iScience最新文献_第10页

NFAT single-deficient murine T cells reduce the risk of aGvHD while controlling cytomegalovirus infection.

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-02-01 eCollection Date: 2025-02-21 DOI: 10.1016/j.isci.2025.111937

Nadine Hundhausen, Snigdha Majumder, Yin Xiao, Sigrun S Haeusl, Helen Goehler, Rishav Seal, Cristina M Chiarolla, Andreas Rosenwald, Matthias Eyrich, Luka Cicin-Sain, Friederike Berberich-Siebelt

{"title":"NFAT single-deficient murine T cells reduce the risk of aGvHD while controlling cytomegalovirus infection.","authors":"Nadine Hundhausen, Snigdha Majumder, Yin Xiao, Sigrun S Haeusl, Helen Goehler, Rishav Seal, Cristina M Chiarolla, Andreas Rosenwald, Matthias Eyrich, Luka Cicin-Sain, Friederike Berberich-Siebelt","doi":"10.1016/j.isci.2025.111937","DOIUrl":"https://doi.org/10.1016/j.isci.2025.111937","url":null,"abstract":"<p><p>NFAT is a family of transcription factors whose activation is inhibited by calcineurin inhibitors (CNIs). In allogeneic hematopoietic stem cell transplantation (allo-HCT), CNIs are employed to prevent and treat graft-versus-host disease (GvHD). Unfortunately, control of cytomegalovirus (CMV), which exacerbates clinical outcomes, is simultaneously lost. Since single NFAT deficiency in T cells ameliorates GvHD in our major mismatch model, we investigated whether protection is maintained during CMV infection. Reassuringly, NFAT-deficient T cells still improved GvHD upon acute CMV infection and after allo-HCT in latently CMV-infected mice, showing reduced proinflammatory and cytotoxic potential. In sharp contrast, CMV-specific NFAT-deficient CD8<sup>+</sup> inflated memory T cells expanded more and with higher levels of interferon gamma (IFN-γ) and GzmB expression, effectively controlling CMV. Notably, NFAT-deficient inflated memory T cells could migrate to non-lymphoid tissues and fight CMV. Therefore, CMV infection does not interfere with the protective effect of NFAT inhibition to attenuate GvHD while allowing an anti-CMV response.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 2","pages":"111937"},"PeriodicalIF":4.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539765","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

Mrgprb4-lineage neurons indispensable in pressure induced pleasant sensation are polymodal.

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-02-01 eCollection Date: 2025-02-21 DOI: 10.1016/j.isci.2025.111940

Longhua Du, Hongyi Cheng, Xiang Cui, Qianan Cao, Xia Li, Shuya Wang, Xiaoxi Wang, Yun Liu, Bing Zhu, Xinyan Gao, Kun Liu

{"title":"Mrgprb4-lineage neurons indispensable in pressure induced pleasant sensation are polymodal.","authors":"Longhua Du, Hongyi Cheng, Xiang Cui, Qianan Cao, Xia Li, Shuya Wang, Xiaoxi Wang, Yun Liu, Bing Zhu, Xinyan Gao, Kun Liu","doi":"10.1016/j.isci.2025.111940","DOIUrl":"10.1016/j.isci.2025.111940","url":null,"abstract":"<p><p>Pharmacogenetic activation of the Mas-related G-protein-coupled receptor b4 (Mrgprb4) neurons in the dorsal root ganglia is positively reinforcing, and these neurons can be activated by innocuous or noxious mechanical stimuli. However, direct evidence regarding the role of these neurons and how they encode diverse somatic inputs remains unclear. To address this, the mild pressure conditioned place preference (MP-CPP) was conducted to evaluate the indispensability of Mrgprb4-lineage neurons in the pleasantness caused by pressure. Mice without Mrgprb4-lineage neurons lost the preference for pressure. The number of Mrgprb4-lineage neurons activated by pressure was significantly higher than that of brush and pinch. The Ca<sup>2+</sup> transients activated by pressure and brush were higher than that of pinch. Further analysis of co-activating mechano-thermosensitive neurons showed that pressure evoked higher fluorescence than that of 0°C and 43°C. In brief, Mrgprb4-lineage neurons are needed to transmit pleasant sensation and exhibit functional polymodality.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 2","pages":"111940"},"PeriodicalIF":4.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539758","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

Uneven effects of global trade on transportation industry sustainability

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-02-01 DOI: 10.1016/j.isci.2025.111939

Kuokuo Zhao , Donglan Zha , Chaoqun Zhang , Guanglei Yang , Qunwei Wang , Hao Ding , Yueming (Lucy) Qiu

{"title":"Uneven effects of global trade on transportation industry sustainability","authors":"Kuokuo Zhao , Donglan Zha , Chaoqun Zhang , Guanglei Yang , Qunwei Wang , Hao Ding , Yueming (Lucy) Qiu","doi":"10.1016/j.isci.2025.111939","DOIUrl":"10.1016/j.isci.2025.111939","url":null,"abstract":"<div><div>The global trade in transportation industry has complex socio-economic, resource, and environmental (SRE) footprints. Linking these footprints with sustainability frameworks is crucial for driving transportation industry sustainability (TI-S). Here, we analyze these footprints and develop a TI-S assessment system with 26 SRE indicators for 16 TI-S targets. We find that global trade increases TI-S scores; developed economies excel in resource and environmental targets, developing economies progress more in employment and tax targets. For South Africa, Russia, and Australia, improvements in the socio-economic target scores do not offset decreases in resource and environmental target scores. In terms of interaction between the targets, global trade enhances synergies among the 16 targets in developed economies; this is not consistently the case for developing economies. These findings highlight the heterogeneous impact of trade on TI-S. The paper closes by proposing measures to promote TI-S progress, which could help inform adjustments in industrial policies.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111939"},"PeriodicalIF":4.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143394366","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

Would widespread adoption of third-generation nuclear power HPR1000 enhance the mitigation of net greenhouse gas emissions?

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-01-31 DOI: 10.1016/j.isci.2025.111923

Bojie Liu , Gengyuan Liu , Hao Li , Jiang Hu , Xin Shang , Jingyue Yao , Tianran Xue , Yichi Zhang , Caocao Chen , Linyu Xu

{"title":"Would widespread adoption of third-generation nuclear power HPR1000 enhance the mitigation of net greenhouse gas emissions?","authors":"Bojie Liu , Gengyuan Liu , Hao Li , Jiang Hu , Xin Shang , Jingyue Yao , Tianran Xue , Yichi Zhang , Caocao Chen , Linyu Xu","doi":"10.1016/j.isci.2025.111923","DOIUrl":"10.1016/j.isci.2025.111923","url":null,"abstract":"<div><div>Amid the rapid deployment of third-generation nuclear power, our understanding of its actual contribution to greenhouse gas (GHG) emission reductions remains limited. In a case study focused on China’s mainstream third-generation nuclear power technology, HPR1000, we constructed a life cycle carbon accounting framework for nuclear power plants (LCCA-NPP). Our analysis encompassed the entire life cycle of HPR1000, including construction, operation, and decommissioning. The total life cycle GHG emissions for HPR1000 range from 10.66 to 11.19 Tg CO<sub>2</sub>e, with the carbon emission intensity of 10.03–10.54 g CO<sub>2</sub>e/kWh. As China advances toward its carbon neutrality objective, the contribution of nuclear power in offsetting carbon emissions from fossil fuels is projected to rise from about 3% in 2020 to 7%–8% by 2030. By the mid-century mark in 2050, it is anticipated that nuclear power will offset roughly 70% of carbon emissions from fossil energy sources.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111923"},"PeriodicalIF":4.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143430026","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

Flagellin in blood and Bifidobacterium pseudocatenulatum in gut are associated with live birth upon IVF-frozen embryo transfer. 血液中的鞭毛蛋白和肠道中的假双歧杆菌与试管婴儿冷冻胚胎移植后的活产有关。

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-01-31 eCollection Date: 2025-02-21 DOI: 10.1016/j.isci.2025.111933

Karie T C Chin, Jensen H C Yiu, Ka Wang Cheung, Lai Chun Yuen, Wylie Yan-Lok Wong, Jieling Cai, Samson W M Cheung, Raymond H W Li, Connie W Woo

{"title":"Flagellin in blood and <i>Bifidobacterium</i> <i>pseudocatenulatum</i> in gut are associated with live birth upon IVF-frozen embryo transfer.","authors":"Karie T C Chin, Jensen H C Yiu, Ka Wang Cheung, Lai Chun Yuen, Wylie Yan-Lok Wong, Jieling Cai, Samson W M Cheung, Raymond H W Li, Connie W Woo","doi":"10.1016/j.isci.2025.111933","DOIUrl":"10.1016/j.isci.2025.111933","url":null,"abstract":"<p><p>The role of gut microbiota in live birth attainment upon <i>in vitro</i> fertilization (IVF) remains unclear. We recruited 67 women, evaluated bacterial constituents in the serum, and analyzed the gut microbiota composition and functions prior to an IVF-frozen embryo transfer (FET). A higher serum flagellin level, residues from flagellated bacteria, was observed in women without live birth after FET. Twelve species showed significant differences in abundance between with and without live birth groups, of which <i>Roseburia inulinivorans</i> and <i>Bifidobacterium pseudocatenulatum</i> were the most important to predict live birth outcome. <i>R. inulinivorans</i> abundances were higher among women with high flagellin levels. The cystathionine β-synthase activity in <i>B. pseudocatenulatum</i>, which may play roles in gut integrity, was a critical factor in the negative correlation with serum flagellin and MCP1 levels. The presence of bacterial residues in the circulation may elicit systemic inflammation and decrease the chances of attaining live birth after FET.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 2","pages":"111933"},"PeriodicalIF":4.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539752","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

Identification of a group of 9-amino-acridines that selectively downregulate regulatory T cell functions through FoxP3

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-01-31 DOI: 10.1016/j.isci.2025.111931

Qian Wei , Håvard Foyn , Johannes Landskron , Shixiong Wang , Inga Hansine Rye , Sigrid Skånland , Hege Elisabeth Giercksky Russnes , Jo Klaveness , Rafi Ahmad , Kjetil Taskén

{"title":"Identification of a group of 9-amino-acridines that selectively downregulate regulatory T cell functions through FoxP3","authors":"Qian Wei , Håvard Foyn , Johannes Landskron , Shixiong Wang , Inga Hansine Rye , Sigrid Skånland , Hege Elisabeth Giercksky Russnes , Jo Klaveness , Rafi Ahmad , Kjetil Taskén","doi":"10.1016/j.isci.2025.111931","DOIUrl":"10.1016/j.isci.2025.111931","url":null,"abstract":"<div><div>FoxP3<sup>+</sup> regulatory T cells (Tregs) are responsible for immune homeostasis by suppressing excessive anti-self-immunity. Tregs facilitate tumor growth by inhibiting anti-tumor immunity. Here, we explored the targeting of FoxP3 as a basis for new immunotherapies. In a high-throughput phenotypic screening of a drug repurposing library using human primary T cells, we identified quinacrine as a FoxP3 downregulator. <em>In silico</em> searches based on the structure of quinacrine, testing of sub-libraries of analogs <em>in vitro,</em> and validation identified a subset of 9-amino-acridines that selectively abrogated Treg suppressive functions. Mechanistically, these acridines interfered with the DNA-binding activity of FoxP3 and inhibited FoxP3-regulated downstream gene regulation. Release from Treg suppression by 9-amino-acridines increased anti-tumor immune responses both in cancer patient samples and in mice in a syngeneic tumor model. Our study highlights the feasibility of screening for small molecular inhibitors of FoxP3 as an approach to pursuing Treg-based immunotherapy.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111931"},"PeriodicalIF":4.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143421662","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

Formation of brain-wide neural geometry during visual item recognition in monkeys

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-01-31 DOI: 10.1016/j.isci.2025.111936

He Chen , Jun Kunimatsu , Tomomichi Oya , Yuri Imaizumi , Yukiko Hori , Masayuki Matsumoto , Yasuhiro Tsubo , Okihide Hikosaka , Takafumi Minamimoto , Yuji Naya , Hiroshi Yamada

{"title":"Formation of brain-wide neural geometry during visual item recognition in monkeys","authors":"He Chen , Jun Kunimatsu , Tomomichi Oya , Yuri Imaizumi , Yukiko Hori , Masayuki Matsumoto , Yasuhiro Tsubo , Okihide Hikosaka , Takafumi Minamimoto , Yuji Naya , Hiroshi Yamada","doi":"10.1016/j.isci.2025.111936","DOIUrl":"10.1016/j.isci.2025.111936","url":null,"abstract":"<div><div>Neural dynamics are thought to reflect computations that relay and transform information in the brain. Previous studies have identified the neural population dynamics in many individual brain regions as a trajectory geometry, preserving a common computational motif. However, whether these populations share particular geometric patterns across brain-wide neural populations remains unclear. Here, by mapping neural dynamics widely across temporal/frontal/limbic regions in the cortical and subcortical structures of monkeys, we show that 10 neural populations, including 2,500 neurons, propagate visual item information in a stochastic manner. We found that visual inputs predominantly evoked rotational dynamics in the higher-order visual area, TE, and its downstream striatum tail, while curvy/straight dynamics appeared frequently downstream in the orbitofrontal/hippocampal network. These geometric changes were not deterministic but rather stochastic according to their respective emergence rates. Our meta-analysis results indicate that visual information propagates as a heterogeneous mixture of stochastic neural population signals in the brain.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111936"},"PeriodicalIF":4.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395016","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

SENP2-based N-terminal truncation of α-synuclein in Lewy pathology propagation.

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-01-31 eCollection Date: 2025-02-21 DOI: 10.1016/j.isci.2025.111935

Katsutoshi Taguchi, Yoshihisa Watanabe, Masaki Tanaka

{"title":"SENP2-based N-terminal truncation of α-synuclein in Lewy pathology propagation.","authors":"Katsutoshi Taguchi, Yoshihisa Watanabe, Masaki Tanaka","doi":"10.1016/j.isci.2025.111935","DOIUrl":"https://doi.org/10.1016/j.isci.2025.111935","url":null,"abstract":"<p><p>α-Synuclein (αSyn) is a major component of Lewy bodies (LBs) and Lewy neurites (LNs), which are pathological features of Parkinson's disease (PD) and dementia with Lewy bodies. In the PD brain, with disease progression, LB/LN formation is propagated from the lower brainstem to the cerebral cortex. Prion-like cell-to-cell seed transmission has been implicated as an underlying mechanism for Lewy-pathology propagation. However, the biochemical properties and production mechanism of those pathogenic seeds are unelucidated. In this study, we ascertained that the seeds released from pathological neurons that harbor LB/LN-like aggregates have the N-terminally truncated form of αSyn. This N-terminal truncation is directly catalyzed by SENP2, which is a well-known deSUMOylation enzyme. After SENP2 processing of recombinant αSyn, the SDS-resistant high-molecular oligomer formation was promoted <i>in vitro</i>. Inhibition of SENP2 activity suppressed aggregate formation and propagation in cultured neurons and mouse brains. Thus, SENP2 might be a therapeutic target in LB diseases.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 2","pages":"111935"},"PeriodicalIF":4.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539838","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

Erratum: Diffusion-limited cytokine signaling in T cell populations.

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-01-31 eCollection Date: 2025-02-21 DOI: 10.1016/j.isci.2025.111900

Patrick Brunner, Lukas Kiwitz, Lisa Li, Kevin Thurley

引用次数: 0

A rapid decline in gender bias relates to changes in subsistence practices over demographic changes in a formerly matrilineal community.

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-01-31 eCollection Date: 2025-02-21 DOI: 10.1016/j.isci.2025.111926

Yaming Huang, Pengpeng Bai, Liqiong Zhou, Ruth Mace, Juan Du

{"title":"A rapid decline in gender bias relates to changes in subsistence practices over demographic changes in a formerly matrilineal community.","authors":"Yaming Huang, Pengpeng Bai, Liqiong Zhou, Ruth Mace, Juan Du","doi":"10.1016/j.isci.2025.111926","DOIUrl":"10.1016/j.isci.2025.111926","url":null,"abstract":"<p><p>This research examines dynamics of kinship systems, emphasizing changes in gender-biased inheritance and social interaction within a formerly matrilineal community. Using demographic data over 70-year of lifespan from 17 Tibetan villages, we observe a significant shift within the predominantly matrilineal inheritance structure: a once-prevalent preference for females in older cohorts has now gone in recent generations. We explore two possible explanations: that this is driven by changes in subsistence system or by changes in sibling configuration. Our investigation reveals that a change from agriculture to non-traditional economy with more market integration marks a pivot from matrilineal to non-unilineal inheritance systems. Moreover, results from economic games conducted in two distinct survey periods (2015 and 2021) indicate that high donations for females in 2015 have become unbiased in 2021. These findings provide concrete evidence of shifts in gender preference both at the level of familial resource allocation and broader societal interactions.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 2","pages":"111926"},"PeriodicalIF":4.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539690","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