Acta biochimica et biophysica Sinica最新文献_第9页

Metabolic reprogramming-the nexus of cellular adaptations, organ crosstalk, and therapeutic innovations in human diseases. 代谢重编程——细胞适应、器官串扰和人类疾病治疗创新的联系。

IF 4.5 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-06-25 DOI: 10.3724/abbs.2026110

Jun Ren, Hartmut Schlüter, Marcel Kwiatkowski, Ling Lin

引用次数: 0

A bifunctional aptamer-siRNA chimera targeting ACE2 for the inhibition of SARS-CoV-2 S pseudovirus entry and replication. 靶向ACE2的双功能适配体- sirna嵌合体抑制sars - cov - 2s假病毒的进入和复制。

IF 4.5 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-06-25 DOI: 10.3724/abbs.2026087

Tao Jiang, Zhiqiang Chen, Wei Li, Xiaohua Ni, Wen Pan, Qihan Wu

{"title":"A bifunctional aptamer-siRNA chimera targeting ACE2 for the inhibition of SARS-CoV-2 S pseudovirus entry and replication.","authors":"Tao Jiang, Zhiqiang Chen, Wei Li, Xiaohua Ni, Wen Pan, Qihan Wu","doi":"10.3724/abbs.2026087","DOIUrl":"https://doi.org/10.3724/abbs.2026087","url":null,"abstract":"The relentless evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of immune-evasive variants underscore an urgent need for novel therapeutic strategies that are resilient to viral mutations. Targeting conserved host factors essential for viral entry represents a promising approach to overcome this challenge. Here, we report the development of a bifunctional therapeutic platform targeting the primary human receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2). Using systematic evolution of ligands by exponential enrichment (SELEX), we isolate a high-affinity DNA aptamer, designated AA2, that binds to human ACE2 with a dissociation constant ( Kd) of 5.41 ± 1.23 nM. Molecular docking and competitive binding assays confirm that AA2 sterically hinders the interaction between the viral spike receptor-binding domain (RBD) and ACE2. Consequently, AA2 demonstrates potent neutralization of SARS-CoV-2 S pseudovirus entry into host cells. To achieve a synergistic antiviral effect, we engineer an aptamer-siRNA chimera (AsiC) by conjugating AA2 to a short interfering RNA (siRNA) targeting the GFP coding region of the pseudovirus genome. This AsiC construct significantly represses viral replication compared to aptamer or siRNA treatment alone, validating a dual mechanism of action that combines receptor blockade with targeted gene silencing. This study establishes a robust proof-of-concept for an ACE2-targeted AsiC, representing a new class of dual-function antiviral therapeutics with the potential to effectively combat current and future ACE2-dependent coronaviruses.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

How distinct hormones sculpt a common receptor: ligand-specific conformational pathways of the insulin receptor. 不同的激素如何塑造一个共同的受体：胰岛素受体的配体特异性构象途径。

IF 4.5 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-06-25 DOI: 10.3724/abbs.2026024

Di Jiang, Dan Tang, Shiqian Qi

引用次数: 0

The tRNA landscape in cancer: from pathogenesis to therapeutic interventions. 癌症中的tRNA景观：从发病机制到治疗干预。

IF 4.5 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-06-25 DOI: 10.3724/abbs.2026093

Ni Jian, Han Ren, Yingqi Huang, Lijuan Ma, Yingchen Zhou, Libo Yu, Weiren Huang

{"title":"The tRNA landscape in cancer: from pathogenesis to therapeutic interventions.","authors":"Ni Jian, Han Ren, Yingqi Huang, Lijuan Ma, Yingchen Zhou, Libo Yu, Weiren Huang","doi":"10.3724/abbs.2026093","DOIUrl":"10.3724/abbs.2026093","url":null,"abstract":"Transfer RNA (tRNA) acts not only as an indispensable adaptor in protein synthesis but also as a key contributor to tumorigenesis when its regulation is disrupted. This review systematically summarizes aberrant tRNA-related mechanisms in cancer, including altered tRNA expression profiles, abnormal post-transcriptional modifications, dysregulated aminoacylation, production of tRNA-derived small RNAs (tdRs), and defects in tRNA trafficking and translational fidelity. Notably, the metabolically abnormal tumor microenvironment actively shapes tRNA reprogramming to facilitate adaptive survival, while dysregulated tRNA elements, such as specific modifications and tdRs, further drive cancer stem cell properties and therapeutic resistance. Collectively, these alterations reprogram the oncoproteome and signaling networks, thereby promoting tumor cell proliferation, metastasis, immune evasion, and drug resistance. Targeting these mechanisms represents a promising strategy for developing novel cancer therapies. Potential approaches include the use of suppressor tRNAs to restore tumor suppressor gene function, the employment of tdRs to modulate oncogenic signaling pathways, or direct inhibition of enzymes involved in tRNA biogenesis. These strategies aim to remodel the dysfunctional tRNA network in cancer and offer new avenues for innovative treatments.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":"58 6","pages":"1187-1212"},"PeriodicalIF":4.5,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Caught the 'Catch' of midnolin: structural basis for broad substrate specificity in ubiquitin-independent proteasomal degradation. 抓住了midnolin的“Catch”：泛素非依赖性蛋白酶体降解中广泛底物特异性的结构基础。

IF 4.5 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-06-25 DOI: 10.3724/abbs.2026006

Chuanyin Li, Ronggui Hu

引用次数: 0

Bioinformatics classification of the MgtE Mg ² ⁺ channel and de novo protein design for the stabilization of its novel subclass. MgtE mg2 +通道的生物信息学分类及其新亚类稳定的从头蛋白设计。

IF 4.5 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-06-25 DOI: 10.3724/abbs.2025224

Zhixuan Zhao, Kimiho Omae, Wataru Iwasaki, Ziyi Zhang, Fazhi Pan, Eun-Jin Lee, Koichi Ito, Motoyuki Hattori

{"title":"Bioinformatics classification of the MgtE Mg 2 + channel and de novo protein design for the stabilization of its novel subclass.","authors":"Zhixuan Zhao, Kimiho Omae, Wataru Iwasaki, Ziyi Zhang, Fazhi Pan, Eun-Jin Lee, Koichi Ito, Motoyuki Hattori","doi":"10.3724/abbs.2025224","DOIUrl":"10.3724/abbs.2025224","url":null,"abstract":"MgtE channels play crucial roles in Mg 2 + homeostasis and are implicated in bacterial survival under antibiotic exposure. Previous structural and biophysical studies have focused predominantly on Thermus thermophilus MgtE, leaving the structural and mechanistic diversity of MgtE family proteins largely unexplored. In this study, via a genome mining approach, we identify diverse MgtE homologs, including a novel subclass termed the \"mini-N type\", which lacks the canonical cytoplasmic N and CBS domains but possesses a unique small N-like domain. Despite extensive expression screening, mini-N-type homologs cannot be stably purified. To address this issue, we design a series of de novo proteins and determine their crystal structures. A selected de novo protein is fused to a mini-N-type MgtE, enabling successful purification and preliminary cryo-EM imaging. Our findings demonstrate that de novo-designed protein fusions serve as powerful tools for stabilizing and purifying otherwise unstable membrane proteins, opening new avenues for structural and functional studies of otherwise inaccessible membrane proteins.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":"58 6","pages":"1402-1412"},"PeriodicalIF":4.5,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The macrophage PELI1-JAK2/STAT3-secretome axis: a potential target for ameliorating septic inflammation and coagulation dysfunction. 巨噬细胞PELI1-JAK2/ stat3 -分泌组轴：改善脓毒性炎症和凝血功能障碍的潜在靶点

IF 4.5 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-06-23 DOI: 10.3724/abbs.2026053

Yi Huang, Lizhen Xuan, Kunlin Zhou, Linli Wang, Yiran He, Xu Wang, Mingchen Han, Shengyu Hao, Minjie Ju

{"title":"The macrophage PELI1-JAK2/STAT3-secretome axis: a potential target for ameliorating septic inflammation and coagulation dysfunction.","authors":"Yi Huang, Lizhen Xuan, Kunlin Zhou, Linli Wang, Yiran He, Xu Wang, Mingchen Han, Shengyu Hao, Minjie Ju","doi":"10.3724/abbs.2026053","DOIUrl":"https://doi.org/10.3724/abbs.2026053","url":null,"abstract":"This study aims to investigate the role of macrophage PELI1 in sepsis-induced inflammation and coagulation dysfunction, focusing on its regulatory mechanism over the secretome through the JAK2/STAT3 signaling pathway. Analysis of a public single-cell RNA-seq dataset from septic patients reveals significant upregulation of PELI1 in CD14 + monocytes from non-survivors. To functionally validate this finding, a murine sepsis model is established using cecal ligation and puncture (CLP). Protein and gene expression levels in lung tissue and plasma are detected by RT-qPCR, western blotting, and ELISA, while lung injury and fibrin deposition are assessed by H&E staining and immunohistochemistry. For in vitro experiments, PELI1 expression is modulated in RAW264.7 macrophages using gene knockdown strategies. Our results confirm that PELI1 is significantly upregulated in septic mice and closely associates with severe inflammatory responses and coagulation dysfunction. Mechanistically, PELI1 knockout suppresses the activation of the JAK2/STAT3 signaling pathway, thereby reducing the production and secretion of key inflammatory cytokines and coagulation factors induced by lipopolysaccharide. Importantly, transfer of the secretome from bone marrow-derived macrophages (BMDM) of PELI1-knockout mice into wild-type septic mice is sufficient to alleviate sepsis pathology, which recapitulates the protective effect observed in genetic knockout. Our findings demonstrate that PELI1 mediates sepsis-induced tissue injury by regulating the secretome via the JAK2/STAT3 pathway, which identifies the PELI1-secretome axis as a potential therapeutic target for this life-threatening condition.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HDAC6 promotes osimertinib resistance evolution in non-small cell lung cancer by activating EGFR degradation through the ubiquitin-proteasome pathway. HDAC6通过泛素-蛋白酶体途径激活EGFR降解，促进非小细胞肺癌的奥希替尼耐药性进化。

IF 4.5 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-06-23 DOI: 10.3724/abbs.2026084

Cheng Yang, Danlei Xu, Zifang Zhu, Zhen Kang, Kangkang Ren, Yihan Yang, Ye Huang, Wei Zhang, Jun Che, Xinping Xu, Xiaolei Li

{"title":"HDAC6 promotes osimertinib resistance evolution in non-small cell lung cancer by activating EGFR degradation through the ubiquitin-proteasome pathway.","authors":"Cheng Yang, Danlei Xu, Zifang Zhu, Zhen Kang, Kangkang Ren, Yihan Yang, Ye Huang, Wei Zhang, Jun Che, Xinping Xu, Xiaolei Li","doi":"10.3724/abbs.2026084","DOIUrl":"https://doi.org/10.3724/abbs.2026084","url":null,"abstract":"Osimertinib is the standard first-line treatment for patients with non-small cell lung cancer (NSCLC) harboring EGFR-sensitive mutations. However, drug resistance inevitably develops, highlighting the critical need for strategies to overcome this resistance and prolong therapeutic efficacy. Understanding the mechanisms underlying drug resistance is essential, and drug-resistant cell models serve as valuable tools for investigating acquired resistance. In this study, we establish an osimertinib resistance evolution model in vitro by continuous high-dose drug induction and identify cell lines exhibiting \"permanent\" resistance to osimertinib (osimertinib resistant, OR). Transcriptome sequencing (RNA-seq), gain- and loss-of-function assay, including lentiviral-mediated overexpression and RNAi knockdown, pharmacological inhibition, and protein degradation analysis reveal significant alterations in genes associated with epigenetic regulation, notably a marked upregulation of histone deacetylase 6 (HDAC6) in OR cells. Knockdown of HDAC6 or pharmacological inhibition of HDAC6 restores the sensitivity of OR cells to osimertinib, whereas overexpression of HDAC6 in sensitive cells reduces drug efficacy and accelerates the onset of resistance. Furthermore, we find that HDAC6 upregulation promotes EGFR degradation, thereby contributing to resistance. Collectively, our findings demonstrate the utility of drug resistance evolution models in identifying key resistance factors. HDAC6 plays a pivotal role in osimertinib resistance, and targeting HDAC6 may represent a novel therapeutic strategy to overcome resistance and enhance treatment efficacy.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"xx"},"PeriodicalIF":4.5,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrating genetically encoded fluorescent sensors to elucidate the spatiotemporal choreography of necrosis by sodium overload. 整合基因编码荧光传感器以阐明钠超载引起的坏死的时空编排。

IF 3.4 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-06-12 DOI: 10.3724/abbs.2026102

Yike Song, Yale Xia, Yin Fu, Jing Yao, Lian Zeng, Yuxi Duan, Ni Su, Xie Li, Xiawei Cheng, Yuzheng Zhao, Yi Yang, Yejun Zou

{"title":"Integrating genetically encoded fluorescent sensors to elucidate the spatiotemporal choreography of necrosis by sodium overload.","authors":"Yike Song, Yale Xia, Yin Fu, Jing Yao, Lian Zeng, Yuxi Duan, Ni Su, Xie Li, Xiawei Cheng, Yuzheng Zhao, Yi Yang, Yejun Zou","doi":"10.3724/abbs.2026102","DOIUrl":"https://doi.org/10.3724/abbs.2026102","url":null,"abstract":"Necrosis by sodium overload (NECSO) is a distinct cell death modality induced by the chemical regulator necrocide 1 (NC1), which targets the transient receptor potential melastatin 4 (TRPM4) channel to drive excessive sodium influx and potassium efflux. This unique necrosis is characterized by the exchange of monovalent ions, a restrained ATP supply, redox disorder and a final membrane rupture as main features. Real-time monitoring of metabolic and redox causality during the whole process in living cells has been technically challenging. To bridge this gap, we integrate an advanced toolset of genetically encoded fluorescent sensors to monitor monovalent ions, energy metabolites, and redox equivalents with high spatiotemporal resolution. By directing these sensors to specific subcellular compartments, we successfully capture the real-time choreography of potassium loss specifically induced by NC1 via TRPM4. Furthermore, we establish a precise detection paradigm for evaluating energy currency by integrating sensors for NADH and ATP that are capable of subcellular imaging. We observe general and rapid NADH accumulation along with an ATP shortage in the mitochondria and cytosol. A concomitant reduction in mitochondrial oxidative stress is observed. This study not only elucidates the metabolic progression of a peculiar type of necrosis but also establishes a robust methodological framework for applying genetically encoded sensors to broader physiological and toxicological research..","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of KDM5A alleviates ferroptosis in myocardial infarction via the GDF15-GPX4 axis. 抑制KDM5A可通过GDF15-GPX4轴减轻心肌梗死中的铁下垂。

IF 3.4 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-06-05 DOI: 10.3724/abbs.2026050

Wenzhao Wei, Ming Zhou, Jiacheng Yue, Kaisheng Jiang, Yang He, Tingting Mai, Jing Wang, Chao Li, Li Quan, Erwen Huang

{"title":"Inhibition of KDM5A alleviates ferroptosis in myocardial infarction via the GDF15-GPX4 axis.","authors":"Wenzhao Wei, Ming Zhou, Jiacheng Yue, Kaisheng Jiang, Yang He, Tingting Mai, Jing Wang, Chao Li, Li Quan, Erwen Huang","doi":"10.3724/abbs.2026050","DOIUrl":"https://doi.org/10.3724/abbs.2026050","url":null,"abstract":"Myocardial infarction (MI) is an acute cardiovascular condition with a poor prognosis, imposing substantial disease and economic burdens worldwide. The histone demethylase KDM5A is known to respond to oxygen levels; however, its role in MI remains unclear. Ferroptosis plays a decisive role in myocardial injury; however, whether it is regulated by KDM5A epigenetically remains unknown. Here, we establish an MI mouse model via left anterior descending coronary artery ligation and a hypoxic HL-1 cardiomyocyte model. Cardiac function, infarct size, and ferroptosis markers (Fe 2 + and MDA) are assessed following KDM5A pharmacological inhibition or genetic manipulation. Epigenetic mechanisms are investigated using Cut&Tag analysis, qPCR, and western blot analysis. The results reveal that KDM5A promotes ferroptosis and aggravates cardiac injury. Inhibition of KDM5A significantly alleviates infarct damage. Cut&Tag analysis indicates that KDM5A binds to the Gdf15 promoter, thereby removing H3K4me3 and suppressing Gdf15 transcription. These changes result in the downregulation of glutathione peroxidase 4 (GPX4) and enhance ferroptosis. These findings suggest that KDM5A drives cardiomyocyte ferroptosis through the GDF15-GPX4 axis. This study identifies KDM5A as an epigenetic regulator of ferroptosis and a promising therapeutic target for MI.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0