Core Insights - An international research team has identified specific gene variations closely associated with high-risk groups for cardiovascular events, which may enhance early screening and personalized prevention of cardiovascular diseases [1][2] Group 1: Research Findings - The study reveals that atherosclerosis, a chronic cardiovascular disease characterized by thickening and hardening of blood vessel walls due to lipid deposits, is often undetected until severe events like myocardial infarction or stroke occur [1] - Researchers have categorized populations into four distinct risk levels for atherosclerosis, with varying probabilities of experiencing cardiovascular events [1] - A particular variant of the IL6R gene has been identified as significantly increasing the likelihood of myocardial infarction in high-risk groups, despite having limited impact on the general population [1] Group 2: Implications for Treatment - Identifying these genetic markers is crucial for developing personalized intervention strategies, allowing for early intervention during asymptomatic stages to potentially halt or reverse the progression of atherosclerosis [2] - The research has been published in the international journal "Cardiovascular Research," and future evaluations will focus on whether drugs targeting the IL6R gene pathway can reverse rapid atherosclerosis progression in specific populations [2]

Core Viewpoint - The research published by Harvard University provides a comprehensive understanding of the developmental transitions of Plasmodium falciparum within Anopheles mosquitoes, revealing critical molecular interactions that could lead to new targets for malaria transmission-blocking vaccines and drugs [2][11]. Group 1: Research Findings - The study utilized dual-channel single-cell RNA sequencing to map the complex interactions between the malaria parasite and the mosquito host, highlighting key developmental stages [2][9]. - It identified crucial molecular transformations during the transition from motile ookinetes to spherical oocysts and the subsequent formation of sporozoites [9]. - The research pinpointed two essential genes, PfATP4 and PfLRS, that are vital for oocyst growth, with their inhibition completely blocking the parasite's development within the mosquito [9][11]. Group 2: Molecular Mechanisms - The study confirmed that the transcription factor PfSIP2 is a critical switch for sporozoite infection of human liver cells, presenting a potential target for blocking malaria transmission [9][10]. - It was found that ookinetes preferentially interact with intestinal progenitor cells during their traversal of the midgut epithelium, which serves as a localization signal for their transformation [9]. - In the later developmental stages, oocysts are tightly wrapped by surrounding midgut muscle fibers, which may help maintain gut integrity and support oocyst fixation [9]. Group 3: Implications for Malaria Control - The research constructs the first panoramic molecular map of the Plasmodium-mosquito interaction, providing new targets for the development of precise transmission-blocking vaccines and drugs [11].

Core Viewpoint - The research reveals a novel metabolic interaction between tumor-associated macrophages (TAM) and hepatocellular carcinoma (HCC) cells, identifying TAM as a source of acetate that drives HCC metastasis through the synthesis of acetyl-CoA [2][3][4]. Group 1: Research Findings - TAM secretes acetate, which is then taken up by HCC cells to support their acetate accumulation [3]. - Lactate produced by HCC cells activates lipid peroxidation-ALDH2 pathways in TAM, promoting the secretion of acetate [3]. - In a mouse model of HCC, knocking out the ALDH2 gene in TAM reduces acetate levels in HCC cells and decreases lung metastasis of HCC [3][4]. Group 2: Implications - The study positions TAM as a critical acetate supply source that drives HCC metastasis, suggesting potential intervention targets in the tumor microenvironment [2][4].

Core Insights - The study reveals the molecular mechanisms by which the JAK2 V617F mutation leads to two different types of myeloproliferative neoplasms (MPN), essential thrombocythemia (ET) and polycythemia vera (PV) [3][4] - The research highlights the significance of different mutation types in determining disease progression, with heterozygous mutations in ET and homozygous mutations in PV [6] - The findings suggest a potential new therapeutic target for ET treatment through AhR inhibition, which shows better specificity and safety compared to existing therapies [8] Group 1: Research Findings - JAK2 V617F mutation is present in over 50% of ET patients and more than 90% of PV patients, indicating its critical role in these diseases [3] - In ET patients, the mutation primarily exists as a heterozygous form, activating the STAT1 – AhR – RUNX1 signaling axis, leading to increased platelet production [6] - In PV patients, the mutation is mostly homozygous, activating the STAT5 signaling pathway, which drives red cell differentiation [6] Group 2: Clinical Implications - The study constructed a humanized JAK2 V617F ET mouse model, demonstrating that AhR inhibition effectively reduces excessive platelet production without affecting other myeloid cells [6] - Ongoing clinical trials on AhR inhibitors in cancer immunotherapy provide a foundation for their rapid application in ET treatment [8] - The research not only addresses a long-standing scientific puzzle but also identifies a new potential target for ET therapy, offering a safer and more sustainable treatment option for patients requiring lifelong management [8]

Core Insights - Researchers at Cambridge University have developed "blood-like cells" using human stem cells, which can simulate multiple key stages of early human development, including the generation of blood stem cells [1][2] - The new human embryo-like model accurately replicates the initiation of the hematopoietic system in embryos, providing a powerful tool for drug screening, early blood and immune system development research, and modeling blood diseases [2] Group 1 - The embryo-like structures exhibit self-organization capabilities, forming the three primary germ layers (ectoderm, mesoderm, and endoderm) by the second day of culture [1] - By day eight, beating heart cells were observed, which in real embryos will eventually develop into the heart [1] - On day thirteen, distinct red blood spots were noted, confirming the generation of functional blood cells, which can differentiate into various blood cell types, including key immune cells [1] Group 2 - The ability to produce human blood cells in the laboratory marks a significant step in regenerative medicine, allowing for the potential creation of blood cells that are genetically matched to patients, thus avoiding immune rejection [2] - The model captures the "second wave" of hematopoiesis during human development, which can produce adaptive lymphocytes, including T cells, opening new avenues for studying blood development in both healthy and cancerous states [2]

Core Insights - The study indicates that gut microbiota can predict the efficacy of consolidation immunotherapy and chemoradiotherapy toxicity in lung cancer patients [3][9] - The research highlights the dynamic changes in gut microbiota during treatment and its correlation with progression-free survival (PFS) and treatment-related lung toxicity [5][6] Group 1: Research Findings - The research team utilized 16S rRNA sequencing to track the dynamic changes in gut microbiota of stage III lung cancer patients undergoing concurrent chemoradiotherapy (CRT) and consolidation immune checkpoint inhibitors (ICI) [5] - In traditional CRT, the composition of gut microbiota remained unaffected, whereas in CRT combined with ICI, patients with longer PFS exhibited higher baseline gut microbiota diversity, which decreased during treatment [6][9] - The abundance of Akkermansia muciniphila (Akk) increased post-chemoradiotherapy, correlating with extended distant metastasis-free survival in patients receiving CRT combined with ICI [6][10] Group 2: Clinical Implications - The study suggests that the overall clinical benefit of CRT combined with ICI is significantly greater compared to CRT alone for locally advanced lung cancer patients [9] - The dynamic changes in Akkermansia muciniphila serve as a potential prognostic indicator for patient survival outcomes [10] - Distinct gut microbiota characteristics were observed in patients who developed severe lung toxicity post-treatment, indicating a possible predictive marker for treatment-related pneumonia [6][10]

Core Viewpoint - The research published by a team from China Pharmaceutical University reveals a novel brain-liver neurocircuit involving VMH Galnt2 neurons that counterregulate hypoglycemia by increasing hepatic glucose production, providing new insights into the mechanisms of hypoglycemia resistance and potential innovative treatment strategies for metabolic diseases related to glucose regulation [3][7]. Summary by Sections Research Findings - The study identifies a biphasic pattern of glucose dynamics in the blood and hypothalamus during prolonged fasting, highlighting an additional threshold-dependent counterregulatory mechanism [4]. - This mechanism is mediated by a neural pathway from the ventromedial hypothalamus (VMH) to the paraventricular nucleus (PVH), then to the lateral paragigantocellular nucleus (LPGi), and finally to the liver, which detects neuroglycopenic states and activates sympathetic signals to drive hepatic glucose production [4]. Key Highlights - The biphasic model explains the counterregulatory response to hypoglycemia [5]. - VMH glucose-inhibitory neurons play a critical functional role in sensing neuroglycopenia [5]. - The brain-liver neural circuit emphasizes the counterregulatory response to hypoglycemia [5]. - Galnt2 serves as both a genetic marker and a molecular brake for VMH glucose-inhibitory neurons, regulating the glucose sensing threshold and metabolic homeostasis [5]. Implications - The study underscores a brain-liver neural pathway originating from VMH Galnt2 neurons that can sense and counterregulate hypoglycemia, potentially guiding the development of innovative treatment strategies for metabolic diseases characterized by abnormal glucose regulation [7].

Core Insights - The research highlights the role of astrocytic Ca2+ signaling as a "gatekeeper" in preventing synaptic depotentiation during motor learning, significantly altering the understanding of astrocytes' function in synaptic strength maintenance and optimization [4][8]. Group 1: Mechanisms of Motor Learning - Motor learning involves the dynamic adjustment of synaptic strength, where synaptic potentiation is crucial for memory and skill formation, while synaptic depotentiation must be regulated to retain newly acquired skills [3][6]. - The study found that motor training induces synaptic potentiation in layer 5 pyramidal neurons of the mouse motor cortex, accompanied by an increase in astrocytic Ca2+ levels [6][7]. Group 2: Role of Astrocytes - Astrocytic Ca2+ activity regulates activity-dependent synaptic plasticity, and its role in learning-related synaptic changes in vivo remains unclear [6]. - Reducing astrocytic Ca2+ levels leads to synaptic depotentiation during motor training, impairing improvements in motor performance [6][7]. Group 3: Implications for Medical Research - The findings suggest potential therapeutic avenues targeting astrocytic signaling pathways for treating conditions like stroke, neurodegenerative diseases, or motor function disorders by modulating astrocytic Ca2+ or adenosine receptor activity [7][8]. - The study emphasizes the complexity and significance of glial cell interactions in functional brain plasticity, marking an exciting new chapter in neuroscience discoveries [8].

编辑丨王多鱼 排版丨水成文 近年来， 以 肥 胖 和 2 型糖尿病 为代表的 内分泌代谢系统疾病已成为严重威胁 人类 健康的重大公共卫生 问题。《 柳叶刀 》的一项研究指出， 2022 年全球肥胖人口已突破 10 亿，占全球总人口的八分之一，且 这一趋势仍在持续上升。肥胖不仅显著增加个体罹患心血管疾病、癌症等多种重大疾病的风险，也给公共 卫生体系带来了沉重负担。 2 型糖尿病在全球范围内 也 呈持续攀升趋势。国际糖尿病联盟 （ IDF ） 数据 显示， 2021 年全球 20–79 岁的成年人中约有 5.89 亿人患糖尿病，占全球成人总数约 10.5% ，预计到 2045 年患者将增至约 7.8 亿人，占比超过 12% ，这意味着几乎每 9 名成年人中就有 1 人受累，其中大 部分为 2 型糖尿病。 随着全球老龄化、城市化、久坐生活方式以及高热量饮食的普及，未来几十年， 2 型糖尿病的患病率还将 持续上升，并将带来更大的心血管、肾脏、神经及眼底疾病负担 。 内分泌代谢系统疾病迫切需要依托大规 模人群遗传学获取高质量证据，识别可用于预防、早筛与精准干预的新分子靶点。 2025 年 10 月 10 日 ，昌平实验 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 肾细胞癌 （RCC） 是泌尿系统常见的恶性肿瘤，其确切病因仍有待探究。 肾透明细胞癌 （ccRCC） 是肾细胞癌最常见的病理类型，约占 70%。 越来越多的证据表明，作为人体关键组成部分的 肠道微生物群 在肿瘤发生以及对治疗的响应方面具有重要影响。尽管已有研究显示某些肠道微生物及其相关活性 产物与 ccRCC 的治疗有关，但肠道微生物组与 ccRCC 形成之间的关系仍不确定。因此，阐明肠道微生物组对 ccRCC 肿瘤进展的潜在影响至关重要。 2025 年 10 月 8 日，上海交通大学医学院附属 仁济医院 翟炜 研究员、上海交通大学医学院 刘尽尧 研究员团队合作，在 Cell 子刊 Cell Reports Medicine 上发 表了题为： Intestinal Lachnospiraceae bacterium -derived propionate inhibits the progression of clear cell renal cell carcinoma 的研究论文。 该研究表明，肠道细菌 Lachnospiraceae bacterium （ L. ...