Hypopharyngeal squamous cell carcinoma (HPSCC) is a rare, highly aggressive malignancy, with recurrence playing a pivotal role in treatment failure and cancer-related mortality. The tumor microenvironment (TME) characteristics and molecular mechanisms driving recurrence in HPSCC remain poorly defined. Primary HPSCC (P-HPSCC) samples (n = 6) and recurrent HPSCC (R-HPSCC) samples (n = 3) were analyzed. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics were employed to dissect the cellular composition and molecular characteristics of the TME. Key regulatory networks were identified through gene expression analysis, pathway enrichment, and intercellular communication profiling. Functional validation experiments were performed to confirm the biological relevance of the pathways identified. ScRNA-seq analysis revealed that malignant epithelial cells (maEpCs) in recurrent tumors exhibited increased stemness, epithelial–mesenchymal transition (EMT), and immune evasion programs. Mechanistically, IGF2BP2 was selectively upregulated in R-HPSCC and functioned as an m6A reader to stabilize SMAD3 mRNA, thereby activating transforming growth factor beta (TGF-β) signaling and facilitating malignant progression. Integrated spatial transcriptomics and functional assays demonstrated that cancer-associated fibroblasts in recurrent tumors promote progression via FN1-mediated signaling. Concurrently, the recurrent TME underwent myeloid remodeling toward an immunosuppressive state, characterized by increased infiltration of SPP1+ tumor-associated macrophages and further enrichment of LAMP3+ dendritic cells with impaired antigen-presenting capacity, alongside aggravated CD8+ T-cell exhaustion, marked by upregulation of CTLA4 as a potential immune escape driver. This study identifies recurrence-associated cellular and molecular features in HPSCC. Recurrent tumors exhibited maEpC reprogramming via IGF2BP2-mediated activation of TGF-β signaling, coupled with FN1-dependent stromal activation and immune evasion marked by myeloid immunosuppressive remodeling and CD8+ T-cell exhaustion, characterized by CTLA4 upregulation. Collectively, these findings reveal a pro-recurrent TME and suggest potential therapeutic targets in R-HPSCC.

Tumor metabolic reprogramming is a hallmark of aggressive head and neck cancer (HNC), with enhanced glycolytic activity representing a major metabolic phenotype. However, how stromal signals in the tumor microenvironment (TME) sustain this process remains unclear. Here, we identify LINC02420 as a long noncoding RNA (lncRNA) enriched in cancer-associated fibroblast-derived extracellular vesicles (CAF-EVs). CAFs delivered LINC02420 to recipient HNC cells through EVs. LINC02420 increased lactate production and cell migration in HNC cells, and enhanced glucose-derived labeling of glycolytic intermediates and lactate. Reducing LINC02420 in donor CAFs attenuated the glycolysis-enhancing and pro-malignant effects of CAF-EVs. Mechanistically, CAF-EV-associated LINC02420 binds AEG-1, encoded by MTDH, and stabilizes AEG-1 protein. Stabilized AEG-1 enhances NF-κB signaling and p65 nuclear translocation. It also supports formation of an AEG-1-p65-p300 transcriptional complex at the HIF1A promoter, thereby increasing HIF1A transcription and glycolysis-related gene expression. In vivo, CAF-derived LINC02420 promoted HNC tumor growth. Clinically, LINC02420 was elevated in HNC tissues and plasma-derived EVs, and high tumor LINC02420 expression was associated with poorer overall survival. These findings identify a CAF-EV-associated lncRNA mechanism linking TME-derived stromal communication to HIF1A-dependent glycolytic regulation and support plasma EV-associated LINC02420 as a potential circulating biomarker for monitoring HNC progression.

Oxidative stress caused by excessive reactive oxygen species (ROS) disrupts skin and oral epithelial homeostasis and contributes to skin aging, inflammation, periodontitis, and mucosal injury. As the principal defenders in both skin and oral mucosal tissues, keratinocytes are important responders to oxidative stress. However, most existing studies have examined skin or oral keratinocytes in isolation, with few comparative investigations of their tolerance, repair capacity, and antioxidant mechanisms under oxidative stress. In this study, we systematically compared immortalized oral keratinocytes (TIGK) and skin keratinocytes (HaCaT) under hydrogen peroxide (H2O2)-induced oxidative stress. Functional analyses, including cell survival, ROS accumulation, stress granule formation, in vitro wound healing, and proliferation recovery assays, were combined with transcriptomic profiling to evaluate differences in antioxidant and pro-oxidant systems. TIGK exhibited significantly higher survival rates, lower ROS accumulation, and superior migratory and proliferative recovery compared with HaCaT after oxidative insult. Transcriptomic analysis further revealed that TIGK consistently expressed higher levels of antioxidant genes and enzymes. In contrast, HaCaT showed greater ROS accumulation and relatively limited antioxidant defenses. The results show that oral and skin keratinocytes adopt distinct adaptive mechanisms under oxidative stress. The intrinsic redox advantage of oral keratinocytes provides new insights into their rapid wound-healing capacity and may inform strategies to enhance epithelial resilience.

We present a dynamic full-field optical coherence tomography (D-FFOCT) system providing both structural and dynamic contrast for label-free imaging of head and neck squamous cell carcinoma (HNSCC). The system simultaneously acquires structural and dynamic contrast, enabling visualization of tissue morphology and intracellular activity. Ex vivo imaging of MTCQ1 xenografts and fresh human HNSCC specimens showed distinct patterns between tumor and normal tissues, consistent with H&E histology. Dynamic contrast remained stable for 4 h after excision. Quantitative ROI analysis revealed significant differences in epithelial morphology and temporal fluctuation metrics, supporting rapid intraoperative optical characterization of HNSCC.

Communication between various cell types following wounding is paramount for proper healing and regeneration of injured tissue. Endothelial cells and fibroblasts are critical cellular players involved in cutaneous wound repair, yet their communication mechanisms are not well understood. It has previously been shown that extracellular vesicles derived from endothelial cells (ECEVs) induce dermal fibroblasts to express a gene signature correlated with FGF2-mediated cancer associated fibroblast (CAF) activation, under the control of transcription factor ETV1. In this report, we utilize loss-of-function studies to define the mechanistic role of ETV1 in conferring this ECEV-induced transcriptomic shift and functional change in fibroblasts. Additionally, we identify highly expressed ECEV microRNAs and examine their potential contribution to the ECEV mechanism through downstream gene modulation. In summary, we describe a plausible mechanism by which both ETV1 and top ECEV microRNAs promote a genotypic and phenotypic shift in dermal fibroblasts that have taken up ECEVs.

The influence of circadian disruption from night shift work and poor sleep on allergic rhinitis (AR) risk remains inadequately characterized. The objective of this study was to advance the understanding of how circadian disruption influence AR risk, thereby providing new insights into the prevention and management of AR. This prospective cohort study analyzed data from the UK Biobank, comprising 256,945 participants for shift work analysis and 374,672 for sleep pattern assessment. Shift work and sleep behaviors were self-reported at baseline. AR incidents were identified through linked hospital records. Multivariable Cox proportional hazards models were employed to estimate hazard ratios (HRs) and 95

Human skin wound healing is a complex process of tissue pattern formation driven by massive cell migration and regeneration, coordinated through intercellular communication. A multiscale tissue modeling framework, the dynamic cellular finite-element method (DyCelFEM), was developed to more realistically study the wound healing process in silico with detailed cellular mechanical interactions and geometric changes. Cells produce and release signaling cytokines that diffuse through the extracellular matrix (ECM) to mediate cell communication. Cell behavior control was integrated into each individual cell, based on cell type and intracellular circuits, to enable individual stochastic decisions regarding growth, proliferation, migration, and death. This allowed cells to respond to environmental changes and signaling from surrounding cells. Model parameters were set based on available biologic data, and 10 independent simulations were conducted for each skin wound healing scenario to obtain the average dynamics and statistics. Simulation results were compared with data from experimental wounds. Results showed that the model was able to correctly reproduce the qualitative emergent behavior observed in histological imaging of wound healing. Additionally, simulations correctly captured the longitudinal dynamics of transforming growth factor β and collagen expression from gene array analysis. The successful capture of experimental observations and data served as a qualification for the model. By comparing simulated wound healing phenotypes under transforming growth factor β levels above and below physiologic normal ones, the model revealed that the ECM is likely to play a key role in transmitting critical cytokine signals to coordinate cell migration and regeneration during wound healing. Dysregulated ECM production, which produces either too much or too little ECM during wound healing, might compromise the outcome. This mechanism suggests that optimal wound healing requires a finely controlled ECM regeneration, and that therapeutics that induce significant increases in ECM might not be beneficial.

BACKGROUND:Head and neck squamous cell cancer (HNSCC) patients with pN1, cM0 status without adverse pathological features are associated with a relatively poor prognosis despite a limited metastatic lymph node burden. The survival benefit of postoperative radiotherapy (PORT) for these patients remains uncertain. Therefore, the objective of this study was to evaluate the necessity of PORT in HNSCC patients with pN1, cM0 status and no adverse pathological features by comparing survival outcomes between patients who received PORT and those who did not. METHOD:The clinical characteristics and follow-up data of HNSCC patients with pN1, cM0 status without adverse pathological features from 2004 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were stratified into the PORT and non-PORT groups. Kaplan-Meier analysis was applied to overall survival (OS) and cancer-specific survival (CSS) to evaluate the association of PORT with the clinical outcomes of these patients. Subgroup analysis was performed to identify the subgroup of patients who might benefit from PORT. RESULTS:Overall, 461 patients were included, with 258 patients who received PORT and 203 patients who did not receive PORT. Patients who received PORT had better OS and CSS than patients who did not receive PORT (5-year OS: 84% vs. 69%, p < 0.001; 5-year CSS: 91% vs. 79%, p < 0.001). According to the subgroup analysis, PORT is associated with a survival benefit in patients with OPSCC and LSCC, who are < 60 years of age, male, single, have grade 1 to 2 tumors, have stage III to IV disease, and undergoing open surgery. CONCLUSION:This study demonstrated that HNSCC patients with pN1, cM0 status without adverse pathological features were significantly associated with better OS and CSS after receiving PORT. These findings support the use of PORT to achieve improved survival for pN1, cM0 HNSCC patients without adverse pathological features, especially those younger than 60 years of age.

Fibrosis is a pathological process affecting multiple organs, in which matrix stiffness-associated mechanotransduction plays a critical initiating and regulatory role. Piezo1/2 channels are key mechanosensors in fibrosis, with cell-type-specific causal roles supported by evidence ranging from association studies to genetic interventions. However, reported findings appear contradictory, with studies suggesting both pro-fibrotic and anti-fibrotic effects. This divergence is not merely biological noise but likely stems from critical differences in experimental models, methodological limitations, and the highly context-dependent nature of Piezo function (varying by cell type, tissue microenvironment, and disease stage). This review critically evaluates the evidence, highlighting methodological pitfalls (e.g., in vitro stiffness models, off‑target drug effects, genetic model caveats) that may underlie discrepancies. We provide a cell‑ and context‑resolved framework to guide future targeting of Piezo channels in anti‑fibrotic strategies.

Laryngeal squamous cell carcinoma (LSCC) is typically diagnosed at advanced stages, highlighting the critical need for early intervention. By integrating single-cell and bulk RNA-seq data from LSCC, vocal cord leukoplakia (VCL), and LSCC precursors, we characterized dynamic remodeling of the tumor microenvironment during LSCC pathogenesis. We identified transcriptional program gene modules that reflect malignant epithelial cells (maEpCs). The infiltration of POSTN+ fibroblasts progressively increases from normal tissue to VCL and further to LSCC, accompanied by enhanced intercellular communication. These fibroblasts interact with maEpCs and endothelial cells via ligands such as MIF, promoting epithelial-mesenchymal transition, cancer stemness, and angiogenesis. Blocking MIF reversed cancer-associated fibroblast-driven invasion and angiogenesis. Here, we further revealed that an immunosuppressive microenvironment arises as early as the precancerous stage, with VCL exhibiting CD8+ T cell exhaustion and abundant LAMP3+ dendritic cells that correlate positively with Tregs and exhausted CD8+ T cells, promoting early immune escape. Additionally, LSCC was uniquely enriched for a pro-tumor SPP1+ macrophage subset with low phagocytic activity and high angiogenic potential, linked to poor prognosis. Our findings uncover key mechanisms driving LSCC malignant progression, offer insights for early diagnosis and prognosis assessment, and highlight MIF as a promising therapeutic target.

Importance Tinnitus, affecting 10% to 15% of the global population, is a debilitating condition often linked to hearing loss and neurological disorders. While air pollution is a known risk factor for respiratory and cardiovascular diseases, its association with tinnitus remains underexplored. Objective This study investigates the association between air pollution, polygenic risk score (PRS), and tinnitus prevalence. Design Cross-sectional analysis. Setting UK Biobank (UKB) population-based cohort. Participants Seventy-nine thousand two hundred seventy-seven individuals from the UKB with available tinnitus, air pollution, and genetic data. Exposures Air pollution measures (PM 2.5 , PM 2.5–10 , PM 10 , NO 2 , and NO x ). A composite air pollution score was calculated, and PRS was derived from 6 tinnitus-associated single-nucleotide polymorphisms. Main outcome measures Prevalence, frequency, and severity of tinnitus. Logistic regression models were used, adjusting for sociodemographic, health, and hearing-related covariates. Results Each interquartile range increase in air pollution score was associated with higher odds of current tinnitus (OR = 1.06, 95% CI: 1.03-1.08, P < .001), particularly transient tinnitus (OR = 1.04, P = .008). PRS was independently associated with prevalent tinnitus ( P < .001), and higher OR were observed among individuals with both high air pollution exposure and high PRS (OR = 1.34, 95% CI: 1.18-1.52, P < .001). Individual pollutants showed weaker associations. Conclusion A joint association of air pollution exposure and genetic susceptibility with tinnitus prevalence was observed in this cross-sectional analysis, highlighting the importance of integrated environmental and genetic assessments in auditory health. Relevance Our findings emphasize the potential value of integrating environmental and genetic factors for risk stratification of tinnitus in populations.

BACKGROUND:To compare outcomes of the combined transcervical-submandibular and transoral endoscopic approach versus the open transcervical parotid approach and transoral endoscopic surgery alone, and to clarify the indications and advantages of the combined technique. METHODS:This retrospective observational study was conducted at a tertiary academic hospital in China between January 2013 and December 2024. A total of 114 consecutive patients with histologically confirmed benign parapharyngeal space tumors underwent the open transcervical parotid approach (n = 48), transoral endoscopic surgery alone (n = 42), or the combined transcervical-submandibular and transoral endoscopic approach (n = 24). Tumor size, intraoperative blood loss, hospitalization duration, tracheotomy rates, en-bloc resection rates, and surgery-related complications were compared among the three groups. RESULTS:The combined surgery group had significantly larger tumors and a lower incidence of surgery-related complications. No statistically significant differences were observed among the three approaches in tracheostomy rates, intraoperative blood loss, operative duration, or hospitalization duration. CONCLUSIONS:The combined approach appears effective in reducing complications associated with resection of large, anatomically complex benign parapharyngeal tumors, particularly those involving critical neurovascular structures. This technique shows clinical value and warrants broader application.

ABSTRACT Background To evaluate the effect of bilateral elective node dissection on the prognosis of patients with T3N0M0 glottic carcinoma. Methods This retrospective cohort study enrolled two cohorts: patients screened from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute, and those treated at the First Affiliated Hospital of Sun Yat‐sen University. Patients screened from the SEER database were divided into untreated, radiotherapy (RT), surgery, and concurrent systemic therapy (ST)/RT groups. Patients from our center were divided into unilateral and bilateral groups based on lymph node dissection. Propensity score‐matching (PSM) was applied to eliminate baseline variations. Kaplan–Meier analysis was used to assess different treatment method effects. Results This study retrieved 2027 and 133 patients from the SEER database and our center, respectively, from 2014 to 2022. After PSM, overall survival (OS) and cancer‐specific survival (CSS) improved in the ST/RT (both p < 0.001) and surgery (both p < 0.001) groups versus the RT group, with no differences between groups (OS, p = 0.45; CSS, p = 0.84). Patients who underwent elective node dissection (END) had better OS (p = 0.025) and CSS (p < 0.001) than those without END. No significant difference was observed in OS (p = 0.110) between the END and ST/RT groups; however, the END group showed significant improvement in CSS (p = 0.007). Patients who underwent bilateral neck dissection had better progression‐free survival than the unilateral group after PSM (p = 0.024). Conclusion Surgery combined with bilateral node dissection can bring better survival prognosis for patients with T3N0M0 glottic carcinoma.

Abstract Background: Improving outcomes for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) requires novel strategies. This phase 2 trial evaluated the efficacy and safety of neoadjuvant adebrelimab (a PD-L1 inhibitor) combined with chemotherapy in untreated, resectable LA-HNSCC. Methods: In this single-center, single-arm study (ChiCTR2400091171), eligible patients had newly diagnosed, resectable stage III-IVA/B LA-HNSCC. Patients received three cycles of neoadjuvant adebrelimab (1200 mg), nab-paclitaxel (260 mg/m²), and carboplatin (AUC 5) every 21 days. Subsequent local therapy (radical radiotherapy or surgery) was based on radiological response. The primary endpoint was objective response rate (ORR, RECIST v1.1). Secondary endpoints included safety, pathologic response, larynx preservation, and biomarker analysis. Results: Twenty-four patients were enrolled (median age 61.5 years; 91.7% male; 70.8% hypopharynx primary). Twenty-three completed all three cycles of neoadjuvant therapy and were evaluated for response by RECIST 1.1. The ORR was 87.5% (21/24) in the intention-to-treat population and 91.3% (21/23) in the per-protocol population, including 5 complete and 16 partial responses. The larynx preservation rate was 95.8%. Pathologic complete response was observed in 3 of 7 surgical patients (42.9%). Significant downstaging occurred in T-stage (66.7%), N-stage (70.8%), and overall stage (54.2%). All patients with p16-positive tumors (8/8) and those with PD-L1 combined positive score ≥20 (8/8) achieved an objective response. Grade 3 adverse events occurred in 41.7% of patients (primarily hematologic toxicities), with no grade 4/5 events. Conclusion: Neoadjuvant adebrelimab plus chemotherapy demonstrated high response rates, promising organ preservation, and manageable toxicity in resectable LA-HNSCC. Biomarker analysis suggests p16 positivity and high PD-L1 expression may correlate with better response. These findings support further investigation in randomized trials. Citation Format: Ruihua Fang, Bixue Huang, Lin Chen, Rongjian Zhan, Yicheng Deng, Weiping Wen, Wenbin Lei. Neoadjuvant adebrelimab plus chemotherapy in untreated locally advanced head and neck squamous cell carcinoma: Efficacy and biomarker insights from a single-arm phase II trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT239.

BACKGROUND:Transfusion-related acute lung injury (TRALI) is a severe complication of blood transfusion, but its molecular mechanisms remain poorly understood. This study aimed to investigate the role of Toll-like receptor 4 (TLR4) and its downstream signaling cascade in the pathogenesis of TRALI. METHODS:Lipopolysaccharide (LPS)-treated PAEC cells and BALB/c mice were used as a model of TRALI. Relative mRNA expression was evaluated via quantitative RT-PCR. Protein abundance in cells/tissues and cell culture supernatant/serum was detected using western blot and ELISA, respectively. Lung tissue injury was evaluated by hematoxylin and eosin staining, and protein expression in lung tissues was analyzed by immunohistochemistry. RESULTS:Expressions of TLR2, TLR4 and myeloid differentiation 2 (MD-2) were significantly elevated in the cellular TRALI model and accompanied by an increase in c-Jun, c-Fos, and P65 phosphorylation and increased expression and secretion of IL-1β, IL-6, IL-8, and TNF-α. The TLR4 inhibitor TAK-242 or MD-2 siRNAs effectively suppressed the molecular alterations induced by LPS in the cellular TRALI model. TAK-242 significantly reduced mortality and lung tissue injury in the TRALI mouse model, decreased TLR2, TLR4 and MD-2 expression, inhibited c-Jun, c-Fos, and p65 phosphorylation, and downregulated IL-1β, IL-6, IL-8, and TNF-α expression. CONCLUSIONS:In this animal model of TRALI, the highly expressed TLR4/MD-2 complex promotes the pathogenesis of TRALI through the activation of the activator protein-1(AP-1) and nuclear factor-κB (NF-κB) signaling pathways and the release of inflammatory mediators. One limitation is the positive study in rodent model but not in humans.

ABSTRACT Background The optimal therapeutic strategy for patients with T2‐3N0‐3 M0 or T1N1‐3 M0 hypopharyngeal squamous cell carcinoma (HPSCC) and the use of postoperative radiotherapy with or without systemic therapy for patients with T1‐2N1M0 HPSCC remain controversial. We aimed to determine whether these additional treatments improve the prognosis in HPSCC. Methods We retrospectively analyzed the databases held by the SEER (surveillance, epidemiology, and end results) program and a tertiary referral center in China to evaluate the survival outcomes of surgical intervention for T2‐3N0‐3 M0 and T1N1‐3 M0 HPSCC and of postoperative radiotherapy for T1‐2N1M0 disease. Results The SEER contained data for 1235 patients with T2‐3N0‐3 M0 or T1N1‐3 M0 HPSCC, of whom 220 underwent surgery as their first treatment and 737 received non‐surgical treatment. There was no statistically significant difference in overall survival (OS) between these two groups. Data were also available for 30 patients in the SEER who were treated by surgery alone (n = 11), surgery plus postoperative radiotherapy (n = 7), or surgery plus postoperative radiotherapy with systemic therapy (n = 12). Similarly, 23 patients at our hospital were identified to have been treated by surgery alone (n = 7), surgery plus postoperative radiotherapy (n = 10), or surgery plus postoperative radiotherapy with systemic therapy (n = 6). The SEER data indicated that postoperative radiotherapy improved OS (hazard ratio 0.281, 95% confidence interval 0.079–0.998; p = 0.036). This finding was supported by the data from our hospital, although the improvement in OS was not statistically significant (hazard ratio 0.360, 95% confidence interval 0.057–2.261; p = 0.224). Postoperative radiotherapy with systemic therapy seemed not to improve OS beyond that achieved by postoperative radiotherapy alone. Conclusions There was no significant difference in OS in patients with T2‐3N0‐3 M0 or T1N1‐3 M0 HPSCC according to whether or not they underwent surgery as first‐line treatment. Surgery plus postoperative radiotherapy was associated with a more favorable prognosis than surgery alone in patients with T1‐2N1M0 HPSCC.

ObjectiveThis study aimed to compare debridement strategies for chronic lower-extremity wounds using a systematic review and Bayesian network meta-analysis.MethodsThis study followed the PRISMA-NMA guidelines. PubMed, Embase, Web of Science, the Cochrane Library, CNKI, Wanfang, and VIP were searched from January 1990 to February 2026. Randomized controlled trials involving venous leg ulcers, arterial or ischemic ulcers, mixed arterial–venous ulcers, or diabetic foot ulcers were included. The outcomes included wound healing, complete debridement, pain score, procedure time, and time to healing. Pairwise meta-analysis and Bayesian network meta-analysis were performed. Surface under the cumulative ranking curve (SUCRA) rankings were interpreted according to the clinical direction of each outcome.ResultsA total of 25 randomized controlled trials were included. For wound healing, biological debridement (BIO) had the highest ranking probability (SUCRA = 99.5%), followed by enzymatic debridement (ENZ) (83.1%) and mechanical debridement (MECH) (65.9%). For complete debridement, biological debridement ranked first (95.7%), followed by enzymatic debridement (70.9%), autolytic debridement (AUTO) (32.2%), and standard care (SC) (1.2%). For pain score, procedure time, and time to healing, lower values represented better outcomes; rankings for these endpoints were therefore interpreted in that direction. Enzymatic and autolytic debridement ranked more favorably for pain score, biological and ultrasound-assisted debridement (US) for procedure time, and biological and autolytic debridement for time to healing. Several comparisons had wide credible intervals, and certainty of evidence was limited by clinical heterogeneity, sparse networks, and methodological limitations.ConclusionThe comparative profile of debridement strategies varied by the outcome. Biological and enzymatic debridement ranked favorably for wound healing and complete debridement, whereas enzymatic and autolytic debridement were associated with lower pain scores. Ultrasound-assisted debridement may be more efficient in terms of procedure time. These findings should be interpreted cautiously because ranking probabilities do not establish clinically decisive superiority, especially when evidence is sparse or heterogeneous.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420261341535.

The response to injury involves a complex series of events, including cellular migration and proliferation, inflammatory processes, and tissue remodeling. The oral mucosa exhibits a more regenerative repair response that resolves with minimal scarring when compared to skin. To investigate mechanisms driving this differential healing response, we integrated gene expression data from adult human palate and skin wounds over seven days with transcription factor binding data and protein-protein interaction data to estimate sample-specific gene regulatory networks. Comparative analysis between unwounded palate and skin networks revealed tissue-specific transcription factor targeting and gene set co-expression. Upon injury, global network changes between tissues were divergent, indicating distinct gene regulatory programs. Gene regulatory analyses revealed that the acute response to injury is characterized by transcription factor mediated gene repression, followed by tissue-specific gene activation at later healing stages. Notably, a subset of palate-specific transcription factors previously linked to regeneration in model organisms correlated with gene targeting and expression during acute injury. Specifically, BATF3 promoted cell migration and re-epithelialization after injury, but not proliferation. In summary, these findings highlight the temporal dynamics of transcription factors in wound response between palate and skin and provide insights into the gene regulatory mechanisms governing regenerative and non-regenerative healing.

The epidermis of the skin and oral mucosa is constantly exposed to various environmental stimuli, including temperature changes. In particularly extreme conditions, such as excess heat or cold, significant injury may occur. Oral and skin keratinocytes exhibit tissue-specific differences in wound healing outcomes and the transcriptomic response to injury. This study investigated if skin and oral keratinocytes also have differential responses to heat- and cold-induced injury. Oral keratinocytes (TIGKs) were found to exhibit an enhanced viability following heat-induced injury compared to skin keratinocytes (HaCaTs). However, there were no discernible differences between skin and oral keratinocyte viability following cold-induced injury. To examine the transcriptomic differences between skin and oral keratinocytes in response to temperature-induced injury, we generated an mRNA-sequencing gene expression dataset. Differentially expressed genes (DEGs) including heat shock proteins (HSPs) were identified between HaCaTs and TIGKs at baseline (37 °C) and after heat- (60 °C) or cold-induced (−25 °C) injury. Our comparative analyses suggest that skin and oral keratinocytes exhibit transcriptomic differences at baseline and in their responses to heat or cold exposure. The enhanced heat tolerance of TIGKs relative to HaCaTs may be due to an advantageous expression of a subset of HSPs at baseline in TIGKs. Our work also provides a source of skin and oral keratinocyte gene expression data following heat- and cold-induced injury that can be used for future analyses.