2025 年 6 月 25 日 ，中国 工程院外籍院士、 加拿大皇家科学院院士、加拿大工程院院士、 宁波东方理工大学讲席教授，物质与能源研究院院长 孙学良 ，在国 际顶尖学术期刊 Nature 期刊发表了题为 ： A cost-effective all-in-one halide material for all-solid-state batteries 的研究论文。 全固态电池需要先进的阴极设计才能实现其高能量密度和经济可行性的潜力。集成一体化 （ all-in-one ） 阴极，消除了无活性的导电添加剂和异质界面，有望 带来显著的能量和稳定性提升，但因材料缺乏足够的锂离子/电子 （ Li + / e − ） 电导率、机械强度和结构稳定性而受到阻碍。 在这项最新研究，研究团队开发了一种经济实惠的 卤化物材 料—— Li 1.3 Fe 1.2 Cl 4 ，克服了集成一体化 阴极面临的难题。利用其框架内可逆的 Fe 2+ /Fe 3+ 氧化还原反应以及快速的 Li + / e − 传输，Li 1.3 Fe 1.2 Cl 4 相对于 Li + /Li 实现了 529.3 Wh/kg 的电极能量密度。 编辑丨王 ...

Core Insights - The article highlights six research papers published in the prestigious journal Cell, with four authored by Chinese scholars, focusing on various scientific advancements in neuroendocrine circuits, cell therapy, exercise, and developmental biology [2]. Group 1: Sleep-Dependent Growth Hormone Release - A study by Academician Dan Yang's team reveals the activity patterns of two types of neurons in the hypothalamus—GHRH and SST neurons—during different sleep stages, regulating growth hormone (GH) secretion [4][5]. - The research uncovers how GH enhances the excitability of locus coeruleus neurons to promote wakefulness, ensuring substantial GH release during sleep while preventing excess [5]. Group 2: iPSC-CAR-NK Cell Therapy for Autoimmune Diseases - A collaborative study led by Professor Xu Huji from the Navy Medical University demonstrates the first successful clinical application of iPSC-derived CD19/BCMA CAR-NK cell therapy in a patient with diffuse cutaneous systemic sclerosis [8][10]. - This research marks a significant breakthrough in using iPSC-derived CAR-NK cells for treating autoimmune diseases, establishing a new paradigm for low-toxicity, broad-spectrum targeted therapies [10]. Group 3: Exercise and Anti-Aging Mechanisms - A team from the Chinese Academy of Sciences identifies betaine as a key molecule that mimics exercise effects, revealing its role in delaying aging by targeting TBK1 to inhibit inflammation and mitigate multi-organ aging processes [13][15]. - This study provides molecular evidence supporting the notion that "exercise is the fountain of youth" and introduces a novel strategy for systemic anti-aging interventions through "exercise-mimicking drugs" [15]. Group 4: Decoding Developmental Dynamics - Researchers from BGI and Southern University of Science and Technology create a 3D single-cell spatiotemporal multi-omics atlas of Drosophila, unveiling key regulators of cell-type differentiation throughout development [17][19]. - This groundbreaking work offers unprecedented molecular insights into developmental biology, laying a foundation for understanding developmental defects and related disease mechanisms [19].

Core Insights - The article discusses the critical role of sleep in the recovery of the body and brain, highlighting its connection to various health issues such as diabetes, obesity, and cardiovascular diseases [2] - It emphasizes the relationship between sleep and the release of growth hormone (GH), which is essential for muscle and bone growth, and how sleep deprivation disrupts hormonal balance [2][10] Research Findings - A study published in the journal Cell by a team led by Academician Dan Yang reveals the precise regulation of GH release during different sleep stages by two types of neurons in the hypothalamus: GHRH neurons and SST neurons [3][6] - The research identifies that GH release is enhanced during both REM and NREM sleep, regulated by the activity of GHRH and SST neurons [6][9] - The study also uncovers a negative feedback loop where GH enhances the excitability of locus coeruleus (LC) neurons, promoting wakefulness and preventing excessive sleep [10] Mechanisms of GH Regulation - GHRH neurons act like an "accelerator" to promote GH release, while SST neurons function as a "brake" to inhibit it [9] - During NREM sleep, GHRH activity increases moderately while SST activity decreases, facilitating GH release [9] - In REM sleep, both GHRH and SST neurons exhibit explosive activation, ensuring a balanced release of GH [9][10] Implications of Findings - The study provides insights into the neuroendocrine mechanisms behind sleep-dependent GH release, linking metabolic states with sleep tendencies [10] - It highlights the importance of sleep in regulating glucose and lipid metabolism, as well as muscle and bone growth, underscoring the health risks associated with sleep deprivation [10]

Core Viewpoint - The study reveals that bile acids activate cancer-associated fibroblasts (CAFs) in cholangiocarcinoma, leading to an immunosuppressive microenvironment, which provides potential targets for immunotherapy [4][10]. Group 1: Research Findings - Bile acids specifically activate GPBAR1 on CAFs, leading to increased expression of CXCL10, which enhances epithelial-mesenchymal transition (EMT) and metastasis in cholangiocarcinoma [6]. - The study found that high levels of bile acids and GPBAR1 expression correlate with poor prognosis and inadequate response to immunotherapy in cholangiocarcinoma patients [7]. - Targeting the GPBAR1-CXCL10 signaling axis can enhance the efficacy of anti-PD-1 monoclonal antibodies in various preclinical models of cholangiocarcinoma [6][8]. Group 2: Implications for Immunotherapy - The bile acid-GPBAR1 signaling axis reprograms CAFs to establish an immunosuppressive microenvironment in cholangiocarcinoma [8]. - CXCL10 produced by CAFs recruits neutrophils and maintains their immature phenotype, contributing to the immunosuppressive tumor microenvironment [8]. - The activation of CXCR3 by the GPBAR1-CXCL10 signaling axis promotes EMT in cholangiocarcinoma cells [8].

Core Viewpoint - The article discusses the approval of Mazdutide, a dual receptor agonist for GLP-1 and GCG, by China's National Medical Products Administration (NMPA) for long-term weight management in adults with obesity or overweight conditions [2][4]. Summary by Sections Drug Approval and Indications - Mazdutide is approved for adults with a BMI ≥ 28 kg/m² (obesity) or BMI ≥ 24 kg/m² (overweight) with at least one weight-related comorbidity [2]. - The drug is designed to work alongside dietary control and increased physical activity for effective long-term weight management [2]. Mechanism of Action - Mazdutide targets both GLP-1 and GCG receptors, suppressing appetite and enhancing energy expenditure, which helps in weight loss and improves liver fat metabolism [2][4]. Clinical Trial Results - The Phase 3 clinical trial (GLORY-1) published in NEJM demonstrated significant weight loss and safety in Chinese adults [3][4]. - In the trial, participants receiving 4 mg and 6 mg doses of Mazdutide showed average weight reductions of -10.09% and -12.55% at 32 weeks, respectively, with 82.0% of the 6 mg group losing at least 5% of their body weight [8][12]. - At 48 weeks, the weight loss was -11.00% for the 4 mg group and -14.01% for the 6 mg group, with 49.5% of the 6 mg group losing over 15% of their body weight [8][12]. Safety Profile - The most common adverse events were gastrointestinal, mostly mild to moderate, with a low discontinuation rate due to side effects (0.5% for the 6 mg group) [11][12]. - The safety profile of Mazdutide is significantly better compared to similar drugs like Semaglutide and Tirzepatide [11][12]. Additional Benefits - Besides weight loss, Mazdutide showed beneficial effects on cardiovascular metabolic indicators, including a reduction in waist circumference and improvements in blood pressure and triglycerides [10][12]. Significance of Research - This research marks a significant advancement in China's drug development capabilities, being the first innovative drug clinical study in the metabolic and endocrine disease field to be published in a top-tier medical journal [4][13].

编辑丨王多鱼 排版丨水成文 2022 年底， ChatGPT 横空出世，这个能够学习并理解人类自然语言的 AI 聊天机器人震惊了全世界，并 掀起了大语言模型 （LLM） 浪潮。 而现在，人工智能公司 InstaDeep 将这种 AI 的这一强大能力带到了生命科学领域，打造了一款名为 ChatNT （ Chat N ucleotide T ransformer ） 的 多模态对话智能体 ， 能像生物学家一样，"读懂" DNA、RNA 和蛋白质的序列信息，并用自然语言 （英语） 与你对话，直接回答你关于这些生物分子的各 种专业问题。 该研究以 ： A multimodal conversational agent for DNA, RNA and protein tasks 为题 ，于 2025 年 6 月 6 日 发表在了 Nature 子刊 Nature Machine Intelligence 上，该论文的作者还包括来自 mRNA 疫苗巨 头 BioNTech 的研究人员。 撰文丨王聪 欢迎进群分享/讨论 生物医学领域 AI 智能体 研究进展 扫码后进群 生物学研究的痛点：模型太多、门槛太高 在基因组学、转 ...

Core Viewpoint - The research published in Science reveals that the insufficient expression of the Aldh1a2 gene leads to inadequate synthesis of retinoic acid (RA), which is the core mechanism behind the failure of ear regeneration in higher mammals like mice. Activating this gene or supplementing with RA can enable ear regeneration in mice [2][3][8]. Group 1: Research Findings - The study identifies Aldh1a2 gene expression deficiency as a critical factor in the failure of ear regeneration in mice, linking it to insufficient RA synthesis [3][8]. - By activating the Aldh1a2 gene or providing external RA, the research demonstrated successful regeneration of the ear in mice after injury [13][14]. - The research utilized advanced techniques such as single-cell RNA sequencing and spatiotemporal omics technology to compare regenerative processes between species with and without ear regeneration capabilities [7][15]. Group 2: Evolutionary Insights - The study highlights evolutionary differences, noting that rabbits, which can regenerate their ears, have multiple active enhancers near the Aldh1a2 gene that are not present in mice, leading to lower expression levels of this gene in the latter [11][17]. - The loss of enhancer activity in the evolutionary lineage of mice and rats explains their inability to regenerate ear tissue after injury [11][17]. - The research provides a theoretical basis for exploring organ reconstruction and regeneration in humans by understanding the mechanisms behind the loss of regenerative capabilities in higher mammals [15].

Core Viewpoint - The article discusses the development of a deep learning system called DeepSLE for detecting systemic lupus erythematosus (SLE) from retinal images, highlighting its potential to improve early diagnosis and management of the disease and its complications [4][5][12]. Group 1: Disease Overview - Systemic lupus erythematosus (SLE) is a severe autoimmune disease affecting approximately 3.4 million people globally, with an estimated 3 million being women [2]. - The likelihood of women developing SLE is several times higher than that of men, with a peak incidence typically occurring between the ages of 15 and 45 [2]. Group 2: Screening Challenges - There is a significant challenge in the early detection of SLE due to the lack of widely accepted, standardized, non-invasive, and cost-effective screening tools, especially for asymptomatic or mildly symptomatic individuals [3]. - Current screening methods for SLE-related complications, such as lupus retinopathy (LR) and lupus nephritis (LN), are not routinely implemented in primary care settings, particularly in resource-limited environments [7]. Group 3: DeepSLE Development - The DeepSLE system was developed using a dataset of 666,383 retinal images from 173,346 participants for pre-training, followed by training and validation on over 254,246 images from 91,598 participants across diverse ethnic backgrounds [9]. - The system demonstrated a robust performance in detecting SLE, achieving an area under the receiver operating characteristic curve (AUC) ranging from 0.822 to 0.969 in a multi-ethnic validation dataset [11]. Group 4: Clinical Implications - DeepSLE offers a digital solution for detecting SLE and its related complications from retinal images, presenting significant clinical application potential [12]. - The system showed higher sensitivity compared to primary care physicians in a prospective reader study, indicating its effectiveness in clinical settings [11].

目前，国内外研究人员已经开发出多种小鼠人源化模型，主要用于研究肝病及免疫相关疾病 （见表 1 ） 。 截至 2019 年 10 月，已有超过 200 篇利用多种类型嵌合小鼠或 PXB 细胞的研究论文发表，这些论文描述 了针对 乙肝病毒 （ HBV ） 或 丙肝病毒 （ HCV ） 药物的疗效研究，或药物代谢与药代动力学 （ DMPK ） 研究，包括吸收、分布、代谢和排泄 （ ADME ） 、药物相互作用 （ DDI ） 以及使用药物或化学物质进 行的肝毒性研究。 | Table 1 Publications using humanized mouse/cells | | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Chimeric mice or cells | PXB- | FRG | TK-NOG | uPA/SCID mouse | uPA/SCID mouse | | uPA/SCID mouse uPA/SCID mouse | PXB- | Total | | | mouse | m ...

Core Viewpoint - The research conducted by the team led by Academician Shi Yigong reveals the structural basis of BAX pore formation, which is crucial for understanding mitochondrial outer membrane permeability during apoptosis [2][3]. Group 1: Research Findings - The study elucidates the assembly principles of various BAX oligomers, providing a structural foundation for BAX-mediated mitochondrial outer membrane permeability [3]. - The research team purified recombinant human BAX protein and confirmed its membrane permeability activity through cytochrome c release experiments based on liposomes [5]. - The activated BAX oligomers were extracted and purified from overexpressed BAX protein in human embryonic kidney 293F cells for cryo-electron microscopy analysis [6]. Group 2: Structural Insights - The study identified that the dimer of BAX is the basic repeating structural unit of its various oligomeric forms (arc, line, and ring) [7]. - The structure of the BAX repeating unit revealed interactions within and between dimers, with the α9 helix facilitating end-to-end stacking to form linear, arc, polygonal, and ring shapes [7]. - Structural characterization was performed on quadrilateral, pentagonal, hexagonal, and heptagonal forms composed of 16, 20, 24, and 28 BAX monomers, respectively [7]. Group 3: Implications of Findings - The results clarify how activated BAX oligomers permeabilize (or rupture) the mitochondrial outer membrane and explain how different shapes (arc, line, and ring) are assembled from the same repeating unit [9].