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Deficient chaperone-mediated autophagy in macrophages aggravates colitis and colitis-associated tumorigenesis in mice 巨噬细胞伴蛋白介导的自噬缺陷加重小鼠结肠炎和结肠炎相关肿瘤发生。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-12-01 DOI: 10.1016/j.mocell.2025.100298

Weichun Zhu , Zehao Chen , Yunqian Gao , Chungang Zhai , Xia Li , Ning Wang , Kang Fu , Wentao Chen , Jieqiong Peng , Dan Xu , Lei Qiao , Wenqiang Chen

Chaperone-mediated autophagy (CMA) is a highly selective form of autophagy responsible for the degradation of specific cytosolic proteins within lysosomes. Recent research has established a significant correlation between CMA and colorectal cancer (CRC). However, the majority of current research focuses on tumor parenchymal cells, with limited attention paid to the expression and role of CMA in tumor stromal cells, particularly in tumor-associated macrophages (TAMs). In this study, we generated myeloid-specific LAMP2A-knockout and knock-in mice to investigate the role of macrophage CMA in dextran sodium sulfate (DSS)-induced colitis and azoxymethane/dextran sodium sulfate-induced CRC. Our findings indicated that the expression of LAMP2A, the rate-limiting component of CMA, was reduced in tumor-associated macrophages of both human and mouse CRC tissues. The knockout of LAMP2A in macrophages exacerbated experimentally induced colitis and colitis-related CRC, whereas its overexpression in macrophages alleviated the progression of colitis and CRC in mice. Notably, we observed increased angiogenesis within the tumor mass of CRC tissues from LAMP2A-mØKO mice. Mechanistically, LAMP2A deficiency elevated the protein levels of HIF-1α, thereby enhancing the secretion of its target genes, vascular endothelial growth factor A and IL-1β, which are 2 important proangiogenic cytokines. Our study suggests that the activation of CMA in macrophages may represent a promising therapeutic strategy for the treatment of CRC.

伴侣介导的自噬（CMA）是一种高度选择性的自噬形式，负责溶酶体内特定细胞质蛋白的降解。最近的研究已经确定了CMA与结直肠癌（CRC）之间的显著相关性。然而，目前的研究大多集中在肿瘤实质细胞，很少关注CMA在肿瘤基质细胞，特别是肿瘤相关巨噬细胞（tumor-associated macrophages, tam）中的表达和作用。在这项研究中，我们制造了骨髓特异性lamp2a敲除和敲入小鼠，以研究巨噬细胞CMA在葡聚糖硫酸钠（DSS）诱导的结肠炎和偶氮氧甲烷(AOM)/DSS诱导的结直肠癌中的作用。我们的研究结果表明，在人和小鼠CRC组织的tam中，CMA的限速成分LAMP2A的表达都降低了。巨噬细胞中LAMP2A的敲除加重了实验性结肠炎和结肠炎相关性CRC，而巨噬细胞中LAMP2A的过表达则减轻了小鼠结肠炎和CRC的进展。值得注意的是，我们观察到LAMP2A-mØKO小鼠CRC组织肿瘤块内血管生成增加。机制上，LAMP2A缺乏升高HIF-1α的蛋白水平，从而增加其靶基因血管内皮生长因子A （VEGFA）和IL-1β的分泌，这是两种重要的促血管生成细胞因子。我们的研究表明，激活巨噬细胞中的CMA可能是治疗结直肠癌的一种有希望的治疗策略。

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Multifaceted role of Iroquois signaling in development and diseases 易洛魁人信号在发育和疾病中的多方面作用。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-12-01 DOI: 10.1016/j.mocell.2025.100296

Ravi Shankar Goutam , Neha Kaushik , Basant Kumar , Woochan Jung , Santosh Kumar , Seung-Hwan Lee , Unjoo Lee , Jaebong Kim

The Iroquois (Iro/Irx) gene family encodes transcription factors that belong to the Three-Amino-Acid Loop Extension-class homeodomain group, distinguished by a conserved Iro-box domain. Iroquois signaling is evolutionarily conserved from invertebrates to vertebrates and plays a vital role in embryonic development. In invertebrates, Iro/Irx genes control tissue compartmentalization, whereas in vertebrates, they regulate gastrulation, neural patterning, and organogenesis. These genes are typically organized in conserved genomic clusters under shared regulatory control, reflecting their coordinated expression and common evolutionary origins. Beyond development, dysregulation of Iroquois genes has been implicated in diverse human diseases. Iro/Irx genes are increasingly associated with congenital disorders, including congenital heart disease and neurodevelopmental abnormalities. Moreover, their emerging role in cancer biology has revealed context-dependent behavior, functioning as either tumor suppressors or oncogenes. Recent findings have also highlighted their potential as clinical biomarkers in neurological and neoplastic diseases. Given their broad developmental and pathological roles, Iroquois genes are gaining recognition as promising candidates for therapeutic targeting and molecular diagnostics. This review integrates their developmental functions with their disease associations to provide a comprehensive overview of the biological and clinical significance of Iroquois signaling.

Iroquois （Iro/Irx）基因家族编码的转录因子属于tale类同源结构域组，以保守的Iro-box结构域为特征。易洛魁人的信号在从无脊椎动物到脊椎动物的进化上是保守的，在胚胎发育中起着至关重要的作用。在脊椎动物中，Iro/Irx基因控制组织区隔化，而在脊椎动物中，它们调节原肠胚形成、神经模式和器官发生。这些基因通常被组织在保守的基因组簇中，在共同的调控下，反映了它们的协调表达和共同的进化起源。除了发育之外，易洛魁人基因失调还与多种人类疾病有关。Irx基因越来越多地与先天性疾病联系在一起，包括先天性心脏病和神经发育异常。此外，它们在癌症生物学中的新作用揭示了环境依赖行为，既可以作为肿瘤抑制因子，也可以作为癌基因。最近的研究结果也强调了它们作为神经和肿瘤疾病临床生物标志物的潜力。鉴于易洛魁人基因在发育和病理方面的广泛作用，易洛魁人基因作为治疗靶向和分子诊断的有前途的候选者正在获得认可。本文综述了易洛魁信号的发育功能及其与疾病的关联，以提供易洛魁信号的生物学和临床意义的全面概述。

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Editorial Board Members/Copyright 编辑委员会成员/版权

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-12-01 DOI: 10.1016/S1016-8478(25)00130-X

引用次数: 0

Brief guide to western blot assays western blot检测的简要指南。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-12-01 DOI: 10.1016/j.mocell.2025.100297

Seokjun G. Ha, Ji-Hoon Park, Mi-Young Kim, Seung-Jae V. Lee

Western blot is an essential method that detects specific proteins using antibodies, which is one of the most widely applied techniques for protein detection. Here, we present a brief guide to western blot, following the overall procedure from the choice of antibodies to quantification. This guide will provide useful information for researchers who are unfamiliar with western blot assays.

Western blot是一种利用抗体检测特异性蛋白质的重要方法，是目前应用最广泛的蛋白质检测技术之一。在这里，我们简要介绍了western blot，从选择抗体到定量的整个过程。本指南将为不熟悉western blot检测的研究人员提供有用的信息。

引用次数: 0

THRAISE: An automated and reproducible web platform for RNA-seq analysis THRAISE：用于RNA-seq分析的自动化和可重复的网络平台。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-12-01 DOI: 10.1016/j.mocell.2025.100299

Hyeon Ho Heo, Soo-Jong Um

Transcriptome-wide High-throughput RNA-seq Analysis Integrated System is a highly streamlined web platform for RNA-seq analysis that requires no programming expertise. Starting from raw NCBI Sequence Read Archive data, it performs the entire analysis pipeline, which includes quality control, alignment, quantification, differential expression, and functional enrichment using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Reactome, and Gene Set Enrichment Analysis. For datasets with limited replicates (n = 1), an alternative workflow is also provided, based on transcripts per million. With real-time monitoring, interactive visualization, and a user-friendly interface, Transcriptome-wide High-throughput RNA-seq Analysis Integrated System enables accessible and reproducible RNA-seq analysis for all researchers.

THRAISE（转录组全范围高通量RNA-seq分析集成系统）是一个高度精简的RNA-seq分析网络平台，不需要编程专业知识。从原始NCBI SRA数据开始，使用GO、KEGG、Reactome和GSEA执行整个分析流程，包括质量控制、比对、定量、差异表达和功能富集。对于具有有限复制（n = 1）的数据集，还提供了基于每百万副本（TPM）的替代工作流。THRAISE具有实时监测，交互式可视化和用户友好的界面，可为所有研究人员提供可访问和可重复的RNA-seq分析。

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Methods for detecting protein-protein interactions 检测蛋白质相互作用的方法。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-11-26 DOI: 10.1016/j.mocell.2025.100301

Seok Chan Cho, Hyun Woo Park

Protein-protein interaction (PPI) is central to all cellular processes and play critical roles in both normal physiology and disease pathogenesis. In this brief guide, we outline the fundamental principles and widely used methods for PPI detection, focusing on 3 key techniques: immunoprecipitation, in vitro pull-down assays, and proximity ligation assay. We also discuss common experimental challenges and provide practical optimization strategies to improve reliability and reproducibility. This resource is designed to aid researchers in molecular and cellular biology, signal transduction, and animal model studies with essential knowledge for selecting and applying PPI detection methods.

蛋白-蛋白相互作用（PPIs）是所有细胞过程的核心，在正常生理和疾病发病机制中都起着关键作用。在这篇简短的指南中，我们概述了PPI检测的基本原理和广泛使用的方法，重点介绍了三种关键技术：免疫沉淀法（IP）、体外拉下法（pull-down assay）和近距离结扎法（PLA）。我们还讨论了常见的实验挑战，并提供了实用的优化策略，以提高可靠性和再现性。该资源旨在帮助研究人员在分子和细胞生物学，信号转导和动物模型研究的基本知识，选择和应用PPI检测方法。

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RE-Aging: A functional analysis platform for human RNA editing associated with aging RE-Aging，一个与衰老相关的人类RNA编辑功能分析平台。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-11-18 DOI: 10.1016/j.mocell.2025.100300

Xinyu Pan , Hui Zhang , Weiwen Huang , Wenbin Ma , Zhou Songyang , Yuanyan Xiong

RNA editing alters mRNA sequences and is linked to aging. We introduce RE-Aging, a platform analyzing age-related RNA editing using GTEx data (259,620 A-to-I and 30,502 C-to-U sites across 27 tissues). Features include site exploration, age correlations, gene annotation, RNA structure analysis, and miRNA binding impact. Supports differential editing analysis (Wilcoxon test) and single-cell RNA editing age mapping for blood cells. Access at http://bioinfo-sysu.com/RE-Aging/.

RNA编辑会改变mRNA序列，并与衰老有关。我们介绍了RE-Aging，这是一个使用GTEx数据（27个组织中259,620个a -to- i和30,502个C-to-U位点）分析年龄相关RNA编辑的平台。功能包括位点探索、年龄相关性、基因注释、RNA结构分析和miRNA结合影响。支持血液细胞的差异编辑分析（Wilcoxon测试）和单细胞RNA编辑年龄图谱。访问网址：http://bioinfo-sysu.com/RE-Aging/。

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Ionotropic receptors mediate arachidic acid perception and food avoidance behavior in Drosophila melanogaster 嗜离子受体介导黑腹果蝇花生酸感知和食物回避行为。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-11-03 DOI: 10.1016/j.mocell.2025.100290

Roshani Nhuchhen Pradhan, Muhammad Atif, Youngseok Lee

Chemosensory functions are essential for animals to distinguish between nutritious and harmful compounds. Fatty acids are vital dietary components, but their taste perception mechanisms remain poorly understood. In Drosophila melanogaster, we identified a cluster of ionotropic receptors (IR7g, IR25a, IR51b, IR67a, and IR76b) that mediate the detection of the long-chain saturated fatty acid, arachidic acid (ARCH), through bitter-sensing gustatory receptor neurons. Our findings demonstrate that high doses of ARCH elicit strong aversive responses and exhibit toxic effects, decreasing survival rates in a dose-dependent manner. ARCH detection was found to require the activation of bitter-sensing gustatory receptor neurons, and the inhibition of sugar-sensing neurons contributed to diminished feeding responses. This study provides critical insights into the molecular and neural mechanisms underlying fatty acid perception in Drosophila, opening new avenues for understanding how animals manage dietary lipid intake and its implications for health.

化学感觉功能对动物区分营养物质和有害物质至关重要。脂肪酸是重要的饮食成分，但其味觉感知机制仍然知之甚少。在黑腹果蝇中，我们发现了一组嗜离子受体（IR7g、IR25a、IR51b、IR67a和IR76b），它们通过苦味感知味觉受体神经元（grn）介导长链饱和脂肪酸花生酸（ARCH）的检测。我们的研究结果表明，高剂量的ARCH引起强烈的厌恶反应，并表现出毒性作用，以剂量依赖的方式降低生存率。ARCH检测需要激活苦味感知神经元，而糖感知神经元的抑制导致了摄食反应的减弱。这项研究为果蝇脂肪酸感知的分子和神经机制提供了重要的见解，为理解动物如何管理饮食脂质摄入及其对健康的影响开辟了新的途径。

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IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-11-01 DOI: 10.1016/S1016-8478(25)00116-5

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Editorial Board Members/Copyright 编辑委员会成员/版权

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-11-01 DOI: 10.1016/S1016-8478(25)00117-7

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