Protecting the non-operative lobe/s of the operative lung can reduce the pneumonia incidence after thoracoscopic lobectomy: a randomised controlled trial.

Lung isolation usually refers to the isolation of the operative from the non-operative lung without isolating the non-operative lobe(s) of the operative lung. We aimed to evaluate whether protecting the non-operative lobe of the operative lung using a double-bronchial blocker (DBB) with continuous positive airway pressure (CPAP) could reduce the incidence of postoperative pneumonia. Eighty patients were randomly divided into two groups (n = 40 each): the DBB with CPAP (Group DBB) and routine bronchial blocker (Group BB) groups. In Group DBB, a 7-Fr BB was placed in the middle bronchus of the right lung for right lung surgery and in the inferior lobar bronchus of the left lung for left lung surgery. Further, a 9-Fr BB was placed in the main bronchus of the operative lung. In Group BB, routine BB placement was performed on the main bronchus on the surgical side. The primary endpoint was the postoperative pneumonia incidence. Compared with Group BB, Group DBB had a significantly lower postoperative pneumonia incidence in the operative (27.5% vs 5%, P = 0.013) and non-operative lung (40% vs 15%) on postoperative day 1. Compared with routine BB use for thoracoscopic lobectomy, using the DBB technique to isolate the operative lobe from the non-operative lobe(s) of the operative lung and providing CPAP to the non-operative lobe(s) through a BB can reduce the incidence of postoperative pneumonia in the operative and non-operative lungs.

Histone H3K9 Lactylation Confers Temozolomide Resistance in Glioblastoma via LUC7L2-Mediated MLH1 Intron Retention.

Temozolomide (TMZ) resistance remains the major obstacle in the treatment of glioblastoma (GBM). Lactylation is a novel post-translational modification that is involved in various tumors. However, whether lactylation plays a role in GBM TMZ resistance remains unclear. Here it is found that histone H3K9 lactylation (H3K9la) confers TMZ resistance in GBM via LUC7L2-mediated intron 7 retention of MLH1. Mechanistically, lactylation is upregulated in recurrent GBM tissues and TMZ-resistant cells, and is mainly concentrated in histone H3K9. Combined multi-omics analysis, including CUT&Tag, SLAM-seq, and RNA-seq, reveals that H3K9 lactylation is significantly enriched in the LUC7L2 promoter and activates LUC7L2 transcription to promote its expression. LUC7L2 mediates intron 7 retention of MLH1 to reduce MLH1 expression, and thereby inhibit mismatch repair (MMR), ultimately leading to GBM TMZ resistance. Of note, it is identified that a clinical anti-epileptic drug, stiripentol, which can cross the blood-brain barrier and inhibit lactate dehydrogenase A/B (LDHA/B) activity, acts as a lactylation inhibitor and renders GBM cells more sensitive to TMZ in vitro and in vivo. These findings not only shed light on the mechanism of lactylation in GBM TMZ resistance but also provide a potential combined therapeutic strategy for clinical GBM treatment.

FSMN-Net: a free space matching network based on manifold convolution for optical molecular tomography.

Optical molecular tomography (OMT) can monitor glioblastomas in small animals non-invasively. Although deep learning (DL) methods have made remarkable achievements in this field, improving its generalization against diverse reconstruction systems remains a formidable challenge. In this Letter, a free space matching network (FSMN-Net) was presented to overcome the parameter mismatch problem in different reconstruction systems. Specifically, a novel, to the best of our knowledge, manifold convolution operator was designed by considering the mathematical model of OMT as a space matching process. Based on the dynamic domain expansion concept, an end-to-end fully convolutional codec further integrates this operator to realize robust reconstruction with voxel-level accuracy. The results of numerical simulations and in vivo experiments demonstrate that the FSMN-Net can stably generate high-resolution reconstruction volumetric images under different reconstruction systems.

miR-26a exerts broad-spectrum antiviral effects via the enhancement of RIG-I-mediated type I interferon response by targeting USP15.

IMPORTANCE: miR-26a serves as a potent positive regulator of type I interferon (IFN) responses. By inhibiting USP15 expression, miR-26a promotes RIG-I K63-ubiquitination to enhance type I IFN responses, resulting in an active antiviral state against viruses. Being an intricate regulatory network, the activation of type I IFN responses could in turn suppress miR-26a expression to avoid the disordered activation that might result in the so-called "type I interferonopathy." The knowledge gained would be essential for the development of novel antiviral strategies against viral infection.

Adaptive Sparsity Orthogonal Least Square with Neighbor Strategy for Fluorescence Molecular Tomography.

Fluorescence molecular tomography (FMT) is a highly sensitive and noninvasive optical imaging technique which has been widely applied to disease diagnosis and drug discovery. However, FMT reconstruction is a highly ill-posed problem. In this work, L0-norm regularization is employed to construct the mathematical model of the inverse problem of FMT. And an adaptive sparsity orthogonal least square with a neighbor strategy (ASOLS-NS) is proposed to solve this model. This algorithm can provide an adaptive sparsity and can establish the candidate sets by a novel neighbor expansion strategy for the orthogonal least square (OLS) algorithm. Numerical simulation experiments have shown that the ASOLS-NS improves the reconstruction of images, especially for the double targets reconstruction.Clinical relevance- The purpose of this work is to improve the reconstruction results of FMT. Current experiments are focused on simulation experiments, and the proposed algorithm will be applied to the clinical tumor detection in the future.

Tyrosine catabolism enhances genotoxic chemotherapy by suppressing translesion DNA synthesis in epithelial ovarian cancer.

Amino acid metabolism has been actively investigated as a potential target for antitumor therapy, but how it may alter the response to genotoxic chemotherapy remains largely unknown. Here, we report that the depletion of fumarylacetoacetate hydrolase (FAH), an enzyme that catalyzes the final step of tyrosine catabolism, reduced chemosensitivity in epithelial ovarian cancer (EOC). The expression level of FAH correlated significantly with chemotherapy efficacy in patients with EOC. Mechanistically, under genotoxic chemotherapy, FAH is oxidized at Met308 and translocates to the nucleus, where FAH-mediated tyrosine catabolism predominantly supplies fumarate. FAH-produced fumarate binds directly to REV1, resulting in the suppression of translesion DNA synthesis (TLS) and improved chemosensitivity. Furthermore, in vivo tyrosine supplementation improves sensitivity to genotoxic chemotherapeutics and reduces the occurrence of therapy resistance. Our findings reveal a unique role for tyrosine-derived fumarate in the regulation of TLS and may be exploited to improve genotoxic chemotherapy through dietary tyrosine supplementation.

Neighbor-based adaptive sparsity orthogonal least square for fluorescence molecular tomography.

Significance: Fluorescence molecular tomography (FMT) is a promising imaging modality, which has played a key role in disease progression and treatment response. However, the quality of FMT reconstruction is limited by the strong scattering and inadequate surface measurements, which makes it a highly ill-posed problem. Improving the quality of FMT reconstruction is crucial to meet the actual clinical application requirements. Aim: We propose an algorithm, neighbor-based adaptive sparsity orthogonal least square (NASOLS), to improve the quality of FMT reconstruction. Approach: The proposed NASOLS does not require sparsity prior information and is designed to efficiently establish a support set using a neighbor expansion strategy based on the orthogonal least squares algorithm. The performance of the algorithm was tested through numerical simulations, physical phantom experiments, and small animal experiments. Results: The results of the experiments demonstrated that the NASOLS significantly improves the reconstruction of images according to indicators, especially for double-target reconstruction. Conclusion: NASOLS can recover the fluorescence target with a good location error according to simulation experiments, phantom experiments and small mice experiments. This method is suitable for sparsity target reconstruction, and it would be applied to early detection of tumors.

IRP1 mediated ferroptosis reverses temozolomide resistance in glioblastoma via affecting LCN2/FPN1 signaling axis depended on NFKB2.

The prognosis of glioblastoma (GBM) patients is poor, and temozolomide (TMZ) resistance has become an important obstacle to its treatment effect. A growing number of researches have revealed the special characteristics of iron metabolism in GBM chemosensitivity. Iron regulatory protein 1 (IRP1) is an important protein for maintaining intracellular iron homeostasis. IRP1 has been indicated to have additional vital roles beyond its conventional metabolic activity, but the underlying mechanisms and biological consequences remain elusive. Here, we unprecedentedly demonstrated that amplifying IRP1 signals can reverse TMZ resistance and suppress tumor growth in vivo via inhibiting NFKB2 in the noncanonical NF-κB signaling pathway. In addition, we identified that NFKB2 affected TMZ sensitivity of GBM by modulating the expression of LCN2 and FPN1. Taken together, this study established a role for the IRP1/NFKB2 pathway in regulating LCN2/FPN1 signaling axis among the progression of TMZ resistance, suggesting a potential innovative GBM therapeutic strategy.

Ligand-Modified Gold Nanoparticles as Mitochondrial Modulators: Regulation of Intestinal Barrier and Therapy for Constipation.

Intestinal metabolism-related diseases, such as constipation, inflammatory bowel disease, irritable bowel syndrome, and colorectal cancer, could be associated with the dysfunction of intestinal mitochondria. The mitochondria of intestinal epithelial cells are of great significance for promoting intestinal motility and maintaining intestinal metabolism. It is necessary for the prophylaxis and therapy of intestinal metabolism-related diseases to improve mitochondrial function. We investigated the effect of 4,6-diamino-2-pyrimidinethiol-modified gold nanoparticles (D-Au NPs) on intestinal mitochondria and studied the regulatory role of D-Au NPs on mitochondria metabolism-related disease. D-Au NPs improved the antioxidation capability of mitochondria, regulated the mitochondrial metabolism, and maintained intestinal cellular homeostasis via the activation of AMPK and regulation of PGC-1α with its downstream signaling (UCP2 and DRP1), enhancing the intestinal mechanical barrier. D-Au NPs improved the intestinal mitochondrial function to intervene in the emergence of constipation, which could help develop drugs to treat and prevent mitochondrial metabolism-related diseases. Our findings provided an in-depth understanding of the mitochondrial effects of Au NPs for improving human intestinal barriers.

Multi-target reconstruction based on subspace decision optimization for bioluminescence tomography.

BACKGROUND AND OBJECTIVE: Bioluminescence tomography (BLT) is a noninvasive optical imaging technique that provides qualitative and quantitative information on the spatial distribution of tumors in living animals. Researchers have proposed a list of algorithms and strategies for BLT reconstruction to improve its reconstruction quality. However, multi-target BLT reconstruction remains challenging in practical clinical applications due to the mutual interference of optical signals and difficulty in source separation. METHODS: To solve this problem, this study proposes the subspace decision optimization (SDO) approach based on the traditional iterative permissible region strategy. The SDO approach transforms a single permissible region into multiple subspaces by clustering analysis. These subspaces are shrunk based on subspace shrinking optimization to achieve spatial continuity of the permissible regions. In addition, these subspaces are merged to construct a new permissible region and then the next iteration of reconstruction is carried out to ensure the stability of the results. Finally, all the iterative results are optimized based on the normal distribution model and the distribution properties of the targets to ensure the sparsity of each target and the non-biasing of the overall results. RESULTS: Experimental results show that the SDO approach can automatically identify and separate different targets, ensuring the accuracy and quality of multi-target BLT reconstruction results. Meanwhile, SDO can combine various types of reconstruction algorithms and provide stable and high-quality reconstruction results independent of the algorithm parameters. CONCLUSIONS: The SDO approach provides an integrated solution to the multi-target BLT reconstruction problem, realizing the whole process including target recognition, separation, reconstruction, and result enhancement, which can extend the application domain of BLT.

In vitro cell culture models to study hepatitis B and D virus infection.

Chronic infection with the hepatitis B virus (HBV) and hepatitis D virus (HDV) can cause a major global health burden. Current medication regimens can repress viral replication and help to control disease progression, but a complete cure is hardly achieved due to the difficulties to eradicate viral templates (cccDNA and integrates). To develop novel curative antiviral therapies for HBV/HDV infection, it is vital to precisely understand the details of the molecular biology of both viruses and the virus-host interactions. One important prerequisite for gaining this aim is the availability of suitable in vitro models that support HBV/HDV infection, replicate both viruses via their authentic template and allow to adequately study host cell responses. The discovery of sodium taurocholate cotransporting polypeptide (NTCP) receptor as the most crucial host factor promoted HBV/HDV research to a new era. Recently, the structure of human NTCP was solved, gaining a deeper understanding of HBV recognition as the bona fide receptor. After decades of continuous efforts, new progress has been achieved in the development of cell culture models supporting HBV/HDV study. This review summarizes the cell culture models currently available, discusses the advantages and disadvantages of each model, and highlights their future applications in HBV and HDV research.

Primary lung cancer in children and adolescents: Analysis of a surveillance, epidemiology, and end results database.

Background: The incidence of primary lung cancer (LC) in children and adolescence was rare. We analyzed data from a SEER database to better define the incidence, clinical characters, pathology, treatment, and outcomes of rare primary malignant pulmonary tumors in childhood and adolescence. Methods: Patients were chosen from the SEER database (SEER*Stat 8.4.0 software) from 2000 to 2019 and all patients were pathologically diagnosed with primary malignant tumors of the lung and bronchus. Demographic characteristics of patients (age, gender, race, primary site, laterality, location, differentiation grade, operation methods, histology, and history of radiotherapy and chemotherapy), as well as TNM stage and survival time, were collected. Results: A total of 301 cases of children ≤19 years of age with a primary malignant pulmonary tumor were reported to the SEER database from 2000 to 2019. There were 143 men (47.5%) and 158 women (52.5%). Whites represented majority of patients (79.7%), followed by Black (13.6%) and others (6.7%). As for the primary site, the main site was the lower lobe (33.2%), followed by the upper lobe (26.9%). Most of the patients (80.4%) underwent surgery. Lobectomy (39.9%) is the main operation method. Only 28 (9.3%) patients received radiotherapy and 112 (37.2) patients received chemotherapy. Carcinoid tumor was the most common histology (29.6%), followed by pulmonary blastoma (PB) (22.3%), mucoepidermoid carcinoma (MEC) (12.3%), adenocarcinoma (10.3%), neuroendocrine tumor (NET) (5.7%), squamous cell carcinoma (SCC) (5.3%), atypical carcinoma (2.3%). The mean follow-up time was 100 months. For the entire group of children and adolescents, the 1-year OS was 89.1%, and the 3-year overall survival (OS) was 79.7%. the 5-year OS was 77.9%, the 10-year OS was 75.7%, and the 15-year OS was 73.9%. And 1-year lung cancer specificity survival (LCSS) was 89.8%, and the 3-year LCSS was 80.4%. the 5-year LCSS was 79.4%, the 10-year LCSS was 77.7%, and the 15-year LCSS was 75.9%. The OS of atypical carcinoma, carcinoid tumor, and MEC were in the top three. Conclusions: Primary LC in children and adolescent were rare and histopathological diverse. Fortunately, children and adolescents with LC had an overall favorable outcome after treatment. Histology, differentiation grade, surgery, TNM stage, and therapeutic modalities have important influence on OS. The further treatment experience of each pathological type would make better evidence-based practice possible.

An adaptive parameter selection strategy based on maximizing the probability of data for robust fluorescence molecular tomography reconstruction.

To alleviate the ill-posed of the inverse problem in fluorescent molecular tomography (FMT), many regularization methods based on L2 or L1 norm have been proposed. Whereas, the quality of regularization parameters affects the performance of the reconstruction algorithm. Some classical parameter selection strategies usually need initialization of parameter range and high computing costs, which is not universal in the practical application of FMT. In this paper, an universally applicable adaptive parameter selection method based on maximizing the probability of data (MPD) strategy was proposed. This strategy used maximum a posteriori (MAP) estimation and maximum likelihood (ML) estimation to establish a regularization parameters model. The stable optimal regularization parameters can be determined by multiple iterative estimates. Numerical simulations and in vivo experiments show that MPD strategy can obtain stable regularization parameters for both regularization algorithms based on L2 or L1 norm and achieve good reconstruction performance.

Multi-target reconstruction strategy based on blind source separation of surface measurement signals in FMT.

Fluorescence molecular tomography (FMT) is a promising molecular imaging technique for tumor detection in the early stage. High-precision multi-target reconstructions are necessary for quantitative analysis in practical FMT applications. The existing reconstruction methods perform well in retrieving a single fluorescent target but may fail in reconstructing a multi-target, which remains an obstacle to the wider application of FMT. In this paper, a novel multi-target reconstruction strategy based on blind source separation (BSS) of surface measurement signals was proposed, which transformed the multi-target reconstruction problem into multiple single-target reconstruction problems. Firstly, by multiple points excitation, multiple groups of superimposed measurement signals conforming to the conditions of BSS were constructed. Secondly, an efficient nonnegative least-correlated component analysis with iterative volume maximization (nLCA-IVM) algorithm was applied to construct the separation matrix, and the superimposed measurement signals were separated into the measurements of each target. Thirdly, the least squares fitting method was combined with BSS to determine the number of fluorophores indirectly. Lastly, each target was reconstructed based on the extracted surface measurement signals. Numerical simulations and in vivo experiments proved that it has the ability of multi-target resolution for FMT. The encouraging results demonstrate the significant effectiveness and potential of our method for practical FMT applications.

Continuous positive airway pressure for treating hypoxemia due to pulmonary vein injury: A case report.

BACKGROUND: Vascular injury during thoracoscopic surgery for esophageal cancer is a rare but life-threatening complication that can lead to severe hypotension and hypoxemia. Anesthesiologists need to provide rapid and effective treatment to save patients' lives. CASE SUMMARY: A 54-year-old male patient was scheduled to undergo a thoracoscopic-assisted radical resection of esophageal cancer through the upper abdomen and right chest. While dissociating the esophagus from the carina through the right chest, unexpected profuse bleeding occurred from a suspected pulmonary vascular hemorrhage. While the surgeon attempted to achieve hemostasis, the patient developed severe hypoxemia. The anesthesiologist implemented continuous positive airway pressure (CPAP) using a bronchial blocker (BB), which effectively improved the patient's oxygenation and the operation was completed successfully. CONCLUSION: CPAP using a BB can resolve severe hypoxemia caused by accidental injury of the left inferior pulmonary vein during surgery.

High post-chemotherapy TIL and increased CD4+TIL are independent prognostic factors of surgically resected NSCLC following neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NCT) has significantly improved the overall survival of patients with operable non-small cell lung cancer (NSCLC). Chemotherapy can remodel the tumor immune microenvironment (TIME) and has an important influence on antitumor immunity. For patients who underwent surgery for resected NSCLC following NCT (NCT-NSCLC), a prognostic value comparison between naïve and post-chemotherapy TIME is absent. We enrolled 89 patients with NCT-NSCLC in this study; the tumor-infiltrating lymphocyte (TIL), CD4+TIL, and CD8+TIL levels in naïve and post-chemotherapy tumor tissues were detected using immunohistochemistry staining and divided into high and low groups. Kaplan-Meier analysis revealed that major pathology response, pathological tumor, node, and metastasis stage post-NCT (ypTNM), high post-chemotherapy TIL, high post-chemotherapy CD8+TIL, low naïve CD4+TIL, low naïve CD4+/CD8+TIL ratio, and increased CD4+TIL levels post-chemotherapy were favorable prognostic factors in patients with NCT-NSCLC. Multivariate Cox analysis found that ypTNM, high post-chemotherapy TIL, and increased CD4+TIL levels post-chemotherapy were independent prognostic factors in patients with NCT-NSCLC. These results indicate that a TIME remodeled by chemotherapy plays an important role in antitumor immunity and has a better prognostic value than the naïve TIME.

Polyhedral Oligomeric Silsesquioxane-Based Nanoparticles for Efficient Chemotherapy of Glioblastoma.

Glioblastoma (GBM) is the most common lethal brain tumor with dismal treatment outcomes and poor response to chemotherapy. As the regulatory center of cytogenetics and metabolism, most tumor chemotherapeutic molecules exert therapeutic effects in the nucleus. Nanodrugs showing the nuclear aggregation effect are expected to eliminate and fundamentally suppress tumor cells. In this study, a nanodrug delivery system based on polyhedral oligomeric silsesquioxane (POSS) is introduced to deliver drugs into the nuclei of GBM cells, effectively enhancing the therapeutic efficacy of chemotherapy. The nanoparticles are modified with folic acid and iRGD peptides molecules to improve their tumor cell targeting and uptake via receptor-mediated endocytosis. Nuclear aggregation allows for the direct delivery of chemotherapeutic drug temozolomide (TMZ) to the tumor cell nuclei, resulting in more significant DNA damage and inhibition of tumor cell proliferation. Herein, TMZ-loaded POSS nanoparticles can significantly improve the survival of GBM-bearing mice. Therefore, the modified POSS nanoparticles may serve as a promising drug-loaded delivery platform to improve chemotherapy outcomes in GBM patients.

Toward real-time automatic treatment planning (RTTP) with a one-step 3D fluence map prediction method and (nonorthogonal) convolution technique.

PURPOSE: To establish and evaluate a (quasi) real-time automated treatment planning (RTTP) strategy utilizing a one-step full 3D fluence map prediction model based on a nonorthogonal convolution operation for rectal cancer radiotherapy. METHODS: The RTTP approach directly extracts 3D projections from volumetric CT and anatomical data according to the beam incident direction. A 3D deep learning model with a nonorthogonal convolution operation was established that takes projections in cone beam space as input, extracts the features along and around the ray-trace path, and outputs a predicted fluence map (PFM) for each beam. The PFM is then converted to the MLC sequence with deliverable MUs to generate the final treatment plan. A total of 314 rectal adenocarcinoma patients with 2198 projection data samples were used in model training and validation. An extra 20 patients were used to test the feasibility of the RTTP method by comparing the plan quality, efficiency, deliverability performance, and physician blinded review results with the manual plans. RESULTS: Overall, the RTTP plans met the clinical dose criteria for target coverage, conformity, homogeneity, and organ-at-risk dose sparing. Compared to manual plans, the RTTP plans showed increases in PTV D1% by only 2.33% (p < 0.001) and a decrease in PTV D99% by 0.45% (p < 0.05). The RTTP plans showed a dose increase in the bladder, with a V50 of 14.01 ± 11.75% vs. 10.74 ± 8.51%, respectively, and no significant increases in the femoral head with the mean dose. The planning efficiency was improved in RTTP planning, with 39 s vs. 944 s in fluence map generation; the deliverability performance was saved by 1.91% (p < 0.001) in total MU. According to the blinded plan review by our physician, 55% of RTTP plans can be directly used in clinical radiotherapy treatment. CONCLUSION: The quasi RTTP method improves the planning efficiency and deliverability performance while maintaining a plan quality close to that of the optimized manual plans in rectal radiotherapy.

A Graph-guided Hybrid Regularization Method For Bioluminescence Tomography.

BACKGROUND AND OBJECTIVE: Bioluminescence tomography (BLT) is a powerful and sensitive imaging technique having great potential in preclinical application, such as tumor imaging, monitoring and therapy, etc. Regularization plays an important role in BLT reconstruction for considering the priori information to overcome the inherent ill-posedness of the inverse problem. Therefore, well-designed regularization term and sophisticated algorithm for solving the consequent optimization problem are key to improve the BLT quality. METHODS: To balance the sparsity, smoothness and morphological characteristics of the bioluminescence targets, we constructed a novel Graph-Guided Hybrid Regularization (GGHR) method by combining graph-guided penalty term with L1 and L2 norm regularizer. To solve the corresponding minimization problem with hybrid penalties, the dual decomposition and Nesterov's smoothing technique were adopted to decouple and transform the non-separable and non-smooth graph-guided penalty term into a differential smooth approximation form, which was solved by the fast iterative shrinkage thresholding algorithm. RESULTS: The performance of the proposed GGHR method was verified and evaluated through a series of simulation, phantom and in vivo experiments. The comparison results demonstrated that the GGHR method outperformed current mainstream reconstruction algorithms in spatial localization, morphology recovery and in vivo practicality. CONCLUSIONS: The proposed GGHR method is a robust and practicality reconstruction algorithm for further highlighting the positive effect of hybrid regularization on BLT applications.

ALKBH5 promotes PD-L1-mediated immune escape through m6A modification of ZDHHC3 in glioma.

N6-methylation of adenosine (m6A) is one of the most frequent chemical modifications in eukaryotic RNAs and plays a vital role in tumorigenesis and progression. Recently, emerging studies have shown that m6A modification by ALKBH5 was associated with immunotherapy response in various types of cancer. However, whether m6A demethylases ALKBH5 participate in regulating the tumor immune microenvironment and the efficacy of immunotherapy in glioblastoma remain unknown. Here, we found that deletion of ALKBH5 significantly inhibited the growth of glioma allografts, rescued the antitumoral immune response, and increased cytotoxic lymphocyte infiltration and proinflammatory cytokines in CSF while significantly suppressing PD-L1 protein expression. m6A-methylated RNA immunoprecipitation sequencing and RNA sequencing identify ZDDHC3 as the direct target of ALKBH5. Mechanically, ALKBH5 deficiency impairs the YTHDF2-mediated stability of ZDHHC3 mRNA, thereby suppressing PD-L1 expression by accelerating PD-L1 degradation in glioma. In addition, genetic deletion or pharmacological inhibition of ALKBH5 with IOX1 enhances the therapeutic efficacy of anti-PD-1 treatment in preclinical mice models. These data suggest that the combination of anti-PD-1 therapy and ALKBH5 inhibition may be a promising treatment strategy in glioma.