The Applicability of Polyetheretherketone and Titanium Mesh in Cranioplasty: A Retrospective Comparative Analysis.

OBJECTIVE: To compare the clinical application effect and safety of polyetheretherketone (PEEK) and titanium mesh (TM) in cranioplasty. METHODS: Four-year retrospective comparison of patients (96 cases) undergoing synthetic cranioplasty with PEEK or TM. The patients were divided into the PEEK group (24 cases) and the TM group (72 cases) according to the implants, and the patient demographics, general conditions before the operation, postoperative complications, length of postoperative hospital stay, total costs, satisfaction with shaping and long-term complications were compared between the 2 groups. RESULTS: Patients in the PEEK group were younger than those in the TM group (P=0.019). Hospitalization costs were significantly higher in the PEEK group than in the TM group (P<0.001). The incidence of postoperative subcutaneous effusion was 33% in the PEEK group and 6.9% in the TM group, which suggests that patients in the PEEK group had a higher risk of postoperative subcutaneous effusion (P=0.001). There was no significant difference in the incidence of long-term complications and cosmetic satisfaction between the 2 groups at 4 years postoperatively. CONCLUSIONS: In this study, both titanium mesh and PEEK are reliable implants for cranioplasty. Titanium mesh is widely used in cranioplasty due to its cost-effective performance. PEEK has gradually gained recognition due to the characteristics of the material and surgical procedure, but the price needs to be further reduced, and attention should be paid to the occurrence and treatment of early postoperative subcutaneous effusion.

Physicochemical Properties and Biological Activities of Quinoa Polysaccharides.

Quinoa, known as the "golden grain" for its high nutritional value, has polysaccharides as one of its sources of important nutrients. However, the biological functions of quinoa polysaccharides remain understudied. In this study, two crude polysaccharide extracts of quinoa (Q-40 and Q-60) were obtained through sequential precipitation with 40% and 60% ethanol, with purities of 58.29% (HPLC) and 62.15% (HPLC) and a protein content of 8.27% and 9.60%, respectively. Monosaccharide analysis revealed that Q-40 contained glucose (Glc), galacturonic acid (GalA), and arabinose (Ara) in a molar ratio of 0.967:0.027:0.006. Q-60 was composed of xylose (xyl), arabinose (Ara), galactose, and galacturonic acid (GalA) with a molar ratio of 0.889:0.036:0.034:0.020. The average molecular weight of Q-40 ranged from 47,484 to 626,488 Da, while Q-60 showed a range of 10,025 to 47,990 Da. Rheological experiments showed that Q-40 exhibited higher viscosity, while Q-60 demonstrated more elastic properties. Remarkably, Q-60 showed potent antioxidant abilities, with scavenging rates of 98.49% for DPPH and 57.5% for ABTS. Antibacterial experiments using the microdilution method revealed that Q-40 inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), while Q-60 specifically inhibited MRSA. At lower concentrations, both polysaccharides inhibited MDA (MD Anderson Cancer Center) cell proliferation, but at higher concentrations, they promoted proliferation. Similar proliferation-promoting effects were observed in HepG2 cells. The research provides important information in the application of quinoa in the food and functional food industries.

Proteus appendicitidis sp. nov., isolated from the appendiceal pus of an appendicitis patient in Yongzhou, China.

A Gram-negative, facultatively anaerobic, short rod-shaped bacterium, designated as strain HZ0627T, was isolated from the appendiceal pus of a patient with appendicitis in Yongzhou, Hunan, China. This strain was subjected to comprehensive phenotypic, phylogenetic, and genomic analyses using polyphasic taxonomic methods. Phylogenetic analysis of the 16S rRNA gene sequence revealed that this strain belonged to the genus Proteus and the family Morganellaceae, whereas that based on the rpoB gene sequence and phylogenomic analysis demonstrated that this strain was distinctly separated from other type strains of Proteus species. Moreover, whole-genome-based analyses, including in silico DNA-DNA hybridization (isDDH) and average nucleotide identity (ANI), revealed that strain HZ0627T had much lower isDDH rates (24.5-55.6%) and ANI (82.04-93.90%) than those of the thresholds (i.e., 70% and 95%, respectively) for species delineation, when compared to the type strains of other Proteus species. The cellular fatty acid profile of strain HZ0627T was dominated by C16:0 (34.5%), cyclo C17:0 (25.8%), C14:0 (12.6%), C16:1 iso I/14:0 3-OH (7.7%), C18:1ω7c/18:1ω6c (6.5%), and C16:1ω7c/16:1ω6c (4.9%), which clearly differentiated it from the documented type strains of Proteus species. In addition, several specific physiological traits, including optimal growth temperature, tolerance to sodium chloride, and carbon source utilization, differed from those of other Proteus species. Therefore, we propose the name Proteus appendicitidis sp. nov. for strain HZ0627T (= CCTCC AB 2022380T = KCTC 92986T), which represents the type strain of this novel Proteus species.

Survival and Prognosis for Patients with Rectal Melanomas in the United States: A SEER-Based Study.

PURPOSE: Limited attention was paid to focus on rectal melanomas (RM). This study aimed to evaluate the survival rate and prognostic factors of RM. METHODS: The data for patients with RM from Surveillance, Epidemiology, and End Results (SEER) database were used to analyze tumor survival. Kaplan-Meier method and log-rank test were employed to estimate cancer-specific survival (CSS) and overall survival (OS). A nomogram was established based on the risk factors of survival by the forest plot for multivariate Cox regression analysis. Receiver operating characteristic (ROC) and calibration curve were conducted for validation. RESULTS: A total of 187 patients with RM were selected to perform survival analyses. The median survival time of OS was 12 months (range: 0-146 months), and the median survival time of CSS was 12 months (range: 0-74 months). Patients' age, tumor size, stage, the number of nodes examined, surgery, and radiation were identified as prognostic indicators for CSS by the forest plot for multivariate Cox regression analysis. The nomogram was validated as a reliable model for CSS. CONCLUSION: Clinicopathologic relevance with tumor prognosis was confirmed in this study. Our nomogram can provide a relatively accurate prediction of the survival rate of patients with RM.

Rapid detection method of bacterial pathogens in surface waters and a new risk indicator for water pathogenic pollution.

In this study, a accurate, rapid quantitative PCR method for the simultaneous detection of 4 kinds of pathogenic bacteria in water was established, and the distribution of pathogenic bacteria in surface waters with different levels of pollution (Yulin region, China) was detected. The results showed that the detection accuracy was 94%; the detection limit was 2.7 in bacterial cells. Salmonella enterica subsp. enterica serovar typhimurium and Salmonella dysenteria were always present in water when the universal primer for pathogenic bacteria abundance detection was greater than 104 copies 100 mL-1. When the detection value is lower than 104 copy 100 mL-1, the bacteria in the water are rarely pathogenic bacteria, so the detection value of 104 copy 100 mL-1 can be used as a new indicator of waterborne pathogen pollution.

N6-methyladenosine reader protein IGF2BP1 suppresses CD8 + T cells-mediated tumor cytotoxicity and apoptosis in colon cancer.

Tumor immune escape is an important manner for colon cancer to escape effective killing by immune system. Currently, the immune checkpoint PD-1/PD-L1-targeted immunotherapy has emerged as a promising therapeutic strategy in colon cancer. Here, present work aims to investigate the biological function of N6-methyladenosine (m6A) reader insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) in regulating colon cancer's immune escape and CD8 + T cells-mediated tumor cytotoxicity and apoptosis. Results illustrated that IGF2BP1 was closely correlated to the colon cancer patients' poor clinical outcome. Functionally, upregulation of IGF2BP1 suppressed the CD8+ T-cells mediated antitumor immunity through reducing their tumor cytotoxicity. Mechanistically, MeRIP-Seq revealed that programmed death ligand 1 (PD-L1) mRNA had a remarkable m6A modified site on 3'-UTR genomic. Moreover, PD-L1 acted as the target of IGF2BP1, which enhanced the stability of PD-L1 mRNA. Overall, these results indicated that IGF2BP1 targeted PD-L1 to accelerate the immune escape in colon cancer by reducing CD8 + T cells-mediated tumor cytotoxicity in m6A-dependent manner. The findings demonstrate the potential of m6A-targeted immune checkpoint blockade in colon cancer, providing a novel insight for colon cancer immune escape and antitumor immunity in further precise treatment.

Ultrasonic extraction of Moringa oleifera seeds polysaccharides: Optimization, purification, and anti-inflammatory activities.

Natural polysaccharides exhibit numerous beneficial properties, such as antioxidant, antitumor, hypoglycemic, and hypolipidemic activities. Moringa oleifera seeds are of high dietary and therapeutic value which drew a lot of attention. However, the regulation effect on anti-inflammatory activity of polysaccharides remains to be studied. Herein, novel bioactive polysaccharides (MOSP-1) were extracted from Moringa oleifera seeds, and the anti-inflammatory properties of MOSP-1 were uncovered. Ultrasound-assisted extraction (UAE) was used to prepare the polysaccharides with optimized conditions (70 °C, 43 min, and liquid-solid-ratio 15 mL/g). Then, DEAE-Sepharose Fast Flow columns were applied to isolate and purify MOSP-1. Rhamnose, arabinose, galactose, and glucose were identified as the monosaccharide constituents of MOSP-1, with a molecular weight of 5.697 kDa. Their proportion in molarity was 1:0.183:0.108:0.860 and 8 types of glycosidic linkages were discovered. Bioactive assays showed that MOSP-1 possessed scavenging activities against DPPH and ABTS radicals, confirming its potential antioxidation efficacy. In vitro experiments revealed that MOSP-1 could reduce the expression of inflammation-related cytokines, inhibit the activation of ERK, JNK, and p38 (the MAPK signaling pathway), and enhance phagocytic functions. This study indicates that polysaccharides (MOSP-1) from Moringa oleifera seeds with anti-inflammatory properties may be used for functional food and pharmaceutical product development.

Effect of wound infiltration of dexmedetomidine in lumbar spine surgery on postoperative wound pain: A meta-analysis.

In a meta-study, we evaluated the effectiveness and security of the combination of topical anaesthetic and dexmedetomidine in the treatment of postoperative pain in patients with lumbar disease. Four databases were systematically searched for possible related articles. Only English-language research was taken into account on the Internet. Furthermore, we only took into account the studies that were published prior to 2023. Only those that fulfilled the eligibility criteria were considered: (1) in adults who were about to undergo spine operation, (2) dexmedetomidine combined with local anaesthesia, (3) Visual Analog Scale scores at 4 and 24 h after the event and (4) this was a randomized or nonrandomized, controlled study. The meta-analysis was carried out with Revman 5.3 software. A ROBINS-I-based instrument was used to evaluate controlled studies. All trials were synthesized by computing the end results with either a fixed or a random effect model, which was dependent on statistical diversity. Five trials showed a marked reduction in wound pain at 4 h after the operation in patients who were treated with dexmedetomidine for lumbar spinal surgery (MD, -0.81; 95% CI, -1.24, -0.35; p = 0.0005). In the case of lumbar spinal operations, the addition of dexmedetomidine to the postoperative treatment resulted in a marked reduction in the pain at 24 h post-operation (MD, -0.64; 95% CI, -0.79, -0.48; p < 0.0001). The quality of the data we evaluated was 'moderate' to 'good'; thus, we have limited confidence in the impact estimation, and the actual impact might be significantly different from what we had expected. Additional studies should concentrate on practices that are well known to cause severe postoperative pain, especially for cases where the improvement of pain management may lead to substantial clinical benefits in terms of reduction of morbidity or cost-effectiveness in terms of quicker healing and release.

Room-Temperature Synthesized Iron/Cobalt Metal-Organic Framework Nanosheets with Highly Efficient Catalytic Activity toward Luminol Chemiluminescence Reaction.

Two-dimensional (2D) iron/cobalt metal-organic framework nanosheets (Fe/Co-MOF NSs) were synthesized via the cooperative self-assembly reaction of Fe3+/Co2+ and terephthalic acid at room temperature. The as-prepared 2D Fe/Co-MOF NSs display superior performance in catalysis of the chemiluminescence (CL) reaction between luminol and H2O2. The CL spectrum, UV-vis absorption spectroscopy, radical scavenger experiments, and electron spin resonance (ESR) spectroscopy are utilized to research the possible CL mechanism of the luminol-H2O2-Fe/Co-MOF NSs system. All results indicate that Fe/Co-MOF NSs present outstanding peroxidase-like activity and could catalyze H2O2 to produce 1O2, O2·-, and ·OH, which could react rapidly with the luminol anion radical and result in strong CL. With the highly efficient CL of the luminol-H2O2-Fe/Co-MOF NSs system, a sensitive sensor for the detection of dopamine (DA) is developed based on the inhibitory effect of DA on the CL intensity. Good linearity over the range of 50-800 nM is achieved with a limit of detection of 20.88 nM (S/N = 3). This research demonstrates that 2D Fe/Co-MOF NSs is a highly effective catalyst for luminol CL reaction and has great application potential in the CL field.

Variations of bile bacterial community alongside gallstone disease progression and key taxa involved in poor outcomes after endoscopic surgery.

Gallstone disease is a prevalent biliary disease worldwide, and bacteria play vital roles in the disease development and progression, as well as the prognosis after endoscopic surgery. However, there have been limited studies to explore the key taxa involved. In this study, bile samples from healthy controls (HCs, liver donors without hepatobiliary disease) and three diseased groups, namely patients with gallbladder stones (GBS), patients with common bile duct stones (CBDS), and patients with stricture in the common bile duct (SCBD), were collected and analyzed. Bacterial community characterization based on 16S rRNA amplicon sequencing showed that bacterial diversities did not change significantly alongside gallstone disease development and progression. The predominant phyla in each group were Proteobacteria, Firmicutes, Bacteroidota, and Fusobacteriota, representing over 80% in abundance of the biliary bacteria community. Specifically, the abundance of Proteobacteria decreased greatly while that of Firmicutes and Bacteroidota increased greatly in the diseased groups when compared to that in HCs. Moreover, linear discriminant analysis identified several genera highly represented in the diseased groups. Among them, Klebsiella, Prevotella, Pseudomonas and Veillonella are persistent in both the HCs group and the diseased groups, indicating an enrichment of local bile bacteria in the diseased bile; while Lachnoanerobaculum, Atopobium, Oribacterium, and Stomatobaculum, those aligned to oral cavity taxa, are persistent in the diseased groups but are transient in the HCs group, and their abundances sequentially increased with the disease development and progression (HCs→GBS→CBDS→SCBD), implying a translocation and colonization of the oral cavity bacteria in the diseased bile. Moreover, co-occurrence network analysis revealed that bacterial infection (e.g., Photobacterium and Plesiomonas) from the intestine was developed during endoscopic surgery with reduced bile bacteria diversity. The results of this study revealed that the bile bacterial community is relatively stable and dominated by a few persistent taxa. Moreover, we hypothesized that translocation and colonization of specific bacteria from the oral cavity happens alongside gallstone disease development and progression, and bacterial infection from the intestinal tract results in poor outcomes after endoscopic surgery.

Incidence, survival, and prognostic factors for patients with gastrointestinal mixed neuroendocrine non-neuroendocrine neoplasms: a SEER population-based study.

BACKGROUND: Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are a group of rare tumors with limited research currently available. This study aimed to analyze the incidence, survival, and prognostic factors of gastrointestinal MiNENs. METHODS: We included data from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019. We compared the clinicopathologic characteristics and survival rates between MiNENs and neuroendocrine tumors (NETs), and calculated the incidence of MiNENs. We utilized univariate and multivariate Cox analysis to assess independent factors of prognosis and established a nomogram to predict 1-, 2-, and 3-year cancer-specific survival (CSS). Calibration and receiver operating characteristic (ROC) curves were drawn to validate the accuracy and reliability of the model. Decision curve analysis (DCA) was used to assess the clinical utility of the model. RESULTS: Patients with gastrointestinal MiNENs had a poorer prognosis than those with NETs. The overall incidence of gastrointestinal MiNENs has been increasing annually. Multivariate Cox regression analysis revealed that tumor size, lymph node metastasis, distant metastasis, and surgery were independent risk factors for CSS in MiNENs patients. Based on these risk factors, the 1-, 2-, and 3-year CSS nomogram model for MiNENs patients was established. Calibration, ROC, and DCA curves of the training and validation sets demonstrated that this model had good accuracy and clinical utility. CONCLUSION: Gastrointestinal MiNENs are rare tumors with an increasing incidence rate. The nomogram model is expected to be an effective tool for personalized prognosis prediction in MiNENs patients, which may benefit clinical decision-making.

Integration of taxa abundance and occurrence frequency to identify key gut bacteria correlated to clinics in Crohn's disease.

Bacteria abundance alternation in the feces or mucosa of Crohn's disease (CD) patients has long been applied to identify potential biomarkers for this disease, while the taxa occurrence frequency and their correlations with clinical traits were understudied. A total of 97 samples from the feces and gut mucosa were collected from CD patients and healthy controls (HCs), 16S rRNA-based analyses were performed to determine the changes in taxa abundance and occurrence frequency along CD and to correlate them with clinical traits. The results showed that bacteria communities were divergent between feces and mucosa, while the taxa abundance and occurrence frequency in both partitions showed similar exponential correlations. The decrease of specific fecal bacteria was much more effective in classifying the CD and HCs than that of the mucosal bacteria. Among them, Christensenellaceae_R-7_group and Ruminococcus were predicted as biomarkers by using random forest algorithm, which were persistently presented (> 71.40% in frequency) in the feces of the HCs with high abundance, whereas transiently presented in the feces (< 5.5% in frequency) and mucosa (< 18.18% in frequency) of CD patients with low abundance. Co-occurrence network analysis then identified them as hub taxa that drive the alternations of other bacteria and were positively correlated to the circuiting monocytes. The loss of specific bacteria in the healthy gut may cause great disturbance of gut microbiota, causing gut bacteria dysbiosis and correlated to immune disorders along CD, which might not only be developed as effective noninvasive biomarkers but also as therapy targets.

Incidence and survival of adenocarcinoma with mixed subtypes in patients with colorectal cancer.

BACKGROUND: Limited attention was paid to adenocarcinoma with mixed subtypes (AM) of the colon and rectum due to its low incidence. This study aims to assess the frequency and survival rates of tumors in the population. METHODS: The data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019. The incidence of tumors was evaluated based on patient gender, age, race, and location. Univariate and multivariate Cox analyses were performed to identify risk factors associated with tumor survival. Additionally, a nomogram was constructed using these risk factors to predict cancer-specific survival (CSS) at 1, 2, and 3 years. Receiver operating characteristic (ROC) and calibration curves were applied to examine the model's accuracy. RESULTS: The overall incidence of colorectal AM reached its highest level in 2016 (2.350 (95% CI: 2.241-2.462)). AM is more frequent in elderly patients and predominantly located in the rectum. By forest plot for multivariable Cox regression analysis, patient age, the number of regional positive lymph nodes and lymph nodes removed, tumor N/M stage, and postoperative chemotherapy were identified as independent risk indicators for CSS. Nomogram was constructed and validated as a feasible prediction model of CSS in patients with colorectal AM. CONCLUSION: The presence of colorectal AM in elderly patients, particularly in the rectum, is frequent and often associated with poor prognosis. Our nomograms can offer a relatively accurate prediction of CSS of patients with AM after tumor resection.

Targeting of SLC25A22 boosts the immunotherapeutic response in KRAS-mutant colorectal cancer.

KRAS is an important tumor intrinsic factor driving immune suppression in colorectal cancer (CRC). In this study, we demonstrate that SLC25A22 underlies mutant KRAS-induced immune suppression in CRC. In immunocompetent male mice and humanized male mice models, SLC25A22 knockout inhibits KRAS-mutant CRC tumor growth with reduced myeloid derived suppressor cells (MDSC) but increased CD8+ T-cells, implying the reversion of mutant KRAS-driven immunosuppression. Mechanistically, we find that SLC25A22 plays a central role in promoting asparagine, which binds and activates SRC phosphorylation. Asparagine-mediated SRC promotes ERK/ETS2 signaling, which drives CXCL1 transcription. Secreted CXCL1 functions as a chemoattractant for MDSC via CXCR2, leading to an immunosuppressive microenvironment. Targeting SLC25A22 or asparagine impairs KRAS-induced MDSC infiltration in CRC. Finally, we demonstrate that the targeting of SLC25A22 in combination with anti-PD1 therapy synergizes to inhibit MDSC and activate CD8+ T cells to suppress KRAS-mutant CRC growth in vivo. We thus identify a metabolic pathway that drives immunosuppression in KRAS-mutant CRC.

Constructing a composite microfiltration carbon membrane by TiO2 and Fe2O3 for efficient separation of oil-water emulsions.

Membrane-based separation technology has attracted enormous attention for oil/water emulsion treatment. Here, composite microfiltration carbon membranes (MCMs) were prepared from the precursor of phenolic resin doping with TiO2 and Fe2O3 via the processes of stereotype and pyrolysis. The functional groups, thermal stability, porous structure, microstructure, morphology, and hydrophilicity of the membrane samples were analyzed by Fourier-transform infrared spectroscopy, thermogravimetric analysis, bubble pressure method, X-ray diffraction, scanning electron microscope, and water contact angle, respectively. The effect of dopant amount on the separation performance of MCMs was investigated. The results show that a mixed matrix system is constructed by TiO2 and Fe2O3 in MCMs, which is beneficial for further optimizing the pore size, porosity, and hydrophilicity of MCMs for oily wastewater treatment by varying the dopant amount. The maximum oil rejections are achieved at 98.9% and 99.6% for MCMs with a dopant content of TiO2 and Fe2O3 at 25%, respectively. In brief, this study offers an attractive strategy for improving the separation performance of MCMs for oily wastewater.

Sensitive and Amplification-Free Electrochemiluminescence Biosensor for HPV-16 Detection Based on CRISPR/Cas12a and DNA Tetrahedron Nanostructures.

Rapid and accurate detection of biomarkers was very important for early screening and treatment of diseases. Herein, a sensitive and amplification-free electrochemiluminescence (ECL) biosensor based on CRISPR/Cas12a and DNA tetrahedron nanostructures (TDNs) was constructed. Briefly, 3D TDN was self-assembled on the Au nanoparticle-deposited glassy carbon electrode surface to construct the biosensing interface. The presence of the target would activate the trans-cleavage activity of Cas12a-crRNA duplex to cleave the single-stranded DNA signal probe on the vertex of TDN, causing the Ru(bpy)32+ to fall from the electrode surface and weakened the ECL signal. Thus, the CRISPR/Cas12a system transduced the change of target concentration into an ECL signal enabling the detection of HPV-16. The specific recognition of CRISPR/Cas12a to HPV-16 made the biosensor have good selectivity, while the TDN-modified sensing interface could reduce the cleaving steric resistance and improve the cleaving performance of CRISPR/Cas12a. In addition, the pretreated biosensor could complete sample detection within 100 min with a detection limit of 8.86 fM, indicating that the developed biosensor possesses the potential application prospect for fast and sensitive nucleic acid detection.

ALKBH5 Drives Immune Suppression Via Targeting AXIN2 to Promote Colorectal Cancer and Is a Target for Boosting Immunotherapy.

BACKGROUND & AIMS: Immune checkpoint blockade therapy benefits only a small subset of patients with colorectal cancer (CRC), and identification of CRC-intrinsic events modulating immune checkpoint blockade efficacy is an unmet need. We found that AlkB homolog 5 (ALKBH5), an RNA N6-methyladenosine eraser, drives immunosuppression and is a molecular target to boost immune checkpoint blockade therapy in CRC. METHODS: Clinical significance of ALKBH5 was evaluated in human samples (n = 205). Function of ALKBH5 was investigated in allografts, CD34+ humanized mice, and Alkbh5 knockin mice. Immunity change was determined by means of flow cytometry, immunofluorescence, and functional investigation. Methylated RNA immunoprecipitation sequencing and RNA sequencing were used to identify ALKBH5 targets. Vesicle-like nanoparticle-encapsulated ALKBH5-small interfering RNA was constructed for targeting ALKBH5 in vivo. RESULTS: High ALKBH5 expression predicts poor prognosis in CRC. ALKBH5 induced myeloid-derived suppressor cell accumulation but reduced natural killer cells and cytotoxic CD8+ T cells to induce colorectal tumorigenesis in allografts, CD34+ humanized mice, and intestine-specific Alkbh5 knockin mice. Mechanistically, AXIN2, a Wnt suppressor, was identified as a target of ALKBH5. ALKBH5 binds and demethylates AXIN2 messenger RNA, which caused its dissociation from N6-methyladenosine reader IGF2BP1 and degradation, resulting in hyperactivated Wnt/ß-catenin. Subsequently, Wnt/ß-catenin targets, including Dickkopf-related protein 1 (DKK1) were induced by ALKBH5. ALKBH5-induced DKK1 recruited myeloid-derived suppressor cells to drive immunosuppression in CRC, and this effect was abolished by anti-DKK1 in vitro and in vivo. Finally, vesicle-like nanoparticle-encapsulated ALKBH5-small interfering RNA, or anti-DKK1 potentiated anti-PD1 treatment in suppressing CRC growth by enhancing antitumor immunity. CONCLUSIONS: This study identified an ALKBH5-N6-methyladenosine-AXIN2-Wnt-DKK1 axis in CRC, which drives immune suppression to facilitate tumorigenesis. Targeting of ALKBH5 is a promising strategy for sensitizing CRC to immunotherapy.