撰文丨王聪 编辑丨王多鱼 排版丨水成文 肺癌 是一种极为常见的恶性肿瘤，是全球癌症相关死亡的主要原因。其中， 非小细胞肺癌 （NSCLC） 约 占所有肺癌病例的 85%， 其预后通常不佳。 免疫治疗领域的最新进展，尤其是 PD-1/PD-L1 单克隆抗体的应用，为 NSCLC 患者带来了新希望。临床 上，关键免疫检查点 PD-L1 表达情况常被评估以选择合适的免疫治疗药物，阻断 PD-1/PD-L1 通路能够 使耗竭的 CD8 + T 细胞重新活跃并恢复其肿瘤杀伤功能。 然而，PD-L1 并非理想的预测性生物标志物，因为一些 PD-L1 低表达的患者仍能从免疫治疗中获益。尽 管免疫治疗在晚期 NSCLC 患者中取得了令人鼓舞的 5 年生存率，但仍有部分患者出现复发或远端转移。 因此，寻找更有效的免疫治疗预测性生物标志物，对于 NSCLC 患者而言 至关重要。 近日，山东第一医科大学附属肿瘤医院 （山东省肿瘤防治研究院、山东省肿瘤医院） 陈大卫 团队在 Therapeutic Advances in Medical Oncology 期刊发表了 题为： Neutrophil extracellular trap ...

Core Viewpoint - OriCell, a subsidiary of Saiye, focuses on cell biology and stem cell technology services, emphasizing the importance of mesenchymal stem cells (MSC) in regenerative medicine and their growing application in clinical trials [2][10]. Group 1: MSC Research and Development - MSCs have unique differentiation potential and immune regulation capabilities, making them a key focus in regenerative medicine [2]. - The National Medical Products Administration (NMPA) has approved nearly 200 clinical trial applications for stem cell products, with the first MSC therapy, "Aimi Maitosai Injection," set to launch in early 2025 for treating hormone-refractory acute graft-versus-host disease [2]. - The application boundaries of MSCs are expanding, serving as a crucial bridge between basic research and clinical translation [2]. Group 2: Research Support and Resources - OriCell has compiled a research guide titled "Mesenchymal Stem Cells: Cultivation and Tri-lineage Induction," aimed at both newcomers and experienced research teams to provide practical technical support [3]. - The guide offers a systematic framework of MSC knowledge, detailing definitions, characteristics from different sources, and biological functions to help establish foundational understanding [5]. - It includes standardized operational processes, breaking down key procedures such as cell passage digestion time, cryopreservation points, and recovery plating density, along with tri-lineage induction steps and identification methods [5]. Group 3: Practical Solutions and Optimization - The guide provides practical solutions to common experimental challenges, analyzing factors like serum quality and culture temperature, and offering validated optimization strategies to avoid typical pitfalls in experiments [5]. - OriCell aims to enhance the confidence in MSC cultivation and induction processes, supporting researchers in overcoming experimental difficulties [7].

2025 年 11 月 13 日法国 波尔多大学的研究人员在 Cell 子刊 Current Biology 上发表了题 为： Obesogenic diet impairs memory consolidation via the hippocampal endocannabinoid system 的研究论文。 该研究表明， 致肥性饮食 （ Obesogenic Diet ） 通过大脑海马体的 内源性大麻素系统 损害 记忆巩固 。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 致肥性饮食 （ Obesogenic Diet ）， 是指容易导致肥胖的饮食模式，通常具有以下特点— 高热量密度 （富含精制糖、饱和脂肪和反式脂肪，例如油炸食品、甜 点、含糖饮料） 、 低营养素密度 （缺乏膳食纤维、维生素和矿物质，例如快餐） 、 过度加工 （超加工食品占比高，例如膨化食品）以及 不规律饮食习惯 （例 如 暴饮暴食、夜间进食、不吃早餐等 ） 。 尽管致肥性饮食会损害人类和啮齿类动物的 大脑记忆功能 ，但其中的具体机制尚不明确。 鉴于大脑的内源性大麻素系统 （endocannabinoid system） 及其 1 型大麻素 ...

Core Viewpoint - A new artificial tongue developed by East China University of Science and Technology can accurately measure the spiciness of various foods, providing a significant advancement in food quality control [1][2][5]. Group 1: Research Overview - The research titled "A Soft and Flexible Artificial Tongue for Pungency Perception" focuses on the precise measurement of spiciness, which is crucial for food quality control [2][5]. - The artificial tongue is made from a gel that includes milk powder, acrylic acid, and choline chloride, which allows it to detect spiciness through changes in electrical conductivity when interacting with capsaicin, the compound responsible for the heat in peppers [6][8]. Group 2: Methodology and Results - The research team tested the artificial tongue with eight different types of peppers, creating a spiciness scale from 0 to 70, ranging from mild to extremely spicy [6][8]. - The results showed a strong correlation between the artificial tongue's measurements and those of trained human taste testers, indicating its potential to replace human taste testing for spicy foods [6][8]. Group 3: Performance Characteristics - The artificial tongue can detect spicy compounds within a wide range (0.0001 - 1% wt %) and demonstrates high sensitivity (0.259% wt % - 1) and a rapid response time of less than 10 seconds [8]. - This technology opens up possibilities for applications in mobile humanoid robots and portable spiciness monitoring devices, enhancing the food industry’s ability to assess flavor profiles [8].

Core Viewpoint - The article discusses the development and clinical trials of BBM-H901, the first gene therapy for Hemophilia B in Asia, which shows promising safety and efficacy results for patients [4][9]. Group 1: Gene Therapy Development - BBM-H901 utilizes FIX-Padua, a high-activity variant of coagulation factor IX, delivered via an AAV vector targeting the liver, providing a new treatment option for Hemophilia B patients [3][4]. - The therapy was developed by a team led by Professor Xiao Xiao from East China University of Science and Technology and has been approved for market in China as "Xinjiao Ning" since April 10, 2025 [3]. Group 2: Clinical Trials - Initial Phase 1 trials involved 10 male patients, followed by a Phase 1/2 dose-escalation study with 6 patients and a Phase 3 confirmatory study with 26 patients to evaluate the efficacy of BBM-H901 [6]. - The Phase 1/2 study tested a dose of 5×10^12 vg/kg and achieved its primary endpoint without observing dose-limiting toxicities, with the most common adverse event being elevated transaminases (33.3%) [6][7]. Group 3: Efficacy Results - In the Phase 3 trial, the average annualized bleeding rate (ABR) dropped to 0.60 within 52 weeks post-infusion, significantly below the pre-defined efficacy threshold of 5.0 [7]. - The average FIX:C level from the AAV vector was 41.9 IU/dL at 52 weeks, with 80.8% of patients experiencing no bleeding during the follow-up period [7][9].

Core Viewpoint - The article discusses the recent announcement of the 2024 Annual Outstanding Paper Awards by Sanofi-Cell Research, highlighting three significant research papers published in Cell Research that have made notable contributions to their respective fields [2]. Group 1: Paper Summaries - The first paper titled "Hypoxia induces mitochondrial protein lactylation to limit oxidative phosphorylation" reveals that hypoxia-induced mitochondrial protein lactylation inhibits oxidative phosphorylation (OXPHOS). The study identifies AARS2 as a lactyltransferase that modifies PDHA1 and CPT2, reducing acetyl-CoA influx and suppressing OXPHOS. SIRT3 can reverse this lactylation, emphasizing the role of lactylation in mitochondrial function regulation [8][13]. - The second paper titled "40 Hz light flickering promotes sleep through cortical adenosine signaling" demonstrates that 40 Hz light flickering increases extracellular adenosine levels in the primary visual cortex via ENT2-mediated transport. The study shows that 30 minutes of 40 Hz light flickering enhances both non-rapid eye movement and rapid eye movement sleep in mice, suggesting a non-invasive strategy for treating insomnia [14][16]. - The third paper discusses a novel design strategy for D-type proteins that can stably target natural L-type proteins or peptides. This research achieves the precise design of enantiomeric protein complexes with high stereospecificity and target specificity, exhibiting significant thermal stability and proteolytic resistance. The findings provide a new platform for disease treatment and biotechnological applications [18].

Core Insights - The article discusses the development of SVAtlas, a comprehensive single extracellular vesicle (EV) omics resource that addresses the challenges of analyzing EV heterogeneity and facilitates clinical applications in disease diagnostics [3][10]. Group 1: Background and Importance of EVs - Extracellular vesicles (EVs) are nano-sized particles secreted by cells, carrying important biomolecules like proteins and nucleic acids, and play a significant role in intercellular communication and disease progression [2]. - The presence of EVs in easily accessible bodily fluids such as blood and urine makes them ideal candidates for liquid biopsy in cancer and neurodegenerative disease research [2]. Group 2: Challenges in EV Research - Traditional bulk analysis techniques struggle to capture the molecular characteristics of individual EVs due to the high heterogeneity within EV populations, which obscures critical disease signals and hinders clinical application [2][5]. - The lack of standardized technology and fragmented data has limited the clinical application of EV biomarkers [2][5]. Group 3: Development of SVAtlas - The research team from Shandong University, led by Hou Qingzhen, constructed the first cross-disease, cross-body fluid, and cross-species single EV multi-omics atlas, named SVAtlas, published in Nucleic Acids Research [3][5]. - SVAtlas integrates self-sequencing data with results from 276 global research projects, covering 31 major diseases, 32 types of tissues and organs, and 10 types of biological fluids, including data from over 137 million single EVs [5]. Group 4: Features and Functionality of SVAtlas - The platform supports analysis of tissue/organ heterogeneity and disease-specific subgroups, providing global clustering, high-heterogeneity subgroup selection, and differential heatmaps to display single EV distribution and characteristics [7]. - SVAtlas includes a dynamic analysis platform with built-in computational biology tools for data browsing, preprocessing, clustering analysis, and interactive visualization, aiding in the identification of disease-specific biomarkers [8]. - The platform features an AI question-and-answer tool based on large language models (LLM) to assist users in navigating complex single EV characterization methods [8]. Group 5: Future Implications - The establishment of SVAtlas marks a new phase in single EV research, enabling standardized and multi-omics integration, allowing researchers to explore EV heterogeneity and discover potential biomarkers on a unified platform [10]. - With the addition of more data and novel omics, SVAtlas is expected to become a crucial tool in liquid biopsy, precision medicine, and disease diagnostics [10].

Core Viewpoint - The study highlights the critical role of mature tertiary lymphoid structures (mTLS) in mediating B cell-driven antitumor immunity in locally advanced rectal cancer (LARC) and discusses the detrimental effects of neoadjuvant therapy (neoTx) on mTLS [4][8]. Group 1: Research Findings - The research team conducted a multi-omics analysis on 161 LARC patient samples from two clinical centers, identifying mTLS and immature TLS (iTLS) through various techniques [6]. - mTLS tumors exhibited significant enrichment of B cells and plasma cells compared to iTLS, with bulk RNA sequencing revealing upregulation of plasma cell and follicular B cell-related gene signatures [6]. - Single-cell RNA sequencing indicated that plasma cells in mTLS not only had a higher proportion but also demonstrated greater clonal diversity and stronger immunoglobulin production capabilities, particularly for IgG and IgA [6]. Group 2: Clinical Implications - The presence of mTLS and high expression of plasma cell marker CD138 were significantly associated with longer overall survival (OS) in patients, suggesting that mTLS and B cell immunity are favorable prognostic markers in rectal cancer [7]. - Analysis of 125 patients undergoing neoTx revealed that while T cell infiltration increased, the proportion of mTLS significantly decreased, indicating that neoTx primarily activates T cell-mediated immunity at the expense of mTLS structures [8]. - In patients who did not respond to neoTx, B cell-related gene signatures and CD20⁺ B cell infiltration were significantly higher despite no increase in mTLS, suggesting a compensatory B cell immune response independent of mTLS, which may relate to treatment resistance [8]. Group 3: Future Directions - The findings underscore the importance of mTLS in the tumor microenvironment of rectal cancer and the complex remodeling effects of standard neoTx on immune responses [8]. - These insights provide a theoretical basis and potential biomarkers for developing new treatment strategies aimed at preserving or leveraging B cell immunity, particularly in conjunction with neoTx [8].

撰文丨王聪 编辑丨王多鱼 该研究发现，被趋化素激活后，GPR1 通过至少四种方式与 β-arrestin 1 结合，体现了两者从"预结合"到"稳定结合"状态的动态过程。这是首次在原子水平阐明 一种 GPCR 与 arrestin 相互作用的动态调控模式，为理解阻遏蛋白介导受体脱敏及内吞的分子机制提供了重要信息，同时也提出了靶向多种构象状态开展药物研 发的必要性，将促进开发特异性靶向阻遏蛋白信号通路的新型偏向性药物。 排版丨水成文 趋化素 （chemerin） 是一种重要的脂肪因子，参与调控脂质代谢和胰岛素敏感性，与肥胖、糖尿病等代谢性疾病的发生发展密切相关。同时，趋化素还能介导免 疫细胞定向迁移至炎症部位，参与机体抵御病原入侵、维持稳态和修复组织损伤等重要生理过程，在炎症与代谢之间发挥"桥梁"作用。 趋化素的生物学效应由其受体介导，包括 CMKLR1 和 GPR1 。其中，CMKLR1 作为一种典型的 G 蛋白偶联受体 （GPCR） ，通过 G 蛋白信号通路驱动脂质 代谢与炎症反应，而 GPR1 则是一种非典型的 GPCR，依赖于阻遏蛋白 （arrestin） 介导的信号通路和受体内吞，清除过量的趋化素。趋化 ...

Core Insights - The article highlights the significant growth in the number of research papers published by Chinese scientists in Cell Press journals over the past decade, indicating advancements in originality, systematic approaches, and openness in Chinese research [2] - In 2024, the total number of research papers published by Chinese institutions in Cell Press journals reached 2,446, marking a 17.6% increase from the previous year and nearly quadrupling the publication volume from 2020 [2] Group 1: Research Output - The number of research papers published by Chinese institutions in Cell Press journals has shown a remarkable increase, with 2,446 papers published in 2024 [2] - This represents a 17.6% increase compared to the previous year and is nearly four times the publication volume from 2020 [2] Group 2: Awarded Papers - Cell Press has selected 50 papers for the "Cell Press 2024 China Annual Papers" across five fields: life sciences, material sciences, medicine, interdisciplinary studies, and sustainable development [2] - Each field includes 10 papers, showcasing the diversity and impact of Chinese research in various scientific domains [2]