Immunogenicity and tolerance induction in vascularized composite allotransplantation.

Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissues such as skin, muscle, bone, nerve, and vessels, as a functional unit (i.e., hand or face) to patients suffering from major tissue trauma and functional deficits. Though the surgical feasibility has been optimized, issues regarding graft rejection remains. VCA rejection involves a diverse population of cells but is primarily driven by both donor and recipient lymphocytes, antigen-presenting cells, macrophages, and other immune as well as donor-derived cells. In addition, it is commonly understood that different tissues within VCA, such as the skin, elicits a stronger rejection response. Currently, VCA recipients are required to follow potent and lifelong immunosuppressing regimens to maximize graft survival. This puts patients at risk for malignancies, opportunistic infections, and cancers, thereby posing a need for less perilous methods of inducing graft tolerance. This review will provide an overview of cell populations and mechanisms, specific tissue involved in VCA rejection, as well as an updated scope of current methods of tolerance induction.

[Species of Chinese materia medica resources based on the fourth national survey of Chinese materia medica resources].

This article outlined the composition and species characteristics of Chinese materia medica(CMM) resources identified in the fourth national survey of CMM resources. The survey was conducted based on field investigations and office collation, adhering to the "four principles", which emphasized the existence of survey records, voucher specimens, actual photographs, and evidence of medicinal use, so as to summarize the species of CMM resources and ensure the scientific integrity and accuracy of the results. According to the results, China had a total of 18 817 CMM resources, including 15 321 medicinal plants, 826 medicinal fungi, 2 517 medicinal animals, and 153 medicinal minerals. Additionally, the fourth national survey of CMM resources also conducted specialized investigations on 3 151 species of unique medicinal plants, 464 species of rare and endangered medicinal plants, and 196 new species in China. These latest statistics on these CMM resources will provide the most up-to-date foundational data for the protection, management, development, and utilization of these resources over an extended period, offering scientific guidance for the development of the traditional Chinese medicine(TCM) industry.

Dynamic Compressive Stress Relaxation Model of Tomato Fruit Based on Long Short-Term Memory Model.

Tomatoes are prone to mechanical damage due to improper gripping forces during automated harvest and postharvest processes. To reduce this damage, a dynamic viscoelastic model based on long short-term memory (LSTM) is proposed to fit the dynamic compression stress relaxation characteristics of the individual fruit. Furthermore, the classical stress relaxation models involved, the triple-element Maxwell and Caputo fractional derivative models, are compared with the LSTM model to validate its performance. Meanwhile, the LSTM and classical stress relaxation models are used to predict the stress relaxation characteristics of tomato fruit with different fruit sizes and compression positions. The results for the whole test dataset show that the LSTM model achieves a RMSE of 2.829×10-5 Mpa and a MAPE of 0.228%. It significantly outperforms the Caputo fractional derivative model by demonstrating a substantial enhancement with a 37% decrease in RMSE and a 36% reduction in MAPE. Further analysis of individual tomato fruit reveals the LSTM model's performance, with the minimum RMSE recorded at the septum position being 3.438×10-5 Mpa, 31% higher than the maximum RMSE at the locule position. Similarly, the lowest MAPE at the septum stands at 0.375%, outperforming the highest MAPE at the locule position by a significant margin of 90%. Moreover, the LSTM model consistently reports the smallest discrepancies between the predicted and observed values compared to classical stress relaxation models. This accuracy suggests that the LSTM model could effectively supplant classical stress relaxation models for predicting stress relaxation changes in individual tomato fruit.

Structural characterisation and anti-colon cancer activity of an arabinogalactan RSA-1 from Raphani semen.

RSA-1 is a polysaccharide obtained from Raphani semen with a relatively clear structure and anti-colon cancer activity. In this study, high-performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) spectroscopy were applied to characterise the complex chain structure of RSA-1. Subsequently, the inhibitory effect on colon cancer growth through apoptosis induction in colon cancer cells was explored. The findings indicate that the main chain of RSA-1 consists of →3)-ß-D-Galp-(1 â†’ and 3,6)-ß-D-Galp-(1 â†’ substituted at C-6 with branched α-L-Araf side chains. RSA-1 disrupts the Bax/Bcl-2 ratio and thus inhibits the viability of colon cancer cells in vitro. Furthermore, it inhibits colon cancer migration by attenuating epithelial-mesenchymal transition. Notably, RSA-1 exhibited negligible impact on the growth of human intestinal epithelial cells within a relevant concentration range. This study establishes a theoretical foundation and provides technical support for the prospective development and application of RSA-1 as a dual-purpose anti-colon cancer drug and functional food.

Genetically determined dietary habits and risk of Alzheimer's disease: a Mendelian randomization study.

Background: Emerging evidence have suggested that dietary habits have potential implication on the development of Alzheimer's disease (AD). However, elucidating the causal relationship between specific dietary factors and AD risk remains a challenge. Therefore, our study endeavors to investigate the causal association between dietary habits and the risk of AD. Materials and methods: We analyzed data on 231 dietary habits sourced from the UK Biobank and MRC-IEU, and AD data obtained from the FinnGen database. Employing a framework based on the classic two-sample Mendelian randomization (MR) study, we utilized the inverse-variance weighted (IVW) method as the primary analysis. Additionally, we conducted Steiger filtering and other methods to mitigate horizontal pleiotropy. The robustness of our overall findings was confirmed through multiple sensitivity analysis methods, and forward MR and reverse MR to address potential reverse causality bias. Results: Our study evaluated the causal effect between 231 dietary habits involving over 500,000 participants of European ancestry, and 10,520 AD cases. Only oily fish intake demonstrated a significant protective causal relationship with AD following FDR correction (raw p-value = 1.28e-4, FDR p-value = 0.011, OR = 0.60, 95%CI: 0.47-0.78). Additionally, six dietary habits potentially influenced AD risk, with protective causal effects observed for average monthly intake of other alcoholic drinks (raw p-value = 0.024, FDR p-value = 0.574, OR = 0.57, 95%CI: 0.35-0.93) and tea intake (raw p-value = 0.047, FDR p-value = 0.581, OR = 0.78, 95%CI: 0.603-1.00). Conversely, detrimental causal effects were observed for the average weekly champagne plus white wine intake (raw p-value = 0.006, FDR p-value = 0.243, OR = 2.96, 95%CI: 1.37-6.38), Danish pastry intake (raw p-value = 0.036, FDR p-value = 0.574, OR = 13.33, 95%CI: 1.19-149.69), and doughnut intake (raw p-value = 0.039, FDR p-value = 0.574, OR = 7.41, 95%CI: 1.11-49.57). Moreover, the protective effect of goat's cheese intake phenotype exhibited statistical significance only in the IVW method (raw p-value<0.05). Conclusion: Our results provide genetic support for a protective causal effect of oily fish intake on AD risk. Additionally, average monthly intake of other alcoholic drinks and tea consumption were also related with a lower risk of AD. Conversely, average weekly champagne plus white wine intake, Danish pastry intake, and doughnut intake were causally associated with increased risk of AD.

Crosstalk among Oxidative Stress, Autophagy, and Apoptosis in the Protective Effects of Ginsenoside Rb1 on Brain Microvascular Endothelial Cells: A Mixed Computational and Experimental Study.

OBJECTIVE: Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1), a component derived from medicinal plants, is known for its pharmacological benefits in IS, but its protective effects on BMECs have yet to be explored. This study aimed to investigate the potential protective effects of GRb1 on BMECs. METHODS: An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools, including gene set enrichment analysis (GSEA), Gene Ontology (GO) classification and enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction network analysis, and molecular docking. Experimental validation was also performed to ensure the reliability of our findings. RESULTS: Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically, GRb1 was found to modulate the interplay between oxidative stress, apoptosis, and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62), autophagy related 5 (ATG5), and hypoxia-inducible factor 1-alpha (HIF-1α) were identified, highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage. CONCLUSION: GRbl protects BMECs against OGD/R injury by influencing oxidative stress, apoptosis, and autophagy. The identification of SQSTM1/p62, ATG5, and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS, providing a foundation for future research into its mechanisms and applications in IS treatment.

Superhydrophobic stereocomplex-type polylactide/ultra-fine glass fibers aerogel for passive daytime radiative cooling.

Passive daytime radiative cooling (PDRC) technology offers a green and sustainable strategy for cooling, eliminating the need for external energy sources through its exceptional efficiency in heat radiation and sunlight reflection. Despite its benefits, the widespread usage of non-biodegradable PDRC materials has unfortunately caused environmental pollution and resource wastage. Furthermore, the effectiveness of outdoor PDRC materials can be significantly diminished by rainfall. In this work, a superhydrophobic composite aerogel composed of stereocomplex-type polylactide and ultra-fine glass fiber has been successfully developed through simple physical blending and freeze-drying, which exhibits low thermal conductivity (36.26 mW m-1 K-1) and superhydrophobicity (water contact angle up to 150°). Additionally, its high solar reflectance (91.68 %) and strong infrared emissivity (93.95 %) enable it to effectively lower surface temperatures during daytime, resulting in a cooling effect of approximately 3.8 °C below the ambient temperature during the midday heat of summer, with a cooling power of 68 W/m2. This aerogel offers an environmentally friendly and sustainable approach for the utilization of radiative refrigeration materials, paving the way for environmental protection and sustainable development.

Nanoplastic pollution changes the intestinal microbiome but not the morphology or behavior of a freshwater turtle.

Humans produce 350 million metric tons of plastic waste per year, leading to microplastic pollution and widespread environmental contamination, particularly in aquatic environments. This subsequently impacts aquatic organisms in myriad ways, yet the vast majority of research is conducted in marine, rather than freshwater systems. In this study, we exposed eggs and hatchlings of the Chinese soft-shelled turtle (Pelodiscus sinensis) to 80-nm polystyrene nanoplastics (PS-NPs) and monitored the impacts on development, behavior and the gut microbiome. We demonstrate that 80-nm PS-NPs can penetrate the eggshell and move into developing embryos. This led to metabolic impairments, as evidenced by bradycardia (a decreased heart rate), which persisted until hatching. We found no evidence that nanoplastic exposure affected hatchling morphology, growth rates, or levels of boldness and exploration, yet we discuss some potential caveats here. Exposure to nanoplastics reduced the diversity and homogeneity of gut microbiota in P. sinensis, with the level of disruption correlating to the length of environmental exposure (during incubation only or post-hatching also). Thirteen core genera (with an initial abundance >1 %) shifted after nanoplastic treatment: pathogenic bacteria increased, beneficial probiotic bacteria decreased, and there was an increase in the proportion of negative correlations between bacterial genera. These changes could have profound impacts on the viability of turtles throughout their lives. Our study highlights the toxicity of environmental NPs to the embryonic development and survival of freshwater turtles. We provide insights about population trends of P. sinensis in the wild, and future directions for research.

A Novel "Microscrew With Tie-Down Sutures" Technique for FGG Anchorage: A Case Report.

The most challenging and time-consuming step in the free gingival graft (FGG) for keratinized mucosa augmentation is the compression suture anchoring the FGG to the periosteum. This article proposed a novel "microscrew with tie-down sutures" technique to anchor the FGG to the recipient site without the traditional trans-periosteum suture. This patient's keratinized mucosa width (KMW) around the healing abutments of teeth #29 and #30 was less than 1 mm. After an apically positioned flap (AFP) was prepared, 2 microscrews were placed at the buccal plate of the alveolar ridge bone, which is the coronal margin of the AFP. Then, the sutures winded between the microscrews and the healing abutments to anchor the FGG. In conclusion, the "microscrew with tie-down sutures" technique offers a feasible and straightforward alternative for the trans-periosteum compression suture, mainly when the periosteum is fragile, thin, or injured.

Method for analyzing urban waterlogging mechanisms based on a 1D-2D water environment dynamic bidirectional coupling model.

Urban waterlogging is a significant global issue. To achieve precisely control urban waterlogging and enhance our understanding of its causes, a novel study method was introduced. This method is based on a dynamic bidirectional coupling model that combines 1D-2D hydrodynamic and water quality simulations. The waterlogging phenomenon in densely populated metropolitan areas of Changzhi city, China, was studied. This study focused on investigating the process involved in waterlogging formation, particularly overflow at nodes induced by the design of the topological structure of the pipe network, constraints on the capacity of the underground drainage system, and the surface runoff accumulation. The complex interplay among these elements and their possible influences on waterlogging formation were clarified. The results indicated notable spatial and temporal variation in the waterlogging formation process in densely populated urban areas. Node overflow in the drainage system emerged as the key influencing factor in the waterlogging formation process, accounting for up to 71% of the total water accumulation at the peak time. The peak lag time of waterlogging during events with short return periods was primarily determined by the rainfall peak moment. In contrast, the peak time of waterlogging during events with long return periods was influenced by the rainfall peak moment, drainage capacity and topological structure of the pipe network. Notably, the access of inflow from both upstream and downstream segments of the pipe network drainage system significantly impacted the peak time of waterlogging, with upstream water potentially delaying the peak time substantially. This study not only provides new insights into urban waterlogging mechanisms but also provides practical guidance for optimizing urban drainage systems, urban planning, and disaster risk management.

H2S-Powered Nanomotors for Active Therapy of Tumors by Inducing Ferroptosis and Lactate-Pyruvate Axis Disorders.

Disruption of the symbiosis of extra/intratumoral metabolism is a good strategy for treating tumors that shuttle resources from the tumor microenvironment. Here, we report a precision treatment strategy for enhancing pyruvic acid and intratumoral acidosis to destroy tumoral metabolic symbiosis to eliminate tumors; this approach is based on PEGylated gold and lactate oxidase-modified aminated dendritic mesoporous silica with lonidamine and ferrous sulfide loading (PEG-Au@DMSNs/FeS/LND@LOX). In the tumor microenvironment, LOX oxidizes lactic acid to produce pyruvate, which represses tumor cell proliferation by inhibiting histone gene expression and induces ferroptosis by partial histone monoubiquitination. In acidic tumor conditions, the nanoparticles release H2S gas and Fe2+ ions, which can inhibit catalase activity to promote the Fenton reaction of Fe2+, resulting in massive ·OH production and ferroptosis via Fe3+. More interestingly, the combination of H2S and LND (a monocarboxylic acid transporter inhibitor) can cause intracellular acidosis by lactate, and protons overaccumulate in cells. Multiple intracellular acidosis is caused by lactate-pyruvate axis disorders. Moreover, H2S provides motive power to intensify the shuttling of nanoparticles in the tumor region. The findings confirm that this nanomedicine system can enable precise antitumor effects by disrupting extra/intratumoral metabolic symbiosis and inducing ferroptosis and represents a promising active drug delivery system candidate for tumor treatment.

An innovative prognostic auxiliary for colon adenocarcinoma based on zinc finger protein genes.

Background: The carcinogenesis and progression of colon adenocarcinoma (COAD) are intensively related to the abnormal expression of the zinc finger (ZNF) protein genes. We aimed to employ these genes to provide a reliable prognosis and treatment stratification tool for COAD patients. Methods: Cox and the least absolute shrinkage and selection operator (LASSO) regression analysis were applied, utilizing The Cancer Genome Atlas (TCGA) metadata, to build a ZNF protein gene-based prognostic model. Using this model, patients in the training cohort and testing cohort (GSE17537) were labelled as either high or low risk. Kaplan-Meier (KM) survival analysis and time-dependent receiver operating characteristic (ROC) curve analysis were performed in the patients with opposite risk status to assess the predictive ability in each cohort. The potentiality of the mechanism was explored by the estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE), single-sample gene set enrichment analysis (ssGSEA), gene set enrichment analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, the degrees of expression of model genes were validated by immunohistochemistry (IHC). Results: The prognostic model consisting of INSM1, PHF21B, RNF138, SYTL4, WRNIP1, ZNF585B, and ZNF514, classified patients into opposite risk statuses. Patients in the high-risk subset had a considerably lower chance of surviving compared to those in the low-risk subset. There is a high probability that these model genes were attached to immune-related biological processes, which can be confirmed by the results of the above mechanistic methods. Moreover, patients in the low-risk subset also significantly outperformed the patients in the high-risk subset when calculating immune cells and function scores. Drug sensitivity and tumor immune dysfunction and exclusion (TIDE) analyses showed a clear difference in the immunological and chemotherapeutic efficacy predictions within the two risk groups. Additionally, the degrees of expression of model genes in high-risk and low-risk subsets presented great discrepancies. Conclusions: The signature may be applied as a predictive classifier to shepherd special medication for COAD patients.

Astrocytes in preoptic area regulate acute nociception-induced hypothermia through adenosine receptors.

AIMS: The preoptic area (POA) of the hypothalamus, crucial in thermoregulation, has long been implicated in the pain process. However, whether nociceptive stimulation affects body temperature and its mechanism remains poorly studied. METHODS: We used capsaicin, formalin, and surgery to induce acute nociceptive stimulation and monitored rectal temperature. Optical fiber recording, chemical genetics, confocal imaging, and pharmacology assays were employed to confirm the role and interaction of POA astrocytes and extracellular adenosine. Immunofluorescence was utilized for further validation. RESULTS: Acute nociception could activate POA astrocytes and induce a decrease in body temperature. Manipulation of astrocytes allowed bidirectional control of body temperature. Furthermore, acute nociception and astrocyte activation led to increased extracellular adenosine concentration within the POA. Activation of adenosine A1 or A2A receptors contributed to decreased body temperature, while inhibition of these receptors mitigated the thermo-lowering effect of astrocytes. CONCLUSION: Our results elucidate the interplay between acute nociception and thermoregulation, specifically highlighting POA astrocyte activation. This enriches our understanding of physiological responses to painful stimuli and contributes to the analysis of the anatomical basis involved in the process.

An In-Situ-Tag-Generation Proximity Labeling Technology for Recording Cellular Interactions.

Obtaining information about cellular interactions is fundamental to the elucidation of physiological and pathological processes. Proximity labeling technologies have been widely used to report cellular interactions in situ; however, the reliance on addition of tag molecules typically restricts their application to regions where tags can readily diffuse, while the application in, for example, solid tissues, is susceptible. Here, we propose an "in-situ-tag-generation mechanism" and develop the GalTag technology based on galactose oxidase (GAO) for recording cellular interactions within three-dimensional biological solid regions. GAO mounted on bait cells can in situ generate bio-orthogonal aldehyde tags as interaction reporters on prey cells. Using GalTag, we monitored the dynamics of cellular interactions and assessed the targeting ability of engineered cells. In particular, we recorded, for the first time, the footprints of Bacillus Calmette-Guérin (BCG) invasion into the bladder tissue of living mice, providing a valuable perspective to elucidate the anti-tumor mechanism of BCG.

Phylogeny of genera in Maleae (Rosaceae) based on chloroplast genome analysis.

In Rosaceae, the replacement of the traditional four-subfamily division (Amygdaloideae or Prunoideae, Maloideae, Rosoideae, and Spiraeoideae) by the three-subfamily division (Dryadoideae, Rosoideae, and Amygdaloideae), the circumscription, systematic position, and phylogeny of genera in Maleae need to be reconsidered. The study aimed to circumscribe Maleae, pinpoint its systematic position, and evaluate the status of all generally accepted genera in the tribe using complete chloroplast genome data. Results indicated that Maleae consisted of pome-bearing genera that belonged to Maloideae as well as four genera (Gillenia, Kageneckia, Lindleya, and Vauquelinia) that were formerly considered to be outside Maloideae. The tribe could be subdivided into four subtribes: Gilleniinae (Gillenia), Lindleyinae (Kageneckia and Lindleya), Vaugueliniinae (Vauquelinia), and Malinae (all other genera; the core Maleae). Among the 36 recognized genera, Aria, Docyniopsis, Chamaemespilus, and Mespilus were not considered distinct and more research is needed to determine the taxonomic status of Rhaphiolepis from Eriobotrya. Within the core Maleae, five groups were revealed, whereas Sorbus L. was split as its members belonged to different groups.

[Comparative analysis of plastomes of Rubus chingii and R. chingii var. suavissimus].

Rubus chingii and R. chingii var. suavissimus are unique dual-purpose plant resources, with significant nutraceutical, pharmaceutical, and economic value, as well as promising prospects for further development. To investigate the genetic structure and evolutionary characteristics of these two varieties, this study conducted plastome sequencing using the Illumina HiSeq XTen sequencing platform. Subsequently, the study performed assembly, annotation, and characterization of the genomes, followed by a comparative plastome and phylogenetic analysis using bioinformatics techniques. The results revealed that the plastomes of R. chingii and R. chingii var. suavissimus exhibited a tetrad structure, comprising a large single-copy region(LSC), a small single-copy region(SSC), and two inverted repeat regions(IRs). The study identified a total of 56 simple sequence repeats(SSRs) after comparative analysis, predominantly consisting of A and T. Furthermore, the structure of the IR boundary genes in both varieties was found to be highly conserved, with only minor nucleotide variations. Additionally, the study identified three highly variable regions: rps16-trnQ-psbK, trnR-atpA, and trnT-trnL, which held promise as potential identification marks for further development and utilization. Phylogenetic analysis results obtained by the maximum likelihood and Bayesian inference methods demonstrated a close clustering of R. chingii and R. chingii var. suavissimus(100% support), with their closest relatives being R. trianthus. This study, focusing on plastome-level genetic distinctions between these two varieties, lays a foundation for future species protection, development, and utilization.

SIRT2 promotes base excision repair by transcriptionally activating OGG1 in an ATM/ATR-dependent manner.

Sirtuin 2 (SIRT2) regulates the maintenance of genome integrity by targeting pathways of DNA damage response and homologous recombination repair. However, whether and how SIRT2 promotes base excision repair (BER) remain to be determined. Here, we found that independent of its catalytic activity SIRT2 interacted with the critical glycosylase OGG1 to promote OGG1 recruitment to its own promoter upon oxidative stress, thereby enhancing OGG1 promoter activity and increasing BER efficiency. Further studies revealed that SIRT2 was phosphorylated on S46 and S53 by ATM/ATR upon oxidative stress, and SIRT2 phosphorylation enhanced the SIRT2-OGG1 interaction and mediated the stimulatory effect of SIRT2 on OGG1 promoter activity. We also characterized 37 cancer-derived SIRT2 mutants and found that 5 exhibited the loss of the stimulatory effects on OGG1 transcription. Together, our data reveal that SIRT2 acts as a tumor suppressor by promoting OGG1 transcription and increasing BER efficiency in an ATM/ATR-dependent manner.

Specific deletion of Mettl3 in IECs triggers the development of spontaneous colitis and dysbiosis of T lymphocytes in mice.

The enzymatic core component of m6A writer complex, Mettl3, plays a crucial role in facilitating the development and progress of gastric and colorectal cancer (CRC). However, its underlying mechanism in regulating intestinal inflammation remains unclear and poorly investigated. First, the characteristics of Mettl3 expression in inflammatory bowel diseases (IBD) patients were examined. Afterward, we generated the mice line with intestinal epithelial cells (IECs)-specific deletion of Mettl3 verified by various experiments. We continuously recorded and compared the physiological status including survival rate etc. between the two groups. Subsequently, we took advantage of staining assays to analyze mucosal damage and immune infiltration of Mettl3WT and Mettl3KO primary IECs. Bulk RNA sequencing was used to pursuit the differential expression of genes (DEGs) and associated signaling pathways after losing Mettl3. Pyroptosis-related proteins were to determine whether cell death was caused by pyroptosis. Eventually, CyTOF was performed to probe the difference of CD45+ cells, especially CD3e+ T-cell clusters after losing Mettl3. In IBD patients, Mettl3 was highly expressed in the inner-nucleus of IECs while significantly decreased upon acute intestinal inflammation. IECs-specific deletion of Mettl3 KO mice triggered a wasting phenotype and developed spontaneous colitis. The survival rate, body weight, and intestinal length observed from 2 to 8 weeks of Mettl3KO mice were significantly lower than Mettl3WT mice. The degree of mucosal damage and immune infiltration in Mettl3KO were even more serious than in their WT littermate. Bulk RNA sequencing demonstrated that DEGs were dramatically enriched in NOD-signaling pathways due to the loss of Mettl3. The colonic epithelium was more prone to pyroptosis after losing Mettl3. Subsequently, CyTOF revealed that T cells have altered significantly in Mettl3KO. Furthermore, there was abnormal proliferation of CD4+ T and markedly exhaustion of CD8 + T in Mettl3KO mice. In severe IBD patients, Mettl3 is located in the inner-nucleus of IECs and declined when intestinal inflammation occurs. Subsequently, Mettl3 prevented mice from developing colitis.