Core Viewpoint - Springer Nature is committed to making research results immediately accessible, shareable, and reusable to promote scientific discovery, emphasizing the importance of Open Access (OA) in democratizing knowledge and innovation [2]. Group 1: Open Access Overview - Open Access refers to the free, immediate, and online availability of research outputs, allowing anyone to access and utilize these results without any access fees [3]. - The article highlights the difference between subscription-based publishing and Open Access publishing, where in subscription models, costs are covered by subscription fees, while in Open Access, authors or their funders pay Article Processing Charges (APC) [6][7]. Group 2: Benefits of Open Access - Open Access articles have higher visibility and citation rates compared to subscription-based articles, leading to greater usage and downloads [11]. - Open Access facilitates broader audience reach, allowing users who cannot access subscription content to easily access OA research [11]. - It enhances interdisciplinary dialogue and collaboration opportunities among researchers globally [11]. - Open Access publications comply with major international funding policies, promoting adherence to open access regulations [11]. Group 3: Springer Nature's OA Journals - Springer Nature offers approximately 700 pure OA journals, which provide significant benefits to authors, including increased usage and download rates compared to traditional publishing [13]. - The company publishes over 2,200 hybrid journals, allowing authors to choose Gold Open Access for their submissions [14]. Group 4: Publishing Process and Integrity - The publishing process for OA and hybrid journals maintains the same high standards, with similar acceptance rates and rigorous peer review [18]. - Springer Nature emphasizes research integrity throughout the publishing process, collaborating with over 174,000 external academic editors and 1.2 million independent peer reviewers to ensure quality [19]. - In 2024, the company received over 2.3 million submissions, with only 482,000 articles published, reflecting a commitment to publishing high-quality research [19].

RNA 病毒 是一种极其简单但高效的生命形式。在生命周期中，RNA 病毒利用有限的基因组，编码几个到 十几个蛋白质，即可完成高效扩增，这要求病毒基因组必须能够高效的循环使用。同时，转录形成的新生 RNA 5' 端带有三磷酸基团，一旦释放到宿主细胞中，会迅速激活宿主细胞的先天免疫反应，因此必须立即 对其 5' 端的三磷酸基团进行加工，形成 " 帽 " （Cap） 结构，从而逃逸宿主天然免疫的攻击。 虽然基因组的高效重复使用、RNA 加帽是 RNA 病毒生命过程中最核心、最基础的生物学事件，但自 1 00 多年前发现第一种 RNA 病毒至今，这两个过程协同发生的机制一直是病毒学领域的关键未解之谜。 2025 年 10 月 22 日 ，清华大学 娄智勇 教授 / 饶子和 院士、 中国医学科学院 北京协和医院 朱兰 教授 团队 与广州国家实验室、南开大学等单位合作，在国际顶尖学术期刊 Cell 上发表了题为： Structural basis for the concurrence of template recycling and RNA capping in SARS-CoV-2 的研究论文。 编辑丨王多鱼 排版 ...

Core Insights - The article discusses the increasing public health burden of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and its progression to Metabolic Dysfunction-Associated Steatohepatitis (MASH), highlighting limited treatment options [2] - A study published in Cell Metabolism reveals that the diene acid analog 326E alleviates MASH by dual targeting ACLY and PPARα, demonstrating its therapeutic potential and good tolerability in human clinical trials [2][5] Group 1: Mechanism and Efficacy - The diene acid ATP-citrate lyase (ACLY) inhibitor 326E significantly reduces liver lipid accumulation and alleviates MASH symptoms in mouse models [3] - 326E works by inhibiting ACLY to decrease de novo lipogenesis (DNL) and acts as an allosteric modulator of PPARα to enhance fatty acid oxidation (FAO), thus addressing MASH [3][8] - The study confirmed the preventive effects of 326E on MASH in non-human primates, further supporting its potential as a treatment [4] Group 2: Clinical Trials and Results - A randomized 1b/2a phase clinical trial in human MASH patients (NCT06491576) showed that 326E has good tolerability and lowers levels of γ-glutamyl transferase (γ-GGT), a key biomarker for liver disease [5][9] - The results from preclinical studies in mice and non-human primates, along with human clinical trials, indicate that 326E has therapeutic potential for MASH through its unique mechanisms of action [8]

Core Viewpoint - Cell therapy presents a promising method for treating liver diseases, with the challenge of obtaining sufficient safe and functional liver cells for transplantation and treatment [3]. Group 1: Research Findings - A research team from the Navy Medical University and Shanghai Jiao Tong University published a paper on large-scale manufacturing of human gallbladder epithelial cells (hGBEC) and derived hepatocytes, which was selected as a cover paper in Trends in Biotechnology [4]. - The team established a component-defined, Matrigel-free culture system for hGBEC, enabling large-scale production under GMP conditions, and successfully generated functional hepatocytes that demonstrated typical liver functions [4][8]. - The production process can yield at least 10^11 cells from a single donor, sufficient to treat multiple adult patients with liver failure, ensuring quality control and biosafety [8]. Group 2: Clinical Implications - The generated hepatocytes exhibit typical liver functions, including albumin secretion, urea production, and drug metabolism, and can be used for drug toxicity testing [8]. - In vivo transplantation of these functional hepatocytes successfully rescued mice with liver failure, indicating potential clinical applications for liver disease treatment [8][10]. - The large-scale and convenient production strategy of hGBEC serves as a biological resource for clinical applications and provides valuable models for liver disease research [10].

Core Viewpoint - The article discusses a novel approach to overcoming tumor resistance to traditional therapies through a CRISPR-based nano-vaccine (AVAX) that targets the HO-1 gene, enhancing the efficacy of photodynamic therapy and activating anti-tumor immunity [3][4]. Group 1: Research Findings - The study published in Nature Biomedical Engineering presents a CRISPR-Cas9 based nano-vaccine (AVAX) that effectively knocks out the HO-1 gene, reversing tumor cell resistance to reactive oxygen species (ROS) and significantly improving photodynamic therapy outcomes [3][4]. - AVAX demonstrated a 20.15% gene editing efficiency for HO-1 in B16F10 melanoma and LL/2 lung cancer models, leading to enhanced photodynamic therapy efficacy and the induction of an autologous vaccine effect [6][8]. - The combination of AVAX and photodynamic therapy achieved a tumor suppression rate of 93%, with edited ROS-sensitive phenotypes being heritable in progeny tumor cells [8]. Group 2: Mechanism and Efficacy - The AVAX platform utilizes a core-shell self-assembly structure for efficient delivery of the CRISPR-Cas9 system, targeting the ROS resistance gene HO-1 [6]. - When combined with PD-L1 antibodies, 50% of tumor-bearing mice exhibited complete tumor regression, with survival extending beyond 50 days [8]. - The treatment led to a significant increase in CD8 T and CD4 T cell infiltration in tumors, while reducing immunosuppressive myeloid cells [9]. Group 3: Safety and Implications - Safety assessments indicated that the nano-vaccine did not exhibit significant toxicity to major organs, and no off-target editing was detected in immune cells [9]. - This research integrates gene editing with immune activation, achieving a strategy of "enhanced sensitivity and reversal of resistance" in tumor treatment [9].

Core Viewpoint - Baichuan Intelligent has launched the Baichuan-M2 Plus, an evidence-enhanced medical large model, which significantly reduces the hallucination rate compared to general models, achieving credibility comparable to experienced clinical doctors [3][15]. Group 1: Product Launch and Features - Baichuan-M2 Plus is an upgrade from the previously open-sourced Baichuan-M2, featuring a significant reduction in hallucination rates, outperforming both DeepSeek and OpenEvidence [3][4]. - The model introduces a six-source evidence reasoning (EAR) paradigm, making it suitable for clinical decision support in various healthcare environments, including China, the US, Japan, and the UK [4][22]. - The model's architecture is designed to ensure that it only uses authoritative medical evidence, avoiding non-professional information from the internet [6][9]. Group 2: Evidence Framework - The six-source evidence framework consists of layers that evolve from original research to real-world feedback, ensuring a comprehensive knowledge system [5][8]. - The layers include original research, evidence reviews, guidelines, practical knowledge, public health education, and regulatory information, creating a robust evidence chain [8][9]. Group 3: Retrieval and Reasoning Mechanisms - M2 Plus employs a PICO framework for structured medical queries, enhancing the precision of evidence retrieval [11][12]. - The model incorporates a "evidence-enhanced training" mechanism that prioritizes citation over speculation, fundamentally changing its response logic [13][15]. - The model's ability to evaluate evidence quality ensures that it prioritizes high-trust information, embedding it seamlessly into its reasoning process [13][15]. Group 4: Performance Metrics - M2 Plus achieved a score of 97 in the USMLE, surpassing the average human score and matching GPT-5, demonstrating its clinical problem-solving capabilities [19][21]. - In the Chinese medical licensing exam, M2 Plus scored 568, significantly higher than the average passing score, showcasing its mastery of clinical guidelines and practices [21]. - The model also performed well in various international medical qualification exams, achieving over 85% accuracy [20][21]. Group 5: Market Position and Applications - Baichuan-M2 Plus is positioned as a "doctor's version of ChatGPT," enhancing the usability of AI in serious medical scenarios [22][23]. - The model is integrated into the Baixiao app, providing a tool for doctors to counteract the challenges posed by general models like DeepSeek [23][24]. - The company aims to continuously improve the applicability of AI in real clinical settings through open-source initiatives and API offerings [24].

Core Insights - Lung cancer is the most prevalent cancer globally, with 2.48 million new cases and 1.8 million deaths annually, primarily due to non-small cell lung cancer (NSCLC) which accounts for over 85% of cases [2] - The recent study published by a team from Sun Yat-sen University identifies LIC1 as a new therapeutic target for NSCLC and highlights the potential of DAA as an autophagy-inducing agent for treatment [3][7] Group 1: Research Findings - The research isolated a small molecule, DAA, from endophytic fungi of Euphorbiaceae plants, which effectively induces autophagic cell death in NSCLC cells [3][5] - DAA shows significant anti-tumor efficacy in NSCLC and enhances sensitivity to anti-PD-1 immunotherapy while exhibiting low toxicity to normal lung fibroblasts [5] - LIC1 was identified as the direct target of DAA, which is overexpressed in NSCLC tumors and associated with poor prognosis [5] Group 2: Mechanism of Action - DAA disrupts the interaction between LIC1 and the stress response effector RuvBL1, enhancing the integrated stress response mediated by the GCN2-eIF2α-ATF4 signaling axis, ultimately promoting autophagic cell death [5]

Core Viewpoint - The integration of AI in education is rapidly evolving, with universities adopting various strategies to incorporate AI tools, raising questions about their impact on student learning and critical thinking [3][10][17]. Group 1: AI Adoption in Universities - Tsinghua University introduced an AI assistant for new students to answer questions about campus life [3] - Ohio State University made AI courses mandatory for all graduates to ensure AI literacy [3] - Sydney University opted for traditional exams to assess students' knowledge without AI assistance [3] Group 2: Student Usage of AI - A global survey in 2024 found that 86% of university students frequently use AI in their studies, with STEM students being the heaviest users [6] - Nearly 90% of students admitted to using generative AI for writing, with 58% using it to explain concepts and 25% editing AI-generated text [6] Group 3: Benefits and Concerns of AI in Education - Supporters argue that AI offers exciting opportunities for education, with studies showing that students using customized AI tutors perform better than those taught solely by human instructors [8] - Concerns arise regarding the potential for AI to hinder learning, as reliance on AI tools may reduce independent thinking and critical analysis skills [9][8] Group 4: Global Strategies and Policies - Universities worldwide are developing AI usage policies, with varying degrees of success; the U.S. has seen a chaotic approach while Australia has implemented coordinated measures [11] - In China, integrating AI into universities is viewed as a national strategy, with Tsinghua University developing a multi-layered AI system for education [12] Group 5: Faculty Perspectives and Market Dynamics - Faculty acceptance of AI is more cautious, with only 60% using AI tools in teaching, and 80% reporting a lack of clear guidelines from their institutions [14] - Tech giants like OpenAI and Google are actively promoting their products in universities, with OpenAI launching a dedicated version of ChatGPT for educational use [14] Group 6: Unresolved Questions on Learning Outcomes - The critical question remains whether students using AI tools genuinely learn more; preliminary findings suggest that while AI users perform better immediately, their retention of knowledge may be weaker over time [17] - The challenge for the education sector is to balance technological innovation with the need for personalized teaching that fosters independent thought and critical thinking [17]

撰文丨王聪 编辑丨王多鱼 排版丨水成文 搞笑诺贝尔奖 （Ig Nobel Prize ） 旨在表彰那些 " 先让人发笑，然后引人深思 "的科学研究。 2024 年 10 月 29 日， 搞笑诺贝尔生理学奖 （Ig Nobel Prize in Physiology） 授予了一项神奇的研究——来自东京理科大学的 武部贵则 （Takanori Takebe） 发现 ，包括小鼠、大鼠和猪在内的哺乳动物可以绕过呼吸系统、通过肛门呼吸。 一年后的 2025 年 10 月 20 日，该团队进行了 首次人体试验，验证了这种肛门呼吸方式在人类中的安全性、耐受性和可行性。 武部贵则 （左一）团队获得 2024 年搞笑诺贝尔生理学奖 这项研究始于新冠疫情期间，当时疫情导致呼吸机严重短缺，从而危及患者生命。 泥鳅 等水生生物进化出了一种独特的肠道呼吸机制，从而得以在长期缺氧的环境中生存。受此启发， 武部贵则 在哺乳动物中验证了 经肛门肠内通气 （EVA） 技 术，该研究以 ： Mammalian enteral ventilation ameliorates respiratory failure 为题，于 2021 年 6 月 ...

Core Viewpoint - The research reveals a novel metabolic interaction between tumor-associated macrophages (TAM) and hepatocellular carcinoma (HCC) cells, identifying TAM as a source of acetate that drives HCC metastasis through the synthesis of acetyl-CoA [2][3][4]. Group 1: Research Findings - TAM secretes acetate, which is then taken up by HCC cells to support their acetate accumulation [3]. - Lactate produced by HCC cells activates lipid peroxidation-ALDH2 pathways in TAM, promoting the secretion of acetate [3]. - In a mouse model of HCC, knocking out the ALDH2 gene in TAM reduces acetate levels in HCC cells and decreases lung metastasis of HCC [3][4]. Group 2: Implications - The study positions TAM as a critical acetate supply source that drives HCC metastasis, suggesting potential intervention targets in the tumor microenvironment [2][4].