Breast cancer (BC) remains a leading cause of cancer-related death among women. There is an urgent need for new therapies with fewer side effects. This study evaluated the anticancer potential of curcumin micro- and nanocapsules on MCF-7 breast cancer cells and explored the underlying molecular mechanisms using bioinformatics analysis.

In Arabidopsis (Arabidopsis thaliana), a family of 5 receptors mediates ethylene responses in roots, with Ethylene Response 1 (ETR1) controlling increases in root hair proliferation and decreases in lateral root formation. To define the ETR1-dependent gene regulatory network (GRN) controlling root development, we profiled the root transcriptome from Col-0 and the etr1-3 gain-of-function and etr1-7 loss-of-function mutants in the presence and absence of ethylene or the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC). We identified 4,522 differentially expressed (DE) transcripts in Col-0 roots that displayed altered abundance in response to ethylene and/or ACC treatment, with larger-magnitude changes induced by ethylene. These included 553 DE transcripts that were ETR1 dependent, defined by a lack of response to treatment with ethylene and/or ACC in ethylene-insensitive etr1-3 and constitutive alteration response in etr1-7 in the presence or absence of treatment relative to time-0 Col-0. These ETR1-dependent transcripts include transcripts from genes associated with ethylene biosynthesis and those encoding transcription factors (TFs). Reporter fusions driven by promoters from ACC OXIDASE 2 (ACO2) and ACO3, which convert ACC to ethylene, were regulated by ACC in root tissues in appropriate locations to control root development, with pACO5-driven GFP detected in root hairs. We examined the abundance of ETR1-dependent transcripts predicted to encode TFs and ACOs in Col-0 and an ein3 eil1 mutant, with and without ACC treatment. Our results suggested that the ETR1 and Ethylene Insensitive 3 (EIN3)/EIN3-like 1 (EIL1) canonical ethylene signaling pathway regulates some, but not all, of these transcriptional responses. Together, these findings reveal features of an ETR1-dependent GRN that controls both ethylene biosynthesis and root growth and development.

Plants reprogramme their metabolism upon pathogen attack, producing compounds that can either enhance immunity or be exploited by pathogens. Metabolomic profiling of wheat during Fusarium graminearum infection revealed pronounced accumulation of phenolamides, driven by activation of their biosynthetic pathways. Notably, exogenous N-feruloylputrescine (Ferput), a representative phenolamide, enhanced resistance to wheat stripe rust, powdery mildew and rice blast but increased susceptibility to Fusarium head blight. Ferput inhibited fungal infection in the lemma while promoting rachis colonisation, indicating pathogen- and tissue-specific effects. Mechanistic analyses showed that Ferput stimulates deoxynivalenol (DON) biosynthesis by inducing TRI gene expression, toxisome formation and DON-associated cellular differentiation, underlying the shift from lemma resistance to rachis susceptibility. Together, these findings highlight the context-dependent roles of phenolamide in plant-pathogen interactions and suggest that, under specific pathological contexts, defence-associated metabolites can be exploited by pathogens to enhance their virulence. This insight underscores the necessity of considering the dual functional roles of plant metabolites when engineering broad-spectrum disease resistance.

This study profiled physiological, biochemical, and transcriptional responses of Solanum nigrum to cadmium (Cd) in potted soil across graded treatments. Growth, assessed as fresh and dry mass, and chlorophyll a declined only at higher doses, whereas carotenoids increased by about 70%. Proline rose by roughly 302% and soluble proteins by 173% in a dose-responsive manner, consistent with up to 9.1-fold increases in P5CS transcripts. Malondialdehyde and hydrogen peroxide increased with Cd, accompanied by antioxidant responses. Shoots accumulated substantial Cd in soil, reaching 170 mg kg-1 DW at 100 mg kg-1 soil Cd, while the tolerance index remained ≥ 60% at the highest dose. The translocation factor exceeded one at all additions and peaked at ~ 1.28 at 50-100 mg kg-1Bioavailability-aware enrichment remained high: BCF_available (shoot) referenced to DTPA-Cd was ~ 19.4 at 12.5-25 mg kg-1 16.9 at 50 mg kg-1, and 12.6 at 100 mg kg-1. Whole-plant removal increased monotonically, with total Cd uptake of approximately 166, 303, 392, and 518 µg plant-1 at 12.5, 25, 50, and 100 mg kg-1, respectively. Candidate transporter transcripts showed distinct dose-dependent patterns in soil: SnYSL3 peaked at the intermediate dose (~ 7.6-fold), whereas HMA3 rose progressively and was highest at 100 mg kg-1 (~ 7.2-fold). Principal component analysis separated treatments and grouped stress markers with P5CS and HMA3 at higher Cd. This work provides a gradient-resolved, soil-based dataset linking Cd partitioning, bioavailability-normalized indices, and total uptake with coordinated shifts in candidate YSL and HMA transporters and key metabolites. The resulting framework establishes a standardized baseline for functional validation and field translation.

Armillaria species have attracted considerable research interest, because they are widely distributed, mostly plant-pathogenic, and exhibit unique characteristics. Abiotic factors influence intra- and interspecies variations in pathogenicity and/or virulence of these fungi. However, the mechanisms involved in causing these variations are not well understood. Iron is an indispensable element in several molecular and biological processes. Yet, excessive abundance of iron can be toxic to organisms due to Fenton-like reactions. This study aimed to gain insights into the type and extent of iron-responsive proteomic and secretomic changes in Armillaria sp. strain CMW4456 cultured in liquid media supplemented with iron using a multiomics approach. Significant iron-dependent alterations of proteins involved in metabolism and growth were observed in the proteomes and secretomes. Iron supplementation at 100 μM did not elicit an oxidative stress response by the fungus. Our analyses revealed three putative siderophore biosynthetic gene clusters (BGCs) in the genome and expression of proteins encoded by some BGC genes in the proteome. This knowledge contributes to a better understanding of the mechanisms employed by an Armillaria sp. in response to iron, gives insights into possible modes for inhibiting or attenuating the pathogenicity and/or virulence of Armillaria spp., and can be valorized for more biotechnological applications.

Breast cancer is the most commonly diagnosed cancer in women globally. Our previous MIRACLE trial (NCT02313051) demonstrated that everolimus plus letrozole (E + L) significantly improves progression-free survival compared with letrozole (L) monotherapy in premenopausal patients with endocrine therapy-resistant, hormone receptor-positive, HER2-non-amplified advanced breast cancer. This study aims to investigate spatially resolved biomarkers linked to survival benefits from E + L to guide precision therapies. Patients from MIRACLE were stratified by overall survival (OS ≤ 3 vs. >3 years). Spatial Whole Transcriptome Atlas analysis was used to evaluate tumor-, immune-, and stroma-specific gene expression, co-expression network patterns, and survival correlations. Among patients with shorter survival (OS ≤ 3 years), we identified a distinctive gene interaction network characterized by tumor-derived S100A9 and CALML5, which is associated with mTORC1 activation. This finding suggests that tasquinimod, an S100A9 inhibitor, could be a viable therapeutic option. Additionally, an interaction between CALML5 and SLPI across tumor and immune areas indicated a potential role in maintaining tumor integrity and mitigating immune-mediated damage. Conversely, patients with longer survival (OS > 3 years) exhibited SERPINA1 as a hub gene linked to estrogen receptor activation, and an interaction between FKBP5 and SESN3 associated with AKT/mTORC1 inhibition within tumor-rich regions. Furthermore, the interaction between MMP11 and COL16A1 in stroma-rich regions suggests that cancer-associated fibroblasts may contribute to improved outcomes. Our study underscores the critical role of spatial gene expression analysis in elucidating the tumor microenvironment and its impact on prognosis in patients undergoing E + L treatment, thereby opening new avenues for targeted interventions.

Amblyopia is a neurodevelopmental disorder, and there are no effective treatment methods for adult amblyopia patients due to the decline in synaptic plasticity in visual cortex. Enriched environment (EE) has been shown to enhance synaptic plasticity, which is mediated, at least in part, by epigenetic mechanisms involving histone acetylation. This study aims to investigate whether histone deacetylase (HDAC) inhibitors can replicate the effects of EE on visual cortical plasticity, thereby offering novel therapeutic insights for adult amblyopia. First, we established adult amblyopia mice model, which were then randomized into five groups: untreated amblyopia, standard housing, EE, vehicle, trichostatin A (TSA) groups, with normal mice serving as controls. To evaluate synaptic plasticity in visual cortex, we measured synaptic marker VGLUT2, synaptic ultrastructure and long-term potentiation (LTP). Additionally, biochemical analyses were conducted to measure alterations of HDACs associated with synaptic integrity. Our findings revealed that EE enhanced synaptic plasticity in visual cortex of adult amblyopia mice and was associated with reduced HDAC3 expression. Similarly, the broad HDAC inhibitor TSA, improved synaptic ultrastructure, increased VGLUT2 expression, and potentiated LTP, functionally resembling several key effects of EE. Importantly, TSA targets multiple HDAC isoforms, and the observed reduction in HDAC3 levels is correlated with, but does not establish, a causal role for HDAC3. These results indicate that broad HDAC inhibition can mimic EE-induced plasticity in adult amblyopia, while highlighting the need for selective HDAC3-targeted approaches to determine mechanistic specificity. Overall, our study provides a foundation for developing epigenetic-based strategies to enhance adult visual cortical plasticity.

Fibers are the main economic product of cotton (Gossypium hirsutum). As an ideal model for studying plant cell development, many factors that influence cotton fiber have been revealed. Previous studies have demonstrated the important role of sphingolipids in fiber development through chemical and genetic methods, but the regulatory module by which sphingolipids regulate fiber development remains unclear. Here, we used the sphingolipid biosynthesis inhibitor fumonisin B1 (FB1) and found that it effectively suppressed the expression of an orthologue of the trihelix transcription factor SIP1 clade-like (GhSIL) in upland cotton. Lipid-protein binding assays also revealed that ceramide (t18:0/24:0) and 24-epibrassinolide (BL) bind to GhSIL protein in vitro. GhSIL was preferentially expressed in elongating fibers. The transcriptome and reverse transcription quantitative PCR analysis revealed that the expression of brassinosteroid synthesis genes was significantly decreased in GhSIL downregulated cotton fibers during the fiber elongation stage. Yeast 1-hybrid assay, dual-luciferase (LUC) assay, and chromatin immunoprecipitation (ChIP) assays showed that GhSIL can directly bind to the GT1-box element in the brassinosteroid-6-oxidase 2 (GhBR6OX2) promoter region to enhance its expression. Overexpression of GhSIL and GhBR6OX2 promoted fiber elongation, consistent with the results of exogenous application of BL in cotton ovule culture in vitro. By contrast, suppressing GhSIL and GhBR6OX2 expression inhibited fiber elongation, which was similar to the exogenous application of brassinazole (BRZ). These results illuminated that sphingolipids regulate fiber cell elongation through the GhSIL-GhBR6OX2-brassinolide module, which reveals a node in the molecular mechanism by which sphingolipids regulate plant growth and development.

Gastric cancer (GC) remains among the cancers with extremely high morbidity and mortality rates worldwide, and chemotherapy resistance limits its therapeutic efficacy. Therapy‑induced senescence (TIS) is vital for inducing chemotherapy resistance and promoting tumor progression, highlighting the need to explore its regulatory mechanisms. To investigate oxaliplatin (OXA)‑induced senescence in GC cells, cellular senescence was assessed by senescence‑associated β‑galactosidase (SA‑β‑Gal) staining, western blotting, immunofluorescence, and reverse transcription‑quantitative polymerase chain reaction for the senescence‑associated secretory phenotype (SASP) factors. Moreover, multi‑omics integration including transcriptomic, proteomic and untargeted metabolomic, was used to identify key regulators and pathways. OXA induced a senescent phenotype characterized by p21 upregulation, SA‑β‑Gal staining, cell cycle arrest and SASP secretion. Integrative multi‑omics analysis revealed that NR4A1 is a central upstream regulator, and the PI3K/AKT pathway is suppressed in OXA‑induced senescence. Notably, survival analysis verified that NR4A1 expression was correlated with the prognosis of patients in GC. Functional studies demonstrated that NR4A1 knockdown attenuated OXA‑induced senescence, restored PI3K/AKT activity, and reduced SASP expression. Metabolomic profiling revealed that OXA‑induced senescence induced metabolic reprogramming, including glycolysis enhancement and oxidative phosphorylation suppression. Notably, NR4A1 knockdown reversed these metabolic alterations. The present study identified NR4A1 as a key regulated gene in chemotherapy‑induced senescence in GC and verified that the NR4A1/AKT‑metabolism axis is vital for the pivotal mechanism of TIS. These findings may provide a novel therapeutic strategy to optimize chemotherapy and develop 'one‑two punch' approaches targeting senescent tumor cells.

Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder with no approved therapeutics targeting the disease mechanism. DM1 is caused by the expression of expanded CUG repeat RNA (CUGexp), which sequester the muscleblind-like (MBNL) family of RNA binding proteins leading to dysregulated alternative splicing and a host of downstream impacts. While previous studies showed that diamidines rescued DM1 dysregulated alternative splicing events, their potential was limited by toxicity and off-target effects. A new class of modified polycyclic compounds (MPCs), based on diamidines, were created and screened in DM1 patient-derived cell lines. This approach identified MPC03 and MPC04 as being capable of rescuing DM1 dysregulated splicing events at low nanomolar concentrations with no obvious toxicity and limited off-target effects. In a DM1 mouse model, treatment with MPC03 and MPC04 reduced CUGexp RNA levels and partially rescued DM1 mis-splicing. Binding data and modeling showed that lead MPCs bind to CUGexp RNA, and in cells lacking CUG repeats, MPC activity was absent, suggesting that these compounds displace sequestered MBNL proteins from CUGexp RNA. Taken together, MPCs show therapeutic promise across multiple DM1 models.

Xizang sheep are vital economic livestock in plateau regions. Traditional surgical castration often induces stress and infection. Although immunization presents an alternative method, the physiological mechanisms underlying its effects in Xizang sheep remain unclear. Therefore, this study integrated serum immune-antioxidant indicators with hypothalamus-pituitary transcriptomics to investigate molecular mechanisms of GnRH immunization. Results indicated that serum IgA, IgG, IgM, SOD, and GSH in the immunization (IM) group were significantly higher than in control (CON) and surgical castration (SN) groups, while IL-6 and TNF-α were significantly reduced (p < 0.05). RNA-seq analysis revealed that hypothalamic CYTB, ATP6, COX, ABLIM1, and ABI3 were significantly upregulated in IM group, whereas SHISA7 and PTPRO were significantly downregulated, with notable enrichment in prion disease, oxidative phosphorylation, and thermogenesis pathways. Pituitary RPL15 was upregulated while RPL10A, CACNA1D, ANK1, DDX3X, and KCNMA1 were significantly downregulated, showing enrichment in myofibril, contractile fiber, sarcomere, and cytosolic ribosome pathways. Association analysis revealed significant positive correlations between IgG and pituitary ATP6, CYTB, TNNI2, as well as hypothalamic COX1, COX, and ND4. In summary, GnRH immunization outperforms surgical castration by modulating hypothalamic-pituitary genes and enhancing immunity and antioxidants in plateau Xizang sheep, achieving integrated neuroendocrine-immune regulation for healthy husbandry of plateau Xizang sheep.

Nitric oxide (NO) is a key signaling molecule that plays a vital role in maintaining homeostasis of physiological processes such as immune responses and neurotransmission. However, excessive NO production during inflammatory responses to infection can lead to cytotoxicity and tissue damage. The nasal epithelial barrier is a crucial first line of immunological defense against viral infections, and it is likely exposed to excessive NO levels during chronic inflammation. Therefore, clarifying the effects of NO on this barrier is thus critical. In this study, we investigated the biological effects of sustained NO exposure on RPMI2650 human nasal epithelial cells. Post-NO exposure transcriptomic analyses revealed significant upregulation of genes involved in the p53 signaling pathway. RT-qPCR analyses confirmed the temporal upregulation of p53 target genes associated with apoptosis and cell cycle regulation. These gene expression changes downregulated cell proliferation and induced cell death. Our findings suggest that excessive NO exposure induces nasal epithelial cell death via the p53 pathway, which over the long term can result in tissue damage and dysfunction under inflammatory conditions. These results provide new insights into how prolonged NO exposure affects the nasal epithelial cells and may contribute to the progression of chronic infectious diseases.

Melanoma, a malignant tumour originating from melanin-producing melanocytes, poses a significant threat to human health, including cutaneous melanoma and uveal melanoma (UM). Although surgical resection remains a primary treatment modality, radiotherapy has emerged as another therapeutic option, particularly for UM. Nevertheless, the adverse effects induced by radiotherapy are considerably pronounced. In this study, we identified WT-161, a selective histone deacetylase 6 (HDAC6) inhibitor, as a potent radiosensitizer for melanoma therapy through high-throughput drug screening. Mechanistically, inhibition of HDAC6 disrupted its interaction with DNA damage repair proteins (DDB2 and DEK) and suppressed gene expression in the DNA damage repair pathway, leading to the accumulation of irradiation-induced DNA damage and tumour regression. Our findings establish HDAC6 as a predictive biomarker for radiation response in melanoma and demonstrate that pharmacological inhibition of HDAC6 with WT-161 could expand the clinical utility of radiotherapy in patients with UM.

Fufang Baizhi Tincture (FFBZD) is a traditional topical Chinese medicine. This study demonstrates that FFBZD regulates melanocytes by modulating apoptosis via Caspase 7 (CASP7) and transcriptional regulation via E1A-associated protein p300 (EP300), thereby influencing vitiligo. These findings further links its traditional use with specific genetic targets and mechanism-based preventive and therapeutic potential.

Activation of hypoxia-inducible factors (HIFs) supports cancer cell survival, yet how HIFs govern cell death remains unclear, despite evidence that HIF-1 acts as a tumor suppressor in cell renal cell carcinoma (ccRCC). Here, we report a cell death-priming role for HIF-1/2 in ccRCC. Through cell viability screens with chemical libraries, we identify SGI1027 and its analog MS1129 as HIF-1/2-dependent cell death inducers that specifically kill VHL-deficient ccRCC cells in vitro and patient-derived xenografts in mice. Mechanistically, SGI1027 and MS1129 induce proteasomal degradation of DNMT1/DNMT3A/DNMT3B proteins, leading to the loss of promoter methylation and subsequent upregulation of TRAIL, DR4, and DR5 in ccRCC cells. HIF-1/2 induces procaspase-10 expression serving a commitment point to activate TRAIL-induced apoptosis in VHL-deficient ccRCC following SGI1027 or MS1129 treatment. Notably, recombinant TRAIL protein synergizes with SGI1027 or MS1129 to kill VHL-deficient ccRCC in mice. Collectively, our study unveils an apoptosis induction strategy that involves hijacking HIFs for ccRCC treatment.

The pathological mechanism of poor osseointegration of implants caused by aseptic loosening of implants is unclear. This study investigated the changes in implant osseointegration induced by titanium ions and explored the relationship between titanium implants, immune cells and osseointegration and the underlying mechanism of aseptic loosening of titanium implants. In vitro, mouse osteoblasts and mouse macrophages were co-cultured in a titanium ion environment that did not affect osteogenic activity. The results showed that the presence of macrophages in this titanium ion environment caused a decrease in osteogenic capacity. In addition, titanium ions lead to M1 polarization of macrophages and the production of inflammatory mediators, the inflammatory response can affect the ability of osteoblasts. Through transcriptome sequencing analysis of osteoblasts, it was found that the angiotensinogen (Agt) was up-regulated in osteoblasts added to the titanium ion group and knockdown or overexpression of Agt could change the effect of titanium ions on osteoblasts through macrophages. These results indicate that the application of gene Agt may provide new ideas for solving aseptic loosening of implants.

The escalating prevalence of multidrug-resistant Salmonella enterica serovar Typhimurium (S. Typhimurium) necessitates the urgent development of innovative therapeutic strategies. Targeting bacterial virulence factors has emerged as a promising alternative to conventional antibiotics. Among these factors, type I fimbriae serve as essential structural determinants for host colonization and pathogenesis. In this study, we investigated the anti-virulence potential of Tectorigenin (TE), a natural flavonoid isolated from the traditional medicinal herb Belamcandae Rhizoma. Our results demonstrate that TE significantly inhibits swarming motility, biofilm formation, and hemagglutination capacity of S. Typhimurium by directly influence key structural and regulatory genes within the fim operon, including fimA, fimD, fimF, fimH, fimI and the regulator STM0551. In vivo experiments further confirmed that TE treatment alleviates clinical symptoms in S. Typhimurium-infected mice, effectively reducing intestinal inflammation and preserving epithelial barrier integrity. Collectively, these findings highlight TE as a potent anti-virulence agent that targets type I fimbriae, offering a novel non-bactericidal approach for the management of S. Typhimurium infections.

Osteoarthritis (OA) is a prevalent degenerative joint disease with no curative treatment currently available. Recent evidence suggests that chondrocyte ferroptosis contributes to OA progression. Chondroitin sulfate (CS), widely used in OA management, exhibits anti-inflammatory and antioxidant properties, yet its role in modulating ferroptosis remains unclear. In this study, we investigated whether CS alleviates OA by inhibiting chondrocyte ferroptosis and explored the underlying mechanisms. Using an in vitro ferroptosis model induced by RSL3 in rat chondrocytes, we found that CS significantly restored cell viability and ameliorated ferroptosis-related changes, including reduction of intracellular and mitochondrial ROS, lipid peroxidation, and iron overload. CS also downregulated the expression of ferroptosis markers PTGS2 and ACSL4, while upregulating SLC7A11 and HSPA8 in a dose-dependent manner. Network pharmacology and transcriptomic analysis identified HSPA8 as a key overlapping gene among CS targets, OA-related differentially expressed genes, and ferroptosis-related genes. In a rat OA model induced by modified Hulth surgery, CS treatment attenuated cartilage degradation, as evidenced by improved OARSI scores, restored COL2A1 expression, and suppressed MMP13. Immunohistochemistry confirmed that CS upregulated SLC7A11 and HSPA8 while downregulating ACSL4. These findings demonstrate that CS mitigates OA progression by inhibiting chondrocyte ferroptosis, potentially through upregulation of HSPA8 and subsequent enhancement of SLC7A11 expression. Our study provides novel insights into the mechanism of CS in OA treatment and highlights ferroptosis as a promising therapeutic target.

Lignin deposition in stone cells is critical for pear fruit quality. However, calcium ions (Ca2+) exert critical regulatory effects on fruit growth and development. Nevertheless, the molecular mechanisms underlying Ca2+-mediated stone cell formation in pear remain poorly characterized. Our study revealed that exogenous application of CaCl2 decreased lignified stone cell formation in "Nanguoli" (Pyrus ussuriensis) fruits and significantly downregulated the expression of lignin biosynthesis-related genes laccase7 (PuLAC7) and peroxidase42 (PuPRX42). Transcriptome sequencing (RNA-seq) identified a transcription factor, PuMYB73, which was significantly inhibited by CaCl2 in pear fruit stone cell formation and lignin accumulation. Yeast one-hybrid (Y1H) and β-glucuronidase (GUS) activity analysis revealed that PuMYB73 directly binds and activates lignin biosynthesis genes PuPRX42 and PuLAC7 promoters, thereby decreasing PuPRX42 and PuLAC7 expression after CaCl2 treatment. Strikingly, PuMYB73 interacts with PuNAC21 to form a Ca2+-responsive module, lowering the transcription of PuPRX42 and PuLAC7 after Ca2+ treatment, which contributed to decreasing pear stone cell production. Collectively, exogenous CaCl2 treatment inhibits stone cell and lignin biosynthesis in pears mediated by the PuMYB73-PuNAC21 regulatory module. Our results revealed that the Ca2+-PuMYB73-PuNAC21-PuLAC7/PuPRX42 regulatory module inhibits lignin biosynthesis, providing important insights into reducing stone cell content in pear via molecular breeding.

The m6A modification plays key roles in RNA metabolism and function and is implicated in various human diseases. In this study, we reported a novel molecular glue strategy for transcript-specific m6A editing using synthetic bifunctional molecules containing an RNA-targeting moiety and a ligand that recruit an endogenous m6A erasing enzyme. Through cyclic γ-AApeptide library screening, we identified a novel peptidomimetic binder to the long noncoding RNA MALAT1 A2577 region, which has a high m6A level. We developed a bifunctional molecular glue by coupling the identified MALAT1-binding cyclic γ-AApeptide to fluorescein, a reported binder to the m6A eraser FTO. We demonstrated that this bifunctional molecular glue successfully recruited FTO to the target RNA site, achieved the m6A erasing, disrupted HNRNPC-MALAT1 binding, and destabilized MALAT1. We anticipate that this novel molecular glue strategy will offer a new direction in developing molecules to regulate RNA modifications.