Research最新文献

{"title":"Noninvasive Monitoring of Programmed Death-Ligand 2 Expression with Positron Emission Tomography using ⁶⁸Ga-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 [⁶⁸Ga]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, [⁶⁸Ga]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 [⁶⁸Ga]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}

{"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}

{"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}

{"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}

{"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> _s reached 0.37 kg m^-1 s^-1/2 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}

{"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}

{"title":"An Integrated Dual-Layer Heterogeneous Polycaprolactone Scaffold Promotes Oral Mucosal Wound Healing through Inhibiting Bacterial Adhesion and Mediating HGF-1 Behavior.","authors":"Gaoying Hong, Zihe Hu, Yanyan Zhou, Mumian Chen, Haiyan Wu, Weiying Lu, Wenjing Jin, Ke Yao, Zhijian Xie, Jue Shi","doi":"10.34133/research.0499","DOIUrl":"10.34133/research.0499","url":null,"abstract":"<p><p>Recently, the high incidence of oral mucosal defects and the subsequent functional impairments have attracted widespread attention. Controlling scaffold geometry pattern has been proposed as a strategy to promote cell behavior and facilitate soft tissue repair. In this study, we innovatively construct an integrated dual-layer heterogeneous polycaprolactone (PCL) scaffold using melt electrowriting (MEW) technology. The outer layer was disordered, while the inner layer featured oriented fiber patterns: parallel (P-par), rhombic (P-rhomb), and square (P-sq). Our findings revealed that the P-rhomb and P-sq scaffolds exhibited superior surface wettability, roughness, and tensile strength compared to the pure disordered PCL scaffolds (P) and P-par. Compared to the commercial collagen membranes, the outer layer of PCL can effectively inhibit bacterial adhesion and biofilm formation. Furthermore, the P-rhomb and P-sq groups demonstrated higher gene and protein expression levels related to cell adhesion and cell migration rates than did the P and P-par groups. Among them, P-sq plays an important role in inducing the differentiation of gingival fibroblasts into myofibroblasts rich in α-smooth muscle actin (α-SMA). Additionally, P-sq could reduce inflammation, promote epithelial regeneration, and accelerate wound healing when used in full-thickness oral mucosal defects in rabbits. Overall, the integrated dual-layer heterogeneous PCL scaffold fabricated by MEW technology effectively inhibited bacterial adhesion and guided tissue regeneration, offering advantages for clinical translation and large-scale production. This promising material holds important potential for treating full-thickness mucosal defects in a bacteria-rich oral environments.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0499"},"PeriodicalIF":11.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847657","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}

{"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 ¹²²R-R-S¹²⁴ 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}

{"title":"Stabilizing Layered Cathodes by High-Entropy Doping.","authors":"Yuan Ma, Zihao Zhou, Torsten Brezesinski, Yanjiao Ma, Yuping Wu","doi":"10.34133/research.0503","DOIUrl":"https://doi.org/10.34133/research.0503","url":null,"abstract":"<p><p>Layered Ni-rich oxide cathodes in lithium-ion batteries (LIBs) often struggle with poor thermal safety and capacity fade. Xin and colleagues' studies in <i>Nature</i> and <i>Nature Energy</i> demonstrate a novel high-entropy (compositionally complex) doping strategy, introducing \"cocktail effects\" from multiple constituents. This approach substantially improves cycling performance and stability, reduces material cost, and may pave the way toward the development of advanced electrodes for next-generation LIBs.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0503"},"PeriodicalIF":11.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506906","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}

{"title":"A Universal Framework for General Prediction of Physicochemical Properties: The Natural Growth Model.","authors":"Jinming Fan, Chao Qian, Shaodong Zhou","doi":"10.34133/research.0510","DOIUrl":"https://doi.org/10.34133/research.0510","url":null,"abstract":"<p><p>To precisely and reasonably describe the contribution of interatomic and intermolecular interactions to the physicochemical properties of complex systems, a chemical message passing strategy as driven by graph neural network is proposed. Thus, by distinguishing inherent and environmental features of atoms, as well as proper delivering of these messages upon growth of systems from atoms to bulk level, the evolution of system features affords eventually the target properties like the adsorption wavelength, emission wavelength, solubility, photoluminescence quantum yield, ionization energy, and lipophilicity. Considering that such a model combines chemical principles and natural behavior of atom aggregation crossing multiple scales, most likely, it will be proven to be rational and efficient for more general aims in dealing with complex systems.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0510"},"PeriodicalIF":11.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506904","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}