Core Viewpoint - The article discusses a groundbreaking study on tau protein disassembly in Alzheimer's disease, highlighting the potential of D-type peptides as a novel therapeutic strategy to combat neurodegenerative diseases [3][15]. Group 1: Alzheimer's Disease and Tau Protein - Alzheimer's disease (AD) is characterized by cognitive decline and is closely associated with the abnormal aggregation of tau protein and β-amyloid protein [2]. - Tau protein aggregation is more strongly correlated with the cognitive symptoms and severity of Alzheimer's disease compared to β-amyloid [2]. Group 2: Research Findings - A study published in Nature by Dr. Ke Hou from UCLA reveals that D-type peptides can disassemble tau fibrils without the need for enzymatic activity or external energy sources [3][15]. - The research introduces a new paradigm in amyloid protein studies, enhancing understanding of protein aggregation dynamics and inspiring innovative treatment strategies for Alzheimer's and other amyloid-related diseases [3][15]. Group 3: D-type Peptides Advantages - D-type peptides exhibit higher specificity and binding affinity compared to small molecules, with lower immunogenicity and resistance to proteolytic degradation [8]. - Previous studies indicated that D-type peptides could decompose tau protein fibers extracted from Alzheimer's patients and improve behavioral deficits in mouse models [8]. Group 4: Mechanism of Action - The study identified that D-type peptides assemble into amyloid-like fibers, which are essential for disassembling tau protein fibers [12]. - The tension released during the transition from left-handed to right-handed helical structures of these peptides is sufficient to disrupt local hydrogen bonds in tau fibers, leading to their disintegration [13][15]. Group 5: Implications for Treatment - The findings suggest that D-type peptides could revolutionize treatment methods for Alzheimer's disease and provide new tools for tackling other neurodegenerative diseases like Parkinson's and Huntington's disease [15]. - The stability, protease resistance, and good biocompatibility of D-type peptides allow them to cross the blood-brain barrier without eliciting harmful immune responses [15].

Core Viewpoint - The article discusses the development of a new type of laser called "metalaser," which enhances the understanding and performance of lasers in various optical and photonic applications [2][5]. Group 1: Introduction to Metalasers - The research team from Harbin Institute of Technology (Shenzhen) has proposed and realized the metalaser, utilizing the interaction between local and non-local responses of dielectric resonant metasurfaces [3][4]. - Traditional lasers require additional optical components to modify laser characteristics, leading to larger systems and limitations due to speckle noise [2]. Group 2: Features and Advantages of Metalasers - The non-local interactions between meta-atoms in planar structures limit laser modes, while local variations in dipole moments precisely shape the beam wavefront [4]. - Metalasers can emit with any desired profile, including focal points, focal lines, vector beams, vortex beams, and even holograms [4]. - The scattering waves from metalasers do not experience resonant amplification like traditional laser modes, resulting in significantly weaker intensity, which minimizes speckle noise issues found in conventional laser holography [4].

Core Insights - The article highlights significant advancements in various fields of research published in the journal Cell, with a notable contribution from Chinese scholars, indicating a strong presence in cutting-edge scientific research [1]. Group 1: Measles Virus Research - A study by Zhang Heqiao and Roger Kornberg's team elucidated the structure of the measles virus polymerase complex and its interaction with non-nucleoside inhibitors, laying the groundwork for rational antiviral drug design [3][4]. Group 2: AI in Protein Engineering - The research team led by Gao Caixia developed a novel AI protein engineering simulation method called AiCE, which integrates structural and evolutionary constraints, enabling efficient protein evolution simulation and functional design without the need for specialized AI model training [7]. Group 3: Vertebrate Genomics - The team from Zhejiang University introduced a high-throughput, sensitive single-nucleus ATAC sequencing technology (UUATAC-seq) to create chromatin accessibility maps, and developed the Nvwa model for predicting cis-regulatory elements, revealing the conserved syntax of vertebrate regulatory sequences [10][11]. Group 4: Primate Brain Research - A study identified cell type-specific enhancers in the macaque brain, establishing tools for understanding primate brain structure and diseases, which could enhance insights into cognitive functions [15]. Group 5: Peripheral Nerve Imaging - Researchers from the University of Science and Technology of China pioneered a high-speed, subcellular resolution imaging technique for whole-mouse peripheral nerves, providing a detailed peripheral nerve atlas and new tools for studying nerve regulation and disease mechanisms [19]. Group 6: Primate Prefrontal Cortex Connectivity - A study reconstructed the whole-brain connectivity network of the macaque prefrontal cortex at the single-neuron level, revealing refined axon targeting and arborization, which is crucial for understanding complex cognitive functions in primates [23]. Group 7: Optogenetics in Drug Discovery - The research led by Felix Wong developed an optogenetics platform for discovering selective modulators of the integrated stress response, identifying compounds that enhance cell death without toxicity, and demonstrating antiviral activity in a herpes simplex virus mouse model [27][28]. Group 8: Engineering Yeast Behavior - A study from Imperial College London established engineering principles for yeast, enabling programmable multicellular behaviors, transforming yeast from a "single-cell factory" to a "multicellular system chassis" [33][34].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 个性化新抗原疫苗已展现出巨大潜力，然而，其免疫原性仍有待提高。 2025 年 7 月 10 日，丹纳·法伯癌症研究所的研究人员在国际顶尖学术期刊 Cell 上发表了题为 ： A multi-adjuvant personal neoantigen vaccine generates potent immunity in melanoma 的研究论文。 该研究开发的 多佐剂个性化 新抗原疫苗 ，在 黑色素瘤 患者中激发了强效免疫。 由于抗原的可获得性以及有效的 T 细胞启动对于实现最大免疫原性至关重要，研究团队在 10 名 黑色素瘤 患者中测试了一种合成长肽疫苗 ，该疫苗采用两种佐 剂 Montanide、聚肌 胞 （poly-ICLC） 配制，并联合局部注射伊匹木单抗 （ Ipilimumab，抗 CTLA4单抗 ） 以及全身使用纳武单抗 （ Nivolumab，抗 PD-1 单抗 ） 。 在所有 9 名完成疫苗接种的黑色素瘤患者中，这些 个性化疫苗诱导了针对大多数免疫新 表位的新生 ex vivo T 细胞响应，并且在 9 名患者中有 6 名产生了 ex vivo C ...

Core Viewpoint - The study presents a novel microglia replacement therapy that effectively halts the progression of the lethal brain disease ALSP in both mice and humans, demonstrating clinical feasibility and long-term efficacy [3][9]. Group 1: Disease Background - Microglia are crucial immune cells in the central nervous system, and their dysfunction can lead to various CNS diseases. CSF1R mutations are linked to congenital microglial deficiency and ALSP, a severe condition with an average survival of only 3 years post-onset in China [2][5]. Group 2: Research Development - The research team developed a microglia replacement strategy, termed MISTER, which replaces pathogenic microglia with wild-type cells to potentially treat ALSP. This strategy was inspired by earlier findings and aimed to address the limitations of previous mouse models [6][7]. Group 3: Experimental Findings - The study utilized two newly generated mouse models that accurately replicate key features of human ALSP, including reduced microglial numbers and cognitive decline. The replacement of mutant microglia with wild-type cells significantly improved neurological function and halted disease progression [7][9]. Group 4: Clinical Application - In a clinical trial involving 8 ALSP patients, the microglia replacement therapy showed promising results, with increased brain glucose metabolism and stable cognitive function over a 24-month follow-up period. This marks the first systematic validation of microglia replacement in human patients [8][9]. Group 5: Implications for Future Research - The findings support the potential of microglia replacement strategies not only for ALSP but also for other CNS diseases associated with microglial dysfunction, indicating a broader therapeutic application [9].

编辑丨王多鱼 排版丨水成文 基于上述发现，研究团队成功将该技术拓展至多个体系，实现了包括 氘代硫酸 、 氘代盐酸 、 氟化氘 、 氘代硝酸 、 氘氧化钾 、 氘氧化钠 等在内的一系列氘代酸和氘代碱的高效制备。以该双极膜重水解离技术 为核心的氘代酸碱制备平台，平均生产成本仅为传统工艺的 20% 左右，且整个生产过程无需使用强腐蚀性 试剂或重金属催化剂，排放趋近于零，环境友好特性突出。据悉，该技术已成功完成工程放大，具备年产 3 吨氘代酸/碱的能力，为其工业化大规模生产奠定了坚实基础。 氘代酸、 氘代 碱 （使用氢的同位素氘代替氢） ，是用于合成氘代药物、改性光电材料以及介导氢同位素 交换反应的高价值大宗化学品。 然而，当前的氘代酸/碱的生产普遍存在着工艺复杂多样、反应条件苛刻、 产物纯化困难、浓缩能耗高等瓶颈问题。 2025 年 7 月 9 日，中国科学技术大学 徐铜文 教授、 汪耀明 特任教 授、 李震宇 教授作为共同通讯作者 （博士后 闫军营 、 副研究员 蒋晨啸 、 特任副研究员 曾雄志 共同第一作者 ） ， 在 Nature 期刊发表了 题为： Synthesis of deuterated acids ...

Core Insights - A significant collaborative research effort involving over 300 scientists from more than 30 institutions has published 10 papers on brain mapping in top-tier journals such as Cell and its sub-journals [2][3] Group 1: Research Findings - The studies reveal various cell types and their connections in the brains of mice and primates, with a notable cover image depicting a macaque gazing at a starry universe, symbolizing the brain's complexity [5] - The first multimodal atlas of the macaque claustrum has been created, identifying 48 cell types through single-nucleus RNA sequencing, highlighting the unique cell types in macaques compared to other species [6][7] - The research integrates single-cell transcriptomics, spatial data, and connectivity analysis, providing a comprehensive understanding of the claustrum's role as an "information hub" in the brain [8] Group 2: Methodological Innovations - A new high-speed imaging technique has been developed for whole-mouse peripheral nerves at subcellular resolution, allowing for unprecedented 3D mapping of the peripheral nervous system [16][20] - This technique enables the visualization of sensory and motor projections, revealing intricate structural features and pathways of the vagus nerve [20][21] Group 3: Implications for Future Research - The identification of cell type-specific enhancers in the macaque brain offers new tools for monitoring and manipulating neuronal activity, advancing the understanding of primate brain structure and cognitive principles [24][28] - The advancements in brain mapping technologies are expected to facilitate research into brain diseases and inspire developments in artificial intelligence systems [30]

Core Viewpoint - The article discusses a groundbreaking study that developed a high-speed 3D imaging technology for mapping the peripheral nervous system (PNS) in mice, significantly enhancing the understanding of its complex structure and functions [4][10]. Group 1: Technological Advancements - The research team from the University of Science and Technology of China introduced a novel imaging technique called blockface-VISoR, achieving subcellular resolution in whole-mouse imaging within 40 hours, which is several times faster than existing methods [4][10]. - This technology allows for the visualization of nerve pathways and connections in the PNS, which has been challenging due to the complexity and size of the mammalian body [3][10]. Group 2: Research Findings - The study successfully created a detailed peripheral nerve map, revealing intricate structures such as spinal motor and sensory nerves, visceral sympathetic nerves, and their interactions with various non-neural tissues and organs [13][21]. - The research utilized multiple labeling techniques, including fluorescent, immuno, and viral markers, to visualize different types of nerves, providing unprecedented insights into the PNS [12][19]. Group 3: Implications and Future Directions - The findings from this research are expected to facilitate a better understanding of the regulatory networks of the peripheral nervous system and the mechanisms of related diseases [4][10]. - The research team plans to share the image datasets online and is working on a platform for researchers to explore these data, which may offer new insights even to professional anatomists [22].

Core Viewpoint - Esophageal squamous cell carcinoma (ESCC) is a significant cause of cancer-related mortality, with current treatments showing limited long-term survival rates, necessitating the development of new therapeutic strategies [2][3]. Group 1: Current Treatment Landscape - Immune checkpoint inhibitors combined with platinum-based chemotherapy are standard treatments for advanced ESCC, but only 10%-20% of patients achieve long-term survival due to drug resistance [2]. - Second-line treatment with Irinotecan has limited efficacy, with an objective response rate (ORR) not exceeding 10% [2]. Group 2: New Treatment Development - A bispecific antibody-drug conjugate (ADC) targeting EGFR and HER3, named BL-B01D1, has been developed by Sichuan BaiLi TianHeng Pharmaceutical Co., Ltd., marking the first clinical trial of this type of drug globally [7]. - The drug is designed to connect a bispecific antibody with a topoisomerase I inhibitor via a cleavable linker [7]. Group 3: Clinical Trial Results - The phase 1b trial of BL-B01D1 involved 82 previously treated ESCC patients, showing an overall confirmed objective response rate (cORR) of 29.3% and a disease control rate of 79.2% at a dose of 2.5 mg/kg [10]. - The trial established a recommended dose for phase 2 trials at 2.5 mg/kg, administered every three weeks, with a 63.3% incidence of grade 3 treatment-related adverse events [12]. Group 4: Collaboration and Future Directions - The collaboration with Bristol-Myers Squibb (BMS) is notable, with a total deal value of up to $8.4 billion, including an $800 million upfront payment, setting a record for domestic innovative drugs [9]. - The research team has initiated phase 3 clinical trials based on the promising results of BL-B01D1 [13].

Core Viewpoint - The article discusses the advancements in single-cell technology and its application in understanding the cellular composition and molecular mechanisms driving cell heterogeneity in plants, particularly focusing on rice as a major crop [2][5]. Group 1: Research Findings - A recent study published in Nature presents a single-cell multi-omics atlas of rice, detailing the chromatin accessibility and RNA expression of 116,564 cells from eight major rice organs [3][6]. - The research identified 54 cell types and described new cellular states, such as a "transitional state" in floral meristem, providing insights into the functional cellular composition of rice at the tissue level [6]. - Key regulatory hubs identified include RSR1, F3H, and LTPL120, which play significant roles in root development, carbon-nitrogen metabolism, and potential plant architecture optimization [6]. Group 2: Technological Contributions - The research team developed the Rice-SCMR, the first intelligent visualization platform for rice single-cell multi-omics, which allows for gene expression and chromatin accessibility searches across 56 annotated cell types [7][10]. - The platform integrates gene regulatory networks, disturbance simulation predictions, and three-dimensional precise localization of GWAS-associated traits, facilitating intelligent design linking genes, cell types, and traits [10]. Group 3: Implications for Agriculture - This study not only provides a unique single-cell multi-omics resource for rice but also enhances the understanding of cell type functions and their potential molecular programs, which could have significant implications for agricultural research and crop improvement [7].