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IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-07-01 Epub Date: 2025-06-13 DOI: 10.1016/S1016-8478(25)00069-X

引用次数: 0

MicroRNA-196a increases apoptosis in B cells through downregulation of FOXO1 MicroRNA-196a通过下调fox01增加B细胞凋亡。

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-07-01 Epub Date: 2025-05-20 DOI: 10.1016/j.mocell.2025.100223

Soyoung Kim , Mina Han , Hyun Ju Hwang , Young-Ho Ahn , Ho Joon Im , Sang-Hyun Hwang , Kyung-Nam Koh , Nayoung Kim

MicroRNAs (miRNAs) are key regulators of cancer pathogenesis, and their expression is often dysregulated in cancer cells. The role of miR-196a-5p has been investigated in various types of cancers. However, it is relatively less understood in B-cell malignancies. This study aimed to investigate the role of miR-196a-5p in B cells by using a human diffuse large B-cell lymphoma cell line, SU-DHL-6, and mouse B lymphocytes. The enforced expression of miR-196a in SU-DHL-6 cells increased daunorubicin-mediated apoptosis. Luciferase assay revealed that FOXO1 was a direct target of miR-196a-5p in SU-DHL-6 cells. The mRNA and protein expression of FOXO1 was downregulated in miR-196a-overexpressing SU-DHL-6 cells. In addition, miR-196a-5p was highly expressed in mouse bone marrow cells, compared with that of splenic B cells, and FOXO1 expression was negatively correlated with miR-196a-5p level. miR-196a-5p was upregulated by B-cell receptor stimulation, which was inversely correlated with FOXO1 expression in splenic B cells. Apoptosis was increased when miR-196a-5p was upregulated in murine primary B cells. These results identify miR-196a-5p as a post-transcriptional regulator of FOXO1 and indicate its importance in regulating B-cell malignancies and activation.

MicroRNAs （miRNAs）是癌症发病的关键调控因子，其表达在癌细胞中经常失调。miR-196a-5p在各种类型的癌症中的作用已被研究，但在b细胞恶性肿瘤中的作用相对较少。本研究旨在通过人弥漫性大B细胞淋巴瘤（DLBCL）细胞系、SU-DHL-6和小鼠B淋巴细胞来研究miR-196a-5p在B细胞中的作用。miR-196a在SU-DHL-6细胞中的强制表达增加了柔红霉素介导的细胞凋亡。荧光素酶检测显示FOXO1是SU-DHL-6细胞中miR-196a-5p的直接靶点。过表达mir -196a的SU-DHL-6细胞中FOXO1 mRNA和蛋白表达下调。此外，miR-196a-5p在小鼠骨髓（BM）细胞中高表达，与脾（SP） B细胞相比，FOXO1表达与miR-196a-5p水平呈负相关。miR-196a-5p在B细胞受体（BCR）刺激下上调，与SP B细胞中FOXO1的表达呈负相关。上调miR-196a-5p可增加小鼠原代B细胞的凋亡。这些结果确定了miR-196a-5p是fox01的转录后调节因子，并表明其在调节B细胞恶性肿瘤和激活中的重要性。

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引用次数: 0

Conformational flexibility of His200 enables catalytic activity in the T200H mutant of carbonic anhydrase II His200的构象灵活性使碳酸酐酶II的T200H突变体具有催化活性。

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-07-01 Epub Date: 2025-05-27 DOI: 10.1016/j.mocell.2025.100226

Seon Woo Lim , Hannah Jeong , Gwang Ho Kim , Duyoung Min , Jin Kyun Kim , Chae Un Kim

Carbonic anhydrase II (CAII) is one of the most efficient enzymes known, catalyzing the reversible hydration of CO₂ to regulate pH and facilitate CO₂ transport in biological systems. Its exceptional catalytic rate depends on a highly ordered active site composed of a Zn²⁺ ion and a hydrogen-bonded water network that supports substrate binding, proton transfer, and product release. Among the residues maintaining this network, Thr200 plays a crucial role by stabilizing key water molecules. To investigate the structural and functional consequences of perturbing this network, we examined the T200H mutant of CAII using high-pressure cryocooling and X-ray crystallography under CO₂ pressures of 0, 5, and 20 atm. The crystallographic snapshots captured the resting (T200H-0atm), substrate-bound (T200H-20atm), and product-bound (T200H-5atm) states of the T200H mutant. In the resting state, His200 disrupts the active site by displacing essential water molecules (W1 and W2), thereby impairing the proton transfer pathway. However, the substrate- and product-bound states reveal that His200 exhibits conformational flexibility, allowing partial restoration of the water network required for catalysis. These findings suggest that His200 functions as a dynamic gatekeeper, modulating access of water, substrate, and product to the active site. This structural plasticity explains how the T200H mutant retains partial catalytic activity despite a mutation that would otherwise severely hinder function. Our results provide new insights into active-site dynamics in CAII and offer a foundation for designing isoform-specific inhibitors or engineered carbonic anhydrase variants with tunable catalytic properties.

碳酸酐酶II （carbon anhydrase II， CAII）是目前已知效率最高的酶之一，它催化二氧化碳的可逆水合作用，调节生物系统中的pH值，促进二氧化碳的运输。其特殊的催化速率取决于由Zn2+离子和氢键水网络组成的高度有序的活性位点，该活性位点支持底物结合，质子转移和产物释放。在维持这一网络的残基中，Thr200起着稳定关键水分子的关键作用。为了研究干扰该网络的结构和功能后果，我们在0、5和20 atm的CO2压力下使用高压冷冻和x射线晶体学研究了CAII的T200H突变体。晶体学快照捕获了T200H突变体的静息（T200H-0atm）、底物结合（T200H-20atm）和产物结合（T200H-5atm）状态。在静息状态下，His200通过取代必需的水分子（W1和W2）破坏活性位点，从而损害质子转移途径。然而，底物结合态和产物结合态表明，His200具有构象灵活性，可以部分恢复催化所需的水网络。这些发现表明，His200作为一个动态看门人，调节水、底物和产物进入活性位点的途径。这种结构可塑性解释了T200H突变体如何保持部分催化活性，尽管突变会严重阻碍功能。我们的研究结果为cai活性位点动力学提供了新的见解，并为设计具有可调催化性能的异构体特异性抑制剂或工程CA变体提供了基础。

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引用次数: 0

A novel high-throughput single-molecule technique DNA curtain: Applications for DNA metabolism 一种新的高通量单分子技术DNA幕：在DNA代谢中的应用。

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-07-01 Epub Date: 2025-05-20 DOI: 10.1016/j.mocell.2025.100224

Soyeong An , Youngseo Kim , Ja Yil Lee

The advancement of single-molecule imaging techniques has significantly enhanced our understanding of biomolecular reactions and cellular processes that remain obscured in ensemble measurements. In particular, DNA curtains are high-throughput hybrid methods integrating total internal reflection fluorescence microscopy, lipid fluidity, microfluidics, and nano-fabrication, enabling the direct visualization of protein-DNA interactions in real time. The techniques have emerged as powerful tools for probing molecular dynamics of diverse DNA metabolic processes, including DNA damage repair and chromatin dynamics. This review not only highlights recent applications of DNA curtain techniques for elucidating mechanisms underlying DNA damage repair and chromatin dynamics, but also shows how DNA curtain techniques have provided novel insights into the interplay between DNA metabolic processes in the chromatin context.

单分子成像技术的进步大大提高了我们对生物分子反应和细胞过程的理解，这些反应和细胞过程在集合测量中仍然模糊不清。特别是，DNA窗帘是一种高通量混合方法，集成了全内反射荧光显微镜、脂质流动性、微流体和纳米制造，能够实时直接可视化蛋白质-DNA相互作用。这些技术已经成为探测各种DNA代谢过程的分子动力学的有力工具，包括DNA损伤修复和染色质动力学。这篇综述不仅强调了DNA幕技术在阐明DNA损伤修复和染色质动力学机制方面的最新应用，而且还展示了DNA幕技术如何为染色质背景下DNA代谢过程之间的相互作用提供了新的见解。

引用次数: 0

SimpleViz: A user-friendly, web-based tool for publication-ready data visualization in bioinformatics SimpleViz：一个用户友好的，基于web的工具，用于生物信息学中出版就绪的数据可视化。

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-07-01 Epub Date: 2025-05-08 DOI: 10.1016/j.mocell.2025.100222

Byeong Seob Oh , Juhee Kim , Minjeong Kwon , Jiwon Bang , Kwang-Jun Lee , Eun-Jin Lee , Yong-Joon Cho

Large-scale datasets are central to bioinformatics research, creating a demand for intuitive visualization tools that transform complex data into accessible graphics. Existing visualization software often comes with high costs or requires coding expertise, limiting accessibility for many researchers. To address this gap, we introduce SimpleViz, a free, web-based platform that enables the creation of professional-quality figures without the need for programming skills. SimpleViz offers gene-level analysis of RNA-seq data and core visualization types such as box/violin/dot plots, volcano plots, principal component analysis plots, and heatmaps, with extensive customization options for detailed adjustments and built-in statistical comparisons. Developed on a Shiny interface, SimpleViz simplifies the process of data upload, visualization generation, and customization, ensuring that users can produce tailored visuals suited for publication. With plans for continuous improvement based on user feedback, SimpleViz provides an adaptable, accessible solution that meets evolving data analysis needs in biomedical research.

大规模数据集是生物信息学研究的核心，它创造了对直观可视化工具的需求，这些工具可以将复杂的数据转换为可访问的图形。现有的可视化软件通常成本很高，或者需要编码专业知识，限制了许多研究人员的可访问性。为了解决这一差距，我们推出了SimpleViz，这是一个免费的基于web的平台，可以在不需要编程技能的情况下创建专业质量的图形。SimpleViz提供RNA-seq数据的基因水平分析和核心可视化类型，如盒/小提琴/点阵图，火山图，PCA图和热图，具有广泛的定制选项，可进行详细调整和内置统计比较。SimpleViz基于Shiny界面开发，简化了数据上传、可视化生成和自定义的过程，确保用户可以生成适合发布的定制视觉效果。SimpleViz计划根据用户反馈进行持续改进，提供了一个适应性强、易于访问的解决方案，以满足生物医学研究中不断发展的数据分析需求。

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引用次数: 0

Effects of heterozygous SMG1 mutations on nonsense-mediated mRNA decay in human pluripotent stem cell model 杂合SMG1突变对人多能干细胞模型中无义介导的mRNA衰变的影响。

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-07-01 Epub Date: 2025-05-20 DOI: 10.1016/j.mocell.2025.100225

Chanyoung Lee , Jin Sook Lee , Yejin Kwon , Aeri Shin , Tae Yeong Jeong , Jiyun Yang , Jung Woo Hwang , Hyeong-In Kim , Hee-Jung Choi , Yoon Ki Kim , Murim Choi , Kyoungmi Kim , Woong Sun , Jong-Hee Chae

Nonsense-mediated mRNA decay (NMD) eliminates transcripts containing premature termination codons, thereby preventing errors in protein synthesis. Serine/threonine-protein kinase SMG1 is a crucial kinase for NMD response, interacting with other regulatory proteins such as SMG8 and SMG9. We identified a de novo heterozygous variant in SMG1 p.Gln2398Glu (c.7192C>G) in a patient with global developmental delay, facial dysmorphism, and oculomotor apraxia. Thus, stem cell models with SMG1 mutations using gene editing technology were established to address the functional consequences of this mutation. While mutations causing the reduction in SMG1 gene dosage by alterations in splicing (c.7192_7194delinsGAA; GAA/+) or frameshift (c.4331_4337del; KO/+) led to a mild but significant reduction of NMD activity, NMD activity was not altered in cells with the SMG1 GAG/+ mutation. Furthermore, cortical organoids from hPSC^GAA/+ exhibited size reduction compared with the control (CTL) or GAG/+, suggesting that reduced NMD activity can affect nervous system development. These findings suggest that hypomorphic SMG1 mutations can cause reduced NMD activity and subsequent biological responses, while the mutation found in the patient alone may not be sufficient to induce pathological symptoms.

无义介导的mRNA衰变（NMD）消除了含有过早终止密码子（ptc）的转录本，从而防止了蛋白质合成中的错误。丝氨酸/苏氨酸蛋白激酶SMG1是NMD应答的关键激酶，与其他调节蛋白如SMG8和SMG9相互作用。我们在一名患有全面发育迟缓、面部畸形和动眼失用症的患者中发现了SMG1 p.Gln2398Glu （c.7192C>G）的新杂合变异。因此，利用基因编辑技术建立SMG1突变干细胞模型，以解决该突变的功能后果。而突变通过剪接的改变导致SMG1基因剂量的减少(c.7192_7194delinsGAA；GAA/+)或移码(c. 4331_437del；KO/+)导致NMD活性轻度但显著降低，SMG1 GAG/+突变细胞的NMD活性未发生改变。此外，与对照（CTL）或GAG/+相比，来自hPSCGAA/+的皮质类器官显示出体积减小，这表明NMD活性降低可以影响神经系统的发育。这些发现表明，SMG1亚型突变可导致NMD活性降低和随后的生物反应，而仅在患者中发现的突变可能不足以诱导病理症状。

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引用次数: 0

Cover and caption 封面及标题

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-06-01 Epub Date: 2025-05-21 DOI: 10.1016/S1016-8478(25)00052-4

引用次数: 0

Open-source software utilization for zebrafish embryos behavior test 利用开源软件进行斑马鱼胚胎行为测试

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-06-01 Epub Date: 2025-04-25 DOI: 10.1016/j.mocell.2025.100221

Thilini Ranasinghe , Seon-Heui Cha

This work described simple methods for measuring locomotive activity using open-source software, ImageJ1.54fFiji, and VirtualDub2. The significance of animal behavior is a mirror of brain activity, which can give information implicated with neurological diseases. Commercial behavioral analysis software frequently needs expertise and expenses high costs due to equip a specific instrument to use of software, thereby encouraging a trend toward open-source alternatives that are both accessible and effective. Here, we explained how to convert video format, measure movement, and produce useful locomotive parameters to aid in the assessment of zebrafish embryos. This method could be easily translated for use in other model systems. This methodology seeks to streamline behavioral quantification in research contexts, encouraging broader research aspects.

这项工作描述了使用开源软件ImageJ1.54fFiji和VirtualDub2测量机车活动的简单方法。动物行为的意义是大脑活动的一面镜子，它可以提供与神经系统疾病有关的信息。商业行为分析软件经常需要专业知识，并且由于配备特定的工具来使用软件而花费高昂的成本，因此鼓励了向可访问且有效的开源替代方案发展的趋势。在这里，我们解释了如何转换视频格式，测量运动，并产生有用的机车参数，以帮助评估斑马鱼胚胎。这种方法可以很容易地转换为用于其他模型系统。这种方法旨在简化研究背景下的行为量化，鼓励更广泛的研究方面。

引用次数: 0

Cholesterol sulfate as a negative regulator of cellular cholesterol homeostasis 硫酸胆固醇作为细胞胆固醇稳态的负调节因子。

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-06-01 Epub Date: 2025-03-14 DOI: 10.1016/j.mocell.2025.100209

Le Ba Nam , Sung-Jin Kim , Tan Khanh Nguyen , Chang-Yun Jeong , June-Yong Lee , Jun-Seok Lee , Jeong Taeg Seo , Seok Jun Moon

Cholesterol sulfate (CS), one of the most abundant cholesterol derivatives, recently emerged as a key regulatory molecule in several physiological processes. Here, we demonstrate multiple mechanisms by which CS reduces intracellular cholesterol levels. CS promotes the proteasomal degradation of 3-hydroxy-3-methylglutaryl-CoA reductase reductase by enhancing insulin-induced gene-mediated ubiquitination, thereby inhibiting cholesterol synthesis. In addition, CS blocks low-density lipoprotein receptor endocytosis, reducing low-density lipoprotein cholesterol uptake. CS further suppresses the proteolytic activation of sterol regulatory element-binding protein 2, a master transcription factor governing cholesterol synthesis and uptake. Using in vitro and in vivo models, we show that CS lowers cholesterol by targeting both the cholesterol synthesis and uptake pathways, while also modulating an important feedback loop via sterol regulatory element-binding protein 2. These findings highlight the potential of CS as a modulator of cholesterol metabolism, offering new therapeutic insights into cholesterol-related disorders.

硫酸胆固醇（CS）是一种含量最丰富的胆固醇衍生物，近年来作为一种关键的生理调控分子而被发现。在这里，我们证明了CS降低细胞内胆固醇水平的多种机制。CS通过增强insg介导的泛素化，促进HMG-CoA还原酶（HMGCR）的蛋白酶体降解，从而抑制胆固醇合成。此外，CS阻断低密度脂蛋白（LDL）受体内吞作用，减少LDL- c摄取。CS进一步抑制甾醇调节元件结合蛋白2 （SREBP2）的蛋白水解激活，SREBP2是控制胆固醇合成和摄取的主要转录因子。通过体外和体内模型，我们发现CS通过靶向胆固醇合成和摄取途径降低胆固醇，同时也通过SREBP2调节一个重要的反馈回路。这些发现突出了CS作为胆固醇代谢调节剂的潜力，为胆固醇相关疾病的治疗提供了新的见解。

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引用次数: 0

Decoding SPP1 regulation: Genetic and nongenetic insights into its role in disease progression 解码SPP1调控：其在疾病进展中的作用的遗传和非遗传见解

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-06-01 Epub Date: 2025-04-08 DOI: 10.1016/j.mocell.2025.100215

Sungju Jung , Jiseon Ha , Jong Hoon Park , Kyung Hyun Yoo

Secreted phosphoprotein 1 (SPP1), also known as osteopontin, is a multifunctional glycoprotein that plays a critical role in various physiological processes, including cell adhesion, chemotaxis, immune regulation, and tissue remodeling. Originally identified as a key component of the bone matrix, SPP1 is now recognized for its broad involvement in numerous tissues and significant impact on both normal physiology and disease progression. Dysregulation of SPP1 has been strongly implicated in the pathogenesis and progression of several diseases, including cancer, cardiovascular diseases, autoimmune disorders, and chronic inflammatory conditions. The expression of SPP1 is tightly regulated by genetic and nongenetic mechanisms. Genetic alterations, such as single-nucleotide polymorphisms, insertions and deletions, and structural variations within the SPP1 gene, have been associated with increased susceptibility to various diseases, influencing disease severity and outcomes. Additionally, nongenetic regulations, including DNA methylation, histone modifications, and long noncoding RNAs, play crucial roles in modulating SPP1 expression in response to environmental and cellular signals. This review provides a comprehensive overview of the genetic and nongenetic regulatory mechanisms governing SPP1 and examines their implications in disease pathogenesis. By integrating recent findings, this review highlights the complex interplay between genetic predispositions and nongenetic regulations in determining SPP1 activity and offers new insights into its role as a potential biomarker and therapeutic target. Understanding these regulatory pathways is essential for the development of targeted interventions for diseases in which SPP1 plays a pivotal role.

分泌磷蛋白1 (SPP1)，又称骨桥蛋白，是一种多功能糖蛋白，在细胞粘附、趋化、免疫调节和组织重塑等多种生理过程中发挥关键作用。SPP1最初被认为是骨基质的关键成分，现在被认为广泛参与许多组织，并对正常生理和疾病进展产生重大影响。SPP1的失调与多种疾病的发病和进展密切相关，包括癌症、心血管疾病、自身免疫性疾病和慢性炎症。SPP1的表达受到遗传和非遗传机制的严格调控。遗传改变，如SPP1基因内的单核苷酸多态性、插入和缺失以及结构变异，与各种疾病的易感性增加有关，影响疾病的严重程度和结果。此外，非遗传调控，包括DNA甲基化、组蛋白修饰和长链非编码rna，在调节SPP1表达以响应环境和细胞信号方面发挥关键作用。这篇综述提供了控制SPP1的遗传和非遗传调控机制的全面概述，并研究了它们在疾病发病机制中的意义。通过整合最近的研究结果，本综述强调了遗传易感性和非遗传调控在决定SPP1活性方面的复杂相互作用，并对其作为潜在生物标志物和治疗靶点的作用提供了新的见解。了解这些调控途径对于开发针对SPP1起关键作用的疾病的靶向干预措施至关重要。

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