Communications Biology最新文献

{"title":"OH2 oncolytic virus inhibits non-small-cell lung cancer metastasis via β-catenin pathway suppression.","authors":"Han Hu, Qi Shen, Lingfang Zhang, Shuaiqi Zhu, Yining Cheng, Haixiao Duan, Fan Zhang, Lin Wang, Yuling Jin, Jinjin Cao, Yang Wang, Binlei Liu","doi":"10.1038/s42003-025-08520-y","DOIUrl":"10.1038/s42003-025-08520-y","url":null,"abstract":"<p><p>The five-year survival rate for non-small-cell lung cancer (NSCLC) remains poor, primarily due to tumor invasion and metastasis. This study evaluates the anti-metastatic potential of the oncolytic virus OH2 in NSCLC. OH2 inhibits migration and invasion of NSCLC by downregulating β-catenin, as demonstrated in vitro and in a lung metastasis model. OH2 reduces β-catenin mRNA levels, suppressing its transcriptional activity and downstream expression of Matrix Metalloproteinases (MMPs), key mediators of extracellular matrix degradation. Proteomic analysis of the secretome confirms reduced MMPs expression following OH2 treatment. Mechanistically, the OH2 tegument protein UL41 is identified as a critical factor that degrades β-catenin mRNA, thus inhibiting β-catenin nuclear transcriptional activity. These findings reveal a novel anti-metastatic mechanism of OH2 via disruption of the β-catenin/MMPs axis and support its potential as a therapeutic candidate for invasive NSCLC.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1115"},"PeriodicalIF":5.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12304221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728460","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":"A novel model of light-induced middle cerebral artery occlusion and recanalization in mice.","authors":"Emilia Conti, Antea Minetti, Lapo Turrini, Noemi Carlini, Cristina Sarti, Anna Maria Gori, Elena Sticchi, Betti Giusti, Cristina Spalletti, Marzia Baldereschi, Anna Letizia Allegra Mascaro, Francesco Saverio Pavone","doi":"10.1038/s42003-025-08398-w","DOIUrl":"10.1038/s42003-025-08398-w","url":null,"abstract":"<p><p>Ischemic stroke caused by the abrupt interruption of blood flow is one of the leading causes of death and disability worldwide. Despite expanding reperfusion treatment indications, a significant proportion of patients (54.5%) experiences poor outcomes, regardless of successful recanalization, emphasizing the need for clinically relevant preclinical stroke models to better understand the mechanisms associated with effective reperfusion. Here, we develop and characterize a novel mouse model of light-induced recanalization following the photothrombotic occlusion of the distal branch of the middle cerebral artery (MCA). The recanalization provides a meaningful reduction of the infarct volume compared to non-recanalized mice. Moreover, the generalized motor impairment is less severe, as measured by the Neuro Deficit score. Ex vivo investigation highlights that light-mediated recanalization mitigates astrocyte complexity in the periinfarct cortex of recanalized mice. Moreover, light-induced recanalization reduces cerebral edema occurrence. Finally, the investigation of circulating biomarkers shows that our model of occlusion and recanalization of the MCA recapitulates the neuroinflammatory cascade of the acute phase of ischemic stroke.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1117"},"PeriodicalIF":5.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12304093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728458","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":"Biphasic protective effects of macrophage migration inhibitory factor in ischemia/reperfusion-induced acute kidney injury.","authors":"Yiwei Du, Chunni Feng, Lu Zhou, Tingting Wang, Heng Ma, Hongbao Liu","doi":"10.1038/s42003-025-08455-4","DOIUrl":"10.1038/s42003-025-08455-4","url":null,"abstract":"<p><p>Ferroptosis is involved in the occurrence and progression of renal ischemia/reperfusion (I/R) injury. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that is closely associated with kidney diseases. However, the underlying mechanisms between MIF and ferroptosis in acute kidney injury (AKI) still remain unclear. In contrast to conventional strategies, we further investigate the dynamic expression and role of MIF in both ischemic and reperfusion phases. In the present study, we establish hypoxia/reoxygenation (H/R) and I/R induced AKI models, verify ferroptosis by detecting pro-ferroptotic changes and associated indicators, and use si-RNA or Adeno-Associated virus (AAV) to knock down the expression of MIF, observing subsequent changes of ferroptosis. The results show that treatment with recombinant MIF reduces lipid ROS generation and MDA levels, upregulating glutathione (GSH) levels, with increasing AMP-activated protein kinase (AMPK) phosphorylation. While the deficiency of MIF blunted its protective effect on renal tubular epithelial cells, which demonstrates that MIF ameliorates ferroptosis injury via activating the AMPK pathway in the ischemia stage and increasing GSH content in the reperfusion stage. In conclusion, our results suggest the nephroprotective role of MIF in inhibiting ferroptosis and provide insight into the prevention and treatment of AKI.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1112"},"PeriodicalIF":5.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12304114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728459","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":"Effect and mechanism of father's companionship on defensive attack behavior of adult male offspring mice.","authors":"Yating Li, Yiran Liu, Xueyong Yin, Xiaohui Yu, Bingyu Li, Xiao Liu, Xiaoyu Liu, Xincheng Li, Ye Zhao, Li Song, Haishui Shi","doi":"10.1038/s42003-025-08531-9","DOIUrl":"10.1038/s42003-025-08531-9","url":null,"abstract":"<p><p>Sociocultural changes in recent decades have promoted fathers' involvement in childcare, which is crucial for the brain and behavioral plasticity of offspring. The study elucidates the effect and mechanism of father's companionship on defensive attack behavior of adult male offspring mice. The study comprises a father companionship group, where offspring cohabited with sire and dam until weaning, and a control group, where offspring cohabited solely with the dam until weaning. The study shows that father's companionship increases defensive attack behavior of adult offspring. Additionally, the metabolite L-aspartic acid is upregulated in the father's companionship group compared to the control group in male offspring, and intracerebroventricular micro-injection of L-aspartic acid confirms its impact on defensive attack behavior. C-Fos immunohistochemistry reveals that c-Fos expression in lateral periaqueductal gray (LPAG) is activated. Subsequently, micro-injection of L-aspartic acid into LPAG increases defensive attack behavior. Additionally, 16S rRNA sequencing reveals a higher abundance of Bilophila and a lower abundance of Bifidobacterium in the father companionship group, which correlates with L-aspartic acid levels, suggesting a gut-brain axis mechanism for the effect of father companionship on defensive attack behavior.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1106"},"PeriodicalIF":5.1,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717693","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":"EEG neural indicator of temporal integration in the human auditory brain with clinical implications.","authors":"Haoxuan Xu, Qianyue Huang, Peirun Song, Yanxin Chen, Qiuyu Li, Yuying Zhai, Xinyu Du, Hangting Ye, Xuehui Bao, Ishrat Mehmood, Hisashi Tanigawa, Wanqiu Niu, Zhiyi Tu, Pei Chen, Tingting Zhang, Lingling Zhang, Xuan Zhao, Li Zhang, Wanshun Wen, Liyu Cao, Xiongjie Yu","doi":"10.1038/s42003-025-08540-8","DOIUrl":"10.1038/s42003-025-08540-8","url":null,"abstract":"<p><p>Temporal integration, the process by which the auditory system combines sound information over a certain period to form a coherent auditory experience, is essential for auditory perception, yet its neural mechanisms remain underexplored. We use a \"transitional click train\" paradigm, which concatenates two click trains with slightly differing inter-click intervals (ICIs), to investigate temporal integration in the human brain. Using a 64-channel electroencephalogram (EEG), we recorded responses from healthy participants exposed to regular and irregular transitional click trains and conducted change detection tasks. Regular transitional click trains elicited significant change responses in the human brain, indicative of temporal integration, whereas irregular trains did not. These neural responses were modulated by length, contrast, and regularity of ICIs. Behavioral data mirrored EEG findings, showing enhanced detection for regular conditions compared to irregular conditions and pure tones. Furthermore, variations in change responses were associated with decision-making processes. Temporal continuity was critical, as introducing gaps between click trains diminished both behavioral and neural responses. In clinical assessments, 22 coma patients exhibited diminished or absent change responses, effectively distinguishing them from healthy individuals. Our findings identify distinct neural markers of temporal integration and highlight the potential of transitional click trains for clinical diagnostics.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1109"},"PeriodicalIF":5.1,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717665","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":"Repression via DNA looping by the Gram-positive global transcriptional regulator ScoC from Geobacillus.","authors":"Smadar Shulami, Noam Hadad, Mnar Ghrayeb, Sergei Pomyalov, Yael Pazy, Liraz Chai, Yuval Shoham, Gil Shoham","doi":"10.1038/s42003-025-08555-1","DOIUrl":"10.1038/s42003-025-08555-1","url":null,"abstract":"<p><p>ScoC of the MarR family is a global regulator of transition phase pathways in Gram-positive bacteria, and in Bacillus subtilis it is estimated to regulate more than 500 genes. ScoC mediated activity is governed by its regulated expression, and by the interplay with other global transcriptional factors allowing for the finetuning of gene expression. Here we show, by transcriptional lacZ-fusions analysis, that ScoC from Geobacillus binds to two operator sites in the promoter region of the oligopeptide permease oppA, and that both binding sites are necessary for repression. Gel retardation assays, atomic force microscopy and fluorescence resonance energy transfer analyses demonstrate that ScoC can induce DNA looping. The crystal structures of ScoC and ScoC complexed with a 23-bp symmetric palindromic DNA from Geobacillus were determined at 3.15 Å and 3.50 Å resolution, respectively. The structures revealed a tetrameric X-shaped assembly composed of two dimers in which each dimeric unit comprises a winged helix-turn-helix DNA-binding motif. Our results expand the architecture of the MarR family regulators and suggest a mechanism by which ScoC interacts with other regulatory factors to modulate gene expression in the transition phase.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1111"},"PeriodicalIF":5.1,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717697","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":"Single-cell antigen receptor sequencing in pigs with influenza.","authors":"Weihong Gu, Darling Melany de Carvahlo Madrid, Yuhan Wen, Sadie Clements, Laurie Touchard, Nathan Bivens, Grant Zane, Mingyi Zhou, Kiho Lee, John P Driver","doi":"10.1038/s42003-025-08507-9","DOIUrl":"10.1038/s42003-025-08507-9","url":null,"abstract":"<p><p>Single-cell RNA sequencing (scRNAseq) has accelerated characterizing cellular phenotypes in pigs under healthy and diseased conditions. To pair scRNAseq with immune receptor profiling, we developed porcine-specific T cell receptor (TCR) and B cell receptor (BCR) enrichment primers that are compatible with the 10 × Genomics VDJ sequencing protocol. Using these assays, we profiled the immune repertoire of cryopreserved lung cells from CD1D-expressing and CD1D-deficient pigs after one or two infections with influenza A virus (IAV) to examine whether natural killer T (NKT) cells influence pulmonary TCR and BCR receptor repertoires. We also profiled T cells longitudinally sampled from the lung fluid of IAV-vaccinated and -infected pigs to track clonal expansion. While all pigs presented highly diverse repertoires, pigs re-exposed to IAV had more expanded T cell clonotypes with activated phenotypes, suggesting potential IAV-reactive clones. Our results demonstrate the utility of high throughput single cell TCR and BCR sequencing in pigs.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1108"},"PeriodicalIF":5.1,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717699","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":"Author Correction: 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/s42003-025-08553-3","DOIUrl":"10.1038/s42003-025-08553-3","url":null,"abstract":"","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1107"},"PeriodicalIF":5.1,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717662","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":"Conserved heavy/light contacts and germline preferences revealed by a large-scale analysis of natively paired human antibody sequences and structural data.","authors":"Pawel Dudzic, Dawid Chomicz, Weronika Bielska, Igor Jaszczyszyn, Michał Zieliński, Bartosz Janusz, Sonia Wróbel, Marguerite-Marie Le Pannérer, Andrew Philips, Prabakaran Ponraj, Sandeep Kumar, Konrad Krawczyk","doi":"10.1038/s42003-025-08388-y","DOIUrl":"10.1038/s42003-025-08388-y","url":null,"abstract":"<p><p>Understanding the pairing preferences and structural interactions between antibody heavy and light chains can enhance our ability to design more effective and specific therapeutic antibodies. Insights from natural antibody repertoires and conserved contact sites help reduce autoreactivity and improve drug safety and efficacy. Current databases represent only a limited portion of the estimated diversity of unique paired antibody molecules. To address this, we introduce PairedAbNGS, a novel database with paired heavy/light antibody chains. To our knowledge, this is the largest resource for paired natural antibody sequences with 58 bioprojects and over 14 million assembled productive sequences. Using this dataset, we investigated heavy and light chain variable (V) gene pairing preferences and found significant biases beyond gene usage frequencies, possibly due to receptor editing favoring less autoreactive combinations. Analyzing the available antibody structures from the Protein Data Bank, we studied conserved contact residues between heavy and light chains, particularly interactions between the CDR3 region of one chain and the FWR2 region of the opposite chain. Examination of amino acid pairs at key contact sites revealed significant deviations of amino acids distributions compared to random pairings, in the heavy chain's CDR3 region contacting the opposite chain, indicating specific interactions might be crucial for proper chain pairing. This observation is further reinforced by preferential IGHV-IGLJ and IGLV-IGHJ pairing preferences. We hope that both our resources and the findings would contribute to improving the engineering of biological drugs. We make the database accessible at https://naturalantibody.com/paired-ab-ngs as a valuable tool for biological and machine-learning applications.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1110"},"PeriodicalIF":5.1,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717664","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":"Serine clamp of Clostridium perfringens binary toxin BECb (CPILEb)-pore confers cytotoxicity and enterotoxicity.","authors":"Toru Yoshida, Chie Monma, Yuki Ninomiya, Sotaro Takiguchi, Shoko Fujita, Yuto Uchida, Noriaki Sakoda, Vladimir A Karginov, Jun-Ichi Kishikawa, Tomohito Yamada, Ryuji Kawano, Hideaki Tsuge","doi":"10.1038/s42003-025-08519-5","DOIUrl":"10.1038/s42003-025-08519-5","url":null,"abstract":"<p><p>BEC (CPILE) is a virulence factor of the pathogen, Clostridium perfringens, which has caused foodborne outbreaks in Japan. BEC is a binary toxin that comprises the enzymatic A-component (BECa) and the B-component (BECb); the latter forms a membrane pore to translocate the A-component into target cells. Although BEC differs from other binary toxins in that the B-component alone shows enterotoxic activity, the reason for this remains unclear. We focus on the narrowest region of BECb-pore formed by not phenylalanine residues conserved in other binary toxins including iota toxin B-component (Ib) but serine residues. Comparisons between BECb and BECb (S405F) where the serine residue forming the narrowest region is substituted to the phenylalanine residue reveal that the serine residue is responsible for both cytotoxicity and enterotoxic activity. Though attempts to prepare the BECb-pore were unsuccessful, we reveal the cryo-EM structure of Ib (F454S) where the phenylalanine residue forming the narrowest region is substituted to the serine residue as a surrogate of BECb. Furthermore, Ib (F454S) increases current conductance to nine times that of Ib due to the larger pore diameter and the hydrophilic nature. These results suggest that BECb functions as a pore-forming toxin and as a translocation channel for BECa.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1102"},"PeriodicalIF":5.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717698","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}