编辑丨王多鱼 排版丨水成文 空间量化是大多数计算病理学任务中的关键步骤，从引导病理学家关注临床感兴趣的区域到发现新型生物标志物背后的组织表型。为了规避人工标注的需求，现 代计算病理学方法更倾向于采用多示例学习方法，这些方法能够准确预测整张切片图像的标签，但这会以丧失空间感知能力为代价。 2025 年 11 月 19 日，西安交通大学 李辰 教授、 龚铁梁 副教授联合英国 剑桥大学的研究人员 （ 高泽宇 博士为论文第一作者 ） ， 在 Nature 子刊 Nature Cancer 上发表了题为： SMMILe enables accurate spatial quantification in digital pathology using multiple-instance learning 的研究论文。 该研究开发了全球首个可实现大规模肿瘤筛查及细粒度量化诊断的 AI 病理模型—— SMMILe ，SMMILe 能够在仅使用简化"病人级诊断标签"的情况下，实现对 全玻片病灶进行精确空间量化，打破了传统弱监督算法"重分类、轻定位"的局限，在无需昂贵人工标注的条件下，能够像绘制地图一样，自动推断出肿瘤在组织 ...

Core Viewpoint - Bayer's YiZhuang Open Innovation Center in Beijing aims to integrate industry, education, research, and entrepreneurship, linking "Chinese innovation" with "global wisdom" as part of its strategy in China [1][3]. Group 1: Innovation Center Launch - The YiZhuang Open Innovation Center is Bayer's first innovation center in China, located in the International Pharmaceutical Innovation Park (BioPark) [3]. - The center will incubate local innovative pharmaceutical companies and enhance the global competitiveness of Chinese innovations [3][5]. - Bayer's commitment to local innovation is reinforced by partnerships with top academic institutions like Tsinghua University and Peking University, focusing on transforming cutting-edge research into new drugs [5][12]. Group 2: Collaboration and Ecosystem - Bayer Co.Lab, a global life sciences co-creation platform, will also be established in Beijing, working alongside the YiZhuang Open Innovation Center to deepen local innovation collaboration [7]. - The first companies to join Bayer Co.Lab include Puhe Pharma, which focuses on innovative small molecule therapies, and Yaojing Gene, specializing in gene therapy [8][14][15]. - The center will facilitate the transformation of early-stage innovations and support the internationalization of local biotech startups [7][10]. Group 3: Events and Partnerships - A series of events, including the "China-Europe Sci-Tech Innovation Community Theme Day," will be held at the new center, promoting dialogue between top scientists and industry leaders from both regions [10]. - Bayer has conducted over 100 joint research projects with Chinese universities over the past decade, establishing itself as a key player in the local biotech landscape [12]. - Bayer's Beijing factory is the largest prescription drug packaging base globally, highlighting its significant investment and operational scale in China [12].

Core Viewpoint - The research published in Nature demonstrates a breakthrough in the application of lanthanide nanocrystals in electroluminescent devices, overcoming insulation challenges through functional ligand design for efficient multicolor light emission control [2][3][5]. Group 1: Research Achievements - The study showcases an efficient electroluminescent strategy based on insulating lanthanide fluoride nanocrystals (4 nm; NaGdF₄:X; X = Tb³⁺, Eu³⁺, or Nd³⁺) with a surface coated by functionalized 2-(diphenylphosphoryl)benzoic acid (ArPPOA) [5][7]. - The strong coupling between ArPPOA and lanthanide nanocrystals facilitates intersystem crossing (ISC) and high-efficiency energy transfer to the nanocrystals, achieving a transfer efficiency of up to 96.7% [7]. - The research achieved full-color multicolor electroluminescence without altering device structure, with the external quantum efficiency of the Tb³⁺ system exceeding 5.9% [7]. Group 2: Implications and Future Directions - The functionalized nanocrystal platform provides a modular strategy for exciton regulation in insulating nanocrystal systems, paving the way for the development of spectrally precise electroluminescent materials [8].

Core Viewpoint - The article discusses the dual role of ADAR1 protein in maintaining immune balance and its involvement in cancer progression, highlighting the potential for developing ADAR1 inhibitors for cancer treatment [3][12]. Group 1: ADAR1 Functionality - ADAR1 is an RNA editing enzyme that converts adenosine (A) to inosine (I) in double-stranded RNA (dsRNA), which is recognized as guanosine (G), thus facilitating RNA-level gene editing [5]. - There are two isoforms of ADAR1: ADAR1p110, which is involved in basic RNA editing and cellular homeostasis, and ADAR1p150, which is induced by interferons and plays a critical role in suppressing excessive immune activation [5]. Group 2: ADAR1 Deficiency and Autoimmunity - Deficiency or mutation of ADAR1, particularly the p150 isoform, can lead to severe autoimmune diseases due to the exposure of unedited endogenous dsRNA, activating various cellular sensors [8][11]. - The sensors activated include MDA5, which triggers interferon expression, and PKR, which halts global protein synthesis, potentially leading to cell death [8][9]. Group 3: ADAR1 in Cancer - ADAR1 can be exploited by cancer cells to evade immune detection by upregulating its expression, thus disguising themselves from the immune system [12]. - Inhibiting ADAR1 could expose cancer cells to immune recognition, simulating a viral infection state and activating immune responses against tumors [12]. Group 4: Development of ADAR1 Inhibitors - The article outlines six strategies for developing ADAR1 inhibitors, including accumulating dsRNA, inhibiting ADAR1's binding to dsRNA, and depleting ADAR1 through targeted degradation [15][16]. - These strategies aim to enhance the immune system's ability to recognize and attack cancer cells by increasing the levels of unedited dsRNA [16]. Group 5: Future Directions - Ongoing research aims to clarify which specific endogenous dsRNAs are most likely to trigger autoimmune responses and to develop selective inhibitors targeting the ADAR1p150 isoform in cancer cells [19][25].

Core Viewpoint - The article discusses the promising results of a phase 1 clinical trial that combines CD19-targeting and BCMA-targeting CAR-T cell therapies for treatment-refractory systemic lupus erythematosus (rSLE), highlighting its safety and potential clinical efficacy [3][10]. Group 1: Clinical Trial Overview - A phase 1 clinical trial was conducted to evaluate the co-infusion of CD19-targeting and BCMA-targeting CAR-T cells in rSLE patients, showing good safety and promising clinical efficacy [3][10]. - The trial involved 15 patients (14 females and 1 male) who had previously undergone lymphocyte-depleting therapy with fludarabine/cyclophosphamide [7][8]. Group 2: Safety and Efficacy Results - During a median follow-up of 712 days, no dose-limiting toxicities were reported, and 86.7% of patients experienced grade 1 cytokine release syndrome, with no neurological toxicities or treatment-related deaths [8][10]. - By week 12, 80% of patients achieved low disease activity status (LLDAS) and DORIS remission criteria, indicating significant clinical improvement [9][10]. Group 3: Mechanism and Immune Response - The study confirmed the elimination of autoreactive CD19+ BCMA+ clones and the reconstitution of initial IgM/IgD B cells, suggesting an improvement in immune homeostasis [9][10]. - Longitudinal monitoring of three patients indicated sustained eradication of pathogenic clones, suggesting potential for cure [10]. Group 4: Expert Commentary - The study received high praise from renowned rheumatology experts, emphasizing the dual-target strategy as a significant advancement in CAR-T cell therapy for systemic lupus erythematosus [10].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 癫痫 是一种常见的谱系障碍，具有多种风险因素和强烈的遗传倾向，通常至少伴有一种共病。癫痫的病因包括遗传基因 突变、结构性病变、感染、代谢紊乱、免疫异常以及其他不明因素。多种精神障碍 （例如焦虑症和抑郁症） 以及躯体 症状障碍 （例如 1 型糖尿病和关节炎） 都与癫痫有着密切关联。 迄今为止，癫痫的临床诊断主要依赖于详尽的病史采集、可靠的发病记录以及发作期间的影像学检查，因为目前尚无现 成的金标准。尽管抗癫痫药物在治疗癫痫症状方面的疗效是明确的，但针对病因的特异性治疗选择仍显不足。 2025 年 11 月 17 日， 青岛大学附属青岛市立医院 谭兰 教授、复旦大学附属华山医院 郁金泰 教授团队合作，在 Cell 子刊 Cell Reports Medcine 上发表了题为： Plasma proteomics identifies proteins and pathways associated with incident epilepsy 的研究论文。 该研究通过血浆蛋白质组学分析，鉴定出了多个与新发癫痫相关的血浆蛋白质和信号通路，并揭示了其对 未来癫痫风险 的预测能力 ...

撰文丨王聪 排版丨水成文 线粒体 （ Mitochondria ） 对于细胞能量的产生以及细胞的整体功能至关重要。 线粒体 DNA （mtDNA） 的突变可引发使人衰弱的疾病，尤其会损害肌肉和神 经细胞等高耗能组织。高精度线粒体 DNA 操作有望揭示潜在的疾病机制并提供针对性治疗方案，但要实现这种精度仍是一项重大挑战。 近几年，出现了线粒体 DNA 编辑方法，然而，这些方法通常难以实现精准的单碱基编辑，通常会产生 旁观者编辑 （ Bystander editing ） ，这成为 了线粒体 DNA 编辑技术更广泛应用的一个主要限制。 2025 年 11 月 1 7 日 ， 西湖大学生命科学学院 卢培龙 团队 和 北京大学未来技术学院/核糖核酸北京研究中心 汪阳明 团队合作 （ 米黎 、 李宇轩 、 吕莘辰 为论文共同第一作者 ） ，在 Nature 子刊 Nature Structural & Molecular Biology 上发表了题为： Computational design of a high-precision mitochondrial DNA cytosine base editor 的研究论 ...

Core Insights - The article discusses the positive impact of AI on breast cancer screening, particularly highlighting a study published in Nature Health that demonstrates the effectiveness of an AI-driven workflow in improving cancer detection rates in the U.S. [2][4] Group 1: AI in Breast Cancer Screening - AI has shown significant results in enhancing early detection and overall screening effectiveness for breast cancer, especially noted in European studies [4] - The study evaluates the AI-supported Assurance Review (ASSURE) workflow across four U.S. states, focusing on optimizing early cancer detection through AI-assisted diagnostic tools [4][6] Group 2: Study Results - Compared to traditional screening processes (N=370,692), the AI-driven workflow (N=208,891) increased the cancer detection rate (CDR) by 21.6% (5.6‰ vs 4.6‰), improved recall rate (RR) by 5.7% (11.1% vs 10.6%), and raised positive predictive value (PPV1) by 15.0% (5.0% vs 4.4%) [6] - The AI workflow demonstrated a CDR increase of 20.4%-22.7% across various racial and breast density subgroups, with no significant differences in CDR, RR, or PPV1 among different populations, indicating equitable clinical benefits [8] Group 3: Nature Health Journal - Nature Health prioritizes research that is original, timely, and impactful on health policy and practice, covering a wide range of health-related studies [8] - The journal emphasizes research conducted in resource-limited settings, including low- and middle-income countries, and considers various types of health research, including qualitative, observational, and real-world evidence studies [8]

Core Insights - The article highlights the significant growth of Chinese researchers' publications in Cell Press journals over the past decade, showcasing advancements in originality, systematic approaches, and openness in Chinese scientific research [2][48]. - In 2024, the total number of research papers published by Chinese institutions in Cell Press journals reached a record high of 2,446, marking a 17.6% increase from the previous year and nearly quadrupling the output from 2020 [3][14]. Publication Growth - The number of papers published in the life sciences field by Chinese scholars was the highest in 2024, totaling 860 papers, with the medical field showing the most notable growth, increasing by 138 papers [6]. - The journal Cell Reports Medicine saw the number of Chinese papers surpass 100 for the first time, while materials science and interdisciplinary fields also experienced steady growth, reaching 554 and 394 papers, respectively [6]. Journal Performance - In 2024, 18 hybrid journals under Cell Press reported growth in the number of Chinese publications, with Joule and Device in materials science showing the highest increases of 32 and 31 papers, respectively [7]. - The medical journal Med saw a remarkable increase, with a total of 32 papers published, reflecting a 2.5-fold increase from the previous year [7]. Open Access Trends - The proportion of papers published in open access (OA) format by Chinese scientists in Cell Press journals approached three-quarters of all Chinese publications, totaling 1,761 papers, which is a 13% increase from the previous year [10]. - The number of OA papers published in hybrid journals rose from 69 to 119, marking a 72.5% increase, indicating a growing commitment to open access among Chinese researchers [11]. Annual Paper Awards - The 2024 Cell Press Annual Paper Awards recognized 50 outstanding papers across five fields, with an additional 25 papers voted as the most popular by the public [14]. Research Institution Landscape - In 2024, the number of Chinese institutions publishing in Cell Press journals exceeded 300 for the first time, with a notable increase of 40 institutions from the previous year [32]. - Sun Yat-sen University led in publication volume with 113 papers, followed by Shanghai Jiao Tong University and Zhejiang University with 106 and 105 papers, respectively [32]. Regional and International Collaboration - Beijing remained the leading region for publications with 442 papers, followed by Guangdong and Shanghai [38]. - The number of countries and regions collaborating with Chinese scholars reached 76, reflecting a 20.6% increase, with the United States being the most frequent collaborator [43][47].

Core Viewpoint - The study reveals the critical role of the transcription factor IRF8 in the differentiation and function of exhausted CD8⁺ T cells in cancer, highlighting its potential as a target for new immunotherapy strategies [2][3][8]. Group 1: Research Findings - The research constructed a chromatin spatial structure map of tumor-specific exhausted CD8⁺ T cells, showing that IRF8 recruits the structural protein CTCF to reshape chromatin architecture and regulate gene expression, thereby influencing the differentiation and anti-tumor functions of exhausted CD8⁺ T cells [3][6]. - During the differentiation of CD8⁺ T cells, extensive chromatin spatial structure remodeling occurs, with 45% of structures in chromatin loops being reorganized as precursor exhausted CD8⁺ T cells (Tpex) transition to terminally differentiated exhausted CD8⁺ T cells (Ttex) [6]. - The absence of IRF8 significantly impairs the differentiation of exhausted CD8⁺ T cells and their anti-tumor functions, indicating its essential role in the spatial proximity reorganization between enhancers and promoters of genes related to T cell exhaustion [6][8]. Group 2: Implications for Immunotherapy - The findings suggest that IRF8-dependent chromatin topology plays a crucial role in the differentiation of exhausted CD8⁺ T cells, providing a potential target for developing new cancer immunotherapy strategies aimed at enhancing CD8⁺ T cell activity and improving anti-tumor immune responses [8].