Core Viewpoint - The recent research published in Science introduces a new model called "Kiss-Shrink-Run" that unifies the mechanisms of synaptic vesicle exocytosis and hyperfast recycling, providing new insights into neural signal transmission and related brain diseases [4][10]. Group 1: Research Background - The study addresses a long-standing debate in neuroscience regarding the mechanisms of synaptic vesicle release, which has persisted for half a century [4]. - Two opposing models, Full-collapse and Kiss-and-run, have been the focus of this debate, but technological limitations have hindered resolution [4][10]. Group 2: Methodology - The research team developed a millisecond time-resolved in situ cryo-electron tomography (cryo-ET) imaging technique to capture the biophysical processes of synaptic vesicle release and rapid recycling [4][5]. - By coupling optogenetic stimulation with rapid freezing techniques, the team was able to capture the instantaneous states of vesicle release at various time intervals (4-300 milliseconds) [5][8]. Group 3: Key Findings - The study revealed a new intermediate state of synaptic vesicles, identified as small vesicles approximately 29 nanometers in diameter, which are hypothesized to represent a transitional phase during vesicle release [5][10]. - The research outlines a complete process of synaptic vesicle release and rapid recycling, indicating that vesicles first form a ~4 nanometer fusion pore ("Kiss") within 4 milliseconds, then shrink to half their original surface area ("Shrink"), and most small vesicles begin to recycle within 70 milliseconds ("Run") [8][10]. Group 4: Implications - This new "Kiss-Shrink-Run" mechanism not only reconciles the two previously conflicting models but also highlights the structural basis for efficient and high-fidelity neural transmission [10]. - The innovative techniques developed in this research may have broader applications for studying dynamic processes within cells [10].

Core Insights - The article discusses the significant public health challenge of infertility, affecting 12.6%-17.5% of couples globally, and highlights the role of in vitro fertilization (IVF) as a primary assisted reproductive technology [3] - A recent study published in Nature Medicine introduces the concept of Oocyte and Early Embryo Competence Defects (OECD) and identifies six subtypes based on clinical characteristics, providing new diagnostic standards and genetic mapping for female infertility [4][7] Group 1: OECD Concept and Subtypes - The study systematically proposes the concept of OECD and categorizes it into six subtypes: Empty Follicle, Oocyte Maturation Arrest, Fertilization Failure, Zygote Arrest, Early Embryonic Arrest, and Mixed Phenotype, along with corresponding diagnostic criteria [4][7] - The research involved whole-exome sequencing of 2,140 female OECD infertility patients to explore the genetic landscape and subtype classification [7] Group 2: Genetic Findings and Implications - The research team identified 183 pathogenic or potentially pathogenic mutations across 28 known genes, with varying diagnostic rates among subtypes; for instance, the Empty Follicle subtype had a diagnostic rate of 53% [9] - The study also identified and validated two potential pathogenic genes, MLH3 and CENPH, and suggested nine previously unreported associated genes, providing biological insights into the potential pathogenic mechanisms of ovarian insufficiency [9] - Overall, the genetic findings explain 12.8%-23.1% of OECD cases, offering valuable information for developing diagnostic genetic screening and standardizing subtype classification for OECD patients [9]

Core Insights - The study reveals the molecular mechanisms by which the JAK2 V617F mutation leads to two different types of myeloproliferative neoplasms (MPN), essential thrombocythemia (ET) and polycythemia vera (PV) [3][4] - The research highlights the significance of different mutation types in determining disease progression, with heterozygous mutations in ET and homozygous mutations in PV [6] - The findings suggest a potential new therapeutic target for ET treatment through AhR inhibition, which shows better specificity and safety compared to existing therapies [8] Group 1: Research Findings - JAK2 V617F mutation is present in over 50% of ET patients and more than 90% of PV patients, indicating its critical role in these diseases [3] - In ET patients, the mutation primarily exists as a heterozygous form, activating the STAT1 – AhR – RUNX1 signaling axis, leading to increased platelet production [6] - In PV patients, the mutation is mostly homozygous, activating the STAT5 signaling pathway, which drives red cell differentiation [6] Group 2: Clinical Implications - The study constructed a humanized JAK2 V617F ET mouse model, demonstrating that AhR inhibition effectively reduces excessive platelet production without affecting other myeloid cells [6] - Ongoing clinical trials on AhR inhibitors in cancer immunotherapy provide a foundation for their rapid application in ET treatment [8] - The research not only addresses a long-standing scientific puzzle but also identifies a new potential target for ET therapy, offering a safer and more sustainable treatment option for patients requiring lifelong management [8]

Core Insights - The 2025 Nobel Prize in Physiology or Medicine was awarded to three scientists for groundbreaking discoveries in regulatory T cells, revealing how the immune system maintains self-balance through "peripheral immune tolerance," which is crucial for understanding autoimmune diseases and developing new cancer immunotherapy strategies [4][5] - Traditional animal models struggle to accurately simulate the human immune system due to species differences, leading to challenges in mechanism research, clinical translation, and model construction [4] - Humanized immune system mice provide a key technology to address these issues, allowing for effective preclinical evaluation of candidate drugs, significantly reducing subsequent development risks, and providing a reliable platform for assessing new cell therapies and bispecific antibodies [5] Course Overview - An online course titled "Applications of Humanized Immune System Mice in Tumor Immunity and Autoimmune Diseases" will be held on October 21, featuring Dr. Yu Jing, a senior scientist at Saiye Bio, focusing on scientific decision-making for obtaining valuable experimental data [5][7] - The course will cover the following topics: 1. Advances in tumor immunity: Translating Nobel-level discoveries into new treatment strategies and related research dynamics [7] 2. Model development history: Reviewing the evolution of models and the characteristics and applicable scenarios of PBMC, HSC, and other construction strategies [7] 3. Optimization strategies and application cases: Emphasizing research on tumor immunity and autoimmune diseases, drug efficacy, and safety evaluation [7] 4. Interactive session: The lecturer will answer common questions related to disease research [7] Research Applications - The huHSC-C-NKG-ProF model has been utilized in significant research, including: 1. CAR-T cell therapy for solid tumors, revealing how Foxp3 regulates CAR-T cell metabolism to enhance treatment efficacy [12] 2. Liver cancer immune evasion studies, identifying ETV5 as a potential biomarker for prognosis and a target for new treatment strategies [12] - Saiye Bio's humanized immune system mice, particularly the huHSC-C-NKG-ProF model, can reconstruct various human immune cells, providing a robust platform for research [13][14] Product Offerings - Saiye Bio offers several humanized immune system models, including: - huHSC-C-NKG-ProF: Full immune system reconstruction with a humanization rate of 40-60% after 8 weeks [16] - huHSC-C-NKG-ProM: Reconstructs lymphoid T and B cells with a similar humanization rate [16] - huHSC-C-NKG-ProN: Focuses on T, B, and NK cells with minimal myeloid development [16] - huHSC-C-NKG: Supports long-term presence of human cells with a lifespan exceeding one year [16] - huPBMC-C-NKG: Primarily reconstructs lymphoid T cells with a fast reconstruction speed [16]

撰文丨王聪 编辑丨王多鱼 排版丨水成文 在生命科学领域，设计一个能够精确响应环境信号的蛋白质，一直是科学家们的梦想。特别是对于跨越细胞膜的蛋白质——它们控制着细胞与外界的信息交流， 如同城市的门户和关卡。 尽管科学家们已经取得了一些进展，例如设计出稳定的膜蛋白支架和跨膜孔道，但要从头开始设计一个能够响应特定刺激 （例如电压变化） 并通过构象变化来控 制离子流动的跨膜蛋白，仍然是一个巨大挑战。 2025 年 10 月 16 日， 西湖大学生命科学学院、西湖实验室及遗传物质表达与重构全国重点实验室 卢培龙 团队，联合西湖实验室/西湖大学 李波 、 黄晶 等 团 队，在国际顶尖学术期刊 Cell 上 发表题为： De novo designed voltage-gated anion channels suppress neuron firing 的研究论文。 该研究 首次从头设计出了 电压门控阴离子通道 —— dVGAC ，这些通道不仅具有独特的结构和工作机制，还能够 在小鼠模型中有效抑制神经元电活动 。 该研究不仅表明科学家已具备 从头设计具有 " 动态开关 " 功能的跨膜蛋白 的能力，更证明此类人工蛋白可在活 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 前列腺癌 是男性中第二常见的癌症，据估计 2022 年有 146 万例新增病例。大约 10%-20% 的晚期前列腺癌会在 5 年内发展为 去势抵抗前列腺癌 （CRPC） ，且至少 84% 的 CRPC 患者在确诊时已出现转移。 前列腺癌细胞依赖 雄激素受体 （AR） 的活性，该受体已成为治疗原发性和晚期前列腺癌的主要靶点，第二代 雄激素受体靶向药物显著提高了患者的无进展生存 期和生存率，但晚期前列腺癌患者的 5 年生存率仍不足 30%。 去势抵抗前列腺癌 （CRPC） 对第二代雄激素靶向治疗表现出固有或获得性耐药性，这给临床治疗带来了挑战。这种耐药性的一个主要原因是存在 AR 剪接变 体，例如 AR-V7 ，被认为是与 CRPC 最相关的 剪接变体亚型 。 近年来，基于 蛋白靶向降解嵌合体 （PROTAC） 技术的创新疗法，能够高效降解 雄激素受体 （AR） ，但它们对 AR-V7 的降解作用相对较弱。因此，如何应 对 AR-V7 带来的 耐药性，已成为前列腺癌临床治疗的一个焦点。 2025 年 10 月 15 日， 中国医学科学院肿瘤医院 邢念增 教授 、国家纳米科学 ...

Core Viewpoint - The article discusses the "winner effect," a psychological phenomenon where previous victories increase the likelihood of future successes, highlighting gender differences in this effect between male and female mice [2][3]. Group 1: Research Findings - A study by Professor Hu Hailan's team at Zhejiang University revealed that female mice exhibit a weaker "winner effect" compared to male mice, attributed to differences in the excitability of a specific type of inhibitory neuron in the dorsomedial prefrontal cortex (dmPFC) [3][11]. - The research utilized a "tunnel experiment" to establish social hierarchies among mice, confirming that female mice can form stable social ranks, albeit through different behavioral strategies than males [5][10]. - The study demonstrated that activating the dmPFC in female mice could reverse their social standing, indicating that this brain region plays a crucial role in regulating social hierarchy for both sexes [7][8]. Group 2: Neural Mechanisms - The research identified that the excitability of parvalbumin interneurons (PV-IN) in the dmPFC is higher in female mice, leading to a less pronounced "winner effect" due to lower long-term potentiation (LTP) in the neural pathways involved [11][12]. - Experiments showed that enhancing PV-IN excitability in male mice diminished their "winner effect," while inhibiting it in female mice strengthened their "winner effect," confirming the critical role of PV-IN in gender differences [12][14]. Group 3: Evolutionary Perspective - The study suggests that the weaker "winner effect" in female mice may have evolutionary advantages, allowing them to balance competition and cooperation, reduce energy expenditure, and maintain social harmony [16][17]. - This neural mechanism difference reflects adaptive evolution in social roles between males and females, providing insights into how specific neuronal excitability can finely tune social behaviors [17].

编辑丨王多鱼 排版丨水成文 题图为 卢培龙 研究员 离子通道 在神经传导、肌肉收缩和细胞信号转导等关键生物学过程中发挥重要作用，其开闭状态受电压、 配体或机械力等特定刺激的精确调控。从头设计能够响应外界刺激并发生构象变化的跨膜蛋白，是蛋白质 工程领域的重要目标，也是技术难点。 由于蛋白质动态结构设计的复杂性，实现具有自定义门控功能的跨膜离子通道从头 设计 ，目前仍是一项 尚未 突破的挑战。成功设计出可响应特定刺激的 动态 跨膜蛋白，不仅有助于深入理解膜蛋白的工作机制 和膜生物学的基本原理，还将拓展其在生物医学与生物技术中的广泛应用前景，带来全新的发展机遇。 2025 年 10 月 16 日 ，西湖大学生命科学学院、西湖实验室及遗传物质表达与重构全国重点实验室 卢培 龙 团队，联合西湖实验室/西湖大学 李波 、 黄晶 等 团队，在国际顶尖学术期刊 Cell 上 发表题为： De novo designed voltage-gated anion channels suppress neuron firing 的研究论文。 经过六年系统攻关，研究团队在 国际上首次实现了 电压门控阴离子通道 （ d e novo ...

Core Insights - The article discusses a groundbreaking spectroscopy technology called RAFAEL, developed by a research team led by Professor Fang Lu from Tsinghua University, which addresses the long-standing resolution-efficiency trade-off in traditional spectroscopy methods [2][3]. Group 1: Technology Overview - RAFAEL technology utilizes integrated lithium niobate photonics to achieve a spectral resolution of 0.5 Å, an optical transmittance of 73.2%, and a spatial resolution of 2048×2048 [3][6]. - The design employs bulk lithium niobate as an interference mask, enabling pixel-level electrically tunable spectral response while maintaining high optical transmittance [6]. Group 2: Performance Metrics - RAFAEL captures snapshot spectra at a frequency of 88 Hz across the 400-1000 nm wavelength range, achieving a spectral resolution of approximately 0.5 Å and a total optical transmittance of 73.2% [6]. - Compared to cutting-edge spectral imaging devices, RAFAEL's optical transmittance is improved by two times, and its spectral resolution capability is enhanced by nearly two orders of magnitude [6]. Group 3: Applications and Impact - RAFAEL can capture the sub-Ångström spectra of up to 5600 stars in a single snapshot, significantly increasing observational efficiency by 100 to 10,000 times compared to the world's top astronomical spectrometers [6]. - This high-performance and easily integrable snapshot spectroscopy technology is expected to drive breakthroughs in various fields, including materials science and astrophysics [6].

Core Insights - On October 15, 2025, a total of 22 papers were published in the prestigious journal Nature, with several authored by Chinese scholars, highlighting the significant contributions of Chinese researchers in various scientific fields [2][4][6][9][12][21][22][24]. Group 1: Research Contributions - Zhang Zhenhua from RWTH Aachen University published a paper on "Deaminative cross-coupling of amines by boryl radical β-scission," focusing on a novel reaction mechanism involving boryl radicals [2]. - A collaborative work by Xu Minyu from National University of Singapore and Zhang Xinglong from Chinese University of Hong Kong discussed "Photocatalytic oxygen-atom transmutation of oxetanes," presenting advancements in photocatalysis [4]. - A team from Shanghai Jiao Tong University, Fudan University, and Nanjing University of Science and Technology introduced "Tin-based perovskite solar cells with a homogeneous buried interface," contributing to solar energy technology [6]. - The Taiwan Precision Medicine Initiative was highlighted in a paper by researchers from Academia Sinica, providing a cohort for large-scale studies in precision medicine [9]. - A study on "Population-specific polygenic risk scores for people of Han Chinese ancestry" was published by researchers from Academia Sinica, focusing on genetic risk assessment [12]. Group 2: Environmental and Material Science - Lin Yucheng from Rutgers University published a paper on "Modern sea-level rise breaks 4,000-year stability in southeastern China," addressing significant environmental changes [17]. - Research on "Patchy nanoparticles by atomic stencilling" was conducted by Chen Qian from the University of Illinois, exploring innovative methods in nanotechnology [19]. - A study on "A conserved H3K14ub-driven H3K9me3 for chromatin compartmentalization" was published by researchers from East China Normal University and the Chinese Academy of Sciences, contributing to the understanding of chromatin biology [21]. - Tsinghua University’s Fang Lu published a paper on "Integrated lithium niobate photonics for sub-ångström snapshot spectroscopy," advancing photonic technologies [22]. - Chen Chi-Fang from UC Berkeley introduced "Efficient quantum thermal simulation," focusing on quantum computing applications [24].