Core Viewpoint - The article discusses the development of a large-scale Pan-Cancer Proteome Atlas (TPCPA) that aims to enhance the understanding of cancer biology and identify therapeutic targets and biomarkers through mass spectrometry-based analysis of protein expression across various cancer types [2][4]. Group 1: Research Overview - The TPCPA covers 22 cancer types, including 18 solid tumors and 4 non-solid tumors, analyzing 999 primary tumor samples and quantifying 9,670 proteins [5][6]. - The study identifies multiple pan-cancer and specific protein biomarkers, potential therapeutic targets, and classifiers for cancer subtypes [2][6]. Group 2: Methodology and Findings - The research utilizes data-independent acquisition mass spectrometry (DIA-MS) to construct the proteome atlas, facilitating a comprehensive analysis of protein expression characteristics both inter- and intra-cancer types [4][6]. - The study highlights specific E3 ubiquitin ligases, such as HERC5 and RNF5, that are highly expressed in esophageal and liver cancers, respectively, as potential targets for protein-targeted degradation therapies [6]. Group 3: Cancer Subtype Classification - An analysis of 195 colorectal cancer cases led to the identification of consensus molecular subtypes (CMS) and two immune subtypes with prognostic value [7]. - A cancer subtype classifier based on 75 proteins was developed, demonstrating excellent performance (AUC greater than 0.98) in internal validation and four independent cohorts, including metastatic cancers [7]. Group 4: Data Accessibility - The research team has made all TPCPA data publicly available for free access and use through a dedicated portal [9].

为何出现发育异常？癌症等疾病因何产生？记者5月26日从同济大学获悉，该校医学院、同济大学 附属东方医院尹贻蒙团队与剑桥大学团队合作，突破了单转录因子调控基因的传统研究模式。研究表 明，不同转录因子通过协同作用识别新型DNA序列，并参与胚胎发育等生命活动，而识别的新型DNA 序列的突变与发育异常、癌症等疾病发生密切相关。相关研究成果日前在线发表于国际学术期刊《自 然》。 此外，研究团队还发现，协同作用致使800多对转录因子识别的新型DNA序列发生改变。 人体生长发育所需要的一切信息都蕴藏在人类基因组之中。转录因子常以协同作用方式解读不同 DNA序列所蕴含的各类信息，通过调控基因的时空特异性表达，参与细胞所有生命活动。若转录因子 或其识别的DNA序列发生突变，就极有可能引发发育异常，甚至导致癌症等多种疾病的产生。 这一发现，为发育异常和癌症等各类疾病的个性化治疗提供了新思路。（黄艾娇 记者王春） 原标题：转录因子协同作用机制揭示 为了深入探究转录因子之间的协同作用机制，研究团队借助高通量筛选技术和计算生物学手段，对 5.8万余种转录因子组合是否可协同识别DNA进行了系统性评估，鉴定出2198对具有协同作用的转录因 ...

Core Viewpoint - The emergence of drug-resistant malaria parasites necessitates the development of new treatment strategies, with a focus on dietary and metabolic interventions to combat malaria infection [2][4]. Group 1: Research Findings - A study published by a team from Shenyang Agricultural University indicates that a ketogenic diet can inhibit the growth of Plasmodium falciparum and confer protection against malaria in mice [3][4]. - The mechanism involves β-hydroxybutyrate (β-OHB), a ketone body produced during a ketogenic diet, which halts the development of malaria parasites, highlighting the potential of dietary strategies in malaria prevention [4][9]. - The study found that high levels of β-OHB in the blood disrupt the biological regulation mechanisms of malaria parasites, leading to their developmental stasis [9][11]. Group 2: Mechanisms of Action - β-OHB not only serves as an energy source but also acts as a signaling molecule that influences metabolic regulation, inflammation, and oxidative stress pathways [8]. - The inhibition of histone deacetylase (HDAC) by β-OHB results in increased histone acetylation levels, which can lead to gene expression alterations and protective effects against oxidative stress in mouse tissues [8][9]. - The research demonstrated that both ketogenic diets and direct supplementation of β-OHB can induce metabolic reprogramming in malaria parasites, reducing their NAD levels and downregulating genes associated with their development and virulence [11]. Group 3: Implications for Malaria Treatment - The findings suggest that dietary and metabolic interventions, particularly through ketogenic diets and β-OHB, could be promising strategies for developing new anti-malarial treatments [4][11]. - The study emphasizes the antimicrobial potential of metabolic interventions, as highlighted in a concurrent article in Nature Metabolism, which discusses the protective effects of β-OHB against malaria [11].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 尽管新冠疫苗的接种率很高，但高度进化的 奥密克戎 （ Omicron） 突变株仍在人群中引发了广泛感染，在某些情况下还导致了反复感染。近期，我国多地出现 新冠感染反弹现象，奥密克戎突变株 XDV 及其亚分支是此轮感染的主要毒株。 随着人群持续受到新突变株的威胁，了解动态交叉反应抗体应答如何演变以及如何影响保护作用至关重要。 2025 年 5 月 20 日，上海交通大学医学院 叶菱秀 、 苏冰 、 瞿介明 等人在 Cell Discovery 期刊发表了题为 ： Multiple infections with Omicron variants increase breadth and potency of Omicron-specific neutralizing antibodie s 的研究论文。 该研究对 48 名 经历了三波奥密克戎感染潮 （BA.5/BF.7、XBB 和 JN.1） 的个体进行了长达 18 个月的中和抗体滴度纵向分析，结果显示， 多次感染奥密克戎 毒株能够增强 可增强奥密克戎特异性中和抗体的广度和效力 ，产生的 高滴度和广谱交叉反应抗体， 可能 ...

Core Viewpoint - The study reveals that maternal immune activation due to viral infection leads to abnormal secretion of extracellular granzyme B (GzmB) by natural killer (NK) cells, which crosses the maternal-fetal barrier, resulting in the accumulation of fetal macrophages and activation of microglia, ultimately causing neurodevelopmental disorders and behavioral defects in offspring [2][3][6]. Group 1: Research Findings - Maternal NK cells activated by viral infection promote the accumulation of activated macrophages in the fetal brain, leading to neurodevelopmental disorders and behavioral defects in offspring [3][6]. - Extracellular granzyme B (GzmB) is released by maternal CD49a+ tissue-resident NK cell subsets under type I interferon stimulation, crossing the maternal-fetal barrier and promoting the accumulation of fetal macrophages expressing interferon-stimulated genes (ISG) and activation of microglia [3][6]. - Targeting extracellular GzmB by systemic administration of serine protease inhibitor Serpina3n or knocking out the GzmB gene in maternal NK cells can alleviate neuroimmune disorders in the fetal brain induced by maternal immune activation [3][6]. Group 2: Implications - The findings indicate that exposure to a disrupted maternal environment reprograms the immune function of decidual NK cells, disrupting the neuroimmune balance in the fetus and increasing the risk of neurodevelopmental disorders in offspring [6].

Group 1 - The core finding of the research is the identification of unique genetic characteristics of T cell clones that may predict the efficacy of cancer immunotherapy, paving the way for personalized treatment approaches [1][2] - Immunotherapy is recognized as a revolutionary breakthrough in cancer treatment, capable of precisely eliminating cancer cells by activating the immune system, but individual patient differences pose significant challenges to its widespread application [1] - The research involved a meta-analysis of single-cell RNA sequencing and T cell receptor sequencing data from numerous cancer patients who underwent immunotherapy, focusing on the relationship between T cell clone characteristics and the success of the therapy [1] Group 2 - The study revealed that while T cell clones exist in both responsive and non-responsive cancer patients, those in responsive patients exhibit a distinct genetic feature and enhanced immune activity due to immunotherapy [2] - It was determined that activating T cell clones present only within tumors, rather than those found in both tumors and blood, is crucial for improving the effectiveness of immunotherapy in treating cancer [2] - This research provides significant insights into the dynamic mechanisms of the human immune system in the cancer fighting process, as published in the latest issue of the journal "Cell Genomics" [2]

据悉，上海交通大学医学院附属精神卫生中心肖世富/岳玲教授团队联合上海科技大学沈定刚/潘永生教 授团队获得的研究成果在知名期刊《阿尔茨海默病预防杂志》(Journal of Prevention of Alzheimer's Disease)上刊登。据悉，轻度认知损害(Mild Cognitive Impairment, MCI)被视为阿尔茨海默病等认知障碍 的前期风险状态。这项研究对认知障碍的早期预测工作显得尤为关键：不仅有助于识别潜在患者，还能 为及时实施有效治疗提供可能，从而延缓疾病进展，改善患者预后。 来源：中国新闻网 中新网上海5月7日电 (记者 陈静) 当下，随着疾病修饰治疗药物(如仑卡奈单抗、多奈单抗)的获批并投 入临床使用，轻度认知损害(MCI)和轻度痴呆阶段成为阿尔茨海默病患者干预的黄金窗口期。记者7日 获悉，中国医学专家获得最新研究成果：成功构建 MCI预测模型，为认知障碍的早期识别提供新方 法。 据介绍，该模型基于结构磁共振图像(MRI)数据，建立了一套深度学习训练框架；通过基于多个感兴趣 区域的网络(MRNet)筛选并整合包括海马体、杏仁核、小脑等10个高区分度脑区特征，并进一步构建了 ...

编辑丨王多鱼 排版丨水成文 染色体外 DNA （extrachromosomal DNA，ecDNA） 是一种独立于染色体存在的环状 DNA 分子，在 30%-50% 的恶性肿瘤患者中被检测到。尽管早在 1965 年研究人员就在神经母细胞瘤中观察到其存在 （当 时称为双微体） ，但受限于技术手段，其存在的生物学意义长期未被阐明。 近年来的研究发现，ecDNA 可携带完整的致癌基因 （例如 MYC、EGFR） 及其增强子序列。当这些基因从 染色体脱落并环化形成 ecDNA 后，原本的表观遗传修饰 （例如 DNA 甲基化和组蛋白修饰） 记忆丢失，导 致癌基因的异常激活。 临床证据表明，携带 ecDNA 的肿瘤患者往往表现出更高的恶性程度、更强的治疗抵抗和更差的临床预后。 因此，靶向 ecDNA 的抗肿瘤策略 （例如干扰其复制与维持、调控表观遗传重塑） 具有重要治疗潜力。然 而，ecDNA 的复制与维持机制、表观遗传重塑及其在肿瘤发生发展中的精确作用，仍是当前研究的核心挑 战。解决这些问题将为开发新型抗癌疗法提供关键突破口。 2025 年 4 月 28 日，中国科学院深圳先进技术研究院定量合成生物学全国重点实验室、 ...