NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance.

The Warburg effect is a hallmark of cancer that refers to the preference of cancer cells to metabolize glucose anaerobically rather than aerobically1,2. This results in substantial accumulation of lacate, the end product of anaerobic glycolysis, in cancer cells3. However, how cancer metabolism affects chemotherapy response and DNA repair in general remains incompletely understood. Here we report that lactate-driven lactylation of NBS1 promotes homologous recombination (HR)-mediated DNA repair. Lactylation of NBS1 at lysine 388 (K388) is essential for MRE11-RAD50-NBS1 (MRN) complex formation and the accumulation of HR repair proteins at the sites of DNA double-strand breaks. Furthermore, we identify TIP60 as the NBS1 lysine lactyltransferase and the 'writer' of NBS1 K388 lactylation, and HDAC3 as the NBS1 de-lactylase. High levels of NBS1 K388 lactylation predict poor patient outcome of neoadjuvant chemotherapy, and lactate reduction using either genetic depletion of lactate dehydrogenase A (LDHA) or stiripentol, a lactate dehydrogenase A inhibitor used clinically for anti-epileptic treatment, inhibited NBS1 K388 lactylation, decreased DNA repair efficacy and overcame resistance to chemotherapy. In summary, our work identifies NBS1 lactylation as a critical mechanism for genome stability that contributes to chemotherapy resistance and identifies inhibition of lactate production as a promising therapeutic cancer strategy.

Inhibitor of cardiolipin biosynthesis-related enzyme MoGep4 confers broad-spectrum anti-fungal activity.

Plant pathogens cause devastating diseases, leading to serious losses to agriculture. Mechanistic understanding of pathogenesis of plant pathogens lays the foundation for the development of fungicides for disease control. Mitophagy, a specific form of autophagy, is important for fungal virulence. The role of cardiolipin, mitochondrial signature phospholipid, in mitophagy and pathogenesis is largely unknown in plant pathogenic fungi. The functions of enzymes involved in cardiolipin biosynthesis and relevant inhibitors were assessed using a set of assays, including genetic deletion, plant infection, lipidomics, chemical-protein interaction, chemical inhibition, and field trials. Our results showed that the cardiolipin biosynthesis-related gene MoGEP4 of the rice blast fungus Magnaporthe oryzae regulates growth, conidiation, cardiolipin biosynthesis, and virulence. Mechanistically, MoGep4 regulated mitophagy and Mps1-MAPK phosphorylation, which are required for virulence. Chemical alexidine dihydrochloride (AXD) inhibited the enzyme activity of MoGep4, cardiolipin biosynthesis and mitophagy. Importantly, AXD efficiently inhibited the growth of 10 plant pathogens and controlled rice blast and Fusarium head blight in the field. Our study demonstrated that MoGep4 regulates mitophagy, Mps1 phosphorylation and pathogenesis in M. oryzae. In addition, we found that the MoGep4 inhibitor, AXD, displays broad-spectrum antifungal activity and is a promising candidate for fungicide development.

Polymer colloidal motors with photodynamic-regulated propulsion.

Artificial colloidal motors capable of converting various external energy into mechanical motion, have emerged as attractive photosensitizer (PS) nanocarriers with good deliverability for photodynamic therapy. However, photoactivated 3O2-to-1O2 transformation as the most crucial energy transfer of the photodynamic process itself is still challenging to convert into autonomous transport. Herein, we report on PS-loaded thiophane-containing semiconducting conjugated polymer (SCP)-based polymer colloidal motors with asymmetric geometry for photodynamic-regulated propulsion in the liquid. The asymmetrical presence of the SCP phases within the colloidal motors would lead to significant differences in the 3O2-to-1O2 transformation and 1O2 release manners between asymmetrical polymer phases, spontaneously creating asymmetrical osmotic pressure gradients across the nanoparticles for powering the self-propelled motion under photodynamic regulation. This photoactivated energy-converting behavior can be also combined with the photothermal conversion of the SCP phases to create two energy gradients exerting diffusiophoretic/thermophoretic force on the colloidal motors for achieving multimode synergistic propulsion. This unique motile feature endows the light-driven PS nanocarriers with good permeability against various physiological barriers in the tumor microenvironment for enhancing antitumor efficacy, showing great potential in phototherapy.

STimage-1K4M: A histopathology image-gene expression dataset for spatial transcriptomics.

Recent advances in multi-modal algorithms have driven and been driven by the increasing availability of large image-text datasets, leading to significant strides in various fields, including computational pathology. However, in most existing medical image-text datasets, the text typically provides high-level summaries that may not sufficiently describe sub-tile regions within a large pathology image. For example, an image might cover an extensive tissue area containing cancerous and healthy regions, but the accompanying text might only specify that this image is a cancer slide, lacking the nuanced details needed for in-depth analysis. In this study, we introduce STimage-1K4M, a novel dataset designed to bridge this gap by providing genomic features for sub-tile images. STimage-1K4M contains 1,149 images derived from spatial transcriptomics data, which captures gene expression information at the level of individual spatial spots within a pathology image. Specifically, each image in the dataset is broken down into smaller sub-image tiles, with each tile paired with 15,000 - 30,000 dimensional gene expressions. With 4,293,195 pairs of sub-tile images and gene expressions, STimage-1K4M offers unprecedented granularity, paving the way for a wide range of advanced research in multi-modal data analysis an innovative applications in computational pathology, and beyond.

A genome-wide association study of alloimmunization in the TOPMed OMG-SCD cohort identifies a locus on chromosome 12.

BACKGROUND: Red cell alloimmunization after exposure to donor red cells is a very common complication of transfusion for patients with sickle cell disease (SCD), resulting frequently in accelerated donor red blood cell destruction. Patients show substantial differences in their predisposition to alloimmunization, and genetic variability is one proposed component. Although several genetic association studies have been conducted for alloimmunization, the results have been inconsistent, and the genetic determinants of alloimmunization remain largely unknown. STUDY DESIGN AND METHODS: We performed a genome-wide association study (GWAS) in 236 African American (AA) SCD patients from the Outcome Modifying Genes in Sickle Cell Disease (OMG-SCD) cohort, which is part of Trans-Omics for Precision Medicine (TOPMed), with whole-genome sequencing data available. We also performed sensitivity analyses adjusting for different sets of covariates and applied different sample grouping strategies based on the number of alloantibodies patients developed. RESULTS: We identified one genome-wide significant locus on chr12 (p = 3.1e-9) with no evidence of genomic inflation (lambda = 1.003). Further leveraging QTL evidence from GTEx whole blood and/or Jackson Heart Study PBMC RNA-Seq data, we identified a number of potential genes, such as ARHGAP9, STAT6, and ATP23, that may be driving the association signal. We also discovered some suggestive loci using different analysis strategies. DISCUSSION: We call for the community to collect additional alloantibody information within SCD cohorts to further the understanding of the genetic basis of alloimmunization in order to improve transfusion outcomes.

ESF1 positively regulates MDM2 and promotes tumorigenesis.

Eighteen S rRNA factor 1 (ESF1) is a predominantly nucleolar protein essential for embryogenesis. Our previous studies have suggested that Esf1 is a negative regulator of the tumor suppressor protein p53. However, it remains unclear whether ESF1 contributes to tumorigenesis. In this current research, we find that increased ESF1 expression correlates with poor survival in multiple tumors including pancreatic cancer. ESF1 is able to regulate cell proliferation, migration, DNA damage-induced apoptosis, and tumorigenesis. Mechanistically, ESF1 physically interacts with MDM2 and is essential for maintaining the stability of MDM2 protein by inhibiting its ubiquitination. Additionally, ESF1 also prevented stress-induced stabilization of p53 in multiple cancer cells. Hence, our findings suggest that ESF1 is a potent regulator of the MDM2-p53 pathway and promotes tumor progression.

Hinesol attenuates DSS-induced ulcerative colitis through the suppression of Src-mediated NF-κB and chemokine signaling pathway.

As a common inflammatory bowel disease, ulcerative colitis (UC) is featured with inflammation, oxidative damage, and the impairment of intestinal mucosal barrier, which bring threat to patients' quality of live. Hinesol, derived from Atractylodes lancea, is a unique sesquiterpenoid. Our study proposed to survey the effects and mechanism of hinesol in UC. UC mouse model was constructed using dextran sulfate sodium (DSS). Lipopolysaccharide (LPS) was applied for RAW264.7 cells stimulation to construct cell inflammatory model. The changes of disease activity index (DAI), body weight, colon length, and intestinal pathology in mice were analyzed to estimate the severity of colitis. Enzyme-linked immunosorbent assay was applied to check the changes of interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor (TNF)-α. The levels of myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-px), catalase (CAT), and malondialdehyde (MDA) were estimated by corresponding reagent kit. The changes of phosphorylated (p)-NF-κB P65, and p-IκBα, ZO-1, Occludin, Claudin-1, Src, XCL1, CCL2, and CXCL16 protein were examined using western blot. Flow cytometry and cell counting kit-8 assay were utilized for assessment of cell apoptosis and viability. We found that DSS reduced mice body weight, increased DAI, shorten colon length, and led to severe enteric mucosal injury, while hinesol improved the above symptoms induced by DSS. In DSS mice, hinesol raised the levels of ZO-1, Occludin, Claudin-1, SOD, GSH-px, and CAT and decreased the levels of TNF-α, IL-18, IL-1ß, IL-6, MPO, and MDA. Additionally, in DSS mice and LPS-stimulated RAW264.7 cells, hinesol inhibited the high expression of Src, XCL1, CCL2, CXCL16, p-NF-κB P65, and p-IκBα. The molecular docking showed that there was a good interaction between hinesol and Src. Moreover, in LPS-stimulated RAW 264.7 cells, Src overexpression partially reversed the inhibition of hinesol on cell apoptosis, pro-inflammatory factors, and oxidative stress. In conclusion, hinesol alleviated DSS-induced colitis, which might have a bearing on the inhibition of Src-mediated NF-κB and chemokine signaling pathway.

Exploring the supplementary potential of all-trans retinoic acid with methotrexate in rheumatoid arthritis: modulation of synovial cell apoptosis and autophagy.

OBJECTIVES: The imbalance between apoptosis and proliferation in fibroblast-like synoviocytes (FLSs) plays a key role in the pathogenesis of rheumatoid arthritis (RA). This study aims to investigate the potential of all-trans retinoic acid (ATRA) as a supplementary therapeutic agent alongside methotrexate (MTX) for RA, by examining its ability to inhibit synovial cell proliferation and enhance apoptosis through the ROS-JNK signalling pathway. METHODS: The viability, apoptosis, and autophagy levels of human rheumatoid arthritis fibroblast-like synovial cells (HFLS-RA) were evaluated, while ROS generation was measured through the DCFH-DA fluorescence microplate assay. Western blotting was used to analyse the expression levels of JNK signalling pathway-related proteins. To assess therapeutic potential in vivo, a collagen-induced arthritis (CIA) model was established in Wistar rats. RESULTS: Small doses of MTX did not significantly affect the viability of HFLS-RAs or induce apoptosis. However, when ATRA was added to the treatment, the therapy markedly inhibited cell proliferation and induced apoptosis and excessive autophagy. Mechanistically, ATRA activated the ROS/JNK signalling pathway in HFLS-RAs. ROS scavengers and JNK inhibitors significantly attenuated ATRA-induced apoptosis and autophagy. In vivo, the combination therapy demonstrated a remarkable enhancement of the anti-arthritic efficacy in CIA rats. CONCLUSIONS: The ability of ATRA to inhibit proliferation in RA FLSs through autophagy and apoptosis underscores its potential as a supplementary therapeutic agent alongside MTX for RA, particularly when compared to the limited impact of MTX on these processes. This combined strategy holds promise for enhancing therapeutic outcomes and warrants further investigation in the management of RA.

Development and validation of machine learning models to predict MDRO colonization or infection on ICU admission by using electronic health record data.

BACKGROUND: Multidrug-resistant organisms (MDRO) pose a significant threat to public health. Intensive Care Units (ICU), characterized by the extensive use of antimicrobial agents and a high prevalence of bacterial resistance, are hotspots for MDRO proliferation. Timely identification of patients at high risk for MDRO can aid in curbing transmission, enhancing patient outcomes, and maintaining the cleanliness of the ICU environment. This study focused on developing a machine learning (ML) model to identify patients at risk of MDRO during the initial phase of their ICU stay. METHODS: Utilizing patient data from the First Medical Center of the People's Liberation Army General Hospital (PLAGH-ICU) and the Medical Information Mart for Intensive Care (MIMIC-IV), the study analyzed variables within 24 h of ICU admission. Machine learning algorithms were applied to these datasets, emphasizing the early detection of MDRO colonization or infection. Model efficacy was evaluated by the area under the receiver operating characteristics curve (AUROC), alongside internal and external validation sets. RESULTS: The study evaluated 3,536 patients in PLAGH-ICU and 34,923 in MIMIC-IV, revealing MDRO prevalence of 11.96% and 8.81%, respectively. Significant differences in ICU and hospital stays, along with mortality rates, were observed between MDRO positive and negative patients. In the temporal validation, the PLAGH-ICU model achieved an AUROC of 0.786 [0.748, 0.825], while the MIMIC-IV model reached 0.744 [0.723, 0.766]. External validation demonstrated reduced model performance across different datasets. Key predictors included biochemical markers and the duration of pre-ICU hospital stay. CONCLUSIONS: The ML models developed in this study demonstrated their capability in early identification of MDRO risks in ICU patients. Continuous refinement and validation in varied clinical contexts remain essential for future applications.

Design, synthesis and structure-activity relationships of novel non-ketolides: 9-Oxime clarithromycin featured with seven-to thirteen-atom-length diamine linkers at 3-OH.

We report here on the structure-activity relationships of hybrids combining 3-descladinosyl clarithromycin with quinolones linked by extended diamine connectors. Several hybrids, exemplified by 23Bc, 23Be, 23Bf, 26Be, and 30Bc, not only restored potency against inducibly resistant pathogens but also exhibited significantly enhanced activities against constitutively resistant strains of Staphylococcus pneumoniae and Staphylococcus pyogenes, which express high-level resistance independent of clarithromycin or erythromycin induction. Additionally, the novel hybrids showed susceptibility against Gram-negative Haemophilus influenzae. Notably, hybrid 23Be demonstrated dual modes of action by inhibiting both protein synthesis and DNA replication in vitro and in vivo. Given these promising characteristics, 23Be emerges as a potential candidate for the treatment of community-acquired bacterial pneumonia.

Thrombocytopenia and hyperprogression after radiotherapy and camrelizumab treatment in an esophageal cancer patient with increased JAK2 gene copies: a case report.

Radiotherapy (RT) and immune checkpoint inhibitor (ICI) are important treatments for esophageal cancer. Some studies have confirmed the safety and effectiveness of using RT in combination with ICI, while serious side effects have been exhibited by some patients. We report a patient with metastatic esophageal cancer who received RT combined with ICI. The patient experienced severe thrombocytopenia, and treatment with thrombopoietin and corticosteroids were ineffective. Finally, the patient developed abscopal hyperprogression outside the radiation field. Interestingly, next-generation sequencing revealed increased JAK2 gene copies in the surgical slices. The JAK2/STAT3 pathway is involved in the regulation of megakaryocyte development. Recurrent thrombocytopenia may activate the JAK2/STAT3 pathway, leading to megakaryocyte differentiation and platelet biogenesis. However, persistent activation of the JAK2/STAT3 pathway has been associated with immune ICI resistance and tumor progression. This case indicates that thrombocytopenia and increased JAK2 gene copies may be risk factors for poor prognosis after ICI and RT treatment.

Mechanism of Brevibacillus brevis strain TR-4 against leaf disease of Photinia×fraseri Dress.

Background: Colletotrichum species are among the most common pathogens in agriculture and forestry, and their control is urgently needed. Methods: In this study, a total of 68 strains of biocontrol bacteria were isolated and identified from Photinia × fraseri rhizosphere soil. Results: The isolates were identified as Brevibacillus brevis by 16S rRNA. The inhibitory effect of TR-4 on Colletotrichum was confirmed by an in vitro antagonistic experiment. The inhibitory effect of TR-4 was 98% at a concentration of 10 µl/ml bacterial solution, protection of the plant and inhibition of C. siamense was evident. Moreover, the secretion of cellulase and chitosan enzymes in the TR-4 fermentation liquid cultured for three days was 9.07 mol/L and 2.15 µl/mol, respectively. Scanning electron microscopy and transmission electron microscopy confirmed that TR-4 destroyed the cell wall of C. siamense, resulting in leakage of the cell contents, thus weakening the pathogenicity of the bacteria.

Sarcopenia and metabolic dysfunction associated steatotic liver disease: Time to address both.

Sarcopenia and metabolic dysfunction associated steatotic liver disease (MASLD) are closely intertwined. Sarcopenia, traditionally a disease of the older adult and chronic disease population, has been closely studied as one of the pathophysiologic conditions at play in the development of MASLD. They share similar risk factors of insulin resistance and physical inactivity. Given similar pathophysiology along the liver-muscle axis, sarcopenia has been studied as a risk factor for MASLD, and vice versa. Current research suggests a bidirectional relationship. Given the chronicity of MASLD as a chronic inflammatory liver disease, it can break down muscle mass and lead to sarcopenia, while sarcopenia promotes intramuscular lipid accumulation that releases cytokines that can aggravate inflammation in the liver. However, for the longest time, a lack of consensus definition for MASLD and sarcopenia made it difficult to study their relationship and outcomes. A recent nomenclature update to diagnosing MASLD has made it easier for researchers to identify cohorts for study. However, no gold standard technique to measure muscle mass or consensus sarcopenia definition has been identified yet. Future studies are needed to reach a consensus and reduce diagnostic variation. With similar pathophysiology and shared risk factors between the two diseases, future research may also identify potential therapeutic targets along the liver-muscle axis that would benefit both sarcopenia and MASLD in order to maximize their outcomes.

Enhancement of Pulmonary Function and Reduction of Complications Through EIT-Guided Yoga Breathing Exercise After Esophagectomy.

BACKGROUND This study aimed to investigate the impact of EIT-guided yoga breathing training on postoperative pulmonary complications (PPCs) for esophageal cancer patients. MATERIAL AND METHODS Total of 62 patients underwent radical resections of esophageal cancer. Esophageal cancer patients were randomized to the standard care group, or the intervention group receiving an additional complete breathing exercise under the guidance of EIT in AICU. Following extubation after the esophagectomy, pulmonary functions were evaluated by EIT with center of ventilation (CoV), dependent silent spaces (DSS), and non-dependent silent spaces (NSS). RESULTS Sixty-one older esophageal cancer patients (31 in the Control group and 30 in the EIT group) were included in the final analysis. Forty-four patients experienced pulmonary complications after esophagectomy, 27 (87.1%) in the Control group and 17 (36.7%) in the EIT group (RR, 0.42 (95% CI: 0.26, 0.69). The most common pulmonary complication was pleural effusion, with an incidence of 30% in the EIT group and 74.2% in the Control group, with RR of 0.40 (95% CI: 0.23, 0.73). Time for the first pulmonary complication was significantly longer in the EIT group than in the Control group (hazard ratio, HR, 0.43; 95% CI 0.21 to 0.87; P=0.019). Patients in the EIT group had significantly higher scores in CoV, DSS, and NSS than in the Control group. CONCLUSIONS Guided by EIT, the addition of the postoperative breathing exercise to the standardized care during AICU could further improve pulmonary function, and reduce postoperative pulmonary complications after esophagectomy.

The underlying mechanisms of oxytetracycline degradation mediated by gut microbial proteins and metabolites in Hermetia illucens.

Hermetia illucens larvae can enhance the degradation of oxytetracycline (OTC) through its biotransformation. However, the underlying mechanisms mediated by gut metabolites and proteins are unclear. To gain further insights, the kinetics of OTC degradation, the functional structures of gut bacterial communities, proteins, and metabolites were investigated. An availability-adjusted first-order model effectively evaluated OTC degradation kinetics, with degradation half-lives of 4.18 and 21.71 days for OTC degradation with and without larval biotransformation, respectively. Dominant bacteria in the larval guts were Enterococcus, Psychrobacter, Providencia, Myroides, Enterobacteriaceae, and Lactobacillales. OTC exposure led to significant differential expression of proteins, with functional classification revealing involvement in digestion, transformation, and adaptability to environmental stress. Upregulated proteins, such as aromatic ring hydroxylase, acted as oxidoreductases modifying the chemical structure of OTC. Unique metabolites, aclarubicin and sancycline identified were possible OTC metabolic intermediates. Correlation analysis revealed significant interdependence between gut bacteria, metabolites, and proteins. These findings reveal a synergistic mechanism involving gut microbial metabolism and enzyme structure that drives the rapid degradation of OTC and facilitates the engineering applications of bioremediation.

The different roles of homocysteine metabolism in hypertension among normal-weight and obese patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with hypertension. However, the differential mechanisms underlying OSA-related hypertension between normal-weight vs. obese patients is limited. METHODS: We studied 92 patients with OSA and 24 patients with continuous positive airway pressure (CPAP) treatment. Blood pressure (BP) was measured twice during awake and continuously monitored during sleep. Obesity was defined as body mass index ≥28 kg/m2. Serum metabolite levels were assessed by metabolomics. RESULTS: Among 59 normal-weight and 33 obese patients, 651 and 167 metabolites showed differences between hypertension and normotension or were associated with systolic and diastolic BP (SBP, DBP) after controlling confounders. These metabolites involved 16 and 12 Kyoto Encyclopedia of Genes and Genomes enrichment pathways in normal-weight and obese patients respectively, whereas 6 pathways overlapped. Among these 6 overlapping pathways, 4 were related to homocysteine metabolism and 2 were non-specific pathways. In homocysteine metabolism pathway, 13 metabolites were identified. Interestingly, the change trends of 7 metabolites associated with SBP (all interaction-p≤0.083) and 8 metabolites associated with DBP (all interaction-p≤0.033) were opposite between normal-weight and obese patients. Specifically, increased BP was associated with down-regulated folate-dependent remethylation and accelerated transsulfuration in normal-weight patients, whereas associated with enhanced betaine-dependent remethylation and reduced transsulfuration in obese patients. Similar findings were observed in ambulatory BP during sleep. After CPAP treatment, baseline low homocysteine levels predicted greater decrease in DBP among normal-weight but not obese patients. CONCLUSIONS: Mechanisms in OSA-related hypertension differ between normal-weight and obese patients, which are explained by different changes in homocysteine metabolism.

A comprehensive workflow for optimizing RNA-seq data analysis.

BACKGROUND: Current RNA-seq analysis software for RNA-seq data tends to use similar parameters across different species without considering species-specific differences. However, the suitability and accuracy of these tools may vary when analyzing data from different species, such as humans, animals, plants, fungi, and bacteria. For most laboratory researchers lacking a background in information science, determining how to construct an analysis workflow that meets their specific needs from the array of complex analytical tools available poses a significant challenge. RESULTS: By utilizing RNA-seq data from plants, animals, and fungi, it was observed that different analytical tools demonstrate some variations in performance when applied to different species. A comprehensive experiment was conducted specifically for analyzing plant pathogenic fungal data, focusing on differential gene analysis as the ultimate goal. In this study, 288 pipelines using different tools were applied to analyze five fungal RNA-seq datasets, and the performance of their results was evaluated based on simulation. This led to the establishment of a relatively universal and superior fungal RNA-seq analysis pipeline that can serve as a reference, and certain standards for selecting analysis tools were derived for reference. Additionally, we compared various tools for alternative splicing analysis. The results based on simulated data indicated that rMATS remained the optimal choice, although consideration could be given to supplementing with tools such as SpliceWiz. CONCLUSION: The experimental results demonstrate that, in comparison to the default software parameter configurations, the analysis combination results after tuning can provide more accurate biological insights. It is beneficial to carefully select suitable analysis software based on the data, rather than indiscriminately choosing tools, in order to achieve high-quality analysis results more efficiently.

Inhibiting the activation of enteric glial cells alleviates intestinal inflammation and comorbid anxiety- and depressive-like behaviors in the ulcerative colitis mice.

Ulcerative colitis (UC) is a common inflammatory bowel disease with a complex origin in clinical settings. It is frequently accompanied by negative emotional responses, including anxiety and depression. Enteric glial cells (EGCs) are important components of the gut-brain axis and are involved in the development of the enteric nervous system (ENS), intestinal neuroimmune, and regulation of intestinal motor functions. Since there is limited research encompassing the regulatory function of EGCs in anxiety- and depression-like behaviors induced by UC, this study aims to reveal their regulatory role in such behaviors and associated intestinal inflammation. This study applied morphological, molecular biological, and behavioral methods to observe the morphological and functional changes of EGCs in UC mice. The results indicated a significant activation of EGCs in the ENS of dextran sodium sulfate -induced UC mice. This activation was evidenced by morphological alterations, such as elongation or terminal swelling of processes. Besides EGCs activation, UC mice exhibited significantly elevated expression levels of pro-inflammatory cytokines in the peripheral blood, accompanied by anxiety- and depression-like behaviors. The inhibition of EGCs activity within the ENS can ameliorate the anxiety- and depression-like behaviors caused by UC. Our data suggest that UC and its resulting behaviors may be related to the activation of EGCs within the ENS. Moreover, the modulation of intestinal inflammation through inhibition of EGCs activation emerges as a promising clinical approach for alleviating UC-induced anxiety- and depression-like behaviors.