Core Viewpoint - The article discusses the development of clinically ready magnetic microrobots for targeted drug delivery, which represents a significant advancement in the field of precision medicine, potentially reducing systemic side effects associated with traditional drug administration methods [5][7]. Group 1: Research Development - Researchers at ETH Zurich have created a magnetic microrobot, approximately the size of a grain of sand (less than 2 mm in diameter), capable of navigating through blood vessels to deliver drugs precisely to targeted areas [5][8]. - The study highlights that about one-third of developed drugs fail to receive approval due to excessive side effects, emphasizing the need for targeted delivery systems [5][7]. Group 2: Technological Breakthroughs - The platform developed by the research team integrates three major breakthroughs: modular design, a clinical-grade navigation system, and safe biodegradable microrobots [8]. - The navigation system utilizes a dual Navion electromagnetic navigation system, providing a workspace of 20×20×20 cm with a magnetic field gradient of up to 1 T/m, ensuring stable navigation within blood vessels [8][11]. - The microrobots are made from a gelatin matrix containing iron oxide nanoparticles for magnetic response, tantalum nanoparticles for X-ray visibility, and therapeutic drugs, all of which are FDA-approved for vascular applications [8][9]. Group 3: Navigation and Drug Delivery Mechanism - The microrobots can adapt to different blood flow environments through three navigation modes: rolling on vessel walls, countercurrent navigation, and downstream navigation, achieving a 95% success rate at bifurcations [11]. - Upon reaching the target site, the microrobots release drugs in a controlled manner using a high-frequency magnetic field, ensuring that drug release is halted if the robot deviates from the target [13][15]. Group 4: Experimental Validation - Experiments in a biomimetic vascular model demonstrated that the microrobots could be accurately navigated to various branches of the middle cerebral artery, with thrombolytic demonstrations showing significant potential for treatment [15]. - Large animal studies confirmed the clinical feasibility of the technology, successfully guiding microrobots to specific arteries in pig and sheep models, indicating potential applications in the central nervous system [15][17]. Group 5: Future Implications - Although clinical applications are still in the future, this research provides a viable technical pathway for precision drug delivery, with the potential to treat conditions such as vascular occlusion, localized infections, or tumors while minimizing systemic exposure [17]. - The research team plans to consider human clinical trials as the next step in the development of this technology [17].

Core Insights - The article discusses a groundbreaking study on ancient RNA from the woolly mammoth, published in Cell, which reveals that RNA can be preserved for thousands of years, potentially transforming the study of extinct species [4][5]. Group 1: Research Findings - The study presents the transcriptome profiles of 10 woolly mammoths, with one specimen dating back approximately 39,000 years, providing detailed transcriptional information related to muscle metabolism and specific regulatory mechanisms [4]. - The research indicates that ancient RNA can survive for millennia, suggesting a new approach to studying extinct organisms and the potential for a multi-dimensional approach integrating genomics, proteomics, and transcriptomics in paleobiological research [5]. - The study successfully identified multiple muscle-specific mRNAs from a 39,000-year-old mammoth specimen, Yuka, and discovered potential novel miRNA candidate sites based on the ancient RNA sequences [9]. Group 2: Methodology and Challenges - The research team developed a methodological framework for isolating ancient RNA, incorporating quality control standards for metagenomic and metatranscriptomic analyses, and addressing the unique characteristics of ancient RNA [8]. - The study highlights the challenges of recovering transcriptional data from extinct species due to the instability of RNA, which degrades quickly unless immediately preserved [7]. - The findings demonstrate that tissue-specific gene expression patterns can be preserved over time, revealing previously unknown aspects of extinct organisms [11].

Core Viewpoint - The article emphasizes the importance of adeno-associated virus (AAV) as a crucial tool for gene delivery in fields such as gene therapy and neuroscience, while addressing the challenges researchers face in the entire process from design to implementation [3][4]. Group 1: Course Announcement - An online course titled "AAV Experimental High-Frequency Issues Breakdown: From Basic Knowledge to Practical Application" will be held on November 20, focusing on 20 core challenges faced by researchers [4][6]. - The course will be led by experienced professionals from Saiye Biotechnology, including the AAV Gene Therapy Project Manager and an AAV Solution Design Engineer [6][8]. Group 2: Learning Outcomes - Participants will gain essential knowledge about AAV-mediated gene delivery mechanisms, selection principles for serotypes and promoters based on target tissues [6]. - The course will cover the applicability and limitations of different administration routes, as well as standardization strategies for virus titer and dosage [6]. - Attendees will learn multi-dimensional effect verification methods and troubleshooting approaches when experimental results are unsatisfactory [6]. Group 3: Company Background - Saiye Biotechnology, established in 2006, is a national high-tech enterprise and recognized as a "little giant" specializing in the life sciences sector, committed to supporting global life sciences with excellent models and services [16].

撰文丨王聪 编辑丨王多鱼 对于 复发性鼻咽癌 ，采用 调强放射治疗 （IMRT） 进行再照射仍是最有效的治疗方法。然而，其疗效仍不尽人意，且 治疗相关的不良事件较为显著，这凸显了需要更先进的治疗策略来提高生存率并降低毒性。 2025 年 11 月 14 日，中山大学肿瘤防治中心 陈明远 教授、 华贻军 教授及中山大学附属第五医院 游瑞 副教授等， 在 Cell 子刊 Med 上发表了题为： TQB2450 plus intensity-modulated radiotherapy in recurrent nasopharyngeal carcinoma: An open-label, single-arm, phase II trial 的研究论文，该论文还被选为当期 封面论文 。 这项 2 期临床试验显示， TQB2450 （ 正大天晴 开发的抗 PD-L1 全人源化单克隆抗体 ） 联合 调强放射治疗 （IMRT） 显示出对 复发性 鼻咽癌 的 良好疗效，且免疫相关毒性可控。 该研究还表明，连续监测血浆 EB 病毒 DNA 可能成为预测这种联合疗法治疗效果的有用工具。综合基因组和空间转录 组学分析表明，T ...

Core Insights - The research published by Fudan University reveals a novel signaling function of Acetyl-Coenzyme A (AcCoA) in regulating mitophagy through the receptor NLRX1, independent of classical pathways like AMPK and mTOR [3][14][16] - This discovery provides new potential targets and strategies for overcoming resistance to KRAS inhibitors in cancer treatment [3][14][16] Group 1: Mechanism of AcCoA in Mitophagy - AcCoA levels decrease during nutrient deprivation, such as short-term fasting, leading to the activation of mitophagy [5][6] - NLRX1 is identified as a key mediator that directly binds to AcCoA, regulating its signaling role in mitophagy [8][11] Group 2: Experimental Validation - In animal models, fasting resulted in a significant decrease in AcCoA levels in tissues, correlating with increased mitophagy [11] - Supplementing with acetate or knocking out NLRX1 gene can block the fasting-induced mitophagy, indicating the critical role of AcCoA and NLRX1 in this process [11][12] Group 3: Implications for Cancer Treatment - The study indicates that KRAS inhibitors downregulate ACLY expression, reducing AcCoA levels and triggering NLRX1-dependent mitophagy, which may contribute to cancer cell resistance [14] - Short-term fasting may have dual effects in cancer treatment, potentially enhancing immune response while also promoting resistance through mitophagy [14][16] Group 4: Future Directions - Targeting the AcCoA-NLRX1 signaling axis may enhance cancer treatment efficacy and could have implications in various metabolic and neurodegenerative diseases [16]

Core Insights - The ADAR (Adenosine deaminases acting on RNA) family plays a crucial role in RNA A-to-I editing, regulating RNA diversity, immune homeostasis, and neural function [3] - ADAR-based RNA editing technology has rapidly developed, offering advantages over CRISPR gene editing, such as avoiding the introduction of foreign editing enzymes and related immunogenicity issues, making it a promising candidate for genetic disease therapies [3] - Mutations in the ADAR1 gene can lead to autoimmune diseases, such as Aicardi-Goutières syndrome, by editing the host's double-stranded RNA (dsRNA) to prevent unnecessary autoimmune responses [3] Research Findings - A series of studies published in Nature in July 2022 elucidated the downstream pathways of ADAR1 gene mutations leading to autoinflammation, identifying ZBP1 as a key effector factor in cell death and inflammation transcription [4][6] - Research from Stanford University highlighted that ADAR1-mediated RNA A-to-I editing is a critical post-transcriptional event preventing innate immune interferon responses triggered by self dsRNA, with reduced editing levels due to genetic factors increasing the risk of inflammatory diseases [8] - A study published in Nature Cancer in February 2025 identified ADAR1 as a druggable target in prostate cancer, leading to the development of the small molecule inhibitor ZYS-1, which demonstrated significant anti-tumor effects and good safety profiles [9] Drug Development and Applications - Extensive research indicates that ADAR1 is not only an RNA editing enzyme but also closely related to autoimmune diseases and cancer, making it an important drug target [12] - Strategies for developing ADAR1-targeted inhibitors include targeting its catalytic domain, regulating upstream and downstream signaling pathways, and employing PROTAC degradation technology, showing broad prospects in treating cancer and autoimmune diseases [12] - A live lecture organized by BioWorld and Yi Qiao Shen Zhou will discuss the role of ADAR-mediated RNA editing in cancer therapy and the significance of ADAR1 as a drug target, featuring insights from experts in the field [12]

Core Insights - The global prevalence of Type 2 Diabetes (T2D) is rising, with 529 million cases reported in 2021, projected to exceed 1.3 billion by 2050, highlighting an increasing public health burden [2] - Current drug therapies, including GLP-1 receptor agonists, have been developed to manage high blood sugar, but a significant portion of patients still experience poor glycemic control due to clinical inertia and patient non-adherence [2] - There is an urgent need for alternative methods that can provide sustained blood sugar control independent of daily patient adherence [2] Group 1 - A multicenter, open-label, single-arm study published in the journal Signal Transduction and Targeted Therapy evaluated catheter-based endovascular denervation for T2D patients with poor glycemic control [3] - The study involved 37 patients, with 30 undergoing endovascular denervation (EDN) treatment between December 2022 and October 2023, assessing safety and efficacy [4] - The primary endpoints included the incidence of major adverse events (MAE) within 30 days post-surgery and changes in HbA1c levels at 6 months [4] Group 2 - Patients had a baseline average HbA1c of 9.0% and fasting blood glucose of 8.6 mmol/L; no MAE were observed within 30 days post-treatment [5] - At 6 months, HbA1c levels decreased by 1.0%, with significant improvements in blood glucose control observed at 1, 3, 6, and 12 months [5] - 37% of patients reported mild to moderate gastrointestinal adverse events, indicating the need for further randomized controlled trials to validate the efficacy of EDN in improving glycemic control in T2D patients [5]

Core Viewpoint - The article highlights the significant advancements in malaria treatment, particularly focusing on the development of a new drug, Ganaplacide–Lumefantrine (GanLum), by Novartis, which shows promise against drug-resistant malaria strains [8][10]. Group 1: Historical Context and Current Situation - In 1972, Chinese scientists, led by Tu Youyou, extracted artemisinin from sweet wormwood, significantly reducing malaria mortality rates and earning Tu the Nobel Prize in 2015 [2]. - The compound artemisinin led to the development of artemether-lumefantrine, marketed as Coartem, which became a first-line treatment for malaria and has saved millions of lives since its approval in 1999 [3][5]. - Malaria, caused by Plasmodium parasites transmitted through mosquito bites, infects hundreds of millions globally each year, resulting in nearly 600,000 deaths, primarily among children under five [5]. Group 2: New Drug Development - Novartis announced promising results from Phase 3 clinical trials for GanLum, a new imidazopyridine-based antimalarial drug, which targets the internal protein transport system necessary for the survival of the malaria parasite in human red blood cells [8]. - The clinical trial involved 1,688 malaria patients across 12 African countries, showing GanLum cleared artemisinin-resistant malaria mutations in about 47 hours, compared to 71 hours for artemether-lumefantrine [8]. - GanLum achieved a cure rate of 97.4%, surpassing the 94% cure rate of the standard treatment, with comparable safety profiles [8]. Group 3: Implications and Future Prospects - GanLum is expected to be effective in areas with known artemisinin resistance and can also be used in regions without resistance to slow down the development of drug resistance [10]. - Novartis is currently seeking regulatory approval for GanLum, with expectations for market availability within 12-18 months, marking the first new class of antimalarial drug approved since artemether-lumefantrine [11].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 KRAS 是人类癌症中最常见的突变癌基因之一，在多达 50% 的 结直肠癌 （CRC） 病例中观察到其发生突变。 KRAS 突变型结直肠癌长期以来一直是一个治疗 难题，治疗选择有限，预后不佳。 近期， KRAS G12C 抑制剂与 EGFR 抗体联合使用获得突破，改变了 KRAS G12C 突变型结直肠癌的治疗策略。这种联合疗法在 KRAS G12C 突变型结直肠癌 患者中实现了 34%-46% 的客观缓解率，促使该联合疗法获得美国 FDA 的加速批准。 KRAS G12C 抑制剂在非小细胞肺癌 （NSCLC） 和结直肠癌 （CRC） 中取得的成功，极大地推动了针对其他常见 KRAS 致癌突变的创新 KRAS 抑制剂的研发。 尽管在 KRAS 突变型结直肠癌中，KRAS 和 EGFR 的双重靶向治疗颇具前景，但患者的响应往往持续时间较短；大多数患者在数月内因耐药性而复发。近期的研 究已确定了这种联合疗法的几种耐药机制，包括继发性 KRAS 突变、 KRAS 上游或下游基因的改变以及其他 RAS 同源物的改变。此外，约三分之一复发的肿瘤 缺乏可检测到的基因组改变，这表明非 ...

Core Insights - The article discusses the development of an innovative system called AI-Newton, which autonomously derives physical laws from raw experimental data without prior physical knowledge, marking a significant step towards AI-driven scientific discovery [2][4]. Group 1: Challenges in Current Scientific Discovery - Current scientific discovery faces two main challenges: long research cycles influenced by human biases and the limitations of existing AI methods, which are often opaque and struggle with complex systems [5]. Group 2: AI-Newton System Design - AI-Newton is inspired by human scientific reasoning but does not rely on human knowledge. It starts from basic observational data and autonomously defines physical concepts, successfully rediscovering core laws of Newtonian mechanics [6][10]. Group 3: Knowledge Discovery Engine - The core architecture of AI-Newton consists of a three-layer knowledge base (symbols, concepts, and laws), mimicking how human physicists organize knowledge, starting from simple concepts to complex physical laws [8]. Group 4: Workflow and Methodology - AI-Newton combines logical reasoning with symbolic regression, selecting experiments and concepts to analyze, and correcting laws through reasoning when they do not hold in new scenarios [12]. Group 5: Experimental Validation - The research team tested AI-Newton on 46 Newtonian mechanics experiments, successfully rediscovering key physical laws such as Newton's second law, conservation of energy, and the law of universal gravitation, averaging the discovery of about 90 physical concepts and 50 universal laws [14][17]. Group 6: Key Features of AI-Newton - AI-Newton exhibits two main features: progressive improvement, where it builds knowledge gradually, and discovery diversity, where the order and timing of discovered concepts and laws vary across different test cases [18][21]. Group 7: Future Prospects - The framework of AI-Newton shows strong potential for expansion, suggesting that with more advanced mathematical tools and natural language integration, it could tackle more complex physical concepts and contribute to the realization of Artificial General Intelligence (AGI) [21].