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Initial Insights into the NET-Associated ceRNA Network in Pulpitis: Transcriptomic and Functional Exploration

Xiaolan Guo,Kailun Wu,Longrui Dang,Sitong Liu,Jing Xu,Runting Wang,Junyang Xu,Yiming Zhong,Zhao Chen,Buling Wu

Background Pulpitis is an oral disease primarily triggered by microbial infections. Current therapeutic strategies lack specific agents targeting the underlying pathogenic mechanisms. Non-coding RNAs (ncRNAs) and their competitive endogenous RNA (ceRNA) networks have emerged as critical regulators of diverse biological processes, offering novel insights into the pathogenesis of pulpitis and the identification of potential therapeutic targets. Methods RNA sequencing was performed on pulp tissues from healthy individuals and pulpitis patients. Bioinformatics tools were employed to analyse sequencing data, identify differentially expressed messenger RNAs (mRNAs), and construct protein-protein interaction (PPI) networks to pinpoint hub genes. A murine pulpitis model was established to investigate the effects of neutrophil extracellular trap (NET) inhibitors on disease progression. A NET-associated ceRNA regulatory network was systematically constructed based on ceRNA theory. In vitro experiments validated the expression patterns of key ncRNAs and mRNAs in pulpitis. Results Differentially expressed mRNAs, long non-coding RNAs (lncRNAs), and Circular RNAs (circRNAs) were identified in pulpitis. Bioinformatics analysis revealed significant activation of NET-related pathways, with sialic acid-binding immunoglobulin-like lectin-9 (SIGLEC9), complement C3 (C3), H2A clustered histone 14 (H2AC14), and H4 clustered histone 11 (H4C11) identified as core regulatory genes. In vivo experiments demonstrated that NET inhibition alleviated dental pulpitis and necrosis. Furthermore, a novel NET-associated ceRNA regulatory network was established, revealing four critical regulatory axes: LINC00466 / hsa-miR-27a-3p / SIGLEC9, hsa_circDNAH11_003 / hsa-miR-877-5p / C3, hsa_circSLC15A4_001 / hsa-miR-30d-3p / H2AC14, and hsa_circGABBR2_009 / hsa-miR-193b-3p / H4C11. These ncRNAs exhibited significant upregulation in inflamed pulp tissues. Conclusion By constructing a comprehensive NET-associated ceRNA network, we elucidate molecular mechanisms underlying dental pulpitis, providing novel evidence for understanding the disease progression. These findings establish a theoretical foundation for developing targeted therapeutic strategies against pulpitis.

Superior RdRp Function Drives the Dominance of Prevalent GI.3 Norovirus Lineages

Qianxin Lu,Huisha Du,Xin Jiang,Bingwen Zeng,Tianhui Li,Ying-Chun Dai

The GI.3 norovirus is the most detected and recombinant-rich genotype within genogroup I, yet the mechanistic basis for its epidemiological success remains poorly understood. This study integrates Bayesian evolutionary analysis with in vitro enzymology to investigate the link between RdRp function and the evolutionary dynamics of GI.3 NoV. We analyzed 831 GI.3 sequences, finding that prevalent strains (GI.3[P3] and GI.3[P13]) exhibited significantly higher evolutionary rates in both the RdRp and VP1 genes than non-prevalent strains (GI.3[P10] and GI.3[P14]). While the RdRp gene displayed a strong molecular clock signal, the VP1 gene’s evolution was more complex, showing cluster-specific trends. Functionally, the RdRps from prevalent strains demonstrated superior enzymatic activity and substrate affinity (Km: GI.3[P13] = 0.092 mM; GI.3[P3] = 0.176 mM) compared to non-prevalent strains (Km: GI.3[P14] = 0.273 mM). Notably, GI.3 RdRp required higher manganese ion concentrations for optimal activity than previously reported for GII strains, suggesting a potential biochemical constraint. Our findings demonstrate a clear correlation between RdRp enzymatic efficiency, evolutionary rate, and strain prevalence. We propose that a highly active RdRp may potentially accelerate VP1 evolution and confer a replicative advantage, underpinning the dominance of specific GI.3 lineages. This work provides crucial experimental evidence linking viral polymerase function to evolutionary and epidemiological outcomes.

RNA-Modified Graphene Oxide-Encapsulated Gold Nanoparticles-Based Stable Fiber Optic MiRNA-126 Sensor

Bing Xu,Liu Yang,Liyun Ding,Zhihui Luo,Zhihong Pan

A dynamic and multilocus metabolic regulation strategy using quorum-sensing-controlled bacterial small RNA

Shao-Heng Bao,Hui Jiang,Ling-Yun Zhu,Ge Yao,Peng-Gang Han,Xiu-Kun Wan,Kang Wang,Tian-Yu Song,Chang-Jun Liu,Shan Wang,Zhe-Yang Zhang,Dong-Yi Zhang,Er Meng

Summary Metabolic regulation strategies have been developed to redirect metabolic fluxes to production pathways. However, it is difficult to screen out target genes that, when repressed, improve yield without affecting cell growth. Here, we report a strategy using a quorum-sensing system to control small RNA transcription, allowing cell-density-dependent repression of target genes. This strategy is shown with convenient operation, dynamic repression, and availability for simultaneous regulation of multiple genes. The parameters A i , A m , and R A (3-oxohexanoyl-homoserine lactone [AHL] concentrations at which half of the maximum repression and the maximum repression were reached and value of the maximum repression when AHL was added manually, respectively) are defined and introduced to characterize repression curves, and the variant LuxR I58N is identified as the most suitable tuning factor for shake flask culture. Moreover, it is shown that dynamic overexpression of the Hfq chaperone is the key to combinatorial repression without disruptions on cell growth. To show a broad applicability, the production titers of pinene, pentalenene, and psilocybin are improved by 365.3%, 79.5%, and 302.9%, respectively, by applying combinatorial dynamic repression.

Molecular Crowding-Driven RNA Condensates Enable Förster Resonance Energy Transfer-Enhanced Small-Molecule Sensing

Yifan Wu,Xuan Ma,Yanger Liu,Zhaoxuan Zhang,Yangzi Zhang,Wenqiang Zhang,Longjiao Zhu,Wentao Xu

Fluorescent RNA aptamers offer promising opportunities for next-generation biosensing but are often limited by low signal-to-background ratios and unstable folding kinetics. In this work, a label-free Förster resonance energy transfer (FRET)-enhanced fluorescent artificial RNA condensate (F-FARCON) is developed for small-molecule sensing, leveraging neutral molecular crowders (e.g., polyethylene glycol 8K), and RNA structural motifs to induce multivalent interactions and drive dynamic self-assembly. As a demonstration, a label-free FRET system is constructed by integrating a histamine-responsive RNA aptamer with thioflavin T (ThT) as the fluorescence donor, which increases the signal-to-noise ratio while reducing sequence complexity and production costs. Molecular crowders optimize the thermodynamic environment of RNA–ligand and RNA–RNA multivalent interactions, thereby improving folding stability, signal amplitude (dynamic range of up to ∼970-fold), and target affinity. The platform exhibits fast kinetics (<15 min), an adjustable detection range (0.1–200 and 5–1000 µM), and high sensitivity (limit of detection, 15.36 nM), with robust performance in complex biological matrices. The platform is further integrated into a freeze-dried paper-based portable device that enables dual-channel fluorescence readout for on-site rapid detection without sophisticated instrumentation. To further validate the modularity of F-FARCON beyond histamine, we reprogrammed the recognition module to target S-adenosyl-L-methionine (SAM), achieving nanomolar limits of detection. By linking crowding-guided assembly to hierarchical photophysical enhancement and analytical performance, the work delineates a generalizable aggregate-science route to versatile, low-cost, and field-deployable fluorescence sensing across food safety, environmental monitoring, and biomedical diagnostics.

Honokiol Inhibits Porcine Reproductive and Respiratory Syndrome Virus Proliferation by Targeting Viral RNA Polymerase

Yao Wang,Yongxiao Chai,Qisheng Qian,Yue Liang,Xin-xin Chen,Guangxu Xing,Liutao Zhao,Songlin Qiao,Rui Li,Gaiping Zhang

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious swine disease and poses a severe economic burden to the global swine industry. Owing to the inadequacy of current prevention and control measures, developing effective antiviral strategies for preventing PRRS epidemics is imperative. Honokiol (HNK) is a bioactive component of the dietary supplement magnolia extract. Here, we demonstrated that HNK exhibited potent antiviral effects against different PRRSV strains in vitro. Mechanistically, HNK was shown to interfere with PRRSV replication rather than attachment, internalization, or release. HNK was further determined to target PRRSV RNA-dependent RNA polymerase to impair viral genomic RNA synthesis. In addition, HNK was found to decrease PRRSV-triggered inflammatory responses. More importantly, HNK was revealed to reduce viral loads and alleviate lung damage in vivo. This study highlights the potential of HNK as an inhibitor of PRRSV and provides novel insights into its antiviral properties.

A nanotechnology-enhanced workflow for direct, sensitive detection of viral RNA in exhaled breath

Xue Zhang,Zikang Tong,Meijie Jia,Yinglu Yuan,Zhenxiu Huang,Jiachen Jiang,Bin Liu,Yijun Yuan,Lei Liu,Jianye Fu,Yang Wang,Xin Wang

Ultrasensitive detection of airborne viral RNA is achieved at 10 PFU L −1 nominal input under controlled aerosol conditions. • Surface spikes provide morphology-dependent protection of captured RNA from RNase degradation. • Nanotechnology-Enhanced Workflow combined with RT-qPCR enables pathogen detection in clinical exhaled breath samples. • Integration with LAMP-CRISPR/Cas12b enables rapid detection of airborne viruses under controlled conditions. The detection of airborne RNA viruses is critically important for public health but remains technically challenging due to the extremely low ambient concentrations. Here, we present a highly sensitive and integrated detection workflow based on engineered spiky silica nanoparticle variants (SSNPRs). Engineered with tunable spike lengths, the SSNPRs concentrate trace viral RNA and protect it from ambient RNase degradation via a morphology-dependent RNA protection mechanism. Combined with an optimized lysis and elution protocol, this method enhances detection sensitivity by 100-fold compared to commercial RNA extraction kits and enables detection at a nominal airborne input equivalent to 10 PFU L −1 under controlled aerosol conditions. We successfully applied this system to detect SARS-CoV-2 and influenza A viruses in the exhaled breath of febrile patients, suggesting that respiratory viral shedding may not always be synchronized with clinical symptoms. Furthermore, by integrating the workflow with a LAMP-CRISPR/Cas12b assay, we demonstrated equipment-minimal detection of airborne coronaviruses. This work demonstrates the potential of SSNPR-2-based nanotechnology to integrate air sampling and molecular detection, providing a proof-of-concept approach for sensitive detection of low-abundance airborne viral RNA under controlled aerosol conditions. This work introduces an innovative “spiky” nanoparticle-based platform for sensitive detection of airborne viruses. By integrating viral RNA enrichment and protection with molecular detection, the approach provides a proof-of-concept strategy for sensitive detection of viral RNA in environmental and exhaled-breath samples and may support the further development of air-based molecular detection approaches with potential relevance to environmental, clinical, and One Health research. Download: Download high-res image (71KB) Download: Download full-size image

CRISPR/Cas13a-mediated interfacial cleaving of hairpin RNA reporter for PEAK1 nucleic acid sensing

Xiwei Zhuang,Zhihao Duan,Xue Ge,Yanling Wang,Yuan Gao,Jianlei Liu,Shaoxiong Zhou,Chijia Zeng,Feiyun Cui,Qin Zhou

Dysregulation of PEAK1 (pseudopodium-enriched atypical kinase 1) plays a critical role in various cellular processes, including cell migration, proliferation and survival. Its aberrant expression or activity has been implicated in the pathogenesis of several diseases, particularly cancer. Early detection allows for the development and application of targeted therapies that can inhibit PEAK1 activity, potentially improving treatment outcomes. This study provides a new method for early diagnosis of PEAK1 by utilizing the specific RNA cleavage ability of Cas13a combined with electrochemical sensing technology. CRISPR/Cas13 has cis cleavage activity and can specifically recognize and cleave target RNA. Subsequently, its trans cleavage activity is activated to non-specifically cleave other single stranded RNAs, resulting in detectable signal changes. In the experiments conducted, high sensitivity for detecting PEAK1 mRNA was achieved by optimizing the interface cleavage of the hairpin reporter probe (ReRNA) molecule. The linear detection range is from 1 pg μL−1 to 10 ng μL−1, with a detection limit of 0.45 pg μL−1. In addition, the results showed that the developed biosensor has good repeatability, reproducibility, and stability, which provides a novel method for the early screening of PEAK1.

β-Cyclodextrin-Modified Laser-Induced Graphene Electrode for Detection of N6-Methyladenosine in RNA

Jingyi Guo,Mei Zhao,Xia Kuang,Zilin Chen,Fang Wang

Laser-induced graphene (LIG) possesses characteristics of easy handling, miniaturization, and unique electrical properties. We modified the surface of LIG by electropolymerizing β-cyclodextrin (β-CD), which was used to immobilize antibodies on the electrode surface for highly sensitive detection of targets.N6-methyladenosine (m6A) is the most prevalent reversible modification in mammalian messenger RNA and noncoding RNA, influencing the development of various cancers. Here, β-CD was electropolymerized to immobilize the anti-m6A antibody, which subsequently recognized the target m6A. This was integrated into the catalytic hydrogen peroxide–hydroquinone (H2O2-HQ) redox system using phos-tag-biotin to generate electrochemical signals from streptavidin-modified horseradish peroxidase (SA-HRP). Under optimal conditions, the biosensor exhibited a linear range from 0.1 to 100 nM with a minimum detection limit of 96 pM. The method was successfully applied to the recovery analysis of m6A from HeLa cells through spiking experiments and aims to inspire strategies for point-of-care testing (POCT).

Unveiling transfer RNA modifications of oil palm and their dynamic changes during fruit ripening

Deng Dehai,Qin Yichao,Lin Xiuying,Chu Meng,Lv Daizhu,Lin Huan

Background The oil palm ( Elaeis guineensis ) is a crucial agricultural commodity, yielding the highest oil output among oil-bearing crops. Despite its significance, productivity challenges persist due to genetic and environmental factors. This study breaks new ground by mapping tRNA modifications in oil palm, exploring their roles during fruit ripening, an area not extensively studied in non-model crops. Results Utilizing advanced RNA mass spectrometry techniques, we identified 48 distinct tRNA modifications across 88 sites, alongside 164 genes associated with tRNA modifying enzymes. This comprehensive mapping reveals the decreasing nature of most tRNA modifications during fruit development, except for adenosine 2’-O methylation (Am). It hints at a gradual weakening of protein translation quality control and highlights a unique role for Am during fruit ripening. Additionally, lipidomic analysis tracked 674 lipids in oil palm fruits, indicating a correlation between tRNA modifications and the accumulation of specific lipids. Conclusions This study mapped tRNA modifications in oil palm for the first time and showed the diversity of dynamic changes in tRNA modifications as the fruits develop.

Targeting a key disulfide linkage to regulate RIG-I condensation and cytosolic RNA-sensing

Wang Bin,Wang Yongqiang,Pan Ting,Zhou Lili,Ran Yu,Zou Jing,Yan Xiaohua,Wen Zhenke,Lin Shixian,Ren Aiming,Wang Fangwei,Liu Zhuang,Liu Ting,Lu Huasong,Yang Bing,Zhou Fangfang,Zhang Long

Maintaining innate immune homeostasis is critical for preventing infections and autoimmune diseases but effective interventions are lacking. Here we identified C864–C869-mediated intermolecular disulfide-linkage formation as a critical step for human RIG-I activation that can be bidirectionally regulated to control innate immune homeostasis. The viral-stimulated C864–C869 disulfide linkage mediates conjugation of an SDS-resistant RIG-I oligomer, which prevents RIG-I degradation by E3 ubiquitin-ligase MIB2 and is necessary for RIG-I to perform liquid–liquid phase separation to compartmentalize downstream signalsome, thereby stimulating type I interferon signalling. The corresponding C865S ‘knock-in’ caused an oligomerization defect and liquid–liquid phase separation in mouse RIG-I, which inhibited innate immunity, resulting in increased viral load and mortality in mice. Using unnatural amino acids to generate covalent C864–C869 linkage and the development of an interfering peptide to block C864–C869 residues, we bidirectionally regulated RIG-I activities in human diseases. These findings provide in-depth insights on mechanism of RIG-I activation, allowing for the development of methodologies that hold promising implications in clinics.

Specific and efficient RNA A-to-I editing through cleavage of an ADAR inhibitor

Li Guangye,Chen Guo,Yuan Guo-Hua,Wei Jia,Ni Qingyang,Wu Jing,Yang Bei,Yang Li,Chen Jia

RNA editing can be a promising therapeutic approach. However, ectopic expression of RNA editing enzymes has been shown to trigger off-target editing. Here we identified adenosine deaminase acting on RNA (ADAR) inhibitors (ADIs) that suppress the activity of the fused ADAR2 deamination domain (ADAR2 DD ). Using these specific ADIs, we develop an RNA transformer adenosine base editor (RtABE) with high specificity. Fusing ADI to ADAR2 DD , RtABE remains inactive until it binds to its target site. After binding to the target site, ADI is cleaved from ADAR2 DD , and RtABE becomes active. RtABE can induce efficient editing in broad sequence contexts, including UAN, AAN, CAN and GAN. Using an adeno-associated virus for delivery of RtABE enables therapeutic RNA correction and restoration of α- l -iduronidase activity in Hurler syndrome mice with no substantial off-target editing. RtABE is a specific and efficient RNA editing system with a broad scope that may be a better alternative to existing RNA editing tools.