撰文丨王聪 编辑丨王多鱼 排版丨水成文 帕金森病 （PD） 是一种无法治愈的神经退行性疾病，通常以隐匿的睡眠障碍和躯体症状开始，逐渐发展 为全身性运动和认知症状。 躯体-认知-行动网络 （ somato-cognitive action network， SCAN ） 的功 能障碍——该网络被认为通过协调觉醒状态、器官生理机能、全身运动计划与行为动机来控制动作执行 ——可能是导致帕金森病多样化临床表现的重要因素。 因此， 针对 SCAN 的特定神经调控，可能有助于治疗并改善帕金森病的症状。 2026 年 2 月 4 日，昌平实验室/北京大学 刘河生 教授 、 任建勋 、 王聃红 及 河南省人民医院 王梅云 教授作为共同通讯作者（ 任建勋 、 张维 为论文共同第一作者 ），在国际顶尖学术期刊 Nature 上发表了 题为： Parkinson's disease as a somato-cognitive action network disorder 的研究论文。 该研究 首次在功能环路层面揭示了帕金森病的关键异常机制 ，揭示了帕金森病是一种 躯体-认知-行动网 络障碍 （ somato-cognitive ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 Clinical Medicine Insights: Oncology 是 Sage 出版社旗下的一本国际化、同行评议的 开放获取期刊 （ Open Access Journal ） 。 该期刊发表有关癌症研究和治疗所有方面的文章，包括但不限于分子生物学、遗传学、病理生理学、流行病学、临床干预、对照试验、癌症患者的诊断和治疗、 治疗学、药理学和药物递送，以及癌症手术技术等主题。该期刊欢迎多种类型的稿件，包括 original research、review、systematic review、meta-analysis、 study protocols 以及 Letters to the Editor， original research 稿件可涵盖实验室、动物或人类/临床研究的各个阶段。 该期刊目前 影响因子 （IF） 为 1.9 ，根据实时影响因子预测， 该期刊将在今年 6 月份更新的影响因子中达到 2.5 分 。 该期刊现在中国 诚邀投稿 ，出版社官方特别推出 投稿福利：如您近期有适合的稿件投稿，欢迎 扫描下方二维码 填写信息 ，申请获取 APC 9 折优惠码 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 胶质母细胞瘤 （GBM） ，是最致命的 原发性中枢神经系统癌症，对目前的免疫治疗手段表现出显著的抗性。其肿瘤微环境是一个免疫荒漠，充满着抑制性因 素，有效攻击肿瘤的 T 细胞少之又少，传统免疫疗法很难奇效，关键在于我们难以直接改变大脑的免疫状态。 脑膜 是保护大脑的一个三层结构保护膜，其最外层为 硬脑膜 ，近年来的研究显示，这是一个活跃的免疫监视中心，能够采样、检查 并呈递中枢神经系统 （CNS） 来源的抗原，激活 T 细胞免疫。因此，如果增强硬脑膜的功能，是否可以从外向内强化大脑的抗肿瘤免疫力？ 2026 年 2 月 4日，中山大学第一附属医院 张弩 教授团队联合北京大学 白凡 教授团队，在国际顶尖学术期刊 Cell 上发表了题为： Meningeal blood vessel blockage enhances antiglioblastoma immunity 的研究论文。 该研究开发了一种硬脑膜界面功能性调控的显微外科方法—— 脑膜血管阻断 （ meningeal blood vessel blockage， MBB） ，证实了该方法能够有效抑制 胶质 母细胞瘤 ...

该研究表明， 活化的 ATF6α 是一种肝肿瘤驱动因子，可限制免疫监视，其可作为免疫检查点阻断 （ICB） 疗法响应的潜在分层标志物，也是肝细胞癌的治疗新 靶点。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 肝细胞癌 （HCC）， 主要源自慢性肝炎中恶性转化的肝细胞，其 占原发性肝癌的 80% - 85%。尽管免疫疗法的进步提高了肝细胞癌患者的生存率，但复杂的 遗传、代谢和炎症相互作用仍是有效治疗的障碍。 肝细胞癌浸润淋巴细胞表达耗竭标志物 （例如 PD-1、CTLA-4） ，导致预后不良。免疫检查点阻断 （阿特珠单抗） 和血管内皮生长因子 （VEGF） 阻断 （贝 伐珠单抗） 以改善 T 细胞介导的肿瘤监视是不可切除肝细胞癌的标准治疗方法。然而，肝细胞癌中的代谢重编程 （包括葡萄糖剥夺和肿瘤内缺氧环境） ，会降 低抗肿瘤治疗效果并增强恶性程度。因此，需要新的策略来克服与代谢相关的肿瘤逃逸和免疫抑制。 2026 年 2 月 4 日， 德国癌症研究中心 Li Xin 作为第一作者，在国际顶尖学术期刊 Nature 上发表了题为： Activated ATF6α is a hepatic tumour driver ...

Core Viewpoint - The article discusses the long-standing public health issue of why certain mosquito species can transmit specific viruses while others cannot, emphasizing the need for a deeper understanding of the biological mechanisms behind mosquito-virus interactions [4][5]. Group 1: Mosquito Species and Virus Transmission - There are over 3,500 known mosquito species, but fewer than 100 can transmit severe human infectious diseases such as dengue, Zika, and malaria [2]. - The main mosquito vectors are categorized into three types: Aedes, Culex, and Anopheles, with Aedes being the primary vector for tropical diseases [2][4]. - Culex mosquitoes are widespread in temperate regions but are ineffective in transmitting tropical viruses like dengue and Zika, limiting the spread of these diseases to tropical and subtropical areas [4]. Group 2: Scientific Questions and Research Findings - Two fundamental scientific questions remain: the biological basis of mosquito-virus interactions and the reasons behind the species-specific transmission of different viruses by various mosquito species [5]. - A study published in Nature by a team from Tsinghua University identified that the acidic environment of the blood lymph in certain mosquitoes allows for the specific interaction between the virus and mosquito proteins, leading to the formation of infectious extracellular vesicles [7][12]. - The research revealed that the interaction between mosquito VCP proteins and viral capsid proteins is crucial for determining the specificity of virus infection in mosquitoes, highlighting the importance of molecular compatibility in virus transmission [10][12].

Core Viewpoint - The study reveals the dual role of intratumoral bacteria in regulating tumor immunity, highlighting the significant impact of bacterial invasion on immune responses and tumor recurrence [3][12][18]. Group 1: Tumor Microenvironment and Immune Response - Tumors are categorized as "hot" (immune-activated) or "cold" (immune-suppressive) based on immune cell infiltration and activity, with cold tumors showing insufficient immune response and resistance to immunotherapy [2]. - The presence of intratumoral bacteria is linked to regional immune-suppressive microenvironments, influencing cancer cell behavior and immune cell function through various mechanisms [2][3]. Group 2: Research Findings on Bacteria and Tumor Cells - The research conducted by Cai Shang's team demonstrates that intracellular bacteria activate the cGAS-STING-IL17B signaling pathway in cancer cells, leading to the induction of neutrophils into an immune-suppressive state, thus promoting tumor recurrence [3][12]. - In contrast, extracellular bacteria induce neutrophil subpopulations with anti-tumor functions, activating immune responses that inhibit tumor recurrence [3][12]. Group 3: Methodology and Experimental Models - A strict model for studying intracellular bacteria was established using organoid-bacteria co-culture systems, allowing for the specific investigation of the physiological functions of intracellular bacteria [8]. - In preclinical mouse models, the presence of intracellular bacteria was found to be a key factor in long-term tumor recurrence, with antibiotic treatment reducing recurrence rates significantly from 65% to 6.7% [9]. Group 4: Immune Cell Dynamics - Single-cell RNA sequencing revealed that intracellular bacteria induce neutrophils with myeloid-derived suppressor cell (G-MDSC) characteristics, while extracellular bacteria promote neutrophils with anti-tumor profiles [11][12]. - The cGAS-STING pathway is crucial for the immune reprogramming induced by bacterial invasion, with IL-17B identified as a key mediator in promoting immune suppression [12][14]. Group 5: Clinical Relevance and Future Directions - The study indicates that the strength of bacterial signals within tumor tissues correlates positively with neutrophil infiltration and is associated with poorer prognosis in breast cancer patients [15][19]. - Future research aims to explore targeted strategies for eliminating or limiting intracellular bacterial invasion, optimizing postoperative antibiotic and immunotherapy combinations to prevent tumor recurrence [19].

Core Viewpoint - Merge Labs is pioneering a non-invasive brain-computer interface (BCI) technology using ultrasound to read brain activity and treat mental disorders, contrasting with invasive methods like those used by Neuralink [2][6]. Group 1: Company Overview - Merge Labs, supported by OpenAI, completed a $252 million seed funding round in January 2026, with investors including OpenAI, Bain Capital, and Gabe Newell [2]. - The company aims to develop a BCI that interacts with a significantly larger number of neurons with less invasiveness compared to existing technologies [6]. Group 2: Technology Comparison - The BCI landscape is divided into two camps: Neuralink's invasive electrode implantation and Merge Labs' non-invasive ultrasound technology [6]. - Merge Labs' ultrasound technology can image and modulate large brain areas by sending high-frequency sound waves, avoiding the risks associated with surgical procedures [6]. Group 3: Ultrasound Technology Mechanism - The ultrasound technology works by emitting high-frequency sound pulses and measuring the echoes that return from different tissue types, allowing for the detection of blood flow changes related to neuronal activity [8]. - The technology can measure blood flow changes in brain regions as small as 100 micrometers, enabling the monitoring of small groups of neurons [8]. Group 4: Genetic Engineering Integration - Merge Labs is exploring the combination of ultrasound with sonogenetics, a gene engineering technique that makes specific brain cells responsive to sound waves, enhancing signal detection and control [10]. - This innovative approach aims to improve the precision of signal reading while significantly reducing invasiveness [10]. Group 5: Scientific Basis and Challenges - Despite its potential, the ultrasound BCI technology is still in its early stages and faces significant scientific and technical challenges, including high costs and hardware miniaturization [12]. - Initial focus will be on medical applications to assist patients with neural damage or diseases, with long-term goals of enhancing human capabilities through safe and convenient technology [12]. Group 6: Future of Human-Machine Interaction - OpenAI's CEO has expressed concerns about invasive methods and advocates for safer alternatives that allow users to interact with AI tools through thought [14]. - Merge Labs aims to blur the lines between humans and AI, representing a new frontier in human-machine integration [14].

编辑丨王多鱼 排版丨水成文 核膜 （nuclear envelope，NE） 是一种高度动态的选择性屏障，在维持核质分隔的同时，参与调控核质转 运、基因组稳定性、基因表达等关键生命过程。然而，随着机体衰老，这层细胞核的"城墙"的形态与功能 会发生严重的破坏，并与早衰综合征、代谢紊乱、肿瘤及神经退行性疾病等多种人类疾病密切相关。然 而，如何保护衰老过程中细胞核"城墙"的完整与健康，长期以来未被阐明。 2026 年 2 月 3 日，中国科学院遗传与发育生物学研究所 田烨 研究员团队在 Nature Metabolism 期刊发 表了题为： Mitochondrial Superoxide Regulates Nuclear Envelope Integrity and Aging via Redox- Mediated Lipid Metabolism 的研究论文。 该揭示了 发育阶段 的 线粒体超氧阴离子 并非破坏性的"坏分子"，而是作为一种关键的" 保护性信号 "， 通过重编程脂质代谢通路，保护核膜完整性并延缓衰老 。该研究还提出， 靶向抑制脂质过氧化这一策略具 有治疗早衰症及改善机体衰老的转化潜力 。值得一 ...

Core Viewpoint - The study highlights that targeting FBXL2 can enhance HER2 expression in HER2-negative triple-negative breast cancer (TNBC) cells, making them more susceptible to trastuzumab deruxtecan (T-DXd) treatment, suggesting a viable therapeutic strategy for HER2-IHC 0 tumors [4][5][6] Group 1 - Trastuzumab deruxtecan (T-DXd) is a HER2-targeted antibody-drug conjugate that has transformed the treatment landscape for HER2-positive solid tumors [3] - The presence of high-density HER2-negative (HER2-IHC 0) cells limits the clinical efficacy of T-DXd [3] - The research published in Nature Cancer indicates that inhibiting FBXL2 can increase HER2 expression on the cell membrane of HER2-negative TNBC cells, enhancing their sensitivity to T-DXd [4][5] Group 2 - The mechanism involves FBXL2 promoting polyubiquitination and proteasomal degradation of HER2 at the K747 site [5] - Small molecules GGTi-2418 and ketoconazole can effectively increase HER2 expression by preventing FBXL2 membrane localization [5] - The study demonstrated that using lipid nanoparticles (LNP) to encapsulate GGTi-2418 and ketoconazole in HER2-IHC 0 TNBC xenograft mouse models resulted in significant and durable tumor regression when combined with T-DXd [5] Group 3 - A concurrent article in Nature Cancer emphasizes that methods to enhance HER2 expression in breast cancer could broaden the patient population eligible for T-DXd treatment [6] - The findings from the study suggest that inhibiting FBXL2 can make HER2-negative breast cancer cells sensitive to T-DXd, leading to significant tumor regression [6]

Core Viewpoint - CAR-T cell therapy is a revolutionary cancer treatment that utilizes genetically modified T cells to target and kill cancer cells, and it has shown promise in treating autoimmune diseases as well [2]. Group 1: Challenges of Traditional CAR-T Therapy - The preparation of CAR-T therapy is complex and expensive, involving blood extraction, genetic modification, and expansion, which can take several weeks and incur high costs [3]. - A pre-treatment with chemotherapy is required to clear the patient's existing lymphocytes before reinfusion, leading to significant side effects [3]. Group 2: Innovations in CAR-T Therapy - Researchers have proposed in vivo CAR-T cell therapy, which allows for the direct generation of CAR-T cells in the body through injection, potentially simplifying and broadening access to CAR-T therapy [4]. - A study published on February 3, 2026, introduced a novel adeno-associated virus variant, AAV6-M2, which can specifically target human T cells and generate CAR-T cells effectively in a mouse model of systemic lupus erythematosus (SLE) [4][5]. Group 3: Mechanism and Efficacy - The AAV6-M2 variant was developed using AI-assisted design and high-throughput screening, allowing it to efficiently target resting T cells without prior activation, which is crucial for in vivo CAR-T cell generation [8]. - In tests on humanized mouse models, a single injection of AAV6-M2-CD19CAR led to a 77.5% conversion rate of CD8+ T cells to CAR-T cells, effectively eliminating B cells and improving symptoms of lupus [10]. Group 4: Safety and Advantages - AAV6-M2 demonstrated significantly reduced liver tropism compared to wild-type AAV, lowering the risk of liver toxicity and enhancing the cost-effectiveness of the treatment [13]. - The study indicates that AAV-mediated CAR delivery can generate functional human CAR-T cells in vivo, marking a shift from personalized treatments to more universal, off-the-shelf products [5][14]. Group 5: Future Prospects - This research signifies a platform innovation, proving that a single systemic injection of an AAV vector can generate durable, functional human CAR-T cells, paving the way for rapid clinical translation [14]. - The application of AAV-mediated gene therapy is expanding from genetic diseases to cancer and autoimmune diseases, opening new avenues for accessible cell and gene therapies [15].