Core Viewpoint - The article discusses the development and potential of the AI-CEMA system, a deep learning-assisted diagnostic tool for intrathoracic lymphadenopathy and lung lesions, which demonstrates diagnostic accuracy comparable to experienced experts [3][5][6]. Group 1: Background on Intrathoracic Lymphadenopathy - Intrathoracic lymphadenopathy is a common challenge faced by pulmonologists, characterized by abnormal enlargement of mediastinal and hilar lymph nodes [2]. - The most common malignant cause of intrathoracic lymphadenopathy is lung cancer, which is the leading cancer globally and the primary cause of cancer-related deaths, with an estimated 2.5 million new cases and 1.8 million deaths in 2022 [2]. Group 2: AI-CEMA System Development - The AI-CEMA system was developed by a team from Shanghai Jiao Tong University and published in Cell Reports Medicine, focusing on the detection and diagnosis of intrathoracic lymphadenopathy using endobronchial ultrasound multimodal videos [3]. - The system utilizes convex probe endobronchial ultrasound (CP-EBUS) multimodal videos to automatically select representative images, identify lymph nodes, and differentiate between benign and malignant nodes [5]. Group 3: Performance and Validation - AI-CEMA was trained on a dataset of 1,006 lymph nodes and validated through a retrospective study, achieving an area under the curve (AUC) of 0.8490, comparable to the expert level AUC of 0.7847 [5]. - The system also successfully applied to lung lesion diagnosis, achieving an AUC of 0.8192, indicating its versatility and effectiveness in clinical settings [5]. Group 4: Clinical Implications - The AI-CEMA system offers a non-invasive diagnostic approach, providing automated and expert-level diagnosis for intrathoracic lymphadenopathy and lung lesions, showcasing significant potential in clinical diagnostics [6][8].

编辑丨王多鱼 排版丨水成文 听力损失 为全球最常见的感觉障碍之一，世界卫生组织 （WHO） 数据显示，全球 20% 的人受不同程度 听力损失的影响，全球 5% 的人患有致残性 （中度以上） 的听力损失，约有 2600 万先天性耳聋患者。 每 1000 名新生儿中约有 2 - 3 名患有先天听力障碍。 听力障碍，不仅仅意味着失聪，更常伴随着言语障碍， "十聋九哑"成为了残酷的现实， 严重损害 儿童言 语及认知功能 等 形成 和发展。约 60% 的先天性耳聋 与 遗传因素 有关，已知的耳聋基因超过 200 个， 以往无任何临床治疗药物。 近半个世纪以来， 人工耳蜗植入 都是临床上极重度以上感音神经性聋的金标准疗法和唯一选择，但其难以 完全恢复自然听觉，对音乐和噪声环境下的言语感知的改善有限，并且外在设备和长期的设备维护也使得 人工耳蜗的接受度很低。近年来，先天性耳聋 基因治疗 作为一种全新的、针对病因的治疗手段，有望恢复 自然听力，引起了领域内的高度关注。 然而，基因治疗后多个维度的感知情况究竟如何？与传统的人工耳蜗植入相比有何优势、劣势？还有待验 证。 2025 年 7 月 21 日，由复旦大学附属眼耳鼻喉科医 ...

Core Viewpoint - Alternating Hemiplegia of Childhood (AHC) is a rare neurodevelopmental disorder with no current treatment to alter its progression, primarily linked to mutations in the ATP1A3 gene, which accounts for approximately 70% of cases [2][6]. Group 1: Disease Overview - AHC manifests within the first 18 months of life, characterized by recurrent symptoms such as hemiplegia, muscle tone disorders, abnormal eye movements, and seizures, along with developmental delays and intellectual disabilities [1][6]. - The ATP1A3 gene encodes the α3 subunit of the Na+/K+-ATPase, crucial for neuronal function, and its dysfunction leads to neuronal hyperexcitability and metabolic imbalances [2]. Group 2: Genetic Insights - Over 50 pathogenic mutations related to AHC have been reported, with three mutations (D801N, E815K, G947R) accounting for over 65% of cases [2]. - The dominant-negative disease mechanism of ATP1A3 mutations complicates traditional gene therapy approaches, as these mutations not only lose function but also interfere with normal protein function [2]. Group 3: Research Breakthroughs - A study published on July 21, 2025, in the journal Cell demonstrated the use of prime editing technology to treat AHC in mouse models, effectively correcting common ATP1A3 mutations and restoring Na+/K+ ATPase activity [3][4]. - The research team achieved correction rates of 48% at the DNA level and 73% at the mRNA level in the brain cortex of treated mice, leading to significant improvements in seizure activity, motor deficits, and cognitive impairments, as well as extended lifespan [9][12]. Group 4: Future Implications - The findings suggest that prime editing could serve as a one-time therapeutic approach for AHC, potentially opening avenues for treating other long-considered untreatable neurological disorders [4][11]. - The study emphasizes the importance of patient-centered research, as highlighted by the involvement of RARE Hope's founder, who advocates for increased accessibility to treatments for rare neurological conditions [11].

Core Viewpoint - The article discusses the potential benefits of a four-day workweek, highlighting a study that shows improvements in employee well-being without a reduction in pay [3][4][11]. Group 1: Study Findings - The largest trial of a four-day workweek found that it led to happier, healthier employees with higher job satisfaction due to increased work efficiency, reduced fatigue, and fewer sleep issues [3][4]. - Employees in the trial reported a reduction in work hours by an average of 5 hours per week, with those reducing hours by 8 or more experiencing lower burnout and improved mental health [8]. - Over 90% of companies that participated in the trial chose to continue the four-day workweek after six months, indicating confidence in maintaining productivity and profits [11]. Group 2: Research Methodology - The study involved 2,896 employees from 141 companies across Australia, New Zealand, the US, Canada, Ireland, and the UK, who had eight weeks to reorganize workflows before the trial [6]. - Employees completed surveys assessing their mental health and job satisfaction before and after the implementation of the four-day workweek [7]. - The research compared the results of trial participants with 285 employees from 12 companies that did not participate, providing a control group for analysis [7]. Group 3: Long-term Effects - Data collected 12 months after the trial indicated that employee happiness remained high, suggesting lasting positive effects of the four-day workweek [9]. - Concerns about employees being unable to complete a five-day workload in four days were addressed, with findings suggesting that better rest leads to fewer mistakes and greater engagement during work hours [10]. Group 4: Limitations and Future Research - The study's conclusions are based on self-reported data from voluntarily participating companies, which may not be representative of all types of organizations [12]. - The authors call for randomized studies to further validate the effects of a four-day workweek [12].

值得注意的是 ， 基质辅助的自体软骨细胞移植术 （Matrix-associated Autologous Chondrocyte Implantation，MACI） 最近已获美国 FDA 批准，用于修复 18-55 岁患者孤立性关节软骨损伤，这表明，细胞疗法有望成为治疗骨关节炎的一种有效手段。然而，自体软骨细胞增殖能力有限，导致 MACI 治疗后康复时间 延长且可修复区域受限。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 骨关节炎 （ Osteoarthritis， OA） 是一种退行性关节疾病，最常影响中老年人群。骨关节炎的进展始于关节软骨的退化，这种退化逐渐侵蚀到软骨下的骨组织 及周围组织，从而导致滑膜炎、膝关节疼痛、活动受限以及畸形。虽然非甾体抗炎药能够缓解轻度骨关节炎的症状 （例如炎症和疼痛） ，但严重病例可能需要进 行全关节置换手术。 成年膝关节中的 关节软骨祖细胞 的身份，以及它们促进软骨再生的调控机制，目前仍知之甚少。 2025 年 7 月 21 日，同济大学生命科学与技术学院 、附属东方医院 岳锐 教授团队联合海南医科大学 邹卫国 教授团队 （ 朱巧玲 、 秦佳晨 、 石婉玉 、 尹峰 为论文 ...

Core Viewpoint - There is a compelling link between gut microbiota and atherosclerosis, a disease characterized by cholesterol and inflammatory cell deposits in arterial walls, leading to potential health issues like stroke and heart attacks [1][5]. Group 1: Research Findings - A study published in Nature identified Imidazole Propionate (ImP), a metabolite produced by gut bacteria, as a driver of atherosclerosis, suggesting new targets for early detection and personalized treatment of cardiovascular diseases [2][10]. - The study highlights the necessity for early intervention in seemingly healthy populations due to rising morbidity and mortality rates associated with cardiovascular diseases [5]. - The research team found a strong correlation between ImP levels and the severity of atherosclerosis in both mouse models and human cohorts [7][10]. Group 2: Mechanism of Action - ImP promotes atherosclerosis through the activation of the imidazoline-1 receptor (I1R) in myeloid cells, indicating a specific signaling pathway that could be targeted for therapeutic purposes [8][10]. - Blocking the ImP-I1R signaling axis can inhibit the development of atherosclerosis induced by either ImP or a high-cholesterol diet, suggesting a potential intervention strategy [8][10]. Group 3: Implications for Treatment - The findings open new avenues for the early diagnosis and personalized treatment of atherosclerosis, emphasizing the importance of understanding gut microbiota's role in cardiovascular health [10].

结构性心脏病 （SHD） ， 是一类日益流行的疾病， 包括影响心脏瓣膜、心室壁或心腔的疾病，例如心脏瓣膜病、右心和左心衰竭、肺动脉高压以及左心室肥 厚，在全球范围内影响着数千万人。 在疾病进程的早期阶段发现患有结构性心脏病 （SHD） 的患者，已被证明能够降低死亡率、减少治疗成本并提高生活质量。然而，由于缺乏常规且经济实惠的筛 查测试，许多有结构性心脏问题的人直到心脏功能严重受损时才被发现。 多种类型的 结构性心脏病，往往在疾病晚期才出现症状。所有类型的 结构性心脏病 都可以通过 超声心动图 明确诊断，但这种诊方法成本高、需要专业知识以及 合适的患者选择，限制了其全面应用。因此，迫切需要更好地对患者进行风险分层，并确定哪些患者应转诊进行超声心动图检查，从而提高结构性心脏病的诊断 率和早期治疗率。 2 025 年 7 月 16 日，哥伦比亚大学和 纽约长老会医院的研究人员合作，在国际顶尖学术期刊 Nature 上发表了题为： Detecting structural heart disease from electrocardiograms using AI 的研究论文。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 雌性生殖干细胞 （FGSC） 是最近发现的存在于哺乳动物出生后卵巢中的生殖系干细胞，其能够分化为卵母细胞，并在移植入卵巢后产生可育后代。长期以来， 人们一直认为，在雌性哺乳动物出生前，雌性生殖细胞在减数分裂前期 I 的双线期停滞不前。FGSC 的发现使得生成新的卵母细胞以恢复受损的女性生殖功能成为 可能，这在生殖医学和再生医学领域引起了极大的关注。 该领域的一个关键挑战在于体外调控 FGSC 在静息和激活状态之间的转换，以确保其固有的干细胞特性得以保持。然而，由于干细胞命运在很大程度上取决于天 然细胞外基质 （ECM） 的生物物理特性，尤其是其粘弹性机械特性，传统的 2D 刚性培养环境 （例如玻璃或塑料培养皿） ，难以提供调节细胞命运所必需的粘 弹性机械信号。这种缺陷会导致干细胞的复制能力下降以及应激相关基因的上调，从而抑制其发育潜能。 上海交通大学 樊春海 院士、 吴际 教授，上海大学 李江 研究员等 Cell 子刊 Cell Biomaterials 上发表了题为： Dictating the fate of female germline stem cells u ...

Core Viewpoint - Triple-negative breast cancer (TNBC) is characterized by high metastasis rates, poor prognosis, and low survival rates, making it the most aggressive and deadly subtype of breast cancer. The lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) makes identifying specific therapeutic targets a pressing challenge in TNBC research [2]. Group 1 - Increasing evidence suggests that non-coding RNAs, such as circular RNA (circRNA) and long non-coding RNA (lncRNA), can encode functional peptides/proteins that play significant regulatory roles in physiological and pathological processes. In TNBC, some peptides encoded by non-coding RNAs have been confirmed to participate in key oncogenic processes, including tumor growth, metastasis, and the development of treatment resistance [2]. - A novel peptide, 66CTG, encoded by lncRNA, has been identified to stabilize the c-Myc proto-oncogene protein, promoting cancer growth in TNBC. This discovery provides a new potential biomarker and therapeutic target for TNBC diagnosis and treatment [3]. - The research team identified an upregulated lncRNA, CDKN2B-AS1, in TNBC, which encodes a 66-amino acid peptide through CUG initiation translation. The peptide 66CTG was confirmed to be endogenously expressed in TNBC cells through CRISPR-Cas9 gene editing and mass spectrometry analysis [6]. Group 2 - Mechanistically, during the late G1 phase of cell division, 66CTG stabilizes c-Myc through competitive interaction with FBW7α, an E3 ligase that mediates the ubiquitination and degradation of c-Myc [7]. - Overall, the findings suggest that 66CTG could be developed as a target for TNBC diagnosis and treatment. The study reveals a regulatory axis where 66CTG interacts with FBW7α to stabilize c-Myc, providing a new mechanistic explanation for the overexpression of c-Myc in TNBC. Patients with overexpression of 66CTG, c-Myc, and Cyclin D1 may benefit from targeted therapy along this signaling axis [9].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 众所周知，人类的性别由性染色体 X 和 Y 决定，XY 为男性，XX 为女性。然而，X染色体上的基因数量远超 Y 染色体，为了保证两性基因表达数量的大致相当， 女性的两条 X 染色体中会有一条随机失活，这种剂量补偿机制是由 X 染色体上的长链非编码基因 X-IST 所介导的。 而对于鸟类 （包括鸡） ，它们的性别由性染色体 Z 和 W 决定，ZW 为雌性，ZZ 为雄性，而 Z 染色体上的基因数量远超 W 染色体，这导致雄性鸟类的基因数量 显著多于雌性，然而，鸟类的剂量补偿程度以及机制，至今仍不清楚。 2025 年 7 月 16 日，德国海德堡大学、英国爱丁堡大学、 瑞典乌普萨拉大学的研究人员在国际顶尖学术期刊 Nature 上发表了题为： A male-essential miRNA is key for avian sex chromosome dosage compensation 的研究论文。 该研究揭示了 鸟类独特的性染色体剂量补偿机制 ，其通过一种 miRNA—— miR-2954 来抑制特定的基因表达，防止雄性鸟类中这些基因过表达，从而确保雄性 鸟类的存活， ...