撰文丨王聪 编辑丨王多鱼 排版丨水成文 类风湿关节炎 （RA） 是一种自身免疫疾病，其特征为持续性滑膜炎和进行性软骨破坏。RA 的传统治疗方法主要包括抗炎药物。尽管这些疗法能够缓解症状，但 对许多患者而言往往效果不佳，且常伴有不良反应。 尽管 RA 的确切病因尚不清楚，但越来越多的证据表明 巨噬细胞 在疾病进展中发挥着关键作用。在 RA 受累关节中占主导地位的 M1 型巨噬细胞通过分泌促炎细 胞因子和活性氧 （ROS） 加剧滑膜炎和软骨损伤。鉴于巨噬细胞表型具有动态性且受局部微环境影响，目前的研究重点在于通过靶向促炎细胞因子或 ROS 来诱 导 M1 向 M2 极化。然而，抑制单个细胞因子并不足以消除炎症，因为炎症是由复杂的细胞因子网络驱动的。 近日，深圳大学医学部 董海峰 教授团队在 Cell 子刊 Cell Biomaterials 上发表了题为 ： Cerium-vanadium nanozyme/DNAzyme system for rheumatoid arthritis therapy through reactive oxygen species scavenging and inflammat ...

Core Viewpoint - The article discusses a groundbreaking research study from the Dalian Institute of Chemical Physics, which presents a two-step method for producing ethylene from carbon dioxide (CO2) using photochemical hydrogen dissociation, achieving nearly quantitative reduction of CO2 to ethylene [2][3]. Group 1 - The research team discovered that under 365 nm wavelength irradiation, an Au-TiO2 composite structure can achieve hydrogen dissociation at room temperature [3]. - The mechanism involves the formation of interfacial electric dipoles from photo-generated electron-hole pairs between gold nanoparticles and the titanium-oxide framework, enhancing hydrogen dissociation capabilities [3]. - The process results in a conversion rate of over 99% from CO2 to ethane, and after 1500 hours of continuous irradiation, the system maintains over 99% selectivity for ethylene [3]. Group 2 - This study provides a new strategy for precise control of C-C coupling and directed conversion of CO2, which is a significant advancement in the field of chemical engineering and sustainability [3].

Core Viewpoint - The article discusses the development of a novel spatial multi-omics technology, Spatial-DMT, which enables the simultaneous mapping of DNA methylation and gene expression at near single-cell resolution, enhancing the understanding of tissue biology and its implications in development and disease [2][5][7]. Group 1: Technology Development - The research team from the University of Pennsylvania developed Spatial-DMT, a new technique for spatial profiling of DNA methylome and transcriptome in tissues [2]. - This technology allows for the generation of high-quality DNA-RNA dual-modal tissue maps, revealing how DNA methylation interacts with transcription to define cell identity and drive developmental programs [5][6]. Group 2: Biological Implications - DNA methylation is a key epigenetic mechanism that regulates gene expression and cell states, with abnormal patterns linked to various diseases, including cancer and autoimmune disorders [4]. - The study highlights the dynamic changes in DNA methylation across different cell types and developmental stages, providing insights into the molecular definitions of cell identity during mammalian development and brain function [5][6]. Group 3: Research Applications - The Spatial-DMT technology was applied to mouse embryos and postnatal mouse brains, allowing for the reconstruction of dynamic changes in the epigenome and transcriptome during embryonic development [6]. - The integration of spatial maps from different developmental stages reveals details of transcriptional regulation mediated by sequence, cell type, and region-specific methylation [6][7].

Core Viewpoint - The article discusses the CRISPR-Cas system as a significant tool in gene editing and disease treatment, highlighting its immune mechanisms and the role of Cas9 in regulating spacer acquisition and immune memory formation [3][8][15]. Group 1: CRISPR-Cas System Overview - The CRISPR-Cas system is a bacterial immune mechanism that utilizes "molecular memory" and "precise cutting" to defend against foreign invaders [3]. - It consists of two main components: the CRISPR array, which serves as a memory bank, and Cas proteins, which are responsible for recognizing and cutting foreign DNA [3][4]. Group 2: Immune Process Stages - The immune process mediated by CRISPR-Cas can be divided into three stages: Adaptation, Expression, and Interference [4]. - During the Adaptation stage, the Cas1-Cas2 complex integrates foreign DNA sequences into the CRISPR array [4]. - The Expression stage involves the transcription of the CRISPR array into pre-crRNA, which is then processed into mature crRNA [4]. - In the Interference stage, Cas proteins form an effector complex with guide RNA to identify and cleave complementary foreign DNA [4]. Group 3: Research Findings on Cas9 - Recent studies reveal that the II-C type system has a unique molecular regulation mechanism during the immune adaptation phase, where apoCas9 significantly enhances spacer acquisition efficiency [8][10]. - The research indicates that apoCas9 acts as both a sensor for crRNA abundance and a regulator of spacer acquisition efficiency, challenging previous beliefs about its inactivity [8][15]. - The study also highlights the importance of the NUC lobe in driving efficient spacer acquisition, while the REC lobe modulates this process through RNA interactions [12][14]. Group 4: Implications and Future Directions - The findings provide insights into how bacteria can quickly replenish their immune memory after CRISPR array contraction, emphasizing the dynamic regulation of immune memory depth [15]. - The research lays a theoretical foundation for future applications in CRISPR-based immune adaptation machines, molecular recording, lineage tracing, and anti-phage engineering [17].

Core Insights - The article discusses a study by a team from Fudan University that reveals the genetic history of prehistoric population interactions in the Yellow River Bend, providing evidence of long-distance interactions among populations from the Central Plains, Steppe, and southern China [3][5][7]. Summary by Sections Research Findings - The study utilized ancient DNA to decode the genetic history of prehistoric populations in the Loess Plateau, showing significant genetic connections between the Shijia culture in the Central Plains and northern Steppe populations, with some individuals from the Xinhua site exhibiting up to 50% southern genetic ancestry [5][6]. - The research indicates that approximately 10%-20% of the genetic contribution in the Xinhua and related groups comes from Neolithic northern Steppe populations, while the Miaozi Gou culture closer to the Steppe shows up to 30% [6][7]. Cultural Implications - The findings suggest that the ancient populations of the Loess Plateau maintained close ties with the Central Plains agricultural society while also absorbing genetic inputs from both northern Steppe and southern regions, reflecting a complex pattern of migration and cultural exchange [7][10]. - The study challenges the traditional view of civilization development as a linear process, instead presenting the formation of Chinese civilization as a result of the convergence of diverse cultures and populations [10]. Historical Context - The Xinhua site, dated around 4100-3850 years ago, is identified as a satellite city of the Shijia culture, with artifacts indicating agricultural and pastoral activities linked to the rise of the Zhou Dynasty [6][7]. - The research highlights the strategic importance of the Loess Plateau as a northern gateway of Chinese civilization, emphasizing the profound impact of north-south interactions in the formation of early Chinese society [7][10].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 准确的肿瘤类型定位对于确定恰当的治疗策略、优化临床结果以及使患者能够接受靶向治疗和临床试验至 关重要。明确肿瘤类型及其原发部位，能让肿瘤科医生根据肿瘤的生物学特性为其制定个性化治疗方案。 分子分析方面的最新进展改进了癌症分类，并推动了个性化医疗的发展。然而，尽管有这些创新，诊断复 杂癌症，尤其是转移性肿瘤，仍是临床面临的一大挑战。 原发灶不明癌症 （CUP） 是肿瘤学中最具挑战性的临床情况之一。CUP 指的是尽管进行了广泛的诊断努 力，包括组织病理学、影像学和分子检测，但原发部位仍无法确定的转移性肿瘤。在全球范围内，CUP 占 所有癌症的 3%-5%，这些癌症通常具有侵袭性，对治疗有抗性，并且预后不良，中位生存期在 6-16 个 月之间。由于原发部位未知，治疗通常采用经验性化疗，其效果不如针对特定部位的疗法。因此，确定肿 瘤的组织来源对于扩大治疗选择和改善预后至关重要。尽管病理学，包括免疫组化、肿瘤形态学和临床发 现，在确定原发肿瘤方面发挥着关键作用，但传统方法在高度转移性或低分化 CUP 病例中往往效果不佳。 这些局限性，再加上观察者之间的差异，凸显了对更可靠诊断方法 ...

Core Viewpoint - The article announces the launch of the open-access journal "Immunity & Inflammation," focusing on significant scientific issues and advancements in the fields of immunology and inflammation [2][4]. Group 1: Journal Overview - "Immunity & Inflammation" is co-edited by prominent figures in immunology, including Nobel laureates and leading researchers from various countries [2][5]. - The journal aims to bridge foundational insights with medical innovations, publishing high-quality original research, reviews, and highlights across basic, translational, and clinical research [6]. Group 2: Research Focus - The journal particularly welcomes studies exploring the dual nature of inflammation, inflammation-driven diseases, novel anti-inflammatory interventions, and groundbreaking findings in immune regulation [6]. - It encourages interdisciplinary research, including the use of artificial intelligence and digital health technologies, and aims to establish new standards in relevant research and practice areas [6]. Group 3: Editorial Commitment - The journal is committed to maintaining the highest standards of scientific ethics, integrity, transparency, and reproducibility [6][7]. - It invites global scientific communities to collaborate and contribute to making "Immunity & Inflammation" a vibrant and impactful academic platform [7].

Core Viewpoint - The article discusses a significant study indicating that influenza vaccination can improve outcomes for patients with acute heart failure, particularly in reducing mortality and readmission rates within a year after hospitalization [3][8]. Group 1: Study Overview - A large-scale, multi-regional, seasonal, hospital-based cluster-randomized controlled trial named PANDA II was conducted in China, involving 7,771 heart failure patients across 164 hospitals from 2021 to 2024 [3][4]. - The study aimed to assess whether influenza vaccination before discharge could enhance survival rates and decrease the likelihood of readmission for acute heart failure patients [3][8]. Group 2: Methodology - Hospitals were randomly assigned to either the intervention group, which provided free influenza vaccinations, or the control group, which followed standard care without vaccination [5][6]. - The vaccination rate in the intervention group was 94.4%, compared to only 0.5% in the control group [5]. Group 3: Results - The composite outcome of all-cause mortality or hospital readmission at 12 months was 41.2% in the vaccination group versus 47.0% in the usual care group, indicating an absolute risk reduction of 5.8% [6][7]. - For secondary outcomes, the all-cause mortality rate at 12 months was 10.0% in the vaccination group compared to 12.8% in the control group, and the readmission rate was 35.4% versus 40.5% [6][7]. Group 4: Implications - The findings suggest that integrating influenza vaccination into the treatment protocol for acute heart failure patients can provide a widely applicable strategy to improve patient outcomes, regardless of healthcare resource availability [8].

Core Viewpoint - The article discusses a groundbreaking study on breast cancer that introduces a high-throughput, high-genomic-resolution single-cell DNA and RNA multi-omics technology called wellDR-seq, which helps decode the origins and progression mechanisms of breast cancer [3][5][9]. Group 1 - The research team, led by Nicholas Navin at the MD Anderson Cancer Center, published their findings in the journal Cell, highlighting the first application of wellDR-seq technology [3][5]. - The study analyzed 33,646 single cells from 12 estrogen receptor-positive (ER+) breast cancer patients, identifying cancer ancestral subclones that may represent the origin cells of breast cancer [5][9]. - wellDR-seq allows for the study of gene dosage relationships at the subclonal level, revealing a near-linear correlation in large chromosomal regions and extensive variation at the single-gene level [6][9]. Group 2 - The research identified that 56% of copy number variation segments showed a near-linear correlation with gene expression, providing insights into the complex relationship between copy number and gene expression at the single-cell level [9]. - The study also identified dosage-sensitive and dosage-insensitive genes, including many breast cancer-related genes and incidental copy number variations in non-cancer cells [6][9]. - wellDR-seq is a versatile method applicable not only to breast cancer but also to other cancers and various biomedical fields, enhancing the understanding of cancer development [9].

Core Viewpoint - Long-term exposure to air pollutants, specifically PM2.5, significantly increases the risk of Lewy body dementia (LBD), highlighting the need for further research on air pollution's role in neurodegenerative diseases and its implications for public health strategies [4][11]. Group 1: Research Findings - A large-scale study involving 56 million individuals indicates a strong association between long-term PM2.5 exposure and hospitalization due to α-synucleinopathies, particularly in patients with LBD compared to those with non-dementia Parkinson's disease [4][7]. - The study demonstrates that α-synuclein plays a critical role in PM2.5-related neurodegenerative diseases, with wild-type mice exposed to PM2.5 for 10 months showing brain atrophy, cognitive deficits, and widespread α-synuclein pathology [8][11]. - PM2.5 exposure induces a pathogenic variant of α-synuclein, termed PM-PFF, which exhibits characteristics similar to those found in human LBD, including accelerated aggregation and increased neurotoxicity [8][11]. Group 2: Mechanisms and Implications - Chronic PM2.5 exposure and PM-PFF inoculation in humanized α-synuclein mice trigger gene expression changes that resemble those in LBD patients, underscoring a specific pathogenic axis for LBD [9][11]. - The findings suggest that PM-PFF could serve as a potential therapeutic target, emphasizing the importance of understanding environmental mechanisms in the pathogenesis of LBD [11].