Cell insight最新文献_第2页

Corrigendum to “The role of TRPV4 in acute sleep deprivation-induced memory impairment: Mechanisms of calcium dysregulation and synaptic plasticity disruption.” [Cell Insight 4 (2025) 100240] “TRPV4在急性睡眠剥夺引起的记忆障碍中的作用：钙调节失调和突触可塑性破坏的机制”的勘误。[Cell Insight 4 (2025) 100240]

Cell insight Pub Date : 2026-02-01 Epub Date: 2025-12-24 DOI: 10.1016/j.cellin.2025.100296

Meimei Guo , Feiyang Zhang , Sha Liu , Yi Zhang , Lesheng Wang , Jian Song , Wei Wei , Xiang Li

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HTATSF1 regulates innate antiviral immune response by orchestrating TRAF3-IRF3 and TRAF6-NF-κB pathways HTATSF1通过协调TRAF3-IRF3和TRAF6-NF-κB通路调控先天抗病毒免疫反应

Cell insight Pub Date : 2026-02-01 Epub Date: 2025-11-26 DOI: 10.1016/j.cellin.2025.100294

Jia-Qing Zeng, Zi-Lun Ruan, Qi Zhang, Xue-Mei Yi, Yun-Da Chen, Ming-Ming Hu, Shu Li

{"title":"HTATSF1 regulates innate antiviral immune response by orchestrating TRAF3-IRF3 and TRAF6-NF-κB pathways","authors":"Jia-Qing Zeng, Zi-Lun Ruan, Qi Zhang, Xue-Mei Yi, Yun-Da Chen, Ming-Ming Hu, Shu Li","doi":"10.1016/j.cellin.2025.100294","DOIUrl":"10.1016/j.cellin.2025.100294","url":null,"abstract":"<div><div>Upon infection, viral DNA/RNA is detected by cGAS/RIG-I-like receptors, triggering the adaptor MITA/STING- or VISA/MAVS-dependent innate antiviral immune response respectively. Both adaptors recruit the conserved TRAF3 and TRAF6 to activate TBK1-IRF3 and TAK1-NF-κB pathways respectively, leading to collaborative induction of antiviral effector genes. How the functions of TRAF3 and TRAF6 bifurcate in innate antiviral signaling remains enigmatic. We identified HTATSF1 as a positive regulator of virus-triggered innate antiviral response. Upon viral infection, HTATSF1 promotes HECTD3-catalyzed K63-linked polyubiquitination of TRAF3, leading to its recruitment of TBK1 and activation of IRF3. In contrast, HTATSF1 promotes recruitment of TAK1 to TRAF6 and activation of the TAK1-IKK-NF-κB axis independently of HECTD3. HTATSF1-deficiency impairs induction of downstream antiviral genes, and HTATSF1-deficient mice exhibit decreased cytokine production and increased mortality upon viral infection. Our findings demonstrate that HTATSF1 is an essential regulator of innate antiviral immune response by orchestrating the TRAF3-IRF3 and TRAF6-NF-κB pathways.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"5 1","pages":"Article 100294"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145738460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Cell insight Pub Date : 2026-02-01 Epub Date: 2026-02-05 DOI: 10.1016/S2772-8927(26)00004-0

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Host-pathogen interactions in African swine fever: From viral entry to systemic disease progression 非洲猪瘟的宿主-病原体相互作用：从病毒进入到全身性疾病进展

Cell insight Pub Date : 2026-02-01 Epub Date: 2025-12-26 DOI: 10.1016/j.cellin.2025.100297

Danyang Zhang , Shilei Zhang , Fayu Yang , Zixiang Zhu , Haixue Zheng

{"title":"Host-pathogen interactions in African swine fever: From viral entry to systemic disease progression","authors":"Danyang Zhang , Shilei Zhang , Fayu Yang , Zixiang Zhu , Haixue Zheng","doi":"10.1016/j.cellin.2025.100297","DOIUrl":"10.1016/j.cellin.2025.100297","url":null,"abstract":"<div><div>African swine fever virus (ASFV), a large and complex double-stranded DNA virus, is the etiological agent of African swine fever (ASF). ASF is a highly contagious and lethal hemorrhagic disease in domestic swine, which poses a persistent threat to global swine production and food security. Despite extensive research efforts, the development of safe and effective vaccines or antivirals remains elusive. This is largely attributable to the incomplete understanding of the intricate replication cycle of ASFV and its multifaceted evasion of host defenses. The mechanisms by which ASFV orchestrates widespread damage within the host to maintain its highly efficient replication and evade host defenses remain a key question in the field. In this comprehensive review, we aim to synthesize the current understanding of the key mechanisms underlying ASFV replication and immune evasion, as well as the associated host damage. By integrating these insights with the clinical and pathological features of ASF, we seek to deepen our comprehension of the viral pathogenic mechanisms and highlight existing research gaps. Ultimately, our goal is to provide valuable guidance for future endeavors in vaccine and antiviral drug development.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"5 1","pages":"Article 100297"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hydrophobic tagging: A promising paradigm for targeted protein degradation 疏水标签：靶向蛋白降解的一个有前途的范例

Cell insight Pub Date : 2026-02-01 Epub Date: 2025-12-04 DOI: 10.1016/j.cellin.2025.100295

Lilan Xin , Hongli Wang , Maoze Yang , Zhangxiao Guo , Man Zhu , Terry W. Moore , Chune Dong , Hai-Bing Zhou

{"title":"Hydrophobic tagging: A promising paradigm for targeted protein degradation","authors":"Lilan Xin , Hongli Wang , Maoze Yang , Zhangxiao Guo , Man Zhu , Terry W. Moore , Chune Dong , Hai-Bing Zhou","doi":"10.1016/j.cellin.2025.100295","DOIUrl":"10.1016/j.cellin.2025.100295","url":null,"abstract":"<div><div>Targeted protein degradation (TPD) has emerged as a groundbreaking therapeutic strategy, overcoming the limitations of traditional occupancy-driven pharmacology. Among TPD strategies, hydrophobic tag (HyT) technology exemplifies this paradigm shift by hijacking cellular protein quality control mechanisms for precise protein elimination. Structurally, HyT molecules integrate a target-specific ligand with a hydrophobic domain that emulates misfolded protein surfaces, facilitating selective recruitment of chaperone systems (e.g., heat shock protein 70, HSP70) and ubiquitin-proteasome system (UPS) activation, circumventing the E3 ligase dependency inherent to proteolysis-targeting chimera (PROTAC) systems. This innovative strategy offers distinct therapeutic benefits, including enhanced tissue-specific accumulation and the capacity to overcome resistance mechanisms. This review highlights the important advances in this rapidly growing field and critical limitations encountered in developing HyT degraders by analyzing the current status and representative examples of HyTs in degrading diverse pathogenic proteins, including oncogenic drivers (e.g., signal transducer and activator of transcription 3, STAT3), neurodegenerative aggregates (tau, α-synuclein), and viral envelope proteins. The critical developments, including the rational design of hydrophobic motifs and possible mechanistic insight into the degradation process of HyTs, have also been discussed.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"5 1","pages":"Article 100295"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of a comparative high-throughput screening platform for identifying glioblastoma subtype specific inhibitors 一种鉴别胶质母细胞瘤亚型特异性抑制剂的比较高通量筛选平台的开发

Cell insight Pub Date : 2025-12-01 Epub Date: 2025-09-29 DOI: 10.1016/j.cellin.2025.100284

Zilai Wang , Pin Zhang , Kiira M. Ratia , Ahmad Daher , Zongmin Zhao , Paul R. Carlier , Yuwei Jiang , Lijun Rong

{"title":"Development of a comparative high-throughput screening platform for identifying glioblastoma subtype specific inhibitors","authors":"Zilai Wang , Pin Zhang , Kiira M. Ratia , Ahmad Daher , Zongmin Zhao , Paul R. Carlier , Yuwei Jiang , Lijun Rong","doi":"10.1016/j.cellin.2025.100284","DOIUrl":"10.1016/j.cellin.2025.100284","url":null,"abstract":"<div><div>Glioblastoma (GBM) is the most lethal primary malignant brain tumor in adults, with the development of effective therapeutic agents largely hampered by vast tumor heterogeneity and the impedance of efficient drug delivery by the blood-brain barrier (BBB). Our prior research has demonstrated that adult neural stem cells (NSCs) and oligodendrocyte precursor cells (OPCs) can act as cells of origin for two distinct GBM subtypes (Type 1and Type 2) in mice, with significant conservation to human Type I and Type II GBM in functional properties and distinct responses to the inhibition by Tucatinib and Dasatinib. Based on these findings, we have established a robust high-throughput screening (HTS) assay to identify lineage-dependent subtype-specific as well as lineage-independent small molecule inhibitors for therapeutic development. Reported in the current study, we conducted a HTS using a kinase inhibitor library (900 compounds) in Type 1 and Type 2 GBM cells. Our primary screen identified 84 common inhibitors, 11 Type 1-specific inhibitors, and 18 Type 2-specific inhibitors. The confirmation screen verified R406 and Ponatinib as selective inhibitors of Type 2 GBM cells, and this was further validated in dose-dependent assays. Additionally, R406 exhibited a synergistic effect with Tucatinib in Type 2 GBM cells, providing a rationale for combination therapy. Our study demonstrated the feasibility of identifying subtype-specific therapeutic vulnerabilities using cell-lineage based GBM models and laid the foundation for expanded HTS studies in larger scale screens in both mouse and human GBM subtypes.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 6","pages":"Article 100284"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hypoxia-induced MT2A-tetrameric PKM2 interaction maintains PKM2 activity in a copper-ion-dependent manner 缺氧诱导的mt2a -四聚体PKM2相互作用以铜依赖的方式维持PKM2的活性

Cell insight Pub Date : 2025-12-01 Epub Date: 2025-09-24 DOI: 10.1016/j.cellin.2025.100277

Ronghui Gao , Qifang Li , Jiahao Guo , Zirou Peng , Chuan Gao , Zirui Zhou , Hankun Hu , Jing Zhang

{"title":"Hypoxia-induced MT2A-tetrameric PKM2 interaction maintains PKM2 activity in a copper-ion-dependent manner","authors":"Ronghui Gao , Qifang Li , Jiahao Guo , Zirou Peng , Chuan Gao , Zirui Zhou , Hankun Hu , Jing Zhang","doi":"10.1016/j.cellin.2025.100277","DOIUrl":"10.1016/j.cellin.2025.100277","url":null,"abstract":"<div><div>Hypoxia is a hallmark of solid tumors associated with tumor malignancy. Mitochondrial metabolic reprogramming is a key step in the process of cellular adaptation to hypoxic stress for tumor growth, but the regulatory mechanisms are not fully understood. In this study, through mitochondrial proteomics analysis, we find that metallothionein-2A (MT2A) is top-ranked among the significantly upregulated proteins in mitochondrial extract in response to hypoxia. Further, we show that hypoxia can induce the mitochondrial translocation of MT2A, a process that is dependent on copper ion. MT2A is highly expressed in hypoxic tumor tissues compared to normoxic ones in breast cancer patients, among whom higher expression of MT2A is associated with a worse prognosis, and it is required for breast tumor growth. Mechanistically, we reveal that copper ion is also essential for hypoxia-induced mitochondrial translocation of Pyruvate kinase M2 (PKM2), and facilitates the interaction of MT2A with the tetrameric form of PKM2 to maintain its activity, thereby promoting glycolysis and oxidative phosphorylation. Thus, our findings reveal the MT2A-copper-PKM2 axis as a potential therapeutic target to treat breast cancer.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 6","pages":"Article 100277"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145327418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Cell insight Pub Date : 2025-12-01 Epub Date: 2025-11-19 DOI: 10.1016/S2772-8927(25)00062-8

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Loop engineering of AtCas9 for effective and broad genome editing AtCas9环工程用于有效和广泛的基因组编辑

Cell insight Pub Date : 2025-12-01 Epub Date: 2025-10-22 DOI: 10.1016/j.cellin.2025.100286

Yue-Lin Zhang , Dong-Chao Huang , Min Duan , Yu-Ming Zhang , An-Hui Huang , Hao Yin , Ying Zhang

{"title":"Loop engineering of AtCas9 for effective and broad genome editing","authors":"Yue-Lin Zhang , Dong-Chao Huang , Min Duan , Yu-Ming Zhang , An-Hui Huang , Hao Yin , Ying Zhang","doi":"10.1016/j.cellin.2025.100286","DOIUrl":"10.1016/j.cellin.2025.100286","url":null,"abstract":"<div><div>Efficient genome editing in mammalian cells is essential for CRISPR-based therapeutics. While extensive efforts focused on combining multiple beneficial point mutations to enhance Cas9 activity, the potential of engineering surface-exposed loops remains largely underexplored. Here, we present loop engineering as a streamlined strategy to enhance Cas9 performance. Substituting loops of thermophilic AtCas9 with counterparts from mesophilic Nme1Cas9 generated the AtCas9-Z7 variant, which significantly improves nuclease and base editing efficiency. Biochemical assays showed that Mg<sup>2+</sup> promotes RNP-DNA interactions, and Z7 maintains high binding affinity under magnesium-limiting condition, a common constraint for Cas9 activity in mammalian cells. Molecular dynamics simulations revealed that Z7 adopts a stable, compact conformation. Importantly, loop engineering can be combined with structure-guided point mutations to further boost activity. The resulting Z7-E78-ABE variant not only achieved a 5.76-fold increase compared to WT AtCas9 and expanded PAM recognition, while enabling editing in primary human T cells, which was not observed with WT AtCas9. Extending this strategy, loop transplantation into GeoCas9 and ThermoCas9 boosted editing efficiency by a median of 14.50-fold and 7.37-fold, respectively, at non-canonical PAMs. Collectively, these results establish loop engineering as a rational and modular approach for Cas9 optimization with therapeutic potential.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 6","pages":"Article 100286"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145467591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Mitochondrial cristae remodeling: Mechanisms, functions, and pathology 线粒体嵴重塑：机制、功能和病理

Cell insight Pub Date : 2025-12-01 Epub Date: 2025-10-16 DOI: 10.1016/j.cellin.2025.100285

Jianglong Yu , Yuanchun Luo , Jiacheng Lin , Zhuofan Li , Zheng Fang , He He , Chaojun Yan , Zhiyin Song

{"title":"Mitochondrial cristae remodeling: Mechanisms, functions, and pathology","authors":"Jianglong Yu , Yuanchun Luo , Jiacheng Lin , Zhuofan Li , Zheng Fang , He He , Chaojun Yan , Zhiyin Song","doi":"10.1016/j.cellin.2025.100285","DOIUrl":"10.1016/j.cellin.2025.100285","url":null,"abstract":"<div><div>Mitochondrial cristae are the principal sites of oxidative phosphorylation and are central to mitochondria-dependent energy metabolism. Rather than static folds, cristae are dynamic bioenergetic compartments that remodel in response to physiological and stress cues. During remodeling, their number, length, width, lateral alignment, curvature/stiffness, and the geometry of crista junctions (CJs) can change. Depending on cellular context, cristae may increase in abundance, tighten or widen, and exhibit opening or closure of CJs, with corresponding effects on respiratory-chain organization and supercomplex assembly. Key regulators include OPA1 (and its proteolytic processing), the MICOS complex that scaffolds CJs, F<sub>1</sub>Fo-ATP synthase dimerization/oligomerization that shapes high-curvature ridges, and cardiolipin, which stabilizes inner-membrane architecture. Abnormal cristae compromise electron transport, ATP production, and mitochondrial metabolism, contributing to neurodegeneration and metabolic disease etc. In this review, we synthesize current insights into the molecular control of cristae ultrastructure and its impact on mitochondrial metabolism, delineate structural features and quantitative readouts, and highlight mechanisms that govern cristae remodeling under physiological and stress conditions, with an emphasis on diseases arising from aberrant crista architecture.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 6","pages":"Article 100285"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145419276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0