Core Viewpoint - GLP-1 class drugs, including semaglutide and tirzepatide, show potential in treating not only type 2 diabetes and obesity but also various neurological and psychiatric disorders, supported by emerging clinical data [1][2][6]. Group 1: Mechanism and Applications - GLP-1 drugs activate GLP-1 receptors to enhance insulin secretion, suppress glucagon secretion, slow gastric emptying, and reduce appetite, leading to weight loss [1]. - These drugs have been approved for treating type 2 diabetes, obesity, cardiovascular diseases, kidney diseases, and metabolic liver diseases [1]. - Recent studies indicate that GLP-1 drugs may have therapeutic benefits for neurodegenerative diseases, substance use disorders, and other neurological conditions [2][3][6]. Group 2: Clinical Evidence and Safety - A review of clinical evidence highlights the potential of GLP-1 drugs in treating Parkinson's disease and Alzheimer's disease, with a focus on their neuroprotective properties [6][7]. - There is increasing evidence that GLP-1 drugs may reduce addictive behaviors in individuals with substance use disorders [6]. - Most patients with neuropsychiatric disorders using GLP-1 drugs have shown acceptable safety profiles, although large-scale confirmatory trials are still lacking [6][13]. Group 3: Future Research Directions - The role of GLP-1 drugs in neurological conditions will continue to evolve as new clinical trial data emerges, providing clearer evidence of their potential uses and limitations [13]. - Despite enthusiasm for GLP-1 drugs in treating central nervous system diseases, no large-scale trials have yet confirmed their efficacy and safety in these areas [13].

Core Viewpoint - The article discusses the urgent need for real-time health monitoring technologies in light of the alarming statistic that nearly 18 million people die from cardiovascular diseases each year, accounting for 32% of global deaths. It highlights the challenges faced by traditional cardiovascular signal monitoring, particularly the trade-off between signal quality and patient comfort [2]. Group 1: Need for AI Completion Technology - Cardiovascular signals, such as PPG, ECG, and BP, are inherently interconnected and complementary, reflecting the health status of the cardiovascular system. However, obtaining complete and high-quality multimodal signals during monitoring is rare [6]. - Wearable devices are prone to interference from motion artifacts, power line disturbances, and muscle contractions, while clinical monitoring is hindered by the high cost of equipment and patient discomfort, making long-term use difficult [6]. Group 2: Breakthrough with UniCardio - UniCardio, a multimodal diffusion transformer model, is developed to "complete" missing or low-quality cardiovascular signals. Its generated signals perform comparably to real signals in detecting abnormal health conditions and assessing vital signs, while ensuring interpretability for human experts [3][8]. - The core innovation of UniCardio lies in unifying the generation tasks of various cardiovascular signals into a single framework, utilizing advanced conditional diffusion models to iteratively reconstruct the required signals [8]. Group 3: Performance of Generated Signals - UniCardio was pre-trained on a dataset containing 339 hours of multimodal recordings and evaluated across various generation tasks, outperforming specialized baseline models in denoising, interpolation, and conversion tasks [12]. - The generated signals exhibit excellent performance in waveform morphology, spectral features, and clinical interpretability, particularly excelling in challenging tasks such as PPG interpolation and ECG conversion [12]. Group 4: Practical Applications in Medical Diagnosis - The reliability of AI-generated signals for health monitoring and medical diagnosis is affirmed through evaluations in real scenarios, showing that denoised signals achieve accuracy, sensitivity, and specificity levels comparable to real signals [14]. - UniCardio significantly improves heart rate estimation and blood pressure assessment, demonstrating its clinical effectiveness and interpretability through the generation of typical abnormal diagnostic features [14]. Group 5: Future Implications of AI-Generated Signals - The emergence of UniCardio signifies a paradigm shift in cardiovascular signal processing, providing a universal and scalable framework for multimodal physiological signal generation [16]. - UniCardio is expected to enhance personalized health monitoring by enabling accurate data collection from wearable signals and synthesizing cardiovascular signals that cannot be captured by wearable sensors [18]. - The technology has broader applications beyond cardiovascular health, potentially impacting psychological and cognitive science research, where physiological signals are used for stress and emotion assessment [18].

Core Viewpoint - The research highlights the role of uridine as an immune metabolite that regulates CD8⁺ T cell activity, revealing a molecular mechanism by which cancer cells suppress anti-tumor immunity by depleting uridine levels in the tumor microenvironment [8]. Group 1: Research Findings - The study published in Cell Metabolism identifies a new mechanism by which uridine mediates N-glycosylation of CD45 protein, promoting CD8⁺ T cell anti-tumor immunity [3]. - It details the process and regulatory mechanisms of uridine depletion in the tumor microenvironment, proposing new therapeutic targets and combination treatment strategies for immune therapy resistance [3]. - The research indicates that SNX17 expression negatively correlates with CD8⁺ T cell infiltration and sensitivity to immune checkpoint blockade (ICB) therapy [5]. Group 2: Mechanisms and Implications - SNX17 regulates the metabolic microenvironment, inhibiting CD8⁺ T cell function, and its knockout leads to significantly increased uridine levels in tumor cell supernatants and tissues, which can activate CD8⁺ T cells and inhibit tumor growth in mice [5]. - The activation mechanism of uridine on CD8⁺ T cells involves its metabolism to UDP-GlcNAc, which promotes N-glycosylation of the key membrane protein CD45, enhancing TCR signaling and effectively activating CD8⁺ T cells [5]. - The upstream mechanism shows that SNX17 stabilizes the transcription factor RUNX2, preventing its lysosomal degradation, which in turn upregulates the expression of uridine-degrading enzyme UPP1, leading to uridine depletion in the tumor microenvironment [6]. Group 3: Clinical Relevance - The findings suggest that SNX17 could serve as a predictive biomarker for resistance to cancer immunotherapy, while uridine may represent a promising candidate for immunotherapeutic drugs [8].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 近日，东京大学和蒙特利尔大学的一项研究登上了 Cell Press 官网头条。 该研究以： Accelerated inorganic materials design with generative AI agents （ 利用生成式 AI 智能体加速无机材料设计 ） 为题，于 2025 年 12 月 17 日，在线发表于 Cell 子刊 Cell Reports Physical Science 上。 该研究开发了一个以 通用大语言模型作为其核心生成引擎的材料发现框架—— MatAgent 。 借助模拟人类专家推理过程的外部工具，并与晶体结构估算和性能评 估模型相结合，MatAgent 能够实现反馈驱动的自主探索广泛的材料空间。针对特定形成能进行的实验表明，MatAgent 在提出具有所需性能的材料方面非常有 效，同时还能保持高成分有效性、独特性和新颖性。该框架的自然语言集成使得在实际工作流程中实现直观约束变得容易。通过为每个成分建议提供明确的推 理，这一框架确保了材料设计过程的可解释性，成为增强专家知识并加速无机材料发现的智能合作伙伴。 在这项新研究中，研究团队开 ...

Core Viewpoint - The research highlights the role of extracellular proteins in supporting T cell immunity, particularly in the context of aging and its impact on immune response [2][4][7]. Group 1: Research Findings - The study published in Cell Reports reveals that even healthy elderly individuals with normal albumin levels (>25g/L) may experience limited T cell functionality during acute viral infections due to relatively lower albumin concentrations [2]. - Activated T cells can internalize extracellular proteins like albumin, degrade them in lysosomes, and release free amino acids such as leucine, which are crucial for maintaining mTORC1 activity and cytokine production, thereby enhancing antiviral and antitumor immunity [4][5]. - The transcription factor TFE3 plays a central regulatory role in this process, with its expression being specifically upregulated during T cell activation, promoting lysosomal biogenesis and protein degradation capabilities [4][5]. Group 2: Clinical Implications - The clinical significance of this pathway has been validated in elderly lung cancer patients, where tumor-infiltrating CD8⁺ T cells showed significantly reduced lysosomal degradation capacity and cytokine secretion compared to middle-aged patients [5]. - The study suggests that the activation of mTORC1 is regulated by both rapid signals from extracellular free amino acids and sustained amino acid signals from lysosomal degradation of extracellular proteins, which may influence the differentiation balance between effector T cells and memory T cells [5][7]. - The functional impairment of elderly T cells arises from both intrinsic lysosomal dysfunction and extrinsic declines in plasma albumin levels [5][7].

Core Viewpoint - The article discusses the significant clinical challenge of peritoneal metastasis in solid tumors and highlights the potential of CAR macrophage (CAR-M) therapy as a promising immunotherapy approach to address this unmet clinical need [2][7]. Group 1: Clinical Challenges and Current Treatments - Peritoneal metastasis from solid tumors poses a major clinical challenge, with current treatments like cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) only benefiting a small subset of patients with very low tumor burden [2]. - Immunotherapy is seen as a promising frontier for treating peritoneal metastasis, but many patients develop escape mechanisms against the immune system, leading to disease progression and poor prognosis [2]. Group 2: CAR-M Therapy Development - The research led by Chinese Academy of Sciences explores 36 different CAR combinations targeting macrophages, utilizing an mRNA lipid nanoparticle (LNP) system for efficient in vivo construction of CAR-M cells necessary for tumor immunotherapy [3][7]. - The study demonstrates that intraperitoneal programming of CAR-M cells can induce robust adaptive immune system activation and significantly enhance the efficacy of standard PD-1/PD-L1 immune checkpoint blockade therapies in resistant models [4][7]. Group 3: Mechanisms and Findings - Customized CAR-M cells with CD3ζ and TLR4 transmembrane domains can trigger strong adaptive immune activation and significantly synergize with PD-1/PD-L1 therapies [7]. - Single-cell RNA sequencing (scRNA-seq) reveals that CAR-M cells reshape the immunosuppressive tumor microenvironment (TME) and promote the formation of TCF1+ PD-1+ exhausted CD8+ T cell populations [4][7]. - Mechanistically, CAR-M cells maintain a pro-inflammatory phenotype while upregulating MHC-I and PD-L1 through interference with the NF-κB pathway [4][7]. Group 4: Conclusion and Future Directions - The study develops an mRNA-LNP delivery system for targeted in vivo programming of CAR-M cells, deepening the understanding of the regulatory and feedback mechanisms of CAR-M therapy in treating solid tumors [10].

排版丨水成文 肾素 （ Renin ） 的合成与释放，是控制体液稳态的 肾素-血管紧张素-醛固酮系统 （ RAAS ） 的限速步骤。RAAS 的一个主要激活因素是肾脏灌注压的降低， 这表明肾脏机械转导与肾素之间存在关联。然而，肾脏中机械力传感器的身份，及其对RAAS的生理意义仍不清楚。 近日，诺贝尔奖得主、斯克里普斯研究所 Ardem Patapoutian 教授团队在 Cell 期刊发表了题为： Renal PIEZO2 is an essential regulator of renin 的研究论 文。 该研究发现，肾素谱系细胞中阳离子通道 PIEZO2 的缺失，会通过升高肾素水平导致 RAAS 失调。该研究观察到 PIEZO2 在产肾素的 球旁细胞 中表达，并且对 其体内钙动力学是必需的。肾素谱系细胞中的 PIEZO2 缺陷会驱动依赖肾素和 MAS 受体的肾小球滤过率偏高，并在急慢性血容量挑战期间调节 RAAS。这项研 究确定了 PIEZO2 是体内球旁细胞钙活性和肾素的重要调控因子。 撰文丨王聪 编辑丨王多鱼 血压的"总开关"：肾素与 RAAS 系统 锁定"嫌疑人"：离子通道 PIEZO2 这项由诺贝 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 疱疹病毒 是广泛存在的双链 DNA 病毒，可终身潜伏并引发多种疾病。尽管靶向 DNA 聚合酶的抗病毒药物有效，但日益增强的耐药性凸显了寻找替代药物的必要 性。 解旋酶-引物酶抑制剂 （ Helicase-primase inhibitor， HPI） 是很有前景的抗病毒药物，但其作用机制尚不明确。此外，对于疱疹病毒而言，解旋酶-引物酶 （H/P） 复合体与 DNA 聚合酶如何协调基因组复制过程，也尚不明确。 2025 年 12 月 29 日，哈佛医学院 Jonathan Abraham 团队 （博士后 于子朔 为论文第一作者） 在国际顶尖学术期刊 Cell 上发表了题为： Mechanisms of HSV-1 helicase–primase inhibition and replication fork complex assembly 的研究论文。 该研究通过 单颗粒冷冻电镜 （cryo-EM） 技术 ，成功"拍摄"到了 单纯疱疹病毒 1 型 （HSV-1） 核心复制机器的工作状态及其被抑制剂"锁死"的瞬间。这项 研究不仅阐明了 解旋酶-引物酶抑制剂 （ Heli ...

Core Viewpoint - The article discusses a significant advancement in the development of disease-modifying osteoarthritis drugs (DMOADs) through a novel drug delivery system that effectively targets diseased chondrocytes, addressing major challenges in osteoarthritis treatment [1][2]. Group 1 - A multifunctional peptide (CMP) mimicking viral glycoproteins was developed to enhance drug delivery to osteoarthritic chondrocytes, overcoming issues related to cartilage penetration, retention, and selective uptake by diseased cells [2][5]. - The research team synthesized CMP, which includes a type II collagen adhesion sequence and a cell-penetrating peptide activated by matrix metalloproteinase-13, allowing the drug-loaded micelles to adhere to cartilage and selectively target diseased chondrocytes [5]. - In mouse models of osteoarthritis, the developed micelles demonstrated longer joint retention times and higher uptake rates in diseased chondrocytes compared to unmodified micelles, indicating improved efficacy [5]. Group 2 - The drug delivery system maintained cartilage metabolic homeostasis, alleviated pathological changes associated with osteoarthritis, and improved symptoms without causing additional toxicity [2][5]. - Overall, the findings suggest that the developed nanomedicine represents a promising candidate for DMOADs and provides an efficient delivery strategy for targeting other therapeutic agents to diseased chondrocytes [2][5].

Group 1: Job Positions - The recruitment includes faculty positions and postdoctoral positions in various research fields such as cancer, tropical pathogens and immunobiology, cardiovascular and metabolic diseases, neuroscience, stem cells and regenerative medicine, and basic medicine [4] - Applicants for faculty positions must hold a PhD or MD/PhD, have completed several years of postdoctoral training or possess relevant industrial research experience, and demonstrate strong independent research capabilities [6][7] - Senior researchers will receive independent lab space, graduate student supervision opportunities, and dedicated funding for research assistants and technical staff [7] Group 2: Compensation and Benefits - Senior researchers will earn an annual salary ranging from 1 million to 1.5 million RMB (pre-tax), while junior researchers will earn between 500,000 and 800,000 RMB (pre-tax) [9] - Research start-up funds are provided, with senior researchers receiving between 6 million and 8 million RMB, and junior researchers receiving 1 million RMB [9] - All faculty members will have access to advanced research facilities, including high-throughput sequencing platforms, confocal microscopy systems, and flow cytometry facilities [9] Group 3: Postdoctoral Researcher Requirements - Candidates for postdoctoral positions should have a solid foundation in their research field, strong scientific literacy, excellent communication skills, and demonstrated innovative potential [11] - Postdoctoral researchers must commit full-time to the position and are not allowed to hold concurrent jobs during their tenure [12] - Preference will be given to candidates with interdisciplinary research experience and a background in tropical medicine or related fields [14] Group 4: Application Materials - Applicants must submit a CV, a 3 to 5-page research plan, and two letters of recommendation [13] - Additional required documents include a copy of the PhD certificate (or official proof of impending graduation) and representative publications [19]