iScience最新文献_第10页

Short-loop engineering strategy for enhancing enzyme thermal stability

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-11 DOI: 10.1016/j.isci.2025.112202

Wenlong Zhu , Yiheng Liu , Hui Cao , Luo Liu , Tianwei Tan

引用次数: 0

Versatile roles of annexin A4 in clear cell renal cell carcinoma: Impact on membrane repair, transcriptional signatures, and composition of the tumor microenvironment

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-11 DOI: 10.1016/j.isci.2025.112198

Maximilian Wess , Manuel Rogg , Constance Gueib-Picard , Annika Merz , Anna L. Kössinger , Tobias Feilen , Grigor Andreev , Martin Werner , Ian J. Frew , Markus Grabbert , Oliver Schilling , Christoph Schell

{"title":"Versatile roles of annexin A4 in clear cell renal cell carcinoma: Impact on membrane repair, transcriptional signatures, and composition of the tumor microenvironment","authors":"Maximilian Wess , Manuel Rogg , Constance Gueib-Picard , Annika Merz , Anna L. Kössinger , Tobias Feilen , Grigor Andreev , Martin Werner , Ian J. Frew , Markus Grabbert , Oliver Schilling , Christoph Schell","doi":"10.1016/j.isci.2025.112198","DOIUrl":"10.1016/j.isci.2025.112198","url":null,"abstract":"<div><div>Clear cell renal cell carcinoma (ccRCC) is the most prevalent renal malignancy with a poor prognosis when metastasized. The invasive growth of cancer cells relates to membrane-damaging forces, but the relevance of plasma membrane repair machinery in ccRCC remains incompletely understood. Employing proteomics, analysis of scRNA-sequencing data, and multiplex imaging, we identified ANXA4 as selectively expressed in ccRCC, with distinct localization patterns at the plasma and nuclear membranes. Genetic titration studies demonstrated that reduced ANXA4 expression impairs membrane repair and invasive capabilities. Further segmentation analysis of ANXA4-low tumors showed a distinct composition of the tumor microenvironment, with increased tumor-infiltrating lymphocytes and acellular extracellular matrix deposition. Transcriptomic analysis demonstrated alterations in epithelial-mesenchymal transition and immune signaling signatures in ANXA4-low tumors. Transcription factor enrichment analysis identified ELF3 as a regulator of invasive properties. Our integrative approach uncovered multiple roles for ANXA4 in modulating membrane repair, transcriptional regulation, and shaping the ccRCC tumor microenvironment composition.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 4","pages":"Article 112198"},"PeriodicalIF":4.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Microglia target synaptic sites early during excitatory circuit disassembly in neurodegeneration

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-11 DOI: 10.1016/j.isci.2025.112201

Alfred Yu , Camille Fang , Li Xuan Tan , Aparna Lakkaraju , Luca Della Santina , Yvonne Ou

{"title":"Microglia target synaptic sites early during excitatory circuit disassembly in neurodegeneration","authors":"Alfred Yu , Camille Fang , Li Xuan Tan , Aparna Lakkaraju , Luca Della Santina , Yvonne Ou","doi":"10.1016/j.isci.2025.112201","DOIUrl":"10.1016/j.isci.2025.112201","url":null,"abstract":"<div><div>During development, microglia prune excess synapses to refine neuronal circuits. In neurodegeneration, understanding the role of microglia-mediated synaptic pruning in circuit remodeling and dysfunction is important for developing therapies aimed at modulating microglial function. Here, we analyzed microglia-mediated synapse disassembly of degenerating postsynaptic neurons in the inner retina. After inducing transient intraocular pressure elevation to injure retinal ganglion cells, microglia increase in number, shift to hyper-ramified morphology, and exhibit greater process movement. Furthermore, due to the greater number of microglia, there is increased colocalization of microglia with synaptic components throughout the inner plexiform layer and with excitatory synaptic sites along individual ganglion cell dendrites. Microglia depletion partially protects ganglion cell function, suggesting that microglia activation may be neurotoxic in early neurodegeneration. Our results demonstrate the important role of microglia in synapse disassembly in degenerating circuits, highlighting that microgliosis is the primary mechanism for increased synapse colocalization early after neuronal injury.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 4","pages":"Article 112201"},"PeriodicalIF":4.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

A Cdk5 inhibitor restores cognitive function and alleviates type 2 diabetes in mice

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-11 DOI: 10.1016/j.isci.2025.112200

Sangita Paul , Remya Chandran , Dileep K. Vijayan , Juhi Bhardwaj , Praveen Singh , Poornima Shetty , Srinivas Cheruku , Sajith Meleveetil , Binukumar Balachandran Krishnamma

{"title":"A Cdk5 inhibitor restores cognitive function and alleviates type 2 diabetes in mice","authors":"Sangita Paul , Remya Chandran , Dileep K. Vijayan , Juhi Bhardwaj , Praveen Singh , Poornima Shetty , Srinivas Cheruku , Sajith Meleveetil , Binukumar Balachandran Krishnamma","doi":"10.1016/j.isci.2025.112200","DOIUrl":"10.1016/j.isci.2025.112200","url":null,"abstract":"<div><div>Type 2 diabetes (T2D) is a metabolic disorder commonly linked with cognitive decline, increasing patients’ susceptibility to dementia. Alzheimer’s disease (AD) has a strong connection with hyperglycemia and insulin dysregulation. Interestingly, certain anti-diabetic drugs have shown potential in reducing T2D-induced cognitive impairment. Previous studies, including ours, have highlighted the dysregulation of cyclin-dependent kinase 5 (Cdk5) activity in both T2D and AD, which may contribute to pathological changes in these conditions. Thus, targeting the Cdk5 kinase could offer a therapeutic approach for T2D and cognitive deterioration. Our research identifies Cdk5 as a key link between T2D and cognitive decline. By screening the KINACore library, we discovered two new brain-penetrant Cdk5 inhibitors, BLINK11 and BLINK15. In a high-fat diet-induced T2D model, these inhibitors improved blood glucose levels, obesity, and cognitive function. BLINK11, in particular, shows promise as a therapeutic candidate for treating cognitive impairment associated with T2D.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 4","pages":"Article 112200"},"PeriodicalIF":4.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Human activity’s impact on urban vegetation in China during the COVID-19 lockdown: An atypical anthropogenic disturbance

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-11 DOI: 10.1016/j.isci.2025.112195

Yujie Li , Shaodong Huang , Panfei Fang , Yuying Liang , Jia Wang

{"title":"Human activity’s impact on urban vegetation in China during the COVID-19 lockdown: An atypical anthropogenic disturbance","authors":"Yujie Li , Shaodong Huang , Panfei Fang , Yuying Liang , Jia Wang","doi":"10.1016/j.isci.2025.112195","DOIUrl":"10.1016/j.isci.2025.112195","url":null,"abstract":"<div><div>The COVID-19 lockdown led to reduced industrial and transportation emissions in Chinese cities, improving air quality and affecting large-scale vegetation. This study examines changes in net primary productivity (NPP) across 283 prefecture-level cities in China (PCC) during the lockdown, focusing on aerosol optical depth (AOD), nighttime light (NTL), temperature, and precipitation. Results from spring 2020 show that 53.5% of cities experienced increased NPP, with greater gains in cities with high industrial and traffic activity due to reduced AOD. Structural equation modeling revealed that urban characteristics, particularly industrial levels, influenced NPP primarily through changes in AOD, with human activity shifts playing a larger role than climate factors. In cities with substantial NPP changes, human activity effects were especially pronounced. These findings highlight the complex interactions among urban characteristics, environmental changes, and vegetation responses, offering insights for ecological management and urban planning in the face of future disruptions.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 4","pages":"Article 112195"},"PeriodicalIF":4.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Brain-like border ownership signals support prediction of natural videos

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-11 DOI: 10.1016/j.isci.2025.112199

Zeyuan Ye , Ralf Wessel , Tom P. Franken

引用次数: 0

Role of the circular RNAs/microRNA/messenger RNA axis in renal cell carcinoma: From gene regulation to metabolism and immunity

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-11 DOI: 10.1016/j.isci.2025.112183

Zhe Xu , Yurong Dong , Kun Cui , Bin Hu , Ying Lu , Xiangjie Liu , Asif Shahzad , Jinshan Zhang , Qiuxin Duan , Ziyuan Bai , Dongmei Peng , Jiaojiao Xia , Wenjing Liu , Zhuoran Teng , Zhe Yang , Qiao Zhang

{"title":"Role of the circular RNAs/microRNA/messenger RNA axis in renal cell carcinoma: From gene regulation to metabolism and immunity","authors":"Zhe Xu , Yurong Dong , Kun Cui , Bin Hu , Ying Lu , Xiangjie Liu , Asif Shahzad , Jinshan Zhang , Qiuxin Duan , Ziyuan Bai , Dongmei Peng , Jiaojiao Xia , Wenjing Liu , Zhuoran Teng , Zhe Yang , Qiao Zhang","doi":"10.1016/j.isci.2025.112183","DOIUrl":"10.1016/j.isci.2025.112183","url":null,"abstract":"<div><div>Renal cell carcinoma (RCC), particularly clear cell RCC (ccRCC), has seen rising incidence and mortality rates. Early detection remains difficult due to nonspecific symptoms, often leading to diagnoses at advanced stages and unfavorable prognoses. Current treatments, including surgery, targeted therapies, and immunotherapies, face limitations such as adverse reactions, drug resistance, and immune evasion. This review discusses the role of circular RNAs (circRNAs) and their involvement in the circRNA/miRNA/mRNA axis during RCC progression. As competitive endogenous RNAs (ceRNAs), circRNAs regulate gene expression and cellular processes, including proliferation, metastasis, apoptosis, and drug resistance. Furthermore, we explore the impact of circRNAs on tumor metabolic reprogramming and their influence on the immune microenvironment. We also summarize the clinical prospects, challenges, and future directions in this field. A comprehensive understanding of these complex interactions may provide new insights into the diagnosis and treatment of RCC, ultimately overcoming existing challenges and improving patient outcomes.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 4","pages":"Article 112183"},"PeriodicalIF":4.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Accessing genetically defined cell types in the superior colliculus with transgenic mouse lines

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-11 DOI: 10.1016/j.isci.2025.112194

Chen Chen , Yuanming Liu , Jianhua Cang

引用次数: 0

Epithelial cell-fate switch triggering ectopic ligand-receptor-mediated JAK-STAT signaling promotes tumorigenesis in Drosophila

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-10 DOI: 10.1016/j.isci.2025.112191

Jiaqi Li , Kiichiro Taniguchi , Weiran Ye , Shu Kondo , Tomoe Kobayashi , Makoto Matsuyama , Kuniaki Saito , Shizue Ohsawa , Tatsushi Igaki

{"title":"Epithelial cell-fate switch triggering ectopic ligand-receptor-mediated JAK-STAT signaling promotes tumorigenesis in Drosophila","authors":"Jiaqi Li , Kiichiro Taniguchi , Weiran Ye , Shu Kondo , Tomoe Kobayashi , Makoto Matsuyama , Kuniaki Saito , Shizue Ohsawa , Tatsushi Igaki","doi":"10.1016/j.isci.2025.112191","DOIUrl":"10.1016/j.isci.2025.112191","url":null,"abstract":"<div><div>Disruption of epithelial architecture is a hallmark of human malignant cancers, yet whether and how epithelial deformation influences tumor progression has been elusive. Here, through a genetic screen in <em>Drosophila</em> eye disc, we explored mutations that potently promoted Ras-activated (Ras<sup>V12</sup>) tumor growth and identified <em>eyes absent</em> (<em>eya</em>), an eye determination gene, whose mutation compromised tissue growth but synergized with Ras<sup>V12</sup> to cause massive overgrowth. Furthermore, induction of cell-fate switch by mis-expression of <em>Abd-B</em> in the eye disc also induced massive Ras<sup>V12</sup> overgrowth. Mechanistically, cell-fate switch caused epithelial invagination accompanied by partial mislocalization of the transmembrane receptor Domeless (Dome) from the apical to the basal membrane of the eye epithelium, where its ligand Unpaired3 (Upd3) is present. This led to JAK-STAT activation that cooperates with Ras<sup>V12</sup> to drive tumor progression. Our data provide a mechanistic explanation for how cell-fate switch and subsequent epithelial deformation creates a cancer-prone environment in the epithelium.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 4","pages":"Article 112191"},"PeriodicalIF":4.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Witness based nonlinear detection of quantum entanglement

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-10 DOI: 10.1016/j.isci.2025.112174

Yiding Wang , Tinggui Zhang , Xiaofen Huang , Shao-Ming Fei

引用次数: 0