Immune checkpoint blockade targeting PD-1 has transformed oncology by reactivating antitumor immunity yet only a subset of patients derives durable benefit. Although neutrophil extracellular traps (NETs) contribute to tumor immune escape and immunotherapy resistance, the upstream key regulator and precise mechanism remain unknown. Here, we revealed that NETs were significantly enriched in human OSCC tumors and correlated with advanced clinical stage, adverse prognosis, and diminished response to immunotherapy. Mitochondrial dynamics critically regulated NET generation, particularly through the action of the fusion protein OPA1. Mechanistically, OPA1 triggered a ROS-AKT-MDM2 signaling axis that drove NET formation. In murine models, intravenous delivery of neutrophil-targeted lipid nanoparticles (LNP) encapsulating si OPA1 potently suppressed NETs, promoted CD8⁺ T cell infiltration, and resensitized resistant tumors to anti-PD-1 therapy. Collectively, our study unveiled neutrophil OPA1 as a promising therapeutic target that drove treatment resistance to PD-1 blockade. These findings identified targeting OPA1 in neutrophils, which reduced NET formation, as a viable strategy to overcome immunotherapy resistance.

6048 Background: Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors of the head and neck. Stage IVB OSCC had long been considered unresectable with extremely poor prognosis, and mainstream guidelines encourage exploring new therapies via clinical trials. This study aimed to evaluate the efficacy and safety of adebrelimab plus cisplatin/docetaxel as neoadjuvant therapy for stage IVB OSCC (NCT06277791). Methods: IVB OSCC patients aged 18–75 years were enrolled and received 2 cycles of neoadjuvant immunochemotherapy (adebrelimab 1200 mg + cisplatin 75 mg/m²/docetaxel 75 mg/m², q3w). Three weeks after neoadjuvant treatment, patients underwent extended primary tumor resection and radical neck dissection, followed by adjuvant radiotherapy/chemoradiotherapy. The primary endpoint was pathological response rate (pCR+MPR); secondary endpoints included radiographic response, R0 resection rate, and safety. Results: 28 patients were enrolled between June 2023 and January 2026. The mean age was 47.8 years, with a male predominance (25, 89.3%). Primary tumors were mainly located in the buccal mucosa (14, 50.0%) and tongue (10, 35.7%). Smoking, alcohol consumption, and betel nut chewing histories were noted in 75.0%, 42.9%, and 64.3% of patients, respectively. Most had an ECOG performance status of 1 (75.0%). 8 cases (28.6%) were classified as cT4b and 20 cases (71.4%) as cN3b at baseline. Three patients (10.7%) were excluded from efficacy analysis due to insufficient data. In the evaluable population (n=25), no complete response (CR) was observed; 8 (28.6%) achieved partial response (PR), 14 (50.0%) stable disease (SD), and 3 (10.7%) progressive disease (PD), with an overall objective response rate (ORR) of 32.0% (8/25). Subgroup ORRs were 33.3% (2/6) for cT4b and 31.6% (6/19) for cN3b. Pathological assessment was available for 25 patients: based on the combined pathological assessment of the primary tumor and lymph nodes, 15 (60.0%) achieved MPR, 1 (4.0%) pCR, resulting in a 64.0% pathological response rate. For subgroups, the pathological response rate was 50.0% in 6 evaluable cT4b (2 MPR, 1 pCR) and 68.4% in 19 evaluable cN3b (13 MPR, no pCR). The R0 resection rate was 100% among 25 surgical patients. Treatment-related adverse events (TRAEs) were mostly grade 1–2. Grade 3 TRAEs occurred in 2 cases (7.2%), with no grade 4/5 events. At data cutoff (median follow-up: 12.0 months), 3 deaths occurred. The estimated 1-year OS rate was 87.9%, with subgroup rates of 89.1% for cN3b (median follow-up: 12.0 months) and 87.5% for cT4b (median follow-up: 19.4 months). Conclusions: Neoadjuvant adebrelimab combined with chemotherapy achieves a high pathological response rate in stage IVB OSCC, with manageable adverse events and favorable safety. Clinical trial information: NCT06277791 .

Accurate detection of atherosclerosis-related microRNAs (miRNAs) remains technically challenging due to their low abundance, high sequence homology, and susceptibility to enzymatic degradation. Herein, we report a fluorescence sensing platform that uniquely integrates catalytic hairpin assembly (CHA) with a Cas12a-regulated DNA walker based on a circular CRISPR RNA (circular-crRNA) architecture. Unlike conventional linear crRNAs, the circular crRNA confers intrinsic resistance to nuclease degradation, substantially enhancing assay robustness in complex biological matrices. Upon target miRNA-initiated CHA, a three-way DNAzyme junction is assembled to site-specifically cleave the circular crRNA, thereby unlocking the dual cis- and trans-cleavage activities of Cas12a. This synergistic activation drives an exceptionally efficient DNA walking process on gold nanoparticle surfaces, achieving signal amplification with a detection limit as low as 0.36 fM and a dynamic range spanning five orders of magnitude. The platform demonstrates excellent specificity, reproducibility, and reliable performance in serum samples, highlighting its potential as a robust and versatile tool for miRNA-based diagnostics.

Importance:Perioperative immunotherapy has improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). The influence of immune checkpoint inhibitor in combination with chemotherapy on surgical outcomes remains to be explored. Objective:To evaluate perioperative toripalimab in combination with chemotherapy on surgical outcomes. Design, Setting, and Participants:This multicenter, double-blind, placebo-controlled phase 3 randomized clinical trial (Neotorch study) enrolled patients with resectable stage III NSCLC and took place at 50 centers in China. Patients who had histologically confirmed resectable stage IIIA or IIIB NSCLC were eligible. These data were analyzed from July 2024 to March 2026. Interventions:Patients were randomized (1:1) to receive toripalimab (240 mg) plus platinum-based chemotherapy or placebo plus platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by maintenance with toripalimab or placebo alone for 13 cycles. Main Outcomes and Measures:Surgical outcomes, including perioperative complications, tumor downstaging, and lymph node downstaging, and their association with event-free survival (EFS), were studied in this post hoc analysis. Results:Among 404 patients enrolled, 314 patients (median [SD] age 60 [6.82] years; 90% of patients were male and 10% were female) underwent surgery (166 in toripalimab group and 148 in placebo group). Percentage of patients canceling surgery (17.8% vs 26.7%; P = .03) was significantly lower in the toripalimab group. Proportions of minimally invasive surgery, R0 resection, and lobectomy were slightly higher in the toripalimab group. Surgical complications were similar between the 2 groups. Rates of postsurgery tumor (80.7% vs 50.7%; P < .001) and lymph node downstaging (67.5% vs 48.6%; P = .001) were both significantly higher with toripalimab than placebo. With a median follow-up of 18.3 months, a better EFS was noticed in the toripalimab group. Tumor and lymph node downstaging in the toripalimab group were both associated with better EFS than nondownstaging (median EFS, not estimable [NE] vs 17.5 months; P = .004 and NE vs 19.2 months; P = .001, respectively), and were also associated with even better EFS than tumor and lymph node downstaging in the placebo group (median EFS, NE vs 22.0 months; P = .002 and NE vs NE; P = .009, respectively). Conclusions and Relevance:In this study, perioperative toripalimab plus chemotherapy showed comparable perioperative outcomes, as with chemotherapy alone without new safety signals, and could help improve survival through effective tumor downstaging in patients with resectable stage III NSCLC. Trial Registration:ClinicalTrials. gov Identifier: NCT04158440.

OBJECTIVE:This study aimed to evaluate overall survival (OS), identify independent prognostic factors, and characterize prognostic heterogeneity across clinical subgroups in a large single-center Chinese cohort of patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS:We retrospectively reviewed 2983 primary OSCC patients undergoing radical surgery between June 2012 and December 2023. OS was analyzed using Kaplan-Meier methods and Cox proportional hazards models. Subgroup analyses were performed according to gender, age, and anatomical site. RESULTS:The 1-, 3-, and 5-year OS rates were 92.0%, 79.6%, and 74.4%, respectively. Multivariate analysis identified age, alcohol consumption, time to presentation (TTP), perineural invasion (PNI), histological grade, pathologic tumor stage (pT stage), and pathologic lymph node stage (pN stage) as independent prognostic factors. Among these, pN stage showed the strongest association with survival, with a stepwise increase in risk from N1 (HR 1.60, 95% CI 1.31-1.96) to N2 (HR 2.34, 95% CI 1.97-2.78; both P < 0.001). Although the prognostic determinants varied across subgroups, pN stage remained a consistent independent predictor across nearly all subgroups defined by gender, age, and anatomical site. CONCLUSIONS:In this large Chinese OSCC cohort, pN stage was the most robust and consistent prognostic determinant across clinical subgroups, underscoring its central role in risk stratification and supporting more individualized prognostic assessment.

Background Immune checkpoint blockade targeting programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) has revolutionized cancer therapy. However, its efficacy is frequently limited by primary and acquired resistance. While inflammatory signals transiently upregulate PD-L1 transcription, post-translational regulation is crucial for its sustained expression in chronically stressed tumors. Whether and how tumor-intrinsic stress-response pathways control PD-L1 stability to promote immune evasion remains incompletely understood.Methods Using human oral squamous cell carcinoma (OSCC) specimens, syngeneic mouse models, single-cell RNA sequencing, and genetic and pharmacological perturbations, we dissected the role of the unfolded protein response effector ATF4 in regulating PD-L1 stability and antitumor immunity. Its therapeutic potential was further evaluated in immunocompetent mice treated with anti-PD-1 therapy.Results We identified ATF4 as a tumor-intrinsic driver of immune evasion. In malignant cells, ATF4 induced reactive oxygen species (ROS), which activated the AKT-mTOR pathway and suppressed autophagy, thereby stabilizing the PD-L1 protein independently of inflammatory cues. Genetic ablation of ATF4 or pharmacological inhibition of ROS-AKT-mTOR signaling restored autophagic flux, reduced PD-L1 levels, and enhanced CD8+ T-cell infiltration and function. When combined with PD-1 blockade, ATF4 targeting further suppressed tumor growth. Clinically, ATF4 expression was inversely correlated with CD8+ T-cell infiltration and autophagy markers, positively correlated with PD-L1 levels, and predicted a poor response to immunotherapy in patients with OSCC.Conclusions Our findings establish ATF4 as a stress-responsive regulator of PD-L1 proteostasis, directly linking tumor-intrinsic stress adaptation to immune checkpoint stabilization and therapy resistance. Targeting the ATF4-ROS-AKT-mTOR axis may represent a promising strategy to overcome resistance to PD-1/PD-L1 blockade.

Background:Immunotherapy research, particularly in the neoadjuvant setting, has largely focused on tumor-intrinsic determinants, with limited attention to host-related factors. Emotional distress (ED), a prevalent condition in cancer patients, remains poorly understood in the context of neoadjuvant immunotherapy (NAIT). Methods:We analyzed a cohort of 68 patients with locally advanced OSCC treated with NAIT. ED was assessed using the EORTC QLQ-C30 to stratify patients, and clinical outcomes were evaluated to determine therapeutic efficacy. Serum neuroendocrine markers were measured to assess neuroendocrine activation. Integrated single-cell, spatial, and multiplexed imaging approaches were employed to characterize immune remodeling and macrophage-Treg interactions. A chronic restraint stress mouse model was established to investigate stress-associated tumor immune remodeling and therapeutic response during anti-PD-1 therapy. Results:Elevated ED was associated with a lower disease control rate and inferior event-free survival. High-distress patients exhibited increased serum cortisol levels, which were associated with less favorable treatment outcomes. Multi-omics analyses suggested an immunosuppressive tumor microenvironment in distressed patients, characterized by regulatory T cell enrichment and increased macrophage-Treg spatial association within organized niches. In vivo, RU486 treatment was associated with reduced tumor burden, improved survival, and partial modulation of immunosuppressive remodeling. Conclusions:Emotional distress may represent a clinically relevant and potentially modifiable host-related factor associated with NAIT outcomes in OSCC. Stress-associated glucocorticoid signaling may contribute to immunosuppressive tumor remodeling and less favorable therapeutic response. These findings provide a rationale for integrating psychosocial assessment and neuroendocrine-targeted interventions into perioperative immunotherapy strategies.

BACKGROUND:Gastric cancer (GC) is a widespread global malignancy, frequently diagnosed at advanced stages owing to the subtle nature of early symptoms and low screening rates. Consequently, there is an imperative need to investigate innovative strategies for the treatment of GC. Exosomes, originating from various sources, act as natural nanocarriers enriched with numerous bioactive molecules, showcasing potential as groundbreaking treatments for GC. MATERIALS AND METHODS:In the present study, exosome-like nanoparticles (ELNs) were successfully purified from Salvia miltiorrhiza Bunge (Danshen) utilizing ultracentrifugation. The impact of these ELNs on human gastric cancer cells (HGC-27) was evaluated via a suite of viability assays, encompassing CCK-8, colony formation, flow cytometry, transwell migration, and wound healing assays. Furthermore, miRNA sequencing was conducted to identify and analyze the highly abundant miRNA within Danshen-derived ELNs, along with its potential biological functions. RESULTS:The HGC-27 cells internalized Danshen-derived ELNs (DS-ELNs), which led to a decrease in cell viability. Concurrently, these ELNs exhibited significant inhibitory effects on cell migration, colony formation, and overall progression of GC in vitro. The functional analysis of the miRNAs harbored by these ELNs indicated that they may serve as a potential therapeutic target for GC. CONCLUSION:In summary, these findings have not only comprehensively characterized the miRNAs present in Danshen-derived exosomes but also provided invaluable insights into the molecular mechanisms by which Danshen exerts its effects in mitigating.

This study investigated whether L-NAME, a nitric oxide synthase (NOS) inhibitor commonly used to model hypertension-associated endothelial dysfunction, can exert direct pro-atherogenic effects on vascular smooth muscle cells (VSMCs) independent of systemic hemodynamic influences. Mouse aortic VSMCs (MOVAS) were treated with non-cytotoxic concentrations of L-NAME (50 µM) or oxidized low-density lipoprotein (ox-LDL, 100 µg/mL), which served as a positive atherogenic control. Lipid accumulation was assessed by Oil Red O staining. The expression of contractile phenotype markers (ACTA2, MYH11, and α-SMA), the synthetic phenotype marker SPP1, and matrix metalloproteinases (MMP-2 and MMP-9) was quantified by qRT-PCR and immunofluorescence. Both L-NAME and ox-LDL treatments caused marked intracellular lipid accumulation in MOVAS cells, consistent with VSMC-derived foam cell formation. L-NAME and ox-LDL reduced the mRNA expression of contractile phenotype markers (ACTA2 and MYH11, p < 0.05) and decreased α-SMA protein expression (p < 0.001). Conversely, both treatments increased the mRNA expression of the synthetic phenotype marker SPP1 (p < 0.05) and matrix-remodeling genes MMP-2 and MMP-9 (p < 0.05). These effects were directionally similar to those induced by ox-LDL. L-NAME directly promotes lipid accumulation and synthetic phenotype-associated marker changes in MOVAS cells under the present in vitro conditions. Because eNOS/NOS activity, intracellular NO levels, rescue pathways, and primary VSMC validation were not assessed, these data should be interpreted as phenotypic evidence that NOS/NO pathway disruption may contribute to VSMC dysfunction rather than definitive proof of a single eNOS-dependent mechanism. Not applicable.

Dental pulp extracellular matrix (DPEM), as a naturally derived scaffold material for dental pulp regeneration, exhibits excellent biocompatibility. This study aims to develop a novel photo-cross-linked hydrogel composed of methacry- lated gelatin (GelMA) loaded with DPEM for application in pulp regeneration. In vitro experiments demonstrated that the GelMA–DPEM hydrogel, fabricated by mixing a 10 mg mL − 1 DPEM solution with a 10

Oral leukoplakia (OLK) is the most common oral potentially malignant disorder and carries a lifetime risk of transformation to oral squamous cell carcinoma (OSCC) of 0.1% to 9.8%. The aim of the current study is to explore salivary proteomics as a non-invasive approach for detecting the malignant transformation from OLK to OLK-associated OSCC (OLK-OSCC). We performed mass spectrometry-based proteomic profiling of saliva from 131 patients (48 OLK and 83 OLK-OSCC patients) and integrated the resulting data with machine learning. Salivary protein diversity was significantly increased in OLK-OSCC patients, and differential expression analysis identified 100 upregulated and 36 downregulated salivary proteins of OLK-OSCC compared with OLK. Using XGBoost and LASSO regression, we developed a nomogram based on a five-protein panel (MMP1, SUMO4, SMS, TMBIM1, and MUC5AC), which achieved high discriminatory performance in the training cohort (AUC = 0.94). The biological relevance of this panel was further supported by single-cell RNA sequencing data, a 4-nitroquinoline 1-oxide-induced murine carcinogenesis model (n = 18), and an independent OSCC tissue cohort (n = 39). Functional correlation analyses suggested that these biomarkers may be associated with an immunosuppressive tumor microenvironment by modulating the infiltration pattern of immune cells. Collectively, these findings characterize the salivary proteomic changes associated with OLK-OSCC and identify a five-protein salivary panel with potential value for OLK surveillance and early detection of malignant transformation.

Background: Cancer-associated fibroblasts (CAFs) are crucial components of the tumor microenvironment (TME), promoting tumor progression and drug resistance in various cancer diseases. Spatial transcriptomics has emerged as a powerful tool to elucidate the spatial distribution of cells and heterogeneous gene expression within tissues, providing support in many studies on TME. This study aims to elucidate the spatial distribution, molecular characteristics, and functional mechanisms of fibroblast subtypes in lung adenocarcinoma (LUAD) using spatial transcriptomics and experimental validation. Methods: Our study applied spatio-temporal enhanced resolution omics-sequencing (Stereo-seq) to investigate the interactions between fibroblasts and lung cancer cells. A co-culture system of A549 lung cancer cells and HFL1 fibroblasts was established to validate the functional roles of identified fibroblast subtypes. Gene knockdown, proliferation, migration, invasion, and ELISA assays were conducted to investigate underlying mechanisms. Results:Spatial transcriptomics revealed significant heterogeneity in LUAD tissues, with identification of a novel fibroblast cluster (C0) characterized by high expression of POSTN, THY1, BGN, and COL1A1, which co-localized with malignant epithelial cells (C5) in high-malignancy regions. Public dataset analysis confirmed C0 as CAFs, enriched in LUAD and associated with poor prognosis. Ligand-receptor analysis highlighted collagen I- and fibronectin 1-mediated interactions between C0 and C5. In vitro, co-culture with A549 induced differentiation of HFL1 into CAFs, with upregulation of COL1A1, COL1A2, and CAF markers. Knockdown of COL1A1 or COL1A2 in fibroblasts significantly reduced collagen I secretion and attenuated cancer cell proliferation, migration, and invasion, while exerting minimal effects on angiogenesis. Conclusions: These findings not only provide a molecular map of lung cancer tissues for further study but also illustrate a novel co-location relationship between fibroblasts and cancer cells within the TME. Our results highlight the potential of CAFs as a promising therapeutic target, complementing existing approaches targeting genetic mutations and immune cells.

Venous malformations (VMs) are common congenital vascular anomalies that usually appear at birth or in childhood. Mutations in the tyrosine kinase with immunoglobulin-like and epidermal growth factor like (EGF-like) domains 2/phosphoinositide 3-kinase (TIE2/PI3K)-related genes within endothelial cells (ECs) disrupt EC function and phenotype. However, VMs do not merely manifest as abnormalities of ECs. Lesions typically feature dilated and tortuous vessels with stagnant blood flow, thrombi or phleboliths, and disorganized structural layers. Histological evidence shows that VMs involve a range of cellular and noncellular components, including ECs, vascular smooth muscle cells, immune cells, platelets, and the extracellular matrix. While gene mutations in ECs may pull the trigger, VM progression depends on complex interactions among various elements, complicating clinical management. Existing studies have identified individual clues (e.g., mutations, cell loss, matrix degradation). However, the failure to define the interlocking logic between these pieces has prevented the assembly of a coherent picture on VM pathophysiology. Developmental biology reveals that embryonic angiogenesis is governed by ECs through tightly regulated intercellular communication. Hijacking of this communication is increasingly recognized as key contributors to VM development. This review maps how intercellular communication—via secretory factors, extracellular vesicles, direct contact, and mechanobiology—coalesces into a cohesive network that drives VM progression, and evaluates these pathways as promising diagnostic and therapeutic targets.

Immunotherapy has revolutionized the treatment of malignant tumors and is now recognized as a first-line option for various cancers. In resectable locally advanced oral squamous cell carcinoma (OSCC), neoadjuvant immunotherapy has been integrated into clinical practice, representing significant progress. While neoadjuvant immunochemotherapy shows promising efficacy in this setting, several critical challenges remain unresolved. These include defining optimal endpoints and response evaluation methods, identifying and managing hyperprogression, determining surgical strategies for patients with significant tumor reduction, assessing the feasibility of de-escalating postoperative adjuvant therapy in those achieving pathological complete response, and managing immune-related adverse events. This consensus addresses these challenges by integrating current evidence with pressing clinical questions and incorporating multidisciplinary expert insights from the OSCC field. The objective is to establish a standardized, unified framework for evaluating and managing these complex issues in resectable locally advanced OSCC.

Objectives Oral squamous cell carcinoma (OSCC) remains challenging due to therapeutic resistance and high recurrence, underscoring the need for novel therapeutic targets and prognostic biomarkers. Peptidoglycan recognition protein 4 (PGLYRP4), an innate immune molecule, has been correlated with improved prognosis in head and neck cancer, yet its functional role in OSCC remains undefined. Here, we characterized the expression pattern, clinical significance, biological function, and mechanism of PGLYRP4 in OSCC, focusing on its role in ferroptosis regulation. Methods PGLYRP4 expression was analyzed using the TCGA database, single-cell RNA sequencing data, and immunohistochemistry on tissue microarrays comprising 133 OSCC and 39 normal oral mucosa samples. Functional roles in proliferation, cell death, and ferroptosis were examined in CAL27 and HN6 cells using pharmacological inducers (RSL3, Erastin, ML162) and immune-derived ferroptotic signals (IFN-γ plus arachidonic acid). Mechanistic studies, including RT-qPCR, cycloheximide chase assays, and pharmacological inhibition of degradation pathways and palmitoylation, were performed to elucidate PGLYRP4-mediated regulation of GPX4. Results PGLYRP4 transcript and PGLYRP4 protein are markedly elevated in OSCC specimens, with expression predominantly confined to malignant cells by scRNA-seq. High PGLYRP4 expression correlates with favorable overall survival in head and neck squamous cell carcinoma (HNSCC) patients. Functionally, PGLYRP4 knockdown promotes proliferation and colony formation while reducing cell death; conversely, overexpression suppresses growth and enhances cell death. PGLYRP4 overexpression leads to elevated intracellular Fe2+ levels and enhances cellular sensitivity to ferroptosis-inducing agents as well as immune-derived ferroptotic signals, rescued by ferrostatin-1. Mechanistically, PGLYRP4 selectively downregulates GPX4 protein with no impact on its mRNA or on other ferroptosis regulators. Genetic rescue confirms that GPX4 depletion abolishes PGLYRP4 knockdown-mediated ferroptosis resistance. Pharmacological studies reveal that PGLYRP4 promotes GPX4 degradation via the lysosome rather than the proteasome, and this process is linked to GPX4 palmitoylation status. Conclusions This study identifies PGLYRP4 as a novel favorable prognostic biomarker and a positive regulator of ferroptosis in OSCC. PGLYRP4 sensitizes OSCC cells to ferroptosis by promoting lysosomal degradation of GPX4 in a palmitoylation-associated manner, establishing a previously unrecognized PGLYRP4-GPX4 regulatory axis that links innate immunity to ferroptosis execution. Clinical significance PGLYRP4 expression carries dual translational promise, serving as both a prognostic marker and a predictive indicator for guiding ferroptosis-based therapies. Assessing PGLYRP4 levels may help stratify OSCC patients, particularly those with HPV-negative or TP53-mutant tumors, eligible for ferroptosis-inducing agents. Intervening in this regulatory axis provides a viable approach for modulating ferroptosis sensitivity and circumventing treatment refractoriness in OSCC.

The relationship between the C/S ratio and pathological response to anti-PD1 therapy.

Dental surgical skills training assumes critical importance for aspiring dentists. Our present study aimed to investigate the effectiveness of innovative DVRS approach in assessing competency and improving skill in preclinical dental surgical skill training. A total of 142 students participated in this study. Within this cohort, 70 students from the 2017 intake were trained using traditional manikins (Group TM), while 72 students from the 2018 were trained using a Digital Virtual Reality Simulator for Dental Surgical Skills (Group DVRS). The scores of the training course between two groups were compared. Additionally, the experiences of students from Group DVRS were collected through a questionnaire survey regarding the use of DVRS in their preclinical training. Pedagogical outcome revealed that the average scores for Group DVRS were slightly higher than Group TM (P < 0.05). The feedback collected via questionnaires from Group DVRS participants reflected their satisfaction with the DVRS, praising its user-friendliness, clarity, training efficacy, and the resultant enhancement in their operational skills. These findings suggest that DVRS is an effective and beneficial tool for preclinical dental surgical skill training.

Effect of Maraviroc treatment on tumor growth.

The CD47/SIRPα axis conveys a 'don't eat me' signal, thereby thwarting the phagocytic clearance of tumor cells. Although blocking antibodies targeting CD47 have demonstrated promising anti-tumor effects in preclinical models, clinical trials involving human cancer patients have not yielded ideal results. Exploring the regulatory mechanisms of CD47 is imperative for devising more efficacious combinational therapies. Here, we report that inhibiting USP2 prompts CD47 degradation and reshapes the tumor microenvironment (TME), thereby enhancing anti-PD-1 immunotherapy. Mechanistically, USP2 interacts with CD47, stabilizing it through deubiquitination. USP2 inhibition destabilizes CD47, thereby boosting macrophage phagocytosis. Single-cell RNA sequencing shows USP2 inhibition reprograms TME, evidenced by increasing M1 macrophages and CD8+ T cells while reducing M2 macrophages. Combining ML364 with anti-PD-1 reduces tumor burden in mouse models. Clinically, low USP2 expression predicts a better response to anti-PD-1 treatment. Our findings uncover the regulatory mechanism of CD47 by USP2 and targeting this axis boosts anti-tumor immunity.