Core Viewpoint - The article discusses a groundbreaking study that introduces an AI-based microfluidic sperm detection and recovery system, named STAR, which successfully enabled clinical pregnancy in a male diagnosed with azoospermia, marking a significant advancement in the treatment of male infertility [3][4][8]. Group 1: Technology and Methodology - The STAR system utilizes high-power imaging technology to scan semen samples from azoospermic males, capable of capturing and analyzing millions of images in under an hour [4]. - The system combines high-speed imaging, microfluidic chips, and deep learning algorithms, processing semen at a flow rate of 400μL per hour and capturing images at 300 frames per second [4]. - A time-consistency filter enhances reliability by confirming sperm detection only if at least three out of ten consecutive frames identify sperm [4]. Group 2: Clinical Application and Results - The STAR system was applied to a couple who had been trying to conceive for nearly 20 years, with the male having undergone multiple sperm retrieval attempts with no success [7]. - Initial manual searches of the male's semen sample showed no sperm, but the STAR system identified 7 sperm (2 active) from 2.5 million images scanned [8]. - The two active sperm were successfully injected into two mature eggs, resulting in a positive pregnancy after 19 years of attempts, demonstrating the potential of AI-guided microfluidic technology in overcoming long-standing barriers in male infertility [8]. Group 3: Implications and Future Research - This breakthrough signifies a potential shift from "no hope" to "hope for parenthood" for many couples facing male infertility challenges [8]. - The research team is planning larger clinical studies to evaluate the reproducibility and effectiveness of the STAR system across a broader patient population [8].

Core Viewpoint - The research highlights the development of a genetically engineered optoenergetic rhodopsin (mt-EcGAPR) that utilizes ambient light to power mitochondria, potentially alleviating retinal neurodegeneration, particularly in glaucoma [3][10]. Group 1: Mitochondrial Function and Disease - Mitochondria are essential for energy production, ion homeostasis, and cell survival, with their proton motive force playing a critical role in ATP synthesis and calcium balance [2]. - Dysregulation of mitochondrial proton motive force is linked to various pathological conditions, including neurodegenerative diseases, metabolic disorders, and aging [2]. Group 2: Research Development - The study introduces mt-EcGAPR, a mitochondrial-targeted proton pump that can harness environmental light to generate energy for mitochondria, thereby mitigating retinal neurodegeneration [3][8]. - The research demonstrates that mt-EcGAPR significantly increases ATP production and reduces reactive oxygen species (ROS) accumulation in a mouse model of glaucoma [8]. Group 3: Mechanism and Implications - Mechanistically, mt-EcGAPR protects retinal ganglion cells by inhibiting endoplasmic reticulum stress-mediated cell death pathways, ultimately improving vision in glaucoma models [8][10]. - This study positions mt-EcGAPR as a promising therapeutic strategy for glaucoma and potentially other neurodegenerative diseases associated with mitochondrial dysfunction [10].

Core Viewpoint - The article discusses the significant breakthrough in spinal cord injury (SCI) treatment through the discovery of Thiorphan, a drug that promotes neuronal regeneration and functional recovery after SCI, offering new hope for patients suffering from paralysis and disability [2][3][6]. Group 1: Research Findings - A study published in Nature identified Thiorphan as a candidate drug that reprograms neurons to enhance recovery after spinal cord injury [3]. - Thiorphan, originally developed as a neutral endopeptidase inhibitor for treating diarrhea, has shown remarkable potential in promoting nerve regeneration and functional recovery in SCI models [11][19]. - In experiments with adult mice, Thiorphan increased total neurite growth by 80% and the longest neurite length by 30%, demonstrating a dose-dependent effect [12]. Group 2: Experimental Validation - In a rat model of severe cervical spinal cord injury, treatment with Thiorphan initiated two weeks post-injury resulted in a twofold increase in forelimb grasp success rate, improving accuracy from 30% to 60% when combined with neural stem cell transplantation [14]. - Anatomical evidence indicated that Thiorphan treatment led to a 60% increase in the regeneration of corticospinal axons, establishing synaptic connections across the injury site [15]. - Thiorphan was also effective in promoting growth in cortical neurons from both adult macaques and a 56-year-old human, with increases of 30.3% in total neurite growth and 23% in the longest neurite length [16]. Group 3: Mechanism of Action - The mechanism of Thiorphan involves upregulating brain-derived neurotrophic factor (BDNF) and phosphorylated AKT, allowing neurons to revert to a developmental state and regain growth capabilities [17]. - Given that Thiorphan has been safely used in humans, the clinical development risk is significantly reduced [19]. Group 4: Future Directions - The research team is exploring more convenient administration methods, including intrathecal injection or systemic delivery, and developing derivatives with better blood-brain barrier permeability [20]. - This study not only identifies a promising candidate for SCI treatment but also establishes a new paradigm for drug development from computer screening to human validation, which could be applied to other neurological and neurodegenerative diseases [20].

Core Viewpoint - The study identifies TRAP1 as a mitochondrial chaperone that is suppressed by cancer, leading to immune evasion, and suggests that restoring TRAP1 can reprogram tumor-associated macrophages (TAM) to enhance anti-tumor immunity, positioning the TRAP1 pathway as a promising new target for cancer immunotherapy [2][9]. Group 1 - TRAP1 is a mitochondrial HSP90 molecular chaperone that acts as a metabolic checkpoint, inhibiting oxidative respiration and limiting the suppressive function of macrophages [5]. - In the tumor microenvironment, TRAP1 expression is downregulated through the TIM4-AMPK signaling pathway, and its absence enhances immune suppressive activity while promoting tumor immune evasion [6]. - Inhibition of TRAP1 increases electron transport chain activity and raises the ratio of α-ketoglutarate to succinate, reshaping mitochondrial homeostasis and leading to enhanced immune suppression through JMJD3-mediated histone demethylation [6]. Group 2 - Targeting TIM4 and JMJD3 to restore TRAP1 can reprogram TAM, disrupt the immune evasion of the tumor microenvironment, and enhance anti-tumor immunity [7]. - The findings establish TRAP1 as a key regulatory factor integrating metabolic and epigenetic control of suppressive TAM functions, highlighting the TRAP1 pathway as a promising new target for cancer immunotherapy [9].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 霸王龙 （ Tyrannosaurus rex ） 是研究最为透彻的已灭绝脊椎动物之一，也是恐龙古生物学的典范研究对象。作为最后幸存的非鸟类恐龙之一，霸王龙是评估白 垩纪末期大灭绝 （ 地球生物史上最大的灾难之一，因小行星撞击导致包括恐龙在内的大量物种灭绝 ） 前夕陆地生物多样性、生态系统结构和生物地理交流的关 键数据。 对霸王龙的古生物学研究，包括其个体发育中的生态位分化、摄食、运动生物力学以及生命史等方面，都依赖于不断扩大的骨骼样本，其中包含多个假定的生长 阶段——然而霸王龙的典型标本群仍存在争议。 一个关键的悬而未决的问题涉及被认为代表 幼年霸王龙 的标本，有人认为这些标本属于一个不同的分类单元—— 矮暴龙 （ Nanotyrannus ） 。 2025 年 10 月 30 日， 北卡罗莱纳州立大学/北卡罗来纳自然科学博物馆的研究人员在国际顶尖学术期刊 Nature 上发表了题为 ： Nanotyrannus and Tyrannosaurus coexisted at the close of the Cretaceous 的研究论文。 该研究表明，之前被认为是 ...

编辑丨王多鱼 排版丨水成文 口服给药因无创、易操作、患者接受度高的特性，是临床及日常健康管理中应用最广泛的给药方式，尤其 在需长期用药或不便开展专业医疗操作的场景中，更是保障治疗连续性的关键。 在急性医疗场景中，传统口服给药依赖患者自主吞咽能力，而注射等侵入性方式需专业操作，两者均难以 满足突发状况下的时效性与安全性需求。 野外人员、认知障碍者等群体，常因药物获取难、无法自主服药 等问题延误救治；精神病患者给药时还可能危及自身与他人安全。虽有无人机递送、生物传感器植入等应 急给药方案，但均不兼容口服制剂，且存在需手术植入、药物储存不安全等弊端。紧急口服给药系统需满 足一键 / 自动激活、 60 秒内完全释药、体内储药等核心需求，现有技术难以兼顾。这些痛点凸显了研发 适配口服制剂的应急响应药物系统的迫切性。 近日， 浙江大学药学院 南科望 研究员 与香港城市大学 于欣格 教授 团队合作 （ 浙江大学化工学院博士 研究生 黄浩 、浙江大学药学院博士后 樊云龙 为论文共同第一作者 ） ，在 Science 子刊 Science Advances 上发表了题为： A gastric retentive robotic ...

Core Viewpoint - The research presents a promising alternative strategy for thrombosis prevention through the development of a nanoscavenger that protects vascular endothelial cells from oxidative stress, addressing the bleeding risks associated with current antiplatelet therapies [5][9]. Group 1: Research Development - A novel reactive oxygen species (ROS) chemotactic nanoscavenger (MDCP) was developed, made from melanin and catalase, to prevent acute thrombosis by protecting endothelial cells [4][7]. - The study demonstrated that pre-injected MDCP can specifically accumulate in damaged blood vessels and effectively clear excess hydrogen peroxide while catalyzing the decomposition of superoxide radicals [7]. Group 2: Mechanism of Action - The MDCP enhances the synthesis of antioxidant metabolites involved in nitric oxide (NO) and glutathione production while reducing the release of inflammatory factors, thereby increasing endothelial cell resistance to ROS-induced apoptosis [7]. - This mechanism helps maintain endothelial integrity, preventing collagen exposure and subsequent platelet activation and thrombosis, with minimal impact on platelet function [9].

Core Insights - The article highlights the significance of neurobiology research in enhancing human understanding of brain and nervous system functions, indicating that breakthroughs in this field are expected in the coming decades [2][4]. Group 1: Award Announcement - The Eppendorf & Science Neurobiology Prize for 2025 has been awarded to Dr. Lü Cheng, marking the second time this award has been given to a Chinese scholar since its establishment in 2002 [4][7]. Group 2: Research Contributions - Dr. Lü Cheng's award-winning research focuses on the assembly of brain neural circuits, particularly in fruit flies, and includes a study published in Science that reveals how olfactory circuits simplify synaptic partner matching through a "dimensionality reduction" strategy [9][21]. - The research demonstrates that the olfactory circuit in fruit flies reduces the complexity of synaptic pairing from three-dimensional space to a one-dimensional linear search, providing key evidence for universal principles in neural circuit development [9][21]. Group 3: Methodology and Findings - The research team developed a technique to specifically label different types of neurons, allowing them to track individual neuron changes throughout development, revealing that all neurons initially extend their dendrites to the surface of the antennal lobe [14][15]. - Each type of olfactory receptor neuron (ORN) follows a specific arc-like trajectory on the surface, ensuring that they only search for their correct synaptic partners in a defined area, significantly improving the accuracy and efficiency of synaptic pairing [17][18]. - Genetic manipulation experiments confirmed that altering the ORN axon trajectories led to a significant decrease in pairing accuracy, validating the proposed model [20]. Group 4: Broader Implications - The findings extend beyond the fruit fly olfactory system, offering insights into the fundamental principles of neural system development and how the brain constructs complex functions [21]. - The "dimensionality reduction" strategy identified in the research may serve as a universal approach in nature for solving complex problems by simplifying decision-making processes, enhancing system robustness and accuracy [22].

Core Insights - The study highlights the role of lipid metabolism dysregulation in promoting chronic microglial activation and neuroinflammation in Alzheimer's disease (AD) [2][6] - MFE-2 is identified as a potential drug target, with the small molecule CKBA showing promise in restoring MFE-2 expression and treating AD [6] Group 1: Research Findings - The expression level of MFE-2, a key enzyme regulating fatty acid β-oxidation, is found to be decreased in microglia from both human AD patients and AD model mice [3] - Specific knockout of MFE-2 in microglia of AD model mice leads to microglial abnormalities, neuroinflammation, and β-amyloid (Aβ) deposition [3] - The absence of MFE-2 promotes lipid accumulation, resulting in excessive arachidonic acid, increased mitochondrial reactive oxygen species (ROS), and production of pro-inflammatory cytokines [3] Group 2: Therapeutic Potential - The natural triterpenoid compound AKBA's derivative CKBA can bind with high affinity to MFE-2, stabilizing its levels and inhibiting excessive microglial activation [3] - CKBA improves neuroinflammation and pathological damage associated with Alzheimer's disease [3][6]

Core Insights - The article discusses the significant impact of physical activity on coronary heart disease (CHD) incidence and mortality, highlighting gender differences in the benefits derived from exercise [2][3][9] Group 1: Research Findings - A recent study published in Nature Cardiovascular Research indicates that women gain greater cardiovascular benefits from exercise compared to men, with a more substantial reduction in CHD risk and overall mortality [3][9] - Among participants without a history of CHD, women who met the recommended 150 minutes of weekly exercise experienced a 22% reduction in CHD risk, while men saw a 17% reduction [6] - For women, exercising 250 minutes weekly led to a 30% reduction in CHD risk, whereas men required 530 minutes to achieve similar benefits [6] Group 2: Mortality Risk Reduction - In participants with existing CHD, women adhering to exercise guidelines had a 70% reduction in all-cause mortality risk, compared to a 19% reduction for men [6][8] - The study emphasizes the importance of tailored exercise recommendations based on gender to improve CHD prevention and management strategies [9] Group 3: Implications for Public Health - The findings underscore the potential of wearable devices in developing gender-specific CHD prevention strategies, which could encourage more women to engage in physical activity and help close the gender gap in exercise participation [9]