Cell Chemical Biology最新文献

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Discovery of bioactive peptidoglycan fragments from Lactobacillaceae that confer intestinal protection in hosts 乳酸菌科生物活性肽聚糖片段的发现，赋予宿主肠道保护作用

IF 8.6 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Chemical Biology

Pub Date : 2026-02-09 DOI: 10.1016/j.chembiol.2026.01.005

Yaquan Liang, Christopher Adamson, Chenyu Li, Evan Wei Long Ng, Yujie Li, Yuan Qiao

Gut bacteria-derived peptidoglycan fragments (PGNs) are key signaling molecules in mammalian hosts. However, the production and functional roles of soluble PGNs secreted by individual gut bacterial species have not been systematically explored. Herein, we used a targeted LC-MS/MS approach to profile PGNs released by bacteria, identifying Lactobacillaceae as the predominant producers of disaccharide PGNs in culture supernatants. We then chemically synthesized such disaccharide PGNs and confirmed their activation of the mammalian sensor NOD2. Notably, priming murine macrophages with disaccharide PGNs induced tolerance to subsequent stimulation by TLR2/4 ligands, suggesting that sustained exposure to bioactive PGNs in the gut may shape host immune responses. Consistently, the administration of the disaccharide PGN, GM-AQK, effectively alleviated gut inflammation in a DSS-induced colitis mouse model. Together, these findings deepen our understanding of PGN-mediated gut microbiota-host crosstalk and position natural disaccharide PGNs as promising postbiotic candidates for the therapeutic modulation of intestinal inflammation.

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引用次数: 0

Mechanosensation promotes broad-spectrum antiviral defense through membrane remodeling. 机械感觉通过膜重塑促进广谱抗病毒防御。

IF 7.2 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Chemical Biology

Pub Date : 2026-02-05 DOI: 10.1016/j.chembiol.2026.01.004

Yuehan Huang, Haoran Guo, Delong Gao, Yubin Tang, Jiaxin Yang, Fushun Ni, Ling Xue, Huili Li, Dongxue Liu, Lili Zhang, Qingran Yang, Shijin Wang, Xiao-Fang Yu, Zhenglei Yu, Junqi Niu, Wei Wei

The capacity to sense mechanical stimuli represents one of the most fundamental characteristics of life, enabling organisms to navigate their environment. Here, we identify the mechano-antiviral response system (MARS), a Piezo1-mediated pathway that confers broad-spectrum antiviral immunity distinct from known innate immune systems. Using enterovirus D68 (EV-D68) as a model, we demonstrate that cellular compression or fluid pressure activates Piezo1-dependent antiviral resistance in non-immune cells. Piezo1 functions as a natural antiviral factor, and its pharmacological activation protects against multiple clinical isolates of EV-D68. Mechanistically, the activation of the biomechanical-Piezo1 axis results in a marked reduction in host cell membrane fluidity, a critical determinant for viral entry. Consequently, MARS restricts the replication of diverse viruses, including rhinovirus and influenza. In vivo studies reveal that Piezo1 agonists or mechanical stimuli alleviate EV-D68-induced neurological damage and lethality. Our findings underscore MARS-mediated membrane remodeling as a non-canonical antiviral strategy, expanding the paradigms of immune stimulation.

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引用次数: 0

Aerobic glycolysis promotes NLRP3 inflammasome activation via NLRP3 lactylation 有氧糖酵解通过NLRP3乳酸化促进NLRP3炎性体活化

IF 8.6 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Chemical Biology

Pub Date : 2026-02-04 DOI: 10.1016/j.chembiol.2026.01.003

Wei Liu, Tianyi Zhang, Bohong Wang, Hang Yin

Bacteria-infected macrophages undergo pyroptosis to release inflammatory cytokines, which contributes to host defense. It has been known that activated macrophages involve metabolic reprogramming. However, the metabolic changes and the role of metabolites in pyroptotic macrophages are not fully understood. Here, we revealed that aerobic glycolysis product, lactate, could promote NLRP3 inflammasome activation induced pyroptosis. We found that endogenous lactate facilitates ASC recruitment to NLRP3 cores on the organelle membrane, thus inducing NLRP3 inflammasome complex formation. Mechanistically, we identified NLRP3 as a target protein modified by lactate, which is lactylated by AARS2. We confirmed lactylated sites on NLRP3 by LC-MS/MS analysis and verified that lactylation at K24 and K565 of NLRP3 facilitates inflammasome activation in macrophage. In vivo, inhibition of lactate production alleviates inflammatory responses in polymicrobial sepsis. Overall, our results indicate the role of lactate in regulating macrophage pyroptosis and the crosstalk between metabolism and innate immunity.

细菌感染的巨噬细胞通过热亡释放炎症细胞因子，有助于宿主防御。众所周知，活化的巨噬细胞涉及代谢重编程。然而，巨噬细胞的代谢变化和代谢物的作用尚不完全清楚。在这里，我们发现有氧糖酵解产物乳酸可以促进NLRP3炎性体激活诱导的焦亡。我们发现内源性乳酸促进ASC募集到细胞器膜上的NLRP3核心，从而诱导NLRP3炎性体复合物的形成。在机制上，我们发现NLRP3是由AARS2乳酸化的乳酸修饰的靶蛋白。我们通过LC-MS/MS分析证实了NLRP3上的乳酸化位点，并证实了NLRP3的K24和K565的乳酸化促进了巨噬细胞炎症小体的激活。在体内，抑制乳酸生成可减轻多微生物脓毒症的炎症反应。综上所述，我们的研究结果表明乳酸在调节巨噬细胞热亡以及代谢与先天免疫之间的串扰中的作用。

引用次数: 0

The HEAT repeat protein MROH7 regulates the inflammatory macrophage response via LBP acetylation HEAT重复蛋白MROH7通过LBP乙酰化调节炎性巨噬细胞反应

IF 8.6 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Chemical Biology

Pub Date : 2026-02-03 DOI: 10.1016/j.chembiol.2026.01.002

Hangchao Zhang, Jian Fu, Yan Guo, Shijie Liu, Xuehua Mei, Xiu Zeng, Wenkai Ren

引用次数: 0

Advances in degradomics technologies to assess proteolytic cleavage events 评价蛋白水解裂解事件的降解组学技术进展

IF 8.6 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Chemical Biology

Pub Date : 2026-02-02 DOI: 10.1016/j.chembiol.2026.01.001

Alexander R. Ziegler, Nichollas E. Scott, Laura E. Edgington-Mitchell

引用次数: 0

An interactive resource mapping the proteome and reactive cysteine landscape across the NCI-60 reveals cell and tissue-specific profiles 通过NCI-60绘制蛋白质组和反应性半胱氨酸景观的交互式资源揭示了细胞和组织特异性概况。

IF 7.2 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Chemical Biology

Pub Date : 2026-01-15 DOI: 10.1016/j.chembiol.2025.12.003

José L. Montaño , Vishnu R. Tejus , Vee Xu , Andrew C. Condon , Andrew K. Ecker , Andreas Langen , Kevin K. Leung , Balyn W. Zaro

The NCI-60 cancer cell line panel is one of the most extensively characterized and publicly accessible resources in cancer research. Here, we expand this platform by generating a comprehensive proteomic and cysteine reactivity atlas using shotgun proteomics and quantitative chemoproteomics. We quantified over 12,000 proteins and identified more than 36,000 reactive cysteines, including over 10,000 hyperreactive sites, across the panel. Our analyses reveal widespread heterogeneity in cysteine reactivity, while conserved hyperreactive cysteines strongly correlate with functional roles. Tissue-specific cysteine reactivity occurred independently of protein abundance, highlighting context-dependent regulation. To enable exploration and integration with existing datasets, we developed an interactive online database that allows users to visualize protein and cysteine coverage and design custom cell line panels. Together, these data and tools illuminate the landscape of cysteine reactivity in cancer and provide a foundational resource to advance future studies in protein function, redox biology, and covalent drug discovery.

NCI-60癌症细胞系面板是癌症研究中最广泛表征和可公开访问的资源之一。在这里，我们通过使用霰弹枪蛋白质组学和定量化学蛋白质组学生成一个全面的蛋白质组学和半胱氨酸反应性图谱来扩展这个平台。我们量化了超过12,000种蛋白质，并确定了超过36,000种活性半胱氨酸，包括整个小组中超过10,000个高反应位点。我们的分析揭示了半胱氨酸反应性的广泛异质性，而保守的高反应性半胱氨酸与功能作用密切相关。组织特异性半胱氨酸反应性独立于蛋白质丰度发生，突出了上下文依赖性调节。为了探索和整合现有的数据集，我们开发了一个交互式在线数据库，允许用户可视化蛋白质和半胱氨酸的覆盖范围，并设计定制的细胞系面板。总之，这些数据和工具阐明了半胱氨酸在癌症中的反应性，并为推进蛋白质功能、氧化还原生物学和共价药物发现的未来研究提供了基础资源。

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引用次数: 0

Cutting without cleaving: How caspase-1 shapes leukemia beyond enzymatic activity 切割而不切割：caspase-1如何超越酶活性塑造白血病

IF 7.2 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Chemical Biology

Pub Date : 2026-01-15 DOI: 10.1016/j.chembiol.2025.12.011

Lukas M. Braun , Robert Zeiser

In this issue of Cell Chemical Biology, Uible et al.¹ uncover a previously unknown non-proteolytic role for caspase-1 (CASP1) in leukemia. CASP1 sustains leukemic growth by coordinating mTORC1-NF-κB signaling as scaffold for RPTOR, rather than regulating IL-1β and pyroptosis. CASP1’s scaffolding function was found as a therapeutic vulnerability in leukemia.

在这一期的《细胞化学生物学》中，Uible等人揭示了caspase-1 （CASP1）在白血病中的非蛋白水解作用。CASP1通过协调mTORC1-NF-κB信号作为RPTOR的支架来维持白血病的生长，而不是调节IL-1β和焦亡。CASP1的支架功能被发现是白血病的治疗脆弱性。

引用次数: 0

Targeting the endocannabinoid-eicosanoid axis to treat pain: Promise and pitfalls 针对内源性大麻素-二十烷类轴治疗疼痛：希望和陷阱

IF 7.2 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Chemical Biology

Pub Date : 2026-01-15 DOI: 10.1016/j.chembiol.2025.12.004

Jürg Gertsch

In this issue of Cell Chemical Biology, Tufail et al.¹ demonstrate that the peripheral diacylglycerol lipase α/β inhibitor A1480LS exerts potent anti-inflammatory and analgesic effects by blocking 2-arachidonoylglycerol synthesis and reducing arachidonate-derived eicosanoid production. However, potential risks from altered protein kinase C signaling due to elevated diacylglycerols warrant further evaluation in future therapeutic applications.

在这一期的《细胞化学生物学》中，Tufail等人1证明外周二酰基甘油脂肪酶α/β抑制剂A1480LS通过阻断2-花生四烯酮酰甘油的合成和减少花生四烯酮衍生的类二十烷酸的产生，具有有效的抗炎和镇痛作用。然而，由于二酰基甘油升高导致的蛋白激酶C信号改变的潜在风险需要在未来的治疗应用中进一步评估。

引用次数: 0

Targeted discovery of aromatic glycosides with dual detoxification effects via a highly customized molecular networking platform 通过高度定制的分子网络平台，有针对性地发现具有双重解毒作用的芳香糖苷。

IF 7.2 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Chemical Biology

Pub Date : 2026-01-15 DOI: 10.1016/j.chembiol.2025.12.001

Wen-Chao Yu , Yan-Lei Yu , Bing-Cheng Dong , Ze-Yu Wang , Au-Qi Du , Song-Wei Li , Buddha Bahadur Basnet , Xiao-Ze Bao , Xuan-Rong Sun , Xing-Nuo Li , Qi Xuan , Qihao Wu , Hong Wang , Bin Wei

Natural products embedded within complex metabolomes are valuable sources of drug leads. Untargeted metabolomics using cosine-based MS² comparisons is widely used for discovering bioactive molecules. To improve annotation accuracy and resolution, alternative algorithms have been developed to complement cosine-based MS² comparison. Here, we present MSanalyst, a user-friendly platform that integrates 46 distinct mass spectral similarity algorithms. Benchmarking with microbial metabolite datasets and over three million MS² spectral pairs demonstrated that complementary algorithms substantially enhance the detection of metabolite-metabolite spectral connections. Applying MSanalyst to Kutzneria viridogrisea DSM 43850 led to the discovery of a class of aromatic glycosides, the kutznaposides. Biological assays and multi-omics analyses revealed that kutznaposides C–F arise from a previously unrecognized menaquinone shunt pathway, enabling the host to mitigate oxidative stress and avoid self-toxicity. Collectively, these findings highlight the potential of MSanalyst to uncover hidden metabolites, metabolic pathways, and their biological functions.

复杂代谢组中的天然产物是药物先导的宝贵来源。使用基于余弦的MS2比较的非靶向代谢组学广泛用于发现生物活性分子。为了提高标注精度和分辨率，已经开发了替代算法来补充基于余弦的MS2比较。在这里，我们提出了MSanalyst，一个用户友好的平台，集成了46种不同的质谱相似算法。对微生物代谢物数据集和超过300万个MS2光谱对进行基准测试表明，互补算法大大增强了代谢物-代谢物光谱连接的检测。将MSanalyst应用于库兹纳氏菌（Kutzneria viridogrisea） DSM 43850中，发现了一类芳香苷类库兹纳氏苷。生物学分析和多组学分析显示，库兹纳苷C-F来自先前未被识别的甲基萘醌分流途径，使宿主能够减轻氧化应激并避免自毒性。总的来说，这些发现突出了MSanalyst揭示隐藏代谢物、代谢途径及其生物学功能的潜力。

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引用次数: 0

Scaffolding-dependent CASP1 constrains excessive cell-intrinsic inflammatory signaling in leukemia 支架依赖性CASP1抑制白血病中过多的细胞内在炎症信号

IF 7.2 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Chemical Biology

Pub Date : 2026-01-15 DOI: 10.1016/j.chembiol.2025.12.002

Emma E. Uible , Issac Choi , Courtnee A. Clough , Aishlin Hassan , Annabelle J. Anandappa , Julianna Fisher , Bibek Karki , Kathleen Hueneman , Kwangmin Choi , Eric J. Vick , William Seibel , Kenneth D. Greis , Lynn Lee , Courtney Jones , Timothy M. Chlon , Jorge Henao-Mejia , Chandrashekhar Pasare , John T. Cunningham , Andrew G. Volk , Daniel T. Starczynowski

Caspase-1 (CASP1) is best known for regulating IL-1β processing and pyroptosis; however, its role in leukemia has not been clearly defined. Here, we show that loss of CASP1 impairs leukemic cell growth, drives differentiation, and reduces leukemic burden in vivo, independent of its CASP1 protease activity. Instead, CASP1 functions as a scaffolding hub, controlling nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling via its interaction with raptor (RPTOR), a component of mTORC1. Deletion of CASP1 or disruption of its CARD domain induces excessive NF-κB activity and impairs leukemic cell function. We further developed a proteolysis-targeting chimera (PROTAC) degrader that selectively depletes Pro-CASP1 and suppresses leukemic cells. These findings reveal CASP1 as a regulator of mTORC1-NF-κB signaling in leukemia and highlight its scaffolding activity as a therapeutic vulnerability.

Caspase-1 （CASP1）最著名的调控IL-1β加工和焦亡；然而，它在白血病中的作用尚未明确。在这里，我们发现CASP1的缺失会损害白血病细胞的生长，驱动分化，并减少体内的白血病负担，而不依赖于CASP1蛋白酶的活性。相反，CASP1作为一个脚手架枢纽，通过与mTORC1的一个组分raptor （RPTOR）的相互作用，控制活化B细胞（NF-κB）信号的核因子kappa-轻链增强子。CASP1的缺失或其CARD结构域的破坏可诱导NF-κB活性过高并损害白血病细胞功能。我们进一步开发了一种靶向蛋白水解的嵌合体（PROTAC）降解物，选择性地消耗Pro-CASP1并抑制白血病细胞。这些发现揭示了CASP1在白血病中作为mTORC1-NF-κB信号的调节因子，并强调了其支架活性作为治疗脆弱性。

{"title":"Scaffolding-dependent CASP1 constrains excessive cell-intrinsic inflammatory signaling in leukemia","authors":"Emma E. Uible , Issac Choi , Courtnee A. Clough , Aishlin Hassan , Annabelle J. Anandappa , Julianna Fisher , Bibek Karki , Kathleen Hueneman , Kwangmin Choi , Eric J. Vick , William Seibel , Kenneth D. Greis , Lynn Lee , Courtney Jones , Timothy M. Chlon , Jorge Henao-Mejia , Chandrashekhar Pasare , John T. Cunningham , Andrew G. Volk , Daniel T. Starczynowski","doi":"10.1016/j.chembiol.2025.12.002","DOIUrl":"10.1016/j.chembiol.2025.12.002","url":null,"abstract":"<div><div>Caspase-1 (CASP1) is best known for regulating IL-1β processing and pyroptosis; however, its role in leukemia has not been clearly defined. Here, we show that loss of CASP1 impairs leukemic cell growth, drives differentiation, and reduces leukemic burden <em>in vivo</em>, independent of its CASP1 protease activity. Instead, CASP1 functions as a scaffolding hub, controlling nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling via its interaction with raptor (RPTOR), a component of mTORC1. Deletion of CASP1 or disruption of its CARD domain induces excessive NF-κB activity and impairs leukemic cell function. We further developed a proteolysis-targeting chimera (PROTAC) degrader that selectively depletes Pro-CASP1 and suppresses leukemic cells. These findings reveal CASP1 as a regulator of mTORC1-NF-κB signaling in leukemia and highlight its scaffolding activity as a therapeutic vulnerability.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"33 1","pages":"Pages 59-73.e10"},"PeriodicalIF":7.2,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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