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Background m6A modification has been proved to play an important role in many biological processes. METTL3 as the main methyltransferase for methylation process has been found to be upregulated in many cancers, including CRC. Here, we investigate m6A modification and the underlying mechanism of METTL3 in the development of CRC. Methods The expression of METTL3 was detected in large clinical patient samples. To evaluate the function of METTL3 in vitro and in vivo, colony formation, CCK-8, cell migration and invasion assays were performed. To find out the downstream target of METTL3, GEO dataset was re-mined. We analyzed expression and metastasis-related miRNA by Pearson correlation, and miR-1246 was selected. Here, to identify the downstream target of miR-1246, Targetscan and miRWalk were used. RIP and luciferase reporter assay further confirmed SPRED2 as the direct target of miR-1246. Results We found that upregulated METTL3 is responsible for abnormal m6A modification in CRC and correlates positively with tumor metastasis. The gain- and loss-of-function indicates that METTL3 promotes cell migration and invasion in vitro and in vivo. Additionally, we confirmed that METTL3 can methylate pri-miR-1246, which further promotes the maturation of pri-miR-1246. By using bioinformatics tools, anti-oncogene SPRED2 was identified as the downstream target of miR-1246, wherein downregulated SPRED2 further reverses the inhibition of the MAPK pathway. Conclusions The present study demonstrates that the METTL3/miR-1246/SPRED2 axis plays an important role in tumor metastasis and provides a new m6A modification pattern in CRC development.

Background N 4 -acetylcytidine (ac 4 C) as a significant RNA modification has been reported to maintain the stability of mRNA and to regulate the translation process. However, the roles of both ac 4 C and its ‘writer’ protein N-acetyltransferase 10 (NAT10) played in the disease especially colorectal cancer (CRC) are unclear. At this point, we discover the underlying mechanism of NAT10 modulating the progression of CRC via mRNA ac 4 C modification. Methods The clinical significance of NAT10 was explored based on the TCGA and GEO data sets and the 80 CRC patients cohort of our hospital. qRT-PCR, dot blot, WB, and IHC were performed to detect the level of NAT10 and ac 4 C modification in CRC tissues and matched adjacent tissues. CCK-8, colony formation, transwell assay, mouse xenograft, and other in vivo and in vitro experiments were conducted to probe the biological functions of NAT10. The potential mechanisms of NAT10 in CRC were clarified by RNA-seq, RIP-seq, acRIP-seq, luciferase reporter assays, etc. Results The levels of NAT10 and ac 4 C modification were significantly upregulated. Also, the high expression of NAT10 had important clinical values like poor prognosis, lymph node metastasis, distant metastasis, etc. Furthermore, the in vitro experiments showed that NAT10 could inhibit apoptosis and enhance the proliferation, migration, and invasion of CRC cells and also arrest them in the G2/M phase. The in vivo experiments discovered that NAT10 could promote tumor growth and liver/lung metastasis. In terms of mechanism, NAT10 could mediate the stability of KIF23 mRNA by binding to its mRNA 3’UTR region and up-regulating its mRNA ac 4 c modification. And then the protein level of KIF23 was elevated to activate the Wnt/β-catenin pathway and more β-catenin was transported into the nucleus which led to the CRC progression. Besides, the inhibitor of NAT10, remodelin, was applied in vitro and vivo which showed an inhibitory effect on the CRC cells. Conclusions NAT10 promotes the CRC progression through the NAT10/KIF23/GSK-3β/β-catenin axis and its expression is mediated by GSK-3β which forms a feedback loop. Our findings provide a potential prognosis or therapeutic target for CRC and remodelin deserves more attention. Graphical Abstract

Long non-coding RNAs (lncRNAs) are emerging as key molecules in human cancer. Highly upregulated in liver cancer (HULC), an lncRNA, has recently been revealed to be involved in hepatocellular carcinoma development and progression. It remains unclear, however, whether HULC plays an oncogenic role in human gastric cancer (GC). In the present study, we demonstrated that HULC was significantly overexpressed in GC cell lines and GC tissues compared with normal controls, and this overexpression was correlated with lymph node metastasis, distant metastasis and advanced tumor node metastasis stages. In addition, a receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic values and the area under the ROC curve of HULC was up to 0.769. To uncover its functional importance, gain- and loss-of-function studies were performed to evaluate the effect of HULC on cell proliferation, apoptosis and invasion in vitro. Overexpression of HULC promoted proliferation and invasion and inhibited cell apoptosis in SGC7901 cells, while knockdown of HULC in SGC7901 cells showed the opposite effect. Mechanistically, we discovered that overexpression of HULC could induce patterns of autophagy in SGC7901 cells; more importantly, autophagy inhibition increased overexpression of HULC cell apoptosis. We also determined that silencing of HULC effectively reversed the epithelial-to-mesenchymal transition (EMT) phenotype. In summary, our results suggest that HULC may play an important role in the growth and tumorigenesis of human GC, which provides us with a new biomarker in GC and perhaps a potential target for GC prevention, diagnosis and therapeutic treatment.

Colorectal cancer (CRC) is a global health challenge, and patient education plays a crucial role in its early detection and treatment. Despite progress in AI technology, as exemplified by transformer-like models such as ChatGPT, there remains a lack of in-depth understanding of their efficacy for medical purposes. We aimed to assess the proficiency of ChatGPT in the field of popular science, specifically in answering questions related to CRC diagnosis and treatment, using the book “Colorectal Cancer: Your Questions Answered” as a reference. In general, 131 valid questions from the book were manually input into ChatGPT. Responses were evaluated by clinical physicians in the relevant fields based on comprehensiveness and accuracy of information, and scores were standardized for comparison. Not surprisingly, ChatGPT showed high reproducibility in its responses, with high uniformity in comprehensiveness, accuracy, and final scores. However, the mean scores of ChatGPT’s responses were significantly lower than the benchmarks, indicating it has not reached an expert level of competence in CRC. While it could provide accurate information, it lacked in comprehensiveness. Notably, ChatGPT performed well in domains of radiation therapy, interventional therapy, stoma care, venous care, and pain control, almost rivaling the benchmarks, but fell short in basic information, surgery, and internal medicine domains. While ChatGPT demonstrated promise in specific domains, its general efficiency in providing CRC information falls short of expert standards, indicating the need for further advancements and improvements in AI technology for patient education in healthcare.

Two α/β-fold hydrolases, KARRIKIN INSENSITIVE2 (KAI2) and Arabidopsis thaliana DWARF14 (AtD14), are necessary for responses to karrikins (KARs) and strigolactones (SLs) in Arabidopsis (Arabidopsis thaliana). Although KAI2 mediates responses to KARs and some SL analogs, AtD14 mediates SL but not KAR responses. To further determine the specificity of these proteins, we assessed the ability of naturally occurring deoxystrigolactones to inhibit Arabidopsis hypocotyl elongation, regulate seedling gene expression, suppress outgrowth of secondary inflorescences, and promote seed germination. Neither 5-deoxystrigol nor 4-deoxyorobanchol was active in KAI2-dependent seed germination or hypocotyl elongation, but both were active in AtD14-dependent hypocotyl elongation and secondary shoot growth. However, the nonnatural enantiomer of 5-deoxystrigol was active through KAI2 in growth and gene expression assays. We found that the four stereoisomers of the SL analog GR24 had similar activities to their deoxystrigolactone counterparts. The results suggest that AtD14 and KAI2 exhibit selectivity to the butenolide D ring in the 2'R and 2'S configurations, respectively. However, we found, for nitrile-debranone (CN-debranone, a simple SL analog), that the 2'R configuration is inactive but that the 2'S configuration is active through both AtD14 and KAI2. Our results support the conclusion that KAI2-dependent signaling does not respond to canonical SLs. Furthermore, racemic mixtures of chemically synthesized SLs and their analogs, such as GR24, should be used with caution because they can activate responses that are not specific to naturally occurring SLs. In contrast, the use of specific stereoisomers might provide valuable information about the specific perception systems operating in different plant tissues, parasitic weed seeds, and arbuscular mycorrhizae.

Molecules with donor–spacer–acceptor configuration have been developed rapidly given their peculiar properties. How to utilize intermolecular interactions and charge transfers for solution-processed organic light-emitting diodes (OLEDs) greatly relies on molecular design strategy. Herein, soluble luminophores with D-spacer-A motif were constructed via shortening the alkyl chain from nonane to propane, where the alkyl chain was utilized as a spatial linker between the donor and acceptor. The alkyl chain blocks the molecular conjugation and induces the existence of aggregation-induced intermolecular CT emission, as well as the improved solubility and morphology in a solid-state film. In addition, the length of the alkyl chain affects the glass transition temperature, carrier transport and balance properties. The mCP-3C-TRZ with nonane as the spacer shows better thermal stability and bipolar carrier transport ability, so the corresponding solution-processable phosphorescent organic light-emitting diodes exhibit superior external quantum efficiency of 9.8% when using mCP-3C-TRZ as a host material. This work offers a promising strategy to establish a bipolar host via utilizing intermolecular charge transfer process in an aggregated state.

Wildfires can encourage the establishment of invasive plants by releasing potent germination stimulants, such as karrikins. Seed germination of Brassica tournefortii , a noxious weed of Mediterranean climates, is strongly stimulated by KAR 1 , the archetypal karrikin produced from burning vegetation. In contrast, the closely-related yet non-fire-associated ephemeral Arabidopsis thaliana is unusual because it responds preferentially to KAR 2 . The α/β-hydrolase KARRIKIN INSENSITIVE 2 (KAI2) is the putative karrikin receptor identified in Arabidopsis . Here we show that B. tournefortii expresses three KAI2 homologues, and the most highly-expressed homologue is sufficient to confer enhanced responses to KAR 1 relative to KAR 2 when expressed in Arabidopsis . We identify two amino acid residues near the KAI2 active site that explain the ligand selectivity, and show that this combination has arisen independently multiple times within dicots. Our results suggest that duplication and diversification of KAI2 proteins could confer differential responses to chemical cues produced by environmental disturbance, including fire. Karrikins are germination stimulants perceived by KAI2 in Arabidopsis . Here the authors show that Brassica tournefortii , a close relative to Arabidopsis , has multiple copies of KAI2 with amino acid substitutions that confer responsiveness to the specific karrikin compounds found in wildfire smoke.

Open-pit mining offers significant benefits, such as enhanced safety conditions and high efficiency, making it a crucial method for use in the modern coal industry. Nevertheless, the comprehensive process of “stripping-mining-discharge-reclamation” inevitably leads to ecological disturbances in the mine and surrounding areas. Consequently, dynamic monitoring and supervision of open-pit mining activities are imperative. Unfortunately, current methods are inadequate for accurately identifying and continuously monitoring bare coal identification using medium spatial resolution satellite images (e.g., Landsat). This is due to the complex environmental conditions around mining areas and the need for specific image acquisition times, which pose significant challenges for large-scale bare coal area mapping. To address these issues, the paper proposes a novel bare coal index (BCI) based on Landsat OLI imagery. This index is derived from the spectral analysis, sensitivity assessment, and separability study of bare coal. The effectiveness and recognition capability of the proposed BCI are rigorously validated. Our findings demonstrate that the BCI can rapidly and accurately identify bare coal, overcoming limitations related to image acquisition timing, thus enabling year-round image availability. Compared to existing identification methods, the BCI exhibits superior resistance to interference in complex environments. The application of the BCI in the Chenqi Coalfield, Shengli Coalfield, and Dongsheng Coalfield in Inner Mongolia, China, yielded an average overall accuracy of 97% and a kappa coefficient of 0.87. Additionally, the BCI was also applied for bare coal area identification across the entire Inner Mongolia region, with a correct classification accuracy of 90.56%. These results confirm that the proposed index is highly effective for bare coal identification and can facilitate digital mapping of extensive bare coal (BC) coverage in open-pit mining areas.

Photoelectrochemical device is a versatile platform for achieving various chemical transformations with solar energy. However, a grand challenge, originating from mass and electron transfer of triphase—reagents/products in gas phase, water/electrolyte/products in liquid phase and catalyst/photoelectrode in solid phase, largely limits its practical application. Here, we report the simulation-guided development of hierarchical triphase diffusion photoelectrodes, to improve mass transfer and ensure electron transfer for photoelectrochemical gas/liquid flow conversion. Semiconductor nanocrystals are controllably integrated within electrospun nanofiber-derived mat, overcoming inherent brittleness of semiconductors. The mechanically strong skeleton of free-standing mat, together with satisfactory photon absorption, electrical conductivity and hierarchical pores, enables the design of triphase diffusion photoelectrodes. Such a design allows photoelectrochemical gas/liquid conversion to be performed continuously in a flow cell. As a proof of concept, 16.6- and 4.0-fold enhancements are achieved for the production rate and product selectivity of methane conversion, respectively, with remarkable durability. Addressing mass and electron transfer challenges hinders practical application of photoelectrochemical (PEC) devices. Here, authors report a simulation-guided development of hierarchical triphase diffusion photoelectrodes, achieving an improved mass transfer and ensuring electron transfer for PEC gas/liquid flow conversion.

Land Surface Temperature (LST) is a critical variable for understanding land–atmosphere interactions and is widely applied in urban heat monitoring, evapotranspiration estimation, near-surface air temperature modeling, soil moisture assessment, and climate studies. MODIS LST products, with their global coverage, long-term consistency, and radiometric calibration, are a major source of LST data. However, frequent data gaps caused by cloud contamination and atmospheric interference severely limit their applicability in analyses requiring high spatiotemporal continuity. This study presents a seamless MODIS LST reconstruction framework that integrates multi-source data fusion and a multi-stage optimization strategy. The method consists of three key components: (1) topography- and land cover-constrained spatial interpolation, which preliminarily fills orbit-induced gaps using elevation and land cover similarity criteria; (2) pixel-level LST reconstruction via random forest (RF) modeling with multi-source predictors (e.g., NDVI, NDWI, surface reflectance, DEM, land cover), coupled with HANTS-based temporal smoothing to enhance temporal consistency and seasonal fidelity; and (3) Poisson-based image fusion, which ensures spatial continuity and smooth transitions without compromising temperature gradients. Experiments conducted over two representative regions—Huainan and Jining—demonstrate the superior performance of the proposed method under both daytime and nighttime scenarios. The integrated approach (Step 3) achieves high accuracy, with correlation coefficients (CCs) exceeding 0.95 and root mean square errors (RMSEs) below 2K, outperforming conventional HANTS and standalone interpolation methods. Cross-validation with high-resolution Landsat LST further confirms the method’s ability to retain spatial detail and cross-scale consistency. Overall, this study offers a robust and generalizable solution for reconstructing MODIS LST with high spatial and temporal fidelity. The framework holds strong potential for broad applications in land surface process modeling, regional climate studies, and urban thermal environment analysis.