Core Insights - The study reveals that glucose metabolism is a critical energy source for tumor proliferation, and targeting glucose metabolism through low-carbohydrate diets is a promising strategy to inhibit tumor growth [2][9] - However, extreme carbohydrate restriction may suppress tumor growth while simultaneously promoting lung metastasis, indicating the need for careful evaluation of metabolic intervention strategies [3][9] Mechanism of Action - Glucose deprivation induces endoplasmic reticulum (ER) stress in tumor cells, activating HRD1 to catalyze the ubiquitination of TRAIL at the K63 site, which is then packaged into exosomes [4] - These exosomes release TRAIL in the lungs, polarizing PVR⁺ macrophages and depleting lung NK cells, thus creating a favorable immune microenvironment for tumor colonization [4] Clinical Implications - The research confirms that low glucose metabolism is associated with higher recurrence rates within two years post-surgery across 15 cancer types [5] - Plasma exosomal TRAIL levels serve as an effective biomarker for predicting lung metastasis after liver cancer surgery, outperforming traditional biomarkers like alpha-fetoprotein (AFP) [6] Key Findings - Low-carbohydrate diets or impaired glucose metabolism can promote lung metastasis [7] - Glucose deprivation creates a pre-metastatic microenvironment dominated by lung macrophages [7] - Exosomal TRAIL leads to the polarization of PVR⁺ macrophages, resulting in the depletion of lung NK cells [7] - Plasma exosomal TRAIL levels can accurately predict early postoperative lung metastasis [7] Research Value - The study systematically elucidates how glucose restriction reshapes distal immune environments and promotes tumor metastasis through an exosome-immune regulatory axis, highlighting the TIGIT pathway as a potential target for combined interventions [9]

Core Viewpoint - The article discusses the advancements in the field of medium-sized rings (MSR) with a focus on non-traditional chiral types, including axial chirality, inherent chirality, and planar chirality, highlighting their synthesis strategies and stability factors [1][5]. Group 1: Overview of Medium-Sized Rings - Medium-sized rings (MSR) consist of 7-11 atoms and exhibit a unique "rigid-flexible" characteristic, making them significant in drug chemistry and functional materials [1]. - The review published by researchers from Zhengzhou University in Nature Reviews Chemistry emphasizes the importance of exploring non-traditional chiral MSRs, which have not been extensively studied compared to traditional central chirality [3][5]. Group 2: Types of Non-Traditional Chirality - Axial Chirality: This type arises from restricted rotation around a non-covalent bond axis, often constructed through dynamic kinetic resolution or asymmetric catalysis [4]. - Inherent Chirality: This chirality originates from the asymmetry of the ring framework itself, typically synthesized via cyclization reactions or template-directed methods [4]. - Planar Chirality: This involves the asymmetric arrangement of substituents within a molecular plane, requiring steric hindrance or ligand control for selective synthesis [4]. Group 3: Progress and Evaluation - The past decade has seen rapid advancements in the synthesis and application of non-traditional chiral MSRs, with significant breakthroughs reported [5]. - The review critically evaluates the key synthesis strategies for these chiral types and discusses the factors influencing the conformational stability of chiral medium-sized rings through structural and energy analysis [5].

Core Viewpoint - The excessive intake of added sugars has become a significant public health issue, particularly among children and adolescents, leading to potential long-term effects on obesity, metabolic disorders, and cognitive functions [2][4]. Group 1: Research Findings - A study published by a team from Beijing Normal University indicates that excessive sucrose consumption during early life alters cortical dynamics and adaptive behavior in adulthood [2][5]. - The research utilized wide-field calcium imaging to monitor the activity of the dorsal cortex in adult mice that had consumed high-sugar beverages since weaning, comparing them to a control group [4]. - Findings revealed that mice consuming high-sugar beverages exhibited changes in cortical dynamics and behavioral flexibility, despite no abnormalities in weight gain or glucose tolerance [4][7]. Group 2: Specific Observations - Mice exposed to sucrose during early life showed reduced cortical responses to sucrose in adulthood [7]. - These mice displayed delayed and prolonged learning-related cortical activity during early learning stages [7]. - There was a noted decrease in functional connectivity between the anterior and posterior cortices in mice that consumed sucrose early in life, along with heightened sensitivity to cue-reward association changes [7].

Core Viewpoint - The article discusses a groundbreaking experimental treatment for a rare genetic condition caused by HPDL gene mutations, which leads to a deficiency in Coenzyme Q10, crucial for mitochondrial function. The treatment involves a precursor molecule, 4-HB, showing significant improvement in a young patient’s condition. Group 1: Patient Case and Treatment - An 8-year-old boy experienced rapid deterioration of health due to HPDL gene mutation, leading to severe mobility issues within months [1][2] - The boy underwent experimental treatment with 4-HB, a precursor to CoQ10, under FDA's special permission, resulting in remarkable recovery [3][4] - After less than a month of treatment, the boy could walk 1 kilometer and eventually engage in activities like running and cycling [4][11] Group 2: Research Background and Findings - The research team, led by Professor Michael Pacold, published findings in Nature, revealing the role of HPDL in converting 4-HMA to 4-HB, essential for CoQ10 synthesis [5][7] - The study demonstrated that primary CoQ10 deficiency-related neurological symptoms could be stabilized or improved by supplementing with precursor substances rather than CoQ10 itself [13] Group 3: Market Potential - The decline of CoQ10 levels is associated with aging and various diseases such as heart disease, diabetes, and Alzheimer's, indicating a potential multi-billion dollar market for restoring CoQ10 levels [14]

Core Viewpoint - The article discusses the challenges and advancements in assessing Variants of Uncertain Significance (VUS) in the ATM gene, which is crucial for DNA damage response and cancer susceptibility [2][5][6]. Group 1: ATM Gene and Its Importance - The ATM gene plays a key role in DNA damage response and is associated with Ataxia Telangiectasia when mutated [2][5]. - Mutations in the ATM gene can lead to increased risks of various cancers, including breast, colorectal, pancreatic, and prostate cancers [5]. - Comprehensive functional assessment of all possible single nucleotide variants (SNVs) in the ATM gene is essential for predicting cancer risk and patient prognosis [5][10]. Group 2: Recent Research Findings - Researchers from Yonsei University published a study in Cell that functionally assessed all 27,513 possible ATM SNVs using prime editing and deep learning [3][10]. - The study identified critical amino acid residues in the kinase domain that cannot tolerate missense mutations [10]. - A deep learning model named DeepATM was developed to predict the functional effects of the remaining 4,421 SNVs with unprecedented accuracy [9][10]. Group 3: Implications for Precision Medicine - The comprehensive evaluation of ATM gene mutations aids in precision medicine and provides a framework for addressing VUS in other genes [12]. - The research findings contribute to cancer risk assessment and prognosis, enhancing the understanding of ATM's role in cancer [9][10].

编辑丨王多鱼 排版丨水成文 有 结核分枝杆菌 （ Mycobacterium tuberculosis ） 感染史的患者，往往会出现不可逆且进行性的 肺损 伤 ，但其潜在机制尚不完全清楚。 2025 年 7 月 14 日，中国科学院动物研究所 刘光慧 研究员联合天津大学海河医院 陈怀永 教授、首都医 科大学宣武医院 王思 教授及中国科学院动物研究所 曲静 研究员团队，在 Nature Microbiology 期刊 发表了 题为： A single-cell transcriptomic atlas reveals senescence and inflammation in the post-tuberculosis human lung 的研究论文。 该研究构建了首个 结核杆菌 感染后肺组织的高精度细胞分子网络，并运用多维度分析策略系统阐明： 细胞 衰老与炎症是结核感染后肺损伤的关键病理特征，而内皮细胞衰老及血管炎症则是这一过程中的核心事件 。并进一步首次阐明了 FOXO3 表达下调协同凝血酶-炎症信号通路驱动结核杆菌感染导致的慢性肺损伤的 分子机制，为该疾病提供了潜在干预靶点。 在这项最新研究中，研究团 ...

Core Viewpoint - The article discusses the discovery of an alternative receptor for adeno-associated viruses (AAV), named AAVR2, which enhances the efficacy of AAV-mediated gene therapy and provides insights into reducing dose-related toxicity associated with AAV vectors [3][8]. Group 1: AAV and Its Applications - AAV is currently the most commonly used vector for in vivo gene therapy, approved for treating various diseases such as retinitis pigmentosa, spinal muscular atrophy, Duchenne muscular dystrophy, and hemophilia [1]. - The clinical success of human gene therapies relies on the safe and effective transduction of AAV into various tissues [2]. Group 2: Research Findings - AAVR2 (CPD) was identified as an alternative receptor that can restore the transduction of E branch AAVs, including AAV8, in the absence of AAVR, and provides a unique entry pathway for unclassified AAV11 and AAV12 [3][6]. - The research team characterized the direct binding between AAV8 capsid and AAVR2 using cryo-electron microscopy, identifying the amino acid residues involved in the interaction [6][9]. - A minimal functional AAVR2 (miniAAVR2) was overexpressed to enhance in vivo AAV transduction, allowing low doses of AAV to achieve similar therapeutic effects [6][9]. Group 3: Implications for AAV Biology - This research provides new insights into AAV biology and offers clinically applicable solutions to mitigate dose-related toxicity associated with AAV vectors [8].

Core Viewpoint - The research conducted by Professor Liu Jin's team at Sun Yat-sen University presents a novel scheme for cavity-induced spontaneous two-photon emission (STPE), achieving a high fidelity of 99.4% for on-demand triggered quantum entangled light sources, which is expected to revolutionize photon quantum science and technology [2][3]. Group 1 - The study reports a STPE phenomenon with brightness comparable to competitive single-photon radiation, originating from a single semiconductor quantum dot coupled to a high-quality microcavity [3]. - The research team utilized photon statistical measurements to reveal quantum characteristics associated with STPE within a cavity quantum electrodynamics system [3]. - The development of a new type of entangled quantum light source using STPE demonstrates nearly perfect entanglement fidelity (99.4%) and the on-demand photon emission characteristics required for atomic quantum radiation sources [3]. Group 2 - This breakthrough provides critical support for the advancement of next-generation quantum precision measurement technologies and the construction of functional photonic quantum information processing chips [3]. - The findings deepen the understanding of two-photon processes in quantum systems and are expected to empower the development of photon quantum technologies through nonlinear quantum radiation [3].

编译丨王聪 编辑丨王多鱼 排版丨水成文 体细胞干细胞，通常被称为 成体干细胞 ，通过稳态更新维持组织，并通过再生反应修复组织。因此，这些干细胞群体必须进化出维持自身活力的机制，以适应其 维持的组织在不同生物体中的不同寿命。然而，随着不同寿命的生物体的衰老，这些干细胞功能的衰退在组织稳态受损以及对损伤或疾病的再生能力下降方面表 现得十分明显。 近日，加州大学洛杉矶分校、斯坦福大学和贝勒医学院的研究人员在 Cell 子刊 Cell Stem Cell 上发表了题为： Hallmarks of stem cell aging 的综述论文。 该综述系统性描述了可用来表征干细胞衰老的五个关键标志—— 1） 静息深度 （ depth of quiescence ） ，2） 自我更新倾向 （ self- renewal propensity ） ，3） 子代细胞命运 （ fate of progeny ） ，4） 再生修复能力 （ resilience ） ，5） 群体异质性 （ population heterogeneity ） 。 并进一步探讨了这些标志的变化如何导致干细胞功能的衰退。这些特征不仅为衰老过程提供了见解 ...

Core Viewpoint - The article discusses the challenges and advancements in the preclinical evaluation of drugs targeting Th2-type immune response diseases, specifically atopic dermatitis and asthma, highlighting the need for improved animal models and evaluation systems [1][2]. Group 1: Disease Mechanisms and Challenges - Atopic dermatitis and asthma are chronic inflammatory diseases driven by abnormal Th2 immune responses, involving pathways such as IL-4, IL-13, and IL-5, as well as epidermal barrier dysfunction and neuroimmune dysregulation [1]. - Despite the clinical application of targeted biologics improving patient outcomes, issues such as individual response variability, acquired resistance, and long-term safety remain unresolved [1]. Group 2: Preclinical Research Dilemmas - Key questions in preclinical research include how to establish more accurate animal models that simulate skin barrier defects in atopic dermatitis and airway hyperreactivity in asthma [1]. - There is a need to optimize the drug efficacy evaluation system for Th2 immune responses to enhance clinical translation rates [1]. - New technologies are required to overcome existing model limitations in simulating neuroimmune interactions [1]. - Personalized preclinical evaluation plans must be designed for candidate drugs with different mechanisms of action [1]. Group 3: Online Course Information - An online course titled "Preclinical Drug Evaluation Models for Th2 Immune Response Diseases: Aiding New Drug Development for Atopic Dermatitis and Asthma" will delve into these topics [2]. - Participants will learn about the latest research advancements in Th2 immune diseases, methods for constructing clinically relevant animal models, and key challenges in developing innovative mouse models [2]. - The course will also cover technical solutions and case studies related to autoimmune disease efficacy platforms, along with an interactive Q&A session with the lecturer [2]. Group 4: Instructor Background - Dr. Yu Jing, a senior scientist in the pharmacodynamics research department at Saiye Bio, specializes in the development of animal models for immune reconstruction, tumor models, metabolic diseases, and autoimmune diseases, with extensive experience in efficacy validation [7]. Group 5: Efficacy Evaluation Platform - Saiye Bio offers a stable efficacy evaluation platform for autoimmune and inflammatory diseases, providing comprehensive pharmacodynamic evaluation and mechanism research services [12]. - The platform includes various models such as induced models, gene editing, and humanized models, focusing on physiological and biochemical indicators, pathological analysis, and immune cell function assessment [9][12].