当前共找到 27 篇文献分享,本页显示第 1 - 20 篇。
1.
白鸟
(2025-10-31 23:36):
#paper Doi:10.1038/s43587-025-00935-w. The X-Age Project to construct a Chinese aging clock.Nat Aging 2025.
1.X-Age项目简介:
近日,中国衰老生物标志物联合体(ABC)启动了“X-Age项目”(又称“耄耋”计划),旨在开发一套针对中国人群的综合衰老评估系统。项目名称中的“X”象征衰老的复杂性、时间维度的延伸(如终身纵向随访)与空间范围的拓展(如多中心、多地区、多器官数据覆盖),以及对前沿技术的探索。此外,“X-Age”与英文“Sage”(智者)谐音,寓意智慧与长寿。
2.项目目标:
生物学年龄不同于时序年龄,它通过评估与衰老相关的生物学变化程度来反映个体的生理状态。该项目旨在为多样化中国人群构建稳健的衰老时钟。
识别稳健的衰老生物标志物,并构建能够捕捉“生物学年龄”的复合衰老时钟,覆盖多样化的中国人群。
3.项目实施:
提出了构建中国人群衰老时钟的方法学框架,以期为健康老龄化研究提供有益参考。
概述了X-Age的核心目标、方法框架与关键成果,包括队列招募、标准化样本采集、多模态数据获取以及时钟模型开发。
通过整合跨学科的专业力量,以深入理解衰老的复杂性与异质性,实现加速衰老的早期发现,并评估衰老干预措施的效果。
4.构建全面的组合式衰老时钟
1) 衰老生物标志物;
2)基于DNA甲基化模式的表观遗传衰老时钟;
3)多组学技术构建的高维衰老时钟;
4)稳健的衰老生物标志物(SenoMarkers);
2.
林海onrush
(2025-10-31 23:18):
#paper, PALQO: Physics-informed Model for Accelerating Large-scale Quantum Optimization,DOI:10.48550/arXiv.2509.20733。这篇论文提出了 PALQO,一种基于物理约束神经网络(PINN)的新方法用于加速大规模变分量子算法(VQAs)的训练。作者将 VQA 的参数更新过程重新表述为非线性偏微分方程(PDE)问题,并利用 PINN 在经典计算机上学习优化动力学,仅需少量量子测量数据即可预测后续参数更新,从而显著减少量子设备调用。理论分析表明,PALQO 具有良好的泛化性能,其所需训练样本数量随参数规模多项式增长。
在横场 Ising 模型、Heisenberg 模型及分子体系(如 LiH、BeH₂)等任务上的实验显示,PALQO 能在保持能量精度(误差约 (10^{-3}))的同时,将量子测量开销降低约90%,实现最高30倍加速。该方法在多体系统和量子化学计算中表现出良好的可扩展性,为在受限量子资源条件下推进大规模量子优化提供了新的思路。
arXiv,
2025-09-25T04:26:02Z.
DOI: 10.48550/arXiv.2509.20733
Abstract:
Variational quantum algorithms (VQAs) are leading strategies to reachpractical utilities of near-term quantum devices. However, the no-cloningtheorem in quantum mechanics precludes standard backpropagation, leading toprohibitive quantum resource costs when applying …
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Variational quantum algorithms (VQAs) are leading strategies to reachpractical utilities of near-term quantum devices. However, the no-cloningtheorem in quantum mechanics precludes standard backpropagation, leading toprohibitive quantum resource costs when applying VQAs to large-scale tasks. Toaddress this challenge, we reformulate the training dynamics of VQAs as anonlinear partial differential equation and propose a novel protocol thatleverages physics-informed neural networks (PINNs) to model this dynamicalsystem efficiently. Given a small amount of training trajectory data collectedfrom quantum devices, our protocol predicts the parameter updates of VQAs overmultiple iterations on the classical side, dramatically reducing quantumresource costs. Through systematic numerical experiments, we demonstrate thatour method achieves up to a 30x speedup compared to conventional methods andreduces quantum resource costs by as much as 90\% for tasks involving up to 40qubits, including ground state preparation of different quantum systems, whilemaintaining competitive accuracy. Our approach complements existing techniquesaimed at improving the efficiency of VQAs and further strengthens theirpotential for practical applications.
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3.
符毓
(2025-10-31 22:50):
#paper doi: 10.48550/arXiv.2510.10903, 2025, Towards a Unified Understanding of Robot Manipulation: A Comprehensive Survey
一篇全面涵盖机器人操作领域的全景视角综述。超 1000 篇参考系统地梳理了机器人操作领域的全景图谱,涵盖硬件与控制基础、任务与数据体系、高低层控制框架,以及跨本体与跨模态的泛化研究,并提出了一个统一的理解框架,揭示机器人如何从“执行任务”走向“理解与学习任务”。
arXiv,
2025-10-13T01:59:27Z.
DOI: 10.48550/arXiv.2510.10903
Abstract:
Embodied intelligence has witnessed remarkable progress in recent years,driven by advances in computer vision, natural language processing, and therise of large-scale multimodal models. Among its core challenges, robotmanipulation stands out …
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Embodied intelligence has witnessed remarkable progress in recent years,driven by advances in computer vision, natural language processing, and therise of large-scale multimodal models. Among its core challenges, robotmanipulation stands out as a fundamental yet intricate problem, requiring theseamless integration of perception, planning, and control to enable interactionwithin diverse and unstructured environments. This survey presents acomprehensive overview of robotic manipulation, encompassing foundationalbackground, task-organized benchmarks and datasets, and a unified taxonomy ofexisting methods. We extend the classical division between high-level planningand low-level control by broadening high-level planning to include language,code, motion, affordance, and 3D representations, while introducing a newtaxonomy of low-level learning-based control grounded in training paradigmssuch as input modeling, latent learning, and policy learning. Furthermore, weprovide the first dedicated taxonomy of key bottlenecks, focusing on datacollection, utilization, and generalization, and conclude with an extensivereview of real-world applications. Compared with prior surveys, our work offersboth a broader scope and deeper insight, serving as an accessible roadmap fornewcomers and a structured reference for experienced researchers. All relatedresources, including research papers, open-source datasets, and projects, arecurated for the community athttps://github.com/BaiShuanghao/Awesome-Robotics-Manipulation.
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4.
半面阳光
(2025-10-31 22:26):
#paper DOI: https://doi.org/10.1016/j.gim.2025.101446. eGenetics in Medicine. 2025. HCSeeker: A classification tool for human genetic variant hot and cold spots designed for PM1 and benign criteria in the ACMG-AMP guideline. PM1是ACMG的变异解读指南中的中等致病性证据标准,内容变是异位于突变热点区域和/或关键且功能明确的无良性变异功能域(如酶的活性位点)时,可视为评估其致病性的中等证据。但由于缺乏可靠的变异热点数据库,PM1标准的应用仍存在局限性。相较于热点区域,冷点区域在指南中未获重视。为优化变异分类,我们建议纳入冷点区域以支持良性分类判定。为此,我们开发了HCSeeker工具,为PM1标准及“良性”标准提供数据支持。HCSeeker采用核密度估计与期望最大化算法识别热点与冷点区域。通过HCSeeker,我们在889个基因中识别出988个热点区域和682个冷点区域,并提供公共数据库(http://www.genemed.tech/hcseeker/)供研究者和临床医生查询变异位置,从而促进美国医学遗传学与基因组学学院及分子病理学协会PM1或“良性”标准的应用。 HCSeeker工具能有效识别基因内的变异热点与冷点区域,从而提升基因变异的可解释性。
5.
钟鸣
(2025-10-31 22:11):
#paper doi:10.1038/s41562-021-01130-8 The rise of affectivism
这是2022年发表的由多个学科近百位知名学者联合撰写的一篇共识性文章,核心观点是情感主义时代正在到来。情感主义是行为主义和认知主义之后的新研究阶段,也是对前两种研究角度的补充.这是因为行为主义只关注了行为,而没有关注认知和情感,而认知主义关注的情感也仅限于记忆等认知过程。从必要性来看,情感影响我们感知世界、驱动我们的行为,还与我们的学习、记忆、决策、幸福感、心理健康等息息相关。从当前的形势看,关于情感主义的研究资金投入、研究产出都在增加;且其他学科以及人工智能等新兴技术也在越来越多的结合情感主义。从研究意义和前景来看,情感科学将对神经科学、心理学、人工智能、人文科学、社会科学都会做出积极贡献。总的来说,本文是对标题所声称观点的下的一系列支撑性结论的集合,强调情感主义的重要意义同时,指引了该领域的新趋势。
6.
哪有情可长
(2025-10-31 17:12):
#paper A pangenome of maize provides genetic insights into drought resistance. Nature Genetics, 27 October 2025,doi:10.1038/s41588-025-02378-w. 该团队的研究对象一直聚焦与玉米抗干旱逆境响应,本论文选择来自热带、亚热带和温带的广泛抗旱性和遗传起源的25种玉米的种质进行从头基因组装,并评估其在苗期抗旱指标、中度干旱、重度干旱下的谷物产量。同时联合前人已经组装的高质量基因组,共51个种质材料组装一个玉米泛基因组。其中核心基因约占24.3%。为了鉴定脱落酸在干旱反应中的作用,以及干旱响应的转录因子,发现超50%的抗旱相关基因表达受遗传变异调控,这与基因启动子区SNP影响转录因子结合的结论一致,也是玉米品种抗旱性差异的重要原因。团队还鉴定出关键抗旱基因及功能变异,ZmUGE2通过增强细胞壁机械强度提升玉米幼苗抗旱性。转基因实验证实,其过表达植株干旱下存活率和产量稳定性更高,敲除植株则抗旱性显著衰退(幼苗死亡率+40%以上)。ZmSIL2通过负调控AP2/ERF等抗逆转录因子参与抗旱响应,其表达量与抗旱性负相关。过表达植株抗旱性下降,敲除植株则因AP2/ERF上调而抗旱性增强,明确了其负调控机理。
7.
小年
(2025-10-31 16:51):
#paper doi:10.1182/blood.2021012778,Schnoeder TM, Schwarzer A, et al. PLCG1 is required for AML1-ETO leukemia stem cell self-renewal
该研究聚焦 AML1-ETO 融合基因驱动的急性髓系白血病(AML)复发难题 —— 此类患者虽缓解率高,但仅 45%-70% 能长期生存,根源在于化疗无法清除具有自我更新能力的白血病干细胞(LSC)。AML1-ETO 融合基因见于 6%-8% 的原发性 AML,在 M2 型中占比达 20%-40%,其诱导的 LSC 残留是疾病复发的核心诱因。为挖掘 LSC 靶向靶点,团队采用 DIA 高分辨率蛋白质组学,对比分析小鼠 AML1-ETO(AE)与 MLL-AF9 驱动的 LSC 及患者 CD34 + 细胞,定量 3000 余种蛋白后发现,磷脂酶 C(PLC)及钙信号通路在 AE-LSC 中显著富集,且 PLCG1 是 PLC 家族中唯一在 AE-AML 及复发患者中高表达的成员。机制研究证实,AML1-ETO 通过结合 PLCG1 启动子区域的基因间调控元件,协同 AP-1(JUN/FOS)、CREB 等转录因子激活其表达,呈剂量依赖性调控关系。在人 AE 阳性细胞系(Kasumi-1、SKNO1)中,CRISPR 敲除 PLCG1 可抑制增殖、诱导髓系分化标记物(CD13/CD14)表达,逆转 AE 介导的干性基因上调。体内实验中,AE/KRAS 突变小鼠的 PLCG1 条件性敲除模型显示,PLCG1 缺失使 LSC 数量减少、体外增殖能力丧失,移植后受体小鼠白血病发生率降低 67%,且对正常造血干细胞无影响。此外,钙调神经磷酸酶抑制剂环孢素 A(CsA)靶向 PLCG1 下游钙信号,可延迟 AE-AML 发病、延长小鼠生存期,且对其他亚型 AML 无效。
该研究首次明确 PLCG1 是 AE-LSC 的特异性依赖靶点,为开发精准清除残留病灶、降低复发的靶向疗法提供了关键依据。
Blood,
2022-2-17.
DOI: 10.1182/blood.2021012778
Abstract:
Abstract In an effort to identify novel drugs targeting fusion-oncogene–induced acute myeloid leukemia (AML), we performed high-resolution proteomic analysis. In AML1-ETO (AE)-driven AML, we uncovered a deregulation of phospholipase C …
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Abstract In an effort to identify novel drugs targeting fusion-oncogene–induced acute myeloid leukemia (AML), we performed high-resolution proteomic analysis. In AML1-ETO (AE)-driven AML, we uncovered a deregulation of phospholipase C (PLC) signaling. We identified PLCgamma 1 (PLCG1) as a specific target of the AE fusion protein that is induced after AE binding to intergenic regulatory DNA elements. Genetic inactivation of PLCG1 in murine and human AML inhibited AML1-ETO dependent self-renewal programs, leukemic proliferation, and leukemia maintenance in vivo. In contrast, PLCG1 was dispensable for normal hematopoietic stem and progenitor cell function. These findings are extended to and confirmed by pharmacologic perturbation of Ca++-signaling in AML1-ETO AML cells, indicating that the PLCG1 pathway poses an important therapeutic target for AML1-ETO+ leukemic stem cells.
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8.
徐炳祥
(2025-10-31 16:38):
#paper doi: 10.1101/gr.212241.116 Genome Research, 2018, FIND: difFerential chromatin INteractions Detection using a spatial Poisson process。差异分析是Hi-C数据分析中一个尚未被完全解决的重要课题。早期研究主要基于广义线性模型,考虑系统偏差的基础上移植基因差异表达分析中所用模型。然而这些模型忽略了Hi-C数据与基因表达数据间一个本质的差别,即Hi-C数据中相邻位点相互作用频率间存在强烈的相关关系,此相关关系的利用将有助于减少差异分析的假阳性并提高结果的稳定性。本文是第一篇系统性证明此相关关系存在的文献。本文指出,具有生物学意义的差异位点不仅本身应具有相互作用频率的显著差异,其一定半径的邻域内也应呈现此种差异。为此作者引入空间Poison过程对邻域内相互作用频率差异建模,并据此开发了一种Hi-C数据一致性度量和差异分析工具FIND。虽然FIND的性能并不十分优越,但其思想为后续三维基因组生物信息学提供了重要启示。
Genome Research,
2018-3.
DOI: 10.1101/gr.212241.116
Abstract:
Polymer-based simulations and experimental studies indicate the existence of a spatial dependency between the adjacent DNA fibers involved in the formation of chromatin loops. However, the existing strategies for detecting …
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Polymer-based simulations and experimental studies indicate the existence of a spatial dependency between the adjacent DNA fibers involved in the formation of chromatin loops. However, the existing strategies for detecting differential chromatin interactions assume that the interacting segments are spatially independent from the other segments nearby. To resolve this issue, we developed a new computational method, FIND, which considers the local spatial dependency between interacting loci. FIND uses a spatial Poisson process to detect differential chromatin interactions that show a significant difference in their interaction frequency and the interaction frequency of their neighbors. Simulation and biological data analysis show that FIND outperforms the widely used count-based methods and has a better signal-to-noise ratio.
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9.
尹志
(2025-10-31 16:37):
#paper Quantum computing and chemistry. doi: 10.1016/j.xcrp.2024.102105 文章从硬件、软件、化学应用(主要是算法)层面综述了现在量子计算在大化学领域的进展,很全面(259篇参考文献)。不过对于纠错算法、错误缓解等算法的讨论比较少。我觉得要想在至少NISQ的时期做出有用的量子计算应用,应用算法巧妙结合错误处理是必不可少的,期待更多这方面的工作。
Cell Reports Physical Science,
2024-9.
DOI: 10.1016/j.xcrp.2024.102105
Abstract:
No abstract available.
10.
Vincent
(2025-10-31 16:28):
#paper https://doi.org/10.48550/arXiv.2510.14901 Arxiv. 2025. Reasoning with Sampling: Your Base Model is Smarter Than You Think. 大语言模型(LLM)+ 强化学习(RL)在众多领域展现出了强大的推理能力,以往研究多集中于探讨强化学习如何赋予基础模型其原本不具备的能力。这篇文章另辟蹊径,提出一个发人深省的问题:是否仅通过采样,而非额外训练,就能让基础模型展现出与强化学习策略相当的推理能力?这篇文章基于模型自身的似然值,提出了一种简单的基于马尔可夫蒙特卡罗(MCMC)的迭代采样方法。实验结果显示,该方法在多种基础模型上均取得了与强化学习算法相当甚至更优的表现。更为重要的是,这一方法避免了强化学习中常见的多样性缺失问题,且无需额外数据或者训练,展现出其在不同领域中的广泛应用潜力
arXiv,
2025-10-16T17:18:11Z.
DOI: 10.48550/arXiv.2510.14901
Abstract:
Frontier reasoning models have exhibited incredible capabilities across awide array of disciplines, driven by posttraining large language models (LLMs)with reinforcement learning (RL). However, despite the widespread success ofthis paradigm, much …
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Frontier reasoning models have exhibited incredible capabilities across awide array of disciplines, driven by posttraining large language models (LLMs)with reinforcement learning (RL). However, despite the widespread success ofthis paradigm, much of the literature has been devoted to disentangling trulynovel behaviors that emerge during RL but are not present in the base models.In our work, we approach this question from a different angle, instead askingwhether comparable reasoning capabilites can be elicited from base models atinference time by pure sampling, without any additional training. Inspired byMarkov chain Monte Carlo (MCMC) techniques for sampling from sharpeneddistributions, we propose a simple iterative sampling algorithm leveraging thebase models' own likelihoods. Over different base models, we show that ouralgorithm offers substantial boosts in reasoning that nearly match and evenoutperform those from RL on a wide variety of single-shot tasks, includingMATH500, HumanEval, and GPQA. Moreover, our sampler avoids the collapse indiversity over multiple samples that is characteristic of RL-posttraining.Crucially, our method does not require training, curated datasets, or averifier, suggesting broad applicability beyond easily verifiable domains.
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11.
李翛然
(2025-10-31 13:28):
#paper The Evolving Quest for Chemical Understanding in the Quantum Age. doi: 10.1021/acs.jctc.5c01299 文章探讨了量子力学进入第二个世纪后理论化学与计算化学的范式转变。文章指出,传统基于轨道(如价键理论、分子轨道理论)和基于密度(如密度泛函理论)的方法虽为领域奠定了计算与概念基础,但机器学习和量子计算的出现引入了全新的表示、推理与理解范式。
作者从本体论、认识论和涌现性视角回顾了过去一个世纪化学理解的发展,强调化学概念(如芳香性、电负性、反应性)并非仅还原为物理基本定律,而是作为连接化学理论与理解的关键支架涌现而来。文章提出一个从化学理论基本变量中获取化学理解的通用框架,并将其扩展至深度学习和量子计算领域,建议通过机器学习特征和量子比特分别挖掘新理解
。
文章倡导以“分层建模”(hierarchical modeling)替代传统的“多尺度建模”,因其能整合跨尺度抽象、捕捉涌现行为,并促进复杂层级系统的概念创新。最终结论认为,化学理解的未来不仅依赖于求解更复杂的物理方程,更需认识论转变,包括概念多元性、认识适应性和对分子系统多层本体结构的深入理解。
该研究呼应了作者此前在《ACS Physical Chemistry Au》(2024年)中的观点,即机器学习和量子计算将推动化学概念理解的新范式,但需克服算法与硬件障碍
Journal of Chemical Theory and Computation,
2025-10-28.
DOI: 10.1021/acs.jctc.5c01299
Abstract:
No abstract available.
12.
cellsarts
(2025-10-31 12:48):
paper DOl:10.18699/vjgb-25-21 2025-04-01影响因子:1.0 JCR分区:3区-农业:综合中科院分区:4区 3D cell culture models: how to obtain and characterize the main models
3D细胞培养模型:如何获得并表征主要模型 多年来,恶性肿瘤研究中的金标准一直是体外培养肿瘤(3D培养)已加入到现代生物医学研究的武器库中。3D培养再现了组织拓扑的组织特异性特征。这使得它们在细胞分化、代谢和药物耐药发外胞,休内异种格植或其关修饰古百具有相子期以程典的价值、这样的学到工经设许多机究小的日于基成的在化的究,其且可以显者家少司物的3的发量,例0在种名字所发领及,在兰用文成中,30号东限进其形可国技术 有可波有文来、唱苏条件 的合间8 以及已地电进空为能进1分个都有其独特的特征,在实验中使用特定模型时应予以考虑。最简单的3D培养是球状体模型,它们是漂浮的球形细胞聚集体。类器官是一种更复杂的3D模型,其中类。在细胞组织方面,3D培养分为“球状体模型”、"然器已程却"河二内器巨利“微华红”。该些模地名通过将不同类型的细胞组合成单一结构,球状体和类器官可以作为形成微组织的基座一种模仿特定组织表由能够自我更新和分化的于细胞(SCs)在模型内形成自组织3D结构。芯片上的器官模型是模拟体内器官和型的混合3D模型,包含组织特异性的细胞外基质(ECM)成分。本综述简要介绍了3D细胞培养的历史。它描述了在实体瘤的免疫肿瘤学码目"球状体准模型"、“类器官模型"、“芯片上的器官”模型和“微组织"的主要特点和前景
Vavilov Journal of Genetics and Breeding,
2025-4-10.
DOI: 10.18699/vjgb-25-21
Abstract:
For many years, the gold standard in the study of malignant tumors has been the in vitro culture of tumor cells, in vivo xenografts or genetically modified animal models. Meanwhile, …
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For many years, the gold standard in the study of malignant tumors has been the in vitro culture of tumor cells, in vivo xenografts or genetically modified animal models. Meanwhile, three-dimensional cell models (3D cultures) have been added to the arsenal of modern biomedical research. 3D cultures reproduce tissue-specific features of tissue topology. This makes them relevant tissue models in terms of cell differentiation, metabolism and the development of drug resistance. Such models are already being used by many research groups for both basic and translational research, and may substantially reduce the number of animal studies, for example in the field of oncological research. In the current literature, 3D cultures are classified according to the technique of their formation (with or without a scaffold), cultivation conditions (static or dynamic), as well as their cellular organization and function. In terms of cellular organization, 3D cultures are divided into “spheroid models”, “organoids”, “organs-ona-chip” and “microtissues”. Each of these models has its own unique features, which should be taken into account when using a particular model in an experiment. The simplest 3D cultures are spheroid models which are floating spherical cell aggregates. An organoid is a more complex 3D model, in which a self-organizing 3D structure is formed from stem cells (SCs) capable of self-renewal and differentiation within the model. Organ-on-a-chip models are chips of microfluidic systems that simulate dynamic physical and biological processes found in organs and tissues in vitro. By combining different cell types into a single structure, spheroids and organoids can act as a basis for the formation of a microtissue – a hybrid 3D model imitating a specific tissue phenotype and containing tissuespecific extracellular matrix (ECM) components. This review presents a brief history of 3D cell culture. It describes the main characteristics and perspectives of the use of “spheroid models”, “organoids”, “organ-on-a-chip” models and “microtissues” in immune oncology research of solid tumors.
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13.
cellsarts
(2025-10-31 12:47):
paper DOl:10.1016/i.aca.2024.342413 2024-05-01影响因子:3.6 JCR分区:2区-分析化学中科院分区:年发文量:35 Review: 3D cell models for organ-on-a-chip applications
综述:用于器官芯片应用的3D细胞模型遞r摘要:二维(2D)培养并不能完全反映人体器官的生理功能和所用疗法的实际效果。因此,三维(3D)模型在牛物分析科学中的应用日益广泛。,反映人体的体内特性,并允许我们获得比标准临床前模型更可靠的结果。这样的3D模型可以用来理解组织/器官对选定的生物物理和生化因素、病理条件(它们形成的机制)、药物筛选或器官。本综述描述了在微流控系统中获得的3D模型。这些包括球状体/聚集体、水凝胶培养、多层结构、类器官或生物材料上的培养。接下来,介绍了在器官芯片系统中形成不同3D培养的方法,并讨论了此类器官芯片系统的例子。最后,涵盖了3D细胞芯片系统的当前应用和未来展望。
Abstract:
No abstract available.
14.
颜林林
(2025-10-31 01:16):
#paper doi:10.1186/s13059-025-03786-1, Genome Biology, 2025, Systematic discovery of subcellular RNA patterns in the gut epithelium. 这篇文章是将空间转录组技术向亚细胞水平推进的一种尝试。文章作者使用了一种名为APEX-seq的技术,配合MERFISH空间转录组技术,来研究成年小鼠的肠道类器官组织,在“顶端-基底”(指肠上皮细胞的两极,顶端指面朝肠腔的一面)轴空间方向上不同基因表达的模式。APEX(抗坏血酸过氧化物酶突变体)经基因工程改造,与顶端特异表达的膜蛋白DPP4融合,在加入过氧化氢(H₂O₂)和生物素-苯酚时,APEX2 能催化自由基在 ≤20 nm 范围内共价标记 RNA,随后裂解、链霉亲和素富集并测序,从而得到空间上处于“顶端”区域的转录组。通过上述技术,本文绘制出 1 000 余基因的顶端-基底极性图谱:营养相关 RNA 顶端成簇且可随进食重塑,机制拆成翻译依赖与独立两路,并鉴定 SNRNP70 为 Lct-3′UTR 介导的胞质定位因子。数据已公开,可作肠上皮区室-平均 RNA 参考图。
Genome Biology,
2025-10-29.
DOI: 10.1186/s13059-025-03786-1
Abstract:
Abstract Background Subcellular RNA localization is crucial for the spatio-temporal control of protein synthesis and underlies key processes during development, homeostasis, and disease. In epithelial cells, RNA can localize asymmetrically …
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Abstract Background Subcellular RNA localization is crucial for the spatio-temporal control of protein synthesis and underlies key processes during development, homeostasis, and disease. In epithelial cells, RNA can localize asymmetrically along the apico-basal axis. Yet, the localization of most transcripts as well as the diversity of patterns that they adopt remains unexplored. Results Here, we use APEX-seq for proximity labeling and MERFISH for spatial transcriptomics to map subcellular transcript localization in intestinal organoids and tissue from adult mice. Many transcripts present localization bias, often localizing in granular structures. We uncover intrinsic and environmental factors that influence the formation of these patterns. Additionally, we identify translation-dependent and -independent localization patterns and pinpoint the role of 3′ untranslated regions and RNA-binding proteins. Conclusions This subcellular RNA atlas presents a detailed resource for understanding intestinal physiology.
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15.
孤舟蓑笠翁
(2025-10-29 20:48):
paper 【doi】https://doi.org/10.1073/pnas.2511715122;【发表年份】2025年;【期刊】PNAS;【标题】The genetic lottery goes to school: Better schools compensate for the effects of students' genetic differences。【内容总结】这项研究想搞清楚好学校能不能帮助那些天生遗传上不占优势的孩子,缩小他们和遗传优势孩子之间的学习差距;为了得到可靠的结论,研究者用了两种巧妙的方法来分别衡量“基因”和“学校环境”的纯粹影响:首先,他们利用挪威一个大型家庭数据库(MoBa)中的父母和孩子三人的基因数据,通过计算孩子的教育多基因指数(PGIEA)并减去父母遗传的部分,得到了孩子自身随机的“基因彩票”部分,这就像是在同一个家庭内部做比较,排除了家庭背景的干扰;其次,他们用挪威全国学生的考试成绩记录,计算了“学校增值”(VAd),这个指标通过比较学生在一学年内的进步程度来评估学校的好坏,并且控制了学生之前的成绩,从而尽量排除了好学生扎堆上好学校造成的偏差;结果发现,对于阅读能力,好学校确实能补偿遗传劣势:在质量高出平均水平的学校(VAd高1个标准差)里,遗传优势(PGIEA高1个标准差)对阅读成绩的提升作用会减弱大约6%,这意味着好学校让遗传差异变得不那么重要了,主要是帮助了遗传禀赋较低的学生;但是,在数学计算能力上,没有发现这种补偿效应,研究者认为这可能是因为数学成绩更依赖于之前打下的基础(持续性更强),所以学校在一年内能改变的空间相对较小;总之,这项研究说明,投资改善学校质量,特别是针对阅读教学,是减少由遗传差异导致的教育不平等的一个有效办法。
Proceedings of the National Academy of Sciences,
2025-10-28.
DOI: 10.1073/pnas.2511715122
Abstract:
In this paper, we investigate whether better schools can compensate for the effects of children’s genetic differences. To this end, we combine data from the Norwegian Mother, Father, and Child …
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In this paper, we investigate whether better schools can compensate for the effects of children’s genetic differences. To this end, we combine data from the Norwegian Mother, Father, and Child Cohort Study (MoBa) with Norwegian register data to estimate the interaction between measures of children’s predisposition to education and school quality. We use MoBa’s genetic data to compute polygenic indices for educational attainment ( PGI EA ). Importantly, MoBa includes genetic data on mother-father-child trios, allowing us to identify causal genetic effects using within-family variation. We calculate school value-added measures from Norwegian register data, allowing us to causally estimate school quality effects. Leveraging the advantages of both data sources, we provide a causally identified study of gene–environment interactions in the school context. We find evidence for substitutability of PGI EA and school quality in reading but not numeracy: A 1 SD increase of school quality decreases the impact of a 1 SD increase of PGI EA on reading test scores by 6%. The substitutability arises through gains of students at the lower end of the PGI EA distribution. This suggests that investments in school quality may help reduce educational inequalities arising from genetic differences between students.
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16.
刘昊辰
(2025-10-27 14:21):
#paper Strongly Solving 2048 4×3. 本文由日本东京大学研究者提出,成功强解了 2048 游戏的 4×3 变体(2048₄ₓ₃),核心关键技术是基于 ”年龄(age)”(定义为棋盘上所有方块数字之和)对状态空间进行划分 —— 状态与后续动作后的过渡态(afterstate)年龄保持不变,过渡态到新状态时年龄因新增方块(2 或 4)增加 2 或 4,据此可分阶段枚举状态并控制内存占用;同时采用Elias-Fano 编码实现状态的紧凑存储,将约 4.4TiB 的原始存储需求压缩至 1.4TiB(最优玩法专用存储仅需 300GiB)。研究结果显示,最常见初始状态(两个 2 方块,年龄 4)的最优策略期望得分为50724.26,可到达状态数与过渡态数分别为1.15×10¹²和7.40×10¹¹,且验证了 “生成大数字方块(如 2048)时难度显著提升” 等玩家直觉。下载地址:https://arxiv.org/pdf/2510.04580
arXiv,
2025-10-06T08:31:59Z.
DOI: 10.48550/arXiv.2510.04580
Abstract:
2048 is a stochastic single-player game involving 16 cells on a 4 by 4 grid,where a player chooses a direction among up, down, left, and right to obtain ascore by …
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2048 is a stochastic single-player game involving 16 cells on a 4 by 4 grid,where a player chooses a direction among up, down, left, and right to obtain ascore by merging two tiles with the same number located in neighboring cellsalong the chosen direction. This paper presents that a variant 2048-4x3 12cells on a 4 by 3 board, one row smaller than the original, has been stronglysolved. In this variant, the expected score achieved by an optimal strategy isabout $50724.26$ for the most common initial states: ones with two tiles ofnumber 2. The numbers of reachable states and afterstates are identified to be$1,152,817,492,752$ and $739,648,886,170$, respectively. The key technique isto partition state space by the sum of tile numbers on a board, which we callthe age of a state. An age is invariant between a state and its successiveafterstate after any valid action and is increased two or four by stochasticresponse from the environment. Therefore, we can partition state space by agesand enumerate all (after)states of an age depending only on states with therecent ages. Similarly, we can identify (after)state values by going along withages in decreasing order.
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17.
孤舟蓑笠翁
(2025-10-19 21:12):
paper 【doi】10.1016/j.cell.2025.09.021;【发表年份】2025年;【期刊】Cell;【标题】CRATER tumor niches facilitate CD8+ T cell engagement and correspond with immunotherapy success。【内容总结】本研究旨在揭示免疫治疗中CD8+ T细胞与肿瘤细胞相互作用的空间动态,发现了一种称为CRATER(癌症抗原呈递和T细胞接触保留区)的特殊肿瘤微环境结构。通过斑马鱼体内长期成像、高分辨率空间转录组学(Slide-seqV2)以及人类黑色素瘤的多重免疫荧光分析,研究发现CRATER是位于肿瘤-基质边界的口袋状区域,富含抗原呈递分子(如B2M和HLA-A),并聚集了最高密度的CD8+ T细胞。在斑马鱼模型中,CD8+ T细胞在CRATER内与黑色素瘤细胞形成长时间接触(类似抗原识别),免疫刺激(如CpG ODN)后CRATER扩大成为CD8+ T细胞激活(IFN-γ表达增加)和肿瘤杀伤(TUNEL+细胞密度在CRATER内显著升高)的主要位点;人类黑色素瘤中,CRATER密度在免疫检查点阻断(ICB)治疗应答者中显著高于非应答者(如治疗后活检显示CRATER线性密度增加),且CRATER内CD163+树突状细胞高表达PD-L1和抗原呈递分子。结论:CRATER是促进CD8+ T细胞介导肿瘤杀伤的关键功能单元,其密度可作为免疫治疗疗效的潜在生物标志物。
Abstract:
T cell-mediated tumor killing underlies immunotherapy success. Here, we used long-term in vivo imaging and high-resolution spatial transcriptomics of zebrafish endogenous melanoma, as well as multiplex imaging of human melanoma, …
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T cell-mediated tumor killing underlies immunotherapy success. Here, we used long-term in vivo imaging and high-resolution spatial transcriptomics of zebrafish endogenous melanoma, as well as multiplex imaging of human melanoma, to identify domains facilitating the immune response during immunotherapy. We identified cancer regions of antigen presentation and T cell engagement and retention (CRATERs) as pockets at the stroma-melanocyte boundaries of zebrafish and human melanoma. CRATERs are rich in antigen-recognition molecules, harboring the highest density of CD8 T cells in tumors. In zebrafish, CD8 T cells formed prolonged interactions with melanoma cells within CRATERs, characteristic of antigen recognition. Following immunostimulatory treatment, CRATERs expanded, becoming the major sites of activated CD8 T cell accumulation and tumor killing. In humans, elevation in CRATER density in biopsies following immune checkpoint blockade (ICB) therapy correlated with a clinical response to therapy. CRATERs are structures that show active tumor killing and may be useful as a diagnostic indicator for immunotherapy success.
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18.
龙海晨
(2025-10-17 21:47):
#paper Ji R, Ng KK, Chen W, Yang W, Zhu H, Cheung TT, Chiang CL, Wong TCL, Kong FM, Wu G, Lo CM. Comparison of clinical outcome between stereotactic body radiotherapy and radiofrequency ablation for unresectable hepatocellular carcinoma. Medicine (Baltimore). 2022 Jan 28;101(4):e28545. doi: 10.1097/MD.0000000000028545. PMID: 35089192; PMCID: PMC8797553.这是一篇对比研究,比较的是两种治疗肝细胞癌(Hepatocellular carcinoma,HCC)的方法,立体定向放射治疗(Stereotactic body radiotherapy ,SBRT)和射频消融(radiofrequency ablation,RFA)。RFA在肝脏肿瘤中的应用受到肿瘤位置的限制(肝顶、靠近内脏的包膜下区域和血管周围位置),这将排除经皮途径插入RFA针的路径。换句话说,在那些会带来严重手术创伤的情况下,需要腹腔镜或开放手术。SBRT已发展成为一种完全无创的 HCC 局部消融疗法。[ 7 ]它是一种外照射放射治疗,通过使用先进的放射计划和实施,以大分割的方式进行,每个分割中的能量剂量很高。 文章回顾性分析2018年1月至2021年1月60例不可切除的HCC患者的临床资料。 SBRT 治疗 22 例,RFA 治疗 38 例。比较短期和长期临床结果。两组之间的基线人口统计学特征没有显着差异。 SBRT 组 (81.8%) 和 RFA 组 (89.4%) 3 个月时的完全缓解率相当。两组之间的局部肿瘤控制率也相似(90.9% vs. 94.7%)。两组均未出现严重并发症(Ⅲa级或以上)。 SBRT组的1年和2年总生存率分别为88.2%和85.7%,RFA组的1年和2年总生存率分别为100%和75%。组间没有统计学显着差异(P =0 .576)。研究发现对于不可切除的 HCC,SBRT 可以达到与 RFA 相似的短期和长期临床结果。
Medicine,
2022-1-28.
DOI: 10.1097/MD.0000000000028545
Abstract:
Abstract Stereotactic body radiotherapy (SBRT) is a novel noninvasive treatment for unresectable hepatocellular carcinoma (HCC). Whether its efficacy is comparable to radiofrequency ablation (RFA), a recommended therapy for unresectable HCC, …
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Abstract Stereotactic body radiotherapy (SBRT) is a novel noninvasive treatment for unresectable hepatocellular carcinoma (HCC). Whether its efficacy is comparable to radiofrequency ablation (RFA), a recommended therapy for unresectable HCC, is unknown. The present study aims to compare the clinical outcome between SBRT and RFA for patients with unresectable HCC. The clinical data of 60 patients with unresectable HCC from January 2018 to January 2021 were retrospectively reviewed. There were 22 cases treated by SBRT and 38 cases by RFA. The short-term and long-term clinical outcomes were compared. There was no significant difference in the baseline demographic characteristics between two groups. The complete remission rate at 3 months was comparable between SBRT group (81.8%) and RFA group (89.4%). Local tumor control rate was also similar between two groups (90.9% vs. 94.7%). There was no severe complication (grade IIIa or above) in both groups. The 1-year and 2-year overall survival rates were 88.2% and 85.7% in SBRT group and 100% and 75% in RFA group, respectively. There was no statistical significant difference between groups (P = .576). SBRT can achieve similar short and long-term clinical outcome as RFA for unresectable HCC. Future prospective clinical study is needed to justify its role in patients with HCC.
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19.
孤舟蓑笠翁
(2025-10-17 20:12):
paper 【doi】10.1038/s41556-025-01769-9;【发表年份】2025年;【期刊】Nature Cell Biology;【标题】Antagonistic stem cell fates under stress govern decisions between hair greying and melanoma。【内容总结】这项研究想搞清楚为什么压力会导致头发变白或黑色素瘤,发现关键在于黑色素干细胞(McSCs)在受到不同基因毒素时的命运选择。简单说,像辐射这样的压力会让McSCs进入“衰老分化”(同时衰老和分化),导致它们从毛囊中消失,头发就变白了,但这能防止黑色素瘤;而像DMBA(一种致癌物)或紫外线这样的压力会通过激活花生四烯酸代谢和毛囊干细胞产生的KIT配体(KITL),阻止McSCs衰老分化,促进它们自我更新和迁移到皮肤表层,从而增加黑色素瘤风险。研究方法上,他们用了小鼠模型进行体内命运追踪(比如用Dct-H2B-GFP或Dct-LacZ标记McSCs)、免疫组化分析、RNA测序(包括单细胞和批量RNA-seq)、流式细胞术分选细胞以及体外实验(如彗星试验测DNA损伤)。结果发现,辐射诱导的DNA双链断裂会激活p53-p21通路,使McSCs在激活后衰老分化并最终被清除(例如,5 Gy辐射导致McSCs数量显著减少),而致癌物处理能上调KITL表达(如DMBA使KITL表达增加),并通过激活下游信号(如NRAS或BRAF突变)绕过这一过程;此外,年龄增长会降低KITL等因子表达,促进头发变白,而KITL过表达能挽救辐射引起的白发。总之,McSCs的命运取决于压力类型:致癌压力促进自我更新和癌症,而细胞毒性压力导致衰老分化和白发,两者在干细胞水平上存在拮抗关系。
20.
孤舟蓑笠翁
(2025-10-16 15:09):
paper 【doi】10.1126/science.adx2678;【发表年份】2025年;【期刊】Science;【标题】A human pan-disease blood atlas of the circulating proteome。【内容总结】这项研究的目标是建立一个全面的“泛疾病血液蛋白质组图谱”,通过分析血液中的蛋白质来更好地理解健康和疾病状态,为精准医疗提供资源。研究人员使用了一种叫做“邻位延伸分析”(Proximity Extension Assay, PEA)的高灵敏度技术,对来自8,262名个体(包括健康人和59种疾病的患者)的血液样本进行了大规模蛋白质分析,测量了多达5,416种蛋白质。他们发现每个人的血液蛋白质谱在两年内是独特且稳定的;在从童年到成年的发育过程中,许多蛋白质水平会随年龄和性别发生显著变化,例如胶原蛋白COL9A1在儿童期很高,青春期后大幅下降;通过机器学习模型,他们能够根据血液蛋白质相当准确地预测年龄(R²=0.85)和性别(AUC=0.99)。重要的是,研究揭示了传统上在单一疾病研究中被认为是特异性的蛋白质标记物,在跨疾病比较中可能并不特异,例如在胰腺癌中升高的FGF1蛋白在细菌感染患者中也升高,这表明炎症等共同生物学途径会导致蛋白质水平的重叠。这项研究创建了一个在线资源(Human Protein Atlas),供科学界探索疾病特异性和共享的血液蛋白质模式,有助于未来的生物标志物发现和疾病机制研究。
Science,
2025-10-9.
DOI: 10.1126/science.adx2678
Abstract:
The human blood proteome provides a holistic readout of health states through the assessment of thousands of circulating proteins. Here, we present a pan-disease resource to enable the study of …
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The human blood proteome provides a holistic readout of health states through the assessment of thousands of circulating proteins. Here, we present a pan-disease resource to enable the study of diverse disease phenotypes within a harmonized proteomics dataset. By profiling protein concentrations across 59 diseases and healthy cohorts, we identified proteins associated with age, sex, and BMI, as well as disease-specific signatures. This study highlights shared and distinct protein patterns across conditions, demonstrating the power of a unified proteomics approach to uncover biological insights. The dataset, covering 8,262 individuals and up to 5,416 proteins, serves as an online resource for exploring disease-specific protein profiles and advancing precision medicine research.
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