Core Viewpoint - The article discusses the significant public health challenge posed by age-related hearing loss, emphasizing the need for deeper understanding of the molecular mechanisms involved in cochlear aging, particularly in primates, to develop targeted treatment strategies [1][2]. Group 1: Research Findings - A collaborative research team published a study in Nature Aging, identifying SLC35F1 deficiency as a key molecular marker and driver of cochlear aging in primates [2][7]. - The study successfully mapped the cellular and molecular characteristics of cochlear aging, revealing critical pathological changes such as hair cell loss and accelerated aging of spiral neurons [4][7]. - The research utilized innovative techniques to dissect primate cochlear tissue and employed single-cell sequencing combined with deep learning to create a high-resolution molecular map of cochlear aging [4][6]. Group 2: Mechanism and Treatment - The study demonstrated that silencing SLC35F1 in hair cells leads to significant cell apoptosis, indicating its crucial role in maintaining hair cell homeostasis [6]. - Long-term administration of metformin showed a rejuvenating effect on aged cochlear tissue in primates, reducing hair cell loss and vascular degeneration, while also decreasing the proportion of aging neurons [6][7]. - Metformin was found to exert protective effects through dual mechanisms: downregulating inflammation-related genes and upregulating key functional genes related to sound perception and neural signaling [6][7]. Group 3: Implications for Future Research - The findings provide a comprehensive understanding of the aging process in primate cochlea, highlighting specific susceptible cell types and their aging drivers, which could lead to innovative targeted therapies for age-related hearing loss [7][8]. - The research lays a solid theoretical foundation for developing clinical intervention strategies aimed at preventing and treating age-related hearing loss [7].

Core Viewpoint - The research team led by Qiaomei Fu has successfully linked a nearly complete Middle Pleistocene human skull fossil from Harbin, China, to the extinct Denisovans, providing the first clear depiction of their appearance and ending 15 years of speculation about their looks [4][26]. Group 1: Research Findings - The skull fossil, dated to be at least 146,000 years old, was found to contain ancient proteins and DNA, confirming its association with Denisovans [4][26]. - The study published in Science and Cell journals represents a significant advancement in understanding the morphology and geographical distribution of Denisovans in Asia during the Middle Pleistocene [26][29]. - The research utilized a novel method to extract host DNA from dental calculus, marking the first successful extraction of such DNA from Pleistocene dental plaque [25][29]. Group 2: Historical Context - The skull was discovered in 1933 by a construction worker in Harbin, who kept it hidden until his death, leading to its eventual donation to Hebei University of Geosciences in 2018 [20][21]. - In 2021, the skull was initially proposed to represent a new human lineage named "Dragon Man" (Homo longi), but subsequent studies indicated its potential classification as a Denisovan [22][24]. - The research team compared ancient protein sequences from the skull with those of Neanderthals, modern humans, and Denisovans, confirming its affiliation with Denisovans [24][26].

Core Viewpoint - The article discusses the development and potential of in vivo CAR-T cell therapy, particularly focusing on Capstan Therapeutics and its innovative approach to treating cancer and autoimmune diseases through a new mRNA delivery system [2][3][19]. Group 1: In Vivo CAR-T Technology - In vivo CAR-T technology allows for the generation of CAR-T cells directly within the body through the injection of lipid nanoparticles (LNP) delivering mRNA, addressing challenges such as complexity, time, and cost associated with traditional CAR-T therapies [2][3]. - Capstan Therapeutics, founded by leading researchers in the field, has secured $340 million in funding to advance this technology for various diseases [2][3]. Group 2: Clinical Trials and Research Findings - Capstan's CAR-T therapy CPTX2309 has commenced Phase 1 clinical trials for treating B cell-mediated autoimmune diseases [3]. - Preclinical studies demonstrated that the proprietary targeted lipid nanoparticles (tLNP) effectively delivered CAR mRNA to CD8+ T cells, showing promising therapeutic prospects and safety in animal models [3][4]. Group 3: Market Potential and Patient Demographics - The patient population for autoimmune diseases is significantly larger than that for B cell malignancies, with approximately 20 million individuals in the U.S. and 10% of the global population affected [6]. - There is a pressing need for scalable, off-the-shelf therapies that do not require chemotherapy preconditioning and can be administered in non-specialized medical centers [6]. Group 4: Mechanism and Efficacy - The research team developed a novel ionizable lipid L828 and optimized the LNP formulation to enhance targeting and accumulation in the liver while minimizing off-target effects [7]. - The CD8-L829-tLNP demonstrated a preference for modifying CD8+ T cells over CD4+ T cells, leading to effective targeting and destruction of B cells in both humanized mouse models and non-human primate models [9][10]. Group 5: Safety and Tolerability - In non-human primate studies, the treatment showed good tolerability, although some adverse effects were noted, such as a known side effect of CAR-T therapy [16]. - The study indicated that the treatment led to a temporary depletion of B cells, suggesting a reset of the immune system, which is crucial for long-term therapeutic benefits [16][19].

Core Viewpoint - OriCell, a subsidiary of Saiye, focuses on cell biology, particularly in the development and optimization of cell culture media and stem cell technology services, aiming to enhance cell cultivation practices [1][18]. Group 1: iPSC Research and Challenges - Induced pluripotent stem cells (iPSCs) hold immense potential for disease treatment, drug screening, and personalized medicine, but they are sensitive to culture conditions, making their cultivation challenging [3][4]. - The complexity and high cost of culture media, along with variability in iPSC batches, can affect differentiation efficiency, proliferation rates, and genetic stability, impacting experimental reproducibility [3][4]. Group 2: Upcoming Event and Product Launch - Saiye will host a cloud classroom on June 24, 2025, focusing on iPSC cultivation methods and applications, featuring the launch of the new "Saiye OriCell iPSC Complete Culture Medium" [4][6]. - The new iPSC Complete Culture Medium is designed to maintain high cell quality and differentiation potential, even after multiple passages, and is free from serum and animal-derived components [11][7]. Group 3: Comprehensive Service Platform - Saiye has developed a one-stop technical service platform for iPSCs, integrating reprogramming, gene editing, and in vitro differentiation technologies, providing a complete solution from disease model construction to detection [14][13]. - The platform aims to facilitate the transition from basic research to clinical applications, accelerating the development of disease research [14]. Group 4: Product Offerings and Promotions - OriCell has a comprehensive collection of stem cell lines and culture media, with ongoing promotions such as "buy three get one free" for mesenchymal stem cell culture media [16]. - The company emphasizes its commitment to providing high-quality products and services, supported by extensive research and customer feedback [16].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 呼吸 似乎是个简单的过程；我们毫不费力地协调着它，也很少去关注它。然而，呼吸实际上是由一个极其复杂且广泛的大脑网络控制的，该网络充当呼吸节律 器，根据生理稳态需求调节自主呼吸模式，同时允许在行为需求时由意志接管呼吸。 每个人的大脑是独一无二的，那么，每个人依赖大脑的呼吸模式，也可能是独一无二的，这些呼吸模式 或许还能反过来反映大脑活动。 2025 年 6 月 12 日，Cell 子刊 Current Biology 上发表了一年题为： Humans have nasal respiratory fingerprints 的研究论文。 该研究表明，人类拥有" 呼吸指纹 "，即独特的鼻腔呼吸模式，而且可用于预测身体指标以及情绪和认知状态。 控制呼吸的大脑网络的关键组成部分位于脑干的延髓 pre-Bötzinger 复合体中，尽管该复合体有节律的爆发活动能够独立于外部输入驱动吸气，但其活动会不断 受到来自整个呼吸系统化学感受器和机械感受器的信息调节。 这种调节依赖于一个庞大的大脑网络，其中包括额外的延髓机制、脑桥机制以及多个皮质和皮质下 结构，它们都参与了呼吸的自主和非自主控 ...

Core Viewpoint - Climate change is likely to exacerbate the frequency and severity of supply-demand imbalances in high penetration wind and solar power systems in the future [2][4]. Group 1 - The research team utilized a scheduling optimization model to assess the potential hourly cost increases due to climate change under fixed and high penetration rates of wind and solar energy [4]. - During extreme periods, which are defined as the top decile of hourly costs, the study predicts that costs may rise significantly in most countries, primarily due to increased investment needs for flexible energy capacity [4]. - In the SSP126 scenario, it is anticipated that 47 countries will see an average hourly cost increase of over 5% during extreme periods, collectively accounting for approximately 43.5% of future global electricity supply, with the highest increase reaching 23.7% [4]. Group 2 - The research findings provide critical insights for constructing future electricity systems that are both climate-resilient and cost-effective [5].

Core Viewpoint - The article discusses the development of LucaOne, a generalized biological foundation model that can simultaneously understand and process nucleic acids (DNA and RNA) and protein sequences, marking a significant advancement in the field of life sciences [4][26]. Group 1: Introduction to LucaOne - LucaOne is the world's first foundational model capable of unifying the understanding of nucleic acids and protein sequences, likened to a "DeepSeek" for life sciences [4]. - The model was pre-trained on sequences from 169,861 species, showcasing its ability to comprehend key biological principles such as the translation of DNA into proteins [4][16]. Group 2: Technical Aspects of LucaOne - The model utilizes a vocabulary of 39 "characters" to encode nucleotides and amino acids, allowing it to read both nucleic acids and proteins [13]. - It employs semi-supervised learning, integrating known biological annotations to enhance its understanding [14]. - LucaOne has 1.8 billion parameters and has been trained on 36.95 billion biological sequence "words," enabling it to extract deep, universal patterns from nucleic acid and protein sequences [16]. Group 3: Performance and Capabilities - LucaOne demonstrated an impressive ability to understand the central dogma of molecular biology without explicit instruction, outperforming specialized models in tasks involving DNA and protein sequence matching [18]. - The model excels in generating embeddings that accurately capture the biological significance of sequences, outperforming other models in clustering similar sequences [19]. - It has shown strong performance across seven challenging bioinformatics tasks, including species classification and protein stability prediction, often using simpler downstream networks compared to specialized models [20][24]. Group 4: Significance and Future Outlook - LucaOne provides a unified framework for understanding the two core molecular carriers of life, breaking down barriers between different molecular types [26]. - The model exemplifies the potential of foundational models in bioinformatics, allowing researchers to develop various biological computational tools efficiently [26]. - It paves the way for deeper and more automated analysis of complex biological systems, such as gene regulatory networks and disease mechanisms [26].

Core Insights - The article highlights the significant contributions of Chinese scholars in the field of research, particularly in the publication of papers in the prestigious journal Nature, with 9 out of 19 papers authored by Chinese researchers [2][3][5][7][9][11][13][15][17][18]. Group 1: Research Contributions - On June 18, 2025, a paper titled "Strategies for climate-resilient global wind and solar power systems" was published by Tsinghua University professors Zhang Qiang and Song Dan as co-corresponding authors [2]. - A paper titled "Unsupervised pretraining in biological neural networks" was authored by postdoctoral researcher Zhong Lin from the Howard Hughes Medical Institute [3]. - The National University of Singapore's Liu Xiaogang and Xiamen University's Liang Liang published a paper on "Optical nonlinearities in excess of 500 through sublattice reconstruction" [5]. - A study titled "Bimodal centromeres in pentaploid dogroses shed light on their unique meiosis" was published by M. Zhang from the Max Planck Institute for Plant Breeding Research [7]. - A paper titled "Kupffer cell programming by maternal obesity triggers fatty liver disease" was authored by postdoctoral researcher Huang Hao from Bonn University [9]. - A research paper on "Allosteric modulation and biased signaling at free fatty acid receptor 2" was published by Professor Zhang Cheng from the University of Pittsburgh [11]. - A study on "Machine-learning design of ductile FeNiCoAlTa alloys with high strength" was co-authored by professors Ma En, Sun Jun, and Zhang Jinyu from Xi'an Jiaotong University [13]. - A paper titled "Single-cell transcriptomic and chromatin dynamics of the human brain in PTSD" was published by Jing Zhang from the University of California, Irvine [15]. - A study titled "R9AP is a common receptor for EBV infection in epithelial cells and B cells" was co-authored by professors Zeng Muxing and Zhong Qian from Sun Yat-sen University [17]. - A paper on "Cryo-EM structure of a natural RNA nanocage" was published by Fudan University's Ma Jinbiao and collaborators [18].

Core Viewpoint - The article discusses the potential of Fibroblast Growth Factor 21 (FGF21) as a therapeutic agent to improve metabolism and promote longevity, particularly in the context of obesity and aging-related metabolic issues [2][5]. Group 1: FGF21 and Aging - Approximately 35% of adults aged 65 and older in the U.S. are classified as obese, highlighting the need for therapies targeting age-related metabolic issues [2][5]. - FGF21 is primarily produced by the liver and acts as an endocrine hormone, responding to various cellular stressors, showing promise in treating metabolic diseases such as type 2 diabetes and non-alcoholic fatty liver disease [5][6]. Group 2: Research Findings - The study published in Cell Metabolism indicates that FGF21 promotes longevity in diet-induced obese mice through metabolic benefits independent of growth suppression [3][8]. - Overexpression of FGF21 in adult mice led to increased lifespan, improved insulin sensitivity, reduced liver fat degeneration, and lower levels of inflammatory immune cells in visceral fat tissue, even without the presence of adiponectin [6][8]. Group 3: Mechanisms of Action - FGF21 overexpression increases energy expenditure in high-fat diet-fed mice without affecting cold tolerance [8]. - The beneficial effects of FGF21 are primarily mediated through adipose tissue, suggesting its potential in treating metabolic syndrome and age-related diseases by promoting healthier metabolic states under dietary stress [9].

Core Viewpoint - The article discusses a significant advancement in understanding early organogenesis in mouse embryos through the creation of a 3D "digital embryo" using single-cell resolution techniques, which provides insights into organ formation and potential mechanisms of congenital malformations [2][10]. Group 1: Early Organogenesis - Early organogenesis is a critical phase in embryonic development characterized by extensive cell fate determination to initiate organ formation, while also being highly susceptible to developmental defects [4]. - At approximately day 7.5 of embryonic development (E7.5), mouse embryos undergo significant morphological changes, marked by the emergence of key structures such as the heart tube and primitive gut [4]. - The complex process of organ formation relies on precise cell migration, localization, and differentiation, regulated by spatiotemporal gene expression patterns and intricate signaling pathways [4][5]. Group 2: Research Methodology - The research team combined spatial transcriptomics methods (Stereo-seq) with cell segmentation techniques to analyze 285 continuous slices from six embryos at early organogenesis stages (E7.5-E8.0), generating a spatial transcriptomic map at single-cell resolution [6]. - A visualization platform named SEU-3D was developed to reconstruct the 3D "digital embryo," accurately reflecting gene expression patterns and cell states in the native embryonic environment [7]. Group 3: Findings and Implications - The research delineated spatial cell maps of endoderm and mesoderm derivatives, revealing complex signaling networks across germ layers and cell types [8]. - A region known as the progenitor determination zone (PDZ) was identified at the anterior interface of the embryo-extrembryonic region at E7.75, indicating coordinated signaling during heart progenitor formation [8]. - The results collectively establish a comprehensive spatiotemporal embryonic atlas at single-cell resolution, accompanied by a network-based exploration tool for navigating spatial gene expression and signaling networks, paving the way for deeper studies into embryonic development and diseases [10].