ADAR （Adenosine deaminases acting on RNA） 家族，是催化 RNA A-to-I 编辑的关键酶类， 是催化 RNA 的 A-to-I 编辑的关键酶类，其在调控 RNA 多样性，以及维持免疫稳态及神经系统功能中发挥着核心作 用。近年来，基于 ADAR 的 RNA 编辑技术得到了快速发展，相比基于 CISRPR 基因编辑技术 ，其 无需 引 入外源编辑酶或效应蛋白 ，避免了递送难题以及相关免疫原性等问题，此外，其不会改变 DNA 改变， 更具 安全性。在遗传疾病治疗中潜力巨大，正被开发为新一代基因编辑疗法。 此外，还有多项 研究表明， ADAR1 不仅是 RNA 编辑酶，还与自身免疫疾病、癌症等疾病密切相关 ，已成 为重要的疾病治疗新靶点。 2018 年 12 月，Dana-Farber 癌症研究所的研究人员在 Nature 期刊发表论文，该研究表明肿瘤细胞中 RNA 编辑酶 ADAR1 的功能缺失会极大地增强肿瘤对免疫疗法的敏感性，并克服了肿瘤对免疫检查点阻断疗 法 （例如抗 PD-1 单抗） 的耐药性 。这项研究提示了 ADAR1 是一种抑制性免疫检查点，通过抑制 ADA ...

Core Insights - The study highlights the role of M2 macrophage-derived migrasomes in enhancing fracture healing through the coordination of CXCL12/CXCR4 signaling and neutrophil-MMP-9/MSC-EphB2 pathways, providing a promising strategy for tissue engineering in fracture repair [3][7]. Group 1: Mechanisms of Action - M2 macrophage-derived migrasomes are found to be rich in CXCL12, which activates the CXCL12/CXCR4 signaling axis to promote the migration of mesenchymal stem cells (MSCs) [6]. - The study reveals that M2-migra regulates the expression of neutrophil-derived MMP-9, enhancing the expression of EphB2 receptors on MSCs, thereby promoting osteogenic differentiation and fracture healing [6][9]. - Compared to M2-exosomes, M2-migra exhibits superior MSC homing capabilities through a dual mechanism involving CXCL12/CXCR4 recruitment and neutrophil-MMP-9/MSC-EphB2 induced osteogenic differentiation [7][9]. Group 2: Experimental Findings - The research team isolated migrasomes and exosomes from polarized M2 and M1 macrophages and co-cultured them with MSCs to assess their effects on MSC migration [5]. - An injectable thermosensitive hydrogel was developed to first release migrasomes to recruit MSCs, followed by the delivery of BMP-2 to enhance osteogenic activity, resulting in accelerated bone healing in mouse models [9][10]. - The study suggests a new paradigm of using immune cell-derived vesicles as programmable delivery vehicles for recruiting and guiding endogenous repair cells, applicable not only for fracture healing but potentially for other tissue regeneration [9].

编辑丨王多鱼 排版丨水成文 撰文丨王聪 阿尔茨海默病 （AD） 是最常见的神经退行性疾病，目前尚无有效的治疗方法。细胞外淀粉样斑块、神经原纤维缠结、 神经炎症以及神经元丢失是阿尔茨海默病神经病理学的特征。 β- 淀粉样蛋白 （Aβ） 是淀粉样斑块的主要成分，它是通过 β-分泌酶 BACE1 和 γ-分泌酶对 淀粉样前体蛋白 （APP） 进行连续切割而产生的。 APP、BACE1 和 γ-分泌酶的失调会增加 Aβ 的生成，而小胶质细胞的功能障碍会 降低对 Aβ 的清除，从而导致 Aβ 的沉积。Aβ 沉积的增加反过来会激活小胶质细胞，促进大量促炎细胞因子的分泌。 肠道微生物群及其代谢物的失调在阿尔茨海默病 （AD） 的发病机制中发挥着关键作用。 丁酸 （Butyrate） 是一种短 链脂肪酸 （SCFA） ，主要由肠道细菌通过膳食纤维的发酵产生，具有多种生理功能，包括调节肠道健康、抗炎和神经 保护作用。近年来，研究发现丁酸在大脑健康及神经退行性疾病 （例如阿尔茨海默病） 中可能发挥有益作用。 提高丁 酸的生物利用度，对于其临床应用至关重要。 2025 年 11 月 17 日，温州医科大学/瓯江实验室 吴伊丽 教授 ...

Core Insights - The article discusses a new research paper published in Nature Sensors, which presents a noise-tolerant human-machine interface based on deep learning-enhanced wearable sensors, capable of accurate gesture recognition and robotic arm control even in dynamic environments [3][22]. Group 1: Motion Interference Challenges - Wearable inertial measurement units (IMUs) show great potential in various fields but often face challenges from motion artifacts during real-world applications, which can obscure gesture signals [6][7]. - Motion artifacts can arise from activities like walking, running, or riding in vehicles, and may vary significantly between individuals [7]. Group 2: Innovative Solutions - The research team developed a sensor system that integrates a six-channel IMU, electromyography (EMG) module, Bluetooth microcontroller, and a stretchable battery, capable of wireless gesture signal capture and transmission [9]. - The sensor features a four-layer design, measuring 1.8×4.5 cm² and 2 mm thick, with over 20% stretchability, ensuring durability and performance even after multiple charge cycles [9]. Group 3: Deep Learning Algorithms - The study collected 19 types of forearm gesture signals and various motion interference signals to create a composite dataset, training three deep learning networks, with the LeNet-5 convolutional neural network (CNN) achieving the best performance metrics [12]. - The CNN demonstrated a recall rate greater than 0.92, precision greater than 0.93, and an F1 score exceeding 0.94, confirming its effectiveness in gesture recognition [12]. Group 4: Transfer Learning for Personalization - To enhance model generalization, the research team applied parameter-based transfer learning, allowing for significant improvements in gesture recognition accuracy with minimal sample data [14]. - The recognition accuracy for 19 gestures improved from 51% to over 92% with just two samples per gesture, significantly reducing data collection time [14]. Group 5: Real-time Gesture Recognition and Robotic Control - The team implemented a sliding window mechanism for continuous gesture recognition, achieving a response time of approximately 275 milliseconds for robotic arm actions based on gesture signals [16]. - The system maintained accurate control of the robotic arm even in the presence of motion interference, demonstrating its robustness [18]. Group 6: Underwater Applications - The human-machine interface has potential applications for divers controlling underwater robots, with the system effectively managing motion artifacts caused by ocean dynamics [20]. - After training on a dataset simulating various wave conditions, the model maintained high accuracy in generating commands for robotic arm actions, showcasing its adaptability in challenging environments [20][22].

编辑丨王多鱼 排版丨水成文 肿瘤新抗原 （Tumour Neoantigen） 是理想的免疫治疗靶标，这些抗原只存在于肿瘤组织中，而在其他组织中不存在。肿瘤新抗原疫苗通过诱导机体产生肿瘤特 异性免疫应答，为精准治疗肿瘤提供了新思路。目前，全世界已有超过 100 项新抗原疫苗相关临床试验。 然而， 由于 新抗原免疫原性低 （仅约 15%–30% 的新抗原能够诱导 T 细胞 产生 ） 、 实体瘤的高度 异质性以及抑制性肿瘤免疫微环境 （ TIME） ，这些个 性化的肿瘤新抗原疫苗在实体瘤的治疗中，响应率低。 相比之下，相比之下，微生物抗原具有明确的定义且免疫原性很强，能够激活特定的记忆 T 细胞以清除肿瘤微环境中的微生物。 受此启发，中国药科大学 杨勇 / 王文广 团队等创新性地构建了一种特异性异源蛋白标记体系，开发了特异性标记 乙型肝炎病毒表面抗原 （ HBsAg ） 的 通用 型肿瘤疫苗系统 （ HBsAg-tagged tumour vaccine system, H-T VAC ） ， 将 肿瘤细胞 " 伪装 " 成高免疫原性的 " 病毒 " ，突破了肿瘤新抗原免疫原性低、 实体瘤异质性强以及抑制性肿瘤免 ...

Core Viewpoint - The study published by Professor Wu Baojian's team from Guangzhou University of Chinese Medicine in Cell Metabolism highlights the role of the intestinal clock in regulating the sleep-wake cycle through maintaining glutamine homeostasis, suggesting potential new targets for enhancing sleep rhythms and treating sleep disorders [2][7]. Summary by Sections Research Findings - The integrity of the intestinal epithelial cells (IEC) is essential for maintaining the circadian sleep-wake cycle [4]. - BMAL1 in the intestinal epithelial cells drives the circadian expression of SLC6A19, promoting glutamine absorption during active periods, which enhances the activity of glutamatergic neurons in the hypothalamus, thereby increasing wakefulness and reducing sleep [4][5]. - A lack of REV-ERBα in intestinal epithelial cells leads to elevated glutamine levels during rest phases, which is causally linked to sleep abnormalities characterized by reduced sleep [4][5]. Implications - The intestinal clock regulates glutamine homeostasis temporally, shaping the circadian sleep-wake cycle, and may serve as a potential target for enhancing sleep rhythms and treating sleep disorders [7].

Core Insights - The article discusses a groundbreaking study on cardiovascular disease, highlighting the limitations of existing laboratory models in accurately replicating the complex environment of human arteries [2][5] - The research introduces a novel extrusion-on-demand (EoD) bioprinting technology that creates arterial models with micron-level structural fidelity and customizable macro geometries, enabling better understanding of vascular disease mechanisms and personalized treatment approaches [3][8] Summary by Sections Research Background - Cardiovascular disease is the leading cause of death globally, yet research has been hindered by inadequate laboratory models that fail to replicate the intricate interactions involved in vascular diseases [2] - Current models are either overly simplified (2D) or lack the necessary structural and functional complexity (3D), leading to unresolved mechanisms and ineffective drug trials [2] Technological Innovation - The EoD bioprinting technology developed in this study allows for the construction of arterial models that accurately reflect the microenvironment of vascular diseases, including specific gene/protein expressions that enhance endothelial function and barrier integrity [5][6] - This technology bridges the gap between simplified in vitro systems and the complex in vivo environments, providing a biomimetic platform for disease mechanism analysis and therapy evaluation [5][9] Key Findings - The printed arterial models successfully replicate hallmark processes of vascular diseases, such as endothelial dysfunction, immune cell infiltration, and foam cell formation under physiologically relevant flow and inflammatory conditions [8][9] - The response of these models to drugs mirrors in vivo results, establishing their value for preclinical testing and therapeutic discovery [8] Implications for Future Research - This research not only presents a sophisticated vascular model but also offers a blueprint for engineering complex disease environments, paving the way for decoding vascular disease progression, identifying therapeutic targets, and accelerating precision medicine [9]

Core Insights - Recent research indicates that autophagy is activated during exercise, mediating the health benefits associated with physical activity. However, the molecular mechanisms regulating skeletal muscle autophagy during exercise remain unclear [3][5]. Group 1: Research Findings - A study published in Cell Chemical Biology reveals that lactate produced during exercise enhances autophagy in skeletal muscle by lactylation of the mTOR protein [3][5]. - Lactate is identified as a positive regulator of autophagy in muscle cells, with levels rapidly increasing after a single exercise session [5]. - The study demonstrates that lactate promotes lactylation at the K921 site of the mTOR protein, inhibiting mTORC1 activity and enhancing autophagy [5][8]. Group 2: Implications - This research fundamentally redefines lactate, transforming it from a mere metabolic byproduct into a key signaling molecule that mediates exercise-induced skeletal muscle adaptation [7][8]. - The findings provide a conceptual framework for understanding how muscle metabolism translates into adaptive responses, opening new avenues for the treatment of muscle and metabolic diseases [8].

Core Viewpoint - The article discusses a significant advancement in the asymmetric synthesis of N-chiral compounds, highlighting a collaborative research effort that successfully achieved the first catalytic asymmetric synthesis of these compounds, which is crucial for future studies in this area [4][5]. Group 1: Research Background - The research was conducted by a team from Southern University of Science and Technology and UCLA, focusing on controlling pyramidal nitrogen chirality through asymmetric organocatalysis [4]. - The study addresses the challenges associated with the instability of nitrogen stereocenters and the limited success in asymmetric synthesis of non-cyclic N-chiral compounds [5][7]. Group 2: Methodology and Findings - The team proposed a method to synthesize challenging non-cyclic N-chiral chlorohydroxylamines through asymmetric chlorination reactions, capturing unstable chiral intermediates to obtain more stable N-chiral molecules [7]. - A significant breakthrough was achieved using a chiral phosphoric acid catalyst, leading to the successful synthesis of 21 N-stereocenters with high enantioselectivity [8]. - The research demonstrated that introducing a rigid bicyclic structure near the nitrogen atom significantly improved the stability of the configuration, reducing racemization [10]. Group 3: Mechanism and Results - The study confirmed that the key step for stereoselectivity was the chlorination reaction, followed by an intramolecular nucleophilic substitution that adhered to the S N 2 mechanism, ensuring effective transfer of chirality [10]. - The final products exhibited enantiomeric excess values greater than 90%, showcasing the method's effectiveness and broad applicability [10].

Core Insights - The article discusses the transformative potential of in vivo CAR-T cell therapy, which aims to overcome the limitations of traditional CAR-T therapies by generating CAR-T cells directly within the patient, thus eliminating complex manufacturing and logistics challenges [2][3][6]. Group 1: In Vivo CAR-T Technology - In vivo CAR-T technology leverages advancements in virology, RNA therapeutics, and nanomedicine to deliver genetic material encoding CAR into endogenous T cells, enhancing clinical efficacy and simplifying the treatment process [2][3][9]. - The technology aims to expand the applicability of CAR-T therapies beyond hematological malignancies to include autoimmune diseases like systemic lupus erythematosus [3][7]. Group 2: Clinical Development and Platforms - The article highlights two main in vivo CAR platforms: engineered viral vectors (such as lentiviruses) that integrate payloads into the host genome, and lipid nanoparticles (LNPs) that enable transient expression of the payload within host cells [9][11]. - Several companies are developing in vivo CAR-T therapies, with various targeting mechanisms and therapeutic payloads aimed at treating conditions like B cell malignancies and solid tumors [10][11]. Group 3: Future Directions and Challenges - The review emphasizes the need for innovation in delivery and engineering technologies to fully realize the potential of CAR-T therapies, addressing current limitations in accessibility and clinical performance [7][15]. - The transition from ex vivo to in vivo CAR-T therapies is expected to redefine the scalability and accessibility of immunotherapies, significantly reducing production costs and enhancing the socio-economic impact of these life-saving treatments [23].