Core Insights - Prostate cancer is the second most common malignant tumor in men globally, characterized by treatment resistance and high recurrence risk, presenting significant challenges for therapy [2] - Immune therapy has shown significant clinical benefits in various solid tumors, but its efficacy in "cold" tumors like prostate cancer remains limited, necessitating strategies to activate immune responses [2] - A recent study published in PNAS reveals that PSAT1 drives a feedback loop that enables prostate cancer cells to evade NK cell immune surveillance, providing new molecular targets and intervention strategies for treating "cold" tumors [2][10] Group 1: Research Findings - The research team found that PSAT1 is significantly overexpressed in prostate cancer tissues and correlates with poor patient prognosis, while its expression is negatively associated with the infiltration of key immune effector cells, particularly NK cells [4] - PSAT1 regulates immune evasion by enhancing the phosphorylation of YBX1, which subsequently increases PSAT1 transcription, forming a stable positive feedback loop [4] - YBX1, upon entering the nucleus, activates the expression of HLA-E, an inhibitory ligand for NK cells, leading to NK cell dysfunction and preventing their ability to kill prostate cancer cells [5] Group 2: Clinical Implications - In vitro and in vivo experiments demonstrated that targeting or inhibiting PSAT1 significantly reduces the immune evasion capability of prostate cancer cells, enhancing NK cell-mediated tumor cell killing and effectively suppressing tumor growth [6] - The combination of PSAT1 knockdown and NK cell infusion shows synergistic effects in inhibiting tumor growth, highlighting the therapeutic potential of disrupting this immune evasion pathway [6] Group 3: Future Directions - The study suggests that targeting the PSAT1-YBX1-HLA-E pathway could convert "cold" tumors into "hot" tumors that are more responsive to NK cell immunotherapy, opening new avenues for treatment [10] - Preliminary data indicate that this mechanism may also be present in other malignancies with high HLA-E expression, such as lung cancer and glioma, suggesting broader therapeutic potential [10]

Core Viewpoint - The article discusses a breakthrough in diagnosing indeterminate pulmonary nodules (IPN) through a new AI-based diagnostic model called TCRNodseek Plus, developed by a team of Chinese researchers. This model leverages T-cell receptor (TCR) profiling to provide a more accurate assessment of lung nodules, moving from morphological guesswork to immunological evidence [1][2]. Research Background - The study titled "Large-Scale T-cell Receptor Repertoire Profiling Unveils Tumor-Specific Signals for Diagnosing Indeterminate Pulmonary Nodules" is set to be published in December 2025 in the journal Cancer Research [2]. Immune Signals in Early Tumor Detection - The research is based on the human immune system's ability to detect abnormalities early in tumor formation, even before imaging features are visible. T-cells, as key players in immune response, exhibit specific TCR patterns when lung cancer cells are present, indicating an "immune storm" [6]. Technical Approach - The research team faced significant challenges in detecting weak tumor-specific signals in blood samples, akin to "finding a needle in a haystack." They constructed a leading lung nodule immune database and optimized detection technologies, achieving a correlation of over 0.97 in PCR amplification [9]. AI-Enabled Diagnostic Model - The TCRNodseek Plus model integrates multiple dimensions of data, including blood immune profiles and imaging features, using advanced machine learning algorithms. In a validation study with 1,107 patients, the model achieved an AUC of 0.84, outperforming the commonly used Mayo model [11]. Decision-Making Logic - The model employs a rigorous "dual-threshold" decision-making logic, ensuring a 95% positive predictive value for high-risk malignant nodules and a 93% negative predictive value for benign nodules. This approach clarifies diagnostic directions for over 60% of patients with indeterminate pulmonary nodules, reducing unnecessary invasive procedures [11]. Global Collaboration Platform - The research team has made the LungTCR database publicly accessible, facilitating global collaboration in lung cancer research. This platform allows clinicians and researchers to upload sequencing data and obtain diagnostic references, breaking down data barriers and promoting standardized applications in lung cancer diagnostics [13].

编辑丨王多鱼 排版丨水成文 在疾病诊断、食品安全与环境监测等应用场景中，检测系统需要在复杂基质干扰、样本量受限与现场操作 条件不稳定等条件下，实现可复现的信号放大、稳定读出与定量判读。纳米酶可通过催化反应实现信号放 大与多类型信号转换，生物芯片平台为微量样本处理、多通道集成与便携化读出提供器件载体。随着检测 任务从单指标走向多指标、从终点读数走向连续监测，信号形态与数据维度进一步增加，经验阈值与人工 判读在一致性、可迁移性与实时性方面存在约束。 因此，有必要从 " 材料与催化机制- 智能化生物芯片- 多场景应用 " 的完整链路出发，对纳米酶与生物芯 片的集成范式、信号转换机制以及 AI 参与的智能化处理路径进行系统梳理，形成可比较的研究框架与面向 应用的技术路线。 近日，北京航空航天大学 常凌乾 、 董再再 及香港城市大学 焦艳丽 作为共同通讯作者 （ 陈冬雨 、 郑旺 、 张志辉 、 于沈平 为共同第一作者 ） ，在 Advanced Science 期刊发表了题为： Nanozymes Integrated Biochips Toward Smart Detection System 的综述论文。 该综述 ...

Core Viewpoint - The research highlights the potential of ancient RNA (aRNA) studies in reconstructing the transcriptomes of extinct species, specifically the woolly mammoth, thereby opening new avenues for integrating genomics, proteomics, and transcriptomics in paleobiology [2][10]. Group 1: Ancient RNA Research - Ancient DNA (aDNA) technology has revolutionized the study of extinct and extant species, enabling the reconstruction of genomes and their ecosystems [1]. - The recent study published in Cell reports the transcriptome profiles of 10 woolly mammoths from the late Pleistocene, with one sample dating back approximately 39,000 years, marking the oldest recorded ancient RNA sequences [2][6]. - The research demonstrates the feasibility of extracting, sequencing, analyzing, and validating transcriptome maps from ancient samples, paving the way for generating aRNA profiles from a wide range of Pleistocene remains [9]. Group 2: Methodology and Findings - The research team developed a framework for isolating aRNA molecules, building on previous studies of historical and ancient samples, and implemented quality control measures through metagenomics and metatranscriptomics [6]. - The study identified several muscle-specific mRNAs from the mammoth samples and discovered potential novel miRNA candidate gene loci based on gene expression evidence from the aRNA sequences [6][7]. - The findings indicate that tissue-specific gene expression patterns have been preserved over time, allowing for the annotation of new non-coding gene loci [7].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 结直肠癌 （CRC） 在全球癌症死亡率中排名第三，其发病率和死亡率一直居高不下。人口老龄化、西式饮食，再加上肥胖和缺乏运动等已知风险因素，导致结直 肠癌的发病率不断上升。尽管近年来在检测方法和治疗手段方面取得了显著进展，包括内镜和手术局部切除、局部消融治疗、靶向治疗和免疫干预等，但结直肠 癌患者的长期预后仍然不佳，尤其是在晚期或转移性病例中。因此，深入研究结直肠癌的分子过程，发现新的治疗靶点和预后生物标志物，对于改善患者的临床 结局至关重要。 2025 年 12 月 26 日 ， 湖南省肿瘤医院/ 中南大学湘雅医学院附属肿瘤医院 袁霞 、 中南大学基础医学院 周艳宏 等， 在 Signal Transduction and Targeted Therapy 期刊发表了题为 ： Inhibin beta A drives colorectal cancer progression through macrophage M2 polarization and mitochondria-dependent ferroptosis suppression 的研究论文。 该研究表 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 在这项最新研究中，研究团队通过对从人类 支气管肺发育不良 （BPD） 肺组织中分离出的内皮细胞进行多组学分析，发现了一种以 NTRK2 （ 神经营养因子受 体酪氨酸激酶-2） 为标志的普通毛细血管内皮细胞 （gCap） 的扩增。 值得注意的是，该研究发现 NTRK2 存在 两种功能不同的亚型 ，它们控制着 gCap 的再生。 全长 NTRK2 （NTRK2-FL） 促进了高氧损伤后的 gCap 修复，而 RBFOX2 介导的 NTRK2-FL 剪接形成 截短体 NTRK2 （NTRK2-T1） 则导致了适应不良的反应和持续的肺泡简化。 接下来，研究团队利用脂质纳米颗粒 （LNP） 递送的 NTRK2-FL mRNA ，以恢复 全长 NTRK2 表达。在 高氧诱导的肺损伤小鼠模型中，该方法显著恢复了肺 部毛细血管密度，改善了 肺泡结构；在 人类诱导多能干细胞 （hiPSC） 来源的血管类器官模型中，该方法 同样促进了新生血管形成，使血管结构更加完整、有 序。 这些发现表明 NTRK2 异构体失衡是内皮功能障碍的关键驱动因素，并支持异构体特异性 RNA 疗法作为血管再生和修 ...

Core Insights - The article discusses the launch of the Game Changer Series by Taylor & Francis and Dove Medical Press, aimed at soliciting groundbreaking research in life sciences and medicine that focuses on mechanism breakthroughs, technological innovations, and translational value [2][3]. Group 1: Research Focus Areas - The series emphasizes research in cutting-edge areas such as tumor biology, immune mechanisms, and novel drug and technology platforms [3]. - Key submission topics include antibody-drug conjugates (ADC) for breast cancer treatment, CAR-T cell therapy, immune checkpoint inhibitors for hepatocellular carcinoma, and BTK inhibitors for hematological malignancies [6][7]. - Additional areas of interest are personalized antimicrobial strategies, AI-driven drug resistance prediction, fecal microbiota transplantation, and HPV vaccines [7]. Group 2: Immune, Inflammation, and Biologics - The series also focuses on immune pathways, precision targeting, and new strategies in biological therapies [9]. - Specific topics include anti-inflammatory biologics for chronic inflammation, targeting the IL-4/IL-13 axis in type 2 inflammation treatment, and personalized biologic therapies for asthma [11]. Group 3: Advanced Technologies and Rare Diseases - The transformative applications of lipid nanoparticles in mRNA therapeutics and the role of AI in healthcare risk management are highlighted as significant advancements [15]. - The series aims to spotlight breakthroughs in rare disease treatments, emphasizing precision medicine [15]. Group 4: Target Audience - The call for submissions is directed at researchers in life sciences, medicine, biotechnology, drug development, and translational research who focus on mechanism innovation and technological breakthroughs [16].

Core Viewpoint - The establishment of the SiBST (Sanhang Brain Science and Technology Research Center) at Northwestern Polytechnical University aims to integrate brain science research with aerospace and marine sciences, focusing on long-term human survival in deep space and deep sea environments [3]. Group 1: Talent Recruitment - The center is actively recruiting high-level young talents globally, with specific positions including Chair Professors, Leading Talents, Young Talents, and other academic roles [3][5][7][10]. - Chair Professors are expected to lead international scientific frontiers and achieve significant scientific accomplishments in major national technology tasks [5]. - Leading Talents should conduct pioneering research in their fields and have a significant impact on social development and scientific progress [8]. - Young Talents must hold a PhD, be under 40 years old, and have demonstrated high academic achievements with potential for leadership in their fields [10]. Group 2: Support and Benefits - The center offers personalized support and benefits for all recruited talents, including competitive salaries, housing allowances, performance bonuses, and additional income opportunities [6][14][15]. - Research support includes substantial startup research funding and guaranteed PhD student positions for the first three years [14]. - Life benefits include access to high-quality educational resources for children and exclusive services for high-level talents, such as VIP services at transportation hubs and healthcare systems [14].

Core Viewpoint - Mazdutide, developed by Innovent Biologics, is a dual receptor agonist targeting GCG and GLP-1, showing promising results in weight loss and liver fat metabolism improvement for obese and overweight adults in China [1][2]. Group 1: Clinical Trial Results - The Phase 3 clinical trial GLORY-1 published in NEJM demonstrated that weekly injections of Mazdutide resulted in significant weight loss and safety in obese or overweight Chinese adults [1]. - In the trial, participants receiving Mazdutide showed a reduction in HbA1c of 1.57% for the 4 mg group and 2.15% for the 6 mg group, compared to a 0.14% reduction in the placebo group [5]. - The weight loss observed was 5.61% for the 4 mg group and 7.81% for the 6 mg group, while the placebo group lost only 1.26% [5]. Group 2: Regulatory Approval - Based on the successful clinical trial results, the National Medical Products Administration (NMPA) approved Mazdutide for long-term weight management in adults with obesity or overweight on June 27, 2025 [2]. Group 3: Additional Research Findings - Two additional Phase 3 studies on Mazdutide for treating type 2 diabetes were published back-to-back in Nature, marking a significant achievement for Chinese drug development in the metabolic and endocrine disease field [2][10]. - In a separate study comparing Mazdutide to Dulaglutide, both doses of Mazdutide showed non-inferiority and superiority in reducing HbA1c compared to Dulaglutide, with treatment differences of -0.24% and -0.30% respectively [9]. - The weight loss was significantly greater in the Mazdutide groups, with differences of -3.78% for the 4 mg group and -5.76% for the 6 mg group compared to Dulaglutide [9].

Core Viewpoint - The article presents a new framework centered on the thymus in understanding immune aging, highlighting its critical role in the decline of immune function and exploring potential intervention strategies [1][4]. Group 1: Thymus and Immune Aging - Immunosenescence is characterized by increased disease susceptibility, reduced vaccine efficacy, and chronic low-grade inflammation, which diminishes the effectiveness of cancer immunotherapy [1][4]. - The thymus is identified as a key organ in the immune system, responsible for training T cells, and its decline is noted to begin as early as puberty, leading to significant reductions in naive T cell numbers and diversity [4][8]. - Unlike other immune organs, thymic atrophy is largely irreversible, making it a critical failure point in the immune axis and a prime target for interventions against immune aging [12][15]. Group 2: Factors Influencing Thymic Decline - Thymic decline is influenced by several factors, including hormonal changes during puberty, infection burden, oxidative stress, and regulation of the FOXN1 gene, which is crucial for thymic epithelial cell function [14][15]. - Clinical observations indicate that individuals who undergo thymectomy experience long-term immune deficiencies, underscoring the thymus's importance in maintaining immune health [8][12]. Group 3: Implications for Future Research - The article emphasizes that protecting thymic function may be essential for long-term immune health, suggesting that strategies to avoid unnecessary infections, reduce chronic inflammation, and maintain hormonal balance could help delay thymic decline [17]. - Targeting thymic regeneration could not only improve the quality of life for the elderly but also lead to breakthroughs in cancer immunotherapy and vaccine development [17][15].