撰文丨王聪 编辑丨王多鱼 排版丨水成文 霍维茨奖 （全称为 路易莎·格罗斯·霍维茨奖 ） ，是生物化学、生理学或生物物理学领域最具声望的科学 奖项之一，由美国 哥伦比亚大学 颁发，授予在基础生物学研究领域做出杰出贡献、对科学和人类健康具有 深远影响的科学家。 霍维茨奖是著名的" 诺奖风向标 "，据统计，此前 118 位霍维茨奖得主中，已有 55 位获得了诺贝尔奖。 例如，mRNA 疫苗先驱 Katalin Kariko 和 Drew Weissman 于 2021 年获霍维茨奖，于同年获诺贝尔生理 学或医学奖；于 2023 年获霍维茨奖，次年获诺贝尔化学奖。miRNA 研究先驱 Victor Ambros 和 Gary Ruvkun 于 2009 年获霍维茨奖，于 2024 年获诺贝尔生理学或医学奖。 近日，哥伦比亚大学公布 2025 年 霍维茨奖 获奖名单—— Kevin Campbell （爱荷华大学） 、 Louis Kunkel （波士顿儿童医院/哈佛医学院） 、 Eric Olson （德州大学西南医学中心） ，他们三人" 因揭示 了肌萎缩症的病因而获奖 "， 该奖项旨在表彰他们在揭示 杜氏肌营养不 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 慢性肾病 （CKD） 已成为全球性的健康危机，其患病率不断上升，并对患者的生活质量和死亡率产生深远影响。在 CKD 的诸多严重并发症中，与 心血管疾病 （CVD） 的关联尤为突出，CVD 导致的死亡占 CKD 患者死亡总数的一半以上，心力衰竭 （HF） 更是其中导致死亡的主要因素。 尽管在理解 CKD 肾功能障碍的病理生理学方面取得了重大进展，但 CKD 患者的心血管并发症发病率的上升凸显了我们知识上的重大空白，尤其是关于肾功能障 碍与心脏疾病之间关联机制的认识不足。这些空白突显了迫切需要新的预测性生物标志物和更有效的治疗靶点来减轻这些并发症。 心力衰竭 （HF） 在 慢性肾病 （CKD） 患者中极为常见，并与肠道微生物群的变化有关，但其潜在机制目前尚不清楚，这给诊断和治疗带来了困难。 2025 年 9 月 16 日，南方医科大学周宏伟、李壮团队联合哈尔滨医科大学第一附属医院李悦团队，在 Cell 子刊 Cell Host & Microbe 上发表了题为： Gut Microbiota-Derived Indole Sulfate Promotes Heart Fai ...

Core Insights - The research indicates that fibroblasts, previously thought to only support myocardial cells structurally, play a significant role in the deterioration of heart failure [1][2] - The study highlights the activation of specific fibroblast populations during heart failure, with the transcription factor c-MYC being notably expressed [1] - The findings suggest a potential new therapeutic strategy targeting non-myocardial cells in heart failure treatment, moving beyond the traditional focus on damaged myocardial cells [2] Group 1: Research Findings - Heart failure is a severe condition characterized by decreased cardiac pumping function, leading to symptoms such as dyspnea, edema, and fatigue, with a high mortality rate [1] - The research team published their findings in the journal "Nature - Cardiovascular Research," demonstrating that c-MYC induces the secretion of chemokine CXCL1, which negatively impacts myocardial cell contraction [1] - Inhibition of c-MYC expression in experimental mice resulted in improved cardiac function and increased survival rates, while forced expression of c-MYC led to significant cardiac decline [1] Group 2: Implications for Treatment - The study analyzed cardiac tissues from heart failure patients, corroborating the findings from experimental mice, indicating potential applicability to human heart failure cases [2] - The research marks a significant step towards establishing new treatment strategies that target non-myocardial cells, addressing the limited treatment options currently available for severe heart failure [2]

Core Insights - A new study from Tsukuba University reveals key molecular pathways regulating immune response and cancer metastasis in triple-negative breast cancer (TNBC) patients, potentially leading to innovative treatment options for this aggressive cancer type [1][2] Group 1: Research Findings - Researchers identified a transmembrane glycoprotein named "non-metastatic melanoma glycoprotein B" that is significantly elevated in TNBC tumor cells, with distinct molecular modification characteristics compared to other cells [1] - The identified glycoprotein promotes the differentiation of upstream cells into tumor-associated macrophages (TAMs), which enhance their immunosuppressive properties [1] - TAMs play a crucial role in tumor progression, invasion, metastasis, and treatment resistance by helping tumor cells evade immune attacks [1] Group 2: Implications for Treatment - Targeting the identified molecular pathway may lead to the development of new immunotherapies, drugs, and combination strategies with existing immune checkpoint blockade therapies, providing innovative treatment options for TNBC and other poor-prognosis cancers [2]

Core Viewpoint - The article discusses a groundbreaking study on breast cancer that introduces a high-throughput, high-genomic-resolution single-cell DNA and RNA multi-omics technology called wellDR-seq, which helps decode the origins and progression mechanisms of breast cancer [3][5][9]. Group 1 - The research team, led by Nicholas Navin at the MD Anderson Cancer Center, published their findings in the journal Cell, highlighting the first application of wellDR-seq technology [3][5]. - The study analyzed 33,646 single cells from 12 estrogen receptor-positive (ER+) breast cancer patients, identifying cancer ancestral subclones that may represent the origin cells of breast cancer [5][9]. - wellDR-seq allows for the study of gene dosage relationships at the subclonal level, revealing a near-linear correlation in large chromosomal regions and extensive variation at the single-gene level [6][9]. Group 2 - The research identified that 56% of copy number variation segments showed a near-linear correlation with gene expression, providing insights into the complex relationship between copy number and gene expression at the single-cell level [9]. - The study also identified dosage-sensitive and dosage-insensitive genes, including many breast cancer-related genes and incidental copy number variations in non-cancer cells [6][9]. - wellDR-seq is a versatile method applicable not only to breast cancer but also to other cancers and various biomedical fields, enhancing the understanding of cancer development [9].

Core Viewpoint - The research reveals that cancer cells hijack iron-rich macrophages in the bone marrow to promote bone metastasis and anemia, opening new avenues for therapies to mitigate both bone metastasis and associated severe anemia [3][12]. Group 1: Mechanism of Cancer Metastasis - Cancer cells effectively "hijack" a specific type of macrophage, known as VCAM1+ CD163+ CCR3+ macrophages, which are responsible for recycling iron in the bone, depriving red blood cells of the iron needed for maturation [5][10]. - The study indicates that the hijacking of these macrophages not only leads to a lack of iron necessary for red blood cell development but also supports tumor growth in the bone [9][10]. Group 2: Implications for Anemia - The cancer cells' action results in the red blood cells being in an immature state, leading to anemia due to insufficient healthy red blood cell production [9][10]. - Tumor cells simulate red blood cells to adapt to the hypoxic environment of the bone tissue, utilizing the stolen iron to produce hemoglobin, which is crucial for oxygen transport [9][12]. Group 3: Research Significance - This research shifts the focus from solely studying cancer cells ("seeds") to understanding the surrounding microenvironment ("soil") that facilitates cancer metastasis [7][8]. - The findings have broader implications beyond metastatic breast cancer, potentially extending to other major cancer types, highlighting the importance of the tumor's manipulation of its environment [12].

染色体外 DNA （ecDNA） 与 肿瘤 之间的关联已被充分证实，其在不同癌症中的作用愈发引人关注。然 而，尽管 ecDNA 被认为源于基因组不稳定性，但驱动 ecDNA 形成过程中 DNA 末端连接的分子机制，以 及控制其选择性基因包装的调控因素仍待阐明。 2025 年 8 月 21 日，南开大学药学院 孙涛 教授、 张恒 博士及 天津医科大学肿瘤医院 黄鼎智 医生等， 在 Cell 子刊 Molecular Cell 上发表了题为： Extrachromosomal DNA biogenesis is dependent on DNA looping and religation by YY1-Lig3-PARylation complex 的研究论文，该论文被选为当期封面论文。 该研究表明， 染色体外 DNA （ecDNA） 的生物发生依赖于由 YY1-Lig3-PARylation 复合物介导的 DNA 环化和重新连接，从而提出了 补充现有理论的 ecDNA 生物发生新模型。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 期刊封面：在一片生机勃勃的森林中潜藏着隐秘的危险——象征着 YY1-Lig3-PAR ...

Core Viewpoint - The study reveals that tumor-antigen-specific cytotoxic CD8+ T cells can be deployed remotely to inhibit lung metastasis of breast cancer, highlighting the importance of effector immune cell deployment in cancer treatment [3][8][11]. Group 1: Research Findings - The abundance of tumor-specific CD103+ CD8+ T cells in tumor-draining lymph nodes (TDLN) is associated with prolonged disease-free survival in breast cancer patients [8]. - CD103+ CD8+ T cells are activated in TDLN and recruited to the lungs via CCL25/CCR9 signaling, effectively suppressing tumor metastasis [8][9]. - Tumor-derived extracellular vesicles (EVs) polarize alveolar macrophages, leading to the release of CCL25 and IDO1, which can inhibit the deployment of CD103+ CD8+ T cells and promote lung metastasis [8][9]. Group 2: Implications for Cancer Treatment - Enhancing the recruitment of CD103+ CD8+ T cells or blocking IDO1 can potentially curb lung metastasis of tumors [9]. - The study emphasizes the adaptive immune system's capability to deploy remotely to protect distant organs from tumor metastasis, suggesting a potential therapeutic strategy in cancer treatment [11].

Core Viewpoint - The study reveals that the decline in leptin levels with age contributes to the accumulation of senescent CD8+ T cells in the tumor microenvironment, leading to weakened anti-tumor effects. Regulating leptin levels may be a promising therapeutic strategy for elderly cancer patients [3][7][10]. Group 1: Aging and T Cell Dysfunction - Aging is a major risk factor for various cancers, with patients aged 65 and above accounting for 60% of new cancer diagnoses [5]. - T cell immune remodeling due to aging results in poor clinical outcomes for cancer patients, as T cells lose physiological functions over time [5]. - Age-related changes in T cells and the impact of systemic metabolic alterations on T cell function and phenotype require further investigation [5]. Group 2: Role of Leptin - Leptin, produced by adipose tissue, informs the brain about the body's fat storage levels, with higher fat leading to increased leptin production [6]. - The study found that decreased leptin levels with age accelerate CD8+ T cell senescence, impairing T cell function in the tumor microenvironment [7][8]. - In human cancer patients, plasma leptin levels are negatively correlated with the degree of CD8+ T cell senescence within tumors [7][8]. Group 3: Implications for Treatment - The findings suggest that enhancing plasma leptin levels through the regulation of adipocyte metabolism may help prevent T cell senescence and improve anti-tumor immunity in elderly patients [10]. - Supplementing leptin could have therapeutic potential for elderly cancer patients [10].

Core Viewpoint - The study highlights the dynamic changes in the tumor microenvironment (TME) across various cancer types and stages, emphasizing the importance of understanding cellular interactions within the TME as a promising therapeutic target [3][7]. Group 1: Research Overview - The research published in Nature Cancer integrates data from 36 cancer types and 746 samples, analyzing over 4 million single cells and spatial transcriptomics data from 6 cancer types [4][5]. - A comprehensive atlas of TME heterogeneity, named TabulaTIME, was established, detailing six major cell lineages and 56 cell subtypes within the TME [7][9]. Group 2: Key Findings - The study identified CTHRC1 as a marker for cancer-associated fibroblasts (CAFs) that are enriched in various cancer types, indicating their role in immune cell infiltration prevention [9]. - The research demonstrated that TabulaTIME can be utilized for analyzing tumor ecotype composition and serves as a reference for cell type annotation, providing insights into potential therapeutic strategies targeting profibrotic ecotypes [9].