Core Insights - Alcohol Use Disorder (AUD) and its severe complications, particularly Alcohol-Related Liver Disease (ALD), pose significant global health challenges, with ALD being a leading cause of liver transplants and impacting mortality rates worldwide [3] - The gut-liver axis plays a crucial role in the pathogenesis of ALD, relying on the translocation of microbes from the gut to the liver, although the specific mechanisms remain poorly understood [3] Group 1: Research Findings - A study published in Nature reveals that chronic alcohol consumption suppresses the expression of mAChR4 in the small intestine, reducing the formation of Goblet Cell Antigen Pathways (GAP) and impairing antimicrobial immunity [4][7] - Activation of IL6ST can reverse this suppression, restoring mAChR4 expression and GAP formation, thereby reducing microbial translocation to the liver and conferring resistance to ALD [4][8] - The mAChR4-IL6ST-ILC3-IL-22 signaling axis is identified as a key mechanism in the immune interactions within the gut-liver axis, challenging traditional views on the pathogenesis of ALD [8][9] Group 2: Therapeutic Implications - Direct activation of mAChR4 in goblet cells is sufficient to prevent alcohol-induced liver pathology, suggesting that targeting mAChR4 agonists could enhance mucosal immunity in individuals at risk for ALD [9][10] - Modulating IL6ST signaling emerges as a viable strategy to restore gut barrier integrity and reinitiate antimicrobial defenses, offering a dual approach to immunotherapy for ALD [9][10] - The study's implications extend beyond ALD, highlighting the role of GAP in maintaining epithelial and immune homeostasis, prompting further exploration in other gut-related diseases characterized by dysbiosis and barrier dysfunction [9][10]

Core Insights - The article discusses the promising potential of genetically engineered natural killer (NK) cell therapies for cancer treatment, emphasizing the need for targeted gene editing to enhance therapeutic efficacy [2][4]. Group 1: Research Findings - A recent study published in Cancer Cell identified critical targets to enhance CAR-NK cell antitumor potency through genome-wide CRISPR screens, specifically highlighting MED12, ARIH2, and CCNC as key genetic targets [2][5]. - The study demonstrated that knocking out MED12, ARIH2, and CCNC significantly improved NK cell antitumor activity against various refractory human cancers in both in vitro and in vivo experiments [5][6]. - The research revealed that CRISPR editing enhanced both the inherent and CAR-mediated functions of NK cells, correlating with increased metabolic adaptability, elevated pro-inflammatory cytokine secretion, and the expansion of cytotoxic NK cell subpopulations [6][7]. Group 2: Implications for Future Therapies - The findings provide valuable resources for developing next-generation NK cell therapies with superior efficacy against cancer [6][7]. - The study's orthogonal screening approach identified targets to overcome NK cell functional impairments within the tumor microenvironment, which is crucial for improving treatment outcomes, especially in solid tumors [4][7]. - Simultaneous knockout of ARIH2 and CCNC in CAR-NK cells was shown to enhance in vivo antitumor efficacy, indicating a strategic approach for future therapeutic applications [7].

Core Viewpoint - The article discusses the development of a nanomedicine (EM-eNM) that engages energy metabolism to maintain mitochondrial homeostasis, alleviate cellular aging, and reverse age-related diseases [4][10]. Group 1: Research Background - Mesenchymal stem cells (MSC) play a crucial role in maintaining balance and promoting tissue repair, but aging impairs their function and regenerative capacity, leading to age-related diseases like osteoporosis [2]. - Mitochondrial dysfunction is a significant feature of aging MSC, characterized by mitochondrial homeostasis disruption, including impaired mitophagy and accumulation of dysfunctional mitochondria [2][9]. Group 2: Nanomedicine Development - The research team developed EM-eNM based on the structure and function of ATP synthase, a key enzyme in energy generation, to restore vitality in aging MSC and prevent skeletal aging [7]. - EM-eNM can penetrate the mitochondria of aging bone marrow MSC, promoting mitochondrial fission, mitophagy, and glycolysis, thereby maintaining the stemness and pluripotency of BMMSC [9]. Group 3: Therapeutic Potential - Systemic administration of EM-eNM via tail vein injection selectively targets bone tissue, significantly reversing osteoporosis-related bone loss in aged mice while restoring the stemness and osteogenic potential of BMMSC in situ [9]. - The study highlights the potential of EM-eNM as a targeted therapy for alleviating cellular aging and age-related diseases [10].

Core Viewpoint - The study reveals that the oligomerization of Shank3 regulates the material properties of postsynaptic density (PSD) condensates, which are crucial for synaptic plasticity and neuronal functions related to learning and memory [3][5][7]. Summary by Sections - The research team from Southern University of Science and Technology published findings indicating that PSD condensates exhibit soft-glass-like properties, with Shank3 protein oligomerization playing a key role in governing these material characteristics [3][5]. - The study found that the reconstructed PSD condensates formed a soft-glass material without signs of irreversible amyloid-like structures. This glass-like formation relies on specific, multivalent interactions among scaffold proteins, which mediate the network flow of PSD proteins [4]. - Disruption of Shank3's SAM domain-mediated oligomerization, observed in patients with Phelan-McDermid syndrome, leads to a softening of PSD condensates, impairing synaptic transmission and plasticity, and resulting in autism-like behaviors in mice [4][5]. - Overall, the research emphasizes the importance of the material properties of PSD condensates in neuronal synaptic functions related to learning and memory [7].

Core Viewpoint - The article discusses the groundbreaking Stereo-cell technology in single-cell sequencing, which overcomes the limitations of traditional methods by enabling multi-modal integration, real-time monitoring, and high-throughput capabilities, thus providing a comprehensive understanding of cellular characteristics and dynamics [4][20]. Group 1: Technology Breakthroughs - Stereo-cell technology achieves multi-modal integration, allowing for the simultaneous capture of cellular morphology, transcriptomics, and protein characteristics, akin to taking a "3D photo" of cells [12][13]. - The technology utilizes high-density DNA nanoball arrays, enabling unbiased capture of hundreds to millions of cells without the physical limitations of traditional methods, thus ensuring accurate identification of rare cell populations [11][9]. - Stereo-cell supports in-situ dynamic monitoring of cells, capturing gene transcription activity changes and spatial-temporal information, which expands the boundaries of single-cell research [15][19]. Group 2: Collaborative Initiatives - The establishment of the "10 Billion Cells Alliance" aims to create a comprehensive cell atlas and decode the underlying principles of life, driving innovation in life sciences from data accumulation to intelligent technology applications [4][20]. - The technology is expected to significantly impact clinical molecular medicine, providing new avenues for patient care and treatment through enhanced cellular analysis [20][21]. Group 3: Future Prospects - Stereo-cell is positioned as a next-generation life data engine, with plans to develop a "three major cell universe database" encompassing life maps, disease maps, and disturbance response maps, inviting global research teams to collaborate [20][22]. - The technology is anticipated to facilitate a transition from billions to trillions of cells in analysis, enabling a comprehensive understanding of cellular fates and functions throughout life [20].

Core Viewpoint - Acute Aortic Syndrome (AAS) remains a severe cardiovascular emergency with a high mortality rate, necessitating rapid and accurate diagnosis to improve patient outcomes [3][4][7] Group 1: AAS Overview - AAS has a mortality rate of approximately 40%-50% within 48 hours of onset, with an hourly increase of 1%-2% if untreated [3] - Clinical symptoms of AAS are often non-specific and variable, complicating timely diagnosis [3][4] - Traditional imaging methods like CTA are costly and have associated risks, while the actual incidence of AAS in patients undergoing CTA is only 2.7% [3][4] Group 2: AI-Based Diagnosis - Alibaba's Damo Academy developed an AI-based warning system called iAorta, which utilizes non-contrast CT scans to identify AAS with high accuracy [5][8] - iAorta demonstrated an area under the curve (AUC) of 0.958 in a multi-center retrospective study and showed sensitivity of 0.913-0.942 and specificity of 0.991-0.993 in large-scale real-world studies [10][20] - The AI system significantly reduced the time for correct diagnosis from an average of 219.7 minutes to 61.6 minutes [10] Group 3: Real-World Applications - iAorta has been tested in various hospitals, successfully identifying AAS in patients who were misdiagnosed or refused further testing [15][19] - In a pilot at Shanghai Chang Hai Hospital, iAorta accurately identified 21 out of 22 AAS patients, with an average diagnosis time of 102.1 minutes [19][20] - The AI system enhances diagnostic accuracy for doctors of all experience levels, with significant improvements noted in interns and general practitioners [20][23] Group 4: Conclusion - The integration of AI in diagnosing AAS represents a significant advancement in emergency medicine, potentially saving lives by preventing diagnostic delays and errors [24][23]

Core Viewpoint - The article discusses the development of a biomimetic nanoimmunotherapy that induces PANoptosis to reshape the desmoplastic tumor microenvironment, enhancing anti-tumor immunity and reducing recurrence risk while inhibiting metastasis [3][8]. Group 1: Challenges in Cancer Immunotherapy - Dendritic cell (DC)-based vaccines face significant challenges in solid tumors, including the lack of tumor-specific antigens and the immunosuppressive stroma present in these tumors [5][6]. - Traditional DC vaccines have limited clinical success due to issues such as antigen degradation and immune tolerance, prompting the exploration of hybrid cells formed by fusing DCs with tumor cells [5][6]. Group 2: Innovative Approaches - The study introduces a therapeutic nano-vaccine, UCNP@MOF@MI@FM (UMMF), which combines dendritic cell and tumor hybrid cell membranes, co-loaded with MTH1 inhibitors and tetrahydrobiopterin (BH4) [6][7]. - This platform aims to induce immunogenic cell death (ICD) through PANoptosis, enhancing the activation of cytotoxic T lymphocytes (CTLs) and reprogramming the tumor microenvironment [6][7]. Group 3: Key Findings - The biomimetic nano-vaccine triggers reactive oxygen species (ROS)-induced immunogenic PANoptosis in a spatiotemporal manner [8]. - Near-infrared (NIR) light programming therapy is effective in reshaping the immunosuppressive tumor microenvironment [8]. - The synergistic effect of BH4 with the UMMF nano-vaccine can combat immune therapy resistance [8].

Core Viewpoint - Springer Nature offers a comprehensive portfolio of open access (OA) journals, providing authors with high-impact publishing options and increased citation opportunities for their research [3]. Group 1: OA Journal Portfolio - Springer Nature has approximately 700 pure OA journals, with 2023 OA articles averaging 6.3 citations each, surpassing industry peers [3]. - Over 500 pure OA journals have an impact factor (IF), with 62% of these journals showing growth in their IF [4]. - 309 pure OA journals are ranked in Q1 across various disciplines, representing 57% of the total [4]. - 450 pure OA journals are in the top 50 of their respective fields, accounting for 83% [4]. - 106 pure OA journals are in the top 10 of their fields, including notable journals like Signal Transduction and Targeted Therapy [4]. Group 2: Historical Context and Development - Springer, founded in 1842, is a renowned publishing brand in science, technology, medicine, humanities, and social sciences, with over 2000 mixed and OA journals [5]. - BMC, a pioneer in OA publishing, has around 300 peer-reviewed OA journals focused on advancing biological, health, and medical sciences [7][8]. Group 3: Specific Journal Highlights - The Discover journal series aims to support rapid publication of research across various scientific fields, targeting a publication timeline of 7-10 weeks [14]. - Nature Partner Journals (npj) collaborate with global scientists and institutions to publish high-quality OA research in diverse scientific areas [19]. - The Communications series under Nature Portfolio emphasizes diverse community engagement and aims to publish research that brings new insights to its fields [23]. - Nature Communications, a highly selective multidisciplinary OA journal, has an impact factor of 15.7 and a total citation count of 911,428 for 2024 [30]. - Scientific Reports, another multidisciplinary OA journal, has an impact factor of 3.9 and a total citation count of 834,622 for 2024 [34]. - Humanities and Social Sciences Communications provides a rigorous platform for research in the humanities and social sciences, with an impact factor of 3.6 for 2024 [35].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 离子通道 是细胞膜上的一类特殊蛋白质，负责调控离子的跨膜流动，在维持细胞电生理活动和信号转导中起关键作用，例如 电压门控钠离子通道 （Na V ） ，通 过快速介导钠离子 （Na + ） 内流触发电信号传导，是 调控可兴奋细胞 （例如神经元、心肌、骨骼肌细胞） 动作电位的关键，其功能异常会导致 持续性钠电流 （ I NaL ） 增强，这是导致 心律失常 、 癫痫、 肌强直 、 偏头痛 和 智力障碍 等多种严重疾病的共同分子机制。 能够精准调控离子通道功能的策略备受期待，然而，包括小分子药物学在内的现有方法存在局限性，且常常会产生脱靶效应。在自然界中， 离子通道的功能通过 进化而来的调节蛋白进行定制，以满足不同的生理需求。过去几十年的结构生物学研究为离子通道-调控蛋白的相互作用提供了前所未有的原子级视角，并揭示了 调控机制。然而，从头设计或合成具有高度特异性的离子通道调控蛋白，一直未能实现。 在自然界中，离子通道的功能可塑性是这些蛋白质的一个显著特征，这通常通过与多种辅助亚基或调控蛋白的结合来实现，这些辅助亚基或调控蛋白经过漫长的 进化以微调特定通道的特性。过去几十年的结 ...

Core Viewpoint - The study highlights the potential of NSD2 inhibitors as a therapeutic strategy for treating lung and pancreatic cancers, particularly in patients with KRAS mutations, and supports the clinical evaluation of combined therapies with KRAS inhibitors [4][9]. Group 1: NSD2 Inhibitors and Their Mechanism - NSD2 inhibitors (NSD2i) can reshape chromatin to treat lung and pancreatic cancers and work synergistically with KRAS G12C inhibitor Sotorasib [4]. - The research demonstrated that targeting NSD2 creates an epigenetic dependency, showing broad therapeutic efficacy in KRAS-driven preclinical cancer models [7]. - NSD2i effectively inhibits NSD2 activity at nanomolar concentrations (IC50) and shows high selectivity for related methyltransferases [7]. Group 2: Efficacy in Cancer Models - Continuous exposure to NSD2i can reverse pathological H3K36me2-driven chromatin plasticity, silencing oncogene expression and significantly reducing the survival rate of pancreatic and lung cancer cells [7]. - NSD2i has shown comparable effects in extending survival in advanced spontaneous KRAS G12C-driven pancreatic and lung cancer mouse models to those of Sotorasib [8]. - The combination of NSD2i and Sotorasib leads to significant tumor regression and even clearance, outperforming the effects of either treatment alone by several times [8]. Group 3: Implications for Treatment Strategies - Targeting the NSD2-H3K36me2 signaling axis presents an effective treatment strategy for refractory cancers, providing a theoretical basis for the clinical evaluation of combined NSD2 and KRAS inhibitors [9].