L E McGee, J S Pereira, T A McEachron, C Mazcko, A K LeBlanc, J A Beck
{"title":"The tumor microenvironment of metastatic osteosarcoma in the human and canine lung.","authors":"L E McGee, J S Pereira, T A McEachron, C Mazcko, A K LeBlanc, J A Beck","doi":"10.1038/s42003-025-07992-2","DOIUrl":"10.1038/s42003-025-07992-2","url":null,"abstract":"<p><p>Osteosarcoma is a rare but aggressive bone tumor that develops spontaneously in human and canine patients and most commonly metastasizes to the lung. The presence of lung metastases significantly decreases the survival rate of patients, with minimal benefit seen with available treatments. Canine osteosarcoma is clinically and molecularly similar to human osteosarcoma and develops approximately ten times more frequently than human osteosarcoma making dogs a promising natural model to study disease progression. The development of new therapies for pulmonary metastases requires an understanding of the interplay between tissue resident cells as well as recruited cell types and how those interactions impact seeding and progression within the new metastatic site. This review explores the tumor microenvironment surrounding pulmonary metastases and how current knowledge in canine and human patients can inform better treatments and outcomes for both populations.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"756"},"PeriodicalIF":5.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076552","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}
Tingting Guo, Jie Yang, Na Zhou, Xiaoli Sun, Changchao Huan, Tao Lin, Guangyu Bao, Jian Hu, Guocai Li
{"title":"Cas3 of type I-Fa CRISPR-Cas system upregulates bacterial biofilm formation and virulence in Acinetobacter baumannii.","authors":"Tingting Guo, Jie Yang, Na Zhou, Xiaoli Sun, Changchao Huan, Tao Lin, Guangyu Bao, Jian Hu, Guocai Li","doi":"10.1038/s42003-025-08124-6","DOIUrl":"https://doi.org/10.1038/s42003-025-08124-6","url":null,"abstract":"<p><p>Acinetobacter baumannii (A. baumannii) is an important pathogen causing various nosocomial infections. CRISPR-Cas system is the adaptive immune system of bacteria, which is also closely related to the drug resistance and virulence of bacteria. However, the effect and mechanism of cas3 (type I-Fa) in A. baumannii is still unclear. In this study, we successfully constructed a cas3 deletion mutant (19606Δcas3) and complemented strain (19606Δcas3/pcas3) to study the regulatory mechanism of type I-Fa cas3 on bacterial virulence. Our results showed that deletion of cas3(type I-Fa) significantly reduced the biofilm formation, virulence and pathogenicity to mice. The organ bacterial load of mice infected with cas3 deletion strain was significantly reduced, the lung inflammation was slightly changed, and the serum cytokine level was also decreased. All results demonstrated that cas3 enhanced the virulence and pathogenicity of A. baumannii. Mechanism analysis showed that deletion of cas3 can lead to the down-regulation of virulence factors such as biofilm formation related factors and outer membrane protein A(ompA). In addition, cas3 was also involved in the regulation of carbon metabolism and oxidative phosphorylation pathway of A. baumannii. Altogether, our study may provide cas3 as a therapeutic target in the future because of the close link to the virulence of A. baumannii.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"750"},"PeriodicalIF":5.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076546","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":"ATF1 and miR-27b-3p drive intervertebral disc degeneration through the PPARG/NF-κB signaling axis.","authors":"Wei Guo, Kun Mu, Jing-Chao Geng, Hai-Yang Xing, Yu Dong, Wen-Dong Liu, Shuan-Chi Wang, Jia-Xiao Shi, Bao-Rui Xing, Jian-Yong Zhao, Xiao-Ming Li","doi":"10.1038/s42003-025-08186-6","DOIUrl":"https://doi.org/10.1038/s42003-025-08186-6","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IDD) is a primary cause of degenerative disc disease; however, the mechanisms underlying it remain unknown. Although great efforts have been made to develop new regenerative therapies, their clinical success is limited. Recent research has indicated that microRNAs (miRNAs) are significantly involved in the progression of IDD. Investigating the role of miRNA intervention in IDD could facilitate the development of therapeutic strategies based on miRNAs. However, circulating miRNAs have not yet been recognized as standard biomarkers for IDD. In this study, we observed that the expression of miR-27b-3p was elevated in the blood and nucleus pulposus (NP) tissue of patients with IDD. Furthermore, reducing the expression of miR-27b-3p was shown to impede the progression of IDD. MiR-27b-3p could reduce the expression of collagen II and ACAN and promote the expression of MMP13 and ADAMT-5 in vitro and in vivo. miR-27b-3p aggravated IDD progression by directly targeting peroxisome proliferator-activated receptor gamma (PPARG), a negative regulator of the NF-κB signal pathway. This study also established that PPARG serves a protective role in IDD. The overexpression of PPARG was able to mitigate the detrimental effects caused by miR-27b-3p in NP cells and animal models of IDD, indicating that miR-27b-3p facilitates the progression of IDD through its interaction with PPARG. Additionally, the transcription factor ATF1 was found to enhance the expression of miR-27b-3p by targeting its promoter region, thereby promoting the degenerative impact of miR-27b-3p on NP cells. Given that miR-27b-3p can promote IDD both in vitro and in vivo, it holds potential as a biomarker, and the inhibition of miR-27b-3p expression may represent a novel therapeutic target for IDD.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"751"},"PeriodicalIF":5.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076545","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}
Katrina R Quinn, Florian Sandhaeger, Nima Noury, Ema Zezelic, Markus Siegel
{"title":"Abstract choice representations during stable choice-response associations.","authors":"Katrina R Quinn, Florian Sandhaeger, Nima Noury, Ema Zezelic, Markus Siegel","doi":"10.1038/s42003-025-08129-1","DOIUrl":"https://doi.org/10.1038/s42003-025-08129-1","url":null,"abstract":"<p><p>An increasing body of evidence has demonstrated neural representations of choices independent of the motor actions used to report them - so-called abstract choices. However, it remains unclear whether such representations arise due to dynamic changes in choice-response associations or reflect a general property of decision-making. Here, we show that in the human brain, choices are represented abstractly even when choice-response associations remain stable over time. We recorded neural activity using magnetoencephalography while participants performed a motion discrimination task, with choice-response mappings held constant within blocks. We found neural information about participants' perceptual choices independent of both motor response and visual stimulus. Choice information increased during the stimulus and peaked after the response. Moreover, choice and response information showed distinct cortical distributions, with choice-related signals strongest in frontoparietal regions. Thus, abstract choice representations are not limited to dynamic or action-independent contexts and may be a general feature of decision-making.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"752"},"PeriodicalIF":5.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076544","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}
Yizhong Zhang, Arshia Naaz, Trishia Yi Ning Cheng, Jovian Jing Lin, Mingtong Gao, Rajkumar Dorajoo, Mohammad Alfatah
{"title":"Systematic transcriptomics analysis of calorie restriction and rapamycin unveils their synergistic interaction in prolonging cellular lifespan.","authors":"Yizhong Zhang, Arshia Naaz, Trishia Yi Ning Cheng, Jovian Jing Lin, Mingtong Gao, Rajkumar Dorajoo, Mohammad Alfatah","doi":"10.1038/s42003-025-08178-6","DOIUrl":"https://doi.org/10.1038/s42003-025-08178-6","url":null,"abstract":"<p><p>Aging is a multifaceted biological process marked by the decline in both mitotic and postmitotic cellular function, often central to the development of age-related diseases. In the pursuit of slowing or even reversing the aging process, a prominent strategy of significant interest is calorie restriction (CR), also known as dietary restriction, and the potential influence of a drug called rapamycin (RM). Both CR and RM have demonstrated the capacity to extend healthspan and lifespan across a diverse array of species, including yeast, worms, flies, and mice. Nevertheless, their individual and combined effects on mitotic and postmitotic cells, as well as their comparative analysis, remain areas that demand a thorough investigation. In this study, we employ RNA-sequencing methodologies to comprehensively analyze the impact of CR, RM, and their combination (CR + RM) on gene expression in yeast cells. Our analysis uncovers distinctive, overlapping, and even contrasting patterns of gene regulation, illuminating the unique and shared effects of CR and RM. Furthermore, the transcriptional synergistic interaction of CR + RM is validated in extending the lifespan of both yeast and human cells.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"753"},"PeriodicalIF":5.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076551","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}
Victoria M Bedell, Priya Dubey, Han B Lee, Dondra S Bailey, Jennifer L Anderson, Allison Jamieson-Lucy, Rui Xiao, Elvin V Leonard, Marni J Falk, Michael A Pack, Mary Mullins, Steven A Farber, Roderic G Eckenhoff, Stephen C Ekker
{"title":"Zebrafishology, study design guidelines for rigorous and reproducible data using zebrafish.","authors":"Victoria M Bedell, Priya Dubey, Han B Lee, Dondra S Bailey, Jennifer L Anderson, Allison Jamieson-Lucy, Rui Xiao, Elvin V Leonard, Marni J Falk, Michael A Pack, Mary Mullins, Steven A Farber, Roderic G Eckenhoff, Stephen C Ekker","doi":"10.1038/s42003-025-07496-z","DOIUrl":"10.1038/s42003-025-07496-z","url":null,"abstract":"<p><p>The zebrafish (Danio rerio) is one of the most widely used research model organisms funded by the United States' National Institutes of Health, second only to the mouse. Here, we discuss the advantages and unique qualities of this model organism. Additionally, we discuss key aspects of experimental design and statistical approaches that apply to studies using the zebrafish model organism. Finally, we list critical details that should be considered in the design of zebrafish experiments to enhance rigor and data reproducibility. These guidelines are designed to aid new researchers, journal editors, and manuscript reviewers in supporting the publication of the highest-quality zebrafish research.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"739"},"PeriodicalIF":5.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981923","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}
Pedro De-la-Torre, Claudia Martínez-García, Paul Gratias, Matthew Mun, Paula Santana, Nurunisa Akyuz, Wendy González, Artur A Indzhykulian, David Ramírez
{"title":"Identification of druggable binding sites and small molecules as modulators of TMC1.","authors":"Pedro De-la-Torre, Claudia Martínez-García, Paul Gratias, Matthew Mun, Paula Santana, Nurunisa Akyuz, Wendy González, Artur A Indzhykulian, David Ramírez","doi":"10.1038/s42003-025-07943-x","DOIUrl":"10.1038/s42003-025-07943-x","url":null,"abstract":"<p><p>Our ability to hear and maintain balance relies on the proper functioning of inner ear sensory hair cells, which translate mechanical stimuli into electrical signals via mechano-electrical transducer (MET) channels, composed of TMC1/2 proteins. However, the therapeutic use of ototoxic drugs, such as aminoglycosides and cisplatin, which can enter hair cells through MET channels, often leads to profound auditory and vestibular dysfunction. To date, our understanding of how small-molecule modulators interact with TMCs remains limited, hampering the discovery of novel drugs. Here, we propose a structure-based drug screening approach, integrating 3D-pharmacophore modeling, molecular dynamics simulations of the TMC1 + CIB2 + TMIE complex, and experimental validation. Our pipeline successfully identified three potential drug-binding sites within the TMC1 pore, phospholipids, and key amino acids involved in the binding of several compounds, as well as FDA-approved drugs that reduced dye uptake in cultured cochlear explants. Our pipeline offers a broad application for discovering modulators for mechanosensitive ion channels.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"742"},"PeriodicalIF":5.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969817","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}
Shengke Wang, Yan Zhou, Yuezhuo Wang, Keshu Tang, Danqi Wang, Jiawen Hong, Pengcheng Wang, Sheng Ye, Jie Yan, Shengkai Li, Zhemin Zhou, Jimei Du
{"title":"Genetic landscape and evolution of Acinetobacter pittii, an underestimated emerging nosocomial pathogen.","authors":"Shengke Wang, Yan Zhou, Yuezhuo Wang, Keshu Tang, Danqi Wang, Jiawen Hong, Pengcheng Wang, Sheng Ye, Jie Yan, Shengkai Li, Zhemin Zhou, Jimei Du","doi":"10.1038/s42003-025-08156-y","DOIUrl":"10.1038/s42003-025-08156-y","url":null,"abstract":"<p><p>As a member of Acinetobacter calcoaceticus-baumannii complex, Acinetobacter pittii has been an emerging concern in nosocomial infection due to its increasing prevalence and multidrug resistance (MDR). However, its population structure remains broadly unknown, hampering efficient tracing of its transmission and evolution. In this study, we developed a distributed core genome multilocus sequence typing (dcgMLST) for A. pittii based on 750 genomes and employed it to map the genetic landscape and evolution of A. pittii. The results demonstrated that two hierarchical clustering (HC) levels effectively correspond to genetic diversity from species (HC1100) to natural populations (HC450), as well as that a predominant lineage, HC1100_4, accounts for 33.9% of A. pittii strains. Subsequent analysis revealed that specific gene gain and loss events within HC1100_4 are linked to adaptations to environmental stress. Moreover, we identified a cluster of multidrug-resistant plasmids PT_712 responsible for the dissemination of bla<sub>NDM-1</sub> genes within the genus of Acinetobacter. This study provides a framework for characterizing genetic diversity, evolutionary dynamics, molecular population distribution, and tracing of A. pittii, which has the potential to improve infection control strategies and public health policy.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"738"},"PeriodicalIF":5.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962656","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":"Inspiring scientific wonder, curiosity and critical thinking in young minds: an interview with Audrey Dussutour.","authors":"","doi":"10.1038/s42003-025-08166-w","DOIUrl":"10.1038/s42003-025-08166-w","url":null,"abstract":"","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"748"},"PeriodicalIF":5.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979013","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}
J K Bruce, L Y Li, Y Tang, E Forster, N J Winsor, P Y Bi, C Krustev, S Keely, J E Lee, J R Rohde, H Y Gaisano, D J Philpott, S E Girardin
{"title":"Gasdermin-D pores induce an inactivating caspase-4 cleavage that limits IL-18 production in the intestinal epithelium.","authors":"J K Bruce, L Y Li, Y Tang, E Forster, N J Winsor, P Y Bi, C Krustev, S Keely, J E Lee, J R Rohde, H Y Gaisano, D J Philpott, S E Girardin","doi":"10.1038/s42003-025-08183-9","DOIUrl":"10.1038/s42003-025-08183-9","url":null,"abstract":"<p><p>Intestinal epithelial-derived IL-18 is critical for homeostatic intestinal barrier function and is secreted through Gasdermin D (GSDMD) pores. Inflammasome activation is a prerequisite for both IL-18 maturation and GSDMD pore formation. However, GSDMD pores also cause pyroptotic cell death, which could be detrimental to the intestinal epithelial barrier. How epithelial cells balance the need to secrete IL-18 and to maintain barrier integrity remains poorly understood. In human intestinal epithelial cell lines and in primary human epithelial intestinal organoids, but not in immune cells, GSDMD plasma membrane pore formation by LPS electroporation and by gram-negative bacterial infection induced a non-conventional p37 caspase-4 fragment that was associated with reduced levels of mature IL-18. By contrast, limiting GSDMD plasma membrane pores pharmacologically and via point-mutagenesis prevented caspase-4 cleavage and increased IL-18 production, suggesting that p37 caspase-4 cleavage may regulate IL-18 maturation in the intestinal epithelium. In support, co-expression of caspase-4 cleavage mutants and IL-18 in HEK293T cells revealed that non-cleavable caspase-4 produced more mature IL-18 than cleaved caspase-4. Overall, these studies suggest that epithelial inflammasomes encode feedback pathways that control the balance between cytokine secretion and cell death. This may be an important mechanism to ensure homeostatic IL-18 production in the intestinal epithelium.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"737"},"PeriodicalIF":5.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992512","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}