iSciencePub Date : 2025-05-14DOI: 10.1016/j.isci.2025.112659
Diandian Cheng , Christopher T. Clark , Quinton Smith
{"title":"Advances in engineered models of peri-gastrulation","authors":"Diandian Cheng , Christopher T. Clark , Quinton Smith","doi":"10.1016/j.isci.2025.112659","DOIUrl":"10.1016/j.isci.2025.112659","url":null,"abstract":"<div><div>Studying human development presents significant ethical and technical challenges. Yet, the integration of stem cell technology and engineering tools has provided unprecedented insights into early lineage specification and the morphogenetic events that shape human development. Pre-gastrulation models, such as blastoids, replicate aspects of blastocyst formation and implantation, enabling research on early lineage specification and embryo-maternal interactions. Gastrulation models, including 2D micropatterned systems and 3D gastruloid constructs, provide valuable insights into cell differentiation, signaling pathways, and tissue organization during germ layer formation. Beyond gastrulation, post-gastrulation models, including somitoids, mimicking early somitogenesis and axial elongation, offer opportunities for studying segmentation and neural tube formation. Together, these systems enable investigation into the peri-gastrulation stage of mammalian development. Here, we discuss the integration of engineering technologies, including micropatterned substrates, microfluidic systems, and synthetic biology tools, in enhancing the precision of these models, allowing for a greater understanding of the early stages of human development.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112659"},"PeriodicalIF":4.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144167580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2025-05-13DOI: 10.1016/j.isci.2025.112650
Honghua Chen , Minhui Zhang , Tianyi Ye , Max A. Wolpert , Nai Ding
{"title":"Low-frequency cortical activity reflects context-dependent parsing of word sequences","authors":"Honghua Chen , Minhui Zhang , Tianyi Ye , Max A. Wolpert , Nai Ding","doi":"10.1016/j.isci.2025.112650","DOIUrl":"10.1016/j.isci.2025.112650","url":null,"abstract":"<div><div>During speech listening, it has been hypothesized that the brain builds representations of linguistic structures like sentences, which are tracked by neural activity entrained to the rhythm of these structures. Alternatively, others proposed that these sentence-tracking neural activities may reflect the predictability or syntactic properties of individual words. Here, to disentangle the neural responses to sentences and words, we design word sequences that are parsed into different sentences in different contexts. By analyzing neural activity recorded by magnetoencephalography, we find that low-frequency neural activity strongly depends on context—the difference between MEG responses to the same word sequence in two contexts yields a low-frequency signal, which precisely tracks sentences. The predictability and syntactic properties of words can partly explain the neural response in each context but not the difference between contexts. In summary, low-frequency neural activity encodes sentences and can reliably reflect how same-word sequences are parsed in different contexts.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112650"},"PeriodicalIF":4.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2025-05-13DOI: 10.1016/j.isci.2025.112649
Alvaro García , M. Isabel Aller , Ana V. Paternain , Juan Lerma
{"title":"Central role of regular firing neurons of centrolateral amygdala in affective behaviors","authors":"Alvaro García , M. Isabel Aller , Ana V. Paternain , Juan Lerma","doi":"10.1016/j.isci.2025.112649","DOIUrl":"10.1016/j.isci.2025.112649","url":null,"abstract":"<div><div>Anxiety and depression are highly prevalent psychiatric disorders with poorly understood neural mechanisms. The amygdala, particularly its hyperactivity, is strongly implicated in anxiety. Mice overexpressing the <em>Grik4</em> gene display anxiety, depression, social deficits, and disrupted amygdala excitability, inducing output circuit imbalance. To dissect the role of specific amygdala neuron populations, we created mice with extra copies of <em>Grik4</em> and floxed native alleles. We normalized <em>Grik4</em> dosage selectively in the basolateral amygdala (BLA) pyramidal cells via stereotaxic injection of AAV-CRE-GFP, using AAV-GFP as a control. Electrophysiological recordings from centrolateral amygdala (CeL) revealed that the normalization of <em>Grik4</em> restored synaptic strength in regular but not late firing neurons. Behaviorally, this intervention reversed anxiety, depression, and social deficits, but not object recognition memory impairments. These results highlight the critical role of regular firing CeL neurons in affective disorders and suggest that targeting their activity may offer new strategies for treating anxiety and depression.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112649"},"PeriodicalIF":4.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2025-05-12DOI: 10.1016/j.isci.2025.112634
Xiao-Fen Qiu (邱晓芬) , Cheng-Ming He (何程明) , Yan-Mei Zeng (曾艳梅) , Xiao-Ling Deng (邓晓玲) , Guo-Lin Liang (梁国林) , Ming-Xing Zhong (钟明星) , Min Zou (邹民) , Xiu-Juan Xiong (熊秀娟) , Jing-Dong Zhang (张敬东) , Yan Ye (叶燕) , Qing Niu (牛卿) , Xiao-Li Chen (陈晓梨)
{"title":"Cytohesin-4/ARF6 facilitates the progression of acute myeloid leukemia through activating PIK3R5/PI3K/AKT pathway","authors":"Xiao-Fen Qiu (邱晓芬) , Cheng-Ming He (何程明) , Yan-Mei Zeng (曾艳梅) , Xiao-Ling Deng (邓晓玲) , Guo-Lin Liang (梁国林) , Ming-Xing Zhong (钟明星) , Min Zou (邹民) , Xiu-Juan Xiong (熊秀娟) , Jing-Dong Zhang (张敬东) , Yan Ye (叶燕) , Qing Niu (牛卿) , Xiao-Li Chen (陈晓梨)","doi":"10.1016/j.isci.2025.112634","DOIUrl":"10.1016/j.isci.2025.112634","url":null,"abstract":"<div><div><em>In silico</em> analysis revealed an elevated expression of cytohesin-4 (CYTH4) in acute myeloid leukemia (AML) cells, correlating with a poorer prognosis for AML patients. However, its role in AML is not fully understood. Our study using loss-of-function assays identified CYTH4 as an oncogene promoting leukemogenesis. Silencing CYTH4 in MV4-11 and THP-1 cells reduced cell proliferation and colony formation, and induced apoptosis and cell-cycle arrest at G0/G1, whereas overexpression had no significant impact. CYTH4 silencing also increased chemosensitivity to cytarabine. In a THP-1 xenograft model, CYTH4 silencing slowed AML progression and reduced leukemic cell homing and infiltration. Mechanistically, CYTH4 silencing inhibited PI3K/AKT pathway by lowering PIK3R5 and decreased ARF6-GTP levels, as confirmed by pull-down assays. Overexpression of PIK3R5 and AKT activation via SC-79 successfully countered the cellular dysfunctions from CYTH4 silencing. Thus, CYTH4 may play a role in AML progression, and targeting its pathway could be a promising anti-leukemic treatment strategy.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112634"},"PeriodicalIF":4.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2025-05-12DOI: 10.1016/j.isci.2025.112640
Ying Tian , Hangpeng Xu , Yanyan Yang , Chuanxi Zhang , Jianping Chen , Junmin Li , Jiabao Lu
{"title":"Functional proteomic insights into the lateral oviduct-associated secretions of a bean bug","authors":"Ying Tian , Hangpeng Xu , Yanyan Yang , Chuanxi Zhang , Jianping Chen , Junmin Li , Jiabao Lu","doi":"10.1016/j.isci.2025.112640","DOIUrl":"10.1016/j.isci.2025.112640","url":null,"abstract":"<div><div>The secretions within the lateral oviduct lumen of the insect female reproductive tract (FRT) play crucial roles in reproduction, yet their protein composition and functional mechanisms remain poorly understood. In this study, we revealed that the lateral oviduct of the bean bug, <em>Riptortus pedestris</em>, is composed of an outer muscle layer and an inner epithelium with a microvillar border. Proteomic analysis identified 159 FRT-highly expressed proteins, with functional characterization focusing on 10 putative secretory proteins, including 2 ovary-specific (<em>RpLoap2</em> and <em>RpLoap4</em>), 7 oviduct-specific (<em>RpLoap3</em> and <em>RpLoap5-10</em>), and 1 ovary-highly expressed (<em>RpLoap1</em>) genes. Notably, RNAi-mediated knockdown of <em>RpLoap2</em> severely impaired choriogenesis, resulting in complete reproductive failure. These findings provide valuable insights into insect reproduction biology from the perspective of lateral oviduct–associated secretions and establish RpLoap2 as essential for successful reproduction in <em>R. pedestris</em>.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112640"},"PeriodicalIF":4.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2025-05-12DOI: 10.1016/j.isci.2025.112636
Fatima Gunter-Rahman , Shayna Mallett , Frédérique White , Pierre-Étienne Jacques , Ravikiran M. Raju , Marie-France Hivert , Eunjung Alice Lee
{"title":"Hypoxia in extravillous trophoblasts links maternal obesity and offspring neurobehavior","authors":"Fatima Gunter-Rahman , Shayna Mallett , Frédérique White , Pierre-Étienne Jacques , Ravikiran M. Raju , Marie-France Hivert , Eunjung Alice Lee","doi":"10.1016/j.isci.2025.112636","DOIUrl":"10.1016/j.isci.2025.112636","url":null,"abstract":"<div><div>While maternal obesity (MO) is associated with neurobehavioral impairment (NBI) in offspring, the underlying mechanisms remain unknown. The placenta is thought to play a role in fetal programming. To elucidate the association between MO and offspring NBI, we performed single-nucleus RNA-seq on maternal- and fetal-facing sides of human term placentas from MO and lean groups. MO placentas showed the upregulation of hypoxia response genes in multiple cell types, and maternal-facing hypoxia gene expression correlated with offspring NBI in an independent birth cohort, Gen3G. Extravillous trophoblasts (EVTs) showed the highest expression of NBI-correlated genes, and EVT NBI-gene expression correlated with hypoxia signatures in two cohorts. Exposing cultured EVTs to hypoxia increased NBI gene expression, and 44% of the association between maternal BMI and NBI-gene expression in EVTs was mediated by hypoxia. Our findings suggest that hypoxia in EVTs is a key process in the neurodevelopmental programming of fetal exposure to MO.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112636"},"PeriodicalIF":4.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2025-05-11DOI: 10.1016/j.isci.2025.112633
Yue Dong , Yuping Wang , Xiaoyun Liu , Yinchang Wang , Ziteng Yue , Zhanjing Wang , Sheng Wang
{"title":"Transcranial near infrared therapy reprograms metabolism to rescue sleep and place cell functionality","authors":"Yue Dong , Yuping Wang , Xiaoyun Liu , Yinchang Wang , Ziteng Yue , Zhanjing Wang , Sheng Wang","doi":"10.1016/j.isci.2025.112633","DOIUrl":"10.1016/j.isci.2025.112633","url":null,"abstract":"<div><div>Sleep disturbances exacerbate Alzheimer’s disease (AD) pathology, accelerating cognitive decline and impairing hippocampal memory functions. This study explores the therapeutic potential of transcranial near-infrared (tNIR) therapy in mitigating hippocampal dysfunction caused by chronic sleep deprivation (SD) in a tauopathy mouse model of AD. Using targeted 808 nm tNIR therapy, we observed restored cerebral blood flow, enhanced metabolic reprogramming favoring oxidative phosphorylation, and reestablished ionic homeostasis. These effects improved hippocampal oscillatory dynamics, including enhanced theta, gamma, and delta power, synchronized sharp-wave ripples (SWRs), and improved the phase-locking of place cell activity to theta and awake SWR oscillations. tNIR therapy also refined spatial encoding precision and reorganized sleep architecture, promoting slow-wave sleep while reducing REM disturbances. These findings position tNIR therapy as a promising non-invasive approach for addressing SD-driven cognitive and neural impairments, offering a novel intervention for sleep-related neurodegeneration in AD.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112633"},"PeriodicalIF":4.6,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2025-05-11DOI: 10.1016/j.isci.2025.112628
Heming Wei , Wenchen Hu , Jingtian Hu , Guoqiang He , Fufei Pang , Sridhar Krishnaswamy , Jan Nedoma , Carlos Marques
{"title":"3D printed near-infrared high-numerical aperture achromatic metalens","authors":"Heming Wei , Wenchen Hu , Jingtian Hu , Guoqiang He , Fufei Pang , Sridhar Krishnaswamy , Jan Nedoma , Carlos Marques","doi":"10.1016/j.isci.2025.112628","DOIUrl":"10.1016/j.isci.2025.112628","url":null,"abstract":"<div><div>Traditional optical Fresnel microlenses have limitations such as large size, limited optical quality for imaging, and low focusing efficiency in achromatic lenses with high NA. In contrast, metalenses rely on their subwavelength structure to modulate the phase distribution, resulting in smaller volumes and superior focusing performance. In this work, we inverse designed and fabricated an achromatic metalens with high-NA and broad wavelength range through direct laser writing using the two-photon polymerization technique. With a focal length of 19 μm, a thickness of 3.6 μm, and a numerical aperture of 0.8, the metalens exhibits an average focusing efficiency of 53.6% and an average half maximum width of 1.27 μm at the working wavelength. The measured average focusing efficiency is 50.4% within the bandwidth range of 1510 nm–1610 nm. The presented work demonstrates the great potential of 3D printing and inverse design for realizing functional meta-devices for aerospace sector.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112628"},"PeriodicalIF":4.6,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2025-05-11DOI: 10.1016/j.isci.2025.112616
Nedim Tüzün , Luc De Meester , Franz Hölker
{"title":"Eco-evolutionary feedbacks under artificial light at night","authors":"Nedim Tüzün , Luc De Meester , Franz Hölker","doi":"10.1016/j.isci.2025.112616","DOIUrl":"10.1016/j.isci.2025.112616","url":null,"abstract":"<div><div>Artificial light at night (ALAN) is an omnipresent anthropogenic stressor disrupting ecological interactions, potentially driving rapid evolutionary change. However, evidence for genetic adaptation to ALAN remains limited, with ecological responses dominating observed effects. Here, we critically review current evidence for evolution under ALAN and propose that interactions between ecological and evolutionary processes—so-called eco-evolutionary feedbacks—may obscure direct evolutionary signals. We argue for more common-garden experiments to disentangle genetic adaptation from environmentally induced plasticity, for multiple study organisms. Using a conceptual framework of an urban freshwater pond and a key ecological interactor, the water flea <em>Daphnia</em>, we illustrate how ALAN may affect key ecological phenomena, including diel vertical migration, parasite infection, and top-down control of algae, and may impose complex and cascading selection pressures. Recognizing interactions between ecological and evolutionary processes provides new insights on how light pollution can influence ecosystem health and inform conservation strategies in increasingly illuminated environments.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112616"},"PeriodicalIF":4.6,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}