Geniposide alleviates imiquimod-induced psoriasis-like skin lesions in mice via inhibition of angiogenesis.

In this study, we aimed to evaluate the protective effect of geniposide (GEN) on imiquimod (IMQ)-induced psoriasis-like skin lesions in mice. Firstly, visual changes of psoriatic skin lesions were observed and the severity was recorded using psoriasis area and severity index (PASI) score. Histological changes were assessed by HE staining for epidermal thickness and Masson's staining for collagen fibers. Then, photographs of microvascular inside the skin were taken for macroscopic observation, and microscopic changes associated with angiogenesis were evaluated. Furthermore, expression of angiogenic factors were analyzed by ELISA, immunohistochemistry and immunofluorescence, separately. Lastly, the expression of VEGFR signaling-related proteins was detected by WB. Compared with control, IMQ drove a significant increment of epidermal thicknesses with higher PASI scores and more dermal collagen deposition. IMQ treatment led to abnormal keratinocyte proliferation, increased microvascular inside skin, growing production of angiogenesis-related factors, up-regulated expression of VEGFR1 and VEGFR2, and enhanced phosphorylation of p38. However, GEN significantly ameliorated the psoriatic skin lesions, the epidermal thickness, the formation of collagen fibers, and abnormal keratinocyte proliferation. Importantly, GEN inhibited angiogenesis, the production of angiogenic factors (VEGF-A, Ang-2, TNF-α, and IL-17A), and the proliferation of vascular endothelial cells. Simultaneously, GEN curbed the expression of VEGFR1, VEGFR2, p38, and P-p38 proteins involved in VEGFR signaling. Of note, the suppressive effect of GEN was reversed in the HUVECs with over-expressed VEGFR1 or VEGFR2 related to the cells without transfection. These findings suggest that VEGFR1 and VEGFR2 participate in the anti-angiogenesis of GEN in IMQ-induced psoriasis-like skin lesions in mice.

Identification of a novel LFNG variant in a Chinese fetus with spondylocostal dysostosis and a systematic review.

Spondylocostal dysostosis (SCDO) encompasses a group of skeletal disorders characterized by multiple segmentation defects in the vertebrae and ribs. SCDO has a complex genetic etiology. This study aimed to analyze and identify pathogenic variants in a fetus with SCDO. Copy number variant sequencing and whole exome sequencing were performed on a Chinese fetus with SCDO, followed by bioinformatics analyses, in vitro functional assays and a systematic review on the reported SCDO cases with LFNG pathogenic variants. Ultrasound examinations in utero exhibited that the fetus had vertebral malformation, scoliosis and tethered cord, but rib malformation was not evident. We found a novel homozygous variant (c.1078 C > T, p.R360C) within the last exon of LFNG. The variant was predicted to cause loss of function of LFNG by in silico prediction tools, which was confirmed by an in vitro assay of LFNG enzyme activity. The systematic review listed a total of 20 variants of LFNG in SCDO. The mutational spectrum spans across all exons of LFNG except the last one. This study reported the first Chinese case of LFNG-related SCDO, revealing the prenatal phenotypes and expanding the mutational spectrum of the disorder.

Novel KMT5B variant associated with neurodevelopmental disorder in a Chinese family: A case report.

Background: We report here the clinical and genetic features of KMT5B-related neurodevelopmental disorder caused by a novel heterozygous frameshift variant in KMT5B in a Chinese family. Case presentation: A 7-year-old Chinese boy with mild-to-moderate intellectual disability, significant language impairment, motor disability, and coordination difficulties presented to our hospital because he "could not speak and did not look at others." He was diagnosed with autism spectrum disorder previously owing to developmental delays in cognition, language expression, and understanding. The child also had variable nonspecific features including macrocephaly, wide button-hole space and nasal bridge, low ear, social behavior disorder, and foot deformities. Exome sequencing (ES) revealed that both the proband and his younger brother had inherited a novel heterozygous frameshift variant c.438_439ins[ASD; KT192064.1:1_310] of the KMT5B gene from their father. Bioinformatics analysis showed that the novel mutation affected the structure of the KMT5B pre-SET domain, mainly in the α-helix region. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, this type of variant was eventually determined to be likely pathogenic (PVS1+PM2_P). Conclusions: Our investigation expands the mutation spectrum of KMT5B to help us to better understand KMT5B-related neurodevelopmental disorder.

Boosting Photothermocatalytic Oxidation of Toluene Over Pt/N-TiO2: The Gear Effect of Light and Heat.

Photothermal catalysis is extremely promising for the removal of various indoor pollutants owing to its photothermal synergistic effect, while the low light utilization efficiency and unclear catalytic synergistic mechanism hinder its practical applications. Here, nitrogen atoms are introduced, and Pt nanoparticles are loaded on TiO2 to construct Pt/N-TiO2-H2, which exhibits 3.5-fold higher toluene conversion rate than the pure TiO2. Compared to both photocatalytic and thermocatalytic processes, Pt/N-TiO2-H2 exhibited remarkable performance and stability in the photothermocatalytic oxidation of toluene, achieving 98.4% conversion and 98.3% CO2 yield under a light intensity of 260 mW cm-2. Furthermore, Pt/N-TiO2-H2 demonstrated potential practical applicability in the photothermocatalytic elimination of various indoor volatile organic compounds. The synergistic effect occurs as thermocatalysis accelerates the accumulation of carboxylate species and the degradation of aldehyde species, while photocatalysis promotes the generation of aldehyde species and the consumption of carboxylate species. This ultimately enhances the photothermocatalytic process. The photothermal synergistic effect involves the specific conversion of intermediates through the interplay of light and heat, providing novel insights for the design of photothermocatalytic materials and the understanding of photothermal mechanisms.

Excited-state Engineering Enables Efficient Deep-blue Light-emitting Diodes Exhibiting BT.2020 Color Gamut.

Organic luminescent materials that exhibit thermally activated delayed fluorescence (TADF) can convert non-emissive triplet excitons into emissive singlet states through a reverse intersystem crossing (RISC) process. Therefore, they have tremendous potential for applications in organic light-emitting diodes (OLEDs). However, with the development of ultra-high definition 4K/8K display technologies, designing efficient deep-blue TADF materials to achieve the Commission Internationale de l'Éclairage (CIE) coordinates fulfilling BT.2020 remains a significant challenge. Here, we propose an effective approach to design deep-blue TADF molecules based on hybrid long- and short-range charge-transfer by incorporation of multiple donor moieties into organoboron multiple resonance acceptors. The resulting TADF molecule exhibits deep-blue emission at 414 nm with a full width at half maximum (FWHM) of 29 nm, together with a thousand-fold increase in RISC rate. OLEDs based on our champion material achieved a record maximum external quantum efficiency (EQE) of 22.8% with CIE coordinates of (0.163, 0.046), approaching the coordinates of the BT.2020 blue standard. Moreover, TADF-assisted fluorescence devices employing our designed material as a sensitizer exhibited an exceptional EQE of 33.1%. Our work thus provides a blueprint for future development of efficient deep-blue TADF emitters, representing an important milestone towards meeting the blue color gamut standard of BT.2020. This article is protected by copyright. All rights reserved.

Ginsenoside CK Alleviates DSS-Induced IBD in Mice by Regulating Tryptophan Metabolism and Activating Aryl Hydrocarbon Receptor via Gut Microbiota Modulation.

Dysbiosis of gut microbiota is believed to be associated with inflammatory bowel disease (IBD). Ginsenoside compound K (CK), the main metabolite of Panax ginseng ginsenoside, has proven effective as an anti-inflammatory agent in IBD. However, the mechanisms by which CK modulates gut microbiota to ameliorate IBD remain poorly understood. Herein, CK demonstrated the potential to suppress the release of proinflammatory cytokines by gut microbiota modulation. Notably, supplementation with CK promoted the restoration of a harmonious balance in gut microbiota, primarily by enhancing the populations of Lactobacillus and Akkermansia. Furthermore, CK considerably elevated the concentrations of tryptophan metabolites derived from Lactobacillus that could activate the aryl hydrocarbon receptor. Overall, the promising alleviative efficacy of CK primarily stemmed from the promotion of Lactobacillus growth and production of tryptophan metabolites, suggesting that CK should be regarded as a prospective prebiotic agent for IBD in the future.

Efficient Charge Transport in Inverted Perovskite Solar Cells via 2D/3D Ferroelectric Heterojunction.

While the 2D/3D heterojunction is an effective method to improve the power conversion efficiency (PCE) of perovskite solar cells (PSCs), carriers are often confined in the quantum wells (QWs) due to the unique structure of 2D perovskite, which makes the charge transport along the out-of-plane direction difficult. Here, a 2D/3D ferroelectric heterojunction formed by 4,4-difluoropiperidine hydrochloride (2FPD) in inverted PSCs is reported. The enriched 2D perovskite (2FPD)2PbI4 layer with n = 1 on the perovskite surface exhibits ferroelectric response and has oriented dipoles along the out-of-plane direction. The ferroelectricity of the oriented dipole layer facilitates the enhancement of the built-in electric field (1.06 V) and the delay of the cooling process of hot carriers, reflected in the high carrier temperature (above 1400 K) and the prolonged photobleach recovery time (139.85 fs, measured at bandgap), improving the out-of-plane conductivity. In addition, the alignment of energy levels is optimized and exciton binding energy (32.8 meV) is reduced by changing the dielectric environment of the surface. Finally, the 2FPD-treated PSCs achieve a PCE of 24.82% (certified: 24.38%) with the synergistic effect of ferroelectricity and defect passivation, while maintaining over 90% of their initial efficiency after 1000 h of maximum power point tracking.

Multifunctional Hydrogel of Recombinant Humanized Collagen Loaded with MSCs and MnO2 Accelerates Chronic Diabetic Wound Healing.

Chronic wound repair is a clinical treatment challenge. The development of multifunctional hydrogels is of great significance in the key aspects of treating chronic wounds, including reducing oxidative stress, promoting angiogenesis, and improving the natural remodeling of extracellular matrix and immune regulation. In this study, we prepared a composite hydrogel, sodium alginate (SA)@MnO2/recombinant humanized collagen III (RHC)/mesenchymal stem cells (MSCs), composed of SA, MnO2 nanoparticles, RHC, and MSCs. The hydrogel has high mechanical properties and good biocompatibility. In vitro, SA@MnO2/RHC/MSCs hydrogel effectively enhanced the formation of intricate tubular structures and angiogenesis and showed synergistic effects on cell proliferation and migration. In vivo, the SA@MnO2/RHC/MSCs hydrogel enhanced diabetes wound healing, rapid re-epithelization, favorable collagen deposition, and abundant wound angiogenesis. These findings demonstrated that the combined effects of SA, MnO2, RHC, and MSCs synergistically accelerate healing, resulting in a reduced healing time. These observed healing effects demonstrated the potential of this multifunctional hydrogel to transform chronic wound care and improve patient outcomes.

Evaluating the impact of childhood BMI on the risk of coronavirus disease 2019: A Mendelian randomization study.

Introduction: Although the correlation between childhood obesity and coronavirus disease 2019 (COVID-19) has been explored, the causality of these remains uncertain. Thus, we conducted a two-sample Mendelian randomization (MR) analysis to identify the causal association. Methods: Instrumental variables of childhood obesity were selected from genome-wide association study involving 61,111 Europeans. Besides, we collected summary statistics of different COVID-19 outcomes (susceptibility, hospitalization, and severity) from genome-wide association study including more than 2 million Europeans. The inverse-variance weighted was applied to assess the causality of childhood obesity with COVID-19. Furthermore, we replicated the above association based on another study. Results: Inverse-variance weighted results suggested that childhood obesity promoted the COVID-19 susceptibility but has not been validated in other approaches. For hospitalization and severity of COVID-19, we found that childhood obesity, respectively, increased 30 and 38% risk (P < 0.001), which were consistent in other MR approaches. Discussion: Our study provides evidence for a causal relationship between childhood BMI and COVID-19 which is consistent with previous studies. Though these explanations are biologically plausible, further studies are warranted to elucidate the role of these. Conclusions: Our study suggests the potential causal associations of childhood obesity with COVID-19, especially hospitalization and severity of COVID-19.

Enhanced plant-derived vesicles for nucleotide delivery for cancer therapy.

Small RNAs (microRNAs [miRNAs] or small interfering RNAs [siRNAs]) are effective tools for cancer therapy, but many of the existing carriers for their delivery are limited by low bioavailability, insufficient loading, impaired transport across biological barriers, and low delivery into the tumor microenvironment. Extracellular vesicle (EV)-based communication in mammalian and plant systems is important for many physiological and pathological processes, and EVs show promise as carriers for RNA interference molecules. However, some fundamental issues limit their use, such as insufficient cargo loading and low potential for scaling production. Plant-derived vesicles (PDVs) are membrane-coated vesicles released in the apoplastic fluid of plants that contain biomolecules that play a role in several biological mechanisms. Here, we developed an alternative approach to deliver miRNA for cancer therapy using PDVs. We isolated vesicles from watermelon and formulated a hybrid, exosomal, polymeric system in which PDVs were combined with a dendrimer bound to miRNA146 mimic. Third generation PAMAM was chosen due to its high branching structure and versatility for loading molecules of interest. We performed several in vivo experiments to demonstrate the therapeutic efficacy of our compound and explored in vitro biological mechanisms underlying the anti-tumor effects of miRNA146, which are mostly related to its anti-angiogenic activity.

Human Breast Milk Exosomal miRNAs are Influenced by Premature Delivery and Affect Neurodevelopment.

SCOPE: This study investigates the exosomal microRNA (miRNA) profiles of term and preterm breast milk, including the most abundant and differentially expressed (DE) miRNAs, and their impact on neurodevelopment in infants. METHODS AND RESULTS: Mature milk is collected from the mothers of term and preterm infants. Using high-throughput sequencing and subsequent data analysis, exosomal miRNA profiles of term and preterm human breast milk (HBM) are acquired and it is found that the let-7 and miR-148 families are the most abundant miRNAs. Additionally, 23 upregulated and 15 downregulated miRNAs are identified. MiR-3168 is the most upregulated miRNA in preterm HBM exosome, exhibiting targeting activity toward multiple genes involved in the SMAD and MAPK signaling pathways and playing a crucial role in early neurodevelopment. Additionally, the effects of miR-3168 on neurodevelopment is confirmed and it is determined that it is an essential factor in the differentiation of neural stem cells (NSCs). CONCLUSION: This study demonstrates that miRNA expression in breast milk exosomes can be influenced by preterm delivery, thereby potentially impacting neurodevelopment in preterm infants.

TEMPO/O2 Synergistically Mediated BiBrO-Photocatalyzed Decarboxylative Phosphorylation of N-Arylglycines.

With both TEMPO and O2 (in air) as the homogeneous redox mediators, BiBrO as the heterogeneous semiconductor photocatalyst, the first example of semi-heterogeneous photocatalytic decarboxylative phosphorylation of N-arylglycines with diarylphosphine oxides was established. A series of α-amino phosphinoxides were efficiently synthesized.

Polygonatum kingianum Polysaccharides Enhance the Preventive Efficacy of Heat-Inactivated Limosilactobacillus reuteri WX-94 against High-Fat-High-Sucrose-Induced Liver Injury and Gut Dysbacteriosis.

Limosilactobacillus reuteri (L. reuteri) is an efficacious probiotic that could reduce inflammation and prevent metabolic disorders. Here, we innovatively found that Polygonatum kingianum polysaccharides (PKP) promoted proliferation and increased stability of L. reuteri WX-94 (a probiotic strain showing anti-inflammation potentials) in simulated digestive fluids in vitro. PKP was composed of galactose, glucose, mannose, and arabinose. The cell-free supernatant extracted from L. reuteri cultured with PKP increased ABTS•+, DPPH•, and FRAP scavenging capacities compared with the supernatant of the medium without PKP and increased metabolites with health-promoting activities, e.g., 3-phenyllactic acid, indole-3-lactic acid, indole-3-carbinol, and propionic acid. Moreover, PKP enhanced alleviating effects of heat-inactivated L. reuteri on high-fat-high-sucrose-induced liver injury in rats via reducing inflammation and regulating expressions of protein and genes involved in fatty acid metabolism (such as HIF1-α, FAßO, CPT1, and AMPK) and fatty acid profiles in liver. Such benefits correlated with its prominent effects on enriching Lactobacillus and short-chain fatty acids while reducing Dubosiella, Fusicatenilacter, Helicobacter, and Oscillospira. Our work provides novel insights into the probiotic property of PKP and emphasizes the great potential of the inactivated L. reuteri cultured with PKP in contracting unhealthy diet-induced liver dysfunctions and gut dysbacteriosis.

Smart Solid-State Interphases Enable High-Safety and High-Energy Practical Lithium Batteries.

With the electrochemical performance of batteries approaching the bottleneck gradually, it is increasingly urgent to solve the safety issue. Herein, all-in-one strategy is ingeniously developed to design smart, safe, and simple (3S) practical pouch-type LiNi0.8Co0.1Mn0.1O2||Graphite@SiO (NCM811||Gr@SiO) cell, taking full advantage of liquid and solid-state electrolytes. Even under the harsh thermal abuse and high voltage condition (100 °C, 3-4.5 V), the pouch-type 3S NCM811||Gr@SiO cell can present superior capacity retention of 84.6% after 250 cycles (based pouch cell: 47.8% after 250 cycles). More surprisingly, the designed 3S NCM811||Gr@SiO cell can efficiently improve self-generated heat T1 by 45 °C, increase TR triggering temperature T2 by 40 °C, and decrease the TR highest T3 by 118 °C. These superior electrochemical and safety performances of practical 3S pouch-type cells are attributed to the robust and stable anion-induced electrode-electrolyte interphases and local solid-state electrolyte protection layer. All the fundamental findings break the conventional battery design guidelines and open up a new direction to develop practical high-performance batteries.

Intracoronary microcatheter indwelling for continuous pumping of low-dose thrombolytic drugs: A new approach to reperfusion in acute myocardial infarction.

Reperfusion therapy of acute myocardial infarction (AMI) refers to physical or chemical recanalization and restoration of blood flow to an occluded coronary artery, and current techniques for reperfusion therapy include intravenous thrombolysis, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). The number of patients receiving emergency CABG in the real world is decreasing due to the disadvantages of CABG and the improvement in PCI procedures. Thrombolytic therapy has some disadvantages such as low recanalization rate, high risk of reocclusion and bleeding, and short time window. On the other hand, intracoronary interventional therapy may meet the requirements of "early, complete and persistent" patency of coronary arteries at different time points. However, in the emergency PCI, although thrombus aspiration via a catheter or balloon dilation is performed, residual thrombus with heavy or low TIMI (thrombolysis in myocardial infarction) myocardial perfusion grading is still observed in some patients, suggesting disordered microcirculation. Currently, the treatment of microcirculatory disturbance in emergency PCI mainly employed injection of tirofiban, adenosine, thrombolytic agent or other drugs into the local area via a microcatheter in a short time, all of which can significantly reduce the thrombus load and improve TIMI perfusion. Herein, we report that a microcatheter was indwelled in the coronary artery for continuous pumping of low-dose thrombolytic drugs as reperfusion therapy in 12 patients with acute and subacute MI.

Molecular Characteristics of JAK2 and Its Effect on the Milk Fat and Casein Synthesis of Ovine Mammary Epithelial Cells.

In addition to its association with milk protein synthesis via the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, JAK2 also affects milk fat synthesis. However, to date, there have been no reports on the effect of JAK2 on ovine mammary epithelial cells (OMECs), which directly determine milk yield and milk contents. In this study, the coding sequence (CDS) region of ovine JAK2 was cloned and identified and its tissue expression and localization in ovine mammary glands, as well as its effects on the viability, proliferation, and milk fat and casein levels of OMECs, were also investigated. The CDS region of ovine JAK2, 3399 bp in length, was cloned and its authenticity was validated by analyzing its sequence similarity with JAK2 sequences from other animal species using a phylogenetic tree. JAK2 was found to be expressed in six ovine tissues, with the highest expression being in the mammary gland. Over-expressed JAK2 and three groups of JAK2 interference sequences were successfully transfected into OMECs identified by immunofluorescence staining. When compared with the negative control (NC) group, the viability of OMECs was increased by 90.1% in the pcDNA3.1-JAK2 group. The over-expression of JAK2 also increased the number and ratio of EdU-labeled positive OMECs, as well as the expression levels of three cell proliferation marker genes. These findings show that JAK2 promotes the viability and proliferation of OMECs. Meanwhile, the triglyceride content in the over-expressed JAK2 group was 2.9-fold higher than the controls and the expression levels of four milk fat synthesis marker genes were also increased. These results indicate that JAK2 promotes milk fat synthesis. Over-expressed JAK2 significantly up-regulated the expression levels of casein alpha s2 (CSN1S2), casein beta (CSN2), and casein kappa (CSN3) but down-regulated casein alpha s1 (CSN1S1) expression. In contrast, small interfered JAK2 had the opposite effect to JAK2 over-expression on the viability, proliferation, and milk fat and milk protein synthesis of OMECs. In summary, these results demonstrate that JAK2 promotes the viability, proliferation, and milk fat synthesis of OMECs in addition to regulating casein expression in these cells. This study contributes to a better comprehension of the role of JAK2 in the lactation performance of sheep.

MXene/Hydrogel-based bioelectronic nose for the direct evaluation of food spoilage in both liquid and gas-phase environments.

Various bioelectronic noses have been recently developed for mimicking human olfactory systems. However, achieving direct monitoring of gas-phase molecules remains a challenge for the development of bioelectronic noses due to the instability of receptor and the limitations of its surrounding microenvironment. Here, we report a MXene/hydrogel-based bioelectronic nose for the sensitive detection of liquid and gaseous hexanal, a signature odorant from spoiled food. In this study, a conducting MXene/hydrogel structure was formed on a sensor via physical adsorption. Then, canine olfactory receptor 5269-embedded nanodiscs (cfOR5269NDs) which could selectively recognize hexanal molecules were embedded in the three-dimensional (3D) MXene/hydrogel structures using glutaraldehyde as a linker. Our MXene/hydrogel-based bioelectronic nose exhibited a high selectivity and sensitivity for monitoring hexanal in both liquid and gas phases. The bioelectronic noses could sensitively detect liquid and gaseous hexanal down to 10-18 M and 6.9 ppm, and they had wide detection ranges of 10-18 - 10-6 M and 6.9-32.9 ppm, respectively. Moreover, our bioelectronic nose allowed us to monitor hexanal levels in fish and milk. In this respect, our MXene/hydrogel-based bioelectronic nose could be a practical strategy for versatile applications such as food spoilage assessments in both liquid and gaseous systems.

Preparation and characterization of quercetin@ZIF-L/GO@AgNPs nanocomposite film for room-temperature strawberry preservation.

Fresh strawberries are easily contaminated by microorganisms after picking. Therefore, how to effectively store and keep fresh strawberries has been a hot topic for scientists to study. In this study, we prepared a leaf shaped metal organic framework nanomaterial loaded with quercetin (Quercetin@ZIF-L) at first, which can achieve effective loading of quercetin (96%) within 45 min and has a controlled release effect under acidic conditions. In addition, by cleverly combining satellite graphene oxide @ silver nanoparticles (GO@AgNPs) with slow precipitation performance, Quercetin@ZIF-L/GO@AgNPs nanocomposite film with larger pore size and larger specific surface area was prepared by scraping method. The characterization data of water flux, retention rate, flux recovery rate and water vapor permeability show that the composite film has good physical properties. The experiment of film packaging showed that the fresh life of strawberry could be extended from 3 to 8 days, which significantly improved the storage and freshness cycle of strawberry. At the same time, the metal migration test proved that the residual amount of silver ion in strawberry met the EU standard and zinc ions are beneficial to the health, enriching the types of high-performance fresh-keeping materials and broadening the application.

Targeting nucleotide metabolic pathways in colorectal cancer by integrating scRNA-seq, spatial transcriptome, and bulk RNA-seq data.

BACKGROUND: Colorectal cancer is a malignant tumor of the digestive system originating from abnormal cell proliferation in the colon or rectum, often leading to gastrointestinal symptoms and severe health issues. Nucleotide metabolism, which encompasses the synthesis of DNA and RNA, is a pivotal cellular biochemical process that significantly impacts both the progression and therapeutic strategies of colorectal cancer METHODS: For single-cell RNA sequencing (scRNA-seq), five functions were employed to calculate scores related to nucleotide metabolism. Cell developmental trajectory analysis and intercellular interaction analysis were utilized to explore the metabolic characteristics and communication patterns of different epithelial cells. These findings were further validated using spatial transcriptome RNA sequencing (stRNA-seq). A risk model was constructed using expression profile data from TCGA and GEO cohorts to optimize clinical decision-making. Key nucleotide metabolism-related genes (NMRGs) were functionally validated by further in vitro experiments. RESULTS: In both scRNA-seq and stRNA-seq, colorectal cancer (CRC) exhibited unique cellular heterogeneity, with myeloid cells and epithelial cells in tumor samples displaying higher nucleotide metabolism scores. Analysis of intercellular communication revealed enhanced signaling pathways and ligand-receptor interactions between epithelial cells with high nucleotide metabolism and fibroblasts. Spatial transcriptome sequencing confirmed elevated nucleotide metabolism states in the core region of tumor tissue. After identifying differentially expressed NMRGs in epithelial cells, a risk prognostic model based on four genes effectively predicted overall survival and immunotherapy outcomes in patients. High-risk group patients exhibited an immunosuppressive microenvironment and relatively poorer prognosis and responses to chemotherapy and immunotherapy. Finally, based on data analysis and a series of cellular functional experiments, ACOX1 and CPT2 were identified as novel therapeutic targets for CRC. CONCLUSION: In this study, a comprehensive analysis of NMRGs in CRC was conducted using a combination of single-cell sequencing, spatial transcriptome sequencing, and high-throughput data. The prognostic model constructed with NMRGs shows potential as a standalone prognostic marker for colorectal cancer patients and may significantly influence the development of personalized treatment approaches for CRC.