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JOURNAL OF LIGHTWAVE TECHNOLOGY · 2024 ·Vol. 42 ·期 16 ·5768-5774 · IF 4.1

Probe-Type Fiber Optic Biosensor Based on Barium Titanate Glass Microsphere Enhanced SPR Effect for Virus RNA Detection

Xuegang Li,Huiying Sun,Yanan Zhang,Yong Zhao,Xue Zhou

In this paper, a groundbreaking probe-type fiber optic biosensor, harnessing the surface plasmon resonance (SPR) effect enhanced by barium titanate glass microspheres, is unveiled for virus RNA detection. The multi-physics simulation was used to verify the sensitivity improvement achieved by introducing barium titanate microspheres on the surface of the optical fiber microspheres probe. Experiments confirmed this, pushing the sensor's limit to an impressive 6802 nm/RIU. Biomarker capture on the microsphere surface subtly alters the local refractive index, triggering a detectable SPR spectral shift. To showcase its prowess, the sensor tackled the reverse-transcribed complementary DNA (cDNA) of COVID-19 RNA. Chemical modification of the gold film and DNA hybridization technology ensured specific cDNA detection. The limit of detection for this target reached a remarkable 1.58 nmol/L. This sensor not only excels in virus RNA detection but also holds immense potential for diagnosing major diseases by pinpointing the concentrations of key biomarkers.

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ANALYTICAL CHEMISTRY · 2025 · IF 6.7

Primer Exchange Reaction with Cascade RNA Transcription for Highly Specific Detection of Exosomal miRNA and Liver Cancer Diagnosis

Yanming Lai,Wei Xiao,Zhiwei Lei,Huiping Long,Jiting Deng,Yiyu Wang,Lu Tao,Xingxing Liu,Jinjun Wu,Qiwei Zhang,Donglin Cao,Heng Xiao

Exosomal microRNAs (miRNAs) serve as dependable and noninvasive biomarkers for early cancer diagnosis. However, the accurate and feasible detection of exosomal miRNAs is often hindered by their low abundance and the requirement of specialized equipment for miRNA detection. In this study, we present a novel approach, termed primer exchange reaction-based fluorescence emission with cascade RNA aptamers transcription (PERFECT) for the highly sensitive detection of exosomal miRNA. The design of this method involves the selective interaction of a DNA probe with the target miRNA, leading to its activation. Once activated, isothermal signal amplification and RNA aptamer transcription are initiated, resulting in an amplified fluorescent signal within 90 min. This method achieves a detection limit of 2.2 fM at 37 °C and 2.7 fM at room temperature (25 °C). We used the PERFECT technology to analyze miR-21 expression levels in cell extracts, cell-derived exosomes, and human plasma-derived exosomes, achieving a diagnostic accuracy of 93.6% in distinguishing hepatocellular carcinoma (HCC) patients. Overall, this study highlights its broad range of detection temperature, simplicity of the detection process, and strong potential for clinical application, rendering it a promising tool for early cancer diagnosis.

CAS / MDL: 1241390-29-3
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AQUATIC TOXICOLOGY · 2024 · IF 4.1

Toxic effects of triclosan on hepatic and intestinal lipid accumulation in zebrafish via regulation of m6A-RNA methylation

Jinyun Li,Lu Fang,Miaocui Xi,Anyu Ni,Qiuhui Qian,Zejun Wang,Huili Wang,Jin Yan

Triclosan (TCS), recognized as an endocrine disruptor, has raised significant concerns due to its widespread use and potential health risks. To explore the impact of TCS on lipid metabolism, both larval and adult zebrafish were subjected to acute and chronic exposure to TCS. Through analyzes of biochemical and physiological markers, as well as Oil Red O (ORO) and hematoxylin and eosin (H&E) staining, our investigation revealed that TCS exposure induced hepatic and intestinal lipid accumulation in larval and adult zebrafish, leading to structural damage and inflammatory responses in these tissues. The strong affinity of TCS with PPARγ and subsequent pathway activation indicate that PPARγ pathway plays a crucial role in TCS-induced lipid buildup. Furthermore, we observed a decrease in m6A-RNA methylation levels in the TCS-treated group, which attributed to the increased activity of the demethylase FTO and concurrent suppression of the methyltransferase METTL3 gene expression by TCS. The alteration in methylation dynamics is identified as a potential underlying mechanism behind TCS-induced lipid accumulation. To address this concern, we explored the impact of folic acid—a methyl donor for m6A-RNA methylation—on lipid accumulation in zebrafish. Remarkably, folic acid administration partially alleviated lipid accumulation by restoring m6A-RNA methylation. This restoration, in turn, contributed to a reduction in inflammatory damage observed in both the liver and intestines. Additionally, folic acid partially mitigates the up-regulation of PPARγ and related genes induced by TCS. These findings carry substantial implications for understanding the adverse effects of environmental pollutants such as TCS. They also emphasize the promising potential of folic acid as a therapeutic intervention to alleviate disturbances in lipid metabolism induced by environmental pollutants.

CAS / MDL: 3380-34-5 59-30-3
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METHODS · 2025 · IF 4.3

Ultrasensitive detection of MMP-2 via T7 RNA polymerase and CRISPR/Cas13a-Enhanced electrochemiluminescence biosensor for COPD diagnosis

Wensi Li,Zhichao Tang,Xiang Zhu,Beijuan Wang,Xiuqin Zhang,Ze Ji,Suhang Cheng

In this work, an electrochemiluminescence (ECL) biosensor integrating T7 RNA polymerase amplification and CRISPR/Cas13a-mediated signal enhancement was developed for the ultrasensitive detection of matrix metalloproteinase-2 (MMP-2), a key biomarker associated with chronic inflammatory diseases such as COPD. A peptide nucleic acid (PNA) probe was designed to respond specifically to MMP-2 cleavage, enabling the release of DNA templates for subsequent T7 RNA polymerase-driven transcription amplification. The generated RNA triggers the collateral cleavage activity of CRISPR/Cas13a, resulting in a significant amplification of the ECL signal. The biosensor’s surface was constructed using a AuNPs/Ti 3 C 2 Tx/Ru(II)-PEI nanocomposite, which enhanced signal transduction and stability. Under optimized conditions, the proposed biosensor achieved a detection limit as low as 62.05 fM, demonstrating superior sensitivity compared to conventional methods, as summarized in Table 1 . The platform also exhibited excellent specificity and anti-interference capability, ensuring reliable detection of MMP-2 in complex biological samples. This study provides a simple yet highly efficient strategy for enzymatic biomarker detection, offering great potential for clinical applications in early disease diagnosis and monitoring.

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TALANTA · 2021 · IF 6.057

Fluorescence on-off-on with small and charge-tunable nanoparticles enables highly sensitive intracellular microRNA imaging in living cells

Chunrong Li,Yanfei Zhang,Jun Chen,Liping Liu,Huihui Yang,Si-Yang Liu,Yuzhi Xu,Zong Dai,Xiaoyong Zou

Nanomaterial-based on-off-on fluorescence sensing strategies are significant particularly in intracellular nucleic acids imaging assay. There still remains challenge to rationally balance fluorescence quenching efficiency and recovery dynamics. We assume that the performance of on-off-on fluorescence sensing strategy can be fundamentally improved on small zero-dimensional (0D) nanomaterial with precisely modulated surface charge. For a proof-of-concept demonstration, silicon nanoparticle (SiNP) with ~4 nm was synthesized and used as the quencher model, of which the surface charge density was modulated by modification of triphenylphosphonium (TPP). The influence of particle size, surface charge and charge density of the nanomaterials on sensing performance was systematically investigated. The strategy showed a low limit of detection (LOD) as 26 pM for target model miR-494, which is one of the lowest in nanomaterial-based on-off-on sensing platforms. And the LOD is even comparable to amplification-based methods in a greatly shortened assay time (2.5 h). The miR-494 expresses in cancerous and normal living cells of human cervical carcinoma (HeLa), human lung carcinoma (A549), human breast cancer (MCF-7), and normal human mammary epithelial (MCF-10A) cells were imaged and localized with significantly improved sensitivity and specificity. These excellent performances insure it a promising candidate as convenient and non-enzymatic sensing platform for miRNA-associated disease detection and early diagnosis.

研究领域: 生物化学 · 分子生物学 · 医学诊断
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Nature Communications · 2025 ·Vol. 16 ·期 1 ·1-19 · IF 15.7

FRET imaging of glycoRNA on small extracellular vesicles enabling sensitive cancer diagnostics

Ren Tingju,Zhang Yingzhi,Tong Yuxiao,Zhang Qi,Wang Tianhao,Wang Yue,Yang Chunguang,Xu Zhangrun

Glycosylated RNAs (glycoRNAs), a recently discovered class of membrane-associated glyco-molecules, remain poorly understood in function and clinical value due to limited detection methods. Here, we show a dual recognition Förster resonance energy transfer (drFRET) strategy using nucleic acid probes to detect N-acetylneuraminic acid-modified RNAs, enabling sensitive, selective profiling of glycoRNAs on small extracellular vesicles (sEVs) from minimal biofluids (10 μl initial biofluid). Using drFRET, we identify 5 prevalent sEV glycoRNAs derived from 7 cancer cell lines. In a 100-patient cohort (6 cancer types and non-cancer controls), sEV glycoRNA profiles achieve 100% accuracy (95% confidence interval) in distinguishing cancers from non-cancer cases and 89% accuracy in classifying specific cancer types. Furthermore, drFRET reveal that sEV glycoRNAs specifically interact with Siglec proteins and P-selectin, which is critical for sEV cellular internalization. The drFRET strategy provides a versatile and sensitive platform for the imaging and functional analysis of sEV glycoRNAs, with promising implications for clinical applications.

研究领域: 分子生物学 · 肿瘤学 · 临床医学 · 生物化学
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2025 · IF 9.7

Brain-targeted polymersomes mediating RNAi of STAT3 sensitize glioblastoma to temozolomide and immunotherapy

Mingyu Xia,Songsong Zhao,Zhiwei Sun,Yan Shi,Wenhai Lin,Zhiyuan Zhong,Fenghua Meng

Glioblastoma (GBM) is among the most aggressive brain tumors, presenting significant therapeutic challenges due to intrinsic and acquired resistance to treatment, alongside a highly immunosuppressive tumor microenvironment (TME). While temozolomide (TMZ) is the standard chemotherapeutic agent with the ability to penetrate the blood–brain barrier (BBB), its clinical efficacy is often limited. Here, we report a strategy employing Apolipoprotein E (ApoE) peptide-functionalized polymersomes loaded with small interfering RNA (siRNA) targeting signal transducer and activator of transcription 3 (Apstat3) to amplify the anti-GBM effects of TMZ and immunotherapy. Apstat3 demonstrated small, uniform particle sizes, stability in siRNA encapsulation, and effective downregulation of STAT3 and O⁶-methylguanine-DNA methyltransferase (MGMT) in GL261 cells, sensitizing these tumor cells to TMZ. The combinatorial approach not only significantly inhibited GBM cell proliferation, migration and invasion but also improved dendritic cells (DCs) maturation under TME-mimicking environment. In orthotopic GL261 mouse models, intravenous injection of Apstat3 co-administered with oral TMZ resulted in a twofold increase in median survival and reshaped the TME. Notably, combined treatment with anti-CTLA4 therapy tripled median survival to 64 days, achieving complete remission observed in 20 % of the mice. This siSTAT3 delivery strategy holds promise for enhancing GBM treatment outcomes.

CAS / MDL: 85622-93-1
研究领域: 肿瘤学 · 药剂学 · 分子生物学
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iScience · 2023 · IF 5.8

CircMAPK9 promotes adipogenesis through modulating hsa-miR-1322/FTO axis in obesity

Shuai Chen,Peng Song,Yu Wang,Zeng Wang,Jiaming Xue,Yicheng Jiang,Yan Zhou,Jie Zhao,Liming Tang

Circular RNA (circRNA) is a special category of non-coding RNA that has garnered increasing attention in the exploration of lipid metabolism. However, the functional regulation mechanisms of circRNAs in obesity diseases remain unclear. By whole transcriptome sequencing, a total of 164 circular RNAs were found to exhibit differential expression between lean and obese individuals. RT-qPCR was used to detect significant expression of circMAPK9 in obese individuals, and it was closely related to BMI. Western blot, triglyceride detection, and Oil Red O staining were employed to investigate the role of circMAPK9/hsa-miR-1322/FTO in adipogenesis. In adipocytes, the connection between hsa-miR-1322 and circMAPK9 was verified using fluorescence in situ hybridization, luciferase reporter assay, and RNA immunoprecipitation. It was found that circMAPK9 competed for binding hsa-miR-1322 in the cytoplasm, weakening the inhibitory effect on FTO and promoting adipogenesis. Our study revealed the regulatory mechanism and important role of circMAPK9 in the process of adipogenesis.

研究领域: 分子生物学 · 基因组学 · 代谢
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Biomolecules · 2019 ·Vol. 9 ·期 11 ·695 · IF 4.694

Transcriptome Mechanism of Utilizing Corn Steep Liquor as the Sole Nitrogen Resource for Lipid and DHA Biosynthesis in Marine Oleaginous Protist Aurantiochytrium sp.

Dong-Sheng Wang,Xin-Jun Yu,Xiao-Yu Zhu,Zhao Wang,Hui-Juan Li,Zhi-Peng Wang

In the current study, corn steep liquor (CSL) is evaluated as an ideal raw agro-material for efficient lipid and docosahexaenoic acid DHA production byAurantiochytriumsp. Low CSL level in medium (nitrogen deficiency) stimulated the biosynthesis of lipids and DHA while inhibiting cellular growth. The transcriptomic profiles of theAurantiochytriumsp. cells are analyzed and compared when cultured under high (H group), normal (N group), and low (L group) levels of CSL in the medium. The discriminated transcriptomic profiles from the three groups indicates that changes in CSL level in medium result in a global change in transcriptome ofAurantiochytriumsp. The overall de novo assembly of cDNA sequence data generated 61,163 unigenes, and 18,129 of them were annotated in at least one database. A total of 5105 differently expressed (DE) genes were found in the N group versus the H group, with 2218 downregulated and 2887 upregulated. A total of 3625 DE genes were found in the N group versus the L group, with 1904 downregulated and 1721 upregulated. The analysis and categorization of the DE genes indicates that the regulation mechanism of CSL involved in the perception and transduction of the limited nitrogen signal, the interactions between the transcription factors (TFs) and multiple downstream genes, and the variations in downstream genes and metabolites, in sequence, are illuminated for the first time in the current study.Keywords:Aurantiochytriumsp.;nitrogen-deficiency;RNA-seq;corn steep liquor (CSL);signal transduction;DHA

研究领域: 生物技术 · 分子生物学
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JOURNAL OF CONTROLLED RELEASE · 2025 · IF 11.5

Structurally-defined non-cationic docosahexaenoic acid based siRNA-micelles for safe and effective combinatorial glioblastoma therapy

Sen Xu,Mengyu Fan,Qimeng Ding,Yibin Wang,Muhammad Ismail,Weimin Ruan,Yan Zou,Dongya Zhang,Meng Zheng

RNA interference (RNAi) has emerged as a highly promising therapeutic strategy for glioblastoma (GBM), yet its clinical efficacy heavily relies on the success of delivery systems. Traditional vehicles, including cationic polymers, lipids, and inorganic nanoparticles, frequently encounter critical challenges such as cationic toxicity, poor blood-brain barrier (BBB) penetration, or poorly-defined structures that hinder their clinical translation. To overcome these challenges, we developed a novel, structurally-defined non-cationic siRNA-micelle system based on siRNA-docosahexaenoic acid (DHA) conjugates. These conjugates self-assemble into stable siRNA-micelles that exhibit prolonged blood circulation, enhanced cellular uptake, and efficient BBB penetration. Due to their non-cationic nature and the inherent safety profile of DHA, these siRNA-DHA micelles exhibit exceptional biocompatibility, potentially minimizing carrier-based toxicity. By simultaneously targeting epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGFA), the siRNA-micelles potently inhibited tumor progression and substantially extended survival in orthotopic GBM mouse models via dual-target modulation. This structurally-defined, non-cationic siRNA delivery platform represents a robust and clinically translatable strategy for GBM treatment, and holds considerable promise for the RNAi-based therapy of other neurological disorders.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Research · 2025 · IF 10.7

Multichannel 3D-Printed Bioactive Scaffold Combined with Small Interfering RNA Delivery to Promote Neurological Recovery after Spinal Cord Injury

Jingjia Ye,Fenglu Li,Zhengfa Wen,Junsheng He,Gaoxing Pan,Xinrang Zhai,Linran Song,Xianzhu Zhang,Xuefei Zhou,Xudong Yao,Yanlang Wang,Jin Zhang,Wei Wei

Enhancing axonal regeneration holds promise for restoring neural circuits and locomotion function after spinal cord injury (SCI), while precise guidance of micrometer-scale axons to their natural regions remains a critical challenge. To address this problem, we developed an integrated 3D-printed scaffold featuring internal parallel channels infused with a bioactive hydrogel containing laminin-derived chimeric RADA 4 -IKVAV peptide. This scaffold combined physical guidance cues with molecular modulation synergistically by constructing an incorporated small interfering RNA delivery platform targeting phosphatase and tensin homolog. Comprehensive validations via immunohistochemistry, single-cell RNA sequencing, and behavioral assays demonstrated that this approach effectively protected surrounding tissues in lesion area, enhanced ability of axonal regeneration, and improved locomotion functional recovery of rats significantly. Mechanistic investigations further revealed that the introduced IKVAV peptide specifically up-regulated Ephrin/Eph signaling pathway genes, driving establishment of functional axon networks. Overall, this strategy potentially helps to develop new clinical approach for efficiently treating SCI.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Nanoscale · 2020 ·Vol. 12 ·期 47 ·24100-24106 · IF 6.895

Biodegradable nanoparticle-assisted and multiplexed imaging of asymmetric RNA expressions in live cells for precise cancer diagnosis and prognosis

Xia Li,Fang Yang,Chunfang Gan,Ruo Yuan,Yun Xiang

The simultaneous imaging of the dynamic expression variations of regulatory RNAs in cells, which remains a major challenge, has important applications in precise disease diagnosis, treatment and prognosis. Here, we describe the establishment of a biodegradable ZnO nanoparticle (NP)-assisted asymmetric amplification approach for the simultaneous imaging of microRNA-21 (miRNA-21) and programmed cell death 4 (PDCD4) mRNA at distinct expression levels in live cells. The DNA signal probe complexes are immobilized on the ZnO NPs and readily delivered into the target cancer cells via the endocytosis pathway. The acidic microenvironment in cancer cells leads to the dissolution of the ZnO NPs to release Zn2+ ions and the intracellular miRNA-21 activates the Zn2+-dependent DNAzyme to cleave the substrate signal probes with the assistance of the Zn2+ cofactor to show green fluorescence for imaging miRNA-21. Meanwhile, the PDCD4 mRNA can displace the other quenched signal probes to generate red fluorescence. Importantly, the PDCD4 mRNA sequences can be recycled and reused by using the DNAzyme-cleaved sequences as the fuel strands through two strand displacement reactions to yield amplified red fluorescence for detecting low levels of PDCD4 mRNA. Moreover, our approach can be used to evaluate the varied expression levels of miRNA-21 and PDCD4 mRNA responsive to different drugs in cells, reflecting its usefulness for precise cancer diagnosis and prognosis upon anticancer drug treatment.

研究领域: 分子生物学 · 癌症研究 · 纳米医学
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