attention cortices, implying less attentional demand for positive faces. These findings offer the largest assessment to date of developmental changes in the neural dynamics supporting facial expression processing and mechanisms relevant to emerging psychopathology.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1395"},"PeriodicalIF":5.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12485218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198592","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

Cognitive and neural mechanisms of mental imagery supporting creative cognition. 支持创造性认知的心理意象的认知和神经机制。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-30 DOI: 10.1038/s42003-025-08513-x

Jing Gu, Xueyang Wang, Cheng Liu, Lin Yang, Jiaxin Fan, Jiangzhou Sun, Yoed Nissan Kenett, Jiang Qiu

{"title":"Cognitive and neural mechanisms of mental imagery supporting creative cognition.","authors":"Jing Gu, Xueyang Wang, Cheng Liu, Lin Yang, Jiaxin Fan, Jiangzhou Sun, Yoed Nissan Kenett, Jiang Qiu","doi":"10.1038/s42003-025-08513-x","DOIUrl":"10.1038/s42003-025-08513-x","url":null,"abstract":"While the role of mental imagery in creative cognition is acknowledged, the specific cognitive and neural mechanisms remain underexplored. This study aims to elucidate the supportive role of mental imagery in creative cognition from a semantic memory perspective, and elucidating its underlying neural substrates. Initially, we conducted a behavioral study and found positive correlation between the vividness of touch imagery with creative performance in a creative writing task. By establishing semantic feature indicators based on writing texts and mediation models, we found that the vividness of touch imagery facilitates creative writing performance by semantic integration and reorganization. A subsequent behavioral study comparing mental imagery and semantic understanding strategies usage in creative writing tasks further confirmed the positive impact of mental imagery on creative cognition, and suggested that semantic reorganization, beyond the role of semantic integration, plays a critical role in how mental imagery enhances creativity. Finally, a functional magnetic resonance imaging (fMRI) study explored the distribution of functional brain networks' edge communities during creative writing under mental imagery and semantic understanding conditions. We found that the sensorimotor network facilitates sensorimotor simulations in creative cognition; the dorsal attention and salience networks collaboratively support the writing process by maintaining goal-directed attention and reorienting attention; the limbic network supports multimodal semantic processing and novel associations; the frontoparietal control network and default mode network contribute to information integration; and a subnetwork of default mode network plays a special role in integrating semantic information related to objects and actions. Collectively, our study sheds light on the cognitive and neural underpinnings of mental imagery supporting creative cognition.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1386"},"PeriodicalIF":5.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198564","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

MFSD12, transcriptionally regulated by PLAGL2, promotes bladder cancer progression. 由PLAGL2转录调控的MFSD12促进膀胱癌的进展。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-30 DOI: 10.1038/s42003-025-08801-6

Jiani He, Changming Dong, Xiandong Song, Xinyu Bao, Zhongkai Qiu, Hao Zhang, Yuanjun Jiang, Tao Liu, Xiaojun Man

{"title":"MFSD12, transcriptionally regulated by PLAGL2, promotes bladder cancer progression.","authors":"Jiani He, Changming Dong, Xiandong Song, Xinyu Bao, Zhongkai Qiu, Hao Zhang, Yuanjun Jiang, Tao Liu, Xiaojun Man","doi":"10.1038/s42003-025-08801-6","DOIUrl":"10.1038/s42003-025-08801-6","url":null,"abstract":"Bladder cancer (BLCA) is one of the most common malignant tumors of the urinary system. Identification of novel molecular signaling targets for the tumorigenesis of BLCA is important. Data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases suggest that major facilitator superfamily domain containing 12 (MFSD12) may act as an important oncogene in BLCA. MFSD12 expression is confirmed to be elevated in BLCA patients. Genetic manipulation of MFSD12 mediated by Tet-inducible lentiviral expression vector is conducted in two BLCA cell lines, including UMUC3 and 5637. Following this manipulation, the cells are subjected to treatment with or without doxycycline. Our results show that MFSD12 knockdown inhibits cell proliferation, migration, and invasion, and arrests the G1 stage-induced cell cycle. Furthermore, silencing of MFSD12 reduces lung metastatic lesions and xenografted tumor formation of BLCA cells. To further explore the effect of MFSD12 on BLCA cells, transcriptomics and metabolomics analyses are performed on MFSD12-overexpressing cells. Subsequently, luciferase reporters and chromatin immunoprecipitation (ChIP)-PCR assays reveal that MFSD12 is regulated positively by pleomorphic adenoma gene like-2 (PLAGL2), an important transcription factor. Collectively, our results indicate that MFSD12 exerts a tumor-promoting effect on BLCA progression, under the modulation of transcription factor PLAGL2.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1402"},"PeriodicalIF":5.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12485097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198618","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 critical human pathogen Acinetobacter baumannii exhibits light-regulated circadian rhythms. 关键的人类病原体鲍曼不动杆菌表现出光调节的昼夜节律。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-30 DOI: 10.1038/s42003-025-08732-2

Valentín Permingeat, Bárbara Edith Perez Mora, María Laura Migliori, Natalia Arana, Julia Fernández, María Belén Allasia, Melisa Luciana Lamberti, Gisela Di Venanzio, Ramiro Esteban Rodriguez, Mario Federico Feldman, Diego Andrés Golombek, María Alejandra Mussi

{"title":"The critical human pathogen Acinetobacter baumannii exhibits light-regulated circadian rhythms.","authors":"Valentín Permingeat, Bárbara Edith Perez Mora, María Laura Migliori, Natalia Arana, Julia Fernández, María Belén Allasia, Melisa Luciana Lamberti, Gisela Di Venanzio, Ramiro Esteban Rodriguez, Mario Federico Feldman, Diego Andrés Golombek, María Alejandra Mussi","doi":"10.1038/s42003-025-08732-2","DOIUrl":"10.1038/s42003-025-08732-2","url":null,"abstract":"Acinetobacter baumannii is recognized as the paradigm of multidrug-resistant superbug, topping the WHO priority list of critical human pathogens. Interestingly, it senses and responds to blue light, which modulates global aspects of its physiology, including pathogenicity. We hypothesized that light could serve as a signal to synchronize the bacterial physiology to the host's behavior and/or to the environment. At environmental temperatures, light regulation is mainly governed by the photoreceptor BlsA. In this work, we identified the existence of daily rhythms in blsA promoter activity displaying a robust response to light, as well as endogenous circadian rhythms in A. baumannii. In fact, we show that blsA promoter activity can be synchronized to 24-hour blue light-dark cycles, which immediately resynchronizes after a phase shift. Upon release to constant darkness, bacterial populations present free-running oscillations with a period close to 24 hours. Furthermore, our data indicate that BlsA is involved in synchronization to light-dark cycles. In fact, under constant darkness without previous entrainment, A. baumannii is rhythmic, but acrophases are not clusterized, behaving as the blsA mutant under light-dark cycles. Our work contributes to the developing field of circadian clocks in bacterial pathogens, which could impact in the microorganisms' lifestyle and pathogenicity.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1385"},"PeriodicalIF":5.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198590","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

Transcriptome-wide mapping of small ribosomal subunits elucidates scanning mechanisms of translation initiation in the mammalian brain. 小核糖体亚基的转录组全图谱阐明了哺乳动物大脑中翻译起始的扫描机制。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-30 DOI: 10.1038/s42003-025-08804-3

Preeti Madhav Kute, Francois P Pauzin, Kornel Labun, Clive R Bramham, Eivind Valen

{"title":"Transcriptome-wide mapping of small ribosomal subunits elucidates scanning mechanisms of translation initiation in the mammalian brain.","authors":"Preeti Madhav Kute, Francois P Pauzin, Kornel Labun, Clive R Bramham, Eivind Valen","doi":"10.1038/s42003-025-08804-3","DOIUrl":"10.1038/s42003-025-08804-3","url":null,"abstract":"Neuronal protein synthesis is highly compartmentalised and regulated, with key roles for translation initiation and elongation factors. Ribosome profiling, the most widely used transcriptome-wide method for measuring translation, captures translation elongation, but not the initiation phase involving small ribosomal subunit (SSU) scanning. Here, we adapted ribosome complex profiling (RCP-seq) for mouse dentate gyrus and cerebral cortex, to characterize translation initiation. In both tissues, SSUs accumulate near the start codon on synaptically localised RNAs, and this 'poised' SSU configuration correlates with enhanced translational efficiency. Upstream open reading frames (uORFs) are associated with less poised SSUs, potentially by disassociating the SSUs. We further find that neuron-specific transcripts recruit more ribosomes and are more efficiently translated than glia-specific transcripts. For neuronal transcripts, monosome-preferring mRNAs show less SSU occupancy relative to polysome-preferring mRNAs, suggesting reduced recruitment of ribosomes. In summary, RCP-seq elucidates translation initiation dynamics and cell-type- and transcript-specific regulation in the mammalian brain.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1399"},"PeriodicalIF":5.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198608","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

Uncovering a fibroblast differentiation-based keloid classification by integration of single-cell and bulk RNA sequencing. 通过整合单细胞和大量RNA测序，揭示基于成纤维细胞分化的瘢痕疙瘩分类。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-30 DOI: 10.1038/s42003-025-08741-1

Wei Zhang, Jianyu Lu, Xirui Tong, Sujie Xie, Shuyuan Xian, Yifan Liu, Jiale Yan, Weijin Qian, Hanlin Sun, Yushu Zhu, Luofeng Jiang, Xinya Guo, Xinran Ding, Yixu Li, Chenguang Bai, Runzhi Huang, Zhaofan Xia, Shizhao Ji

{"title":"Uncovering a fibroblast differentiation-based keloid classification by integration of single-cell and bulk RNA sequencing.","authors":"Wei Zhang, Jianyu Lu, Xirui Tong, Sujie Xie, Shuyuan Xian, Yifan Liu, Jiale Yan, Weijin Qian, Hanlin Sun, Yushu Zhu, Luofeng Jiang, Xinya Guo, Xinran Ding, Yixu Li, Chenguang Bai, Runzhi Huang, Zhaofan Xia, Shizhao Ji","doi":"10.1038/s42003-025-08741-1","DOIUrl":"10.1038/s42003-025-08741-1","url":null,"abstract":"Keloids are dermal fibroproliferative skin disorders caused by abnormal wound healing, resulting in impaired skin function and aesthetic defects. Abnormal fibroblast proliferation and excessive collagen deposition are involved in keloid formation. This study investigated the role of fibroblast differentiation in keloid development. Single-cell and bulk RNA sequencing data of keloids were comprehensively analyzed, and 25 clinically relevant differentially expressed fibroblast-differentiation-related genes (DEFDRGs) were identified. Based on DEFDRGs, a keloid diagnostic classification system comprising three subtypes was constructed, indicating that DEFDRGs could serve as therapeutic targets. Additionally, multiple microarray datasets, protein sequencing data, and immunohistochemical analyses of key markers in clinical keloid samples were used for further verification. In conclusion, this study established a molecular classification of keloids based on fibroblast differentiation, contributing to the further understanding of keloid pathogenesis and providing new insights for diagnosis and treatment.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1387"},"PeriodicalIF":5.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198624","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

Casein kinase I isoforms contribute to platelet activation and thrombogenesis via RIPK3-MLKL signaling. 酪蛋白激酶I亚型通过RIPK3-MLKL信号通路参与血小板活化和血栓形成。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-30 DOI: 10.1038/s42003-025-08868-1

Vipin Singh, Mohammad Ekhlak, Susheel N Chaurasia, Debabrata Dash

{"title":"Casein kinase I isoforms contribute to platelet activation and thrombogenesis via RIPK3-MLKL signaling.","authors":"Vipin Singh, Mohammad Ekhlak, Susheel N Chaurasia, Debabrata Dash","doi":"10.1038/s42003-025-08868-1","DOIUrl":"10.1038/s42003-025-08868-1","url":null,"abstract":"Platelets are small, enucleate blood cells having life span of 10-12 days that play fundamental role in hemostasis and thrombosis. Casein Kinase 1 (CK1) is a serine/threonine-specific protein kinase that governs multiple cellular processes including circadian rhythm, morphogen signaling and apoptosis; however, its role in platelet biology and thrombogenesis remains unexplored. Employing a CK1-specific pharmacological inhibitors, we demonstrate here a pivotal role of CK1 in agonist-induced platelet activation. Inhibition of CK1 disrupts platelet functions that include aggregation, integrin activation, interaction with leukocytes, and thrombus formation under arterial shear ex vivo as well as in a murine model of thrombosis. CK1 maintains mitochondrial integrity by stabilizing inner mitochondrial membrane that propels energy metabolism in activated platelets. Notably, CK1 inhibition suppresses phosphorylation of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL), key arbiters of platelet activation leading to necroptosis, thus mechanistically linking CK1 activity to platelet prothrombotic responses. Downregulation of CK1 did not affect primary hemostasis nor platelet viability while significantly deferring thrombus formation, which underscores its potential as a safe therapeutic option against thrombotic disorders. This study uncovers an emerging role of CK1 in unleashing of prothrombotic phenotype and positions CK1 as a potential target for antithrombotic measures.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1384"},"PeriodicalIF":5.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12485074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198506","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

Targeting ALOX5 ameliorates renal tubular injury in ischemia-reperfusion-induced acute kidney injury via inhibition of ferroptosis. 靶向ALOX5通过抑制铁下垂改善缺血再灌注诱导的急性肾损伤肾小管损伤。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-30 DOI: 10.1038/s42003-025-08803-4

Liming Huang, Qiao Tang, Guoli Li, Yanpei Hou, Sipei Chen, Qi Yao, Yanwen Luo, Lin Xiong, Yaling Zhang, Hongsha Yang, Li Wang, Guisen Li, Yi Li, Yunlin Feng

{"title":"Targeting ALOX5 ameliorates renal tubular injury in ischemia-reperfusion-induced acute kidney injury via inhibition of ferroptosis.","authors":"Liming Huang, Qiao Tang, Guoli Li, Yanpei Hou, Sipei Chen, Qi Yao, Yanwen Luo, Lin Xiong, Yaling Zhang, Hongsha Yang, Li Wang, Guisen Li, Yi Li, Yunlin Feng","doi":"10.1038/s42003-025-08803-4","DOIUrl":"10.1038/s42003-025-08803-4","url":null,"abstract":"Ischemia-reperfusion injury (IRI)-induced acute kidney injury (AKI) could be potentially lethal in clinic. We found lipoxygenases-5 (ALOX5) was upregulated in renal tubular cells in IRI-induced AKI; however, its underlying mechanism is not clear. In this study, we explore the function of ALOX in IRI-induced AKI using human renal proximal tubular epithelial cells (HK-2) and C57BL/6 mice. Alox5 knock-out mouse is constructed. Products of polyunsaturated fatty acids metabolized by ALOX5 in the kidney tissue are measured by UHPLC-HRMS/MS platform. Ferroptosis is measured upon ALOX5 intervention and Benzbromarone (BBR) intervention. The results indicate that in IRI-induced AKI, ALOX5 is up-regulated in the renal tubular epithelial cells and exacerbates the accumulation of lipid peroxides, which in turns enhances ferroptosis in the renal tubular cells and finally contributes to cell injury. BBR specifically interacts with ALOX5 and reduces the accumulation of lipid peroxide, thus alleviating the cell damage caused by IRI and improving the renal function of experimental mice. In conclusion, ALOX5 enhances the accumulation of lipid peroxide in the renal tubular cells in IRI-induced AKI and targeting ALOX5 might ameliorate renal tubular injury via inhibiting ferroptosis in this clinical setting.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1403"},"PeriodicalIF":5.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198602","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