Core Viewpoint - The article highlights the successful administration of the first patient with hyperchylomicronemia receiving the targeted base editing drug CS-121, developed by Zhengxu Biotech, marking a significant advancement in gene therapy for hyperlipidemia [2][10]. Group 1: Clinical Research and Patient Outcomes - The first patient treated in the clinical research (IIT) for CS-121 injection has been discharged after showing a significant decrease in fasting triglyceride (TG) levels within three days post-administration [2][10]. - The patient had a history of fasting TG levels exceeding 12.5 mmol/L, which led to multiple episodes of acute pancreatitis [2][10]. Group 2: Disease Background - Hyperchylomicronemia is a metabolic disorder characterized by elevated chylomicron levels in the blood, often leading to severe hypertriglyceridemia (sHTG) and potential complications such as acute pancreatitis [5][6]. - The condition includes familial chylomicronemia syndrome (FCS) and multifactorial chylomicronemia syndrome (MCS), with FCS being a rare autosomal recessive disorder and MCS influenced by various factors [6]. Group 3: Treatment Challenges and Innovations - Current treatment strategies for hyperchylomicronemia focus on maintaining fasting TG levels below 5.7 mmol/L to mitigate the risk of acute pancreatitis, but existing medications have limited efficacy [7]. - The CS-121 injection utilizes a novel base editing technology (tBE) to precisely edit the APOC3 gene, aiming for a long-lasting reduction in TG levels with a single administration [9]. Group 4: Mechanism and Safety - The tBE technology allows for targeted editing without causing double-strand breaks in DNA, thus minimizing safety risks associated with traditional CRISPR methods [9]. - Preclinical studies have validated the safety and long-term efficacy of CS-121, showing no off-target effects in various tissues [9].

Core Insights - The article discusses a significant study on CAR-T cell therapy, highlighting its potential for long-lasting remission in cancer patients while also addressing the associated adverse events that can impact patient outcomes [2][3]. Group 1: Adverse Events and Patient Outcomes - The study reveals a series of adverse events related to CAR-T cell therapy that are closely linked to patient outcomes, particularly emphasizing the high mortality rate associated with cardiac events, which necessitates monitoring of cardiac function during treatment [3]. - High reports of adverse events related to infections and respiratory issues underline the importance of preventing and controlling infectious diseases during CAR-T therapy [4]. - Cytokine release syndrome and other immune and neurological adverse events are generally associated with a lower mortality rate, suggesting that these events may indicate the effectiveness of CAR-T cell therapy [4]. Group 2: Prognostic Implications of Adverse Events - The research team analyzed the prognostic significance of adverse events across different clinical subgroups, finding that neurotoxicity has opposing prognostic implications depending on the target of the CAR-T cells; for CD19-targeted therapy, neurotoxicity indicates better prognosis, while for BCMA-targeted therapy, it correlates with higher mortality risk [4]. - The study innovatively created a map of adverse events with prognostic significance in CAR-T cell therapy, providing valuable data for safety monitoring and offering new insights for improving treatment outcomes and patient prognosis [4]. Group 3: Research Collaboration and Funding - The study was co-authored by researchers from Shanghai Jiao Tong University School of Medicine, Wenzhou Medical University, and Renji Hospital, indicating a collaborative effort in advancing CAR-T cell therapy research [5]. - The research received funding from the National Natural Science Foundation and the Shanghai Science and Technology Commission, highlighting institutional support for this important work [5].

Core Insights - On November 5, 2025, a total of 26 papers were published in the prestigious journal Nature, with 8 authored by Chinese scholars, highlighting the significant contribution of Chinese researchers to global scientific discourse [2][4][7][9][11][13][15][17]. Group 1: Research Contributions - The paper titled "Adenosine signalling drives antidepressant actions of ketamine and ECT" was co-authored by researchers from Beijing Brain Science and Brain-like Research Institute and the Changchun Institute of Applied Chemistry, focusing on the mechanisms of antidepressant effects [2]. - A study on "Transcriptomic and spatial organization of telencephalic GABAergic neurons" was published by researchers from the Allen Institute for Brain Science, contributing to the understanding of GABAergic neuron organization [4]. - The research "Spatial dynamics of brain development and neuroinflammation" from Yale University explores the interplay between brain development and neuroinflammation [7]. - Another significant paper from the Allen Institute discusses "Continuous cell-type diversification in mouse visual cortex development," shedding light on the diversity of cell types during visual cortex development [9]. - The paper "Fair human-centric image dataset for ethical AI benchmarking" from Sony AI addresses ethical considerations in AI through the development of a new image dataset [11]. - Research on "Vector-stimuli-responsive magnetorheological fibrous materials" from Hong Kong Polytechnic University presents innovative materials with potential applications in various fields [13]. - The study "Targeting FSP1 triggers ferroptosis in lung cancer" from NYU Grossman School of Medicine investigates a novel approach to induce cell death in lung cancer [15]. - A paper titled "Myriad Aryne Derivatives from Carboxylic Acids" from the University of Minnesota discusses the synthesis of various aromatic compounds, contributing to the field of organic chemistry [17].

Core Viewpoint - The article discusses the challenges of postoperative tumor recurrence in cancer treatment and introduces an innovative strategy using engineered dying cancer cells in immunotherapeutic hydrogels to prevent recurrence [2][5][8]. Group 1: Postoperative Challenges - Surgical resection remains the primary treatment for solid tumors, but residual microscopic tumors at surgical margins often lead to recurrence, resulting in poor prognosis and lower overall survival rates [2][5]. - The tumor microenvironment (TME) plays a crucial role in treatment outcomes, and there is evidence that surgical procedures may inadvertently promote tumor spread and alter existing anti-tumor immunity [2][5]. Group 2: Innovative Research Findings - A recent study published in Cell Biomaterials presents a "cancer-treating-cancer" strategy that utilizes immunotherapeutic hydrogels to capture engineered dying cancer cells (DCC) to prevent cancer recurrence [3][5]. - The study demonstrates an in situ sprayable fibrin hydrogel system that combines chemically engineered DCC with the anti-cancer agent β-elemene (ELE) to enhance anti-tumor immune responses and inhibit local tumor recurrence [5][6]. Group 3: Mechanisms of Action - The hydrogel allows for sustained release of DCC and ELE, triggering immune activation through antigen release and immunogenic signals [6]. - β-elemene enhances cytotoxicity and promotes immunogenic cell death, leading to the induction of memory T cells for long-lasting anti-tumor protection [6][8].

Core Insights - The article discusses a groundbreaking research study published in Nature that utilizes AI for the de novo design of antibodies with atomic-level precision, potentially transforming the traditional antibody development process [1][21]. Traditional Antibody Development Challenges - There are over 160 approved antibody drugs globally, with a market value projected to reach $445 billion in the next five years [3]. - The core challenge in antibody development is the rapid acquisition of antibodies that can precisely bind to specific targets [3]. - Traditional methods rely on animal immunization or random library screening, which are time-consuming, costly, and often yield limited success [4]. AI Revolution: RFdiffusion Design - The RFdiffusion AI protein design tool, developed by David Baker's team at the University of Washington, allows for the design of antibodies from scratch [6]. - RFdiffusion2, a specialized version of this tool, was launched in April and is tailored for antibody design [6]. Capabilities of RFdiffusion2 - RFdiffusion2 can design antibodies that target any desired epitope with atomic-level precision [8]. - It focuses on designing the CDR regions, which are critical for antigen recognition, and samples various binding modes between antibodies and targets [8]. Experimental Validation - The research team designed variable heavy chains (VHH) for four disease-related targets, demonstrating that AI-designed antibodies can bind to target sites with nanomolar affinity [11]. - Cryo-electron microscopy confirmed that the binding modes of the designed antibodies closely matched the computational models, with a backbone structure deviation of only 1.45 Å [13]. Advancements in Antibody Design - After successfully designing single-domain antibodies, the team tackled the more complex single-chain variable fragment (scFv) design, which includes six CDRs [15]. - They employed a clever assembly strategy to combine heavy and light chains from different designs, successfully creating specific scFv antibodies [15]. Affinity Maturation - Initial designs had relatively low affinity (micromolar level), but the team improved the affinity by two orders of magnitude using the OrthoRep system, achieving nanomolar to sub-nanomolar levels [18]. - Importantly, cryo-electron microscopy confirmed that the matured antibodies retained the original binding modes and epitope specificity [19]. Revolutionary Medical Implications - This technology could revolutionize the antibody drug development process, shifting from a trial-and-error approach to a precise design-based method [21]. - AI-designed antibodies offer new solutions for targeting difficult disease targets, such as intracellular proteins or specific conformations of membrane proteins [21]. - As the technology matures, AI de novo antibody design is expected to become a standard tool in biomedicine, providing new treatment options for various diseases [22].

Core Viewpoint - The study highlights that adenosine signaling drives the antidepressant effects of ketamine and electroconvulsive therapy (ECT), presenting a potential target for developing scalable non-invasive antidepressant therapies [4]. Group 1: Mechanism of Action - Ketamine and ECT rapidly alleviate symptoms of treatment-resistant depression, but their mechanisms remain unclear, which is crucial for improving treatment precision [5]. - The research team identified adenosine signaling as the core pathway through which these interventions exert their antidepressant effects using mouse models [5]. Group 2: Key Findings - Experiments with genetically encoded adenosine sensors and real-time optical recordings showed that both therapies induce a significant surge in adenosine levels in key emotional regulation brain regions, including the medial prefrontal cortex (mPFC) and hippocampus [6]. - Disruption of A1 and A2A adenosine receptors genetically or pharmacologically eliminates the antidepressant effects of ketamine and ECT, establishing the critical role of adenosine signaling in these effects [6]. Group 3: Implications for Treatment - Adenosine signaling specifically in the mPFC drives the antidepressant effects, with ketamine enhancing adenosine levels through metabolic regulation without causing excessive neuronal activity [8]. - The research team developed ketamine derivatives that enhance adenosine signaling and demonstrate better antidepressant effects with fewer side effects at therapeutic doses [8]. - Acute intermittent hypoxia, a non-drug intervention that lowers oxygen levels, can also increase brain adenosine levels and produce antidepressant effects, similar to ketamine and ECT [8].

Core Insights - The study identifies Mesothelin (MSLN) as a biomarker and potential therapeutic target for bone destruction in rheumatoid arthritis (RA) [4][8] - MSLN levels are significantly elevated in RA patients and collagen-induced arthritis (CIA) animal models, indicating its role in disease pathology [6][9] Group 1: Research Findings - MSLN is involved in various biological processes, particularly in regulating immune responses, but its role in osteoclastogenesis is not well understood [6] - Inhibition of MSLN through pharmacological and genetic methods significantly impairs osteoclast differentiation and bone resorption [6] - Downregulation of MSLN in animal models effectively reduces bone destruction [6] Group 2: Mechanism of Action - MSLN interacts directly with PI3K, leading to the activation of the PI3K/AKT signaling pathway, which promotes the expression and translocation of NFATc1, thereby facilitating osteoclast differentiation [6][9] - MSLN is upregulated in the synovial tissue and plasma of RA patients, driving osteoclast differentiation and mediating pathological bone destruction [9] Group 3: Implications for Treatment - Targeting MSLN may represent a novel therapeutic strategy for addressing bone destruction associated with rheumatoid arthritis [8][9]

Core Viewpoint - The article discusses a recent study published in the journal Cell, revealing that during recovery from catabolic states, the body actively limits protein intake as a protective mechanism against potential harm, challenging traditional views on dietary needs post-illness [3][4][8]. Group 1: Research Findings - The study found that mice recovering from catabolic damage voluntarily restricted protein intake, even at the cost of overall caloric intake [4][10]. - Three specific amino acids—glutamine (Q), lysine (K), and threonine (T)—were identified as necessary and sufficient for the aversion to protein during recovery [4][12]. - The aversion to protein is driven by ammonia production in the gut, which is sensed by enterochromaffin cells through a TRPA1-dependent mechanism, leading to serotonin release that signals the brain to induce anorexia [4][14]. Group 2: Implications for Clinical Nutrition - The findings suggest that the traditional recommendation for high protein intake in recovering patients may be counterproductive and potentially harmful [8][16]. - It is recommended that protein intake should be personalized based on the patient's recovery stage and health status, particularly for those with impaired ammonia detoxification capabilities [16]. - The study emphasizes the importance of understanding the biological mechanisms behind appetite regulation, which could lead to more scientifically grounded rehabilitation nutrition strategies [16].

Core Viewpoint - Urolithin A (UA) is a compound produced from foods rich in ellagitannins, such as pomegranates and raspberries, that activates mitophagy and improves mitochondrial health, showing potential in combating age-related immune decline and inflammation [3][4][7]. Group 1: Research Findings - A study published in Immunity demonstrated that UA can promote the expansion of T memory stem cells (Tscm), providing a rejuvenated immune system that can suppress cancer growth [3]. - A randomized, double-blind, placebo-controlled trial indicated that short-term oral administration of UA (1000 mg daily for 4 weeks) can regulate the composition and function of immune cells, supporting its potential against age-related immune decline [4][7]. - The trial involved 50 healthy middle-aged participants, with results showing that UA increased peripheral initial CD8+ T cells and improved their fatty acid oxidation capacity by 14.72 percentage points [7][8]. Group 2: Immune Cell Changes - UA treatment resulted in changes to the phenotype of CD8+ T cells, indicating a metabolic reprogramming of human immune cells [9][10]. - Enhanced mitochondrial biogenesis and an increase in peripheral blood CD56dim CD16bright NK cells were observed, along with improved TNF secretion and monocyte phagocytosis [11]. - Exploratory single-cell RNA sequencing revealed that UA drives transcriptional changes in immune cell populations, regulating pathways related to inflammation and metabolism [11][12]. Group 3: Overall Implications - Overall, the findings suggest that short-term supplementation of UA can modulate the composition and function of human immune cells, supporting its potential to counteract age-related immune decline and inflammatory aging [13].

以下文章来源于赛业生物订阅号 ，作者小赛 就在几天前（10月31日）， 神舟二十一号载人飞船携4只特殊的"小鼠航天员"出征太空 ——这是我国首次 在空间站开展啮齿类哺乳动物饲养实验，为人类长期太空生存研究探路。小鼠能顺利出差的背后，其实离不 开从地面到太空的全链条饲养技术支撑：转棒测试抗眩晕、迷宫挑战空间识别，堪比人类航天员的体能考 核；空间站里，气密隔离设计、微重力饲料供应系统，每一处都精准匹配小鼠的生物习性。 太空饲养的精细要求，恰恰印证了大小鼠饲养的核心逻辑：无论是地面实验室还是太空舱，读懂生物习性、 把控环境细节，都是保障实验价值的关键，甚至决定了整个研究项目的推进效率。然而， 多数实验室在实际 饲养管理中，常面临"痛点分散、低效摸索"的困境： ➢前期规划准备缺乏系统性： SPF 级饲养环境如何校准？笼具垫料等如何选择？ 赛业生物订阅号 . 分享生命科学领域的前沿资讯、解读行业动态、讲解实用的学科知识、实验方法和技巧。 ➢日常操作无统一标准： 不同阶段小鼠是否要调整垫料更换频率？饲料储存条件怎么设置更合适？ ➢饲养过程应急响应不足： 突发小鼠拒食、活动异常等问题如何处理？有没有快速排查流程与处置方案？ ...