ADVANCED FUNCTIONAL MATERIALS
·
2026
·
IF 19.9
Haolong Chen,Jiahui Liu,Shuai Liu,Fuyuan Yang,Qiuyun Yin,Ziyu Bao,Wenyu He,Xi Zhang,Jin-Zhou Liu,Zishao Wang,Tai-Cheng Zhou,Qiu-e Cao,Jian Ling,Rong Sheng Li
Multidrug-resistant Gram-negative bacteria present a critical challenge for both diagnosis and therapy because diagnostic and therapeutic molecules have difficulty entering Gram-negative bacteria, and these molecules can also be expelled by bacteria using efflux pumps. Here, we report a supramolecular intrabacterial assembly peptide (IAP) that enables selective bacterial internalization via siderophore-like uptake. After internalization, IAP undergoes intra-bacterial RNA-triggered transformation from monodisperse molecules to nanofibrils, which bypass efflux pumps and enhance intra-bacterial retention. The transformation from monodisperse molecules to nanofibrils enhances r 1 relaxivity of Gd magnetic resonance imaging (MRI) motif of IAP from 9.9 ± 0.2 m M − 1 ·s − 1 (monodisperse state) to 24.5 ± 1.1 m M − 1 ·s − 1 (nanofibril state), enabling activated T 1 -weighted MRI and fluorescence imaging for Gram-negative bacteria in vivo. Beyond imaging, the IAP-RNA nanofibrils inside bacteria inhibit protein synthesis, induce reactive oxygen species accumulation, and disrupt the bacterial envelope. The multiple bacterial death pathways give IAP excellent efficacy against drug-resistant Gram-negative in both pneumonia and diabetic wound infection models, and no detectable resistance after prolonged exposure. This work presents a chemically encoded supramolecular strategy for activatable imaging and therapy based on intra-bacterial supramolecular assembly.
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MICROCHEMICAL JOURNAL
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2025
·
IF 5.1
Jingyi Guo,Xi Cheng,Huiyan Cao,Youping Deng,Fang Wang
N6-methyladenosine (m6A) is the most prevalent epigenetic RNA modification in eukaryotes, playing critical roles in RNA metabolism and disease progression. Current detection methods for m6A, such as mass spectrometry and antibody-based assays, face limitations in sensitivity, cost, or complexity. Electrochemical biosensors offer a promising alternative but struggle with nonspecific binding and low signal-to-noise ratios. This work addresses these challenges by developing a highly sensitive and selective electrochemical sensor for m6A quantification in complex biological samples. We designed a laser-induced graphene electrode (AuNPs/LIG) functionalized with gold nanoparticles and 11-mercaptoundecanoic acid (MUA) to immobilize anti-m6A antibodies via Protein A (PrA)-directed coupling. The sensor exploited steric hindrance and electrostatic repulsion from m6A-bound RNA to suppress electron transfer of the Fe[(CN) 6 ] 3− redox probe, yielding a current response proportional to m6A concentration. The assay achieved a linear range of 0.001–10 nM with a detection limit of 0.284 pM, surpassing our previous work by a large margin in terms of sensitivity. Validation in HeLa cell RNA and undiluted human serum confirmed high accuracy and minimal interference from nonspecific RNA. This method of m6A detection offers unparalleled advantages in sensitivity, real-time quantification, and cost-effective miniaturization, while future advancements in material science and multiplexed detection integration could revolutionize its clinical translation for point-of-care diagnostics in m6A-related diseases, such as cancer and metabolic disorders.
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NUCLEIC ACIDS RESEARCH
·
2025
·Vol. 53
·期 10
·
IF 13.1
Wang Qi,Du Yuhao,Yan Shen,Lu Ziang,Tang Yongling,Xiao Feng,Zhou Fuling,Zhou Xiang
N4-Acetylcytidine (ac4C) is an emerging epitranscriptomic mark involved in regulating RNA stability, translation, and gene expression. Despite its emerging role in gene regulation and disease, current methods for in situ detection of ac4C-modified RNA lack sensitivity and specificity. To overcome these challenges, we developed fluorine metabolic labeling mediated proximity ligation assay (FMPLA), a method combining fluorine-based metabolic labeling with a proximity ligation assay for precise detection of newly synthesized fluoro-metabolically labeled ac4C sites. This approach enables high-sensitivity visualization of multiple RNA species, and provides insights into the abundance and spatial dynamics of ac4C-modified RNAs during the cell cycle and under chemotherapeutic stress. Additionally, FMPLA reveals distinct RNA modification patterns in drug-resistant cancer cells, highlighting its potential in studying functions and mechanisms of RNA ac4C modification.
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BIOSENSORS & BIOELECTRONICS
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2025
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IF 10.5
Junlan Liu,Yuan Gao
The exceptionally sensitive and specific CRISPR-Cas systems have revolutionized molecular diagnostics, but their application remains largely confined to nucleic acid targets. To overcome this limitation and enable one-pot, mix-and-read detection of non-nucleic acid analytes, we present a generalizable CRISPR-Cas13a sensing platform that utilizes a hybrid DNA:RNA strand displacement-based switch to conditionally activate Cas13a. The switch leverages Cas13a's strict requirement for single-stranded RNA activators to mediate non-RNA target-triggered activation while protecting functional DNA elements from collateral cleavage. By integrating the modular Cas13a switch with various functional DNAs, including DNAzyme, aptazyme, and duplexed aptamer, we constructed a suite of one-pot sensors capable of detecting non-RNA targets such as lead ion, ATP, and thrombin. These CRISPR-Cas13a sensors demonstrate enhanced sensitivity, high selectivity, and robust performance in complex biological matrices. The high modularity of the CRISPR-Cas13a sensor allows rapid reconfiguration for new targets by simply altering the output sequence of functional DNA without extensive re-engineering. This versatile and robust sensing strategy expands the application landscape of CRISPR-Cas systems and lays the foundation for flexible, sensitive, and one-pot detection of a wide array of clinically and environmentally relevant targets.
研究领域:
分子诊断学
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合成生物学
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生物传感器
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CRISPR技术
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核酸化学
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生物分析化学
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ADVANCED MATERIALS
·
2025
·
IF 26.8
Jiacheng Yu,Qitong Feng,Jintao Zheng,Han Liu,Hui Liu,Runzhi Zhou,Xiaohong Jiang,Haoyang Yan,Zheng Liang,Mingxi Chen,Omer Yehezkeli,Haifeng Dong,Lin Li,Bo Peng,Nicolas H. Voelcker,Jiacan Su,Keying Guo
RNA biomarkers are vital for diagnosing infections, cancer, and neurodegenerative diseases. RT-qPCR is sensitive but complex and equipment-intensive, limiting point-of-care use. Herein, for the first time, an organic electrochemical transistor (OECT) biosensor is reported utilizing small molecules as recognition elements for rapid, ultrasensitive and amplification-free detection of RNA. The biosensor leverages “click chemistry” to precisely immobilize screened and chemically edited small molecules to the OECT gate, enabling efficient target RNA binding. To further enhance sensitivity and reduce detection time, a rapid sample incubation module utilizing alternating current (AC) electrokinetic acceleration without the influence of electric currents and thermal effects strategy is employed to accelerate biomolecule transport and increase binding kinetics. This approach is validated using a model system incorporating C5, a chemically optimized small-molecule ligand that selectively binds SARS-CoV-2 RNA. The resulting biosensor achieves real-time, amplification-free RNA detection within three minutes, and the results are transmitted to electronic devices via Bluetooth. Notably, it shows impressive sensitivity (0.3 aM) and excellent long-term stability, retaining functional sensitivity for five months under ambient storage. This work establishes a new paradigm for RNA biosensing, demonstrating the power of integrating small-molecule recognition, electrochemical transduction and AC field enhancement for next-generation rapid diagnostics.
研究领域:
生物传感器
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分子诊断
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生物电子学
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RNA检测
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即时检测
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电化学传感
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Scientific Reports
·
2026
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IF 4.9
Jiang Qi,Weng Xiaoyu,Chai Yi,Ragan Katherine B.,Liu Zhengjin,Li Zhongwu,Wang Bonnie,Jin Olivia,Gopinath Ashwin,Zhang David Yu,Chen Wei
High-frequency longitudinal RNA sequencing has emerged as a powerful approach for capturing dynamic transcriptional responses to therapeutic interventions, yet traditional differential expression analysis fails to identify genes with temporal variability that lack static expression differences. We used our previously developed computational framework for identifying Temporally Varying Genes (TVGs) from daily blood samples collected over 10–21 days in Sprague–Dawley rats treated with hepatotoxic compounds including tetracycline, isoniazid, carbon tetrachloride, and valproate. Our methodology employs variance-based scoring to detect genes exhibiting significant temporal fluctuations under treatment conditions. Unsupervised hierarchical clustering of TVGs identified three distinct temporal patterns: early-transient responses, sustained activation, and late-phase upregulation, each enriched for specific biological processes. Principal component analysis demonstrated clear treatment-induced transcriptomic shifts from baseline “Healthy Region” clusters to treatment-adapted “Response Region” states, with sample trajectories reflecting dose-dependent temporal dynamics. Cross-compound analysis revealed 186 commonly regulated genes across all treatments, representing conserved hepatotoxicity signatures, while compound-specific responses highlighted distinct mechanistic pathways. This approach enables kinetic-pharmacodynamic modeling that distinguishes primary drug targets from secondary adaptive responses, advancing precision medicine applications through dynamic molecular portraits of drug action and individual treatment variability.
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NUCLEIC ACIDS RESEARCH
·
2026
·Vol. 54
·期 8
·
IF 15
Gong Meilin,Tang Xiaoqi,Xie Zuowei,Niu Ben,Deng Ruijia,Fu Wenjuan,Yang Yingjie,Tang Yu,Luo Jie,Sheng Jing,Zhang Ying,Chen Ming,Chang Kai
Cell-surface glycoRNA plays a crucial role in cellular behavior, yet its RNA substrate signatures and membrane transport mechanism remain unclear. Here, we developed GlycoRNA-Lighted In situ Nano-Tracking (GLINT), an approach for the visualization of distinct RNA-specific glycosignatures. GLINT employs a modular, localized concatenated DNA circuit based on a proximity ligation-mediated dual hierarchical hybridization chain reaction (HCR). Metabolically labeled sialic acid probe and RNA-specific probes are combined into a dual-recognition module through proximity ligation. The module subsequently initiates a dual hierarchical HCR cascade, enabling ultrasensitive in situ tracking of U1, U3, U35a, Y5, and U8 glycoRNAs at the single-cell level. Leveraging GLINT technology, glycoRNAs were confirmed to be transported intracellularly via a SNARE protein-mediated secretory extracellular mechanism. Furthermore, the identification of ten subtypes of breast cancer cells was achieved based on the level of distinct RNA-specific glycosignatures on the cell surface. GLINT demonstrates great potential for tracking RNA-specific glycosignatures, offering a powerful tool for in situ cell subtyping and exploration of RNA-related glycosylation processes.
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International Journal of Genomics
·
2025
·Vol. 2025
·期 1
·2494933
·
IF 1.9
Yiyang Hu,Xueyan Song,Haichang Li
Hyperuricemia (HUA) is a metabolic disorder characterized by elevated serum uric acid (UA) level, which would trigger inflammatory processes contributing to kidney damage. Acupuncture stimulation of BL23, a therapeutic strategy in traditional Chinese medicine (TCM), has been reported to promote diuresis and suppress the immune system and seems to be efficacious in HUA. In this study, we aimed to investigate the effect of electroacupuncture (EA) at BL23 on HUA and HUA-induced kidney inflammation and dysfunction in mice. Mice received EA once daily after being given intragastric potassium oxonate (500 mg/kg) and adenine (100 mg/kg). EA administration not only decreased the levels of serum UA, creatinine, blood urea nitrogen, urinary UA, and protein, along with increased urinary CREA excretion, but also decreased the inflammatory cytokines productions (IL-1 β , IL-6, and TNF- α ) in serum. scRNA-seq of treated kidneys revealed that EA at BL23 suppressed the NLRP3 inflammasome complex, the IL-6/JAK/STAT3 signaling pathway, and the production of IL-6 and IL-1 β in HUA mice. Western blot analyses verified that EA suppressed the HUA-induced NLRP3 inflammasome activation by promoting autophagy. In conclusion, the study demonstrated that EA at BL23 exhibited anti-HUA and nephroprotective effects by inhibiting both the NLRP3 inflammasome and the IL-6/JAK/STAT3 signaling pathway, reducing renal inflammation and supporting its therapeutic potential for HUA-associated kidney injury.
研究领域:
中医针灸学
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肾病学
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免疫学
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分子生物学
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转录组学
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Cell Death Discovery
·
2025
·Vol. 11
·期 1
·542
·
IF 7
Ji Kai,Zhou Leqi,Zhang Tianshuai,Fan Hao,Xie Gang,Man Wenjiang,Wang Can,Tian Yucheng,Chen Li,Wang Guimin,Liu Mulin,Zhu Bing,Zhang Wei,Yu Guanyu
Increasing evidence indicates that RNA-binding proteins and the reprogramming of lipid metabolism play crucial roles in tumorigenesis. However, the extent to which members of these families contribute, and whether targeting metabolic genes to affect overall protein production in cancer cells, remains largely unknown. This study analyzes CRC tissue samples and databases to reveal the high expression of hnRNP A1 in CRC and its critical role in tumorigenesis, proliferation, migration, and prognosis. Through combined sequencing analyses, we identified a novel mechanism by which PPARα regulates lipid metabolism. Our data indicate that hnRNP A1 is central to lipid metabolism reprogramming in CRC, promoting lipid accumulation by regulating PPARα mRNA stability, thereby influencing cell proliferation and apoptosis. Overall, hnRNP A1 could serve as a novel target for CRC therapy. Its involvement in cancer development offers new biological insights and potential therapeutic strategies. As a potential biomarker and therapeutic target, it presents novel approaches for the clinical management of CRC.
研究领域:
肿瘤学
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分子生物学
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癌症代谢
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RNA生物学
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细胞信号传导
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Open Medicine
·
2023
·Vol. 18
·期 1
·
IF 2.1
Jing Wang,Yiyu Shen,Xiaoguang Wang,Zhongcheng Zhou,Zhengxiang Zhong,Tianyuan Gu,Bin Wu
Our pre-investigation has revealed that long non-coding RNA (LncRNA) AL137789.1 has the potential to predict the survival of patients with pancreatic carcinoma (PCa). Accordingly, the mechanism underlying the implication of AL137789.1 in PCa is covered in the current study. The non-tumor and paired tumor tissues were collected. Kaplan–Meier curve was employed to estimate the survival of PCa patients with high or low expression of AL137789.1. The proliferation, migration, invasion, and cell cycle of PCa cells were determined, and the cytotoxicity of CD8 + T cells was evaluated as well. Levels of AL137789.1, E-cadherin, N-cadherin, and Vimentin were quantified. According to the experimental results, AL137789.1 was highly expressed in PCa and related to a poor prognosis of patients. Overexpressed AL137789.1 enhanced the proliferation, migration, and invasion of PCa cells, increased the cell population at G2/M and S phases yet decreased that in G0/G1 phase, and diminished the cytotoxicity of CD8 + T cells. Also, overexpressed AL137789.1 elevated levels of N-cadherin and Vimentin, while lessening E-cadherin levels. However, the silencing of AL137789.1 produced contrary effects. Collectively, lncRNA AL137789.1 plays a tumor-promotive role in PCa by enhancing the progression and immune escape.
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IET Nanobiotechnology
·
2023
·Vol. 17
·期 3
·224-233
·
IF 2.3
Junjie Zhao,Niu Niu,Fan Yang,Haitao Liu,Weibo Qi
Background Multidrug resistance is the biggest barrier on the way to chemotherapy for lung adenocarcinoma (LUAD). For some LUAD patients with cisplatin (DDP) resistance and poor prognoses, the authors put forward RNA nanoparticles (NPs) carrying miR-301b-3p Inhibitor. Methods The NPs were composed of miR-301b-3p, A549 aptamer (A549apt), and Cyanine 5 in a bottom-up manner with a 3-way-junction (3WJ) structure. Diameter, assembly process, and morphology of NPs were observed by Dynamic Light Scattering, Native-Polyacrylamide Gel Electrophoresis, and Atomic Force Microscopy. Cell internalisation, toxicity, proliferation, migration, invasion, and apoptosis were assayed by confocal laser scanning microscope, CCK8, colony formation assay, Transwell, western blot, and flow cytometry. Results 3WJ-apt-miR was evenly distributed, with diameter of 19.61 ± 0.49 nm and triangular branching structures. The accurate delivery of this NP in vivo was ensured by A549 aptamer featuring specific targeting, with smaller side effects than traditional chemotherapy. Such nanomaterials were effectively internalized by cancer cells, with normal cell activity intact. Cancer cell proliferation, invasion, and migration were suppressed, and DDP sensitivity was enhanced, causing DNA damage and facilitating apoptosis of DDP-resistant cells. Conclusion Based on RNA self-assembling, the authors researched the effect of miRNA on DDP sensitivity in LUAD regarding gene regulation. 3WJ-apt-miR paves the way for clinical tumour therapy.
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Frontiers in Bioscience-Landmark
·
2023
·Vol. 28
·期 5
·102
·
IF 3.1
Deqian Qiao,Yiling Liu,Yunlong Lei,Chundong Zhang,Youquan Bu,Yishu Tang,Ying Zhang
Background: rRNA-derived small RNAs (rsRNAs) represent a novel class of small non-coding RNAs (sncRNAs), produced by the specific cleavage of rRNAs; however, their roles in tumor development are unclear. In the present study, we explored the effect of a kind of rsRNA-28S, which originates from 28S rRNA, on the chemoresistance of prostate cancer cells and the mechanisms underlying its effect. Methods: Quantitative reverse transcription PCR (RT-PCR) was performed to quantify rsRNA-28S levels in serum samples taken from prostate cancer patients. DU-145R cells, which are resistant to both paclitaxel and docetaxel, were generated from parental DU-145 cells. Northern blot was conducted to detect cellular rsRNA-28S levels following drug treatments. To verify the effect of rsRNAs-28S on chemoresistance, antisense oligonucleotides were utilized to block rsRNA-28S functions, and a series of assays were further performed, such as cell viability, cell proliferation, colony formation and tumor sphere formation. The target gene of rsRNA-28S was explored using dual-luciferase reporter gene assay. Results: The rsRNA-28S level was reduced in the serum samples of patients who received chemotherapy compared to that of patients who did not. Furthermore, the rsRNA-28S level was remarkably declined in DU-145R cells, and drug treatments decreased the levels of rsRNA-28S in DU-145 and DU-145R cells. Moreover, rsRNA-28S inhibition enhanced the chemoresistance of prostate cancer cells as well as their cancer stem cell characteristics. Mechanistically, the prostaglandin I2 synthase (PTGIS) gene transcript was verified as a target of rsRNA-28S, as rsRNA-28S inhibited the translation of PTGIS mRNA by directly binding the 3′ untranslated region of PTGIS mRNA. rsRNA-28S inhibition was also found to increase PTGIS abundance, and PTGIS overexpression significantly enhanced prostate cancer cell chemoresistance. Conclusions: Our findings indicate that rsRNA-28S attenuates prostate cancer cell chemoresistance by downregulating its target gene PTGIS. This study not only greatly contributes to systematic identification and functional elucidation of chemoresistance relevant rsRNAs, but also promotes rsRNA-included combinatorial therapeutic regimens for cancer.
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