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].

Core Viewpoint - Colorectal cancer (CRC) is the third most common cancer globally, with nearly 2 million new cases annually, and the second leading cause of cancer-related deaths, claiming nearly 1 million lives each year. The study published by Wuhan University researchers identifies a significant single nucleotide mutation (rs10871066) associated with increased risk of precancerous lesions and colorectal cancer, revealing underlying oncogenic mechanisms [2][5]. Group 1 - The research utilized multi-omics data from 533 colorectal tissue samples, ranging from normal tissues to early adenomas and cancers, to establish a dynamic epigenetic map [5]. - A total of 7,492 differential cis-regulatory elements (CREs) were identified, linked to 5,490 target genes [5]. - High-throughput CRISPR interference (CRISPRi) screening revealed 265 functional CREs associated with colorectal cancer cell proliferation [5]. Group 2 - A polygenic risk score (PRS) model based on functional CRE mutations effectively predicted colorectal cancer and precancerous lesions in 476,770 individuals [5]. - The functional mutation rs10871066 is significantly correlated with increased risk of precancerous lesions and colorectal cancer [5]. - Mechanistically, rs10871066 mediates the conversion from silencers to enhancers through FOXP1 and TCF7L2, leading to the upregulation of KLF5 and activation of oncogenic pathways, while also upregulating PIBF1 to inhibit natural killer (NK) cell cytotoxicity [5].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 轴突退行 （axonal degeneration） 是神经系统疾病中常见的一种病理变化，表现为轴突肿胀、碎裂和萎缩等，这会进一步导致神经细胞胞体的死亡和退化，与 各种神经退行性疾病的发生密切相关，包括阿尔茨海默病、帕金森病等中枢神经系统疾病以及化疗和糖尿病引起的外周神经损伤等。 SARM1 是 轴突退行 的关键执行者，通过其 TIR 结构域的 NAD 酶活 性导致 NAD⁺ 耗竭 而发挥作用。在正常情况下，SARM1 处于自抑制状态，但它会在轴突损 伤时被激活；然而，其中的潜在机制尚不清楚。 2025 年 8 月 22 日，清华大学生物医学交叉研究院/北京生命科学研究所 王晓东 院士、 郑三多 研究员等，在 Nature 子刊 Nature Chemical Biology 上发表了 题为： SARM1 activation promotes axonal degeneration via a two-step phase transition 的研究论文。该研究揭示了 SARM1 的激活通过两步相变促进 轴突 变性 。 首先，NMN （ NAD⁺ 的前体 ） 启动了 ...