Core Viewpoint - The research conducted by BGI and Southern University of Science and Technology has created a groundbreaking 3D single-cell spatiotemporal multi-omics atlas of Drosophila development, providing unprecedented insights into the molecular mechanisms of cell-type differentiation and developmental biology [2][4][25]. Group 1: Research Methodology - The research team utilized BGI's proprietary spatiotemporal omics technology, Stereo-seq, along with single-cell sequencing techniques (scRNA-seq and scATAC-seq) to sample key stages of Drosophila development, generating over 3.8 million spatially resolved single-cell transcriptomes [3][7]. - The Spateo algorithm was employed to reconstruct high-precision 3D models, allowing for detailed analysis of tissue morphology and gene expression dynamics [7]. Group 2: Key Findings - The study systematically analyzed the spatiotemporal dynamics of cell-type differentiation in Drosophila, revealing critical regulatory networks that govern developmental processes [4][9]. - A "differentiation trajectory map" was constructed, elucidating the molecular mechanisms behind cell fate determination, with transcription factors acting as key regulators [9][22]. - The research identified previously uncharacterized transcription factors that play significant roles in the nervous, digestive, and endocrine systems, expanding the understanding of developmental regulation [9][22]. Group 3: Developmental Patterns - The 3D multi-omics atlas revealed the spatial patterns of tissue differentiation, with distinct developmental modes observed in the fat body and fore/hind gut [11][13]. - The fat body exhibited a dispersed differentiation pattern, while the fore/hind gut showed a centralized characteristic, providing new evidence for understanding embryonic gut formation [13]. Group 4: Central Nervous System Development - The study highlighted key nodes in the morphological remodeling of the central nervous system, identifying new regulatory factors associated with neural progenitor cell migration [14][22]. - The dynamic changes in midgut cell types and their spatial organization were tracked, revealing that midgut stem cells had already "prepared" for future differentiation during the larval stage [18][19]. Group 5: Implications for Human Health - Drosophila serves as a crucial model organism in various biological fields, sharing approximately 70% of disease-related genes with humans, thus providing valuable insights into human developmental diseases [9][25]. - The findings regarding the regulation of copper cells in the midgut may offer new mechanisms for understanding organ development in humans [22].

Core Insights - On June 25, 2025, a total of 22 papers were published in the prestigious journal Nature, with 9 authored by Chinese scholars, highlighting the significant contribution of Chinese researchers to global scientific advancements [2][4][7][9][11][13][15][17][19]. Group 1: Research Contributions - The paper titled "Decoding 4-vinylanisole biosynthesis and pivotal enzymes in locusts" was co-authored by Academician Kang Le from the Chinese Academy of Sciences and Professor Lei Xiaoguang from Peking University [2]. - Professor Sun Xueliang from Western University and Ningbo Oriental Institute of Technology published a paper on "A cost-effective all-in-one halide material for all-solid-state batteries" [4]. - The research "Efficient near-infrared harvesting in perovskite–organic tandem solar cells" was co-authored by Professor Hou Yi from National University of Singapore and Professor Du Xiaoyan from Shandong University [7]. - The study "Rescuing dendritic cell interstitial motility sustains antitumour immunity" was authored by Researcher Zhou Ting from Westlake University [9]. - Professors Chen Peng and Yi Chengqi from Peking University published a paper on "RNA codon expansion via programmable pseudouridine editing and decoding" [11]. - The paper "Controlling diverse robots by inferring Jacobian fields with deep networks" was authored by Sizhe Li from MIT [13]. - The research titled "In-line NMR guided orthogonal transformation of real-life plastics" was co-authored by Professor Martin from Peking University and Researcher Xu Shutao from the Dalian Institute of Chemical Physics [15]. - The study "Mechanism of cytarabine-induced neurotoxicity" was co-authored by Dr. Liu Jiacheng from the National Cancer Institute and Researcher Wang Dongpeng from the Institute of Biophysics, Chinese Academy of Sciences [17]. - Professor Duan Xiangfeng from UCLA published a paper on "A cation-exchange approach to tunable magnetic intercalation superlattices" [19]. Group 2: Structural and Functional Studies - The research "Structural and functional characterization of human sweet taste receptor" was co-authored by Researcher Hua Tian and Professor Liu Zhijie from ShanghaiTech University [20]. - The paper "Modular arene functionalization by differential 1,2-diborylation" was co-authored by Professor Dong Guangbin from the University of Chicago and Professor Liu Peng from the University of Pittsburgh [22]. - The study "Gating and noelin clustering of native Ca2+-permeable AMPA receptors" was authored by Chengli Fang from Oregon Health & Science University [24].

Core Viewpoint - The OTC2025 forum focuses on the advanced applications of organoids and 3D cell culture, discussing topics such as disease modeling, drug screening, AI-driven organ-on-chip technologies, and quality control in organoid cultivation [1][4]. Group 1: Forum Overview - The forum will take place on July 24-25 in Shanghai, featuring over 50 speakers and more than 800 attendees [1]. - Organized by Shanghai Aoshun Pharmaceutical, Shanghai Bai'ao Tai Pharmaceutical Technology, and Yao Jingtong Bio, with support from various academic and medical institutions [1]. Group 2: Agenda Highlights - The main sessions include discussions on tumor organoid drug sensitivity testing, bone organoids, and AI applications in drug screening [4][5]. - Specific topics include retinal organoid technology, high-throughput analysis of tumor organoids, and the application of organoids in disease modeling and drug screening [5][6][7]. Group 3: Key Participants - Notable speakers include experts from prestigious institutions such as Peking University, Macau University, and various research institutes [5][6][7]. - The forum will also feature discussions on the integration of AI in analyzing large-scale organoid data for personalized drug screening [52]. Group 4: Industry Trends - The forum emphasizes the importance of developing automated cultivation systems to enhance organoid production efficiency and reduce costs [54]. - There is a focus on combining 3D bioprinting and microfluidic technologies to improve the complexity and functionality of organoids [54].

Core Viewpoint - The article discusses the introduction of AlphaGenome, a new AI tool by DeepMind that predicts the effects of single nucleotide mutations in human DNA sequences, enhancing the understanding of gene regulation and disease biology [2][3]. Group 1: AlphaGenome Overview - AlphaGenome is a DNA sequence model that can process up to 1 million base pairs and predict various molecular characteristics related to gene regulation [2][9]. - The model builds on previous DeepMind models like Enformer and complements AlphaMissense, focusing on the 98% of the genome that is non-coding and crucial for gene regulation [10][12]. Group 2: Unique Features of AlphaGenome - AlphaGenome offers high-resolution predictions in the context of long DNA sequences, allowing for detailed biological insights without compromising on sequence length or resolution [12]. - It provides comprehensive multi-modal predictions, enabling scientists to gain a deeper understanding of complex gene regulation processes [13]. - The model can efficiently score mutations, assessing their impact on various molecular characteristics in just one second [14]. - AlphaGenome can directly model splicing sites, which is significant for understanding rare genetic diseases [15]. - It achieves state-of-the-art performance across various genomic prediction benchmarks, outperforming or matching existing models in multiple evaluations [16][18]. Group 3: Applications and Research Directions - AlphaGenome can aid in disease understanding by accurately predicting the effects of gene disruptions, potentially identifying new therapeutic targets [23]. - Its predictions can guide the design of synthetic DNA with specific regulatory functions [24]. - The model accelerates basic research by helping to map key functional elements of the genome [25]. - DeepMind researchers have utilized AlphaGenome to explore mechanisms related to cancer mutations, demonstrating its capability to link non-coding mutations to disease genes [26][27]. Group 4: Limitations and Future Directions - Despite its advancements, AlphaGenome faces challenges in capturing the effects of regulatory elements that are far apart in the genome [32]. - The model has not been specifically designed or validated for individual genome predictions, limiting its application in complex traits or diseases influenced by broader biological processes [32]. - DeepMind is continuously improving the model and collecting feedback to address these limitations [32]. - Currently, the API is open for non-commercial use, focusing on scientific research rather than direct clinical applications [32].

Core Viewpoint - The study highlights the critical role of dendritic cell (DC) interstitial motility in sustaining anti-tumor immunity, revealing that impaired migration in a disordered tumor microenvironment (TME) promotes tumor immune evasion, while enhancing this motility offers promising directions for dendritic cell-centered immunotherapy [5][15]. Group 1: Research Findings - The research published by the team from Westlake University indicates a gradual decline in migratory conventional dendritic cells (mig-cDC) in tumor-draining lymph nodes (tdLN) during tumor progression, which hampers the initial activation of tumor-specific T cells and their subsequent delivery to the TME, leading to immune evasion [4][11]. - A genome-wide CRISPR screening identified phosphodiesterase 5 (PDE5) and its substrate cGMP as key regulators of dendritic cell migration, with late-stage tumors disrupting cGMP synthesis in dendritic cells, thereby reducing their migratory capacity [4][12]. - The use of the PDE5 inhibitor sildenafil was shown to restore cGMP levels and enhance the migration of mig-cDC to tdLN, thereby maintaining anti-tumor immunity [12][14]. Group 2: Mechanisms and Implications - The study elucidates the NOS2-NO-sGC-PDE5 signaling axis, which maintains cGMP levels and determines dendritic cell migration ability, emphasizing the importance of this pathway in anti-tumor immunity [13]. - Sildenafil, commonly known for treating erectile dysfunction, has been observed to have anti-tumor effects, which this research provides an immunological mechanism for, suggesting its potential in enhancing dendritic cell function in cancer therapy [14][15]. - The findings suggest that enhancing the interstitial motility of dendritic cells could be a promising strategy for developing dendritic cell-based immunotherapies, addressing the challenges posed by the TME [5][15].

Core Viewpoint - The research reveals the mechanism of how certain sea slugs, specifically Sacoglossan, integrate chloroplasts from algae into their cells, allowing them to perform photosynthesis, a process previously thought to be exclusive to plants [5][11]. Group 1 - The study published in the journal Cell discusses the integration of stolen chloroplasts in sea slugs for animal photosynthesis [5]. - Sacoglossan sea slugs can selectively retain chloroplasts from ingested algae, maintaining their photosynthetic capabilities for up to a year [7]. - The newly discovered organelle, named "kleptosome," encapsulates the chloroplasts, providing an environment conducive to photosynthesis [8]. Group 2 - The kleptosome utilizes ATP-sensitive ion channels to create an internal environment that supports chloroplast longevity and function [10]. - When the sea slugs are deprived of food, they change color from green to orange, indicating the digestion of stored chloroplasts for nutrients [10]. - The findings highlight the evolutionary adaptability of animal cells under pressure, showcasing convergent evolution in other photosynthetic animals like corals and sea anemones [11]. Group 3 - The research emphasizes the long-term acquisition and evolutionary integration of symbiotic organelles into complex cellular structures [13]. - The initial interest in the study stemmed from a misconception about sea slugs consuming corals, leading to the discovery of their unique photosynthetic abilities [13].

Core Viewpoint - The study reveals the metabolic heterogeneity of sarcopenia and identifies N-methylglycine as a potential risk factor for sarcopenia, suggesting its supplementation could be a new strategy for intervention [3][6][8]. Group 1: Research Findings - The research team conducted a comprehensive plasma metabolomics and lipidomics analysis on two cohorts comprising 1,013 individuals, highlighting a significant decrease in plasma N-methylglycine levels in elderly and sarcopenic patients [6][8]. - In mouse experiments, exogenous supplementation of N-methylglycine was shown to promote anti-inflammatory macrophage polarization, effectively reducing fat accumulation during aging while maintaining skeletal muscle quality at a higher level [3][6]. - The study demonstrated that N-methylglycine activates the GCN2 signaling pathway, enhancing anti-inflammatory macrophage polarization, promoting thermogenesis in adipose tissue, and facilitating muscle regeneration [6][8]. Group 2: Clinical Implications - The research provides scientific evidence for the potential clinical translation of N-methylglycine supplementation as a strategy to prevent sarcopenia in the elderly [3][8]. - The findings suggest that N-methylglycine supplementation can significantly increase fat thermogenesis, reduce white fat, and enhance lean body mass, emphasizing its role in muscle damage repair [8].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 通过筛查进行早期检测，对于降低 胃癌 （GC） 死亡率至关重要。然而，在大多数高发地区，由于资源有限、依从性低以及上消化道内镜筛查的检出率欠佳，大 规模筛查仍面临挑战。因此，迫切需要更高效的胃癌筛查方案。 2025 年 6 月 24 日 ，阿里达摩院 张灵 及浙江省肿瘤医院 程向东 、 徐志远 、 石磊 、 温州市平阳县人民医院 苏缪广 、 宁波市奉化区人民医院 裘邯军 等人在 国际顶尖医学期刊 Nature Medicine 上发表了题为： AI-based large-scale screening of gastric cancer from noncontrast CT imaging 的研究论文。 该研究开发了基于 AI 的大规模胃癌筛查模型—— " GRAPE "，其利用平扫 CT 图像和 AI 实现 大规模、高效的胃癌筛查。该研究显示， GRAPE 显著优于专业放 射科医生，敏感性提高了 21.8%，特异性提高了 14.0%，尤其是在早期胃癌方面。 更重要的是，真实世界评估显示， 在两家地区医院中， GRAPE 识别出高危人群的胃癌检出率分别为 24.5% ...

Core Viewpoint - The article discusses the molecular mechanisms underlying the health benefits of exercise and introduces betaine as a potential exercise mimetic for geroprotection, providing a new strategy for anti-aging interventions [1][3][22]. Group 1: Research Findings - The research team conducted a six-year study that systematically analyzed the molecular and cellular responses of the human body to acute and long-term exercise, identifying the kidneys as a key organ responding to exercise effects [2][11]. - Betaine was found to be a core molecular messenger for delaying aging, targeting and inhibiting the natural immune hub kinase TBK1, which helps to alleviate inflammation and slow down the aging process in multiple organs [2][15]. - The study established a multi-modal data coupling analysis framework, breaking down the complex biological responses to exercise into a quantifiable dynamic network [9][20]. Group 2: Mechanisms of Exercise-Induced Anti-Aging - The research revealed distinct effects of acute versus long-term exercise, with acute exercise triggering a "survival stress-type" metabolic storm, while long-term exercise promotes a health-oriented metabolic-immune homeostasis [11][12]. - Long-term exercise was shown to rejuvenate T lymphocytes by enhancing genomic and epigenetic stability, activating NRF2 pathways to suppress inflammatory factors, and promoting T cell survival and proliferation [12][14]. - The study demonstrated that long-term exercise significantly increases kidney betaine levels, with choline dehydrogenase (CHDH) identified as a key regulatory enzyme in this process [13][14]. Group 3: Implications of Betaine as an Exercise Mimetic - Betaine was shown to effectively simulate the benefits of long-term exercise, improving various aging-related cellular phenotypes in human diploid cells and extending healthy lifespan in aged mice [14][22]. - The study confirmed that betaine specifically binds to and inhibits TBK1 kinase activity, blocking downstream inflammatory signaling pathways, thus reducing immune cell infiltration and inflammatory factor release [15][20]. - The findings suggest that betaine could serve as a potential anti-aging alternative for elderly populations who cannot tolerate high-intensity exercise, marking a new paradigm in the development of exercise-mimicking drugs [20][22].

Core Viewpoint - The research on the human sweet taste receptor reveals its unique asymmetric dimer structure and ligand recognition mechanism, providing a molecular basis for the design of new artificial sweeteners and drug development strategies targeting sweet receptors [4][9]. Group 1: Research Findings - The study published in Nature characterizes the high-resolution three-dimensional structure of the human sweet taste receptor in both apo and sucralose-bound states [4][6]. - The research team identified that sucralose binds specifically to the Venus flytrap domain of TAS1R2, highlighting the receptor's asymmetric dimer structure [7][9]. - The study utilized mutagenesis and molecular dynamics simulations to depict the recognition pattern of sweeteners within TAS1R2, revealing conformational changes and unique activation mechanisms upon ligand binding [7][9]. Group 2: Research Team and Contributions - The research was conducted by a team from ShanghaiTech University, with key contributors including researchers Huatian and Zhijie Liu, along with several doctoral and postdoctoral researchers [9]. - This study marks another breakthrough in the field of chemical sensing molecular mechanisms, following previous reports on bitter taste receptors [9].