该研究开发了一种 通过氮原子插入对吡咯烷进行 骨架编辑 的新方法，为吡咯烷的氮基骨架编辑搭建了多功能平台，显著拓展了药物化学的 合成工具箱。 编辑丨王多鱼 排版丨水成文 鉴于含氮杂环化合物在生物活性分子中的普遍存在，向饱和环中插入一个氮原子为拓展类药化学空间提供了一种强效但尚未充分开发的骨架跃迁 （scaffold- hopping） 策略，骨架跃迁，即通过改变核心骨架结构优化分子性质的药物设计方法。 2025 年 7 月 17 日，南京大学化学化工学院 陆红健 教授团队在国际顶尖学术期刊 Science 上发表了 题为： Skeletal editing of pyrrolidines by nitrogen- atom insertion 的研究论文。 设置 星标 ，不错过精彩推文 开放转载 骨架编辑 （skeletal editing） ，是一种直接改变分子骨架原子组成 （例如插入/删除原子） 的策略。 在这项最新研究中，研究团队提出了一种骨架编辑方法， 可在温和、操作简单的条件下，利用市售的 O-二苯基膦羟胺 （ O -diphenylphosphinyl hydroxylamine） 将氮原子直接插 ...

Core Viewpoint - The article discusses a groundbreaking alternative therapy for treating methicillin-resistant Staphylococcus aureus (MRSA) infections, which poses a significant threat due to its antibiotic resistance and high mortality rates globally [1][2][4]. Group 1: Research Findings - A study published in Nature Biotechnology introduces a novel method using antibody-polysialic acid conjugates (APC) to encapsulate MRSA in a calcium shell, effectively neutralizing its activity while enhancing the host's immune response [3][4][6]. - The research demonstrates that systemic administration of APC can efficiently and safely treat chronic lung infections and chronic osteomyelitis caused by MRSA in mouse models [8][10]. - The mechanism involves attracting calcium ions to the bacterial cell wall, leading to calcification that disrupts MRSA's energy metabolism and essential metabolic pathways, resulting in bacterial death [6][8]. Group 2: Implications and Future Applications - This innovative approach not only targets MRSA but may also be applicable to other antibiotic-resistant infections due to the critical role of cell wall teichoic acids in Gram-positive bacteria [10]. - The study highlights the potential for APC to stimulate immune responses, increasing the expression of calprotectin and S100A8/S100A9 in macrophages, thereby promoting bacterial clearance [8].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 胰腺神经分布密集， 胰腺导管腺癌 （PDAC） 在各类癌症中 神经侵犯 （ Neural Invasion， NI） 的发生率最高 （80%-100%） 。 神经侵犯也已被确认为胰 腺癌预后不良的独立预测因素。鉴于神经侵犯在局部复发、转移和疼痛产生方面的重要作用，靶向神经侵犯可能是胰腺导管腺癌 （PDAC） 的一种治疗策略。 之前的研究强调了神经侵袭中癌细胞与神经之间相互信号转导的重要性，涉及神经营养因子、趋化因子和轴突导向分子。在体外模型和小鼠模型研究中，间质细 胞和免疫细胞也被证明会对神经侵犯产生影响。然而，将这些发现转化为临床应用已被证明颇具挑战性。 2025 年 7 月 17 日，重庆医科大学/北京大学生物医学前沿创新中心 张泽民 院士、广东省人民医院 陈汝福 教授、 张庆玲 教授、深圳湾实验室 陈敏敏 副研究 员作为共同通讯作者，在 Cancer Cell 期刊发表了题为： Integrated single-cell and spatial transcriptomics uncover distinct cellular subtypes involved ...

Core Viewpoint - The article discusses a groundbreaking study published in the New England Journal of Medicine (NEJM) that reports the birth of eight healthy "three-parent babies" through mitochondrial donation, which offers hope for families affected by mitochondrial diseases [2][3][11]. Group 1: Mitochondrial Diseases and Their Treatment - Mitochondrial diseases, caused by pathogenic mutations in mitochondrial DNA (mtDNA), primarily affect high-energy organs such as the heart, brain, and muscles, often leading to severe health issues and lack of effective treatments [2][5]. - The technique involves transferring the nucleus of an egg from a mother with pathogenic mtDNA into a donor egg that has had its nucleus removed, allowing for the birth of children without the mother's mitochondrial diseases [5][7]. Group 2: Birth of "Three-Parent Babies" - A total of 22 women with pathogenic mtDNA mutations underwent mitochondrial donation treatment, resulting in the successful birth of eight children (including a set of twins), with the oldest being over two years old and the youngest under five months [16]. - Among the eight children, five have shown no health issues, while others experienced minor, treatable conditions, indicating initial success in preventing mitochondrial diseases [16][18]. Group 3: Ethical Considerations and Future Outlook - The technique raises significant ethical questions and has been the subject of intense debate, leading to the UK being the first country to legislate and regulate mitochondrial donation for clinical use [9][20]. - Despite the promising results, researchers urge caution due to the small sample size and short follow-up period, as some children still carry low levels of maternal pathogenic mtDNA, necessitating further long-term studies to confirm safety and efficacy [20].

Core Insights - The article discusses the critical role of thyroid hormone transport to the brain for normal neural development, mediated by the transport proteins MCT8 and OATP1C1 [2][3]. Group 1: Research Findings - A recent study published in the journal Cell by researchers from Baylor College of Medicine and the National Institutes of Health provides structural insights into the transport mechanisms of thyroid hormones via MCT8 and OATP1C1 [4][5]. - The study utilized cryo-electron microscopy to analyze the structures of MCT8 and OATP1C1 in complex with active thyroid hormones T3 and its precursor T4, achieving resolutions of 2.9 Å and 2.3 Å respectively [7]. - Key findings include the high transport specificity of MCT8 for thyroid hormones, the selective transport mechanism of OATP1C1 for thyroxine, and the discovery of a conserved extracellular regulatory site in OATP1C1 that can be allosterically inhibited by E1G [9][11].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 炎症 对于维持体内平衡以及保护组织和器官的完整性至关重要。然而，过度的炎症反应可能会导致严重的组织损伤。炎症反应的强度、持续时间和影响必须根据 炎症诱因的存在以及病理结果的程度进行调节。我们对于炎症的保护作用和病理作用的诸多认识，都与炎症反应如何影响器官功能有关。相比之下，我们对于特 定组织的状态如何影响炎症反应，仍知之甚少。 维持稳定的 pH 值 是组织内环境稳定的普遍特征。不同的组织和器官维持着不同的间质 pH 值环境，这些环境在炎症期间常常会受到干扰。例如，血液的 pH 值 被严格控制在 7.35-7.45 之间，而脓毒症中的严重酸中毒与不良预后相关；淋巴结副皮质区的 pH 值在 6.3-7.1 之间，在感染期间会变得更酸； 实体瘤通常表现 出酸性环境。这些都表明了 组织微环境偏离正常生理 pH 值 的酸化与炎症密切相关。 2025 年 7 月 17 日，波士顿儿童医院/哈佛大学医学院 周旭 教授团队与耶鲁大学 R uslan Medzhitov 教授 团队合作 （博士后 吴中洋 为论文第一作者） ，在国 际顶尖学术期刊 Cell 上发表了题为： Regulati ...

Core Viewpoint - The combination of lithium metal anodes and high nickel cathodes is seen as a potential breakthrough for achieving energy densities exceeding 500 Wh/Kg, with stable electrolyte interfaces being crucial for safety and longevity [2] Group 1 - The research team from Huazhong University of Science and Technology and Zhejiang University published a paper in Nature on July 16, 2025, discussing a microemulsion electrolyte design strategy that bypasses the need for lithium ion solvation structure regulation [4] - The mechanism involves liquid-liquid interfacial tension driving fluorinated droplets to migrate towards both electrodes, enhancing the interface construction of both electrodes in a synergistic manner [4] - The use of microemulsion electrolytes resulted in two soft-pack full batteries achieving energy densities of 531 Wh/Kg and 547 Wh/Kg, with capacity retention rates of 81% and 79% after 189 and 155 cycles, respectively [4] Group 2 - The introduction of the concept of liquid-liquid interfacial tension provides a new perspective for interface regulation and electrolyte design, paving the way for the development of high-voltage lithium metal batteries [4]

Core Viewpoint - The article highlights the significant contributions of Chinese scholars in the field of research, particularly noting that 10 out of 25 papers published in the prestigious journal Nature on July 16, 2025, were authored by Chinese researchers, showcasing the growing influence and capabilities of Chinese academia in global scientific research [2][5][7][8][10][13][16][19][21][24]. Summary by Relevant Sections - **Research Contributions**: On July 16, 2025, multiple research papers were published in Nature, with notable contributions from various universities, including Wuhan University, the University of Chicago, Cornell University, Nanyang Technological University, Tsinghua University, Rutgers University, and others, indicating a strong presence of Chinese scholars in high-impact research [2][5][7][8][10][13][16][19][21][24]. - **Specific Research Topics**: The papers cover a wide range of topics, including the impact of climate change on hospitalization, advancements in spectroscopy, dynamic kinetic resolution in chemistry, and innovations in battery technology, reflecting the diverse research interests and expertise of the authors [2][5][7][8][10][13][16][19][21][24]. - **Collaborative Efforts**: Many of the papers feature collaborations among researchers from different institutions, emphasizing the importance of teamwork and interdisciplinary approaches in advancing scientific knowledge [2][5][7][8][10][13][16][19][21][24].

Core Viewpoint - The article discusses the promising potential of CLDN18.2 as a therapeutic target for gastric and gastroesophageal junction adenocarcinoma, highlighting the development and clinical trial results of the antibody-drug conjugate (ADC) IBI343 [1][4][9]. Group 1: IBI343 Overview - IBI343 is an ADC developed by Innovent Biologics, consisting of a fully humanized anti-CLDN18.2 monoclonal antibody, a DNA topoisomerase I (TOP-1) inhibitor, and a cleavable linker, with a drug-to-antibody ratio of 4 [2]. - The clinical trial results published in Nature Medicine indicate that IBI343 shows good tolerability and manageable safety, with a low incidence of gastrointestinal adverse events in patients with high CLDN18.2 expression [3][4]. Group 2: Clinical Trial Results - A total of 127 patients with advanced gastric or gastroesophageal junction adenocarcinoma were enrolled in the phase 1 trial, with 19 in the dose escalation phase and 108 in the dose expansion phase [7]. - At a dose of 10 mg/kg, 2 out of 6 participants experienced dose-limiting toxicities, including one case of grade 4 bone marrow suppression and one case of grade 4 neutropenia [8]. - The recommended phase 2 dose is 6 mg/kg every 3 weeks, showing an objective response rate of 29% and a median progression-free survival of 5.5 months in patients with high CLDN18.2 expression [9]. Group 3: Future Research Directions - Ongoing phase 3 multicenter, randomized, controlled studies and future research on the combination of IBI343 with other therapies, particularly immunotherapies, may provide further evidence supporting IBI343 as a new treatment option for gastric and gastroesophageal junction adenocarcinoma and other CLDN18.2-expressing solid tumors [10][11].

Core Viewpoint - CLDN18.2 is identified as a potential therapeutic target for gastric cancer and gastroesophageal junction adenocarcinoma, with the antibody-drug conjugate SHR-A1904 showing promising results in a Phase 1 clinical trial [1][4]. Group 1: Clinical Trial Overview - The Phase 1 clinical trial evaluated SHR-A1904 in 95 patients with advanced gastric or gastroesophageal junction cancer who were CLDN18.2 positive [4]. - The trial included a dose escalation phase (0.6–8.0 mg/kg), with dose-limiting toxicities observed at 4.8 mg/kg and 6.0 mg/kg, but the maximum tolerated dose was not reached [4]. - Common treatment-related adverse events included anemia (75.8%), nausea (67.4%), hypoalbuminemia (64.2%), and leukopenia (58.9%) [4]. Group 2: Efficacy Results - In patients with assessable efficacy, the confirmed objective response rate was 24.2% for the 6.0 mg/kg dose group and 25.0% for the 8.0 mg/kg dose group [5]. - The median progression-free survival was 5.6 months for the 6.0 mg/kg group and 5.8 months for the 8.0 mg/kg group [5]. Group 3: Research Team - The paper was co-authored by Dr. Xu Ruihua and Dr. Qiu Miaozhen from Sun Yat-sen University Cancer Prevention and Treatment Center, along with other contributors [6].