Core Viewpoint - The research highlights the potential of genetically engineered human mesenchymal progenitor cells (SRC) to counteract aging in primates, suggesting a new paradigm for anti-aging cell therapy [2][12]. Group 1: Aging Mechanism and Cell Therapy - The study investigates the mechanisms of aging regulation and employs synthetic biology to reprogram longevity gene pathways, successfully creating SRC with triple resistance to aging, stress, and malignant transformation [3][7]. - SRC cells exhibit significant anti-aging activity and strong environmental adaptability, while also demonstrating excellent safety features to avoid tumorigenic risks post-transplantation [8]. Group 2: Experimental Results - In a 44-week trial involving elderly crab-eating macaques (equivalent to 60-70 years in human age), SRC therapy resulted in reduced systemic aging indicators, such as cellular senescence, chronic inflammation, and tissue degeneration, with no adverse reactions detected [10]. - Notably, SRC treatment improved brain structure and cognitive function, reversing the biological age of immature neurons by 6-7 years and oocytes by 5 years, as confirmed by machine learning-based aging clock analysis [10]. Group 3: Mechanism of Action - The restorative effects of SRC are partially attributed to their exosomes, which play a crucial role in promoting cellular rejuvenation, inhibiting chronic inflammation, and maintaining genomic and epigenomic stability, providing new insights into pathways for delaying systemic aging [10].

多细胞生物的生命活动需要成千上万的基因在空间上有序的各种细胞类型中协调运作。要理解组织功能的基础，就需要剖析体内各种细胞和组织表型的遗传控制 机制。然而，一直是个重大挑战，传统方法要么只能测量基因表达情况 （单细胞策略） ，要么只能观察细胞形态 （显微成像） ，始终无法同时捕捉多个维度的 信息。 2025 年 6 月 12 日， 哈佛大学 庄小威 教授团队在国际顶尖学术期刊 Cell 上发表了题为： Perturb-Multimodal: A platform for pooled genetic screens with imaging and sequencing in intact mammalian tissue 的研究论文。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 该研究开发了一种名 为 Perturb-Multi 的新技术，将成像技术与测序技术结合，首次实现在哺乳动物整个组织中对数百个基因并行扰动，同步完成基因表达谱、 亚细胞形态和空间位置的三维解析。 通过成像技术，能够识别单个细胞中的扰动情况，同时测量其基因表达谱和亚细胞形态。利用单细胞测序技术，测量了对相同干扰的完整转录组反应。 研究团队应用 ...

Core Viewpoint - Understanding the thermal transport mechanisms at material interfaces is crucial for advancing semiconductor technology, particularly for miniaturized devices operating at extremely high power densities [1]. Group 1: Research Findings - The research team from Peking University published a paper in Nature on June 11, 2025, exploring phonon transport dynamics across interfaces using electron microscopy [2]. - The study utilized in-situ vibrational electron energy loss spectroscopy (EELS) to measure temperature gradient distributions at the AlN-SiC interface with nanometer resolution, overcoming previous measurement challenges [3]. - A steep temperature drop was observed within approximately 2 nanometers of the interface, allowing for the direct extraction of the interfacial thermal resistance (ITR) [4]. Group 2: Implications and Mechanisms - The mismatch in phonon mode thermal conductivity at the interface leads to a significant generation of non-equilibrium phonons in adjacent regions during thermal transport [4]. - The findings reveal the (sub)nanometer scale phonon transport dynamics and confirm the phonon inelastic scattering mechanisms involving interface modes, providing important guidance for thermal interface engineering design [5].

Core Viewpoint - The research highlights the development of engineered human mesenchymal progenitor cells (SRC) that exhibit triple resistance to aging, stress, and malignant transformation, providing a customizable cell therapy paradigm for aging intervention in primates [3][12]. Group 1: Research Background and Mechanism - Aging is characterized by the depletion of stem cell reserves, leading to decreased tissue regeneration and homeostasis, which is a key feature of aging and age-related diseases [2]. - The study published in Cell by a collaborative research team from the Chinese Academy of Sciences and Capital Medical University focuses on the mechanisms of aging regulation and the potential of SRC to counteract aging in primates [2][3]. Group 2: Development of SRC Technology - The research team utilized synthetic biology to reprogram longevity gene pathways, successfully constructing SRC with enhanced anti-aging properties [3]. - The SRC technology has evolved through various iterations, including SRC 1.0 and SRC 2.0, which involved precise genetic modifications to enhance antioxidant defenses and integrate anti-aging functionalities [6][8]. Group 3: Efficacy and Safety of SRC - The SRC cells demonstrated significant anti-aging activity and environmental adaptability, with excellent safety profiles, effectively resisting adverse effects in a primate model [8][9]. - A 44-week intervention study using SRC in aged primates showed no adverse events, confirming the safety and immune tolerance of SRC transplantation [9][11]. Group 4: Mechanistic Insights and Outcomes - SRC cells were found to release exosomes that promote cellular rejuvenation, suppress chronic inflammation, and maintain genomic stability, contributing to the delay of systemic aging [11]. - The intervention led to improvements in cognitive function, reduction of degenerative changes in multiple tissues, and a significant reversal of biological aging markers in various organs [11][12]. Group 5: Clinical Translation and Future Prospects - The study establishes a theoretical framework for stem cell transplantation to mitigate aging, addressing long-standing controversies in the field [13]. - The research opens pathways for scalable production of universal cell interventions, providing new solutions for aging and related diseases, and sets a new standard for evaluating anti-aging effects in cell therapy products [14][16]. - Future research will focus on optimizing clinical-grade production processes and understanding the interactions between SRC and the host immune system to enhance treatment strategies [18][19].

以下文章来源于中华肿瘤杂志 ，作者罗伟仁 中华肿瘤杂志 . 《中华肿瘤杂志》官方公众号 罗伟仁. 重新思考肿瘤[J]. 中华肿瘤杂志, 2025, 47(6): 463-467. DOI: 10.3760/cma.j.cn112152-20250401-00145. 摘 要 在过去半个世纪的全球抗癌斗争中，无论是肿瘤基础研究还是临床实践，几乎所有探索均围绕"体细胞突 变"这一理论展开，比如在分子分型、个体化精准医学、基因治疗、新抗原肿瘤疫苗研发以及测序技术开 发等诸多方面。即便近年备受瞩目的肿瘤微环境研究，包括肿瘤免疫方向，其最终归因仍往往指向癌细胞 或微环境细胞中的某些特定基因和突变。然而，"体细胞突变"范式并未为临床带来真正有效的肿瘤治愈路 径，倘若继续以该理论为主导框架，显然难以在肿瘤的理解与治疗上取得实质性进步。因此，在肿瘤研究 史的这个关键十字路口，一场彻底的新思维变革迫在眉睫。文章阐述了肿瘤系统为理解肿瘤本质所带来的 新视角，肿瘤生态学的基本原理及其在治疗中的潜在应用，并探讨了生态病理学这一新兴领域的理论框架 与研究意义。呼吁要摒弃当前主导的肿瘤线性还原旧范式，更重要的是，致力于为后基因组时代的新 ...

Core Viewpoint - The research developed human airway submucosal gland (SMG) organoids to study respiratory inflammation and infection, marking a significant advancement in organoid research and its applications in drug development and regenerative medicine [2][3]. Group 1: Research Background - The study was led by Hans Clevers' team, with Lin Lin as the first author, and published in Cell Stem Cell on June 12, 2025 [2]. - The development of organoids began in 2009 with the cultivation of intestinal organoids from mouse intestinal stem cells, which opened the era of organoid research [2]. Group 2: Importance of SMG - SMG plays a crucial role in mucus secretion and host defense, containing various cell types that contribute to airway moisture and pathogen resistance [7]. - Recent studies indicate that SMG aids in the repair and regeneration of airway epithelium after injury, suggesting its potential as a reservoir of multipotent progenitor cells [8]. Group 3: Research Findings - The research established human organoids from primary bronchial tissues to explore the unique physiological characteristics of SMG and surface airway epithelium (SAE) [9]. - Single-cell RNA sequencing confirmed that the organoid models accurately replicate the inherent cellular heterogeneity of each tissue type, with SMG organoids rich in MUC5B-producing cells [9]. Group 4: Key Highlights - The study successfully cultivated SMG organoids from human bronchial tissue [10]. - ANPEP/CD13 was identified as a specific marker for glandular secretory cells [10]. - The research demonstrated that cytokines related to chronic obstructive pulmonary disease (COPD) trigger different inflammatory responses in the organoids [10]. Group 5: Conclusion - The SMG organoid model serves as a new tool for investigating the complex roles of SMG in human airways, providing a more physiologically relevant system for studying responses to infection and inflammation [12].

Core Viewpoint - The article discusses the development of a long-acting IL-2 release platform using pressure-fused biomineral tablets, which enhances antitumor immune response and addresses the limitations of traditional IL-2 therapies [3][4][10]. Group 1: Long-acting Drug Delivery - Long-acting formulations can maintain drug release for weeks, months, or even years, improving patient compliance and therapeutic efficacy [2]. - Biominers like calcium carbonate (CaC) and calcium phosphate (CaP) are promising materials for constructing long-acting formulations due to their high biocompatibility and stability [2][6]. Group 2: Research Development - The research team developed a dynamic control platform for IL-2 release through the fusion of amorphous CaC and CaP under high pressure (2 GPa) [6][7]. - A hybrid biomineral with the formula Ca(CO3)x(PO4)2(1−x)/3 was created, demonstrating crystallization-driven release behavior to optimize IL-2's in vivo fate [7]. Group 3: Experimental Results - The formulation consisted of 7.5 mg of CaC nanoparticles, 2.5 mg of CaP nanoparticles, and 30 µg of IL-2, which were completely fused under pressure to form a transparent IL-2@Ca(CO3)1/2(PO4)1/3 tablet [8]. - The Ca(CO3)1/2(PO4)1/3 tablet reshaped the immunosuppressive tumor microenvironment, enhancing the distribution of IL-2 and preferentially activating cytotoxic T cells and memory T cells, leading to weeks of IL-2 retention [9]. Group 4: Antitumor Efficacy - In a melanoma model in female mice, the Ca(CO3)1/2(PO4)1/3 tablet exhibited excellent antitumor effects, inhibiting local tumor recurrence and preventing the growth of untreated distal tumors while maintaining a long-term T cell response [10].

Core Insights - The article discusses the significant role of mitochondria in mammalian development and introduces a new method for enforced mitophagy that allows for the reduction or complete removal of mitochondria, revealing their influence on pluripotency and embryonic development [3][15]. Group 1: Research Findings - The study published by Professor Wu Jun's team at the University of Texas Southwestern Medical Center demonstrates that enforced mitophagy can lead to a reduction in mitochondrial quantity, which subsequently delays pre-implantation embryonic development in mice [3][11]. - The research indicates that pluripotent stem cells (PSCs) lacking mitochondria can survive for 3-5 days in vitro but cease to divide, suggesting that these cells can compensate for the absence of mitochondria by taking over energy production and other functions typically performed by mitochondria [8][13]. - The study also reveals that the enforced mitophagy method can be applied across different species and cell types, potentially opening new avenues for research and treatment of mitochondrial diseases [8][15]. Group 2: Methodology - The enforced mitophagy technique involves expressing the PRKN protein in cells, which promotes the degradation of dysfunctional mitochondria, followed by treatment with mitochondrial uncouplers to stimulate extensive mitophagy [6][8]. - The research team successfully generated PSCs devoid of mitochondria and assessed the gene expression changes, finding that 788 genes became less active while 1696 genes became more active, indicating a shift in cellular function [8][13]. - The study further explores the fusion of human PSCs with those from non-human primates, revealing that these hybrid cells selectively retain human mitochondrial DNA, demonstrating the interchangeability of mitochondrial support for pluripotency across species [9][13]. Group 3: Implications - The findings suggest that a significant reduction in mitochondrial content can hinder embryonic development, with a 65% loss leading to implantation failure and a 33% loss resulting in developmental delays [11][13]. - The research provides a powerful tool for investigating the roles of mitochondria in cellular functions, organ development, aging, and evolutionary biology, potentially impacting future therapeutic strategies for mitochondrial diseases [15].

Core Viewpoint - The research emphasizes the importance of understanding the interaction between tumor microenvironment and systemic immune macroenvironment for developing more effective cancer diagnosis and treatment strategies [2]. Group 1: Research Development - A novel organoid co-culture model, the Gel-Liquid Interface (GLI) co-culture model, was developed to explore systemic anti-tumor immunity in lung cancer [3]. - The research team established a lung cancer organoid (LCO) paired with peripheral blood mononuclear cells (PBMC) using the GLI model, enhancing the interaction between immune cells and tumor organoids to better simulate systemic anti-tumor immune responses in vivo [4]. Group 2: Findings and Implications - The study demonstrated that the GLI model's response under anti-PD-1 (αPD1) treatment accurately reflects the immune treatment outcomes of corresponding lung cancer patients [5]. - Functional multi-omics analysis in the GLI model revealed various tumor immune processes mediated by T cells derived from PBMC, characterizing circulating tumor-reactive T cells with an effector memory-like phenotype (GNLY+ CD44+ CD9+) as potential indicators of immunotherapy effectiveness [6]. - Key findings indicate that the GLI co-culture model reflects the immune treatment outcomes of lung cancer patients, reveals the infiltration and activation of peripheral T cells post immune checkpoint inhibitor (ICI) treatment, and shows that PBMC-derived T cells transform into more cytotoxic tumor-reactive T cells under ICI influence [7]. Group 3: Overall Conclusion - Overall, the research results suggest that the GLI co-culture model can be utilized for developing diagnostic strategies for precision immunotherapy and aids in understanding its underlying mechanisms [9].

在原子级薄的二维 （2D） 半导体中调整载流子密度颇具挑战性，这是因为其固有的物理空间有限，难以掺入电荷掺杂剂。 2025 年 6 月，湖南大学化学化工学院 段曦东 教授团队在国际顶尖学术期刊 Science 上发表了题为 ： Gate-driven band modulation hyperdoping for high- performance p-type 2D semiconductor transistors 的研究论文 【1】 。 该研究利用栅极驱动能带调制超掺杂，用于高性能 p 型二维半导体晶体管的制备， 创下了 同类器件 新纪录。 值得一提的是，早在 2017 年 ， 段曦东和段镶锋教授作为共同通讯作者，在 Science 期刊发表论文 【2】 ，实现了 2D 异质节、多异质节以及超晶格的可控外延 生长，这是湖南大学首次作为第一单位发表 Science 论文。 编辑丨王多鱼 排版丨水成文 在这项最新研究中， 段曦东团队表明 ，在 III 型范德华异质结构中，层间电荷转移掺杂可通过外部栅极进行大幅调节，从而实现超掺杂效应。系统化的栅控霍尔 测量表明，调制的载流子达到了 每平方厘米 1.49×10 ...