JOURNAL OF BIOLOGICAL CHEMISTRY
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2026
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IF 4.1
Dongsheng Xing,Hongwei Cao,Yan Yang,Shengyang Liu,Hanbing Yu,Zhenyu Liu,Kunrong Wang,Xin Wei,Aihui Yan
Tristetraprolin (TTP), which encodes an RNA-binding protein, was identified as a biomarker in three types of IgE-driven allergic tissues. Remarkably, in the nasal mucosa of the ragweed pollen-induced AR mouse model, TTP mRNA levels were increased approximately threefold. TTP overexpression in AR mice alleviated nasal inflammation and epithelial barrier damage, accompanied by reduced frequency of nasal spray and nasal friction, eosinophils/neutrophils/macrophages/goblet cells infiltration, and Th2 cytokines interleukin (IL)-4, IL-5, and IL-13 secretion. The impact of TTP on the activation and differentiation of Th2 cells was assessed by utilizing naïve CD4 T cells isolated from mice. We found that TTP significantly suppressed Th2 activation and differentiation, as evidenced by the decreased levels of cytokines and the percentage of Th2. Transcriptomic profiling of CD4+ T cells (with/without TTP overexpression) was analyzed, and 14 down-regulated genes containing AU-rich elements (AREs) were obtained. The study concentrated on downregulated E3 ubiquitin ligase tripartite motif 18 (TRIM18) in TTP-overexpressed CD4+ T cells. Specifically, TTP protein bound to the ARE located at positions +3640 to +3644 (5’-UAUUU-3’) within the 3’UTR of mouse TRIM18, and this interaction reduces TRIM18 mRNA stability, a process that depends on the active-site residue Cys-139 within the second CCCH-type zinc finger motif of TTP. TRIM18 overexpression weakened the effects in CD4+ T cells induced by TTP overexpression. Collectively, TTP suppresses Th2 activation and differentiation in AR by modulating TRIM18 mRNA stability, highlighting their interaction as a critical pathway in allergic inflammation.
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Cell Reports
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2026
·Vol. 45
·期 1
·116808
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IF 6.9
Jie Fu,Xin Zong,Hong Zhang,Luoyi Zhu,Tao Gong,Yuanzhi Cheng,Fengqin Wang,Zeqing Lu,Caiqiao Zhang,Mingliang Jin,Yizhen Wang
Summary NLRP3 inflammasome activation requires both transcriptional priming and complex assembly, but how RNA m 6 A methylation coordinates these steps remains unclear. Here, we show that m 6 A levels increase during macrophage NLRP3 inflammasome activation and that METTL3 loss suppresses this activation. Myeloid-specific Mettl3 knockout mice display reduced inflammation and improved metabolic outcomes in lipopolysaccharide (LPS)-induced sepsis, monosodium urate (MSU)-induced arthritis, and diet-induced obesity. Integrated chromatin-associated RNA sequencing (chrRNA-seq), kethoxal-assisted single-stranded DNA sequencing (KAS-seq), and chrRNA-methylated RNA immunoprecipitation (MeRIP)-seq analyses show that METTL3 installs m 6 A co-transcriptionally on nascent Jak1 , Nlrp3 , and Il1β RNAs and that METTL3 regulates dynamic transcription and chromatin accessibility while selectively maintaining Nlrp3 / Il1β transcription. YTHDF1-driven translation of Jak1 activates the JAK1-STAT3-C/EBPβ axis to initiate Nlrp3 / Il1β transcription, and m 6 A-YTHDF1 translation of Nlrp3 / Il1β amplifies protein output, forming a coupled transcriptional-translational circuit. Pharmacologic STAT3 inhibition and METTL3 catalytic rescue validate this pathway and identify METTL3-mediated m 6 A as a therapeutic target for inflammasome-driven diseases.
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CHEMICAL ENGINEERING JOURNAL
·
2026
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IF 12.5
Shuang Guo,Jiashuo Xu,Huiquan Wang,Wen Li,Tao Meng,Zhe Zhao,Zhiguang Niu,Xiaoqun Gong
We reported a TdT combined with CRISPR/Cas12a driven cascade amplification platform for the sensitive detection of both heavy metal ions and viral targets. • Integrated with reverse fluorescence-enhanced lateral flow strip for visual readout, this platform achieves LODs of 2.5 × 10 −15 M for Pb 2+ and 3.6 × 10 −16 M for DENV-RNA. • The modular design allows flexible replacement of recognition modules, offering a universal solution for on-site rapid monitoring of diverse pollutants in complex environmental matrices. Currently, constructing flexible detection platforms capable of identifying diverse hazardous substances remains a significant challenge. Conventional detection methods are limited by target specificity and lack cross-class universality. Herein, we developed a general platform for sensitive detection of lead ions (Pb 2+ ) and dengue virus (DENV) as two distinct model targets. This platform specifically converted different types of targets into detectable nucleic acid molecules, which would be further recognized and signal amplified by the cascade cycling isothermal amplification system composed of terminal deoxynucleotidyl transferase (TdT) and CRISPR/Cas12a system. TdT has the property of extending the 3′ end of DNA molecule in a template-independent manner, providing long poly-T nucleic acid sequence for binding lots of crRNA, so as to activate the trans-cleavage activity of Cas12a to cleave the hairpin DNA reporters with exposing numerous novel 3′ ends for the same cycle. By combining this strategy with the reverse fluorescence-enhanced lateral flow test strip, the platform achieves a limit of detection (LOD) of 2.5 × 10 −15 M and 3.6 × 10 −16 M for Pb 2+ and DENV-RNA, respectively. Moreover, the detection platform for Pb 2+ in environmental water samples showed excellent agreement with standard methods. It also demonstrated high sensitivity for DENV-RNA detection in complex samples, confirming its reliability and broad applicability potential in practical scenarios. Download: Download high-res image (103KB) Download: Download full-size image
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ACTA PHARMACOLOGICA SINICA
·
2026
·
IF 10.4
Xu Lu,Ma Yan,Yao Wang,Qiu Ya-ju,Xu Chao,Xu Fang-yue,Zou Zhi-miao,Dai Wu-min,Gong Wan-gang,Ma De-ning,Chen Xiao-wan,Ye Wen-kai,Huang Yi-yun,Chen Hai-tao,Hong Lue,Mo Jia-ping,Feng Jian-guo,Yu En-yan,Chen Wei,Zhang Yu-hua,Yao Qing-hua,Li Xia
5-Fluorouracil (5-FU) resistance in colorectal cancer (CRC) involves oxidative stress mechanisms, but the role of epitranscriptomic regulation remains unclear. This study investigates how oxidative post-translational modifications of the N6-methyladenosine (m 6 A) methyltransferase METTL16 contribute to 5-FU resistance. Parental (HCT8, HCT15) and 5-FU-resistant CRC cells were compared using redox proteomics, m 6 A-seq, RNA-seq, and functional assays. METTL16 S-glutathionylation was assessed via streptavidin pulldown and mass spectrometry. IGF2BP3’s role was validated through knockdown/overexpression, patient-derived organoids (PDOs), and xenograft models. Clinical relevance was evaluated in 112 CRC patient tissues and data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Drug synergy was tested using isoliquiritigenin (ISO) combined with 5-FU. Resistant cells exhibited elevated global protein S-glutathionylation and reduced m 6 A RNA methylation. METTL16 underwent site-specific S-glutathionylation at Cys548, leading to its degradation and subsequent m 6 A loss. Integrative omics identified IGF2BP3 as a key METTL16 target: reduced m 6 A on IGF2BP3 mRNA enhanced its nuclear export, splicing, and overexpression. IGF2BP3 knockdown sensitized resistant cells to 5-FU in vitro and in vivo, while overexpression conferred resistance. Mechanistically, IGF2BP3 destabilized CFTR mRNA (an ABC transporter), reducing 5-FU uptake. Clinically, high IGF2BP3 correlated with poor survival and 5-FU resistance in CRC patients. Targeting IGF2BP3 with ISO synergized with 5-FU, overcoming resistance in cells and xenografts. Oxidative stress-induced METTL16 S-glutathionylation drives 5-FU resistance by reducing m 6 A modification, enabling IGF2BP3 overexpression and CFTR suppression. IGF2BP3 is a biomarker of clinical resistance, and its targeting with ISO represents a promising combinatorial strategy to restore 5-FU efficacy in CRC.
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JOURNAL OF CHROMATOGRAPHY A
·
2025
·
IF 4
Ziang Yan,Jingyang Zhao,Xuan Lin,Zhengjun Li,Weiqing Zhou,Xiangming Na,Zhiguo Su,Songping Zhang
Imidazolium-based ionic liquids (ILs) as ligand have shown great potentials in biomacromolecule separation by chemically coupling the cationic functional group of the ILs to solid supports. Whether and how the counterions affect the adsorption of biomacromolecule, however remains unclear. In this work, GigaMIm chromatographic media was prepared by coupling an ionizable 1-methylimidazole (MIm) to giga-porous microspheres and paired with four different counterions including Cl − , H 2 PO 4 − , benzoate ion (BZA − ), and 4-hydroxybenzenesulfonate (HBS − ). The types of the counterions on GigaMIm was found to significantly influence the adsorption kinetics and isotherms of yeast RNA and BSA, as well as the chromatographic separation of RNA-BSA mixture. Compared to the media paired with inorganic ions (Cl − and H 2 PO 4 − ), those paired with benzene ring-containing counterions (HBS − and BZA − ) exhibited slightly slower pore diffusion kinetics and lower adsorption capacities for both RNA and BSA, but provided better separation resolution for their mixture. Molecular docking suggested that enhanced hydrogen bonding between MIm⁺/HBS⁻ or MIm⁺/BZA⁻ and biomolecules contributed to improved resolution. The counterion-tuning strategy was further validated by separation of eGFP mRNA from in vitro transcription system. Compared to GigaMIm-Cl, purification using GigaMIm-HBS obtained higher mRNA recovery (38.42% vs. 30.94%) with high mRNA purity and lower T7 polymerase residual (0.16% vs. 0.21%). These findings demonstrate that modulating counterions in ILs-based media may offer a promising strategy for optimizing nucleic acid and protein separation.
研究领域:
生物分离工程
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分子生物学
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分析化学
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药物分析
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生物材料
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ACS Omega
·
2025
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IF 4.3
Na Du,Guochao Xu,Yao Zhang,Jing Hou,Ying Wang,Yiran Li,Bing Xu
Nosocomial infection is a major global cause of mortality, posing significant public health challenges. Recent studies have identified RNA biomarkers, including microRNA (miRNA) and circular RNA (circRNA), as promising diagnostic tools for nosocomial infection, providing essential information for timely clinical intervention. In this study, we developed a versatile and label-free circRNA and miRNA detection platform based on a Cas13a/crRNA complex-based target recognition that triggers a primer exchange reaction (PER)-driven DNA walker. In this method, the Cas13a/crRNA complex is used to specifically identify target RNA biomarkers and to induce subsequent signal amplification strategies following cleavage of uracil (UUU, trU)-containing locked “sensing probe” based on trans-cleavage of Cas13a. Taking the merit of the high specific target recognition capability of Cas13a/crRNA, false signals or unintended circRNA degradation can be greatly avoided. The PER performed on the surface of streptavidin-coated magnetic beads (sMBs) motivated the walking of primer sequences, greatly amplifying fluorescence signals. Based on this design, the proposed method exhibits high sensitivity and precision, with detection limits as low as 0.41 fM for miRNA-21 and 3.12 fM for cZNF292. These findings suggest that this strategy could advance the identification of RNA biomarkers and hold considerable potential for future applications in diagnosing nursing infections.
研究领域:
分子诊断
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CRISPR技术
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核酸检测
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传染病监测
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生物传感器
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FOOD AND CHEMICAL TOXICOLOGY
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2023
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IF 4.3
Xin Wang,Guangyun Ran,Yufen Liao,Bowen Gong,Chutian Wu,Rong Tan,Ying Liu,Shiyu Zhang,Ying Peng,Weiwei Li,Jiang Zheng
Safrole (SFL) is an IARC class 2B carcinogen. To better understand the mechanism involved in SFL toxicity, we explored the potential interactions between SFL metabolites and RNA. Three guanosine adducts (G1-G3), two adenosine adducts (A1-A2), and two cytosine adducts (C1–C2) were detected by LC-MS/MS in mouse liver S9 incubations, cultured mouse primary hepatocytes, and liver tissues of mice after exposure to SFL. These adducts were chemically synthesized, and one of the guanosine adducts was structurally characterized by 1 H-NMR. Studies in vitro and in vivo showed that SFL was oxidized by cytochrome P450 enzymes to the corresponding 1′-hydroxyl metabolite which was further metabolized by sulfotransferases to form allylic sulfate esters. The formed reactive intermediate(s) subsequently reacted with bases of RNA, leading to RNA adduction, which could play a partial role in the toxicities of SFL through the alteration of RNA biochemical properties and interruption of RNA functions.
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Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 7
·1478-1485
·
IF 7
Chengjie Duan,Yan Chen,Zhiqiang Hou,Dayong Li,Jin Jiao,Weihao Sun,Yang Xiang
Heteromultivalent scaffolds with different repeated monomers have great potential in biomedicine, but convenient construction strategies for integrating various functional modules to achieve multiple biological functions are still lacking. Here, taking advantage of the heteromultivalent effect of dendritic nucleic acids and the specific biochemical properties of microRNAs (miRNAs), we assembled novel heteromultivalent nucleic acid scaffolds by biomimetic co-assembly of DNA–RNA building blocks. In our approach, two miRNAs were used to initiate and maintain dendritic structures in an interdependent manner; so, the heteromultivalent nanostructure can only form in the presence of both miRNAs. The proposed nanostructure can be used for one-step analysis of two miRNAs in an AND logic format. Taking miR-18b-5p and miR-342-3p which are associated with Alzheimer's disease as an example, a FRET sensing system was fabricated for the simultaneous analysis of two miRNAs within one hour at picomolar concentration. Further studies show that the designed device may have the potential to distinguish between AD patients and the healthy population by analysis of two miRNAs in CSF (cerebrospinal fluid) samples, suggesting its possible applicability in clinics.
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Frontiers in Microbiology
·
2022
·
IF 6.064
Shi Zhihui,He Xiaoxian,Zhang Hailiang,Guo Xuena,Cheng Yanfei,Liu Xuelian,Wang Zhaoyue,He Xiuping
Carotenoids are unsaturated compounds with terpene groups. Among them, astaxanthin has strong antioxidant properties. It is widely used in aquaculture, food, medicine, and cosmetics with a broad market prospect. Phaffia rhodozyma is an important microorganism that synthesizes astaxanthin, but its wild strains have low pigment content, long growth cycle, and low fermentation temperature. Therefore, it is important to research the genetic improvement of the physiological and biochemical properties of P. rhodozyma. In this study, the atmospheric and room temperature plasma mutagenesis technology was adopted, through the functional evolution of the carotenoid production performance; then, through the comparative analysis of the genomics and transcriptomics of the wild strain and evolved strain, the key factor GST1 gene that affects carotenoid synthesis was discovered.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2022
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IF 5.518
Pan Cheng,Cancan Ji,Wei Hu,Peng Huang,Qihao Guo,Ming Xia,Qin Cheng,Jia Xu,Ke Liu,Dong Wang
Construction of ion-exchange chromatography membrane with appropriate pore size and high-density ligands is essential to improve its working efficiency and service life for the separation and purification of biomacromolecules such as RNA . Herein, surface aminated ethylene vinyl alcohol copolymer (EVOH) ion-exchange chromatography nanofibrous membrane (PEI-NFM) with 0.7 µm pore size was fabricated by sea-island spinning and in situ crosslinking (EVOH nanofibers reacted with glutaraldehyde (GA) and polyethyleneimine (PEI) in dispersion). Morphological and chemical characterization of PEI-NFM indicated that GA and PEI crosslinked on the surface of nanofibers uniformly. Benefiting from the 3D network scaffold structure stacked by nanofibers and high-density amine groups, PEI-NFM exhibits high saturated capacity toward RNA (191.16 mg/g), and still possesses more than 93% of its initial adsorption capacity after ten times cyclic adsorption-elution. Moreover, PEI-NFM packed syringe-driven filter shows high water flux of 10.38 L/h at 0.1 MPa and a high dynamic adsorption performance toward RNA (144.07 mg/g at 1 mm/min). Besides, PEI-NFM exhibits high-recognition binding property toward RNA mixed with other biomacromolecules by adjusting pH of mixed solution to make other biomacromolecules positively charged. This work provides a facile strategy for the preparation of high performance and long service life ion-exchange chromatography membrane.
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MICROCHEMICAL JOURNAL
·
2023
·
IF 4.8
Yang Mei,Si Yang,Chenxi Li,Xinyu Li,Yuewen Yu,Rong Liu,Wenliang Chen,Xiaoli Wang,Kexin Xu
Mercury ion (Hg 2+ ) detection plays a crucial role in safeguarding the environment and protecting human health. In this study, we developed a microfluidic biosensing platform that utilizes a phosphorothioate-RNA (PS-RNA) probe and gold-coated magnetic nanoparticles to quantify Hg 2+ visually. The PS-RNA probe was linked to gold-coated magnetic nanoparticles via Au–S interaction and biotin–avidin interaction and then combined with polystyrene microspheres to form a self-assembled structure called a magnetic bead-AuNP-probe-polystyrene (MAPP) bead. We designed and fabricated a microfluidic chip that contained only a magnetic separator and a particle trap. The presence of Hg 2+ cut the PS-RNA probe, leading to the separation of magnetic beads and polystyrene microspheres. The MAPP was removed by the magnetic separator, while the cut polystyrene microspheres flowed along the channel and accumulated in the particle trap, forming a long visible strip. The length of the polystyrene microsphere strip was proportional to the Hg 2+ concentration. The microfluidic biosensing platform exhibited high sensitivity and specificity for Hg 2+ detection, with a detection limit of 21.9 nM. By integrating the microfluidic magnetic manipulation system with a sensitive nucleic acid probe, we developed an automated and visual biosensor that is a valuable reference for the on-site visual detection of heavy metal ions.
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JOURNAL OF HAZARDOUS MATERIALS
·
2021
·
IF 10.588
Danting Wang,Xuedong Wang,Haishan Huang,Huili Wang
Herein, we demonstrated that triclosan (TCS) induced neurotoxicity mediated by pre-mRNA alternative splicing (AS). TCS exposure resulted in a series of phenotypic malformations, abnormal locomotor behavior, circadian rhythm disorder and inhibited AChE activity. High throughput mRNA sequencing revealed that TCS regulated the AS events of nerve-related genes. Meanwhile, abnormal expression was observed in marker genes related to nerve cell migration, axon guidance and myelination. The expression of mitochondrial apoptosis activator bcl2l11 was significantly increased under TCS exposure. Interestingly, CELF2 as one of the important RNA-binding proteins was closely related to the AS events, and its mRNA and protein expression levels were significantly increased in zebrafish brain under acute or chronic TCS exposure. Functional knock-down and over-expression of celf2 confirmed that TCS led to nervous system injury and developmental defects through the CELF2-mediated AS events of genes ( mbpa , mef2d , u2af2b and matn3b ). Histopathological injury, phenotypic malformation, abnormal locomotor behavior and changes in neuromarkers all confirmed the biological functions of CELF2 in zebrafish brain. These findings demonstrate that TCS might regulate some of the AS events of nerve-related genes through upregulating the expression of CELF2. Thus, CELF2 may serve as a target for the prevention, diagnosis and treatment of contaminant-induced neurological diseases.
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