Core Viewpoint - The study reveals that HEBP2-mediated glutamine competition between tumor cells and macrophages dictates the efficacy of immunotherapy in triple-negative breast cancer (TNBC), identifying GSTP1 as a new therapeutic target to enhance treatment outcomes [3][4]. Group 1: Research Findings - The research team developed a single-cell RNA sequencing (scRNA-seq) immune therapy cohort (N=27) and a spatial transcriptomics cohort (N=88) to elucidate the metabolic interactions related to TNBC treatment efficacy [5]. - High expression of HEBP2 in tumor cells, characterized by active glutathione metabolism, and CCL3+ macrophages, characterized by oxidative metabolism, indicate effective immunotherapy, showing a negative correlation in quantity and spatial distribution [5]. - HEBP2 disrupts the cytoplasmic phase separation of the transcription factor FOXA1, promoting its nuclear translocation, which upregulates GSTP1 expression and glutamine consumption in tumor cells [5][6]. Group 2: Implications for Treatment - The metabolic shift induced by HEBP2 leads to ferroptosis in CCL3+ macrophages, impairing anti-tumor immunity [5]. - The use of GSTP1 inhibitors (Ezatiostat) can block this pathway, preventing excessive glutamine consumption by tumor cells, thereby protecting macrophages and restoring anti-tumor immunity, making TNBC more sensitive to cancer immunotherapy (anti-PD-1 monoclonal antibodies) [5][7]. - The findings establish a metabolic checkpoint regulated by the HEBP2/GSTP1 signaling axis, pioneering the assessment of immune metabolic weaknesses at the single-cell level [6][7].

Core Viewpoint - The rising global obesity rates are leading to increased risks of diseases such as type 2 diabetes and cardiovascular diseases. GLP-1 class weight loss drugs, particularly Semaglutide, are rapidly gaining popularity and transforming the obesity treatment landscape [2][11]. Group 1: Clinical Study Overview - A clinical study published in the New England Journal of Medicine evaluated the efficacy and safety of oral Semaglutide at a dose of 25 mg for weight management in overweight or obese adults without diabetes over a 71-week period [2][3]. - The study involved 307 participants from 22 centers in Canada, Germany, Poland, and the USA, randomly assigned to receive either oral Semaglutide or a placebo [5]. Group 2: Weight Loss Results - By week 64, participants taking oral Semaglutide experienced an average weight loss of 13.6%, compared to 2.2% in the placebo group, resulting in a difference of 11.4 percentage points [7]. - The proportion of participants achieving weight loss of at least 5% was 79.2% in the Semaglutide group versus 31.1% in the placebo group [7]. Group 3: Cardiovascular and Metabolic Improvements - Oral Semaglutide showed significant advantages in various cardiovascular and metabolic risk factors, including reductions in body weight, waist circumference, and improvements in glycemic control [8]. - Among participants with prediabetes, 71.1% in the Semaglutide group normalized their blood sugar levels by week 64 [8]. Group 4: Safety and Adverse Events - Adverse events were reported in 93.1% of the Semaglutide group compared to 85.3% in the placebo group, with gastrointestinal events being the most common [8]. - The incidence of nausea was 46.6% in the Semaglutide group versus 18.6% in the placebo group, while vomiting rates were 30.9% and 5.9%, respectively [8]. Group 5: Conclusion and Future Implications - The study concluded that a daily oral dose of 25 mg Semaglutide is an effective weight management option for overweight or obese adults and may provide a non-injection alternative for GLP-1 based treatments [11]. - This research lays the groundwork for further formulation testing of this significant weight loss medication, potentially leading to more user-friendly oral tablet forms [11].

Core Viewpoint - The article discusses a newly discovered heat production mechanism in brown fat that does not rely on mitochondrial UCP1, highlighting the role of peroxisomes and a specific protein ACOX2 in energy metabolism and thermogenesis [4][5][8]. Group 1: Research Findings - The study published in Nature reveals that peroxisomes in brown fat can produce heat through the metabolism of branched-chain fatty acids (mmBCFA) via ACOX2, independent of UCP1 [5][8]. - Mice lacking ACOX2 showed reduced cold tolerance, lower body temperature, and impaired insulin sensitivity, indicating the importance of ACOX2 in metabolic regulation [8][9]. - Overexpression of ACOX2 in genetically modified mice led to increased thermogenesis, improved cold tolerance, and better insulin sensitivity, suggesting a potential therapeutic target for obesity and metabolic disorders [5][8]. Group 2: Implications for Human Health - The research suggests that dietary interventions to increase mmBCFA levels could enhance this newly identified thermogenic pathway, potentially aiding in weight loss and metabolic health [9]. - Evidence indicates that individuals with higher mmBCFA levels tend to have lower body mass index (BMI), supporting the relevance of this pathway in human metabolism [9]. - The long-term goal of the research team is to explore methods to elevate mmBCFA levels or activate ACOX2 to stimulate peroxisomal thermogenesis for weight management and metabolic improvement [9].

Core Viewpoint - The recent study from Oxford University indicates that any level of alcohol consumption increases the risk of dementia, challenging the notion that moderate drinking may have neuroprotective effects [4][10]. Group 1: Study Overview - The study published in BMJ Evidence-Based Medicine is the largest comprehensive observational and genetic research to date, showing a direct correlation between alcohol consumption and dementia risk [4][6]. - It utilized data from two major biobanks: the Million Veteran Program (MVP) and the UK Biobank (UKB), covering diverse populations [6]. Group 2: Research Findings - The observational analysis revealed a U-shaped association between alcohol consumption and dementia risk, where non-drinkers and heavy drinkers (40+ drinks per week) had a 41% and 51% higher risk of dementia, respectively, compared to light drinkers (less than 7 drinks per week) [7]. - Genetic analysis showed that higher genetic risk for alcohol consumption correlates with increased dementia risk, with a linear trend observed rather than a U-shaped one [8]. Group 3: Implications - The findings suggest that the previously held belief of "moderate drinking being neuroprotective" may stem from reverse causation, where early cognitive decline leads to reduced alcohol consumption [10]. - The study emphasizes the importance of considering reverse causation and residual confounding factors in alcohol and dementia research, indicating that reducing alcohol intake could be a significant strategy for dementia prevention [10].

Core Viewpoint - The research conducted by the team led by Shen Qilong from the Shanghai Institute of Organic Chemistry decodes the redox behavior of copper in Ullmann-type coupling reactions, providing new insights into the catalytic mechanisms involved [2][3][5]. Group 1 - The study reveals the reaction process between well-defined Cu(I) complexes and electron-deficient aryl iodides, leading to the formation of separable Cu(III)-aryl complexes, which subsequently undergo reductive elimination to form C(sp²)−CF₃ bonds [4]. - The research demonstrates that the copper species undergo an oxidation-reduction cycle involving Cu(I)/Cu(III)/Cu(II)/Cu(III)/Cu(I), highlighting the complexity of copper's behavior in these reactions [4][5]. - The team successfully interrupted the catalytic cycle using temperature control and captured the reactivity of copper species through various spectroscopic methods, allowing for an in-depth mechanistic analysis [4][5].

Core Viewpoint - The article discusses the relationship between nasal microbiota, specifically Staphylococcus aureus, and depressive behavior, highlighting the role of sex hormone degradation in this process [4][5][11]. Group 1: Research Findings - A study published in Nature Microbiology indicates that nasal Staphylococcus aureus can promote depressive behavior in mice by degrading sex hormones [4][5]. - The enzyme 17β-hydroxysteroid dehydrogenase expressed by Staphylococcus aureus degrades testosterone and estradiol in mice, leading to decreased levels of dopamine and serotonin in the brain, which induces depressive-like behavior [5][11]. - Analysis of nasal microbiota shows a positive correlation between the abundance of Staphylococcus aureus and depression scores in both depressed patients and healthy controls [9]. Group 2: Implications - The findings suggest a significant link between nasal microbiota and brain function, particularly in the context of neuropsychiatric disorders, which has been under-researched [8]. - The study provides new insights into the nose-brain axis, indicating that nasal colonization by certain bacteria may influence mental health through hormonal pathways [11].

编辑丨王多鱼 排版丨水成文 近日， 沈阳化工大学 和 中国科学院大连化学物理研究所 的 一篇观点文章登上了 登上了 Cell Press 官网头条。 该文章题为 ： Shaping the future of green methanol （ 塑造绿色甲醇的未来 ） ，文章于 2025 年 9 月 18 日在线发表于 Cell 子刊 Chem Catalysis 上， 通 讯作者为中国科学院大连化学物理研究所 邓德会 研究员、 胡景庭 副研究员，第一作者为沈阳化工大学 Cui Xinyue 、 中国科学院大连化学物理研究所 Hou Deshan 。 沈阳化工大学为文章第一署名单位。 甲醇 是一种重要的平台化学品和替代燃料，最近，甲醇因作为有前景的 储氢载体 而备受关注。 全球向碳中和经济的转型，加上日益严格的环境法规，正在推动基于 可再生氢 （通过可再生能源驱动的水电解制得） 和 捕获的二氧化碳原料 的 绿色甲醇合成 技术 的发展。这种电能到液体的技术，代表了化学制造领域的一场范式转变，它能有效地将间歇性的可再生能源 电力 转化为 可储存的液体燃料或化学品 ，同时 实现碳循环的闭环。 然而，通过二氧化碳加氢来 ...

Core Viewpoint - The article discusses the challenges in the diagnosis and treatment of Idiopathic Pulmonary Fibrosis (IPF) and highlights recent advancements in nanotechnology for improving these aspects [2][4][14]. Diagnosis Challenges - Current diagnostic methods for IPF are limited by low accuracy, high invasiveness, and time consumption, leading to delays in diagnosis and missed treatment opportunities [2][11]. - Nanoparticle biosensor platforms show great potential for non-invasive early screening by detecting biomarkers like miRNA in serum with high sensitivity and efficiency [11]. Treatment Challenges - Existing IPF treatments have limited efficacy, often accompanied by adverse effects due to low bioavailability and off-target effects [2]. - Inhalation drug delivery systems using nanocarriers can achieve higher drug concentrations in the lungs while reducing systemic side effects, thus enhancing therapeutic efficacy [13]. Nanotechnology Applications - The article outlines the use of functionalized nanoparticles for imaging, which can significantly improve the contrast in MRI, allowing for clearer visualization of early lesions [11]. - Various innovative nanocarriers, such as lipid nanoparticles, mesoporous nanoparticles, and nano-metal-organic frameworks, are introduced to enhance drug delivery efficiency [13]. Integrated Diagnosis and Treatment - The integration of treatment delivery and real-time monitoring through unified nanoplatforms is crucial for personalized medicine in IPF [13]. - The use of nanotechnology for tracking transplanted mesenchymal stem cells (MSCs) via in vivo imaging can optimize treatment outcomes by allowing real-time monitoring of cell survival and distribution [13]. Future Directions - The article discusses the challenges and translational barriers faced by cutting-edge technologies in clinical applications and provides insights for future research directions in developing more effective IPF diagnostic and therapeutic strategies [14].

ENCODE 计划揭示了人类基因组超过 80% 的基因组区域能够转录产生"暗物质"之称的 RNA。根据 RNA 的 5' 端是否具有帽子修饰结构，这些可以被分为两大 类：1）帽子结构的 （capped RNA，capRNA） ；2）非帽 RNA （noncapped RNA，napRNA） 。除 mRNA 和部分长非编码外，其余几乎所有均属于 napRNA。 这些 napRNA 不仅通过作为非编码 RNA （ncRNA） 调控多种生物学过程，还作为加工产物解析特定的 RNA 生物生成过程。然而，由于其长度异质性、末端修 饰多样性以及复杂的二级结构等，鉴定这些 napRNA 面临巨大挑战。 为应对这一挑战，中山大学生命科学学院 杨建华 / 李斌 / 屈良鹄 教授团队开发了 NAP-seq 技术，并于 2025 年 9 月 17 日在 Nature Protocols 期刊发表了题 为： NAP-seq for full-length noncapped RNA sequencing 的论文，系统介绍了该方法的设计原理与实验步骤。 编辑丨王多鱼 排版丨水成文 图1. NAP-seq的设计原理和实验步骤 NAP-s ...

Core Viewpoint - The research indicates that lithium carbonate can induce necroptosis in myofibroblasts, significantly reversing established pulmonary fibrosis in mouse models, offering new hope for millions of patients globally [3][4]. Group 1: Research Findings - Pulmonary fibrosis is characterized by the destruction of alveolar structures and collagen deposition, leading to irreversible lung function decline and high mortality risk [2]. - Current approved drugs, pirfenidone and nintedanib, can only slow disease progression but cannot reverse fibrosis [2]. - The study utilized a mouse model of irreversible pulmonary fibrosis induced by bleomycin and silica particles, demonstrating that lithium carbonate treatment resulted in significant structural improvements in the lungs [4]. Group 2: Mechanism of Action - Lithium carbonate promotes the release of low levels of TNF-α from alveolar macrophages, which sends potential death signals to myofibroblasts [5]. - Lithium ions inhibit the activation of pro-caspase-8 in myofibroblasts, leading to the activation of the necroptosis pathway and overcoming the anti-apoptotic barrier of these cells [5]. Group 3: Implications for Treatment - The research suggests that while existing drugs merely slow down fibrosis progression, lithium carbonate effectively removes the driving force behind fibrosis by targeting myofibroblasts [7]. - This study not only provides new treatment hope for pulmonary fibrosis patients but also offers theoretical support for interventions in other organ fibrosis diseases, such as liver, kidney, and heart fibrosis [7].