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Cholesteric Cellulose Liquid Crystal Fibers by Direct Drawing. 用直接拉丝法制造胆甾纤维素液晶纤维。
IF 11 1区 综合性期刊
Research Pub Date : 2024-11-07 eCollection Date: 2024-01-01 DOI: 10.34133/research.0527
Zhuohao Zhang, Qiao Wang, Yinuo Li, Chong Wang, Xinyuan Yang, Luoran Shang
{"title":"Cholesteric Cellulose Liquid Crystal Fibers by Direct Drawing.","authors":"Zhuohao Zhang, Qiao Wang, Yinuo Li, Chong Wang, Xinyuan Yang, Luoran Shang","doi":"10.34133/research.0527","DOIUrl":"https://doi.org/10.34133/research.0527","url":null,"abstract":"<p><p>Polymer fibers are attracting increasing attention as a type of fundamental material for a wide range of products. However, to incorporate novel functionality, a crucial challenge is to simultaneously manipulate their structuring across multiple length scales. In this research, a facile and universal approach is proposed by directly drawing a pre-gel feedstock embedding a cellulose cholesteric liquid crystal (CLC). An in situ photo-polymerization process is applied, which not only allows for the continuous drawing of the filaments without breakup but also makes the final CLC fibers a colored appearance. More importantly, the multiscale properties of the fibers, such as their diameter, morphology, and the internal liquid crystalline ordering of the molecules (and thus structural color), can be manipulated by several controlling parameters. Combining this cross-scale tunability with a smart functional hydrogel system results in the formation of fibers with structural coloration, self-healing, electrical conduction, and thermal-sensing abilities. We believe that this platform can be extended to other hydrogel systems and will help unlock a wide variety of real-life applications.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0527"},"PeriodicalIF":11.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Holographic Ultrasound Modulates Neural Activity in a 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Mouse Model of Parkinson's Disease. 全息超声调节 1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的帕金森病小鼠模型的神经活动。
IF 11 1区 综合性期刊
Research Pub Date : 2024-11-06 eCollection Date: 2024-01-01 DOI: 10.34133/research.0516
Hui Zhou, Fei Li, Zhengrong Lin, Long Meng, Dan Chen, Qingping Zhang, Lili Niu
{"title":"Holographic Ultrasound Modulates Neural Activity in a 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Mouse Model of Parkinson's Disease.","authors":"Hui Zhou, Fei Li, Zhengrong Lin, Long Meng, Dan Chen, Qingping Zhang, Lili Niu","doi":"10.34133/research.0516","DOIUrl":"10.34133/research.0516","url":null,"abstract":"<p><p>Ultrasound (US) has emerged as a noninvasive neurostimulation method for motor control in Parkinson's disease (PD). Previous in vivo US neuromodulation studies for PD were single-target stimulation. However, the motor symptoms of PD are linked with neural circuit dysfunction, and multi-target stimulation is conducted in clinical treatment for PD. Thus, in the present study, we achieved multi-target US stimulation using holographic lens transducer based on the Rayleigh-Sommerfeld diffraction integral and time-reversal methods. We demonstrated that holographic US stimulation of the bilateral dorsal striatum (DS) could improve the motor function in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. The holographic US wave (fundamental frequency: 3 MHz, pulse repetition frequency: 500 Hz, duty cycle: 20%, tone-burst duration: 0.4 ms, sonication duration: 1 s, interstimulus interval: 4 s, spatial-peak temporal-average intensity: 180 mw/cm<sup>2</sup>) was delivered to the bilateral DS 20 min per day for consecutive 10 d after the last injection of MPTP. Immunohistochemical c-Fos staining demonstrated that holographic US significantly increased the c-Fos-positive neurons in the bilateral DS compared with the sham group (<i>P</i> = 0.003). Moreover, our results suggested that holographic US stimulation of the bilateral DS ameliorated motor dysfunction (<i>P</i> < 0.05) and protected the dopaminergic (DA) neurons (<i>P</i> < 0.001). The neuroprotective effect of holographic US was associated with the prevention of axon degeneration and the reinforcement of postsynaptic densities [growth associated protein-43 (<i>P</i> < 0.001), phosphorylated Akt (<i>P</i> = 0.001), β3-tubulin (<i>P</i> < 0.001), phosphorylated CRMP2 (<i>P</i> = 0.037), postsynaptic density (<i>P</i> = 0.023)]. These data suggested that holographic US-induced acoustic radiation force has the potential to achieve multi-target neuromodulation and could serve as a reliable tool for the treatment of PD.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0516"},"PeriodicalIF":11.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
eMCI: An Explainable Multimodal Correlation Integration Model for Unveiling Spatial Transcriptomics and Intercellular Signaling. eMCI:用于揭示空间转录组学和细胞间信号转导的可解释多模态相关整合模型
IF 11 1区 综合性期刊
Research Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.34133/research.0522
Renhao Hong, Yuyan Tong, Hui Tang, Tao Zeng, Rui Liu
{"title":"eMCI: An Explainable Multimodal Correlation Integration Model for Unveiling Spatial Transcriptomics and Intercellular Signaling.","authors":"Renhao Hong, Yuyan Tong, Hui Tang, Tao Zeng, Rui Liu","doi":"10.34133/research.0522","DOIUrl":"10.34133/research.0522","url":null,"abstract":"<p><p>Current integration methods for single-cell RNA sequencing (scRNA-seq) data and spatial transcriptomics (ST) data are typically designed for specific tasks, such as deconvolution of cell types or spatial distribution prediction of RNA transcripts. These methods usually only offer a partial analysis of ST data, neglecting the complex relationship between spatial expression patterns underlying cell-type specificity and intercellular cross-talk. Here, we present eMCI, an explainable multimodal correlation integration model based on deep neural network framework. eMCI leverages the fusion of scRNA-seq and ST data using different spot-cell correlations to integrate multiple synthetic analysis tasks of ST data at cellular level. First, eMCI can achieve better or comparable accuracy in cell-type classification and deconvolution according to wide evaluations and comparisons with state-of-the-art methods on both simulated and real ST datasets. Second, eMCI can identify key components across spatial domains responsible for different cell types and elucidate the spatial expression patterns underlying cell-type specificity and intercellular communication, by employing an attribution algorithm to dissect the visual input. Especially, eMCI has been applied to 3 cross-species datasets, including zebrafish melanomas, soybean nodule maturation, and human embryonic lung, which accurately and efficiently estimate per-spot cell composition and infer proximal and distal cellular interactions within the spatial and temporal context. In summary, eMCI serves as an integrative analytical framework to better resolve the spatial transcriptome based on existing single-cell datasets and elucidate proximal and distal intercellular signal transduction mechanisms over spatial domains without requirement of biological prior reference. This approach is expected to facilitate the discovery of spatial expression patterns of potential biomolecules with cell type and cell-cell communication specificity.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0522"},"PeriodicalIF":11.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Noninvasive Monitoring of Programmed Death-Ligand 2 Expression with Positron Emission Tomography using 68Ga-labeled Peptide Antagonist in Preclinical and Exploratory Human Studies. 在临床前和探索性人体研究中使用 68Ga 标记的多肽拮抗剂通过正电子发射断层扫描对程序性死亡配体 2 的表达进行无创监测
IF 11 1区 综合性期刊
Research Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.34133/research.0523
Yajie Zhao, Xiaoqin Yin, Ming Zhou, Wanqian Rao, Xuan Ji, Xiaobo Wang, XiaoXiong Xiao, Shuo Hu
{"title":"Noninvasive Monitoring of Programmed Death-Ligand 2 Expression with Positron Emission Tomography using <sup>68</sup>Ga-labeled Peptide Antagonist in Preclinical and Exploratory Human Studies.","authors":"Yajie Zhao, Xiaoqin Yin, Ming Zhou, Wanqian Rao, Xuan Ji, Xiaobo Wang, XiaoXiong Xiao, Shuo Hu","doi":"10.34133/research.0523","DOIUrl":"10.34133/research.0523","url":null,"abstract":"<p><p>While the expression of programmed death ligand-1 (PD-L1) is associated with response to immune therapy, PD-L1-negative patients may still benefit from immune treatment. Programmed death ligand-2 (PD-L2), another crucial immune checkpoint molecule interacting with PD-1, correlates with the efficacy of various tumor immune therapies. This study investigates the expression of PD-L2 in non-small cell lung cancer (NSCLC) patients following anti-PD-1 therapy and its predictive value for clinical survival outcomes. Additionally, we explore the noninvasive, real-time, and dynamic quantitative analysis potential of PD-L2 positron emission tomography (PET) imaging in transplanted tumors. We utilized [<sup>68</sup>Ga]Ga-labeled peptide HN11-1 for PD-L2 PET imaging. The results indicate a higher response rate to anti-PD-1 therapy in patients positive for both PD-L1 and PD-L2, with PD-L2 status independently predicting progression-free survival (PFS) with pembrolizumab treatment. Furthermore, [<sup>68</sup>Ga]Ga-HN11-1 PET imaging demonstrates specificity in assessing PD-L2 status. Overall, we confirm the correlation between high PD-L2 expression and favorable PFS in NSCLC patients post anti-PD-1 therapy and highlight the promising potential of [<sup>68</sup>Ga]Ga-HN11-1 as a specific tracer for PD-L2 in preclinical and initial human trials.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0523"},"PeriodicalIF":11.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Coordinated Interactions between the Hippocampus and Retrosplenial Cortex in Spatial Memory. 空间记忆中海马和后叶皮层之间的协调互动
IF 11 1区 综合性期刊
Research Pub Date : 2024-10-31 eCollection Date: 2024-01-01 DOI: 10.34133/research.0521
Ruiqing Hou, Ziyue Liu, Zichen Jin, Dongxue Huang, Yue Hu, Wenjie Du, Danyi Zhu, Leiting Yang, Yuanfeng Weng, Tifei Yuan, Bin Lu, Yingwei Wang, Yong Ping, Xiao Xiao
{"title":"Coordinated Interactions between the Hippocampus and Retrosplenial Cortex in Spatial Memory.","authors":"Ruiqing Hou, Ziyue Liu, Zichen Jin, Dongxue Huang, Yue Hu, Wenjie Du, Danyi Zhu, Leiting Yang, Yuanfeng Weng, Tifei Yuan, Bin Lu, Yingwei Wang, Yong Ping, Xiao Xiao","doi":"10.34133/research.0521","DOIUrl":"10.34133/research.0521","url":null,"abstract":"<p><p>While a hippocampal-cortical dialogue is generally thought to mediate memory consolidation, which is crucial for engram function, how it works remains largely unknown. Here, we examined the interplay of neural signals from the retrosplenial cortex (RSC), a neocortical region, and from the hippocampus in memory consolidation by simultaneously recording sharp-wave ripples (SWRs) of dorsal hippocampal CA1 and neural signals of RSC in free-moving mice during the delayed spatial alternation task (DSAT) and subsequent sleep. Hippocampal-RSC coordination during SWRs was identified in nonrapid eye movement (NREM) sleep, reflecting neural reactivation of decision-making in the task, as shown by a peak reactivation strength within SWRs. Using modified generalized linear models (GLMs), we traced information flow through the RSC-CA1-RSC circuit around SWRs during sleep following DSAT. Our findings show that after spatial training, RSC excitatory neurons typically increase CA1 activity prior to hippocampal SWRs, potentially initiating hippocampal memory replay, while inhibitory neurons are activated by hippocampal outputs in post-SWRs. We further identified certain excitatory neurons in the RSC that encoded spatial information related to the DSAT. These neurons, classified as splitters and location-related cells, showed varied responses to hippocampal SWRs. Overall, our study highlights the complex dynamics between the RSC and hippocampal CA1 region during SWRs in NREM sleep, underscoring their critical interplay in spatial memory consolidation.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0521"},"PeriodicalIF":11.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
High-Resolution Imaging and Morphological Phenotyping of C. elegans through Stable Robotic Sample Rotation and Artificial Intelligence-Based 3-Dimensional Reconstruction. 通过稳定的机器人样本旋转和基于人工智能的三维重建技术,实现高分辨率成像和 elegans 形态表型。
IF 11 1区 综合性期刊
Research Pub Date : 2024-10-30 eCollection Date: 2024-01-01 DOI: 10.34133/research.0513
Peng Pan, Pengsong Zhang, Sharanja Premachandran, Ran Peng, Shaojia Wang, Qigao Fan, Yu Sun, John A Calarco, Xinyu Liu
{"title":"High-Resolution Imaging and Morphological Phenotyping of <i>C. elegans</i> through Stable Robotic Sample Rotation and Artificial Intelligence-Based 3-Dimensional Reconstruction.","authors":"Peng Pan, Pengsong Zhang, Sharanja Premachandran, Ran Peng, Shaojia Wang, Qigao Fan, Yu Sun, John A Calarco, Xinyu Liu","doi":"10.34133/research.0513","DOIUrl":"10.34133/research.0513","url":null,"abstract":"<p><p>Accurate visualization and 3-dimensional (3D) morphological profiling of small model organisms can provide quantitative phenotypes benefiting genetic analysis and modeling of human diseases in tractable organisms. However, in the highly studied nematode <i>Caenorhabditis elegans,</i> accurate morphological phenotyping remains challenging because of notable decrease in image resolution of distant signal under high magnification and complexity in the 3D reconstruction of microscale samples with irregular shapes. Here, we develop a robust robotic system that enables the contactless, stable, and uniform rotation of <i>C. elegans</i> for multi-view fluorescent imaging and 3D morphological phenotyping via the precise reconstruction of 3D models. Contactless animal rotation accommodates a variety of body shapes and sizes found at different developmental stages and in mutant strains. Through controlled rotation, high-resolution fluorescent imaging of <i>C. elegans</i> structures is obtained by overcoming the limitations inherent in both widefield and confocal microscopy. Combining our robotic system with machine learning, we create, for the first time, precise 3D reconstructions of <i>C. elegans</i> at the embryonic and adult stages, enabling 3D morphological phenotyping of mutant strains in an accurate and comprehensive fashion. Intriguingly, our morphological phenotyping discovered a genetic interaction between 2 RNA binding proteins (UNC-75/CELF and MBL-1/MBNL), which are highly conserved between <i>C. elegans</i> and humans and implicated in neurological and muscular disorders. Our system can thus generate quantitative morphological readouts facilitating the investigation of genetic variations and disease mechanisms. More broadly, our method will also be amenable for 3D phenotypic analysis of other biological samples, like zebrafish and <i>Drosophila</i> larvae.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0513"},"PeriodicalIF":11.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Special Issue for the School of Materials Science and Engineering at Southeast University. 东南大学材料科学与工程学院特刊。
IF 11 1区 综合性期刊
Research Pub Date : 2024-10-29 eCollection Date: 2024-01-01 DOI: 10.34133/research.0519
ZhengMing Sun
{"title":"Special Issue for the School of Materials Science and Engineering at Southeast University.","authors":"ZhengMing Sun","doi":"10.34133/research.0519","DOIUrl":"https://doi.org/10.34133/research.0519","url":null,"abstract":"","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0519"},"PeriodicalIF":11.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Highly Robust, Compressible, Anisotropic, and Fire-Retardant Polyimide/Hydroxyapatite Nanowires/Reduced Graphene Oxide Aerogel for Rapid Adsorption of Viscous Oil Assisted by Sunlight. 高稳健性、可压缩性、各向异性和阻燃性聚酰亚胺/羟基磷灰石纳米线/还原石墨烯氧化物气凝胶,用于在阳光辅助下快速吸附粘性油。
IF 11 1区 综合性期刊
Research Pub Date : 2024-10-29 eCollection Date: 2024-01-01 DOI: 10.34133/research.0512
Pan Huang, Yongxiang Sun, Lin Yang, Haoyu Yang, Ying Hu, Jifang Liu, Xuwen Peng, Hongbo Zeng
{"title":"Highly Robust, Compressible, Anisotropic, and Fire-Retardant Polyimide/Hydroxyapatite Nanowires/Reduced Graphene Oxide Aerogel for Rapid Adsorption of Viscous Oil Assisted by Sunlight.","authors":"Pan Huang, Yongxiang Sun, Lin Yang, Haoyu Yang, Ying Hu, Jifang Liu, Xuwen Peng, Hongbo Zeng","doi":"10.34133/research.0512","DOIUrl":"https://doi.org/10.34133/research.0512","url":null,"abstract":"<p><p>Improving the adsorption efficiency of porous adsorbent materials for organic liquids with high viscosity is crucial for addressing oil spill incidents. In this study, a high-performance aerogel adsorbent composed of polyimide (PI), hydroxyapatite nanowires (HAPnws), and reduced graphene oxide (rGO) has been fabricated, which leverages reduced flow tortuosity through anisotropic structures and solar-assisted viscosity reduction via photothermal materials. The prepared anisotropic PI/HAP/rGO aerogel, with directional channels, shows unique mechanical properties with high stiffness along the axial direction and compressibility along the radial direction. PI/HAP/rGO, featuring vertically aligned channels, demonstrated superior adsorption efficiency (the adsorption coefficient <i>K</i> <sub>s</sub> reached 0.37 kg m<sup>-1</sup> s<sup>-1/2</sup> for an engine oil with a viscosity of ~144 mPa·s) for oil of varying viscosities compared to similar aerogels with uniform pores, because of the substantially reduced flow tortuosity. The photothermal properties of rGO further enhance the adsorption speed of PI/HAP/rGO for viscous oil under sunlight, including crude oil with ultrahigh viscosity. In addition, PI/HAP/rGO exhibits excellent fire resistance, allowing for reusability via both adsorption-compression and adsorption-combustion cycles. The robust and compressible PI/HAP/rGO aerogels with high adsorption efficiency for viscous oil and fire resistance represent an ideal solution for practical oil spill treatment, and this approach also offers inspiration for the development of advanced adsorbent materials.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0512"},"PeriodicalIF":11.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ibrutinib Promotes Atrial Fibrillation by Disrupting A-Kinase Anchoring Protein 1-Mediated Mitochondrial Quality Surveillance in Cardiomyocytes. 伊布替尼通过破坏心肌细胞中A-激酶锚定蛋白1介导的线粒体质量监测促进心房颤动
IF 11 1区 综合性期刊
Research Pub Date : 2024-10-29 eCollection Date: 2024-01-01 DOI: 10.34133/research.0509
Yukun Li, Xinmeng Liu, Rong Lin, Xiaodong Peng, Xuesi Wang, Fanchao Meng, Shuqi Jin, Wenhe Lv, Xiaoying Liu, Zhuohang Du, Songnan Wen, Rong Bai, Yanfei Ruan, Hao Zhou, Rongjun Zou, Ribo Tang, Nian Liu
{"title":"Ibrutinib Promotes Atrial Fibrillation by Disrupting A-Kinase Anchoring Protein 1-Mediated Mitochondrial Quality Surveillance in Cardiomyocytes.","authors":"Yukun Li, Xinmeng Liu, Rong Lin, Xiaodong Peng, Xuesi Wang, Fanchao Meng, Shuqi Jin, Wenhe Lv, Xiaoying Liu, Zhuohang Du, Songnan Wen, Rong Bai, Yanfei Ruan, Hao Zhou, Rongjun Zou, Ribo Tang, Nian Liu","doi":"10.34133/research.0509","DOIUrl":"10.34133/research.0509","url":null,"abstract":"<p><p><b>Background:</b> Ibrutinib, a potent Bruton's tyrosine kinase inhibitor with marked efficacy against hematological malignancies, is associated with the heightened risk of atrial fibrillation (AF). Although ibrutinib-induced AF is linked to enhanced oxidative stress, the underlying mechanisms remain unclear. <b>Objective:</b> This research aimed to explore the molecular mechanism and regulatory target in ibrutinib-induced AF. <b>Methods:</b> We performed in vivo electrophysiology studies using ibrutinib-treated mice, and then employed proteomic and single-cell transcriptomic analyses to identify the underlying targets and mechanisms. The effects of A-kinase anchoring protein 1 (AKAP1) depletion on mitochondrial quality surveillance (MQS) were evaluated using both in vivo and ex vivo AKAP1 overexpression models. <b>Results:</b> Atrial AKAP1 expression was significantly reduced in ibrutinib-treated mice, leading to inducible AF, atrial fibrosis, and mitochondrial fragmentation. These pathological changes were effectively mitigated in an overexpression model of ibrutinib-treated mice injected with an adeno-associated virus carrying Akap1. In ibrutinib-treated atrial myocytes, AKAP1 down-regulation promoted dynamin-related protein 1 (DRP1) translocation into mitochondria by facilitating DRP1 dephosphorylation at Ser637, thereby mediating excessive mitochondrial fission. Impaired MQS was also suggested by defective mitochondrial respiration, mitochondrial metabolic reprogramming, and suppressed mitochondrial biogenesis, accompanied by excessive oxidative stress and inflammatory activation. The ibrutinib-mediated MQS disturbance can be markedly improved with the inducible expression of the AKAP1 lentiviral system. <b>Conclusions:</b> Our findings emphasize the key role of AKAP1-mediated MQS disruption in ibrutinib-induced AF, which explains the previously observed reactive oxygen species overproduction. Hence, AKAP1 activation can be employed to prevent and treat ibrutinib-induced AF.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0509"},"PeriodicalIF":11.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11518619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diacylglycerol O-acyltransferase 2, a Novel Target of Flavivirus NS2B3 Protease, Promotes Zika Virus Replication by Regulating Lipid Droplet Formation. 二酰甘油 O-酰基转移酶 2 是弗拉维夫病毒 NS2B3 蛋白酶的一个新靶点,它通过调节脂滴的形成促进寨卡病毒的复制。
IF 11 1区 综合性期刊
Research Pub Date : 2024-10-24 eCollection Date: 2024-01-01 DOI: 10.34133/research.0511
Xiaotong Luo, Yunxiang Yuan, Xiaocao Ma, Xin Luo, Jiannan Chen, Cancan Chen, Xiaoyi Yang, Jinna Yang, Xuanfeng Zhu, Meiyu Li, Yang Liu, Ping Zhang, Chao Liu
{"title":"Diacylglycerol O-acyltransferase 2, a Novel Target of Flavivirus NS2B3 Protease, Promotes Zika Virus Replication by Regulating Lipid Droplet Formation.","authors":"Xiaotong Luo, Yunxiang Yuan, Xiaocao Ma, Xin Luo, Jiannan Chen, Cancan Chen, Xiaoyi Yang, Jinna Yang, Xuanfeng Zhu, Meiyu Li, Yang Liu, Ping Zhang, Chao Liu","doi":"10.34133/research.0511","DOIUrl":"https://doi.org/10.34133/research.0511","url":null,"abstract":"<p><p>Various lipid metabolism-related factors are essential for Zika virus (ZIKV) replication. In this study, we revealed a crucial role of diacylglycerol O-acyltransferase 2 (DGAT2) in ZIKV replication using a short hairpin RNA-based gene knockdown technique. The replication of ZIKV was significantly inhibited by DGAT2 depletion in multiple cell lines and restored by trans-complementation with DGAT2. Mechanistically, DGAT2 is recruited in the viral replication complex by interacting with non-structural (NS) proteins. Among them, both human and murine DGAT2s can be cleaved by NS2B3 at the <sup>122</sup>R-R-S<sup>124</sup> site. Interestingly, the cleavage product of DGAT2 becomes more stable and is sufficient to promote the lipid droplet (LD) formation independent of its enzymatic activity. This work identifies DGAT2 as a novel target of the viral protease NS2B3 and elucidates that DGAT2 is recruited by viral proteins into the replication complex, thereby playing a proviral role by promoting LD formation, which advances our understanding of host-flavivirus interaction.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0511"},"PeriodicalIF":11.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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