iScience最新文献_第6页

Targeted labeling and depletion of alveolar macrophages using VeDTR mouse technology

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-02-09 DOI: 10.1016/j.isci.2025.111975

Yuki Nakayama , Miwa Sasai , Ayumi Kuratani , Masaaki Okamoto , Daisuke Okuzaki , Kentaro Yamamoto , Chikako Ono , Masaya Yamaguchi , Shigetada Kawabata , Noriko Shinjyo , Yasutaka Okabe , Yoshiharu Matsuura , Manabu Ato , Masahiro Yamamoto

{"title":"Targeted labeling and depletion of alveolar macrophages using VeDTR mouse technology","authors":"Yuki Nakayama , Miwa Sasai , Ayumi Kuratani , Masaaki Okamoto , Daisuke Okuzaki , Kentaro Yamamoto , Chikako Ono , Masaya Yamaguchi , Shigetada Kawabata , Noriko Shinjyo , Yasutaka Okabe , Yoshiharu Matsuura , Manabu Ato , Masahiro Yamamoto","doi":"10.1016/j.isci.2025.111975","DOIUrl":"10.1016/j.isci.2025.111975","url":null,"abstract":"<div><div>Alveolar macrophages (AMs) are essential for maintaining lung homeostasis. However, their roles in respiratory infections have been controversial because the methods of depleting them have often suffered from poor cell selectivity. To resolve this problem, we here used VeDTR technology to generate a transgenic mouse line in which AMs can be specifically depleted using diphtheria toxin. When various respiratory infections were examined using this system, we found that AMs prevented the proliferation of <em>Mycobacterium abscessus</em>. This result differed from previous findings using clodronate liposomes to deplete macrophages. We also revealed that the disappearance of AMs contributes to the reduction of bacterial load in the lungs and that AMs are indispensable for GM-CSF-mediated defense against <em>M. abscessus</em> infection. Taken together, the development of an AM-specific depletion system has provided an opportunity to study the roles of AMs in various respiratory infections from a different perspective.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111975"},"PeriodicalIF":4.6,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454918","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

Systematic benchmarking of tools for structural variation detection using short- and long-read sequencing data in pigs

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-02-08 DOI: 10.1016/j.isci.2025.111983

Sang He , Bangmin Song , Yueting Tang , Xiaolu Qu , Xingzheng Li , Xintong Yang , Qi Bao , Lingzhao Fang , Jicai Jiang , Zhonglin Tang , Guoqiang Yi

{"title":"Systematic benchmarking of tools for structural variation detection using short- and long-read sequencing data in pigs","authors":"Sang He , Bangmin Song , Yueting Tang , Xiaolu Qu , Xingzheng Li , Xintong Yang , Qi Bao , Lingzhao Fang , Jicai Jiang , Zhonglin Tang , Guoqiang Yi","doi":"10.1016/j.isci.2025.111983","DOIUrl":"10.1016/j.isci.2025.111983","url":null,"abstract":"<div><div>Evaluating diverse structural variation (SV) detection-relevant programs leveraging different algorithms has become a pressing need in humans and farm animals. We addressed this by sequencing five genetically diverse pig individuals (breeds) with short- and long-read DNA-sequencing platforms. We created the SV benchmark set for each breed and assessed the performance of 16 SV calling-relevant tools. Results showed that long-read platforms enabled detecting many SVs missed by short-read platforms with similar precision. Benchmark SVs, mainly 200–500 bp insertions/deletions, had high validation rates. The assembly-based SV calling program SVIM-asm showed superior detection performance and resource consumption. The SVs with more supporting reads, sizes under 1 kb, outside simple repeat area, in low GC content and runs of homozygosity regions, had higher detection accuracy. Alignment-based tools performed well even at 5 <span><math><mrow><mo>×</mo></mrow></math></span> depth. Our study provides systematic guidance for an optimal SV calling pipeline in pigs and other farm animals.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111983"},"PeriodicalIF":4.6,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444280","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

Observational studies of exposure to tobacco and nicotine products: Best practices for maximizing statistical precision and accuracy

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-02-08 DOI: 10.1016/j.isci.2025.111985

Gal Cohen , Steven Cook

{"title":"Observational studies of exposure to tobacco and nicotine products: Best practices for maximizing statistical precision and accuracy","authors":"Gal Cohen , Steven Cook","doi":"10.1016/j.isci.2025.111985","DOIUrl":"10.1016/j.isci.2025.111985","url":null,"abstract":"<div><div>Non-randomized observational studies can track risk-induction and -reduction associated with real-world use of non-combusted nicotine and tobacco products. The objective of this analysis was to evaluate the precision and accuracy of recent studies and to identify opportunities for further optimizing future study designs. The ROBINS framework for minimizing statistical bias was translated to specific considerations that spanned the selection and quantification of cohorts, exposure, and outcomes. These principles were then considered within the context of a recent comprehensive meta-analysis, representing 107 observational studies, which evaluated the effects of using electronic cigarettes (ECs), combusted cigarettes (CCs) and dual use of both. The meta-analysis had previously reported the relative risk from all-sources, including tobacco use and non–tobacco use. We now report the product use–specific risk associated with displacing CCs with ECs indicated from the primary references, along with observations regarding the precision of characterization of CC and EC exposure in the cited studies.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111985"},"PeriodicalIF":4.6,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527537","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

Generation of primordial germ cell-like cells by two germ plasm components, dnd1 and nanos3, in medaka (Oryzias latipes)

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-02-08 DOI: 10.1016/j.isci.2025.111977

Toshiya Nishimura , Takafumi Fujimoto

{"title":"Generation of primordial germ cell-like cells by two germ plasm components, dnd1 and nanos3, in medaka (Oryzias latipes)","authors":"Toshiya Nishimura , Takafumi Fujimoto","doi":"10.1016/j.isci.2025.111977","DOIUrl":"10.1016/j.isci.2025.111977","url":null,"abstract":"<div><div>In teleost fish, primordial germ cells (PGCs), the precursors of eggs and sperm, develop from cells that inherit maternal germ plasm (GP). Although numerous GP component genes have been identified, the minimum set of genes essential for germline formation remains unknown. Herein, we provide evidence that <em>dnd1</em> and <em>nanos3</em> synergistically induce PGC-like cells from the blastomeres of medaka embryos. One-cell stage embryos injected with <em>dnd1</em> and <em>nanos3</em> mRNA (DN-OE) showed developmental arrest before gastrulation and upregulation of PGC markers. Transplantation experiments revealed that most transplanted DN-OE blastomeres migrated into the gonadal ridge of host embryos, resulting in the production of functional eggs and sperm. Furthermore, the combination of genome editing and PGC induction techniques successfully generated transgenic knock-in medaka, demonstrating enhanced, precise, and stable gene integration. Identifying essential GP genes for PGC formation advances our understanding of germ cell development mechanisms and their biotechnological applications.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111977"},"PeriodicalIF":4.6,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444833","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

Serum-biomarker-based population screening model for hepatocellular carcinoma

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-02-08 DOI: 10.1016/j.isci.2025.111981

Wenmin Liao , Wenbin Lin , Zhonglian He , Chenyang Feng , Yuying Liu , Zixian Wang , Ruizhi Wang , Meifang He , Shuqin Dai , Ying Sun , Wei Wei , Peisong Chen , Chaofeng Li

{"title":"Serum-biomarker-based population screening model for hepatocellular carcinoma","authors":"Wenmin Liao , Wenbin Lin , Zhonglian He , Chenyang Feng , Yuying Liu , Zixian Wang , Ruizhi Wang , Meifang He , Shuqin Dai , Ying Sun , Wei Wei , Peisong Chen , Chaofeng Li","doi":"10.1016/j.isci.2025.111981","DOIUrl":"10.1016/j.isci.2025.111981","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) early identification is crucial for improving patient outcomes. Current screening methods are often complex and costly. This study developed a simplified, cost-effective HCC screening model using serum marker data. A diverse study population from two Chinese hospitals was recruited, including cancer patients, hospital patients, and healthy individuals. A two-stage screening model was created: LASSO logistic regression for preliminary screening, followed by logistic regression incorporating alpha-fetoprotein (AFP). The model’s performance was evaluated in multiple cohorts. Across five populations, the model showed strong performance with AUC-ROC ranging from 0.868 to 0.907, accuracy between 87.43% and 96.96%, and sensitivity over 75% with specificity above 90%. Compared with solely AFP models, the second-stage model improved HCC risk estimates in healthy populations, with significantly higher AUC (0.930 vs. 0.827) and net reclassification improvement (NRI) up to 56.2%. This two-stage model offers a practical, cost-efficient tool for early HCC detection, addressing a significant public health need.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111981"},"PeriodicalIF":4.6,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454916","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

The impact of high humidex on the risk of hospital admissions for urinary system diseases in Lanzhou, China: A time-series analysis

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-02-07 DOI: 10.1016/j.isci.2025.111968

Ke Xu , Qian Li , Yong-qin Cao , Li Ma , Xu-song Zhang , Jing-ze Yu , Miao-xin Liu , An-ning Zhu , Tian Tian , Ye Ruan

{"title":"The impact of high humidex on the risk of hospital admissions for urinary system diseases in Lanzhou, China: A time-series analysis","authors":"Ke Xu , Qian Li , Yong-qin Cao , Li Ma , Xu-song Zhang , Jing-ze Yu , Miao-xin Liu , An-ning Zhu , Tian Tian , Ye Ruan","doi":"10.1016/j.isci.2025.111968","DOIUrl":"10.1016/j.isci.2025.111968","url":null,"abstract":"<div><div>There is scant research on the association between humidex exposure and urinary system diseases. Hospitalization records from Lanzhou city were collected for the period 2015 to 2019, alongside daily meteorological and air pollution data for the study duration. Daily humidex was calculated using temperature and relative humidity indices. The study employed a combined approach of generalized additive models and distributed lag non-linear models (DLNMs) to estimate the exposure-lag-response relationship between humidex and hospital admissions for urinary system diseases, as well as for subgroups of diseases (urolithiasis and tubule-interstitial diseases). A total of 55,365 patients with urinary system diseases were included. The single lag effect of overall urinary system diseases was most significant on lag13 with the relative risk (RR) = 1.066 (95% confidence interval [CI]: 1.011, 1.124), while the cumulative lag effect over lag0–14 was most significant with RR = 1.387 (95% CI: 1.240, 1.550). The goal of this study was to establish an early warning system and allocate medical resources effectively to reduce hospital admissions for urinary system diseases.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111968"},"PeriodicalIF":4.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454977","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

Episodic rhythmicity is generated by a distributed neural network in the developing mammalian spinal cord

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-02-07 DOI: 10.1016/j.isci.2025.111971

Jonathan J. Milla-Cruz , Adam P. Lognon , Michelle A. Tran , Stephanie A. Di Vito , Carlotta Löer , Anchita Shonak , Matthew J. Broadhead , Gareth B. Miles , Simon A. Sharples , Patrick J. Whelan

{"title":"Episodic rhythmicity is generated by a distributed neural network in the developing mammalian spinal cord","authors":"Jonathan J. Milla-Cruz , Adam P. Lognon , Michelle A. Tran , Stephanie A. Di Vito , Carlotta Löer , Anchita Shonak , Matthew J. Broadhead , Gareth B. Miles , Simon A. Sharples , Patrick J. Whelan","doi":"10.1016/j.isci.2025.111971","DOIUrl":"10.1016/j.isci.2025.111971","url":null,"abstract":"<div><div>Spinal circuits generate locomotor rhythms, but the mechanisms behind episodic locomotor behaviors remain unclear. This study investigated dopamine-induced episodic rhythms in isolated neonatal mouse spinal cords to understand these mechanisms. The episodic rhythms were generally synchronous and propagated rostro-caudally, although occasional asynchrony was observed. Electrical stimulation of the L5 dorsal root entrained the episodic rhythms, suggesting afferent control and a distributed network. Even after transection or ventrolateral funiculus (VLF) lesions, episodic activity persisted in isolated thoracic or sacral segments, implying VLF-coupled networks. Rhythmicity was observed in VLF and dorsal root axons and was independent of cholinergic excitation via motoneurons, GABA<sub>A</sub> receptors, or dorsal inhibitory circuits. These findings suggest a flexibly coupled, distributed spinal interneuron network underlies episodic rhythmicity, providing a foundation for future investigations into how spinal circuits are modulated to produce diverse motor outputs.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111971"},"PeriodicalIF":4.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454976","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: Lymphopenia-induced lymphoproliferation drives activation of naive T cells and expansion of regulatory populations.

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-02-07 eCollection Date: 2025-02-21 DOI: 10.1016/j.isci.2025.111958

S Eldershaw, K Verma, W Croft, T Rai, F A M Kinsella, C Stephens, H Chen, J Nunnick, J Zuo, R Malladi, P Moss

引用次数: 0

WTX-L/β-arrestin2/LCN2 axis controls vulnerability to ferroptosis in gastric cancer

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-02-07 DOI: 10.1016/j.isci.2025.111964

Yangwei Xu , Xuexia Qian , Guixing Cai , Zhihao Lin , Weiye Huang , Chuangyuan Wang , Hongmei Wu , Yiqiong Zhang , Jingbo Sun , Qingling Zhang

{"title":"WTX-L/β-arrestin2/LCN2 axis controls vulnerability to ferroptosis in gastric cancer","authors":"Yangwei Xu , Xuexia Qian , Guixing Cai , Zhihao Lin , Weiye Huang , Chuangyuan Wang , Hongmei Wu , Yiqiong Zhang , Jingbo Sun , Qingling Zhang","doi":"10.1016/j.isci.2025.111964","DOIUrl":"10.1016/j.isci.2025.111964","url":null,"abstract":"<div><div>Gastric cancer (GC) is one of the most prevalent and lethal cancers worldwide. Ferroptosis is a form of iron-dependent regulated cell death emerging as a promising strategy for cancer therapy, whereas the regulation mechanism remains unclear. WTX has been recognized as a potential tumor suppressor, but attempts at targeted therapy have not achieved substantial progress. Further research into the structure, function, and mechanisms is urgently needed. Herein, we identified a long isoform of WTX (WTX-L) as a potent ferroptosis effector in GC. Mechanistically, WTX-L competitively interacts with β-arrestin2, disrupting its direct binding to IκBα and subsequently activating the NF-κB/LCN2 pathway. LCN2 further triggers ferroptosis by significantly increasing the labile Fe<sup>2+</sup> pool and promoting excessive lipid peroxidation. Blockade of the WTX-L/β-arrestin2/NF-κB/LCN2 axis significantly diminished the activity of ferroptosis inducers (erastin and RSL3) <em>in vivo</em>. Collectively, these findings reveal that targeting the ferroptosis vulnerabilities through WTX-L may represent a promising strategy for GC.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111964"},"PeriodicalIF":4.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512178","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

Balancing postural control and motor inhibition during gait initiation

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-02-07 DOI: 10.1016/j.isci.2025.111970

Lorenzo Fiori , Surabhi Ramawat , Isabel Beatrice Marc , Valentina Giuffrida , Alberto Ranavolo , Francesco Draicchio , Pierpaolo Pani , Stefano Ferraina , Emiliano Brunamonti

{"title":"Balancing postural control and motor inhibition during gait initiation","authors":"Lorenzo Fiori , Surabhi Ramawat , Isabel Beatrice Marc , Valentina Giuffrida , Alberto Ranavolo , Francesco Draicchio , Pierpaolo Pani , Stefano Ferraina , Emiliano Brunamonti","doi":"10.1016/j.isci.2025.111970","DOIUrl":"10.1016/j.isci.2025.111970","url":null,"abstract":"<div><div>This study examines the relationship between stopping a planned gait initiation due to sudden environmental changes and maintaining body stability. Using a gait initiation version of the Stop Signal Task (SST), we studied changes in anticipatory postural adjustments (APAs) during gait initiation and suppression. We found that trial-level variables, such as the time to start or stop stepping, interacted with biomechanical factors like the center of mass displacement relative to the base of support affecting performance. A critical biomechanical threshold was identified, beyond which stopping movement was unlikely. These findings highlight the strong link between limb action control and body equilibrium, offering a framework within a motor control paradigm. By integrating biomechanical elements, the model effectively simulates real-life scenarios, identifying key variables for studying neural correlations between action and postural control, and aiding in the development of injury prevention and rehabilitation tools for individuals with movement and posture impairments.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111970"},"PeriodicalIF":4.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474147","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