Core Viewpoint - The article discusses the development of a robust computational framework called MAPLE for predicting methylation age and disease risk, which addresses the limitations of traditional epigenetic clocks and has significant potential for clinical applications in aging and health management [3][4][26]. Group 1: Background and Need for MAPLE - Aging is characterized by increased morbidity and declining quality of life, creating significant social and economic burdens [2]. - Breakthrough research indicates that interventions like caloric restriction and epigenetic reprogramming can extend lifespan and healthspan, but precise quantification of biological age and aging rate is necessary for clinical application [2]. - DNA methylation (DNAm) changes are key markers of aging, with whole-genome DNAm serving as a potential biological age assessment tool [2]. Group 2: MAPLE Development and Performance - MAPLE employs pairwise learning to determine the relative relationship between two DNA methylation profiles regarding age or disease risk, effectively reducing technical biases while identifying biological signals related to aging or disease [4][9]. - In 31 benchmark tests, MAPLE achieved a median absolute error of 1.6 years, outperforming five other competitive methods [4][12]. - MAPLE demonstrated excellent performance in disease risk assessment, with an average area under the curve (AUC) of 0.97 for disease identification and 0.85 for pre-disease state detection [4][19]. Group 3: Advantages of MAPLE - Traditional epigenetic clocks face challenges such as batch effects, which significantly hinder their clinical application [7][26]. - MAPLE's innovative approach focuses on relative relationships rather than absolute predictions, allowing for better comparability across diverse datasets [9][26]. - The two-stage training process of MAPLE enhances sample size and reduces overfitting risks, contributing to its superior performance [9][12]. Group 4: Clinical Applications and Future Prospects - MAPLE not only accurately predicts biological age but also serves as a health risk warning system, providing valuable time for early intervention [20][28]. - The framework is expected to play a crucial role in personalized anti-aging interventions, early disease risk screening, and understanding the biological mechanisms of aging [28]. - As MAPLE continues to be validated, it may become a standard component of health assessments, aiding in the management of healthy aging and offering new hope for age-related health challenges [28].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 科学文献正在呈现指数级增长，在各学科领域都带来了日益严峻的挑战。每年都有数十万种新的化学反应被报道，然而，将它们转化为可操作的实验却成了一个 障碍。 化学家的困境：信息海洋中的摸索 随着科学文献的爆炸式增长，化学领域研究人员正面临前所未有的挑战。每年有数十万个新的化学反应被报道，但将这些知识转化为实验室中的可行方案，仍严 重依赖专家的个人经验与耗时的手动检索， 这种传统方法效率低下且难以规模化。 近期， 大语言模型 （LLM） 的应用展现出了一定的前景，但能够可靠地对各种新化合物进行多样转化的 AI 系统，仍难以实现。 2 026 年 1 月 19 日，耶鲁大学的研究人员在国际顶尖学术期刊 Nature 上发表了 题为： Collective intelligence for AI-assisted chemical synthesis 的研究论 文。 该研究开发了一个名为 MOSAIC 的 AI 系统，它能够 生成 带有置信度指标、可重复且可直接执行的 复杂化学合成实验方案 。在实验验证中，这一 AI 系统取得 了 71% 的整体成功率，实现了超过 35 种新化合物的 ...

Core Viewpoint - Fasting-mimicking diet (FMD) shows potential benefits in inducing clinical response, remission, and biochemical improvement in patients with mild to moderate Crohn's disease, outperforming standard dietary support [3][8]. Group 1: Fasting-Mimicking Diet (FMD) - FMD involves a 5-day low-calorie diet each month, designed to mimic fasting while ensuring essential nutrient intake, making it easier for individuals to adhere to [2]. - The study published in Nature Medicine indicates that FMD can significantly reduce inflammation and improve metabolic health in healthy individuals, but its effects on Crohn's disease were previously unstudied [7]. Group 2: Clinical Trial Findings - In a randomized controlled trial, 69.2% of patients in the FMD group achieved the primary outcome of a 70-point reduction in Crohn's Disease Activity Index (CDAI) compared to 43.8% in the control group [7]. - Secondary outcomes showed that 64.6% of the FMD group reached clinical remission, while only 37.5% of the control group did [7]. - FMD group exhibited a 22.0% decrease in fecal calprotectin levels, an inflammation marker, while the control group saw an 8.0% increase [7]. Group 3: Mechanistic Insights - Exploratory analyses revealed that FMD led to reductions in key inflammatory lipid mediators and immune response transcripts, correlating with decreased Crohn's disease activity [8].

Core Viewpoint - The emergence of GLP-1 receptor agonists, such as semaglutide and tirzepatide, has transformed obesity treatment, enabling rapid weight loss of 15%-20%. However, approximately 50% of obese patients discontinue these medications within a year, leading to significant weight regain and the need to understand post-medication weight changes [6][10]. Research Background: Current Status and Challenges in Obesity Treatment - Nearly 2 billion adults globally are affected by overweight or obesity, which significantly increases the risk of various complications and premature death. Behavioral weight management programs (BWMP) have traditionally been the cornerstone of obesity treatment, focusing on low-calorie diets and increased physical activity. The introduction of new weight loss medications is changing the treatment landscape [6][5]. Research Methodology: Rigorous Evidence Synthesis - The research team systematically reviewed seven databases and trial registries, including 37 studies with 9,341 participants. The average treatment duration was 39 weeks, with an average follow-up of 32 weeks post-medication. Various weight loss medications were analyzed, focusing on both weight changes and cardiovascular metabolic markers [8][7]. Key Findings: Dual Regain of Weight and Health Indicators - On average, participants lost 8.3 kg during medication use, but weight began to rebound post-discontinuation at a rate of 0.4 kg per month, leading to a full return to baseline weight in approximately 1.7 years. Newer medications like semaglutide and tirzepatide showed even faster rebound rates of 0.8 kg per month, returning to baseline in about 1.5 years. Cardiovascular metabolic benefits also diminished within 1.4 years after stopping medication [10][4]. Comparative Analysis: Differences Between Medication and Behavioral Interventions - While medication resulted in a greater average weight loss of 3.2 kg, the rebound rate was significantly faster compared to behavioral interventions, which had a rebound rate of only 0.1 kg per month, taking about 3.9 years to return to baseline weight. This indicates that behavioral interventions may equip participants with sustainable weight management skills, unlike medication, which primarily reduces hunger and increases satiety [12][14]. Insights and Recommendations: Rational Perspective on Weight Loss Medications - The research emphasizes that obesity is a chronic relapsing disease that may require long-term treatment for sustained health benefits. Evidence suggests that continuous use of semaglutide for four years can successfully maintain weight loss. Given the high discontinuation rates of weight loss medications, it is crucial to recognize that these drugs alone may not suffice for long-term weight control. Sustainable healthy lifestyle changes remain fundamental in obesity prevention and treatment [15][16].

2026 年 1 月 16 日， 德克萨斯大学 MD 安德森癌症中心和意大利 Nouscom 公司的研究人员合作，在 Nature Medicine 期刊发表了题为 ： Nous-209 neoantigen vaccine for cancer prevention in Lynch syndrome carriers: a phase 1b/2 trial 的临床研究论文。 该论文公布了 Nous-209 新抗原疫苗用于林奇综合征携带者癌症拦截的 1b/2 期临床试验数据，证实了 Nous-209 在林奇综合征中的安全性以及有效刺激对新抗 原的免疫力的能力，支持其用于癌症拦截的开发。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 林奇综合征 （ Lynch Syndrome， LS） 是遗传性癌症综合征中最为常见的类型之一，约每 300 人中就有 1 人患病。患有林奇综合征的人携带四个 DNA 错配修 复 （MMR） 基因 （ MLH1 、 MSH2/EPCAM 、 MSH6 和 PMS2 ） 中的一个 杂合生殖系突变 ，这 使他们一生中患结直肠癌的风险为 50%-80%，患子宫 内膜癌的风险为 40%-60% ...

Core Viewpoint - The study highlights that Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) accelerates the progression and metastasis of Pancreatic Ductal Adenocarcinoma (PDAC) through the macrophage migration inhibitory factor-CD44 axis [5][8]. Group 1: Research Findings - MASLD significantly increases the overall risk of PDAC, with a risk ratio of 3.48 observed in the population with MASLD [7]. - A strong correlation between MASLD and liver metastasis was confirmed in clinical cohort studies, with an odds ratio of 7.06 [7]. - Experimental mouse models demonstrated that MASLD enhances tumor cell stemness, immune evasion, and the formation of cell adhesion plaques in metastatic liver tissue [7]. Group 2: Mechanism and Implications - MASLD-induced MIF secretion promotes the migration, stemness, and adhesion of CD44-positive PDAC cells [8]. - Targeting MIF through genetic means or using the MIF isomerase inhibitor IPG1576 significantly reduced liver metastasis in preclinical models [8]. - The study emphasizes the MIF-CD44 signaling axis as a promising therapeutic target and the importance of developing personalized treatment plans for PDAC patients with concurrent MASLD [8].

2026 年 1 月 19 日， 中国科学院深圳先进技术研究院 钟超 / 安柏霖 团队联合 深圳大学医学部 黄鹏 团队，在 Nature Biotechnology 期刊发表了题为： Engineered living glues secrete therapeutic proteins for treatment of inflammatory bowel disease 的研究论文。 该研究设计了一种 可由病理环境直接驱动的" 智能活胶水 " ，为 炎症性肠病 （IBD） 的精准干预提供了全新思路。这种由基因编码、自主响应疾病信号的智能 活胶水体系，可在肠道出血病灶处原位发生 生物黏附 并持续发挥治疗作用，阐明了工程化活体材料通过疾病信号驱动，实现精准定位与长期治疗的新策略。 编辑丨王多鱼 排版丨水成文 炎症性肠病 （ Inflammatory Bowel Disease ， IBD ） 是一类以肠道慢性炎症、黏膜反复损伤和出血为特征的疾病。现有临床治疗主要依赖糖皮质激素、免疫抑 制剂和生物制剂，虽可在一定程度上缓解炎症，但往往难以实现病灶的精准定位与持续修复，且长期使用易出现副作用或疗效衰减。 因此，开 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 心理压力 （ Psychological Stress ） 与 肝脏疾病 的关联日益受到关注，但其潜在机制尚不明确。 2026 年 1 月 16 日，山东大学齐鲁医学院 梁晓红 教授团队在 Nature 子刊 Nature Metabolism 上发表了题为： Chronic stress drives liver cancer by impairing the hepatic kynurenine pathway and immune surveillance 的研究论文。 该研究表明， 慢性压力 通过损害肝脏的 犬尿氨酸代谢途径 和 免疫监视 而驱动 肝癌 ，该研究揭示了肝脏中存在着将 神经系统与免疫监视联系起来的 应激压力 响应的代谢检查点，其可作为肝癌治疗的新靶点。 在这项最新研究中，研究团队发现， 慢性压力 会破坏 脑-肝神经环路 ，导致肝脏 CD8 + T 细胞免疫功能受损，进而加速肝癌进展。 通过使用雄性小鼠的致癌基因驱动的肝癌模型和致癌物诱导的肝癌模型，研究团队发现，心理压力会干扰儿茶酚胺/β2-肾上腺素能受体 （ADRB2） 信号通路， 从而抑制肝细胞 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 新陈代谢是生物学的一个重要组成部分，通过 RNA 的转录和翻译过程实现快速且广泛的重编程。代谢还控制着负责可逆 RNA 修饰 （例如 m 6 A） 的酶的活 性。 m 6 A 是高等真核生物中 mRNA 上最常见的内部修饰。m 6 A 具有广泛的影响，已被证明参与 RNA 稳定性、剪接和翻译的调控，而 m 6 A 的失调则与多种发育 疾病以及癌症的发展密切相关。m 6 A 修饰由 METTL3–METTL14 复合物催化，这是一种 S-腺苷甲硫氨酸 （SAM） 依赖的 RNA 甲基转移酶。FTO 作为首个 RNA 去甲基化酶的发现，则突显了 m 6 A 修饰的可逆性和动态性。 代谢在影响表观遗传学和细胞命运决定方面发挥着重要作用。然而，代谢酶和代谢物以及它们在 RNA 表观遗传学中的调控机制，目前仍不清楚。 然而，甲硫氨酸代谢是否涉及独立于 S-腺苷甲硫氨酸 （SAM） 的表观遗传机制，以及此类机制在肿瘤发生中发挥何种作用，目前仍不清楚。 在这项最新研究中，研究团队发现， 腺苷高半胱氨酸酶 （Adenosylhomocysteinase，AHCY） - 腺苷 （ADO） ...

Core Viewpoint - The study indicates that vegetarian diets, particularly strict vegan diets, are negatively correlated with the likelihood of becoming centenarians among Chinese adults aged 80 and older, with vegetarians having a 19% lower chance and vegans a 29% lower chance compared to omnivores [2][6]. Study Design and Methodology - The research is a nested case-control study involving 5,203 participants aged 80 and above from a nationwide survey initiated in 1998, categorizing them into omnivores and vegetarians, with further subdivisions into pescatarians, lacto-ovo vegetarians, and strict vegans [4]. - The primary outcome measured was the likelihood of reaching 100 years of age by the end of the follow-up in 2018, using multivariable unconditional logistic regression for association analysis [4]. Key Findings - A total of 1,459 centenarians were identified and matched with 3,744 non-centenarians, revealing that vegetarians had a lower likelihood of becoming centenarians (OR=0.81), with strict vegans showing an even lower likelihood (OR=0.71) [5]. - No significant association was found for pescatarians (OR=0.84) and lacto-ovo vegetarians (OR=0.86) regarding centenarian status [5]. - Significant associations were observed in individuals with a BMI < 18.5 kg/m² (OR=0.72), while no significant association was noted in those with a BMI ≥ 18.5 kg/m² (OR=0.92) [5]. Implications - The results suggest that a vegetarian diet, especially a strict vegan diet, is associated with a reduced likelihood of reaching 100 years of age, emphasizing the importance of a balanced and high-quality diet that includes both animal and plant-based food components for longevity, particularly in underweight elderly individuals [6]. - It is recommended that vegetarians consider incorporating fish, eggs, and dairy products to prevent nutritional imbalances and the negative impacts of low body weight on long-term survival [6].